Veronica Hackenthal, MD

For older heart failure patients or patients with comorbidities, a heart pump is often used for long-term or permanent treatment in place of a heart transplant. A study presented at the International Society for Heart and Lung Transplantation held in Orlando last week shows that heart pumps may work just as well as a heart transplant in these patients.

“These findings are significant because we now know that older patients can take full advantage of a growing treatment for heart failure. It’s exciting to know that this population won’t be deprived of the benefits of this successful treatment,” said the study’s lead author Daniel Goldstein, M.D., in a press release.

Many older patients are medically frail and not eligible for heart transplant, which can increase the risk for adverse events such as clotting, stroke and bleeding.

Dr. Goldstein, of Montefiore Medical Center, Bronx, New York, conducted a randomized controlled trial (MOMENTUM3) of two left ventricular assist devices in patients with advanced heart failure:  HeartMate 3 (HM3) and HeartMate II (HMII). HM3 is a newer version of HMII and has received CE marking in the European Union as well as FDA approval for short-term (bridge-to-transplant) and long-term (destination therapy)  therapy.

The study included 1,028 patients with advanced heart failure who were randomized to HM3 or HMII regardless of whether the pump was to be used as bridge-to-transplant or as destination (long-term) therapy.

Results showed 76.9 percent in the HM3 group compared to 64.5 percent in the HMII group met the primary endpoint, or survival at two years free of disabling stroke or reoperation to replace the pump. The HM3 group also had lower rates of stroke of any severity, as well as lower rates of major bleeding, including gastrointestinal bleeding.

Patients who used the pump as destination therapy had an overall survival of 77 percent at two years. During that time, for every 100 patients in the destination therapy category, implantation of HM3 prevented 110 hemocompatibility related adverse events, such as pump thrombosis, stroke or bleeding.

That represents a “large benefit,” according to Mandeep Mehra, M.D., Harvard Medical School, and author of a related study published in March in the New England Journal of Medicine.

The findings suggest that the categories of bridge-to-transplant and destination therapy are fluid. Only about 50 percent of patients who used the HM3 as bridge-to-transplant actually received a transplant over two years. On the other hand, 13.5 percennt of patients who were considered ineligible for transplant and used HM3 for destination therapy actually went on to transplant.  That suggests that some patients improved so much on HM3 that they were able to move into the transplant category. Thirty-five percent of patients who were in a gray zone categorized as “bridge to candidacy,” were able to receive a transplant.

The researchers suggest that the labels for LVADs may need to be abandoned.
	“The labels are arbitrary and, in fact, may impact a patient’s treatment plan. We need to abolish them from consideration,” Dr. Goldstein said in the press release.

Goldstein D, MR Mehra, MOMENTUM 3 Investigators.   1 - Clinical Outcomes by Intended Goal of Therapy in the MOMENTUM 3 Clinical Trial: Final Analysis of the 1028 Patient Full Cohort. Session PLENARY 1 – Opening Plenary Session. Presented on April 4 2019 at the 39th Annual Meeting and Scientific Sessions of The International Society for Heart & Lung Transplantation. Orlando, Florida. April 3-6.

Mehra MR, Uriel N, Naka Y, et al. A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report. N Engl J Med. 2019 Mar 17. doi: 10.1056/NEJMoa1900486.

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Heart pumps may work just as well as heart transplants for older heart failure patients and complex cases, finds a study presented at the ISHLT annual meeting.

Heart Pump may Expand Treatment Options for Elderly with Heart Failure

More evidence for the biomarker circulating tumor DNA (ctDNA) as a means to test for the presence of a rare, but deadly cancer in organ transplant recipients was presented at the International Society for Heart and Lung Transplantation meeting held in Orlando last week.

The study showed that screening for ctDNA could lead to earlier diagnosis and better management of post-transplant lymphoproliferative disorder (PTLD), an aggressive form of cancer that often affects two to 10 percent of heart transplant recipients within five years of the transplant. PTLD has vague symptoms like fatigue, weight loss and night sweats.  So, diagnosis is often delayed, and death rates are high.

“It’s heartbreaking when a patient almost dies of end-stage heart disease, only to get cancer. We hope this work can go a long way in impacting survival rates for organ transplant recipients,” according to a statement issued by the study’s lead author Kiran Khush, M.D.

About 50 percent of PTLD is caused by the Epstein-Barr virus (EBV), but monitoring for EBV does not reliably predict who will develop lymphoma. 

Using Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq) on tumor tissue from PTLD and other lymphomas, researchers developed a PTLD mutation panel with over 300 genes commonly mutated in humans and associated with PTLD and EBV.

Including an array of mutations allows the test to be more specific for PTLD mutations.

The study included stored blood samples from heart and lung transplant patients who developed PTLD.

