Collagen Biomarker Associated With Atrial Fibrillation and Heart Failure Risk

MedicalResearch.com Interview with:
Susana Ravassa PhD

Program of Cardiovascular Diseases, CIMA
University of Navarra, and IdiSNA
Navarra Institute for Health Research
Pamplona, Spain 

MedicalResearch.com: What is the background for this study?

Response: Atrial fibrillation (AF) is an evolving epidemic responsible for substantial morbidity, mortality and health-care expenditure. In particular, when AF and heart failure (HF) occur in combination, clinical evolution is particularly poor. Left atrial (LA) myocardial interstitial fibrosis (MIF) is the main structural lesion in AF and considered as the main factor responsible for the perpetuation of this pathology. In addition, it is known that MIF is associated with a lower effectiveness of the treatment of AF by pulmonary vein isolation with catheter ablation. Therefore, the identification of biomarkers related to MIF, as an affordable and minimally invasive approach, is of great interest to detect patients at risk of AF, as well as to monitor their response to the LA ablation therapy.

We had previously demonstrated that the deleterious impact of MIF in the heart is due to alterations in both the quality (i.e., extent of cross-linking among collagen fibrils and type of collagen fibers that determine their rigidity and resistance to degradation [collagen cross-linking or CCL]) and the quantity (i.e., extent of collagen fibers that occupy the myocardial tissue [collagen deposition or CD]) of fibrotic tissue. We have shown that certain circulating biomarkers related to collagen type I metabolism are associated with CCL and CD. On the one hand, the serum carboxy-terminal propeptide of procollagen type I (PICP), released during the conversion of procollagen type I into fibril-forming mature collagen type I, is directly correlated with myocardial CD.

On the other hand, the ratio of serum carboxy-terminal telopeptide of collagen type I to serum matrix metalloproteinase-1 (serum CITP:MMP-1 ratio) is inversely correlated with myocardial CCL, as the higher is the cross-linking among collagen type I fibrils the lower will be the cleavage of CITP by MMP-1 during the process of degradation of the fiber. Interestingly, we have previously reported that the combination of these biomarkers identifies patients with heart failure presenting with a complex pattern of MIF characterized by both increased CCL and CD (CCL+CD+) showing a higher risk of adverse clinical evolution as compared with heart failure  patients without this combination of biomarkers. As both increased CCL and CD have been found in the left atrial myocardium in patients with AF, we designed this investigation to explore whether the CCL+CD+ combination of biomarkers is associated with AF. Continue reading

Flu Linked to Marked Increase in Heart Failure Admissions

MedicalResearch.com Interview with:

Sonja Kytomaa MAResearch AssociateBrigham and Women’s Hospital

Sonja Kytomaa

Sonja Kytomaa MA
Research Associate
Brigham and Women’s Hospital

Scott D. Solomon, MDThe Edward D. Frohlich Distinguished ChairProfessor of MedicineHarvard Medical SchoolSenior PhysicianBrigham and Women’s HospitalInternational Associate Editor, European Heart Journal

Dr. Scott Solomon

Scott D. Solomon, MD
The Edward D. Frohlich Distinguished Chair
Professor of Medicine
Harvard Medical School
Senior Physician
Brigham and Women’s Hospital
International Associate Editor, European Heart Journal

 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Influenza is associated with an increased risk of cardiovascular events, yet few studies have explored the temporal association between influenza activity and hospitalizations, especially due to heart failure (HF).

Our aim with this study was to explore the temporal association between influenza activity and hospitalizations for HF and myocardial infarction (MI) in the general population. We related the number of MI and HF hospitalizations by month, which were sampled from 4 US communities and adjudicated in the surveillance component of the Atherosclerosis Risk in Communities (ARIC) study, to monthly influenza-like illness activity, as reported by the Centers for Disease Control and Prevention. We found that a 5% increase in influenza activity was associated with a 24% increase in HF hospitalizations rates, while overall influenza was not significantly associated with MI hospitalizations. Influenza activity in the months before hospitalization was not associated with either outcome.

