Acquired Cardiovascular Disease

PHOENIX – In the clinical opinion of Dr. Nevin M. Katz, caring for critical care patients after cardiothoracic surgery requires a multidisciplinary team.

“It used to be just the surgeons and the residents and anesthesiologists, but in this era, it’s a broad team,” Dr. Katz said at the annual meeting of the Society of Thoracic Surgeons. “Coordination of the team, which includes surgeons, anesthesiologists, physician assistants, bedside nurses, nurse practitioners, perfusionists, pharmacists, respiratory therapists, and nutritionists is very important, and it’s important that members of the team be on the same page.”

Dr. Katz, a cardiovascular surgeon/intensivist at Johns Hopkins University, Baltimore, went on to offer tips for managing right ventricular failure in cardiac surgical patients. He recommends that clinicians consider five basic parameters of hemodynamic management: the heart rate and rhythm; the preload; the afterload; contractility; and the surgical result, including the potential for an anatomic problem and the risk of cardiac tamponade. “One must also consider a cardiac assist device,” he said.

He recommended that the cardiac index goal for cardiovascular patients in the ICU be in the range of 2.2-4.4 L per min/m². The recommended hemodynamic goals also included systemic blood pressure ranges with a systolic pressure of 90-140 mm Hg and a mean arterial pressure of 70-90 mm Hg; a left arterial pressure or pulmonary capillary wedge pressure of 5-18 mm Hg, a right arterial pressure or central venous pressure of 5-15 mm Hg, and a systemic vascular resistance of 800-1,200 dynes per sec/cm⁵. “When treating right ventricular failure or complex patients, I think advanced PA [pulmonary artery] catheters are valuable, although they’re not absolutely necessary,” he said.

Complementary technologies available in most ICUs can help clinicians manage these patients, particularly ultrasound. With ultrasound, “we can determine where the patient is on the ventricular function curve, regional versus global dysfunction, right ventricular versus left ventricular dysfunction, valve dysfunction, and cardiac tamponade,” said Dr. Katz, who also created the Foundation for the Advancement of Cardiothoracic Care, also known as FACTS-Care. “It’s a very important monitoring modality.”

An important goal in managing patients with right ventricular failure is to establish an optimal heart rate and rhythm. “We have modalities to treat bradycardia and heart block,” he said. “Loss of atrial contraction is very important. If we can avoid atrial fibrillation, that’s good. Ventricular arrhythmias can be a problem, and nowadays we can treat atrioventricular and ventricular dyssynchrony.”

Optimal preload requires a focus on volume responsiveness, Dr. Katz continued. “Where is the patient on that ventricular function curve?” he asked. “With the advanced PA catheters, there are ways to look at that. You would like to be on the ascending part of that curve.” Clinicians can also use pulsus paradoxus, a variation of systemic arterial pulse volume. “That will indicate that perhaps you’re low in volume, but you can use stroke volume variation with an advanced PA catheter,” he said. “If your stroke volume variation is greater than 15% you’re on the ascending part of the curve. But if your stroke volume variation is less than 15%, your volume is probably optimal and you’re not going to be volume responsive.”

Clinicians who lack the benefit of an advanced PA catheter can assess volume responsiveness with passive leg raising.

Low preload causes of RV failure include hypovolemia, bleeding, third-spacing, high urine output, and cardiac tamponade. High preload can be a problem, too, from excess fluid administration, tricuspid or pulmonary valve regurgitation, or from left to right shunting.

Overall, optimal management of RV failure depends on the coordination of the multidisciplinary critical care team.

Dr. Katz reported having no financial disclosures.

[email protected]

PHOENIX – In the clinical opinion of Dr. Nevin M. Katz, caring for critical care patients after cardiothoracic surgery requires a multidisciplinary team.

“It used to be just the surgeons and the residents and anesthesiologists, but in this era, it’s a broad team,” Dr. Katz said at the annual meeting of the Society of Thoracic Surgeons. “Coordination of the team, which includes surgeons, anesthesiologists, physician assistants, bedside nurses, nurse practitioners, perfusionists, pharmacists, respiratory therapists, and nutritionists is very important, and it’s important that members of the team be on the same page.”

Dr. Katz, a cardiovascular surgeon/intensivist at Johns Hopkins University, Baltimore, went on to offer tips for managing right ventricular failure in cardiac surgical patients. He recommends that clinicians consider five basic parameters of hemodynamic management: the heart rate and rhythm; the preload; the afterload; contractility; and the surgical result, including the potential for an anatomic problem and the risk of cardiac tamponade. “One must also consider a cardiac assist device,” he said.

He recommended that the cardiac index goal for cardiovascular patients in the ICU be in the range of 2.2-4.4 L per min/m². The recommended hemodynamic goals also included systemic blood pressure ranges with a systolic pressure of 90-140 mm Hg and a mean arterial pressure of 70-90 mm Hg; a left arterial pressure or pulmonary capillary wedge pressure of 5-18 mm Hg, a right arterial pressure or central venous pressure of 5-15 mm Hg, and a systemic vascular resistance of 800-1,200 dynes per sec/cm⁵. “When treating right ventricular failure or complex patients, I think advanced PA [pulmonary artery] catheters are valuable, although they’re not absolutely necessary,” he said.

Complementary technologies available in most ICUs can help clinicians manage these patients, particularly ultrasound. With ultrasound, “we can determine where the patient is on the ventricular function curve, regional versus global dysfunction, right ventricular versus left ventricular dysfunction, valve dysfunction, and cardiac tamponade,” said Dr. Katz, who also created the Foundation for the Advancement of Cardiothoracic Care, also known as FACTS-Care. “It’s a very important monitoring modality.”

An important goal in managing patients with right ventricular failure is to establish an optimal heart rate and rhythm. “We have modalities to treat bradycardia and heart block,” he said. “Loss of atrial contraction is very important. If we can avoid atrial fibrillation, that’s good. Ventricular arrhythmias can be a problem, and nowadays we can treat atrioventricular and ventricular dyssynchrony.”

Optimal preload requires a focus on volume responsiveness, Dr. Katz continued. “Where is the patient on that ventricular function curve?” he asked. “With the advanced PA catheters, there are ways to look at that. You would like to be on the ascending part of that curve.” Clinicians can also use pulsus paradoxus, a variation of systemic arterial pulse volume. “That will indicate that perhaps you’re low in volume, but you can use stroke volume variation with an advanced PA catheter,” he said. “If your stroke volume variation is greater than 15% you’re on the ascending part of the curve. But if your stroke volume variation is less than 15%, your volume is probably optimal and you’re not going to be volume responsive.”

Clinicians who lack the benefit of an advanced PA catheter can assess volume responsiveness with passive leg raising.

Low preload causes of RV failure include hypovolemia, bleeding, third-spacing, high urine output, and cardiac tamponade. High preload can be a problem, too, from excess fluid administration, tricuspid or pulmonary valve regurgitation, or from left to right shunting.

Overall, optimal management of RV failure depends on the coordination of the multidisciplinary critical care team.

Dr. Katz reported having no financial disclosures.

[email protected]

PHOENIX – In the clinical opinion of Dr. Nevin M. Katz, caring for critical care patients after cardiothoracic surgery requires a multidisciplinary team.

“It used to be just the surgeons and the residents and anesthesiologists, but in this era, it’s a broad team,” Dr. Katz said at the annual meeting of the Society of Thoracic Surgeons. “Coordination of the team, which includes surgeons, anesthesiologists, physician assistants, bedside nurses, nurse practitioners, perfusionists, pharmacists, respiratory therapists, and nutritionists is very important, and it’s important that members of the team be on the same page.”

Dr. Katz, a cardiovascular surgeon/intensivist at Johns Hopkins University, Baltimore, went on to offer tips for managing right ventricular failure in cardiac surgical patients. He recommends that clinicians consider five basic parameters of hemodynamic management: the heart rate and rhythm; the preload; the afterload; contractility; and the surgical result, including the potential for an anatomic problem and the risk of cardiac tamponade. “One must also consider a cardiac assist device,” he said.

He recommended that the cardiac index goal for cardiovascular patients in the ICU be in the range of 2.2-4.4 L per min/m². The recommended hemodynamic goals also included systemic blood pressure ranges with a systolic pressure of 90-140 mm Hg and a mean arterial pressure of 70-90 mm Hg; a left arterial pressure or pulmonary capillary wedge pressure of 5-18 mm Hg, a right arterial pressure or central venous pressure of 5-15 mm Hg, and a systemic vascular resistance of 800-1,200 dynes per sec/cm⁵. “When treating right ventricular failure or complex patients, I think advanced PA [pulmonary artery] catheters are valuable, although they’re not absolutely necessary,” he said.