Results showed that ctDNA was identifiable in all patients who developed PTLD, and that ctDNA was found as early as one-and-a-half years before clinical diagnosis.

Levels of ctDNA correlated with EBV titers in EBV positive cancer. Both ctDNA levels and EBV titers rose before diagnosis, and both fell with response to treatment. That suggests measuring ctDNA may be helpful for monitoring response to treatment.

“PTLD patients have detectable ctDNA prior to clinical diagnosis. Development of screening tools utilizing such as ctDNA would facilitate early detection of PTLD in the transplant population, and would enable us to monitor response to therapy,” the authors concluded.

Researchers hope to partner with other transplant centers worldwide to continue the development of this test.  They also plan to develop noninvasive tests to improve early detection of lung, colorectal and other common cancers among transplant recipients.


	Khush K, Soo J, Schroers-Martin J, et al. “Early detection of post-transplant lymphoproliferative disorder using circulating tumor DNA.” Session BSTR Basic and Translational Research. Presented April 3, 2019 at the 39th annual meeting of the International Society for Heart & Lung Transplantation. Orlando, Florida.

More evidence for the biomarker ctDNA to test for the presence of a rare, but deadly cancer in organ transplant patients was presented at ISHLT annual meeting this month.

ctDNA Could Detect Post-Transplant Cancer Early

Patients with Medicare Advantage are more likely to receive guideline-recommended care for coronary artery disease than patients with Medicare Fee for Service. But whether that translates into better outcomes remains unclear, according to a study published in the February 20 online issue of 

The study is the first nationwide comparison of quality of care for coronary artery disease among Medicare Advantage beneficiaries as compared to Medicare Fee for Service.

“As Medicare Advantage continues to enroll a higher proportion of beneficiaries each year, it will be important to monitor both quality and outcomes of care to determine whether these patterns ultimately lead to better outcomes in Medicare,” wrote study authors who were led by Jose Figueroa, M.D., MPH, Harvard Medical School, Boston.

Roughly one-third of Medicare beneficiaries are enrolled in Medicare Advantage, which provides a managed care private plan option. It also offers incentives to physicians for providing evidence-based care. Enrollment in Medicare Advantage has risen substantially over the last decade. Current political pressure to support market-driven health reform may further increase enrollment. That underscores the importance of understanding whether quality of care and healthcare outcomes differ between Medicare Advantage and Medicare Fee for Service.

To shed light on the issue, researchers analyzed data from the Practice Innovation and Clinical Excellence (PINNACLE) study, a national quality improvement registry of outpatient cardiology.  The study included data from about 35,000 people with coronary artery disease enrolled in Medicare Advantage and about 172,000 people with coronary artery disease enrolled in Medicare Fee for Service. 

Medicare Advantage beneficiaries were significantly more likely than those with Medicare Fee for Service to receive guideline-recommended treatment for secondary prevention of cardiac events, including Î²-blockers, ACE-inhibitors or ARBs, statins, or all three medications when eligible.

After controlling for age, sex, race/ethnicity, current tobacco use and cardiac-related comorbidities, those with Medicare Advantage remained 10 percent more likely to receive guideline-recommended care.

Other outcomes, like blood pressure and LDL levels, did not differ between those with Medicare Advantage and Medicare Fee for Service.

“Whether or not our findings of higher quality with similar intermediate outcomes represent high-value care under Medicare Advantage compared with Fee for Service Medicare is an important area for future work,” authors wrote.

Participation in the PINNACLE registry is voluntary and may have influenced practices to provide higher quality care, which could have affected results.

Veronica Hackethal, M.D., MSc, is a medical journalist based in New York City who is a long-time contributor to the Modern Medicine Network publications. Her writing has also appeared in the New York Times, Chicago Tribune, NBCNews.com, Reuters Health, Nature Medicine News and Medscape. She is a graduate of Harvard University, Oxford University and Columbia College of Physicians and Surgeons (M.D.).


	Figueroa JF, Blumenthal DM, Feyman Y, et al. Differences in management of coronary artery disease in patients with Medicare Advantage vs traditional fee-for-service Medicare among cardiology practices. 

. Published online February 20, 2019. doi:10.1001/jamacardio.2019.0007

Patients with Medicare Advantage are more likely to receive guideline-recommended care for coronary artery disease than patients with Medicare Fee for Service. But whether that translates into better outcomes remains unclear, a study shows.

Guideline-Recommended CAD Care Better with Medicare Advantage than Fee For Service

Statins decrease major vascular events like stroke and heart attack regardless of age. While the evidence is less robust for people over age 75, evidence suggest this age group may also benefit, finds a new study in 

Statins are one of the mainstays for preventing cardiovascular events in people with high cholesterol.  While many studies have confirmed their benefits, few have included people over age 75.  That has left lingering questions about the safety and efficacy of statins in older people.