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Mesenchymal Stem Cells May Reduce Complications in Heart Failure Patients with LVAD

MedicalResearch.com Interview with:

Annetine C. Gelijns, PhDChair, Department of Population Health Science & PolicyEdmond A. Guggenheim Professor of Health PolicyCo-Director, InCHOIR

Dr. Gelijns

Annetine C. Gelijns, PhD
Professor and System Chair
Population Health Science and Policy
Icahn School of Medicine at Mount Sinai

Alan J Moskowitz, MDProfessor, Population Health Science and PolicyDepartment of Population Health Science & PolicyIcahn School of Medicine at Mount SinaiNew York, NY 10029-6574

Dr. Moskowitz


Alan J Moskowitz, MD

Professor of Population Health Science and Policy
Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this study? Where do these mesenchymal cells come from? 

Response: Implantable LVADs significantly improve the survival and quality of life of advanced heart failure patients. However, these devices are associated with substantial adverse events, including infection and thromboembolic events. Moreover, whereas these devices improve myocardial function, few patients recover sufficient function to be explanted from their LVAD. These observations have focused attention on stem cells as a possible adjunctive therapy to further augment cardiac recovery.

Mesenchymal precursor cells (MPCs), which are obtained from healthy donors and culture-expanded, have been shown in animal and early human studies to improve cardiac function. Using temporary weaning as a signal of cardiac recovery, we conducted an exploratory trial in the Cardiothoracic Surgical Trials Network (CTSN), which found that MPCs increased the probability of temporary weaning from full LVAD support compared to sham-control patients. Therefore, this signal of efficacy led the CTSN to design our current follow-up trial evaluating the efficacy and safety of a higher dose of MPCs in LVAD patients.

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Validation of MEESSI Score for Acute Heart Failure Risk

MedicalResearch.com Interview with:
Desiree Nadine Wussler MD
Cardiovascular Research Institute
Universitätsspital Basel

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Acute heart failure is the most common cause of hospitalization in patients 50 years or older with more than 2 millions of hospitalizations annually in both Europe and the United States.

As most patients with  acute heart failure present to the emergency department, an early risk stratification is of crucial importance in order to decide whether to hospitalize a patient or even treat him in an intensive care unit setting.

Recently, the MEESSI Acute heart failure risk score was developed to predict 30-day mortality in patients presenting with acute heart failure to emergency departments in Spain.  However, it was unknown whether it also performs well in other countries. When externally validating the MEESSI-Score in unselected AHF patients treated in another European country, we report the following major findings.

  1. After stratifying patients into the original MEESSI-AHF Score risk groups, a pronounced difference in 30-day mortality was found.
  2. The MEESSI-Score showed excellent discrimination for every applied model.
  3. In patients assigned to low and intermediate risk of 30-day mortality, the MEESSI-score showed near ideal calibration.
  4. After recalibration there was also a high concordance of the predicted 30-day mortality according to the MEESSI Score and the observed mortality in patients stratified to high and very high-risk.

MedicalResearch.com: What should readers take away from your report?

Response: The MEESSI Score seems to be a highly promising tool for stratifying patients presenting to the emergency department with acute heart failure according to their risk. However, recalibration may be needed when introducing the score to new populations. Furthermore, recalibration could also be important when outcome frequencies change due to novel therapies and consecutive improved outcomes. To the best of our knowledge, except for the MEESSI-Score there is no other heart failure risk score which could be adapted to changed outcome frequencies that easily. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: In my opinion the next step would be a clinical trial. In such a study, patients should be either randomized to a control group in which risk stratification and the following further treatment are left to the discretion of the attending physician or to the intervention group in which patients are stratified into different risk groups according to their MEESSI Score. In this setting the clinical implications and additional application areas of the MEESSI Score could be further characterized. 

Citation:

Wussler D, Kozhuharov N, Sabti Z, Walter J, Strebel I, Scholl L, et al. External Validation of the MEESSI Acute Heart Failure Risk ScoreA Cohort Study. Ann Intern Med. [Epub ahead of print ] doi: 10.7326/M18-1967

 

Feb 1, 2019 @ 11:48 am

 

 

 

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Can New Heart Failure Patients Drink Alcohol?

