Cardiovascular Conference at Snowmass

SNOWMASS, COLO. – Differentiating constrictive pericarditis from restrictive cardiomyopathy in patients with right heart failure with a normal ejection fraction is “one of the most difficult diagnostic challenges in cardiology today,” but reliable results can be achieved using a careful step-by-step approach, Dr. Rick A. Nishimura said at the Annual Cardiovascular Conference at Snowmass.

Under current terminology for heart failure, cardiologists speak of HFrEF, or heart failure with reduced ejection fraction, and HFpEF, or heart failure with preserved ejection fraction. But there is a third group of patients who are often mistakenly thought to have HFpEF: those with severe right heart failure and a normal ejection fraction, classically caused by constrictive pericarditis or restrictive cardiomyopathy.

Unlike patients with HFpEF, these people are not hypertensive and they don’t have pulmonary congestion. Instead, they present predominantly with ascites, peripheral edema, fatigue, and marked elevation in jugular venous pressure, noted Dr. Nishimura, professor of medicine at the Mayo Clinic in Rochester, Minn.

Before elaborating on his own tried-and-true, step-by-step approach, he highlighted several diagnostic procedures he considers less than reliable. One is advanced imaging with CT or MRI looking for the pericardial thickening that is widely viewed as an anatomic hallmark of constrictive pericarditis.

“Remember, 22% of patients with proven constrictive pericarditis actually have a normal pericardium on CT or MRI, because it’s their fibrotic epicardium that’s causing the constrictive pericarditis. And roughly 70% of patients are going to have some thickened pericardium after radiation therapy or coronary artery bypass graft surgery without having constrictive pericarditis. So CT and MRI are helpful, but they’re not going to be diagnostic,” according to the cardiologist.

Similarly, while it’s often been said that constrictive pericarditis can be diagnosed based upon a classic trio of hemodynamic findings obtained through heart catheterization – namely, early rapid filling with a left ventricular end-diastolic pressure equal to the right ventricular end-diastolic pressure, a right ventricular end-diastolic pressure greater than one-third of the right ventricular systolic pressure, and a pulmonary artery pressure below 50 mm Hg – these criteria didn’t reliably separate the last 100 patients who came to the catheterization lab at the Mayo Clinic with either constrictive pericarditis or restrictive cardiomyopathy, he continued.

Dr. Nishimura’s approach to the work-up of patients with unexplained right heart failure and a normal ejection begins with the history and physical examination. The history in a patient with constrictive pericarditis is classically one of radiation therapy years earlier for a malignancy, or prior CABG surgery. And the physical exam has to reveal the presence of high neck veins.

“If you don’t see high neck veins due to elevated jugular venous pressure with rapid x and y descents, the patient doesn’t have constrictive pericarditis, no matter what the echocardiogram shows,” Dr. Nishimura asserted.

If those findings are present, however, then on 2-D echocardiography he’s looking for three things that point to constrictive pericarditis: a brisk septal shudder due to rapid filling in early diastole with every heart beat; an early diastolic posterior motion of the intraventricular septum, known as the septal bounce, that occurs as a consequence of the less compliant ventricular walls; and dilation of the inferior vena cava indicative of increased right atrial pressure.

When all three findings are present on 2-D echo, he turns to Doppler echo for hemodynamic information. If Doppler shows a reduction in transmitral driving pressure from the lungs to the heart during inspiration, as the intrathoracic pressure drops but the left ventricular pressure does not, the work-up is done. That patient has constrictive pericarditis and needs to be referred to surgery for pericardiectomy, which will bring rapid improvement.

In roughly one-quarter of patients with constrictive pericarditis, however, that full constellation of 2-D and Doppler echocardiographic findings isn’t present. It then becomes necessary to move on to cardiac catheterization. The first two things to look for in the cath lab are elevated end-equalization of diastolic pressures and low cardiac output.

“If they’re in the cath lab and they’ve got normal filling pressures and a normal cardiac output, they do not have clinically significant constrictive pericarditis, no matter what the echo shows. So those two things are necessary to see, but of course they’re not diagnostic. So we go further,” Dr. Nishimura said.

A patient with constrictive pericarditis will have enhanced ventricular interaction arising from the restraint imposed by a rigid, diseased pericardium. That’s crucial. This increased ventricular interaction is manifest as an increase in the size of the right ventricle during inspiration while the area of the left ventricle is getting smaller.

In contrast, during inspiration and expiration in a patient with restrictive cardiomyopathy, as the right ventricle gets smaller, so does the left ventricle.

“The ratio of the right ventricle to left ventricle area under the curve during inspiration versus expiration gives a very nice distinction between constrictive pericarditis and restrictive cardiomyopathy. Enhanced ventricular interaction is the most sensitive and specific finding for constrictive pericarditis,” according to Dr. Nishimura.

He added that, in addition to constrictive pericarditis and restrictive cardiomyopathy, there is a third and underappreciated cause of right heart failure with a normal ejection fraction: severe tricuspid regurgitation. This abnormality may not be readily apparent upon echocardiography in a patient with a pacemaker lead or automatic implantable cardioverter-defibrillator lead, which can cause acoustic shadowing that results in underestimation of the severity of tricuspid regurgitation. The clue here is the observation of hepatic vein systolic flow reversal, which can only be caused by severe tricuspid regurgitation.

“Think tricuspid regurgitation in patients who have a pacemaker lead or AICD, and also in older women with longstanding atrial fibrillation who dilate their tricuspid annulus and develop more and more tricuspid regurgitation. Take those patients to the cath lab and do a right ventriculogram, which will show tricuspid regurgitation,” Dr. Nishimura advised.

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Differentiating constrictive pericarditis from restrictive cardiomyopathy in patients with right heart failure with a normal ejection fraction is “one of the most difficult diagnostic challenges in cardiology today,” but reliable results can be achieved using a careful step-by-step approach, Dr. Rick A. Nishimura said at the Annual Cardiovascular Conference at Snowmass.

Under current terminology for heart failure, cardiologists speak of HFrEF, or heart failure with reduced ejection fraction, and HFpEF, or heart failure with preserved ejection fraction. But there is a third group of patients who are often mistakenly thought to have HFpEF: those with severe right heart failure and a normal ejection fraction, classically caused by constrictive pericarditis or restrictive cardiomyopathy.

Unlike patients with HFpEF, these people are not hypertensive and they don’t have pulmonary congestion. Instead, they present predominantly with ascites, peripheral edema, fatigue, and marked elevation in jugular venous pressure, noted Dr. Nishimura, professor of medicine at the Mayo Clinic in Rochester, Minn.

Before elaborating on his own tried-and-true, step-by-step approach, he highlighted several diagnostic procedures he considers less than reliable. One is advanced imaging with CT or MRI looking for the pericardial thickening that is widely viewed as an anatomic hallmark of constrictive pericarditis.

“Remember, 22% of patients with proven constrictive pericarditis actually have a normal pericardium on CT or MRI, because it’s their fibrotic epicardium that’s causing the constrictive pericarditis. And roughly 70% of patients are going to have some thickened pericardium after radiation therapy or coronary artery bypass graft surgery without having constrictive pericarditis. So CT and MRI are helpful, but they’re not going to be diagnostic,” according to the cardiologist.

Similarly, while it’s often been said that constrictive pericarditis can be diagnosed based upon a classic trio of hemodynamic findings obtained through heart catheterization – namely, early rapid filling with a left ventricular end-diastolic pressure equal to the right ventricular end-diastolic pressure, a right ventricular end-diastolic pressure greater than one-third of the right ventricular systolic pressure, and a pulmonary artery pressure below 50 mm Hg – these criteria didn’t reliably separate the last 100 patients who came to the catheterization lab at the Mayo Clinic with either constrictive pericarditis or restrictive cardiomyopathy, he continued.

Dr. Nishimura’s approach to the work-up of patients with unexplained right heart failure and a normal ejection begins with the history and physical examination. The history in a patient with constrictive pericarditis is classically one of radiation therapy years earlier for a malignancy, or prior CABG surgery. And the physical exam has to reveal the presence of high neck veins.

“If you don’t see high neck veins due to elevated jugular venous pressure with rapid x and y descents, the patient doesn’t have constrictive pericarditis, no matter what the echocardiogram shows,” Dr. Nishimura asserted.

If those findings are present, however, then on 2-D echocardiography he’s looking for three things that point to constrictive pericarditis: a brisk septal shudder due to rapid filling in early diastole with every heart beat; an early diastolic posterior motion of the intraventricular septum, known as the septal bounce, that occurs as a consequence of the less compliant ventricular walls; and dilation of the inferior vena cava indicative of increased right atrial pressure.

When all three findings are present on 2-D echo, he turns to Doppler echo for hemodynamic information. If Doppler shows a reduction in transmitral driving pressure from the lungs to the heart during inspiration, as the intrathoracic pressure drops but the left ventricular pressure does not, the work-up is done. That patient has constrictive pericarditis and needs to be referred to surgery for pericardiectomy, which will bring rapid improvement.

In roughly one-quarter of patients with constrictive pericarditis, however, that full constellation of 2-D and Doppler echocardiographic findings isn’t present. It then becomes necessary to move on to cardiac catheterization. The first two things to look for in the cath lab are elevated end-equalization of diastolic pressures and low cardiac output.

“If they’re in the cath lab and they’ve got normal filling pressures and a normal cardiac output, they do not have clinically significant constrictive pericarditis, no matter what the echo shows. So those two things are necessary to see, but of course they’re not diagnostic. So we go further,” Dr. Nishimura said.

A patient with constrictive pericarditis will have enhanced ventricular interaction arising from the restraint imposed by a rigid, diseased pericardium. That’s crucial. This increased ventricular interaction is manifest as an increase in the size of the right ventricle during inspiration while the area of the left ventricle is getting smaller.

In contrast, during inspiration and expiration in a patient with restrictive cardiomyopathy, as the right ventricle gets smaller, so does the left ventricle.

“The ratio of the right ventricle to left ventricle area under the curve during inspiration versus expiration gives a very nice distinction between constrictive pericarditis and restrictive cardiomyopathy. Enhanced ventricular interaction is the most sensitive and specific finding for constrictive pericarditis,” according to Dr. Nishimura.

He added that, in addition to constrictive pericarditis and restrictive cardiomyopathy, there is a third and underappreciated cause of right heart failure with a normal ejection fraction: severe tricuspid regurgitation. This abnormality may not be readily apparent upon echocardiography in a patient with a pacemaker lead or automatic implantable cardioverter-defibrillator lead, which can cause acoustic shadowing that results in underestimation of the severity of tricuspid regurgitation. The clue here is the observation of hepatic vein systolic flow reversal, which can only be caused by severe tricuspid regurgitation.

“Think tricuspid regurgitation in patients who have a pacemaker lead or AICD, and also in older women with longstanding atrial fibrillation who dilate their tricuspid annulus and develop more and more tricuspid regurgitation. Take those patients to the cath lab and do a right ventriculogram, which will show tricuspid regurgitation,” Dr. Nishimura advised.

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Differentiating constrictive pericarditis from restrictive cardiomyopathy in patients with right heart failure with a normal ejection fraction is “one of the most difficult diagnostic challenges in cardiology today,” but reliable results can be achieved using a careful step-by-step approach, Dr. Rick A. Nishimura said at the Annual Cardiovascular Conference at Snowmass.

Under current terminology for heart failure, cardiologists speak of HFrEF, or heart failure with reduced ejection fraction, and HFpEF, or heart failure with preserved ejection fraction. But there is a third group of patients who are often mistakenly thought to have HFpEF: those with severe right heart failure and a normal ejection fraction, classically caused by constrictive pericarditis or restrictive cardiomyopathy.

Unlike patients with HFpEF, these people are not hypertensive and they don’t have pulmonary congestion. Instead, they present predominantly with ascites, peripheral edema, fatigue, and marked elevation in jugular venous pressure, noted Dr. Nishimura, professor of medicine at the Mayo Clinic in Rochester, Minn.

Before elaborating on his own tried-and-true, step-by-step approach, he highlighted several diagnostic procedures he considers less than reliable. One is advanced imaging with CT or MRI looking for the pericardial thickening that is widely viewed as an anatomic hallmark of constrictive pericarditis.