Complementary technologies available in most ICUs can help clinicians manage these patients, particularly ultrasound. With ultrasound, “we can determine where the patient is on the ventricular function curve, regional versus global dysfunction, right ventricular versus left ventricular dysfunction, valve dysfunction, and cardiac tamponade,” said Dr. Katz, who also created the Foundation for the Advancement of Cardiothoracic Care, also known as FACTS-Care. “It’s a very important monitoring modality.”

An important goal in managing patients with right ventricular failure is to establish an optimal heart rate and rhythm. “We have modalities to treat bradycardia and heart block,” he said. “Loss of atrial contraction is very important. If we can avoid atrial fibrillation, that’s good. Ventricular arrhythmias can be a problem, and nowadays we can treat atrioventricular and ventricular dyssynchrony.”

Optimal preload requires a focus on volume responsiveness, Dr. Katz continued. “Where is the patient on that ventricular function curve?” he asked. “With the advanced PA catheters, there are ways to look at that. You would like to be on the ascending part of that curve.” Clinicians can also use pulsus paradoxus, a variation of systemic arterial pulse volume. “That will indicate that perhaps you’re low in volume, but you can use stroke volume variation with an advanced PA catheter,” he said. “If your stroke volume variation is greater than 15% you’re on the ascending part of the curve. But if your stroke volume variation is less than 15%, your volume is probably optimal and you’re not going to be volume responsive.”

Clinicians who lack the benefit of an advanced PA catheter can assess volume responsiveness with passive leg raising.

Low preload causes of RV failure include hypovolemia, bleeding, third-spacing, high urine output, and cardiac tamponade. High preload can be a problem, too, from excess fluid administration, tricuspid or pulmonary valve regurgitation, or from left to right shunting.

Overall, optimal management of RV failure depends on the coordination of the multidisciplinary critical care team.

Dr. Katz reported having no financial disclosures.

[email protected]

SNOWMASS, COLO. – Ivabradine and sacubitril/valsartan are paradigm-changing drugs approved last year for the treatment of heart failure with reduced ejection fraction – and it’s entirely reasonable to begin using them now in the appropriate patients, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

The impressive positive results seen in the pivotal trials for these novel agents – the SHIFT trial for ivabradine (Corlanor) and PARADIGM-HF for sacubitril/valsartan (Entresto) – have rocked the heart failure world.

The studies showed that, in the right patients, these two medications improve heart failure morbidity and mortality significantly beyond what’s achievable with the current gold standard, guideline-directed medical therapy. That’s exciting because even though great therapeutic strides have been made during the past 15 years, symptomatic patients with heart failure with reduced ejection fraction (HFrEF) treated with optimal guideline-directed pharmacotherapy still have substantial residual risk for heart failure hospitalization and death, noted Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

The U.S. heart failure guidelines panel hasn’t yet addressed the use of either of these recently approved drugs, but Dr. Desai provided his best sense of the data and how he thinks physicians might start using them now.

Ivabradine and sacubitril/valsartan are first-in-class agents with novel mechanisms of action. Ivabradine’s demonstrated safety and efficacy in the SHIFT trial confirmed the hypothesis that elevated heart rate is a legitimate therapeutic target in HFrEF.

Sacubitril/valsartan, an angiotensin II receptor/neprilysin inhibitor formerly known as LCZ696, provides what is to date a unique ability to enhance the activity of endogenous vasoactive peptides, including natriuretic peptides, bradykinin, substance P, adrenomedullin, and calcitonin gene–related peptide. These peptides are antifibrotic, antihypertrophic, and they promote vasodilation and diuresis, thus counteracting the adverse effects of neurohormonal activation. But in HFrEF, these vasoactive peptides are less active and patients are less sensitive to them.

Ivabradine

This selective sinus node inhibitor decreases heart rate and has essentially no other effects. The drug has been available for years in Europe, and the European Society of Cardiology (ESC) has had sufficient time to integrate ivabradine into its guidelines for pharmacotherapy in HFrEF.

The ESC treatment algorithm for HFrEF (Eur Heart J. 2012 Jul;33[14]:1787-847) is built upon a foundation of thiazide diuretics to relieve signs and symptoms of congestion along with a beta-blocker and an ACE inhibitor or angiotensin receptor blocker (ARB). In a patient who still has New York Heart Association class II-IV symptoms after those drugs are titrated to guideline-recommended target levels or maximally tolerated doses, a mineralocorticoid receptor antagonist – either spironolactone or eplerenone – is added. And, in a patient who still remains symptomatic, has a left ventricular ejection fraction of 35% or less, is in sinus rhythm, and has a heart rate of 70 beats per minute or more, it’s time to consider adding ivabradine.

“This is how our own guidelines may elect to incorporate ivabradine, but of course, we don’t know yet,” Dr. Desai observed.

In the randomized, double-blind SHIFT trial involving 6,558 HFrEF patients who fit the description of ivabradine candidates described in the ESC guidelines, those who received ivabradine titrated to a maximum of 7.5 mg twice daily experienced a 26% reduction in hospital admissions for worsening heart failure, compared with placebo, a 26% reduction in deaths from heart failure, and fewer adverse events than the control group (Lancet. 2010 Sep 11;376[9744]:875-85).

The important question is who should get ivabradine and who should just get a little more beta-blocker in order to slow the heart rate. The fact is, many heart failure patients simply can’t tolerate the guideline-recommended target dose of beta-blocker therapy, which is 12.5 mg twice daily of carvedilol or its equivalent. Indeed, only 26% of SHIFT participants were able to do so.

“My interpretation of the SHIFT trial is that the goal is to reduce heart rate by any means necessary; preferentially, with a beta-blocker, and with ivabradine as an adjunct in patients who can’t get to target doses,” the cardiologist said.

Sacubitril/valsartan

In the landmark double-blind, 8,442-patient PARADIGM-HF trial, the group randomized to sacubitril/valsartan had a 20% reduction in the primary endpoint of cardiovascular death or heart failure hospitalization over 27 months of follow-up, compared with controls on enalapril at the guideline-recommended dose of 10 mg twice a day. The number needed to treat (NNT) was 21. Moreover, all-cause mortality was reduced by 16% (N Engl J Med. 2014 Sep 11;37[11]:993-1004).

In a recent follow-up cause of death analysis, Dr. Desai and his coinvestigators reported that 81% of all deaths in PARADIGM-HF were cardiovascular in nature. The NNT for sacubitril/valsartan in order to prevent one cardiovascular death was 32. The risk of sudden cardiac death was reduced by 80%, while the risk of death due to worsening heart failure was decreased by 21% (Eur Heart J 2015 Aug 7;36[30]:1990-7).

In another secondary analysis from the PARADIGM-HF investigators, the use of the angiotensin receptor/neprilysin inhibitor was shown to prevent clinical progression of surviving patients with heart failure much more effectively than enalapril. The sacubitril/valsartan group was 34% less likely to have an emergency department visit for worsening heart failure, 18% less likely to require intensive care, and 22% less likely to receive an implantable heart failure device or undergo cardiac transplantation. The reduction in the rate of heart failure hospitalization became significant within the first 30 days (Circulation. 2015 Jan 6;131[1]:54-61).

Moreover, the absolute benefit of sacubitril/valsartan in PARADIGM-HF was consistent across the full spectrum of patient risk (J Am Coll Cardiol. 2015 Nov 10;66[19]:2059-71).

To put this into perspective, Dr. Desai continued, for every 1,000 HFrEF patients switched from an ACE inhibitor or ARB to sacubitril/valsartan, the absolute benefit over the course of 27 months includes 31 fewer cardiovascular deaths, 28 fewer hospitalizations for heart failure, and 37 fewer hospitalizations for any reason.

“This is potent therapy for patients with HFrEF who have the right phenotype,” he observed.

While substitution of sacubitril/valsartan for an ACE inhibitor or ARB may be appropriate in many patients with chronic HFrEF who continue to have NYHA Class II-IV symptoms on guideline-directed medical therapy, several caveats apply, according to Dr. Desai.