MedicalResearch.com Interview with:

David L. Brown, MD, FACC Professor of Medicine Cardiovascular Division Washington University School of Medicine St. Louis, MO 63110

Dr. Brown

David L. Brown, MD, FACC
Professor of Medicine
Cardiovascular Division
Washington University School of Medicine
St. Louis, MO 63110

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The genesis of this study was a patient asking me if he could continue to have a nightly cocktail or two after he was hospitalized with the new diagnosis of heart failure.

The main findings are that moderate drinking after the diagnosis of heart failure in older adults is probably safe and is associated with longer survival. These types of studies can not prove a causal relationship between alcohol consumption and survival. 

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RAS Inhibitor Linked to Reduced Heart Failure and Mortality After TAVR

MedicalResearch.com Interview with:

Taku Inohara MD, PhD Duke Clinical Research Institute,  Duke University Medical Center, Durham, North Carolina Department of Cardiology  Keio University School of Medicine, Tokyo, Japan

Dr. Inohara

Taku Inohara MD, PhD
Duke Clinical Research Institute,
Duke University Medical Center,
Durham, North Carolina
Department of Cardiology
Keio University School of Medicine, Tokyo, Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Transcatheter aortic valve replacement (TAVR) has been increasingly used for treating patients with severe aortic stenosis.

Owing to the advancement of TAVR technology, the mortality and heart failure (HF) readmission after TAVR is decreasing over time, but 4.3% experienced readmission due to HF and 23.7% died within 1 year after TAVR. Inhibition of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin-receptor blockers (ARBs) is known to improve clinical outcomes in patients with heart failure, but there remains unknown whether a RAS inhibitor is associated with a reduction in mortality and heart failure readmission after TAVR.

Using the STS/ACC TVT Registry, a nationwide TAVR Registry in the US, we analyzed 15896 propensity-matched patients who underwent TAVR and found that receiving a prescription for a RAS inhibitor at discharge, compared with no prescription, was associated with a reduced risk for mortality ( 12.5% vs 14.9%) and HF readmission (12.0% vs 13.8%).

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Data Support National Guidelines for ARNI Therapy in Eligible Patients with Heart Failure with Reduced Ejection Fraction

MedicalResearch.com Interview with:
Pratyaksh K. Srivastava, MD
Division of General Internal Medicine, UCLA
Gregg C. Fonarow, MD
Ahmanson-UCLA Cardiomyopathy Center
UCLA  Medical Center, Los Angeles
Associate Editor, JAMA Cardiology

MedicalResearch.com: What is the background for this study? 

Response: Angiotensin Receptor-Neprilysin Inhibitors represent a novel class of heart failure therapeutics that have been shown to significantly improve mortality among patients with heart failure with reduced ejection fraction (HFrEF).

In the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with Angiotensin Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril-valsartan was associated with a 20% relative risk reduction in the primary outcome of death from cardiovascular causes or first hospitalization for worsening heart failure over a median follow up of 27 months.

In our current study, we present long term (5-year) absolute risk reductions associated with the addition of angiotensin receptor-neprilysin inhibition to standard HFrEF background therapy using data from PARADIGM-HF. We utilize the number needed to treat (NNT) to quantify absolute risk reduction, and ultimately compare 5-year NNT values for sacubitril-valsartan to those of well-established HFrEF therapeutics for the outcome of all-cause mortality.

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Study Finds Medicare Readmissions Penalties Have Not Increased Mortality from Heart Failure

MedicalResearch.com Interview with:

Teryl K. Nuckols, MD Vice Chair, Clinical Research Director, Division of General Internal Medicine Cedars Sinai Los Angeles, California

Dr. Nuckols

Teryl K. Nuckols, MD
Vice Chair, Clinical Research
Director, Division of General Internal Medicine
Cedars Sinai
Los Angeles, California

MedicalResearch.com: What is the background for this study?

Response: The Medicare Hospital Readmissions Reduction Program (HRRP) penalizes hospitals with increased 30-day readmission rates among seniors admitted with heart failure (HF).  Heart failure readmission rates declined markedly following the implementation of this policy. Two facts have raised concerns about whether the HRRP might have also inadvertently increased 30-day heart failure mortality rates.