“Remember, 22% of patients with proven constrictive pericarditis actually have a normal pericardium on CT or MRI, because it’s their fibrotic epicardium that’s causing the constrictive pericarditis. And roughly 70% of patients are going to have some thickened pericardium after radiation therapy or coronary artery bypass graft surgery without having constrictive pericarditis. So CT and MRI are helpful, but they’re not going to be diagnostic,” according to the cardiologist.

Similarly, while it’s often been said that constrictive pericarditis can be diagnosed based upon a classic trio of hemodynamic findings obtained through heart catheterization – namely, early rapid filling with a left ventricular end-diastolic pressure equal to the right ventricular end-diastolic pressure, a right ventricular end-diastolic pressure greater than one-third of the right ventricular systolic pressure, and a pulmonary artery pressure below 50 mm Hg – these criteria didn’t reliably separate the last 100 patients who came to the catheterization lab at the Mayo Clinic with either constrictive pericarditis or restrictive cardiomyopathy, he continued.

Dr. Nishimura’s approach to the work-up of patients with unexplained right heart failure and a normal ejection begins with the history and physical examination. The history in a patient with constrictive pericarditis is classically one of radiation therapy years earlier for a malignancy, or prior CABG surgery. And the physical exam has to reveal the presence of high neck veins.

“If you don’t see high neck veins due to elevated jugular venous pressure with rapid x and y descents, the patient doesn’t have constrictive pericarditis, no matter what the echocardiogram shows,” Dr. Nishimura asserted.

If those findings are present, however, then on 2-D echocardiography he’s looking for three things that point to constrictive pericarditis: a brisk septal shudder due to rapid filling in early diastole with every heart beat; an early diastolic posterior motion of the intraventricular septum, known as the septal bounce, that occurs as a consequence of the less compliant ventricular walls; and dilation of the inferior vena cava indicative of increased right atrial pressure.

When all three findings are present on 2-D echo, he turns to Doppler echo for hemodynamic information. If Doppler shows a reduction in transmitral driving pressure from the lungs to the heart during inspiration, as the intrathoracic pressure drops but the left ventricular pressure does not, the work-up is done. That patient has constrictive pericarditis and needs to be referred to surgery for pericardiectomy, which will bring rapid improvement.

In roughly one-quarter of patients with constrictive pericarditis, however, that full constellation of 2-D and Doppler echocardiographic findings isn’t present. It then becomes necessary to move on to cardiac catheterization. The first two things to look for in the cath lab are elevated end-equalization of diastolic pressures and low cardiac output.

“If they’re in the cath lab and they’ve got normal filling pressures and a normal cardiac output, they do not have clinically significant constrictive pericarditis, no matter what the echo shows. So those two things are necessary to see, but of course they’re not diagnostic. So we go further,” Dr. Nishimura said.

A patient with constrictive pericarditis will have enhanced ventricular interaction arising from the restraint imposed by a rigid, diseased pericardium. That’s crucial. This increased ventricular interaction is manifest as an increase in the size of the right ventricle during inspiration while the area of the left ventricle is getting smaller.

In contrast, during inspiration and expiration in a patient with restrictive cardiomyopathy, as the right ventricle gets smaller, so does the left ventricle.

“The ratio of the right ventricle to left ventricle area under the curve during inspiration versus expiration gives a very nice distinction between constrictive pericarditis and restrictive cardiomyopathy. Enhanced ventricular interaction is the most sensitive and specific finding for constrictive pericarditis,” according to Dr. Nishimura.

He added that, in addition to constrictive pericarditis and restrictive cardiomyopathy, there is a third and underappreciated cause of right heart failure with a normal ejection fraction: severe tricuspid regurgitation. This abnormality may not be readily apparent upon echocardiography in a patient with a pacemaker lead or automatic implantable cardioverter-defibrillator lead, which can cause acoustic shadowing that results in underestimation of the severity of tricuspid regurgitation. The clue here is the observation of hepatic vein systolic flow reversal, which can only be caused by severe tricuspid regurgitation.

“Think tricuspid regurgitation in patients who have a pacemaker lead or AICD, and also in older women with longstanding atrial fibrillation who dilate their tricuspid annulus and develop more and more tricuspid regurgitation. Take those patients to the cath lab and do a right ventriculogram, which will show tricuspid regurgitation,” Dr. Nishimura advised.

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The plethora of comorbidities typically present in patients with heart failure with preserved ejection fraction is increasingly thought to be a key driver of the cardiac structural remodeling and poor clinical outcomes characteristic of this increasingly common condition.

“The new message is that even though HFpHF [heart failure with preserved ejection fraction] is a problem of the heart involving diastolic filling and structural remodeling of the ventricle, it’s also a problem of factors outside the heart. Outcomes are driven not just by the cardiac abnormalities, but by the comorbidities that are so common in this elderly population,” Dr. Akshay S. Desai said at the annual Cardiovascular Conference at Snowmass.

“The evolving theoretical model is one that emphasizes the role these comorbidities play, not just in remodeling of the heart, but also in microvascular inflammation, with its consequences for inflammatory cell migration, transforming growth factor–beta activation, myocardial fibrosis, oxidative stress, endothelial inflammation, and downstream impairment of cyclic guanosine monophosphate signaling,” explained Dr. Desai of Brigham and Women’s Hospital, Boston.

He credited Dr. Walter J. Paulus of the Institute for Cardiovascular Research at VU University Medical Center, Amsterdam, as being the primary developer of the new paradigm, which veers away from the traditional emphasis upon excessive afterload as the primary driver of diastolic dysfunction.

As elaborated in detail by Dr. Paulus, the noncardiac comorbidities that are so highly prevalent in HFpEF – especially obesity, diabetes, chronic obstructive pulmonary disease, hypertension, chronic kidney disease, and anemia – induce a systemic inflammatory state which promotes diastolic left ventricular stiffness, cardiac hypertrophy, and the development of heart failure. Dr. Paulus has buttressed his theoretical framework with endomyocardial biopsy studies that document abnormal myocyte structure and function (J. Am. Coll. Cardiol. 2013;62:263-71).

Dr. Desai said the fresh perspective provided by Dr. Paulus is most welcome because it is easily tested, and also because it points to new pathways for treatment. New therapeutic targets are needed desperately because of the striking lack of progress to date in treatment of HFpEF. No drug has been convincingly shown effective in reducing the morbidity and mortality of HFpEF, although a secondary analysis of the flawed TOPCAT trial did strongly suggest spironolactone may reduce the risks of mortality and heart failure hospitalizations (Circulation 2015;131:34-42).

Clinical trials that are now planned or underway as a consequence of the new HFpEF paradigm are investigating novel treatment strategies targeting low myocardial nitric oxide bioavailability and endothelial dysfunction. Agents under study include statins, interleukin-1 receptor antagonists, oral nitrates aimed at boosting cellular levels of nitric oxide, the oral soluble guanylate cyclase stimulator riociguat (Adempas), and the phosphodiesterase-5 inhibitor sildenafil.

Also, all eyes are on the 4,300 patient, 37-country, phase III, randomized PARAGON HF study which began last summer. PARAGON is evaluating LCZ696, the combined angiotensin receptor neprilysin inhibitor that scored a smashing success in heart failure with reduced ejection fraction in the landmark PARADIGM-HF study (N. Engl. J. Med. 2014;371:993-1004).

The rising prevalence of diabetes, obesity, and other proinflammatory chronic conditions could help explain the increasing proportion of patients with heart failure who have HFpEF.

“Depending on where you draw the cut point for preserved ejection fraction, you could say half or as many as 60% of patients hospitalized for decompensated heart failure do so in the setting of preserved ejection fraction,” Dr. Desai observed.

It’s noteworthy that the trajectory of decline following hospitalization for heart failure is similar in HFpEF and heart failure with reduced ejection fraction.

While awaiting the outcome of clinical trials of novel treatments, and with so little evidence-based therapy available at this point, physicians should redouble their efforts to aggressively manage hypertension and other comorbidities in an effort to prevent HFpEF or slow its progression. The favorable TOPCAT results in the Western Hemisphere are also worthy of consideration, the cardiologist argued.

Dr. Desai reported serving as a consultant to 5AM Ventures, AtCor Medical, Novartis, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The plethora of comorbidities typically present in patients with heart failure with preserved ejection fraction is increasingly thought to be a key driver of the cardiac structural remodeling and poor clinical outcomes characteristic of this increasingly common condition.

“The new message is that even though HFpHF [heart failure with preserved ejection fraction] is a problem of the heart involving diastolic filling and structural remodeling of the ventricle, it’s also a problem of factors outside the heart. Outcomes are driven not just by the cardiac abnormalities, but by the comorbidities that are so common in this elderly population,” Dr. Akshay S. Desai said at the annual Cardiovascular Conference at Snowmass.

“The evolving theoretical model is one that emphasizes the role these comorbidities play, not just in remodeling of the heart, but also in microvascular inflammation, with its consequences for inflammatory cell migration, transforming growth factor–beta activation, myocardial fibrosis, oxidative stress, endothelial inflammation, and downstream impairment of cyclic guanosine monophosphate signaling,” explained Dr. Desai of Brigham and Women’s Hospital, Boston.

He credited Dr. Walter J. Paulus of the Institute for Cardiovascular Research at VU University Medical Center, Amsterdam, as being the primary developer of the new paradigm, which veers away from the traditional emphasis upon excessive afterload as the primary driver of diastolic dysfunction.

As elaborated in detail by Dr. Paulus, the noncardiac comorbidities that are so highly prevalent in HFpEF – especially obesity, diabetes, chronic obstructive pulmonary disease, hypertension, chronic kidney disease, and anemia – induce a systemic inflammatory state which promotes diastolic left ventricular stiffness, cardiac hypertrophy, and the development of heart failure. Dr. Paulus has buttressed his theoretical framework with endomyocardial biopsy studies that document abnormal myocyte structure and function (J. Am. Coll. Cardiol. 2013;62:263-71).

Dr. Desai said the fresh perspective provided by Dr. Paulus is most welcome because it is easily tested, and also because it points to new pathways for treatment. New therapeutic targets are needed desperately because of the striking lack of progress to date in treatment of HFpEF. No drug has been convincingly shown effective in reducing the morbidity and mortality of HFpEF, although a secondary analysis of the flawed TOPCAT trial did strongly suggest spironolactone may reduce the risks of mortality and heart failure hospitalizations (Circulation 2015;131:34-42).

Clinical trials that are now planned or underway as a consequence of the new HFpEF paradigm are investigating novel treatment strategies targeting low myocardial nitric oxide bioavailability and endothelial dysfunction. Agents under study include statins, interleukin-1 receptor antagonists, oral nitrates aimed at boosting cellular levels of nitric oxide, the oral soluble guanylate cyclase stimulator riociguat (Adempas), and the phosphodiesterase-5 inhibitor sildenafil.

Also, all eyes are on the 4,300 patient, 37-country, phase III, randomized PARAGON HF study which began last summer. PARAGON is evaluating LCZ696, the combined angiotensin receptor neprilysin inhibitor that scored a smashing success in heart failure with reduced ejection fraction in the landmark PARADIGM-HF study (N. Engl. J. Med. 2014;371:993-1004).

The rising prevalence of diabetes, obesity, and other proinflammatory chronic conditions could help explain the increasing proportion of patients with heart failure who have HFpEF.

“Depending on where you draw the cut point for preserved ejection fraction, you could say half or as many as 60% of patients hospitalized for decompensated heart failure do so in the setting of preserved ejection fraction,” Dr. Desai observed.

It’s noteworthy that the trajectory of decline following hospitalization for heart failure is similar in HFpEF and heart failure with reduced ejection fraction.

While awaiting the outcome of clinical trials of novel treatments, and with so little evidence-based therapy available at this point, physicians should redouble their efforts to aggressively manage hypertension and other comorbidities in an effort to prevent HFpEF or slow its progression. The favorable TOPCAT results in the Western Hemisphere are also worthy of consideration, the cardiologist argued.

Dr. Desai reported serving as a consultant to 5AM Ventures, AtCor Medical, Novartis, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The plethora of comorbidities typically present in patients with heart failure with preserved ejection fraction is increasingly thought to be a key driver of the cardiac structural remodeling and poor clinical outcomes characteristic of this increasingly common condition.