It’s important to be aware of the PARADIGM-HF eligibility criteria, because it’s only in patients who fit that profile that sacubitril/valsartan provides evidence-based therapy. There are as yet no data to support the drug’s use in patients with new-onset HFrEF, acute decompensated HFrEF, in patients who are immediately post-MI, or in those with advanced chronic kidney disease, he emphasized.

“I think you have to be mindful of eligibility because the label that’s applied to this drug is basically ‘patients with HFrEF who are treated with guideline-directed medical therapy.’ There’s no specific requirement that you follow the detailed eligibility criteria of the PARADIGM-HF trial, but you should realize that the drug is known to be effective only in patients who fit the PARADIGM-HF eligibility profile,” he said.

Dr. Desai gave a few clinical pearls for prescribing sacubitril/valsartan. For most patients, the initial recommended dose is 49/51 mg twice daily. In those with low baseline blood pressure and tenuous hemodynamics, it’s appropriate to initiate therapy at 24/26 mg BID. It’s important to halt ACE inhibitor therapy 36 hours prior to starting sacubitril/valsartan so as to avoid overlap and consequent increased risk of angioedema. And while serum n-terminal prohormone brain natriuretic peptide (NT-proBNP) remains a useful biomarker to monitor heart rate severity and response to treatment while a patient is on sacubitril/valsartan, BNP is not because serum levels of that biomarker rise with neprilysin inhibition.

Dr. Desai reported receiving research support from Novartis and St. Jude Medical and serving as a consultant to those companies as well as Merck and Relypsa.

[email protected]

SNOWMASS, COLO. – Ivabradine and sacubitril/valsartan are paradigm-changing drugs approved last year for the treatment of heart failure with reduced ejection fraction – and it’s entirely reasonable to begin using them now in the appropriate patients, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

The impressive positive results seen in the pivotal trials for these novel agents – the SHIFT trial for ivabradine (Corlanor) and PARADIGM-HF for sacubitril/valsartan (Entresto) – have rocked the heart failure world.

The studies showed that, in the right patients, these two medications improve heart failure morbidity and mortality significantly beyond what’s achievable with the current gold standard, guideline-directed medical therapy. That’s exciting because even though great therapeutic strides have been made during the past 15 years, symptomatic patients with heart failure with reduced ejection fraction (HFrEF) treated with optimal guideline-directed pharmacotherapy still have substantial residual risk for heart failure hospitalization and death, noted Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

The U.S. heart failure guidelines panel hasn’t yet addressed the use of either of these recently approved drugs, but Dr. Desai provided his best sense of the data and how he thinks physicians might start using them now.

Ivabradine and sacubitril/valsartan are first-in-class agents with novel mechanisms of action. Ivabradine’s demonstrated safety and efficacy in the SHIFT trial confirmed the hypothesis that elevated heart rate is a legitimate therapeutic target in HFrEF.

Sacubitril/valsartan, an angiotensin II receptor/neprilysin inhibitor formerly known as LCZ696, provides what is to date a unique ability to enhance the activity of endogenous vasoactive peptides, including natriuretic peptides, bradykinin, substance P, adrenomedullin, and calcitonin gene–related peptide. These peptides are antifibrotic, antihypertrophic, and they promote vasodilation and diuresis, thus counteracting the adverse effects of neurohormonal activation. But in HFrEF, these vasoactive peptides are less active and patients are less sensitive to them.

Ivabradine

This selective sinus node inhibitor decreases heart rate and has essentially no other effects. The drug has been available for years in Europe, and the European Society of Cardiology (ESC) has had sufficient time to integrate ivabradine into its guidelines for pharmacotherapy in HFrEF.

The ESC treatment algorithm for HFrEF (Eur Heart J. 2012 Jul;33[14]:1787-847) is built upon a foundation of thiazide diuretics to relieve signs and symptoms of congestion along with a beta-blocker and an ACE inhibitor or angiotensin receptor blocker (ARB). In a patient who still has New York Heart Association class II-IV symptoms after those drugs are titrated to guideline-recommended target levels or maximally tolerated doses, a mineralocorticoid receptor antagonist – either spironolactone or eplerenone – is added. And, in a patient who still remains symptomatic, has a left ventricular ejection fraction of 35% or less, is in sinus rhythm, and has a heart rate of 70 beats per minute or more, it’s time to consider adding ivabradine.

“This is how our own guidelines may elect to incorporate ivabradine, but of course, we don’t know yet,” Dr. Desai observed.

In the randomized, double-blind SHIFT trial involving 6,558 HFrEF patients who fit the description of ivabradine candidates described in the ESC guidelines, those who received ivabradine titrated to a maximum of 7.5 mg twice daily experienced a 26% reduction in hospital admissions for worsening heart failure, compared with placebo, a 26% reduction in deaths from heart failure, and fewer adverse events than the control group (Lancet. 2010 Sep 11;376[9744]:875-85).

The important question is who should get ivabradine and who should just get a little more beta-blocker in order to slow the heart rate. The fact is, many heart failure patients simply can’t tolerate the guideline-recommended target dose of beta-blocker therapy, which is 12.5 mg twice daily of carvedilol or its equivalent. Indeed, only 26% of SHIFT participants were able to do so.

“My interpretation of the SHIFT trial is that the goal is to reduce heart rate by any means necessary; preferentially, with a beta-blocker, and with ivabradine as an adjunct in patients who can’t get to target doses,” the cardiologist said.

Sacubitril/valsartan

In the landmark double-blind, 8,442-patient PARADIGM-HF trial, the group randomized to sacubitril/valsartan had a 20% reduction in the primary endpoint of cardiovascular death or heart failure hospitalization over 27 months of follow-up, compared with controls on enalapril at the guideline-recommended dose of 10 mg twice a day. The number needed to treat (NNT) was 21. Moreover, all-cause mortality was reduced by 16% (N Engl J Med. 2014 Sep 11;37[11]:993-1004).

In a recent follow-up cause of death analysis, Dr. Desai and his coinvestigators reported that 81% of all deaths in PARADIGM-HF were cardiovascular in nature. The NNT for sacubitril/valsartan in order to prevent one cardiovascular death was 32. The risk of sudden cardiac death was reduced by 80%, while the risk of death due to worsening heart failure was decreased by 21% (Eur Heart J 2015 Aug 7;36[30]:1990-7).

In another secondary analysis from the PARADIGM-HF investigators, the use of the angiotensin receptor/neprilysin inhibitor was shown to prevent clinical progression of surviving patients with heart failure much more effectively than enalapril. The sacubitril/valsartan group was 34% less likely to have an emergency department visit for worsening heart failure, 18% less likely to require intensive care, and 22% less likely to receive an implantable heart failure device or undergo cardiac transplantation. The reduction in the rate of heart failure hospitalization became significant within the first 30 days (Circulation. 2015 Jan 6;131[1]:54-61).

Moreover, the absolute benefit of sacubitril/valsartan in PARADIGM-HF was consistent across the full spectrum of patient risk (J Am Coll Cardiol. 2015 Nov 10;66[19]:2059-71).

To put this into perspective, Dr. Desai continued, for every 1,000 HFrEF patients switched from an ACE inhibitor or ARB to sacubitril/valsartan, the absolute benefit over the course of 27 months includes 31 fewer cardiovascular deaths, 28 fewer hospitalizations for heart failure, and 37 fewer hospitalizations for any reason.

“This is potent therapy for patients with HFrEF who have the right phenotype,” he observed.

While substitution of sacubitril/valsartan for an ACE inhibitor or ARB may be appropriate in many patients with chronic HFrEF who continue to have NYHA Class II-IV symptoms on guideline-directed medical therapy, several caveats apply, according to Dr. Desai.

It’s important to be aware of the PARADIGM-HF eligibility criteria, because it’s only in patients who fit that profile that sacubitril/valsartan provides evidence-based therapy. There are as yet no data to support the drug’s use in patients with new-onset HFrEF, acute decompensated HFrEF, in patients who are immediately post-MI, or in those with advanced chronic kidney disease, he emphasized.

“I think you have to be mindful of eligibility because the label that’s applied to this drug is basically ‘patients with HFrEF who are treated with guideline-directed medical therapy.’ There’s no specific requirement that you follow the detailed eligibility criteria of the PARADIGM-HF trial, but you should realize that the drug is known to be effective only in patients who fit the PARADIGM-HF eligibility profile,” he said.