First, before the policy was implemented, hospitals with higher heart failure readmission rates had lower 30-day HF mortality rates, suggesting that readmissions are often necessary and beneficial in this population. Second, 30-day HF mortality rose nationally after the HRRP was implemented, and the timing of the increase has suggested a possible link to the policy.

Are hospitals turning patients away, putting them at risk of death, or is the increase in heart failure mortality just a coincidence? To answer this question, we compared trends in 30-day HF mortality rates between penalized hospitals and non-penalized hospitals because 30-day HF readmissions declined much more at hospitals subject to penalties under this policy.

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New Biomarker Allows ‘Liquid Biopsy’ of Heart Muscle

MedicalResearch.com Interview with:

Robin M. Shaw, MD, PhD Wasserman Foundation Chair in Cardiology in honor of S. Rexford Kennamer MD Division of Cardiology, Smidt Heart Institute Department of Medicine, Cedars-Sinai Medical Center, Division of Cardiology, Department of Medicine University of California, Los Angeles, California

Dr. Shaw

Robin M. Shaw, MD, PhD
Wasserman Foundation Chair in Cardiology
in honor of S. Rexford Kennamer MD
Division of Cardiology, Smidt Heart Institute
Department of Medicine, Cedars-Sinai Medical Center,
Division of Cardiology, Department of Medicine
University of California,
Los Angeles, California

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: At present, doctors do not have a clinical tool that assesses the biochemical health of heart muscle.  Biomarkers are available that tests the amount of fluid in the heart, and whether a heart is overloaded (which can be resolved with diuretics).  However, we don’t have biomarkers that assess the state of heart muscle itself.  As a result, doctors can use biomarkers to determine whether, when a patient has trouble breathing, there is heart failure present.

However, biomarkers do not work when the patient does not have symptoms or when we already know the patient has heart failure and are trying to make clinical management decisions about the condition.

Current biomarkers also don’t work to assess the health of the heart before symptoms develop which is to detect cellular changes in muscle before overall heart function is impaired. The new biomarker, CS, address the above unmet needs.  CS is based on cBIN1 which is a heart muscle protein that is essential for the heart to both contract and relax.  cBIN1 decrease when hearts are stressed such as in heart failure.  cBIN1 is also released into the blood stream, so it can be detected from a simple blood draw.  CS is determined from the inverse of cBIN1, so low cBIN1 in blood will give a high CS signal.  A low cBIN1, or a high CS, indicates failing heart muscle, and an increased likelihood for being admitted to the hospital with acute heart failure within the next twelve months.  Continue reading

Heart Failure Medications Underutilized in Medical Practice

MedicalResearch.com Interview with:

Dr. Greene

Stephen J. Greene, MD
Fellow, Division of Cardiology
Duke University Medical Center
Durham, NC, USA

Stephen J. Greene, MD Fellow, Division of Cardiology Duke University Medical Center Durham, NC, USA

Dr. Fonarow

Gregg C. Fonarow, MD, FACC, FAHA, FHFSA
Eliot Corday Professor of Cardiovascular Medicine and Science
UCLA

 


MedicalResearch.com: What is the background for this study?

Response: Heart failure is a very common medical condition impacting roughly 6 million men and women in the United States, and associated with impaired quality of life, frequent hospitalizations, and high rates of death.

There are over 300,000 deaths each year in the US among patients with heart failure. Half of heart failure patients have heart failure because of a weak heart muscle where the heart cannot eject a normal amount of blood with each heartbeat, a term called “reduced ejection fraction.” Fortunately, there are multiple medications proven in large clinical trials to make people with heart failure with reduced ejection fraction live longer and feel better.

We also have target doses for these medications, which are the doses used in the trials where the medication proved its benefit. These medications and the target doses are strongly recommended in professional guidelines to improve patient outcomes.

To make sure patients have the best outcomes possible, it is important that we work to get patients on these proven medications if at all possible. Unfortunately, prior research has suggested that many patients eligible for these medications in regular outpatient practice do not receive them.

