Tag: heart failure

Categories : Cardiovascular Disease Neurodegenerative DiseasesTags :

Unexpected Cognitive Effect of ARNI Therapy in Heart Failure

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Despite fears about cognitive decline in heart failure patients taking angiotensin receptor-neprilysin inhibition (ARNI), an observational study found that the drug instead had a protective effect.

Adults with systolic heart failure taking sacubitril/valsartan (Entresto) starting from 2015–2019 had fewer neurocognitive diagnoses up to 5 years later compared with a those staying on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) alone.

  • Alzheimer’s disease: 1.11% on ARNI vs 1.24% on ACE inhibitors/ARBs
  • Dementia: 4.18% vs 6.49%
  • Cognitive decline: 11.82% vs 14.53%

On the basis of the PARAGON-HF trial,  sacubitril/valsartan won a broad heart failure indication, reaching into the normal ejection fraction range, for prevention of cardiovascular death and hospitalisation.

“Experimental studies with sacubitril/valsartan have fueled theoretical concerns about neurocognitive side effects, but long-term clinical data are scarce,” noted Prabhjot Grewal, MD, of Stony Brook University Hospital in New York, who reported the findings for the Heart Failure Society of America annual virtual meeting.

She explained that neprilysin inhibition by sacubitril could theoretically inadvertently interfere with the degradation of beta amyloid in the central nervous system, where neprilysin is expressed, in addition to the kidneys where it is most abundant.

However there are many factors in cognitive decline in heart failure, such as the circulatory deficit itself; vascular dementia resulting from comorbidities such as hypertension and vascular disease; and Alzheimer’s disease or Lewy body dementia. By ameliorating heart failure and improving blood pressure, drugs such as ACE inhibitors and sacubitril/valsartan could protect cognition, according to Mandeep Mehra, MBBS, MSc, of Brigham and Women’s Hospital and Harvard Medical School in Boston.

“Thus, even if a drug like sacubitril may cause worsening of one type of cognitive decline, it may be counterbalanced by positive effects on other domains since the reasons for cognitive decline in such patients are almost always multi-factorial and the signals may therefore be obfuscated in general analyses,” explained Mehra, who was not involved in the study.

The authors acknowledged that the observational study lacked systematic characterisation, and also leaves room for residual confounding despite propensity matching.

“This is why we require a prospective study that includes mechanistic end points (degree of beta amyloid protein deposition) in concert with functional outcomes (sensitive measures of cognitive decline) while ensuring that sufficient time is allowed to be evaluated since these are slow and subtle effects,” Mehra said, adding that the PERSPECTIVE trial will likely publish findings in 2022.

Source: MedPage Today

Categories : Cardiovascular DiseaseTags :

Study Evaluates Efficacy and Tolerability of Ultrafiltration

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A new study evaluates the efficacy and renal tolerability of ultrafiltration in acute decompensated heart failure.

Acute decompensated heart failure (ADHF) is a life-threatening and costly disease. Controversy remains regarding the efficacy and renal tolerability of ultrafiltration for treating ADHF. This article by Yajie Liu and Xin Yuan from the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China, and published in Cardiovascular Innovations and Applications, evaluated this clinical issue.

After searching databases for relevant trials, their quality and outcomes were evaluated with the use of the risk of the bias assessment tool and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, respectively. Risk ratio and the standardised or weighted mean differences were computed and pooled with fixed-effects or random-effects models.

The 19-study meta-analysis, involving 1281 patients, found that ultrafiltration was superior to control for weight loss (1.24kg) and fluid removal (1.55L) and was associated with a significant increase in serum creatinine level compared with the control treatments (0.15 mg/dL).
No significant effects were found for serum N-terminal prohormone of brain natriuretic peptide level, length of hospital stay, all-cause mortality, or all-cause rehospitalisation in the ultrafiltration group.

Overall, the meta-analysis found that use of ultrafiltration in patients with ADHF is superior to control treatments for weight loss and fluid removal but has adverse renal effects and lacks significant effects on long-term prognosis.

Source: News-Medical.Net

Categories : Cardiovascular DiseaseTags :

Lung Fibrosis Drug Pirfenidone Shines in Heart Failure Trial

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Pirfenidone, a drug to treat lung fibrosis, has shown in early trial phases that it could also help patients who suffer from a common form of heart failure.

Trialed by University of Manchester and Manchester University NHS Foundation Trust doctors and scientists, in conjunction with Liverpool Clinical Trials Centre, pirfenidone could offer a much-needed viable treatment for heart failure with preserved ejection fraction (HFpEF). The study was published in Nature Medicine.