Dr. Desai gave a few clinical pearls for prescribing sacubitril/valsartan. For most patients, the initial recommended dose is 49/51 mg twice daily. In those with low baseline blood pressure and tenuous hemodynamics, it’s appropriate to initiate therapy at 24/26 mg BID. It’s important to halt ACE inhibitor therapy 36 hours prior to starting sacubitril/valsartan so as to avoid overlap and consequent increased risk of angioedema. And while serum n-terminal prohormone brain natriuretic peptide (NT-proBNP) remains a useful biomarker to monitor heart rate severity and response to treatment while a patient is on sacubitril/valsartan, BNP is not because serum levels of that biomarker rise with neprilysin inhibition.

Dr. Desai reported receiving research support from Novartis and St. Jude Medical and serving as a consultant to those companies as well as Merck and Relypsa.

[email protected]

SNOWMASS, COLO. – Ivabradine and sacubitril/valsartan are paradigm-changing drugs approved last year for the treatment of heart failure with reduced ejection fraction – and it’s entirely reasonable to begin using them now in the appropriate patients, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

The impressive positive results seen in the pivotal trials for these novel agents – the SHIFT trial for ivabradine (Corlanor) and PARADIGM-HF for sacubitril/valsartan (Entresto) – have rocked the heart failure world.

The studies showed that, in the right patients, these two medications improve heart failure morbidity and mortality significantly beyond what’s achievable with the current gold standard, guideline-directed medical therapy. That’s exciting because even though great therapeutic strides have been made during the past 15 years, symptomatic patients with heart failure with reduced ejection fraction (HFrEF) treated with optimal guideline-directed pharmacotherapy still have substantial residual risk for heart failure hospitalization and death, noted Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

The U.S. heart failure guidelines panel hasn’t yet addressed the use of either of these recently approved drugs, but Dr. Desai provided his best sense of the data and how he thinks physicians might start using them now.

Ivabradine and sacubitril/valsartan are first-in-class agents with novel mechanisms of action. Ivabradine’s demonstrated safety and efficacy in the SHIFT trial confirmed the hypothesis that elevated heart rate is a legitimate therapeutic target in HFrEF.

Sacubitril/valsartan, an angiotensin II receptor/neprilysin inhibitor formerly known as LCZ696, provides what is to date a unique ability to enhance the activity of endogenous vasoactive peptides, including natriuretic peptides, bradykinin, substance P, adrenomedullin, and calcitonin gene–related peptide. These peptides are antifibrotic, antihypertrophic, and they promote vasodilation and diuresis, thus counteracting the adverse effects of neurohormonal activation. But in HFrEF, these vasoactive peptides are less active and patients are less sensitive to them.

Ivabradine

This selective sinus node inhibitor decreases heart rate and has essentially no other effects. The drug has been available for years in Europe, and the European Society of Cardiology (ESC) has had sufficient time to integrate ivabradine into its guidelines for pharmacotherapy in HFrEF.

The ESC treatment algorithm for HFrEF (Eur Heart J. 2012 Jul;33[14]:1787-847) is built upon a foundation of thiazide diuretics to relieve signs and symptoms of congestion along with a beta-blocker and an ACE inhibitor or angiotensin receptor blocker (ARB). In a patient who still has New York Heart Association class II-IV symptoms after those drugs are titrated to guideline-recommended target levels or maximally tolerated doses, a mineralocorticoid receptor antagonist – either spironolactone or eplerenone – is added. And, in a patient who still remains symptomatic, has a left ventricular ejection fraction of 35% or less, is in sinus rhythm, and has a heart rate of 70 beats per minute or more, it’s time to consider adding ivabradine.

“This is how our own guidelines may elect to incorporate ivabradine, but of course, we don’t know yet,” Dr. Desai observed.

In the randomized, double-blind SHIFT trial involving 6,558 HFrEF patients who fit the description of ivabradine candidates described in the ESC guidelines, those who received ivabradine titrated to a maximum of 7.5 mg twice daily experienced a 26% reduction in hospital admissions for worsening heart failure, compared with placebo, a 26% reduction in deaths from heart failure, and fewer adverse events than the control group (Lancet. 2010 Sep 11;376[9744]:875-85).

The important question is who should get ivabradine and who should just get a little more beta-blocker in order to slow the heart rate. The fact is, many heart failure patients simply can’t tolerate the guideline-recommended target dose of beta-blocker therapy, which is 12.5 mg twice daily of carvedilol or its equivalent. Indeed, only 26% of SHIFT participants were able to do so.

“My interpretation of the SHIFT trial is that the goal is to reduce heart rate by any means necessary; preferentially, with a beta-blocker, and with ivabradine as an adjunct in patients who can’t get to target doses,” the cardiologist said.

Sacubitril/valsartan

In the landmark double-blind, 8,442-patient PARADIGM-HF trial, the group randomized to sacubitril/valsartan had a 20% reduction in the primary endpoint of cardiovascular death or heart failure hospitalization over 27 months of follow-up, compared with controls on enalapril at the guideline-recommended dose of 10 mg twice a day. The number needed to treat (NNT) was 21. Moreover, all-cause mortality was reduced by 16% (N Engl J Med. 2014 Sep 11;37[11]:993-1004).

In a recent follow-up cause of death analysis, Dr. Desai and his coinvestigators reported that 81% of all deaths in PARADIGM-HF were cardiovascular in nature. The NNT for sacubitril/valsartan in order to prevent one cardiovascular death was 32. The risk of sudden cardiac death was reduced by 80%, while the risk of death due to worsening heart failure was decreased by 21% (Eur Heart J 2015 Aug 7;36[30]:1990-7).

In another secondary analysis from the PARADIGM-HF investigators, the use of the angiotensin receptor/neprilysin inhibitor was shown to prevent clinical progression of surviving patients with heart failure much more effectively than enalapril. The sacubitril/valsartan group was 34% less likely to have an emergency department visit for worsening heart failure, 18% less likely to require intensive care, and 22% less likely to receive an implantable heart failure device or undergo cardiac transplantation. The reduction in the rate of heart failure hospitalization became significant within the first 30 days (Circulation. 2015 Jan 6;131[1]:54-61).

Moreover, the absolute benefit of sacubitril/valsartan in PARADIGM-HF was consistent across the full spectrum of patient risk (J Am Coll Cardiol. 2015 Nov 10;66[19]:2059-71).

To put this into perspective, Dr. Desai continued, for every 1,000 HFrEF patients switched from an ACE inhibitor or ARB to sacubitril/valsartan, the absolute benefit over the course of 27 months includes 31 fewer cardiovascular deaths, 28 fewer hospitalizations for heart failure, and 37 fewer hospitalizations for any reason.

“This is potent therapy for patients with HFrEF who have the right phenotype,” he observed.

While substitution of sacubitril/valsartan for an ACE inhibitor or ARB may be appropriate in many patients with chronic HFrEF who continue to have NYHA Class II-IV symptoms on guideline-directed medical therapy, several caveats apply, according to Dr. Desai.

It’s important to be aware of the PARADIGM-HF eligibility criteria, because it’s only in patients who fit that profile that sacubitril/valsartan provides evidence-based therapy. There are as yet no data to support the drug’s use in patients with new-onset HFrEF, acute decompensated HFrEF, in patients who are immediately post-MI, or in those with advanced chronic kidney disease, he emphasized.

“I think you have to be mindful of eligibility because the label that’s applied to this drug is basically ‘patients with HFrEF who are treated with guideline-directed medical therapy.’ There’s no specific requirement that you follow the detailed eligibility criteria of the PARADIGM-HF trial, but you should realize that the drug is known to be effective only in patients who fit the PARADIGM-HF eligibility profile,” he said.

Dr. Desai gave a few clinical pearls for prescribing sacubitril/valsartan. For most patients, the initial recommended dose is 49/51 mg twice daily. In those with low baseline blood pressure and tenuous hemodynamics, it’s appropriate to initiate therapy at 24/26 mg BID. It’s important to halt ACE inhibitor therapy 36 hours prior to starting sacubitril/valsartan so as to avoid overlap and consequent increased risk of angioedema. And while serum n-terminal prohormone brain natriuretic peptide (NT-proBNP) remains a useful biomarker to monitor heart rate severity and response to treatment while a patient is on sacubitril/valsartan, BNP is not because serum levels of that biomarker rise with neprilysin inhibition.

Dr. Desai reported receiving research support from Novartis and St. Jude Medical and serving as a consultant to those companies as well as Merck and Relypsa.