Most of this research is several years old, and there have been a lot of efforts to improve the quality of heart failure care in the meantime. In our study, we wanted to see if there have been improvements in the use and dosing of proven heart failure medications in modern-day practice. We also wanted to determine which patient factors were associated with not receiving a medication, or receiving the medication at a below target dose.

Continue reading

More Protein Associated With Moderate Increase in Heart Failure in Men (except for fish and eggs)

MedicalResearch.com Interview with:
“mmmm Meat” by Glen MacLarty is licensed under CC BY 2.0
Jyrki Virtanen, PhD
Adjunct professor of nutritional epidemiology
Heli Virtanen, MSc

University of Eastern Finland
Institute of Public Health and Clinical Nutrition
Kuopio, Finland 


MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies have found that animal sources of protein may have an adverse impact on the risk of cardiovascular diseases, like myocardial infarct, whereas plant sources of protein have had an opposite impact.

In this study we investigated that how protein intake from different dietary sources is associated with developing heart failure in men during the study’s follow-up. During the mean follow-up time of about 22 years, 334 men developed heart failure.

The main finding of the study was that higher protein intake was associated with a moderately higher risk of heart failure and the findings were similar with protein from most dietary sources, although the association was stronger with protein from animal sources. Only protein from fish and eggs were not associated with the risk in our study. Continue reading

Which Diabetes Meds Reduce Heart Failure and Death?

MedicalResearch.com Interview with:

Sean Lee Zheng BM BCh MA MRCP Cardiovascular Division King's College Hospital London British Heart Foundation Centre of Research Excellence London, UK

Dr. Zheng

Sean Lee Zheng BM BCh MA MRCP
Cardiovascular Division
King’s College Hospital London
British Heart Foundation Centre of Research Excellence
London, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The growing prevalence of type 2 diabetes and its associated burden on cardiovascular disease is a global problem. A number of drug treatments effective in lowering blood glucose are now available, with the three latest drug classes developed being the DPP-4 inhibitors, GLP-1 agonists and SGLT-2 inhibitors. While the use of medications from these three classes are increasing, it remains unknown how they compare in lowering the risk of death or cardiovascular disease. This leads to clinical uncertainty when it comes to introducing new medicines for our patients. Our study aimed to use data from randomized clinical trials in a network meta-analysis, allowing these three drug classes to be compared with one another.

Our study, which included 236 studies enrolling 176310 participants, showed that the use of SGLT-2 inhibitors or GLP-1 agonists were associated with a lower risk of death than with DPP-4 inhibitors. SGLT-2 inhibitors had additional beneficial effects on heart failure events compared with the other two drug classes.

Continue reading

Sacubitril/Valsartan Reduces Physical and Social Limitations in Heart Failure Patients

MedicalResearch.com Interview with:
Dr. Alvin Chandra  MD first author  and
Dr. Scott David Solomon M.D.
Director, Noninvasive Cardiology
Professor, Harvard Medical School
Cardiovascular Medicine
Brigham and Women’s Hospital
Boston, Massachusetts

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In general, the quality of life of heart failure with reduced ejection fraction patients is quite impaired, and  similar to that of patients on dialysis.

PARADIGM-HF was the largest trial of heart failure patients and showed that sacubitril/valsartan was superior to the gold-standard enalapril in reducing cardiovascular death, heart failure hospitalization and all-cause mortality. In addition, patients on sacubitril/valsartan, when compared to enalapril, showed significant improvement in overall quality of life.

In this study we looked in more detail at the individual components of “quality of life” and found that in virtually all domains and activities, patients who were randomized to sacubitril/valsartan reported improvement in their limitations  compared to those who were randomized to enalapril. These activities included jogging, doing hobbies, and household chores, with the largest improvement seen in  sexual activities limitations.

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Readmissions After LVAD For Heart Failure High, Mostly For Non-Cardiac Causes

MedicalResearch.com Interview with:
Dr. Sahil Agrawal, MBBS MD

Division of Cardiology, St. Luke’s University Health Network, Bethlehem, PA
Dr Lohit Garg MD
Division of Cardiology
Lehigh Valley Health Network, Allentown 

MedicalResearch.com: What is the background for this study?