Just under a third of 55-year-olds will develop heart failure, and 2 to 3 of every 10 people diagnosed die within a year. In about half of patients with heart failure, the forward pumping function of the heart is normal, referred to as heart failure with preserved ejection fraction (HFpEF).

While a number of processes lead to heart failure, fibrosis of the heart muscle is thought to be an important mechanism in around half to two-thirds of patients with HFpEF and is associated with adverse outcomes.

Study leader Dr Chris Miller, National Institute for Health Research Clinician Scientist at The University of Manchester, said: “Heart failure is as devastating an illness as some of the most common cancers, however its profile is much lower and treatment options for HFpEF are very limited.

“Using cardiac MRI, we were able to select patients in whom heart scarring is important. Pirfenidone then reduced that scarring.”

Pirfenidone inhibits the biological processes involved in scar formation.

The study enrolled 94 patients with heart failure, normal forward pumping function of the heart and evidence of fluid retention, randomising half to a pirfenidone treatment group and half to placebo.

Eligible patients had cardiac MRI scanning, and those who had evidence of heart scarring, as indicated by a measurement called ‘extracellular volume’. 

A second cardiac MRI was conducted a year later to measure change in heart scarring, and researchers found that extracellular volume fell by 1.21% on average in patients who took pirfenidone compared with those receiving placebo.

“Based on data from previous studies, this amount of reduction in heart scarring could translate into a substantial reduction in rates of death and admission to hospital for heart failure, however larger trials are needed to determine this,” said Dr Miller.

Additionally, fluid retention also improved in patients taking pirfenidone compared to those receiving placebo, measured using a blood test called NT-proBNP.

Dr Miller added: “Though further investigation is required, the associated improvement in fluid retention provides support for heart scarring having a causal role in heart failure and being an effective treatment target”.

The most common side effects were nausea, insomnia and rash, which are similar to that which lung patients can experience taking the drug. The results are “exciting”, Dr Miller said, but added that further trials are needed.

Source: University of Manchester

Categories : Cardiovascular Disease Implants and ProsthesesTags :

Ventricular Assist Device Pulled from Market due to Failures

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Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

The HeartWare system, a left ventricular assist device (LVAD) for advanced heart failure patients, is being discontinued immediately, according to the Food and Drug Administration.

The manufacturer, Medtronic, is halting global distribution and sale of its HeartWare system in the wake of observational evidence of increased neurological adverse events and mortality for its LVAD compared with similar mechanical circulatory support (MCS) devices.

Last December, some HeartWare LVADs were recalled because of complaints that the pump may delay or fail to start. So far 100 of these complaints have been received, including 14 patient deaths and 13 cases where an explant was necessary, the FDA noted.

“We have been carefully monitoring the adverse events associated with this device and support its removal from the marketplace,” said Bram Zuckerman, MD, director of the Office of Cardiovascular Devices at the FDA’s Center for Devices and Radiological Health, in a statement.

Medtronic now advises physicians to immediately stop new implants of the HeartWare device, but does not recommend explants.

The company is working on a plan for ongoing support of the some 4000 patients around the world who currently have this LVAD. It received commercial approval for use in the US in November 2012.

The FDA named Abbott’s HeartMate 3 as one alternative LVAD for patients with end-stage heart failure. This device features a magnetic levitation system that keeps the rotor separate without mechanical contact.

“The FDA is working closely with both Medtronic and Abbott to ensure patient care is optimised during this transition period and that there is an adequate supply of devices available to provide this patient population with options for end-stage heart failure treatment,” said Dr Zuckerman.

In a separate press release, Abbott reassured the public that it has the ability to meet increased demand for MCS devices as a result of HeartWare withdrawal from clinical use.

Source: MedPage Today

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

Averting Heart Failure by Shutting Down a Heart Protein

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Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

Shutting down a protein found in cardiac muscle could be a new mechanism to treat post-heart attack heart failure, according to research led by the University of Cambridge.

New drugs are needed to improve the heart’s pumping ability after damage from a heart attack. Drugs that strengthen the contraction of failing heart muscle have been deemed unsafe, leaving a gap in the heart attack and heart failure armamentarium.

Researchers now believe that they might have identified a new drug target—a protein called MARK4.

In research funded by the British Heart Foundation (BHF), Cambridge scientists found levels of MARK4 were elevated in mouse hearts after a heart attack. When they compared mice with and without MARK4 in the heart, they found hearts lacking the protein pumped blood 57% more efficiently. This protective effect was seen 24 hours after a heart attack and persisted over the entire follow-up period of four weeks.