[email protected]

LivaNova announced that the U.S. Food and Drug Administration has announced the approval of their Perceval Sutureless Heart Valve. The approval was issued Jan. 8 and is effective immediately, and LivaNova indicated that it will begin commercial distribution of the device in the United States over the coming quarter.

According to an FDA summary document, the Perceval Sutureless Heart Valve is a bioprosthetic valve designed to replace a diseased native or a malfunctioning prosthetic aortic valve via open heart surgery. The self-expanding stent frame consists of a tissue component made from bovine pericardium and a self-expandable nitinol stent, along with a dedicated delivery system that allows physicians to position and anchor the valve suturelessly.

The Perceval heart valve is supplied unmounted and must be loaded onto an accompanying holder by reducing the valve size using a supplied polycarbonate collapser. The holder is used for sternal approaches and includes a rigid shaft with an end section that houses the valve prosthesis during delivery. A separate holder, approximately 3 cm longer, is also available for minimally invasive procedures. After implantation, the physician uses the a post-dilation catheter to expand the valve in situ.

Perceval’s approval was based upon the results of a pivotal European study performed to assess the device, the CAVALIER (Safety and Effectiveness Study of Perceval S Valve for Extended CE Mark) trial. The prospective, multicenter, nonrandomized clinical study was conducted at 26 investigational sites in Austria, Belgium, England, France, Germany, and the Netherlands.

Patients were treated between Feb. 23, 2010, and Sept. 30, 2013, and the database for the PDA-assessed data collected through Nov. 5, 2014, and included 658 patients.

The differences between the New York Heart Association (NYHA) class at 12 months and the baseline were calculated. In total, 77.5% of patients showed a decrease of NYHA equal to at least one class, whereas 19.7% of patients remained stable over the time. Only 2.8% of patients showed a worsened clinical status.

Reduction in mean gradients and increase in effective orifice area were both observed at 1 year follow-up, according to the FDA report.

At the 1-, 2-, and 3-year follow-up time points, 75.1% or greater of the implanted patients with available data had improved by one to three classes and at the 4-year follow-up time point 72.6% of the patients had improved by one to three classes, according to the report. In addition, at the 1-, 2-, and 3-year follow-up time points, 92.9% or greater of the patients were in NYHA Class I and Class II, and at the 4-year follow-up time point, 86.3% of the patients were in NYHA Class I and Class II.

Although there was a predominance of women in the study population (64.4%), patients of both sexes demonstrated acceptable hemodynamic outcomes and significant improvement in functional status, according to the FDA summary.

Sutureless valves are considered to have a promising future according to a recent international consensus panel recommendationpublished online in the European Journal of Cardio-Thoracic Surgery (2015 Oct 29. doi: 10.1093/ejcts/ezv369). The report assessed various benefits of sutureless and rapid deployment technology, and concluded these devices “may represent a helpful tool in aortic valve replacement for patients requiring a biological valve.” However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves, they concluded.

[email protected]

LivaNova announced that the U.S. Food and Drug Administration has announced the approval of their Perceval Sutureless Heart Valve. The approval was issued Jan. 8 and is effective immediately, and LivaNova indicated that it will begin commercial distribution of the device in the United States over the coming quarter.

According to an FDA summary document, the Perceval Sutureless Heart Valve is a bioprosthetic valve designed to replace a diseased native or a malfunctioning prosthetic aortic valve via open heart surgery. The self-expanding stent frame consists of a tissue component made from bovine pericardium and a self-expandable nitinol stent, along with a dedicated delivery system that allows physicians to position and anchor the valve suturelessly.

The Perceval heart valve is supplied unmounted and must be loaded onto an accompanying holder by reducing the valve size using a supplied polycarbonate collapser. The holder is used for sternal approaches and includes a rigid shaft with an end section that houses the valve prosthesis during delivery. A separate holder, approximately 3 cm longer, is also available for minimally invasive procedures. After implantation, the physician uses the a post-dilation catheter to expand the valve in situ.

Perceval’s approval was based upon the results of a pivotal European study performed to assess the device, the CAVALIER (Safety and Effectiveness Study of Perceval S Valve for Extended CE Mark) trial. The prospective, multicenter, nonrandomized clinical study was conducted at 26 investigational sites in Austria, Belgium, England, France, Germany, and the Netherlands.

Patients were treated between Feb. 23, 2010, and Sept. 30, 2013, and the database for the PDA-assessed data collected through Nov. 5, 2014, and included 658 patients.

The differences between the New York Heart Association (NYHA) class at 12 months and the baseline were calculated. In total, 77.5% of patients showed a decrease of NYHA equal to at least one class, whereas 19.7% of patients remained stable over the time. Only 2.8% of patients showed a worsened clinical status.

Reduction in mean gradients and increase in effective orifice area were both observed at 1 year follow-up, according to the FDA report.

At the 1-, 2-, and 3-year follow-up time points, 75.1% or greater of the implanted patients with available data had improved by one to three classes and at the 4-year follow-up time point 72.6% of the patients had improved by one to three classes, according to the report. In addition, at the 1-, 2-, and 3-year follow-up time points, 92.9% or greater of the patients were in NYHA Class I and Class II, and at the 4-year follow-up time point, 86.3% of the patients were in NYHA Class I and Class II.

Although there was a predominance of women in the study population (64.4%), patients of both sexes demonstrated acceptable hemodynamic outcomes and significant improvement in functional status, according to the FDA summary.

Sutureless valves are considered to have a promising future according to a recent international consensus panel recommendationpublished online in the European Journal of Cardio-Thoracic Surgery (2015 Oct 29. doi: 10.1093/ejcts/ezv369). The report assessed various benefits of sutureless and rapid deployment technology, and concluded these devices “may represent a helpful tool in aortic valve replacement for patients requiring a biological valve.” However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves, they concluded.

[email protected]

LivaNova announced that the U.S. Food and Drug Administration has announced the approval of their Perceval Sutureless Heart Valve. The approval was issued Jan. 8 and is effective immediately, and LivaNova indicated that it will begin commercial distribution of the device in the United States over the coming quarter.

According to an FDA summary document, the Perceval Sutureless Heart Valve is a bioprosthetic valve designed to replace a diseased native or a malfunctioning prosthetic aortic valve via open heart surgery. The self-expanding stent frame consists of a tissue component made from bovine pericardium and a self-expandable nitinol stent, along with a dedicated delivery system that allows physicians to position and anchor the valve suturelessly.

The Perceval heart valve is supplied unmounted and must be loaded onto an accompanying holder by reducing the valve size using a supplied polycarbonate collapser. The holder is used for sternal approaches and includes a rigid shaft with an end section that houses the valve prosthesis during delivery. A separate holder, approximately 3 cm longer, is also available for minimally invasive procedures. After implantation, the physician uses the a post-dilation catheter to expand the valve in situ.

Perceval’s approval was based upon the results of a pivotal European study performed to assess the device, the CAVALIER (Safety and Effectiveness Study of Perceval S Valve for Extended CE Mark) trial. The prospective, multicenter, nonrandomized clinical study was conducted at 26 investigational sites in Austria, Belgium, England, France, Germany, and the Netherlands.

Patients were treated between Feb. 23, 2010, and Sept. 30, 2013, and the database for the PDA-assessed data collected through Nov. 5, 2014, and included 658 patients.

The differences between the New York Heart Association (NYHA) class at 12 months and the baseline were calculated. In total, 77.5% of patients showed a decrease of NYHA equal to at least one class, whereas 19.7% of patients remained stable over the time. Only 2.8% of patients showed a worsened clinical status.

Reduction in mean gradients and increase in effective orifice area were both observed at 1 year follow-up, according to the FDA report.

At the 1-, 2-, and 3-year follow-up time points, 75.1% or greater of the implanted patients with available data had improved by one to three classes and at the 4-year follow-up time point 72.6% of the patients had improved by one to three classes, according to the report. In addition, at the 1-, 2-, and 3-year follow-up time points, 92.9% or greater of the patients were in NYHA Class I and Class II, and at the 4-year follow-up time point, 86.3% of the patients were in NYHA Class I and Class II.

Although there was a predominance of women in the study population (64.4%), patients of both sexes demonstrated acceptable hemodynamic outcomes and significant improvement in functional status, according to the FDA summary.