“The new message is that even though HFpHF [heart failure with preserved ejection fraction] is a problem of the heart involving diastolic filling and structural remodeling of the ventricle, it’s also a problem of factors outside the heart. Outcomes are driven not just by the cardiac abnormalities, but by the comorbidities that are so common in this elderly population,” Dr. Akshay S. Desai said at the annual Cardiovascular Conference at Snowmass.

“The evolving theoretical model is one that emphasizes the role these comorbidities play, not just in remodeling of the heart, but also in microvascular inflammation, with its consequences for inflammatory cell migration, transforming growth factor–beta activation, myocardial fibrosis, oxidative stress, endothelial inflammation, and downstream impairment of cyclic guanosine monophosphate signaling,” explained Dr. Desai of Brigham and Women’s Hospital, Boston.

He credited Dr. Walter J. Paulus of the Institute for Cardiovascular Research at VU University Medical Center, Amsterdam, as being the primary developer of the new paradigm, which veers away from the traditional emphasis upon excessive afterload as the primary driver of diastolic dysfunction.

As elaborated in detail by Dr. Paulus, the noncardiac comorbidities that are so highly prevalent in HFpEF – especially obesity, diabetes, chronic obstructive pulmonary disease, hypertension, chronic kidney disease, and anemia – induce a systemic inflammatory state which promotes diastolic left ventricular stiffness, cardiac hypertrophy, and the development of heart failure. Dr. Paulus has buttressed his theoretical framework with endomyocardial biopsy studies that document abnormal myocyte structure and function (J. Am. Coll. Cardiol. 2013;62:263-71).

Dr. Desai said the fresh perspective provided by Dr. Paulus is most welcome because it is easily tested, and also because it points to new pathways for treatment. New therapeutic targets are needed desperately because of the striking lack of progress to date in treatment of HFpEF. No drug has been convincingly shown effective in reducing the morbidity and mortality of HFpEF, although a secondary analysis of the flawed TOPCAT trial did strongly suggest spironolactone may reduce the risks of mortality and heart failure hospitalizations (Circulation 2015;131:34-42).

Clinical trials that are now planned or underway as a consequence of the new HFpEF paradigm are investigating novel treatment strategies targeting low myocardial nitric oxide bioavailability and endothelial dysfunction. Agents under study include statins, interleukin-1 receptor antagonists, oral nitrates aimed at boosting cellular levels of nitric oxide, the oral soluble guanylate cyclase stimulator riociguat (Adempas), and the phosphodiesterase-5 inhibitor sildenafil.

Also, all eyes are on the 4,300 patient, 37-country, phase III, randomized PARAGON HF study which began last summer. PARAGON is evaluating LCZ696, the combined angiotensin receptor neprilysin inhibitor that scored a smashing success in heart failure with reduced ejection fraction in the landmark PARADIGM-HF study (N. Engl. J. Med. 2014;371:993-1004).

The rising prevalence of diabetes, obesity, and other proinflammatory chronic conditions could help explain the increasing proportion of patients with heart failure who have HFpEF.

“Depending on where you draw the cut point for preserved ejection fraction, you could say half or as many as 60% of patients hospitalized for decompensated heart failure do so in the setting of preserved ejection fraction,” Dr. Desai observed.

It’s noteworthy that the trajectory of decline following hospitalization for heart failure is similar in HFpEF and heart failure with reduced ejection fraction.

While awaiting the outcome of clinical trials of novel treatments, and with so little evidence-based therapy available at this point, physicians should redouble their efforts to aggressively manage hypertension and other comorbidities in an effort to prevent HFpEF or slow its progression. The favorable TOPCAT results in the Western Hemisphere are also worthy of consideration, the cardiologist argued.

Dr. Desai reported serving as a consultant to 5AM Ventures, AtCor Medical, Novartis, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Early feasibility trials of transcatheter mitral valve replacement in patients with significant functional mitral regurgitation have received Food and Drug Administration approval and are about to commence in the United States.

“This is deja vu all over again. This is TAVR [transcatheter aortic valve replacement] 10 years ago. And we’re about to see the same level of investment and enthusiasm in the mitral space that we saw in TAVR 10 years ago,” Dr. Michael J. Mack predicted at the Annual Cardiovascular Conference at Snowmass.

As a pioneer of TAVR in the United States, he knows very well what that looks like. While serving as president of the Society of Thoracic Surgeons, he forged an epic cross-specialty collaboration with then–ACC President Dr. David R. Holmes Jr. that led to creation of an unprecedented joint STS/ACC TAVR Registry and fostered the concept of the heart team approach.

Dr. Mack said that at present, there are five “very promising” devices for transcatheter mitral valve replacement (TMVR), four with human experience. Three of the five – the Edwards Fortis, Neovasc Tiara, and the Tendyne device – have received FDA approval for early human feasibility trials, to begin imminently.

“Eighteen of these procedures have been done worldwide, all in Europe or Paraguay. This is a new day at the FDA, and the FDA – with a worldwide experience of only 18 – is allowing three early feasibility trials of 15 patients each at three U.S. centers, starting immediately. By the end of the year there will be experience with 45 transcatheter mitral valve replacements in the United States,” observed Dr. Mack, medical director of Baylor Health Care System in Plano, Tex.

All three devices under evaluation will be placed via a transapical approach using a mini-thoracotomy. This has proved to be a much simpler delivery route than the transfemoral approach. The TMVR procedure relies heavily upon 3-D echocardiography and fluoroscopy.

“There’s now a very robust field of mitral valve imaging, just like we’ve seen over the last 10 years for the aortic valve,” Dr. Mack said. “We’re learning a lot about mitral valve anatomy and papillary muscle positioning that we didn’t know before. What we’ve learned from TAVR is all coming over to the mitral space.”

The rationale for TMVR is that the open surgical experience has shown recurrent mitral regurgitation is vastly more common after mitral valve repair than replacement.

Nevertheless, transcatheter mitral valve repair is already here, and its role may grow substantially. The MitraClip device received FDA approval in Fall 2013 for percutaneous repair of severely symptomatic primary degenerative mitral regurgitation in patients who have a reasonable life expectancy but prohibitive surgical risk due to comorbidities. The device is designed to clip the valve leaflets together without surgical suturing. Roughly 1,500 MitraClip procedures have been done to date in the United States, and the initial commercial experience will be presented as a late-breaker at the annual ACC meeting in San Diego in March.

Together with cardiologist Dr. Gregg W. Stone, Dr. Mack is co–principal investigator of the COAPT trial, in which the MitraClip is being studied as a treatment for significant functional or secondary mitral regurgitation, as opposed to the primary degenerative mitral regurgitation for which it’s already indicated. If this major clinical trial yields positive results, the role of the MitraClip will greatly expand.

The COAPT trial is sponsored by Abbott Vascular. Dr. Mack reported receiving research grants from Abbott and Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Early feasibility trials of transcatheter mitral valve replacement in patients with significant functional mitral regurgitation have received Food and Drug Administration approval and are about to commence in the United States.

“This is deja vu all over again. This is TAVR [transcatheter aortic valve replacement] 10 years ago. And we’re about to see the same level of investment and enthusiasm in the mitral space that we saw in TAVR 10 years ago,” Dr. Michael J. Mack predicted at the Annual Cardiovascular Conference at Snowmass.

As a pioneer of TAVR in the United States, he knows very well what that looks like. While serving as president of the Society of Thoracic Surgeons, he forged an epic cross-specialty collaboration with then–ACC President Dr. David R. Holmes Jr. that led to creation of an unprecedented joint STS/ACC TAVR Registry and fostered the concept of the heart team approach.

Dr. Mack said that at present, there are five “very promising” devices for transcatheter mitral valve replacement (TMVR), four with human experience. Three of the five – the Edwards Fortis, Neovasc Tiara, and the Tendyne device – have received FDA approval for early human feasibility trials, to begin imminently.

“Eighteen of these procedures have been done worldwide, all in Europe or Paraguay. This is a new day at the FDA, and the FDA – with a worldwide experience of only 18 – is allowing three early feasibility trials of 15 patients each at three U.S. centers, starting immediately. By the end of the year there will be experience with 45 transcatheter mitral valve replacements in the United States,” observed Dr. Mack, medical director of Baylor Health Care System in Plano, Tex.

All three devices under evaluation will be placed via a transapical approach using a mini-thoracotomy. This has proved to be a much simpler delivery route than the transfemoral approach. The TMVR procedure relies heavily upon 3-D echocardiography and fluoroscopy.

“There’s now a very robust field of mitral valve imaging, just like we’ve seen over the last 10 years for the aortic valve,” Dr. Mack said. “We’re learning a lot about mitral valve anatomy and papillary muscle positioning that we didn’t know before. What we’ve learned from TAVR is all coming over to the mitral space.”

The rationale for TMVR is that the open surgical experience has shown recurrent mitral regurgitation is vastly more common after mitral valve repair than replacement.

Nevertheless, transcatheter mitral valve repair is already here, and its role may grow substantially. The MitraClip device received FDA approval in Fall 2013 for percutaneous repair of severely symptomatic primary degenerative mitral regurgitation in patients who have a reasonable life expectancy but prohibitive surgical risk due to comorbidities. The device is designed to clip the valve leaflets together without surgical suturing. Roughly 1,500 MitraClip procedures have been done to date in the United States, and the initial commercial experience will be presented as a late-breaker at the annual ACC meeting in San Diego in March.

Together with cardiologist Dr. Gregg W. Stone, Dr. Mack is co–principal investigator of the COAPT trial, in which the MitraClip is being studied as a treatment for significant functional or secondary mitral regurgitation, as opposed to the primary degenerative mitral regurgitation for which it’s already indicated. If this major clinical trial yields positive results, the role of the MitraClip will greatly expand.

The COAPT trial is sponsored by Abbott Vascular. Dr. Mack reported receiving research grants from Abbott and Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Early feasibility trials of transcatheter mitral valve replacement in patients with significant functional mitral regurgitation have received Food and Drug Administration approval and are about to commence in the United States.

“This is deja vu all over again. This is TAVR [transcatheter aortic valve replacement] 10 years ago. And we’re about to see the same level of investment and enthusiasm in the mitral space that we saw in TAVR 10 years ago,” Dr. Michael J. Mack predicted at the Annual Cardiovascular Conference at Snowmass.

As a pioneer of TAVR in the United States, he knows very well what that looks like. While serving as president of the Society of Thoracic Surgeons, he forged an epic cross-specialty collaboration with then–ACC President Dr. David R. Holmes Jr. that led to creation of an unprecedented joint STS/ACC TAVR Registry and fostered the concept of the heart team approach.

Dr. Mack said that at present, there are five “very promising” devices for transcatheter mitral valve replacement (TMVR), four with human experience. Three of the five – the Edwards Fortis, Neovasc Tiara, and the Tendyne device – have received FDA approval for early human feasibility trials, to begin imminently.

“Eighteen of these procedures have been done worldwide, all in Europe or Paraguay. This is a new day at the FDA, and the FDA – with a worldwide experience of only 18 – is allowing three early feasibility trials of 15 patients each at three U.S. centers, starting immediately. By the end of the year there will be experience with 45 transcatheter mitral valve replacements in the United States,” observed Dr. Mack, medical director of Baylor Health Care System in Plano, Tex.

All three devices under evaluation will be placed via a transapical approach using a mini-thoracotomy. This has proved to be a much simpler delivery route than the transfemoral approach. The TMVR procedure relies heavily upon 3-D echocardiography and fluoroscopy.

“There’s now a very robust field of mitral valve imaging, just like we’ve seen over the last 10 years for the aortic valve,” Dr. Mack said. “We’re learning a lot about mitral valve anatomy and papillary muscle positioning that we didn’t know before. What we’ve learned from TAVR is all coming over to the mitral space.”

The rationale for TMVR is that the open surgical experience has shown recurrent mitral regurgitation is vastly more common after mitral valve repair than replacement.

Nevertheless, transcatheter mitral valve repair is already here, and its role may grow substantially. The MitraClip device received FDA approval in Fall 2013 for percutaneous repair of severely symptomatic primary degenerative mitral regurgitation in patients who have a reasonable life expectancy but prohibitive surgical risk due to comorbidities. The device is designed to clip the valve leaflets together without surgical suturing. Roughly 1,500 MitraClip procedures have been done to date in the United States, and the initial commercial experience will be presented as a late-breaker at the annual ACC meeting in San Diego in March.