The team was first in identifying that MARK4 fine-tunes a structural network within the heart muscle cell—called the microtubule network—that attaches to the machinery governing heart muscle cells contraction and relaxation. When MARK4 levels were increased after a heart attack, microtubules were tightly anchored onto the contractile machinery in the heart, increasing resistance and hindering normal function. When MARK4 levels were reduced, microtubules were loosely anchored, making contraction and relaxation easier.

Following a heart attack the speed of contraction in MARK4-lacking muscle cells increased by 42 percent and the speed of relaxation increased by 47 percent, compared to muscle cells from mice that had the MARK4 protein. They were also almost on par with healthy heart muscle performance, attesting to the power of reducing MARK4.

Based on these findings, the researchers suggested that drugs to switch off MARK4 could be a new way to improve recovery and help the heart to pump blood more efficiently in people with failing hearts.

Dr Xuan Li, BHF Intermediate Research Fellow at University of Cambridge BHF Centre of Research Excellence, said: “After years of research we’ve revealed an entirely new and promising way that could help the recovery of failing hearts.

“It’s early days, and we now need to test the longer-term effects of switching off MARK4. But if drugs to do that prove successful, the life-changing benefits could be seen in people with other types of heart disease as well as those who’ve had a heart attack and developed heart failure.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “Heart attacks are a major cause of disability worldwide—people who’ve had a major heart attack are at much greater risk of developing chronic heart failure. There are around 920 000 people living with heart failure in the UK, and we desperately need drugs to drastically improve the heart’s function in these patients.

“These findings are a positive step forward. Further research is needed to refine and test drugs that can target MARK4 before we’ll see them given to people who’ve had a heart attack and develop heart failure.”

Source: University of Cambridge

Categories : Ageing Cardiovascular Disease ExerciseTags :

Tailored Heart Failure Rehabilitation Improves Outcomes

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An innovative early cardiac rehabilitation intervention customised for the individual improved physical function, frailty, quality of life, and depression in hospitalised heart failure patients. 

Photo from Olivier Collett on Unsplash

These findings were published  in the New England Journal of Medicine and also presented at the American College of Cardiology’s 70th Annual Scientific Session.  

“Designing earlier and more personalised individual-specific approaches to heart failure rehab shows great promise for improving outcomes for this common but complex condition that is one of the leading causes of hospitalisation for older adults,” said National Institute on Aging (NIA) Director Richard J Hodes, MD. “These results mark encouraging progress on a path to better overall quality of life and physical function for the millions of older Americans who develop heart failure each year.”

The study team was led by Dalane W Kitzman, MD, professor of cardiovascular medicine and geriatrics/gerontology at Wake Forest School of Medicine, Winston-Salem, North Carolina, and they followed 349 clinical trial participants with heart failure enrolled in “A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients” (REHAB-HF). On average, participants had five comorbidities that reduced of function — diabetes, obesity, high blood pressure, lung disease or kidney disease.

In an earlier pilot study, Kitzman and colleagues found striking deficits in strength, mobility and balance, along with the expected loss of endurance in older patients with acute heart failure, who were mostly fail or pre-fail. The team decided to focus on improving patients’ physical function, weakened already by chronic heart failure and age, and which was worsened by the traditional cardiac hospital experience involving lots of bedrest and resulting in loss of functions often persisting after discharge.

To address this. The REHAB-HF team designed earlier and more customised exercise programs focusing on improving balance, strength, mobility and endurance. They also began REHAB-HF during a patient’s hospital stay when possible rather than the usual six weeks post-discharge. After discharge, participants shifted to outpatient sessions three times per week for three months.

Compared to a control group getting usual cardiac rehab care, REHAB-HF participants showed significant gains in measures of physical functioning and overall quality of life, including tests for lower extremity function and mobility, and a six-minute walk test. Self-perception of their health status and depression improved in surveys compared to pre-trial baselines. Over 80% of REHAB-HF participants reported they were still doing their exercises six months after study completion.

“These findings will inform choices of heart failure rehabilitation strategies that could lead to better physical and emotional outcomes,” said Evan Hadley, M.D., director of NIA’s Division of Geriatrics and Clinical Gerontology. “Tailored interventions like REHAB-HF that target heart failure’s related decline in physical abilities can result in real overall benefits for patients.”

The study did not show significant differences in related clinical events including rates of hospital readmission for any reason or for heart-failure related rehospitalizations. The research team plans to further explore that and other issues through future expansions of REHAB-HF into larger and longer-term trials with broader participant subgroups.

Source: National Institute on Aging

Journal information: Kitzman et al. Rehabilitation Intervention in Older Patients with Acute Heart Failure with Preserved versus Reduced Ejection Fraction. New England Journal of Medicine. 2021 May 16 doi: 10.1056/NEJMoa2026141.