Sutureless valves are considered to have a promising future according to a recent international consensus panel recommendationpublished online in the European Journal of Cardio-Thoracic Surgery (2015 Oct 29. doi: 10.1093/ejcts/ezv369). The report assessed various benefits of sutureless and rapid deployment technology, and concluded these devices “may represent a helpful tool in aortic valve replacement for patients requiring a biological valve.” However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves, they concluded.

[email protected]

In Germany, almost all of the marked increase in the use of transcatheter aortic valve replacement (TAVR) since the procedure’s introduction in 2007 occurred in patients unsuited to a surgical approach because of their advanced age or elevated risk, according to an analysis published online Dec. 17 in the New England Journal of Medicine.

The surgical aortic valve replacement (SAVR) is still the standard of care, but many have questioned how the relatively new transcatheter approach has affected clinical practice overall, said Dr. Jochen Reinöhl of the Heart Center, University of Freiburg (Germany) and his associates.

To assess the evolution of treatment since TAVR was introduced, the investigators analyzed data from the Institute for the Hospital Remuneration System, which tracks all patient data regarding diagnoses, comorbidities, and procedures throughout the country. They focused on all 88,573 admissions for isolated surgical aortic valve replacements (55,992 procedures) and for isolated TAVR (32,581 procedures) performed in Germany during 2007-2013.

The number of TAVR procedures increased markedly over time, from 144 to 9,147 per year, while the number of SAVRs declined only slightly, from 8,622 to 7,048 per year. Patients aged 80 years and older accounted for almost all of the dramatic increase in transcatheter procedures, the investigators said (N Engl J Med. 2015 Dec 17;373:2438-47 [doi:10.1056/NEJMoa1500893]).

Overall in-hospital mortality was significantly higher with TAVR (6.5%) than with SAVR (2.8%), for an odds ratio of 2.41. This likely reflects the significantly greater risk of patients selected for TAVR, compared with those undergoing surgery, they said.

Mortality decreased over time in both patient groups, from 3.8% to 2.2% with surgery and from 13.2% to 5.4% with TAVR. In the case of TAVR, this decline is likely from a “learning curve” effect among clinicians, improvements in patient care, and advances in treatment devices. In the case of surgery, the mortality decline is probably due in part to the shift of high-risk patients from SAVR to the transcatheter approach, Dr. Reinöhl and his associates said.

Similarly, complications were significantly more common with TAVR. The need for permanent pacemaker implantation was the most frequently reported complication of TAVR, occurring in 17.7% of the transcatheter group but only 4.0% of the surgical group. Stroke rates (2.5% vs. 1.8%) and rates of acute kidney injury (5.5% vs. 3.0%) followed a similar pattern. In contrast, bleeding complications were more frequent with surgery (14.0% vs. 8.2%).

In Germany, almost all of the marked increase in the use of transcatheter aortic valve replacement (TAVR) since the procedure’s introduction in 2007 occurred in patients unsuited to a surgical approach because of their advanced age or elevated risk, according to an analysis published online Dec. 17 in the New England Journal of Medicine.

The surgical aortic valve replacement (SAVR) is still the standard of care, but many have questioned how the relatively new transcatheter approach has affected clinical practice overall, said Dr. Jochen Reinöhl of the Heart Center, University of Freiburg (Germany) and his associates.

To assess the evolution of treatment since TAVR was introduced, the investigators analyzed data from the Institute for the Hospital Remuneration System, which tracks all patient data regarding diagnoses, comorbidities, and procedures throughout the country. They focused on all 88,573 admissions for isolated surgical aortic valve replacements (55,992 procedures) and for isolated TAVR (32,581 procedures) performed in Germany during 2007-2013.

The number of TAVR procedures increased markedly over time, from 144 to 9,147 per year, while the number of SAVRs declined only slightly, from 8,622 to 7,048 per year. Patients aged 80 years and older accounted for almost all of the dramatic increase in transcatheter procedures, the investigators said (N Engl J Med. 2015 Dec 17;373:2438-47 [doi:10.1056/NEJMoa1500893]).

Overall in-hospital mortality was significantly higher with TAVR (6.5%) than with SAVR (2.8%), for an odds ratio of 2.41. This likely reflects the significantly greater risk of patients selected for TAVR, compared with those undergoing surgery, they said.

Mortality decreased over time in both patient groups, from 3.8% to 2.2% with surgery and from 13.2% to 5.4% with TAVR. In the case of TAVR, this decline is likely from a “learning curve” effect among clinicians, improvements in patient care, and advances in treatment devices. In the case of surgery, the mortality decline is probably due in part to the shift of high-risk patients from SAVR to the transcatheter approach, Dr. Reinöhl and his associates said.

Similarly, complications were significantly more common with TAVR. The need for permanent pacemaker implantation was the most frequently reported complication of TAVR, occurring in 17.7% of the transcatheter group but only 4.0% of the surgical group. Stroke rates (2.5% vs. 1.8%) and rates of acute kidney injury (5.5% vs. 3.0%) followed a similar pattern. In contrast, bleeding complications were more frequent with surgery (14.0% vs. 8.2%).

In Germany, almost all of the marked increase in the use of transcatheter aortic valve replacement (TAVR) since the procedure’s introduction in 2007 occurred in patients unsuited to a surgical approach because of their advanced age or elevated risk, according to an analysis published online Dec. 17 in the New England Journal of Medicine.

The surgical aortic valve replacement (SAVR) is still the standard of care, but many have questioned how the relatively new transcatheter approach has affected clinical practice overall, said Dr. Jochen Reinöhl of the Heart Center, University of Freiburg (Germany) and his associates.

To assess the evolution of treatment since TAVR was introduced, the investigators analyzed data from the Institute for the Hospital Remuneration System, which tracks all patient data regarding diagnoses, comorbidities, and procedures throughout the country. They focused on all 88,573 admissions for isolated surgical aortic valve replacements (55,992 procedures) and for isolated TAVR (32,581 procedures) performed in Germany during 2007-2013.

The number of TAVR procedures increased markedly over time, from 144 to 9,147 per year, while the number of SAVRs declined only slightly, from 8,622 to 7,048 per year. Patients aged 80 years and older accounted for almost all of the dramatic increase in transcatheter procedures, the investigators said (N Engl J Med. 2015 Dec 17;373:2438-47 [doi:10.1056/NEJMoa1500893]).

Overall in-hospital mortality was significantly higher with TAVR (6.5%) than with SAVR (2.8%), for an odds ratio of 2.41. This likely reflects the significantly greater risk of patients selected for TAVR, compared with those undergoing surgery, they said.

Mortality decreased over time in both patient groups, from 3.8% to 2.2% with surgery and from 13.2% to 5.4% with TAVR. In the case of TAVR, this decline is likely from a “learning curve” effect among clinicians, improvements in patient care, and advances in treatment devices. In the case of surgery, the mortality decline is probably due in part to the shift of high-risk patients from SAVR to the transcatheter approach, Dr. Reinöhl and his associates said.

Similarly, complications were significantly more common with TAVR. The need for permanent pacemaker implantation was the most frequently reported complication of TAVR, occurring in 17.7% of the transcatheter group but only 4.0% of the surgical group. Stroke rates (2.5% vs. 1.8%) and rates of acute kidney injury (5.5% vs. 3.0%) followed a similar pattern. In contrast, bleeding complications were more frequent with surgery (14.0% vs. 8.2%).

Over the past 3 decades surgery for aortic root replacement has seen a dramatic decline in rates of death and complications, but there have been few studies comparing which technique would be best for specific patients, and those that have been done have been limited by selection bias or small patient numbers.

But a team of investigators from Weill Cornell Medical College in New York have analyzed results of three different aortic root replacement (ARR) procedures over a 17-year period and found that the rates of death during surgery and complications were less than 1% regardless of the technique. They published their results in the Journal of Thoracic and Cardiovascular Surgery (2015;150:1120-9).

American Association for Thoracic Surgery/JTCVS

“In the current era, aortic root replacement can be performed with very low perioperative risk in high-volume aortic centers,” said Dr. Mario Gaudino and coauthors. “The type of operation performed does not affect early or late survival.”

They compared results of three different approaches to ARR performed in 890 consecutive patients in their institution from May 1997 to January 2014: mechanical composite valved graft (mCVG) in 289 patients; biologic composite valved graft (bCVG) in 421; and valve-sparing reconstruction (VSR) in 180. Then the researchers applied propensity matching to neutralize the differences in the baseline characteristics between the different procedures.