Together with cardiologist Dr. Gregg W. Stone, Dr. Mack is co–principal investigator of the COAPT trial, in which the MitraClip is being studied as a treatment for significant functional or secondary mitral regurgitation, as opposed to the primary degenerative mitral regurgitation for which it’s already indicated. If this major clinical trial yields positive results, the role of the MitraClip will greatly expand.

The COAPT trial is sponsored by Abbott Vascular. Dr. Mack reported receiving research grants from Abbott and Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The ongoing COAPT trial will not only determine the future of the MitraClip device for transcatheter mitral valve repair, it will also answer a key broader question: Does fixing functional mitral regurgitation even provide meaningful clinical benefit?

“This is an extremely important study because we don’t know whether correcting secondary [mitral regurgitation (MR)] does anything to change the prognosis or survival in the disease. The [Food and Drug Administration] gets kudos for insisting on this study. This will be a major trial in which we learn whether interrupting functional MR adds anything to guideline-directed medical therapy or not,” Dr. Michael J. Mack predicted at the Annual Cardiovascular Conference at Snowmass.

The distinction between primary degenerative MR and secondary functional MR is key. In primary MR, the problem is that the valve itself has worn out. Secondary MR is a disease of the left ventricle, not the mitral valve. The source of the valve problem in secondary MR lies in a dilated left ventricle, which causes stretching of the valve annulus and displacement of the papillary muscles. This left ventricular dilation can be caused by either ischemic or nonischemic dilated cardiomyopathy. Regardless, functional MR is a disorder of left ventricular remodeling in which anatomically normal valve leaflets don’t coapt sufficiently.

The MitraClip device is designed for percutaneous repair of MR in patients deemed at unacceptable risk for surgery. The device clips the valve leaflets together without surgical suturing. The MitraClip won FDA approval in fall 2013 for repair of severely symptomatic primary degenerative mitral regurgitation in patients who have a reasonable life expectancy but prohibitive surgical risk due to comorbidities. Roughly 1,500 MitraClip procedures have been done to date in the United States, and the initial commercial experience will be presented as a late-breaker at the annual meeting of the American College of Cardiology in San Diego in March.

Functional MR is a whole different story. The FDA decided that for the MitraClip to gain an additional indication for functional or secondary MR, a randomized controlled trial would be required. Moreover, after considerable debate among valve experts, the FDA decreed that the control group should consist of patients on guideline-directed medical therapy since – much to the surprise of many physicians and surgeons – to date there is actually no persuasive evidence that surgical repair or replacement is effective therapy for functional MR, explained Dr. Mack, former president of the Society of Thoracic Surgeons and medical director at Baylor Health Care System in Plano, Tex.

Dr. Mack and Columbia University cardiologist Dr. Gregg W. Stone serve as co–principal investigators of COAPT, scheduled to include about 420 high-surgical-risk patients with severely symptomatic secondary MR at 75 U.S. sites. Patients will be followed clinically and by transthoracic echocardiography for 5 years, with the primary endpoint being the 2-year rates of survival and freedom from repeat hospitalization for heart failure.

Patients with both ischemic and nonischemic cardiomyopathies are being enrolled. However, their outcomes will be analyzed separately because investigators believe these disorders may not respond in the same way to any interventional therapy.

“I think that nonischemic cardiomyopathy is an idiopathic disease of unknown etiology, and probably multiple etiologies. It’s reasonable to think that in ischemic MR there’s something we can treat and in that way prevent a progressive process from ongoing, and even cause some reverse remodeling. I don’t think we have any clue in nonischemic cardiomyopathies as to what the disease causes are and whether correcting the secondary MR will cause reverse remodeling. So if I were to bet one way or another on which one’s going to respond better to MitraClip therapy, I would say ischemic cardiomyopathy,” the surgeon said.

As to who’s at prohibitive surgical risk and therefore potentially eligible for percutaneous repair, the criteria established for use of the MitraClip for its approved indication also apply to candidates for the COAPT trial. These criteria include an STS mortality score of 8%-10% or more, a porcelain aorta, severe COPD, advanced liver disease, frailty, severe mitral annular calcification, what surgeons call a “hostile chest” due to prior sternectomy or other causes, and/or severe pulmonary hypertension. The determination is to be made jointly by a cardiologist and surgeon functioning within a local heart team.

Enrollment in the COAPT study has been “extremely difficult” because of widespread, albeit misplaced, pro-surgery bias, but the roster should be filled by the end of the year, Dr. Mack said.

He observed that a major disadvantage of the MitraClip is that it does only one thing: clip the leaflets together.

“In surgery, at least for primary MR, we never do one thing. We’ll resect, we’ll put cords in, we’ll do an annuloplasty,” he explained.

In the future – post COAPT – a likely scenario is that the MitraClip will routinely be employed together with a complementary percutaneous posterior mitral annuloplasty procedure, he said. The top candidate, in his view, is the Valtech Cardioband device.

“That’s the one with the most experience and success for transcatheter mitral annuloplasty. It’s done under 3-D transesophageal echocardiographic guidance. Thirty patients have been enrolled in a European feasibility trial, with a device success rate of 88%. Eighty-five percent of those 30 patients are none-to-trace MR at 6 months’ follow-up,” said Dr. Mack.

Dr. Bernard J. Gersh said that he totally agrees with Dr. Mack’s prediction of divergent outcomes in COAPT depending upon whether patients have ischemic or nonischemic dilated cardiomyopathy.

“As you look at the history of surgical procedures, those that are directed to a mechanism are successful, and those that are directed to the consequences of something are not. Idiopathic dilated cardiomyopathy is a totally different disease – it’s dysfunctional cells, we don’t really know why, and there’s very little fibrosis or scar. It’s a completely different mechanism. So I agree: If I had to bet, it’d be that it’s in ischemic MR that the MitraClip is relevant,” said Dr. Gersh, professor of medicine at the Mayo Clinic in Rochester, Minn.

The COAPT trial is sponsored by Abbott Vascular. Dr. Mack reported receiving research grants from Abbott and Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The ongoing COAPT trial will not only determine the future of the MitraClip device for transcatheter mitral valve repair, it will also answer a key broader question: Does fixing functional mitral regurgitation even provide meaningful clinical benefit?

“This is an extremely important study because we don’t know whether correcting secondary [mitral regurgitation (MR)] does anything to change the prognosis or survival in the disease. The [Food and Drug Administration] gets kudos for insisting on this study. This will be a major trial in which we learn whether interrupting functional MR adds anything to guideline-directed medical therapy or not,” Dr. Michael J. Mack predicted at the Annual Cardiovascular Conference at Snowmass.

The distinction between primary degenerative MR and secondary functional MR is key. In primary MR, the problem is that the valve itself has worn out. Secondary MR is a disease of the left ventricle, not the mitral valve. The source of the valve problem in secondary MR lies in a dilated left ventricle, which causes stretching of the valve annulus and displacement of the papillary muscles. This left ventricular dilation can be caused by either ischemic or nonischemic dilated cardiomyopathy. Regardless, functional MR is a disorder of left ventricular remodeling in which anatomically normal valve leaflets don’t coapt sufficiently.

The MitraClip device is designed for percutaneous repair of MR in patients deemed at unacceptable risk for surgery. The device clips the valve leaflets together without surgical suturing. The MitraClip won FDA approval in fall 2013 for repair of severely symptomatic primary degenerative mitral regurgitation in patients who have a reasonable life expectancy but prohibitive surgical risk due to comorbidities. Roughly 1,500 MitraClip procedures have been done to date in the United States, and the initial commercial experience will be presented as a late-breaker at the annual meeting of the American College of Cardiology in San Diego in March.

Functional MR is a whole different story. The FDA decided that for the MitraClip to gain an additional indication for functional or secondary MR, a randomized controlled trial would be required. Moreover, after considerable debate among valve experts, the FDA decreed that the control group should consist of patients on guideline-directed medical therapy since – much to the surprise of many physicians and surgeons – to date there is actually no persuasive evidence that surgical repair or replacement is effective therapy for functional MR, explained Dr. Mack, former president of the Society of Thoracic Surgeons and medical director at Baylor Health Care System in Plano, Tex.

Dr. Mack and Columbia University cardiologist Dr. Gregg W. Stone serve as co–principal investigators of COAPT, scheduled to include about 420 high-surgical-risk patients with severely symptomatic secondary MR at 75 U.S. sites. Patients will be followed clinically and by transthoracic echocardiography for 5 years, with the primary endpoint being the 2-year rates of survival and freedom from repeat hospitalization for heart failure.

Patients with both ischemic and nonischemic cardiomyopathies are being enrolled. However, their outcomes will be analyzed separately because investigators believe these disorders may not respond in the same way to any interventional therapy.

“I think that nonischemic cardiomyopathy is an idiopathic disease of unknown etiology, and probably multiple etiologies. It’s reasonable to think that in ischemic MR there’s something we can treat and in that way prevent a progressive process from ongoing, and even cause some reverse remodeling. I don’t think we have any clue in nonischemic cardiomyopathies as to what the disease causes are and whether correcting the secondary MR will cause reverse remodeling. So if I were to bet one way or another on which one’s going to respond better to MitraClip therapy, I would say ischemic cardiomyopathy,” the surgeon said.

As to who’s at prohibitive surgical risk and therefore potentially eligible for percutaneous repair, the criteria established for use of the MitraClip for its approved indication also apply to candidates for the COAPT trial. These criteria include an STS mortality score of 8%-10% or more, a porcelain aorta, severe COPD, advanced liver disease, frailty, severe mitral annular calcification, what surgeons call a “hostile chest” due to prior sternectomy or other causes, and/or severe pulmonary hypertension. The determination is to be made jointly by a cardiologist and surgeon functioning within a local heart team.

Enrollment in the COAPT study has been “extremely difficult” because of widespread, albeit misplaced, pro-surgery bias, but the roster should be filled by the end of the year, Dr. Mack said.

He observed that a major disadvantage of the MitraClip is that it does only one thing: clip the leaflets together.

“In surgery, at least for primary MR, we never do one thing. We’ll resect, we’ll put cords in, we’ll do an annuloplasty,” he explained.

In the future – post COAPT – a likely scenario is that the MitraClip will routinely be employed together with a complementary percutaneous posterior mitral annuloplasty procedure, he said. The top candidate, in his view, is the Valtech Cardioband device.

“That’s the one with the most experience and success for transcatheter mitral annuloplasty. It’s done under 3-D transesophageal echocardiographic guidance. Thirty patients have been enrolled in a European feasibility trial, with a device success rate of 88%. Eighty-five percent of those 30 patients are none-to-trace MR at 6 months’ follow-up,” said Dr. Mack.

Dr. Bernard J. Gersh said that he totally agrees with Dr. Mack’s prediction of divergent outcomes in COAPT depending upon whether patients have ischemic or nonischemic dilated cardiomyopathy.

“As you look at the history of surgical procedures, those that are directed to a mechanism are successful, and those that are directed to the consequences of something are not. Idiopathic dilated cardiomyopathy is a totally different disease – it’s dysfunctional cells, we don’t really know why, and there’s very little fibrosis or scar. It’s a completely different mechanism. So I agree: If I had to bet, it’d be that it’s in ischemic MR that the MitraClip is relevant,” said Dr. Gersh, professor of medicine at the Mayo Clinic in Rochester, Minn.

The COAPT trial is sponsored by Abbott Vascular. Dr. Mack reported receiving research grants from Abbott and Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The ongoing COAPT trial will not only determine the future of the MitraClip device for transcatheter mitral valve repair, it will also answer a key broader question: Does fixing functional mitral regurgitation even provide meaningful clinical benefit?

“This is an extremely important study because we don’t know whether correcting secondary [mitral regurgitation (MR)] does anything to change the prognosis or survival in the disease. The [Food and Drug Administration] gets kudos for insisting on this study. This will be a major trial in which we learn whether interrupting functional MR adds anything to guideline-directed medical therapy or not,” Dr. Michael J. Mack predicted at the Annual Cardiovascular Conference at Snowmass.