To address these questions, the Cholesterol Treatment Trialists' Collaboration analyzed 28 large research clinical trials of statin therapy compared to placebo or usual care. The analysis included over 185,000 individuals, of which 8 percent were over age 75. Participants took statins for about five years, on average.

For each 1.0 mmol/L decrease in LDL that resulted from statin use, the risk of major vascular events decreased by 21 percent overall. All age groups showed a significant decrease in major vascular events associated with statin use.

There was a significant trend towards smaller risk reduction with increasing age for major coronary events like heart attacks.

However, while results also showed a trend toward smaller risk reduction with increasing age for vascular mortality and major vascular events, the results were not significant. After excluding four trials of patients with heart and renal failure (who may benefit less from statins), results showed that older individuals still benefited from statins, in terms of reduced risk for vascular death and major vascular events.

Risk reduction for stroke and coronary revascularization procedures (like CABG) did not differ by age.

Results showed less evidence of benefits for statins in people over age 75 who do not already have vascular disease. But this is a small group for which more studies are needed.

Statins were not tied to cancer death, cancer incidence, or non-vascular death.

The researchers emphasized that the absolute benefit of decreasing LDL with statins may be substantial in older individuals. That’s because the absolute risk of major vascular events increases exponentially with age in untreated individuals.

They concluded: “Statin therapy produces significant reductions in major vascular events, irrespective of age. There is less definitive direct evidence of benefit in the primary prevention setting among patients older than 75 years, but evidence supports the use of statin therapy in older people considered to have a sufficiently high risk of occlusive vascular events.”

Veronica Hackethal,MD, MSc, is a medical journalist based in New York City who is a long-time contributor to the Modern Medicine Network publications. Her writing has also appeared in the New York Times, Chicago Tribune, NBCNews.com, Reuters Health, Nature Medicine News and Medscape. She is a graduate of Harvard University, Oxford University and Columbia College of Physicians and Surgeons (MD).

Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. 

. 2019;393:407-415. doi: 10.1016/S0140-6736(18)31942-1.

Statins decrease major vascular events like stroke and heart attack regardless of age. While the evidence is less robust for people over age 75, evidence suggest this age group may also benefit, a new study shows.

Research Supports Statins in the Elderly

Adding a neprilysin inhibitor to an angiotensin receptor blocker may benefit patients hospitalized for acute decompensated heart failure (ADHF) more than an angiotensin receptor blocker alone, according to the PIONEER-HF trial published online on Feb. 7 in the 

Each year, over one million people in the U.S. are hospitalized with acute decompensated heart failure, of which about 12 percent die. Yet the standard of care for treating decompensated heart failure has remained about the same for the past 45 years.

Sacubitril is a newer drug that inhibits neprilysin, an enzyme involved in blood pressure control.  Sacubutril combined with valsartan has been found to be effective in decreasing the risk of cardiovascular death in outpatients with heart failure.  But studies have not included patients hospitalized for heart failure.

To test the safety and efficacy of sacubitril-valsartan in this group, researchers conducted a randomized, double-blind controlled trial. The study took place at 129 hospitals in the U.S. Researchers randomized 440 patients hospitalized for heart failure to sacubitril-valsartan and 441 to enalapril for eight weeks. Most (72.1 percent) were male, and 35.9 percent were black. 

Both groups showed a decrease over time in NT-proBNP concentration, a biomarker that may predict cardiovascular events. But the sacubutril-valsartan group showed a significantly greater decrease compared to the enalapril group, and this decrease appeared as early as the first week.

The benefits for sacubutril-valsartan (Entresto, Novartis) appeared similar regardless of age, race (white vs black), kidney function and severity of heart failure.

Both groups had similar rates of adverse events. About 20 percent in each group discontinued treatment, mainly because of adverse events. 

“The results of the PIONEER-HF trial extend the evidence base regarding the use of sacubitril–valsartan to populations for which there had been limited or no data,” wrote first author Eric Velazquez, M.D., of Yale University School of Medicine and colleagues.


	Velazquez EJ, Morrow DA, DeVore AD, et al. “Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure,” 

. Feb. 7, 2019. ePpub, Nov. 11, 2018. DOI: 10.1056/NEJMoa1812851.

Adding a neprilysin inhibitor to an angiotensin receptor blocker may benefit patients hospitalized for acute heart failure more than an angiotensin receptor blocker alone, a study shows.

Sacubutril-Valsartan Better than Enalapril for Acute Heart Failure

Source: Guaricci AI, Lorenzoni V, Guglielmo M, et al. Prognostic relevance of subclinical coronary and carotid atherosclerosis in a diabetic and nondiabetic asymptomatic population. Clin Cardiol. 2018;41:769-777.

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