The overall rate of death from the operation was 0.2%, but the two patients who died did so in the first 5 years of the study. There were no deaths in the VSR group, and the incidence of complications after surgery was less than 0.5%. Three-year survival was 94.8% and 5-year survival was 89.4%, and reintervention rates at 5 years were 0% for the mCVG group, 2.4% for the bCVG group, and 7.3% for those who had VSR. “Although mCVG remains the gold standard for durability, bCVG and VSR are excellent options for those who either cannot take or wish to avoid long-term anticoagulation,” Dr. Gaudino and colleagues said.

At the time of surgery, 332 patients (37.3%) had at least one associated cardiac procedure, led by arch replacement (149 patients) and coronary artery bypass (81 patients). Eighty-four patients (9.4%) had two or more associated procedures. The bCVG and mCVG groups had the highest rates of associated cardiac procedures.

Before propensity matching, bCVG patients were older and had more comorbidities and worse functional class, while the mCVG group had higher rates of redo procedures and urgent or emergent operations. Connective tissue disorders were most common in the VSR group.

The results paralleled data from the Society of Thoracic Surgery’s Adult Cardiac Surgery Database, Dr. Gaudino and colleagues said, including a fivefold increase in the number of root replacements performed annually during the study period and a shift away from the traditional mCVG operation to widespread adoption of the bCVG and VSR procedures in the later years of the study.

“Surgeons with extensive experience in aortic surgery can tailor their choice of ARR to the procedure that best suits the individual patient based on their baseline characteristics,” Dr. Gaudino and coauthors said.

Dr. Gaudino and his coauthors had no disclosures. 

Over the past 3 decades surgery for aortic root replacement has seen a dramatic decline in rates of death and complications, but there have been few studies comparing which technique would be best for specific patients, and those that have been done have been limited by selection bias or small patient numbers.

But a team of investigators from Weill Cornell Medical College in New York have analyzed results of three different aortic root replacement (ARR) procedures over a 17-year period and found that the rates of death during surgery and complications were less than 1% regardless of the technique. They published their results in the Journal of Thoracic and Cardiovascular Surgery (2015;150:1120-9).

American Association for Thoracic Surgery/JTCVS

“In the current era, aortic root replacement can be performed with very low perioperative risk in high-volume aortic centers,” said Dr. Mario Gaudino and coauthors. “The type of operation performed does not affect early or late survival.”

They compared results of three different approaches to ARR performed in 890 consecutive patients in their institution from May 1997 to January 2014: mechanical composite valved graft (mCVG) in 289 patients; biologic composite valved graft (bCVG) in 421; and valve-sparing reconstruction (VSR) in 180. Then the researchers applied propensity matching to neutralize the differences in the baseline characteristics between the different procedures.

The overall rate of death from the operation was 0.2%, but the two patients who died did so in the first 5 years of the study. There were no deaths in the VSR group, and the incidence of complications after surgery was less than 0.5%. Three-year survival was 94.8% and 5-year survival was 89.4%, and reintervention rates at 5 years were 0% for the mCVG group, 2.4% for the bCVG group, and 7.3% for those who had VSR. “Although mCVG remains the gold standard for durability, bCVG and VSR are excellent options for those who either cannot take or wish to avoid long-term anticoagulation,” Dr. Gaudino and colleagues said.

At the time of surgery, 332 patients (37.3%) had at least one associated cardiac procedure, led by arch replacement (149 patients) and coronary artery bypass (81 patients). Eighty-four patients (9.4%) had two or more associated procedures. The bCVG and mCVG groups had the highest rates of associated cardiac procedures.

Before propensity matching, bCVG patients were older and had more comorbidities and worse functional class, while the mCVG group had higher rates of redo procedures and urgent or emergent operations. Connective tissue disorders were most common in the VSR group.

The results paralleled data from the Society of Thoracic Surgery’s Adult Cardiac Surgery Database, Dr. Gaudino and colleagues said, including a fivefold increase in the number of root replacements performed annually during the study period and a shift away from the traditional mCVG operation to widespread adoption of the bCVG and VSR procedures in the later years of the study.

“Surgeons with extensive experience in aortic surgery can tailor their choice of ARR to the procedure that best suits the individual patient based on their baseline characteristics,” Dr. Gaudino and coauthors said.

Dr. Gaudino and his coauthors had no disclosures. 

Over the past 3 decades surgery for aortic root replacement has seen a dramatic decline in rates of death and complications, but there have been few studies comparing which technique would be best for specific patients, and those that have been done have been limited by selection bias or small patient numbers.

But a team of investigators from Weill Cornell Medical College in New York have analyzed results of three different aortic root replacement (ARR) procedures over a 17-year period and found that the rates of death during surgery and complications were less than 1% regardless of the technique. They published their results in the Journal of Thoracic and Cardiovascular Surgery (2015;150:1120-9).

American Association for Thoracic Surgery/JTCVS

“In the current era, aortic root replacement can be performed with very low perioperative risk in high-volume aortic centers,” said Dr. Mario Gaudino and coauthors. “The type of operation performed does not affect early or late survival.”

They compared results of three different approaches to ARR performed in 890 consecutive patients in their institution from May 1997 to January 2014: mechanical composite valved graft (mCVG) in 289 patients; biologic composite valved graft (bCVG) in 421; and valve-sparing reconstruction (VSR) in 180. Then the researchers applied propensity matching to neutralize the differences in the baseline characteristics between the different procedures.

The overall rate of death from the operation was 0.2%, but the two patients who died did so in the first 5 years of the study. There were no deaths in the VSR group, and the incidence of complications after surgery was less than 0.5%. Three-year survival was 94.8% and 5-year survival was 89.4%, and reintervention rates at 5 years were 0% for the mCVG group, 2.4% for the bCVG group, and 7.3% for those who had VSR. “Although mCVG remains the gold standard for durability, bCVG and VSR are excellent options for those who either cannot take or wish to avoid long-term anticoagulation,” Dr. Gaudino and colleagues said.

At the time of surgery, 332 patients (37.3%) had at least one associated cardiac procedure, led by arch replacement (149 patients) and coronary artery bypass (81 patients). Eighty-four patients (9.4%) had two or more associated procedures. The bCVG and mCVG groups had the highest rates of associated cardiac procedures.

Before propensity matching, bCVG patients were older and had more comorbidities and worse functional class, while the mCVG group had higher rates of redo procedures and urgent or emergent operations. Connective tissue disorders were most common in the VSR group.

The results paralleled data from the Society of Thoracic Surgery’s Adult Cardiac Surgery Database, Dr. Gaudino and colleagues said, including a fivefold increase in the number of root replacements performed annually during the study period and a shift away from the traditional mCVG operation to widespread adoption of the bCVG and VSR procedures in the later years of the study.

“Surgeons with extensive experience in aortic surgery can tailor their choice of ARR to the procedure that best suits the individual patient based on their baseline characteristics,” Dr. Gaudino and coauthors said.

Dr. Gaudino and his coauthors had no disclosures. 

ORLANDO – The 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator isn’t reliably applicable to HIV-positive adults in its present form because it consistently underpredicts their MI risk, Dr. Michael J. Feinstein reported at the American Heart Association scientific sessions.

That’s the bad news. The good news is that “a simple, data-derived refit of the pooled cohort equations may improve the model’s performance in HIV-positive individuals,” said Dr. Feinstein of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

Tweaking the risk calculator to enhance its accuracy in the HIV-positive population is particularly important because this population is growing in size and aging. And as Dr. Feinstein and coinvestigators showed in another study presented at the AHA meeting, the proportion of deaths due to cardiovascular disease in HIV-positive adults is shooting upward as they live longer because of treatment advances.

The investigators’ analysis of data from the Centers for Disease Control and Prevention national Wonder database showed that the proportion of deaths due to cardiovascular disease more than doubled between 1999 and 2013. Meanwhile, proportionate cardiovascular disease mortality declined by 22% in the general population and by 28% among individuals with inflammatory polyarthropathies.

That the ACC/AHA risk calculator in its present form doesn’t perform adequately in HIV-positive individuals hadn’t previously been shown, but it doesn’t really come as a surprise, according to Dr. Feinstein. After all, it’s known that this population is at 1.5- to 2-fold increased risk for MI and roughly 5-fold increased risk for sudden cardiac death, compared to the general population, where the risk calculator works best.