The distinction between primary degenerative MR and secondary functional MR is key. In primary MR, the problem is that the valve itself has worn out. Secondary MR is a disease of the left ventricle, not the mitral valve. The source of the valve problem in secondary MR lies in a dilated left ventricle, which causes stretching of the valve annulus and displacement of the papillary muscles. This left ventricular dilation can be caused by either ischemic or nonischemic dilated cardiomyopathy. Regardless, functional MR is a disorder of left ventricular remodeling in which anatomically normal valve leaflets don’t coapt sufficiently.

The MitraClip device is designed for percutaneous repair of MR in patients deemed at unacceptable risk for surgery. The device clips the valve leaflets together without surgical suturing. The MitraClip won FDA approval in fall 2013 for repair of severely symptomatic primary degenerative mitral regurgitation in patients who have a reasonable life expectancy but prohibitive surgical risk due to comorbidities. Roughly 1,500 MitraClip procedures have been done to date in the United States, and the initial commercial experience will be presented as a late-breaker at the annual meeting of the American College of Cardiology in San Diego in March.

Functional MR is a whole different story. The FDA decided that for the MitraClip to gain an additional indication for functional or secondary MR, a randomized controlled trial would be required. Moreover, after considerable debate among valve experts, the FDA decreed that the control group should consist of patients on guideline-directed medical therapy since – much to the surprise of many physicians and surgeons – to date there is actually no persuasive evidence that surgical repair or replacement is effective therapy for functional MR, explained Dr. Mack, former president of the Society of Thoracic Surgeons and medical director at Baylor Health Care System in Plano, Tex.

Dr. Mack and Columbia University cardiologist Dr. Gregg W. Stone serve as co–principal investigators of COAPT, scheduled to include about 420 high-surgical-risk patients with severely symptomatic secondary MR at 75 U.S. sites. Patients will be followed clinically and by transthoracic echocardiography for 5 years, with the primary endpoint being the 2-year rates of survival and freedom from repeat hospitalization for heart failure.

Patients with both ischemic and nonischemic cardiomyopathies are being enrolled. However, their outcomes will be analyzed separately because investigators believe these disorders may not respond in the same way to any interventional therapy.

“I think that nonischemic cardiomyopathy is an idiopathic disease of unknown etiology, and probably multiple etiologies. It’s reasonable to think that in ischemic MR there’s something we can treat and in that way prevent a progressive process from ongoing, and even cause some reverse remodeling. I don’t think we have any clue in nonischemic cardiomyopathies as to what the disease causes are and whether correcting the secondary MR will cause reverse remodeling. So if I were to bet one way or another on which one’s going to respond better to MitraClip therapy, I would say ischemic cardiomyopathy,” the surgeon said.

As to who’s at prohibitive surgical risk and therefore potentially eligible for percutaneous repair, the criteria established for use of the MitraClip for its approved indication also apply to candidates for the COAPT trial. These criteria include an STS mortality score of 8%-10% or more, a porcelain aorta, severe COPD, advanced liver disease, frailty, severe mitral annular calcification, what surgeons call a “hostile chest” due to prior sternectomy or other causes, and/or severe pulmonary hypertension. The determination is to be made jointly by a cardiologist and surgeon functioning within a local heart team.

Enrollment in the COAPT study has been “extremely difficult” because of widespread, albeit misplaced, pro-surgery bias, but the roster should be filled by the end of the year, Dr. Mack said.

He observed that a major disadvantage of the MitraClip is that it does only one thing: clip the leaflets together.

“In surgery, at least for primary MR, we never do one thing. We’ll resect, we’ll put cords in, we’ll do an annuloplasty,” he explained.

In the future – post COAPT – a likely scenario is that the MitraClip will routinely be employed together with a complementary percutaneous posterior mitral annuloplasty procedure, he said. The top candidate, in his view, is the Valtech Cardioband device.

“That’s the one with the most experience and success for transcatheter mitral annuloplasty. It’s done under 3-D transesophageal echocardiographic guidance. Thirty patients have been enrolled in a European feasibility trial, with a device success rate of 88%. Eighty-five percent of those 30 patients are none-to-trace MR at 6 months’ follow-up,” said Dr. Mack.

Dr. Bernard J. Gersh said that he totally agrees with Dr. Mack’s prediction of divergent outcomes in COAPT depending upon whether patients have ischemic or nonischemic dilated cardiomyopathy.

“As you look at the history of surgical procedures, those that are directed to a mechanism are successful, and those that are directed to the consequences of something are not. Idiopathic dilated cardiomyopathy is a totally different disease – it’s dysfunctional cells, we don’t really know why, and there’s very little fibrosis or scar. It’s a completely different mechanism. So I agree: If I had to bet, it’d be that it’s in ischemic MR that the MitraClip is relevant,” said Dr. Gersh, professor of medicine at the Mayo Clinic in Rochester, Minn.

The COAPT trial is sponsored by Abbott Vascular. Dr. Mack reported receiving research grants from Abbott and Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Reports of the demise of catheter-based renal denervation therapy for resistant hypertension in light of the disappointing SYMPLICITY HTN-3 trial results are greatly exaggerated, according to Dr. Bernard J. Gersh.

“I think what we can say about renal denervation is that the initial enthusiasm has been tempered and the number of unanswered questions is not decreasing. But the concept, I assure you, still maintains its promise,” the cardiologist said at the annual Cardiovascular Conference at Snowmass.

Expectations for SYMPLICITY HTN-3 were sky high in the cardiology and business worlds on the basis of the prior unblinded SYMPLICITY HTN-1 and -2 studies showing renal denervation (RDN) achieved spectacular reductions in systolic blood pressure of 25-30 mm Hg in patients with multidrug-resistant hypertension. As the chair of the SYMPLICITY HTN-3 data safety monitoring board, he knew the outcome prior to release of the results, and he was struck that during that period the talk at cardiology conferences was only of next-generation RDN catheters and expanded indications, such as heart failure and even metabolic syndrome. Absolutely no one seemed to entertain the possibility that the results wouldn’t be positive.

So the general reaction to the SYMPLICITY HTN-3 results was profound, crushing disappointment. The trial, which was the first blinded, controlled study of RDN, showed significant reduction in blood pressure at 6 months in the RDN recipients, but a similar reduction in medically managed controls who underwent a sham RDN procedure, making for a neutral study outcome (N. Engl. J. Med. 2014;370:1393-59).

Yet the physiologic basis remains strong for RDN as a treatment for hypertension, heart failure, and perhaps other cardiovascular disorders in which sympathetic nervous system activation plays a crucial role, according to Dr. Gersh, who chaired the data safety monitoring board for SYMPLICITY HTN-3 and is a professor of medicine at the Mayo Clinic in Rochester, Minn.

He cited a recommended review written by a pioneer in the field, Dr. Murray Esler of Australia, who observed that increased renal sympathetic nervous system activity increases the secretion rate of renin, reduces renal blood flow, and boosts renal tubular sodium reabsorption while reducing urinary sodium excretion, all actions that contribute to hypertension (Exp. Physiol. 2011;96:611-22).

Dr. Gersh ticked off many potential explanations for the neutral outcome in SYMPLICITY HTN-3, including the placebo effect; regression to the mean; operator inexperience; limitations of the current technology; and the likelihood that a fair number of study participants didn’t have true treatment-resistant hypertension, but were merely resistant to taking their medication until they entered a structured, supervised randomized trial setting. The power of a placebo procedure is not to be underestimated, the cardiologist emphasized. He cited a striking illustration from another field of medicine, in which a recent meta-analysis of 137 controlled studies in more than 33,000 patients with knee osteoarthritis showed that intra-articular placebo injections outperformed oral naproxen, celecoxib, and placebo in terms of pain relief (Ann. Intern. Med. 2015;162:46-54).

Regression to the mean definitely occurred in SYMPLICITY HTN-3, as evidenced by the fact that reductions in office systolic blood pressure (SBP) averaged 25.7 and 19.7 mm Hg, respectively, in RDN recipients and controls with a baseline greater than 184 mm Hg, compared with 13.8 and 9.8 mm Hg in those with a lower baseline SBP, of 170-184 mm Hg, Dr. Gersh continued.

Operator inexperience was likely a factor in the study outcomes: Nearly one-third of the operators dad done just one procedure. And while the study protocol called for four to six ablations per side, a recent secondary analysis of SYMPLICITY HTN-3 showed that the greater the number of ablations, the greater the drop in SBP. Patients who received at least seven ablations per side averaged a nearly threefold larger blood pressure reduction at 6 months, compared with those who got five or six per side (Eur. Heart J. 2015;36:219-27).

Some 39% of study participants had a medication change because of side effects during the 6-month trial. This confounds attempts to assess the true impact of RDN. To answer this question, the Food and Drug Administration recently granted Boston Scientific approval to test RDN in a sham-controlled trial in patients with mild to moderate hypertension after a 4-week medication washout period. The 6-month trial is due to start shortly. This is an important study because it will demonstrate whether RDN in its present form actually works.

“Clearly, what we’ve learned in SYMPLICITY HTN-3 is ‘resistant’ hypertension is amenable to expert pharmacologic control. This raises an interesting question: If renal nerve denervation works, could we offer it as an alternative to taking two or three drugs for the next 10 or 20 years? That might be, in certain patient populations, a very attractive option. That’s why we’ve got to show whether this procedure works well,” according to Dr. Gersh.

Now that SYMPLICITY HTN-3 has provided a reality check, the necessary next steps include improving the technology. Current levels of achieved RDN using only proximal ablation are suboptimal. What’s needed are higher-energy, multipolar electrodes that deliver energy both proximally and distally; such equipment is well along in development.

A thornier limitation involves the lack of a method for immediate testing of the completeness of an RDN procedure in a given patient. Unlike in coronary stent placement, where an interventional cardiologist can immediately see angiographically whether the device is properly seated, RDN operators have no way to tell intraprocedurally whether effective RDN has been achieved. Two methods now under investigation are intra-arterial adenosine and urinary biomarkers of nerve degradation.

The pathophysiology of hypertension is variable, so efforts are underway to identify patient subsets in which sympathetic nervous system overactivity is a primary underlying mechanism and RDN should have its greatest impact.

“I think renal denervation is still worthy of investigation, particularly in patients with resistant hypertension and perhaps other disease states characterized by sympathetic overactivity, such as heart failure,” Dr. Gersh concluded. “How do I think it’s going to all turn out? I just don’t know. We’ll see. We need the trials. I don’t think we should close the book on this very exciting technique. I simply don’t know what the trials are going to show.”

SYMPLICITY HTN-3 was funded by Medtronic. Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for trials sponsored by Baxter, Medtronic, and Teva Pharmaceuticals.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Reports of the demise of catheter-based renal denervation therapy for resistant hypertension in light of the disappointing SYMPLICITY HTN-3 trial results are greatly exaggerated, according to Dr. Bernard J. Gersh.

“I think what we can say about renal denervation is that the initial enthusiasm has been tempered and the number of unanswered questions is not decreasing. But the concept, I assure you, still maintains its promise,” the cardiologist said at the annual Cardiovascular Conference at Snowmass.

Expectations for SYMPLICITY HTN-3 were sky high in the cardiology and business worlds on the basis of the prior unblinded SYMPLICITY HTN-1 and -2 studies showing renal denervation (RDN) achieved spectacular reductions in systolic blood pressure of 25-30 mm Hg in patients with multidrug-resistant hypertension. As the chair of the SYMPLICITY HTN-3 data safety monitoring board, he knew the outcome prior to release of the results, and he was struck that during that period the talk at cardiology conferences was only of next-generation RDN catheters and expanded indications, such as heart failure and even metabolic syndrome. Absolutely no one seemed to entertain the possibility that the results wouldn’t be positive.

So the general reaction to the SYMPLICITY HTN-3 results was profound, crushing disappointment. The trial, which was the first blinded, controlled study of RDN, showed significant reduction in blood pressure at 6 months in the RDN recipients, but a similar reduction in medically managed controls who underwent a sham RDN procedure, making for a neutral study outcome (N. Engl. J. Med. 2014;370:1393-59).

Yet the physiologic basis remains strong for RDN as a treatment for hypertension, heart failure, and perhaps other cardiovascular disorders in which sympathetic nervous system activation plays a crucial role, according to Dr. Gersh, who chaired the data safety monitoring board for SYMPLICITY HTN-3 and is a professor of medicine at the Mayo Clinic in Rochester, Minn.

He cited a recommended review written by a pioneer in the field, Dr. Murray Esler of Australia, who observed that increased renal sympathetic nervous system activity increases the secretion rate of renin, reduces renal blood flow, and boosts renal tubular sodium reabsorption while reducing urinary sodium excretion, all actions that contribute to hypertension (Exp. Physiol. 2011;96:611-22).

Dr. Gersh ticked off many potential explanations for the neutral outcome in SYMPLICITY HTN-3, including the placebo effect; regression to the mean; operator inexperience; limitations of the current technology; and the likelihood that a fair number of study participants didn’t have true treatment-resistant hypertension, but were merely resistant to taking their medication until they entered a structured, supervised randomized trial setting. The power of a placebo procedure is not to be underestimated, the cardiologist emphasized. He cited a striking illustration from another field of medicine, in which a recent meta-analysis of 137 controlled studies in more than 33,000 patients with knee osteoarthritis showed that intra-articular placebo injections outperformed oral naproxen, celecoxib, and placebo in terms of pain relief (Ann. Intern. Med. 2015;162:46-54).

Regression to the mean definitely occurred in SYMPLICITY HTN-3, as evidenced by the fact that reductions in office systolic blood pressure (SBP) averaged 25.7 and 19.7 mm Hg, respectively, in RDN recipients and controls with a baseline greater than 184 mm Hg, compared with 13.8 and 9.8 mm Hg in those with a lower baseline SBP, of 170-184 mm Hg, Dr. Gersh continued.

Operator inexperience was likely a factor in the study outcomes: Nearly one-third of the operators dad done just one procedure. And while the study protocol called for four to six ablations per side, a recent secondary analysis of SYMPLICITY HTN-3 showed that the greater the number of ablations, the greater the drop in SBP. Patients who received at least seven ablations per side averaged a nearly threefold larger blood pressure reduction at 6 months, compared with those who got five or six per side (Eur. Heart J. 2015;36:219-27).

Some 39% of study participants had a medication change because of side effects during the 6-month trial. This confounds attempts to assess the true impact of RDN. To answer this question, the Food and Drug Administration recently granted Boston Scientific approval to test RDN in a sham-controlled trial in patients with mild to moderate hypertension after a 4-week medication washout period. The 6-month trial is due to start shortly. This is an important study because it will demonstrate whether RDN in its present form actually works.

“Clearly, what we’ve learned in SYMPLICITY HTN-3 is ‘resistant’ hypertension is amenable to expert pharmacologic control. This raises an interesting question: If renal nerve denervation works, could we offer it as an alternative to taking two or three drugs for the next 10 or 20 years? That might be, in certain patient populations, a very attractive option. That’s why we’ve got to show whether this procedure works well,” according to Dr. Gersh.

Now that SYMPLICITY HTN-3 has provided a reality check, the necessary next steps include improving the technology. Current levels of achieved RDN using only proximal ablation are suboptimal. What’s needed are higher-energy, multipolar electrodes that deliver energy both proximally and distally; such equipment is well along in development.

A thornier limitation involves the lack of a method for immediate testing of the completeness of an RDN procedure in a given patient. Unlike in coronary stent placement, where an interventional cardiologist can immediately see angiographically whether the device is properly seated, RDN operators have no way to tell intraprocedurally whether effective RDN has been achieved. Two methods now under investigation are intra-arterial adenosine and urinary biomarkers of nerve degradation.

The pathophysiology of hypertension is variable, so efforts are underway to identify patient subsets in which sympathetic nervous system overactivity is a primary underlying mechanism and RDN should have its greatest impact.

“I think renal denervation is still worthy of investigation, particularly in patients with resistant hypertension and perhaps other disease states characterized by sympathetic overactivity, such as heart failure,” Dr. Gersh concluded. “How do I think it’s going to all turn out? I just don’t know. We’ll see. We need the trials. I don’t think we should close the book on this very exciting technique. I simply don’t know what the trials are going to show.”

SYMPLICITY HTN-3 was funded by Medtronic. Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for trials sponsored by Baxter, Medtronic, and Teva Pharmaceuticals.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Reports of the demise of catheter-based renal denervation therapy for resistant hypertension in light of the disappointing SYMPLICITY HTN-3 trial results are greatly exaggerated, according to Dr. Bernard J. Gersh.

“I think what we can say about renal denervation is that the initial enthusiasm has been tempered and the number of unanswered questions is not decreasing. But the concept, I assure you, still maintains its promise,” the cardiologist said at the annual Cardiovascular Conference at Snowmass.

Expectations for SYMPLICITY HTN-3 were sky high in the cardiology and business worlds on the basis of the prior unblinded SYMPLICITY HTN-1 and -2 studies showing renal denervation (RDN) achieved spectacular reductions in systolic blood pressure of 25-30 mm Hg in patients with multidrug-resistant hypertension. As the chair of the SYMPLICITY HTN-3 data safety monitoring board, he knew the outcome prior to release of the results, and he was struck that during that period the talk at cardiology conferences was only of next-generation RDN catheters and expanded indications, such as heart failure and even metabolic syndrome. Absolutely no one seemed to entertain the possibility that the results wouldn’t be positive.

So the general reaction to the SYMPLICITY HTN-3 results was profound, crushing disappointment. The trial, which was the first blinded, controlled study of RDN, showed significant reduction in blood pressure at 6 months in the RDN recipients, but a similar reduction in medically managed controls who underwent a sham RDN procedure, making for a neutral study outcome (N. Engl. J. Med. 2014;370:1393-59).

Yet the physiologic basis remains strong for RDN as a treatment for hypertension, heart failure, and perhaps other cardiovascular disorders in which sympathetic nervous system activation plays a crucial role, according to Dr. Gersh, who chaired the data safety monitoring board for SYMPLICITY HTN-3 and is a professor of medicine at the Mayo Clinic in Rochester, Minn.

He cited a recommended review written by a pioneer in the field, Dr. Murray Esler of Australia, who observed that increased renal sympathetic nervous system activity increases the secretion rate of renin, reduces renal blood flow, and boosts renal tubular sodium reabsorption while reducing urinary sodium excretion, all actions that contribute to hypertension (Exp. Physiol. 2011;96:611-22).

Dr. Gersh ticked off many potential explanations for the neutral outcome in SYMPLICITY HTN-3, including the placebo effect; regression to the mean; operator inexperience; limitations of the current technology; and the likelihood that a fair number of study participants didn’t have true treatment-resistant hypertension, but were merely resistant to taking their medication until they entered a structured, supervised randomized trial setting. The power of a placebo procedure is not to be underestimated, the cardiologist emphasized. He cited a striking illustration from another field of medicine, in which a recent meta-analysis of 137 controlled studies in more than 33,000 patients with knee osteoarthritis showed that intra-articular placebo injections outperformed oral naproxen, celecoxib, and placebo in terms of pain relief (Ann. Intern. Med. 2015;162:46-54).

Regression to the mean definitely occurred in SYMPLICITY HTN-3, as evidenced by the fact that reductions in office systolic blood pressure (SBP) averaged 25.7 and 19.7 mm Hg, respectively, in RDN recipients and controls with a baseline greater than 184 mm Hg, compared with 13.8 and 9.8 mm Hg in those with a lower baseline SBP, of 170-184 mm Hg, Dr. Gersh continued.

Operator inexperience was likely a factor in the study outcomes: Nearly one-third of the operators dad done just one procedure. And while the study protocol called for four to six ablations per side, a recent secondary analysis of SYMPLICITY HTN-3 showed that the greater the number of ablations, the greater the drop in SBP. Patients who received at least seven ablations per side averaged a nearly threefold larger blood pressure reduction at 6 months, compared with those who got five or six per side (Eur. Heart J. 2015;36:219-27).

Some 39% of study participants had a medication change because of side effects during the 6-month trial. This confounds attempts to assess the true impact of RDN. To answer this question, the Food and Drug Administration recently granted Boston Scientific approval to test RDN in a sham-controlled trial in patients with mild to moderate hypertension after a 4-week medication washout period. The 6-month trial is due to start shortly. This is an important study because it will demonstrate whether RDN in its present form actually works.

“Clearly, what we’ve learned in SYMPLICITY HTN-3 is ‘resistant’ hypertension is amenable to expert pharmacologic control. This raises an interesting question: If renal nerve denervation works, could we offer it as an alternative to taking two or three drugs for the next 10 or 20 years? That might be, in certain patient populations, a very attractive option. That’s why we’ve got to show whether this procedure works well,” according to Dr. Gersh.

Now that SYMPLICITY HTN-3 has provided a reality check, the necessary next steps include improving the technology. Current levels of achieved RDN using only proximal ablation are suboptimal. What’s needed are higher-energy, multipolar electrodes that deliver energy both proximally and distally; such equipment is well along in development.

A thornier limitation involves the lack of a method for immediate testing of the completeness of an RDN procedure in a given patient. Unlike in coronary stent placement, where an interventional cardiologist can immediately see angiographically whether the device is properly seated, RDN operators have no way to tell intraprocedurally whether effective RDN has been achieved. Two methods now under investigation are intra-arterial adenosine and urinary biomarkers of nerve degradation.

The pathophysiology of hypertension is variable, so efforts are underway to identify patient subsets in which sympathetic nervous system overactivity is a primary underlying mechanism and RDN should have its greatest impact.

“I think renal denervation is still worthy of investigation, particularly in patients with resistant hypertension and perhaps other disease states characterized by sympathetic overactivity, such as heart failure,” Dr. Gersh concluded. “How do I think it’s going to all turn out? I just don’t know. We’ll see. We need the trials. I don’t think we should close the book on this very exciting technique. I simply don’t know what the trials are going to show.”

SYMPLICITY HTN-3 was funded by Medtronic. Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for trials sponsored by Baxter, Medtronic, and Teva Pharmaceuticals.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – In a major reversal of longstanding opinion, thought leaders in cardiothoracic surgery now increasingly favor mitral valve replacement over repair in patients with severe ischemic mitral regurgitation.

The overwhelming preference among both surgeons and cardiologists has been for mitral valve repair, but recent randomized trial evidence shows that mitral valve replacement provides a more durable correction with no increase in adverse events. That’s persuaded many surgical leaders to move towards replacement until improved repair strategies can be developed, Dr. Vinod H. Thourani said at the Annual Cardiovascular Conference at Snowmass.

“When I do a replacement in a patient, the cardiologist will call me and ask why. He’ll say, ‘I was hoping you were going to do a repair.’ Now we have to completely change our mentality about this,” said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University in Atlanta.

That need for a mind-shift goes for cardiothoracic surgeons as well as cardiologists, he added, pointing to an analysis of the Society of Thoracic Surgeons adult cardiac surgery database for 2008-2012 showing roughly a 65%-35% preference for repair over replacement.

The evidence favoring mitral valve replacement is so new it didn’t make it into the deliberations that generated the freshly minted 2014 ACC/AHA guidelines on valvular heart disease management (J. Am. Coll. Cardiol. 2014;63:e57-185), which state that “there is no conclusive evidence for superiority of repair or replacement” in severe ischemic mitral regurgitation (MR). That statement is no longer true, in Dr. Thourani’s view.

He highlighted a multicenter randomized trial conducted by the Cardiothoracic Surgical Trials Network (CSTN) in which 251 patients with severe ischemic mitral regurgitation were randomized to repair or replacement. The primary endpoint – change in left ventricular end-systolic volume index indicative of reversal of ventricular remodeling – improved similarly in both groups. Nor did the two treatment groups differ significantly in 30-day and 12-month mortality or rates of stroke, heart failure, bleeding, infection, and other major adverse events. The eye opener was that 32.6% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2.3% in the replacement group (N. Engl. J. Med. 2014;370:23-32).

“This study was done at a group of high-functioning academic centers where surgeons are supposed to know how to do repair and do replacement, yet one-third of our patients have come back with moderate to severe MR after repair. This has opened up a lot of discussion among surgeons as to what we should be doing,” noted Dr. Thourani, who participated in the trial.

One-year mortality was 14.2% in the repair group and a statistically similar 17.6% in the valve-replacement group, but Dr. Thourani anticipates a steeper mortality rise ahead for the repair group. “It’ll be interesting to see where these patients living with recurrent MR will be at the 2- and 5-year marks,” he said.