“Most data suggest that even in the setting of optimally treated HIV and undetectable viral load there’s still an underlying viral reservoir that appears to be driving inflammation and atherothrombotic and even nonatherothrombotic events in this population,” he said.

Dr. Feinstein and coworkers evaluated the 2013 ACC/AHA risk calculator in 11,901 HIV-positive black or white adults enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) database for whom 5-year follow-up was available; 52% of the subjects were aged 40 or older at baseline.

Running each of these nearly 12,000 subjects through the risk calculator, the predicted result was that 103 of them would have an acute MI during the 5-year follow-up period. In reality, 132 MIs were observed. The discrepancy between the risk calculator predictions and observed MI rates was greatest in the 63% of HIV-positive subjects deemed at low risk, with an estimated 10-year risk of atherosclerotic cardiovascular disease of less than 5%.

Among white men, the risk calculator was remarkably consistent in underpredicting MIs. Regardless of whether the risk calculator put their estimated 10-year risk at less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, or at least 10%, the actual observed MI rates were 67%-68% greater across the board than predicted.

Dr. Feinstein and coworkers refit the ACC/AHA risk calculator on a trial basis by incorporating variables related to HIV-positivity into the risk equations. Then they reanalyzed the tool’s performance in the same nearly 12,000 HIV-infected subjects. They found the discrimination and calibration of the revised risk equations improved substantially and met the standard of “acceptable” by statisticians’ standards.

The next step in this ongoing CNICS project will be to validate the provisionally refit risk calculator’s performance in a separate database of HIV-infected adults with adjudicated MIs. If the results are again positive, it will be a relatively straightforward matter to introduce the revisions into the ACC/AHA risk calculator, particularly since the senior coinvestigator in this project is Dr. Donald M. Lloyd-Jones, also of Northwestern University, who played a central role in developing the 2013 risk calculator.

Dr. Feinstein reported having no financial conflicts regarding this study.

[email protected]

ORLANDO – The 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator isn’t reliably applicable to HIV-positive adults in its present form because it consistently underpredicts their MI risk, Dr. Michael J. Feinstein reported at the American Heart Association scientific sessions.

That’s the bad news. The good news is that “a simple, data-derived refit of the pooled cohort equations may improve the model’s performance in HIV-positive individuals,” said Dr. Feinstein of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

Tweaking the risk calculator to enhance its accuracy in the HIV-positive population is particularly important because this population is growing in size and aging. And as Dr. Feinstein and coinvestigators showed in another study presented at the AHA meeting, the proportion of deaths due to cardiovascular disease in HIV-positive adults is shooting upward as they live longer because of treatment advances.

The investigators’ analysis of data from the Centers for Disease Control and Prevention national Wonder database showed that the proportion of deaths due to cardiovascular disease more than doubled between 1999 and 2013. Meanwhile, proportionate cardiovascular disease mortality declined by 22% in the general population and by 28% among individuals with inflammatory polyarthropathies.

That the ACC/AHA risk calculator in its present form doesn’t perform adequately in HIV-positive individuals hadn’t previously been shown, but it doesn’t really come as a surprise, according to Dr. Feinstein. After all, it’s known that this population is at 1.5- to 2-fold increased risk for MI and roughly 5-fold increased risk for sudden cardiac death, compared to the general population, where the risk calculator works best.

“Most data suggest that even in the setting of optimally treated HIV and undetectable viral load there’s still an underlying viral reservoir that appears to be driving inflammation and atherothrombotic and even nonatherothrombotic events in this population,” he said.

Dr. Feinstein and coworkers evaluated the 2013 ACC/AHA risk calculator in 11,901 HIV-positive black or white adults enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) database for whom 5-year follow-up was available; 52% of the subjects were aged 40 or older at baseline.

Running each of these nearly 12,000 subjects through the risk calculator, the predicted result was that 103 of them would have an acute MI during the 5-year follow-up period. In reality, 132 MIs were observed. The discrepancy between the risk calculator predictions and observed MI rates was greatest in the 63% of HIV-positive subjects deemed at low risk, with an estimated 10-year risk of atherosclerotic cardiovascular disease of less than 5%.

Among white men, the risk calculator was remarkably consistent in underpredicting MIs. Regardless of whether the risk calculator put their estimated 10-year risk at less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, or at least 10%, the actual observed MI rates were 67%-68% greater across the board than predicted.

Dr. Feinstein and coworkers refit the ACC/AHA risk calculator on a trial basis by incorporating variables related to HIV-positivity into the risk equations. Then they reanalyzed the tool’s performance in the same nearly 12,000 HIV-infected subjects. They found the discrimination and calibration of the revised risk equations improved substantially and met the standard of “acceptable” by statisticians’ standards.

The next step in this ongoing CNICS project will be to validate the provisionally refit risk calculator’s performance in a separate database of HIV-infected adults with adjudicated MIs. If the results are again positive, it will be a relatively straightforward matter to introduce the revisions into the ACC/AHA risk calculator, particularly since the senior coinvestigator in this project is Dr. Donald M. Lloyd-Jones, also of Northwestern University, who played a central role in developing the 2013 risk calculator.

Dr. Feinstein reported having no financial conflicts regarding this study.

[email protected]

ORLANDO – The 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator isn’t reliably applicable to HIV-positive adults in its present form because it consistently underpredicts their MI risk, Dr. Michael J. Feinstein reported at the American Heart Association scientific sessions.

That’s the bad news. The good news is that “a simple, data-derived refit of the pooled cohort equations may improve the model’s performance in HIV-positive individuals,” said Dr. Feinstein of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

Tweaking the risk calculator to enhance its accuracy in the HIV-positive population is particularly important because this population is growing in size and aging. And as Dr. Feinstein and coinvestigators showed in another study presented at the AHA meeting, the proportion of deaths due to cardiovascular disease in HIV-positive adults is shooting upward as they live longer because of treatment advances.

The investigators’ analysis of data from the Centers for Disease Control and Prevention national Wonder database showed that the proportion of deaths due to cardiovascular disease more than doubled between 1999 and 2013. Meanwhile, proportionate cardiovascular disease mortality declined by 22% in the general population and by 28% among individuals with inflammatory polyarthropathies.

That the ACC/AHA risk calculator in its present form doesn’t perform adequately in HIV-positive individuals hadn’t previously been shown, but it doesn’t really come as a surprise, according to Dr. Feinstein. After all, it’s known that this population is at 1.5- to 2-fold increased risk for MI and roughly 5-fold increased risk for sudden cardiac death, compared to the general population, where the risk calculator works best.

“Most data suggest that even in the setting of optimally treated HIV and undetectable viral load there’s still an underlying viral reservoir that appears to be driving inflammation and atherothrombotic and even nonatherothrombotic events in this population,” he said.

Dr. Feinstein and coworkers evaluated the 2013 ACC/AHA risk calculator in 11,901 HIV-positive black or white adults enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) database for whom 5-year follow-up was available; 52% of the subjects were aged 40 or older at baseline.

Running each of these nearly 12,000 subjects through the risk calculator, the predicted result was that 103 of them would have an acute MI during the 5-year follow-up period. In reality, 132 MIs were observed. The discrepancy between the risk calculator predictions and observed MI rates was greatest in the 63% of HIV-positive subjects deemed at low risk, with an estimated 10-year risk of atherosclerotic cardiovascular disease of less than 5%.

Among white men, the risk calculator was remarkably consistent in underpredicting MIs. Regardless of whether the risk calculator put their estimated 10-year risk at less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, or at least 10%, the actual observed MI rates were 67%-68% greater across the board than predicted.

Dr. Feinstein and coworkers refit the ACC/AHA risk calculator on a trial basis by incorporating variables related to HIV-positivity into the risk equations. Then they reanalyzed the tool’s performance in the same nearly 12,000 HIV-infected subjects. They found the discrimination and calibration of the revised risk equations improved substantially and met the standard of “acceptable” by statisticians’ standards.

The next step in this ongoing CNICS project will be to validate the provisionally refit risk calculator’s performance in a separate database of HIV-infected adults with adjudicated MIs. If the results are again positive, it will be a relatively straightforward matter to introduce the revisions into the ACC/AHA risk calculator, particularly since the senior coinvestigator in this project is Dr. Donald M. Lloyd-Jones, also of Northwestern University, who played a central role in developing the 2013 risk calculator.

Dr. Feinstein reported having no financial conflicts regarding this study.

[email protected]