In a subsequent analysis, the CSTN investigators examined whether baseline clinical and echocardiographic characteristics in patients randomized to repair could identify a subgroup at high risk for recurrent moderate-to-severe mitral regurgitation or death within 2 years post surgery. They identified a predictive model that shows promise, with a favorable area under the receiver operating characteristic curve of 0.82.

The model is based on 10 factors: age; gender; race; body mass index; New York Heart Association class; effective regurgitant orifice area; basal aneurysm/dyskinesia; and history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias (J. Thorac. Cardiovasc. Surg. 2014 Nov 6. pii: S0022-5223(14)01772-3).

Of these 10 variables, the standout predictor was basal aneurysm/dyskinesia. “If you repair those patients, they have a really high likelihood of having worse outcomes,” according to Dr. Thourani.

This analysis of the CSTN repair subgroup shed new light on the MR-recurrence phenomenon. Roughly 30% of patients had recurrent moderate or severe MR at 1 month after surgery. By 24 months, that figure had climbed to 46%. There was little progression from moderate to severe MR over time, but MR recurrence was a dynamic phenomenon: Roughly 10% of affected patients experienced reversal of recurrent MR at various time points.

The randomized CSTN findings showing better results with mitral valve replacement were supported by the results of the Italian Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR). This was a multicenter observational study of 1,006 patients with ischemic MR, 30% of whom underwent valve replacement while 70% had a repair. In a propensity-matched multivariate logistic regression analysis, mitral valve repair was associated with a 2.84-fold increased risk of reoperation within 8 years (J. Thorac. Cardiovasc. Surg. 2013;145:128-39).

Although mitral annuloplasty remains the current standard of care for repair of severe ischemic MR in 2015, “we’re realizing this isn’t necessarily the right thing to do” because of that high recurrent MR rate, Dr. Thourani said. There is a growing understanding that a subannular component is required to achieve a truly successful repair. A variety of promising subannular approaches are being developed. He is particularly enthusiastic about his own group’s work involving creation of a papillary muscle sling to achieve papillary approximation – the results have been encouraging in roughly 40 treated sheep and pigs. Human studies are coming.

Ischemic MR develops secondary to an acute MI, which imposes volume overload on the left ventricle, with increasing wall stress, left ventricular remodeling and heart failure, papillary muscle disarray, annular dilation, and MR. The incidence of heart failure within 5 years is threefold higher if an MI occurs with ischemic MR than without it, the surgeon observed.

The CSTN studies were sponsored by the National Institutes of Health and the Canadian Institutes of Health. Dr. Thourani reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott, Boston Scientific, Medtronic, and Sorin.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – In a major reversal of longstanding opinion, thought leaders in cardiothoracic surgery now increasingly favor mitral valve replacement over repair in patients with severe ischemic mitral regurgitation.

The overwhelming preference among both surgeons and cardiologists has been for mitral valve repair, but recent randomized trial evidence shows that mitral valve replacement provides a more durable correction with no increase in adverse events. That’s persuaded many surgical leaders to move towards replacement until improved repair strategies can be developed, Dr. Vinod H. Thourani said at the Annual Cardiovascular Conference at Snowmass.

“When I do a replacement in a patient, the cardiologist will call me and ask why. He’ll say, ‘I was hoping you were going to do a repair.’ Now we have to completely change our mentality about this,” said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University in Atlanta.

That need for a mind-shift goes for cardiothoracic surgeons as well as cardiologists, he added, pointing to an analysis of the Society of Thoracic Surgeons adult cardiac surgery database for 2008-2012 showing roughly a 65%-35% preference for repair over replacement.

The evidence favoring mitral valve replacement is so new it didn’t make it into the deliberations that generated the freshly minted 2014 ACC/AHA guidelines on valvular heart disease management (J. Am. Coll. Cardiol. 2014;63:e57-185), which state that “there is no conclusive evidence for superiority of repair or replacement” in severe ischemic mitral regurgitation (MR). That statement is no longer true, in Dr. Thourani’s view.

He highlighted a multicenter randomized trial conducted by the Cardiothoracic Surgical Trials Network (CSTN) in which 251 patients with severe ischemic mitral regurgitation were randomized to repair or replacement. The primary endpoint – change in left ventricular end-systolic volume index indicative of reversal of ventricular remodeling – improved similarly in both groups. Nor did the two treatment groups differ significantly in 30-day and 12-month mortality or rates of stroke, heart failure, bleeding, infection, and other major adverse events. The eye opener was that 32.6% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2.3% in the replacement group (N. Engl. J. Med. 2014;370:23-32).

“This study was done at a group of high-functioning academic centers where surgeons are supposed to know how to do repair and do replacement, yet one-third of our patients have come back with moderate to severe MR after repair. This has opened up a lot of discussion among surgeons as to what we should be doing,” noted Dr. Thourani, who participated in the trial.

One-year mortality was 14.2% in the repair group and a statistically similar 17.6% in the valve-replacement group, but Dr. Thourani anticipates a steeper mortality rise ahead for the repair group. “It’ll be interesting to see where these patients living with recurrent MR will be at the 2- and 5-year marks,” he said.

In a subsequent analysis, the CSTN investigators examined whether baseline clinical and echocardiographic characteristics in patients randomized to repair could identify a subgroup at high risk for recurrent moderate-to-severe mitral regurgitation or death within 2 years post surgery. They identified a predictive model that shows promise, with a favorable area under the receiver operating characteristic curve of 0.82.

The model is based on 10 factors: age; gender; race; body mass index; New York Heart Association class; effective regurgitant orifice area; basal aneurysm/dyskinesia; and history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias (J. Thorac. Cardiovasc. Surg. 2014 Nov 6. pii: S0022-5223(14)01772-3).

Of these 10 variables, the standout predictor was basal aneurysm/dyskinesia. “If you repair those patients, they have a really high likelihood of having worse outcomes,” according to Dr. Thourani.

This analysis of the CSTN repair subgroup shed new light on the MR-recurrence phenomenon. Roughly 30% of patients had recurrent moderate or severe MR at 1 month after surgery. By 24 months, that figure had climbed to 46%. There was little progression from moderate to severe MR over time, but MR recurrence was a dynamic phenomenon: Roughly 10% of affected patients experienced reversal of recurrent MR at various time points.

The randomized CSTN findings showing better results with mitral valve replacement were supported by the results of the Italian Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR). This was a multicenter observational study of 1,006 patients with ischemic MR, 30% of whom underwent valve replacement while 70% had a repair. In a propensity-matched multivariate logistic regression analysis, mitral valve repair was associated with a 2.84-fold increased risk of reoperation within 8 years (J. Thorac. Cardiovasc. Surg. 2013;145:128-39).

Although mitral annuloplasty remains the current standard of care for repair of severe ischemic MR in 2015, “we’re realizing this isn’t necessarily the right thing to do” because of that high recurrent MR rate, Dr. Thourani said. There is a growing understanding that a subannular component is required to achieve a truly successful repair. A variety of promising subannular approaches are being developed. He is particularly enthusiastic about his own group’s work involving creation of a papillary muscle sling to achieve papillary approximation – the results have been encouraging in roughly 40 treated sheep and pigs. Human studies are coming.

Ischemic MR develops secondary to an acute MI, which imposes volume overload on the left ventricle, with increasing wall stress, left ventricular remodeling and heart failure, papillary muscle disarray, annular dilation, and MR. The incidence of heart failure within 5 years is threefold higher if an MI occurs with ischemic MR than without it, the surgeon observed.

The CSTN studies were sponsored by the National Institutes of Health and the Canadian Institutes of Health. Dr. Thourani reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott, Boston Scientific, Medtronic, and Sorin.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – In a major reversal of longstanding opinion, thought leaders in cardiothoracic surgery now increasingly favor mitral valve replacement over repair in patients with severe ischemic mitral regurgitation.

The overwhelming preference among both surgeons and cardiologists has been for mitral valve repair, but recent randomized trial evidence shows that mitral valve replacement provides a more durable correction with no increase in adverse events. That’s persuaded many surgical leaders to move towards replacement until improved repair strategies can be developed, Dr. Vinod H. Thourani said at the Annual Cardiovascular Conference at Snowmass.

“When I do a replacement in a patient, the cardiologist will call me and ask why. He’ll say, ‘I was hoping you were going to do a repair.’ Now we have to completely change our mentality about this,” said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University in Atlanta.

That need for a mind-shift goes for cardiothoracic surgeons as well as cardiologists, he added, pointing to an analysis of the Society of Thoracic Surgeons adult cardiac surgery database for 2008-2012 showing roughly a 65%-35% preference for repair over replacement.

The evidence favoring mitral valve replacement is so new it didn’t make it into the deliberations that generated the freshly minted 2014 ACC/AHA guidelines on valvular heart disease management (J. Am. Coll. Cardiol. 2014;63:e57-185), which state that “there is no conclusive evidence for superiority of repair or replacement” in severe ischemic mitral regurgitation (MR). That statement is no longer true, in Dr. Thourani’s view.

He highlighted a multicenter randomized trial conducted by the Cardiothoracic Surgical Trials Network (CSTN) in which 251 patients with severe ischemic mitral regurgitation were randomized to repair or replacement. The primary endpoint – change in left ventricular end-systolic volume index indicative of reversal of ventricular remodeling – improved similarly in both groups. Nor did the two treatment groups differ significantly in 30-day and 12-month mortality or rates of stroke, heart failure, bleeding, infection, and other major adverse events. The eye opener was that 32.6% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2.3% in the replacement group (N. Engl. J. Med. 2014;370:23-32).

“This study was done at a group of high-functioning academic centers where surgeons are supposed to know how to do repair and do replacement, yet one-third of our patients have come back with moderate to severe MR after repair. This has opened up a lot of discussion among surgeons as to what we should be doing,” noted Dr. Thourani, who participated in the trial.

One-year mortality was 14.2% in the repair group and a statistically similar 17.6% in the valve-replacement group, but Dr. Thourani anticipates a steeper mortality rise ahead for the repair group. “It’ll be interesting to see where these patients living with recurrent MR will be at the 2- and 5-year marks,” he said.

In a subsequent analysis, the CSTN investigators examined whether baseline clinical and echocardiographic characteristics in patients randomized to repair could identify a subgroup at high risk for recurrent moderate-to-severe mitral regurgitation or death within 2 years post surgery. They identified a predictive model that shows promise, with a favorable area under the receiver operating characteristic curve of 0.82.

The model is based on 10 factors: age; gender; race; body mass index; New York Heart Association class; effective regurgitant orifice area; basal aneurysm/dyskinesia; and history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias (J. Thorac. Cardiovasc. Surg. 2014 Nov 6. pii: S0022-5223(14)01772-3).

Of these 10 variables, the standout predictor was basal aneurysm/dyskinesia. “If you repair those patients, they have a really high likelihood of having worse outcomes,” according to Dr. Thourani.

This analysis of the CSTN repair subgroup shed new light on the MR-recurrence phenomenon. Roughly 30% of patients had recurrent moderate or severe MR at 1 month after surgery. By 24 months, that figure had climbed to 46%. There was little progression from moderate to severe MR over time, but MR recurrence was a dynamic phenomenon: Roughly 10% of affected patients experienced reversal of recurrent MR at various time points.

The randomized CSTN findings showing better results with mitral valve replacement were supported by the results of the Italian Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR). This was a multicenter observational study of 1,006 patients with ischemic MR, 30% of whom underwent valve replacement while 70% had a repair. In a propensity-matched multivariate logistic regression analysis, mitral valve repair was associated with a 2.84-fold increased risk of reoperation within 8 years (J. Thorac. Cardiovasc. Surg. 2013;145:128-39).

Although mitral annuloplasty remains the current standard of care for repair of severe ischemic MR in 2015, “we’re realizing this isn’t necessarily the right thing to do” because of that high recurrent MR rate, Dr. Thourani said. There is a growing understanding that a subannular component is required to achieve a truly successful repair. A variety of promising subannular approaches are being developed. He is particularly enthusiastic about his own group’s work involving creation of a papillary muscle sling to achieve papillary approximation – the results have been encouraging in roughly 40 treated sheep and pigs. Human studies are coming.

Ischemic MR develops secondary to an acute MI, which imposes volume overload on the left ventricle, with increasing wall stress, left ventricular remodeling and heart failure, papillary muscle disarray, annular dilation, and MR. The incidence of heart failure within 5 years is threefold higher if an MI occurs with ischemic MR than without it, the surgeon observed.

The CSTN studies were sponsored by the National Institutes of Health and the Canadian Institutes of Health. Dr. Thourani reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott, Boston Scientific, Medtronic, and Sorin.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The residual SYNTAX score is a powerful indicator of 5-year all-cause mortality after percutaneous coronary intervention for triple-vessel or unprotected left main coronary artery disease, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Cardiologists will find the residual SYNTAX score enormously valuable in shared decision making as to whether an individual with complex coronary artery disease is a reasonable candidate for PCI or better off with coronary artery bypass graft (CABG), predicted Dr. Holmes, professor of medicine at the Mayo Clinic in Rochester, Minn.

“I think the residual SYNTAX score is incredibly important. We need to be cognizant of it in our patient selection. I think we’ll see more and more use of it going forward,” the cardiologist said.

The SYNTAX score, as well as the residual SYNTAX score, grew out of the SYNTAX trial (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), a multicenter, prospective, randomized study of PCI versus CABG in 1,800 all-comers with triple-vessel or unprotected left main coronary artery disease (CAD) who were deemed eligible for both revascularization strategies. The trial was led by a who’s who of prominent American and European interventional cardiologists and heart surgeons, including Dr. Holmes (N. Engl. J. Med. 2009;360:961-72)

“SYNTAX is probably the most pivotally important trial in cardiovascular revascularization strategies in the past 10 years or so. An important thing to remember from this study is that the SYNTAX score should be used in all patients with multivessel disease,” he said.

The SYNTAX score (www.syntaxscore.com) is an objective, quantitative measure of CAD complexity that takes into account factors including total occlusions, lesion tortuosity and length, calcifications, and bifurcations. It was calculated preprocedurally in all study participants.

Five years of follow-up established the baseline SYNTAX score to be a useful guide as to whether surgery or PCI is the better strategy in a given individual. Patients in the top tertile for SYNTAX score, with a score of 33 or greater, had a significantly lower 5-year mortality if randomized to CABG: 11.4%, compared with 19.2% for PCI. Mortality didn’t differ between surgically and percutaneously revascularized patients with an intermediate-range SYNTAX score of 23-32, although the composite major adverse cardiac and cerebrovascular event (MACCE) rate was significantly lower in the CABG arm at 25.8%, compared with 36% for PCI. In contrast, among patients with a SYNTAX score of 22 or less, MACCE rates were similar regardless of treatment strategy.

Based on the 5-year MACCE rates, SYNTAX investigators estimated that 71% of all patients with triple-vessel or unprotected left main coronary artery disease are best treated with CABG, adding that, for the remaining 29%, PCI is “a very reasonable alternative” (Lancet 2013;381:629-38).

The mean baseline SYNTAX score in the trial was 28.4. The mean residual score was 4.5. The residual SYNTAX score measures the extent of remaining obstructive coronary disease after revascularization. SYNTAX investigators validated the residual SYNTAX score as a potent predictor of 5-year mortality and other adverse outcomes in a separate analysis of 5-year outcomes in the 903 subjects randomized to PCI.

This analysis was done to validate the concept of “reasonable incomplete revascularization,” which the SYNTAX investigators concluded was a residual SYNTAX score of 8 or less. That’s because 5-year all-cause mortality in patients with a residual SYNTAX score of greater than 0-8 wasn’t significantly different than the 8.5% rate in the 43% of PCI recipients with a residual SYNTAX score of 0, which is indicative of complete revascularization. In contrast, the 17% of patients with a residual score above 8 had a 35% mortality rate (Circulation 2013;128:141-51).

Dr. Holmes recommended that cardiologists who are considering whether to recommend PCI or CABG for patients with multivessel CAD make a baseline estimate of the likely residual SYNTAX Score based upon what they can reasonably expect to achieve with PCI. For example, if a patient has multiple total occlusions and the cardiologist isn’t comfortable tackling such lesions, the estimated residual SYNTAX score is likely to be sufficiently high to point to CABG as the better option.

“If you don’t think you can provide pretty complete revascularization to viable myocardium, then much more consideration should be given to surgery,” he said.

Dr. Holmes reported serving as a consultant to Boston Scientific, which funded the SYNTAX trial.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The residual SYNTAX score is a powerful indicator of 5-year all-cause mortality after percutaneous coronary intervention for triple-vessel or unprotected left main coronary artery disease, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Cardiologists will find the residual SYNTAX score enormously valuable in shared decision making as to whether an individual with complex coronary artery disease is a reasonable candidate for PCI or better off with coronary artery bypass graft (CABG), predicted Dr. Holmes, professor of medicine at the Mayo Clinic in Rochester, Minn.

“I think the residual SYNTAX score is incredibly important. We need to be cognizant of it in our patient selection. I think we’ll see more and more use of it going forward,” the cardiologist said.

The SYNTAX score, as well as the residual SYNTAX score, grew out of the SYNTAX trial (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), a multicenter, prospective, randomized study of PCI versus CABG in 1,800 all-comers with triple-vessel or unprotected left main coronary artery disease (CAD) who were deemed eligible for both revascularization strategies. The trial was led by a who’s who of prominent American and European interventional cardiologists and heart surgeons, including Dr. Holmes (N. Engl. J. Med. 2009;360:961-72)

“SYNTAX is probably the most pivotally important trial in cardiovascular revascularization strategies in the past 10 years or so. An important thing to remember from this study is that the SYNTAX score should be used in all patients with multivessel disease,” he said.

The SYNTAX score (www.syntaxscore.com) is an objective, quantitative measure of CAD complexity that takes into account factors including total occlusions, lesion tortuosity and length, calcifications, and bifurcations. It was calculated preprocedurally in all study participants.

Five years of follow-up established the baseline SYNTAX score to be a useful guide as to whether surgery or PCI is the better strategy in a given individual. Patients in the top tertile for SYNTAX score, with a score of 33 or greater, had a significantly lower 5-year mortality if randomized to CABG: 11.4%, compared with 19.2% for PCI. Mortality didn’t differ between surgically and percutaneously revascularized patients with an intermediate-range SYNTAX score of 23-32, although the composite major adverse cardiac and cerebrovascular event (MACCE) rate was significantly lower in the CABG arm at 25.8%, compared with 36% for PCI. In contrast, among patients with a SYNTAX score of 22 or less, MACCE rates were similar regardless of treatment strategy.

Based on the 5-year MACCE rates, SYNTAX investigators estimated that 71% of all patients with triple-vessel or unprotected left main coronary artery disease are best treated with CABG, adding that, for the remaining 29%, PCI is “a very reasonable alternative” (Lancet 2013;381:629-38).

The mean baseline SYNTAX score in the trial was 28.4. The mean residual score was 4.5. The residual SYNTAX score measures the extent of remaining obstructive coronary disease after revascularization. SYNTAX investigators validated the residual SYNTAX score as a potent predictor of 5-year mortality and other adverse outcomes in a separate analysis of 5-year outcomes in the 903 subjects randomized to PCI.

This analysis was done to validate the concept of “reasonable incomplete revascularization,” which the SYNTAX investigators concluded was a residual SYNTAX score of 8 or less. That’s because 5-year all-cause mortality in patients with a residual SYNTAX score of greater than 0-8 wasn’t significantly different than the 8.5% rate in the 43% of PCI recipients with a residual SYNTAX score of 0, which is indicative of complete revascularization. In contrast, the 17% of patients with a residual score above 8 had a 35% mortality rate (Circulation 2013;128:141-51).

Dr. Holmes recommended that cardiologists who are considering whether to recommend PCI or CABG for patients with multivessel CAD make a baseline estimate of the likely residual SYNTAX Score based upon what they can reasonably expect to achieve with PCI. For example, if a patient has multiple total occlusions and the cardiologist isn’t comfortable tackling such lesions, the estimated residual SYNTAX score is likely to be sufficiently high to point to CABG as the better option.

“If you don’t think you can provide pretty complete revascularization to viable myocardium, then much more consideration should be given to surgery,” he said.

Dr. Holmes reported serving as a consultant to Boston Scientific, which funded the SYNTAX trial.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The residual SYNTAX score is a powerful indicator of 5-year all-cause mortality after percutaneous coronary intervention for triple-vessel or unprotected left main coronary artery disease, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

Cardiologists will find the residual SYNTAX score enormously valuable in shared decision making as to whether an individual with complex coronary artery disease is a reasonable candidate for PCI or better off with coronary artery bypass graft (CABG), predicted Dr. Holmes, professor of medicine at the Mayo Clinic in Rochester, Minn.

“I think the residual SYNTAX score is incredibly important. We need to be cognizant of it in our patient selection. I think we’ll see more and more use of it going forward,” the cardiologist said.

The SYNTAX score, as well as the residual SYNTAX score, grew out of the SYNTAX trial (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), a multicenter, prospective, randomized study of PCI versus CABG in 1,800 all-comers with triple-vessel or unprotected left main coronary artery disease (CAD) who were deemed eligible for both revascularization strategies. The trial was led by a who’s who of prominent American and European interventional cardiologists and heart surgeons, including Dr. Holmes (N. Engl. J. Med. 2009;360:961-72)

“SYNTAX is probably the most pivotally important trial in cardiovascular revascularization strategies in the past 10 years or so. An important thing to remember from this study is that the SYNTAX score should be used in all patients with multivessel disease,” he said.

The SYNTAX score (www.syntaxscore.com) is an objective, quantitative measure of CAD complexity that takes into account factors including total occlusions, lesion tortuosity and length, calcifications, and bifurcations. It was calculated preprocedurally in all study participants.

Five years of follow-up established the baseline SYNTAX score to be a useful guide as to whether surgery or PCI is the better strategy in a given individual. Patients in the top tertile for SYNTAX score, with a score of 33 or greater, had a significantly lower 5-year mortality if randomized to CABG: 11.4%, compared with 19.2% for PCI. Mortality didn’t differ between surgically and percutaneously revascularized patients with an intermediate-range SYNTAX score of 23-32, although the composite major adverse cardiac and cerebrovascular event (MACCE) rate was significantly lower in the CABG arm at 25.8%, compared with 36% for PCI. In contrast, among patients with a SYNTAX score of 22 or less, MACCE rates were similar regardless of treatment strategy.

Based on the 5-year MACCE rates, SYNTAX investigators estimated that 71% of all patients with triple-vessel or unprotected left main coronary artery disease are best treated with CABG, adding that, for the remaining 29%, PCI is “a very reasonable alternative” (Lancet 2013;381:629-38).

The mean baseline SYNTAX score in the trial was 28.4. The mean residual score was 4.5. The residual SYNTAX score measures the extent of remaining obstructive coronary disease after revascularization. SYNTAX investigators validated the residual SYNTAX score as a potent predictor of 5-year mortality and other adverse outcomes in a separate analysis of 5-year outcomes in the 903 subjects randomized to PCI.

This analysis was done to validate the concept of “reasonable incomplete revascularization,” which the SYNTAX investigators concluded was a residual SYNTAX score of 8 or less. That’s because 5-year all-cause mortality in patients with a residual SYNTAX score of greater than 0-8 wasn’t significantly different than the 8.5% rate in the 43% of PCI recipients with a residual SYNTAX score of 0, which is indicative of complete revascularization. In contrast, the 17% of patients with a residual score above 8 had a 35% mortality rate (Circulation 2013;128:141-51).

Dr. Holmes recommended that cardiologists who are considering whether to recommend PCI or CABG for patients with multivessel CAD make a baseline estimate of the likely residual SYNTAX Score based upon what they can reasonably expect to achieve with PCI. For example, if a patient has multiple total occlusions and the cardiologist isn’t comfortable tackling such lesions, the estimated residual SYNTAX score is likely to be sufficiently high to point to CABG as the better option.

“If you don’t think you can provide pretty complete revascularization to viable myocardium, then much more consideration should be given to surgery,” he said.

Dr. Holmes reported serving as a consultant to Boston Scientific, which funded the SYNTAX trial.

bjancin@frontlinemedcom.com