Response: Readmissions among advanced heart failure patients are common and contribute significantly to heath care related costs. Rates and causes of readmissions, and their associated costs among patients after durable left ventricular assist device (LVAD) implantation have not been studied in a contemporary multi-institutional setting. We studied the incidence, predictors, causes, and costs of 30-day readmissions after LVAD implantation using Nationwide Readmissions Database (NRD) in our recently published study.

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Cardiovascular Trials Need Better Characterization of Heart Failure in Diabetics

MedicalResearch.com Interview with:

Stephen J. Greene, MD Division of Cardiology Duke University Medical Center Durham, NC

Dr. Greene

Stephen J. Greene, MD
Division of Cardiology
Duke University Medical Center
Durham, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In 2008, the United States FDA issued an industry guidance specifying that diabetes drugs should routinely be tested in large cardiovascular outcome trials to confirm cardiovascular safety. The guidance specifically mentioned cardiovascular safety in terms of MACE, or major adverse cardiac events, including cardiovascular death, myocardial infarction, and stroke.  Largely because of this, these trials have traditionally had a focus on cardiovascular disease in terms of atherosclerotic events. Heart failure was not mentioned in the FDA document and these trials have had a lesser focus on it.

As the years have gone by, we have learned more and more about the connection between diabetes and heart failure. There is tremendous overlap between the two patient populations. Also, as more and more of the large cardiovascular outcome trials have been completed, we have seen multiple examples of various glucose lowering therapies either increasing or decreasing risk of heart failure events. Given all these data on heart failure/ diabetes interactions, the goal of our research was to carefully examine all of the completed large cardiovascular outcome trials of diabetes therapies to systematically describe the type of heart failure-related data they capture. As an initial step in improving heart failure characterization in these trials, we wanted to first describe what trials have already been doing and where the gaps in understanding heart failure in these trials exist.

Overall, we found major gaps in the amount and quality of the heart failure data capture in these trials. We looked at 21 large trials, including over 150,000 patients. Rates of patients with baseline heart failure were inconsistently provided, and among those trials that did provide it, heart failure patients tended to be underrepresented compared to the general population. Patients with baseline heart failure were also poorly characterized, with minimal data on functional status, ejection fraction, or heart failure medications. Only 6 trials reported rates of new-onset heart failure and the definitions used were non-specific. Most trials tended to report rates of heart failure hospitalization, but did not include data on fatal or other types of heart failure events. Only 2 trials included heart failure events within the primary study endpoint. More details are included in our full manuscript, which was published in the Journal of the American College of Cardiology to coincide with our presentation at the ACC conference.

Continue reading

Women Who Walk Briskly At Least Twice Per Week Have Lower Risk of Heart Failure

MedicalResearch.com Interview with:
Dr. Somwail Rasla, MD

Primary Care Center
Brown University, Pawtucket, RI

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Heart failure (HF) is a major global epidemic. The risk of heart failure rises with age, It triples for women above age 60.
Studies have found an inverse relationship between the risk of heart failure hospitalization and midlife fitness.Walking is the most common form of physical activity reported in women
and older adults. T
his study aims at exploring the association of walking pace (speed), walking frequency and duration with the risk of incident acute hospitalized HF (HHF).

Continue reading

Risk Factors For Sudden Death in Heart Failure with Preserved Ejection Fraction

MedicalResearch.com Interview with:

Muthiah Vaduganathan, MD MPH Heart and Vascular Center Brigham and Women's Hospital 

Dr. Vaduganathan

Muthiah Vaduganathan, MD MPH
Heart and Vascular Center
Brigham and Women’s Hospital 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The prevalence of heart failure with preserved ejection fraction (HFpEF) is rising globally, yet no medical therapies are currently available to alter its natural history and its progression remains incompletely understood.

Sudden death may represent a target for therapy in this disease entity. In 1,767 patients with HFpEF enrolled in the Americas region of the TOPCAT trial, we found that sudden death accounts for ~20% of all deaths. Male sex and insulin-treated diabetes mellitus identify patients at higher risk for sudden death. Sudden death was numerically lower but not statistically reduced in those randomized to spironolactone.

Continue reading

Decision Aids Can Help Heart Failure Patients Determine If They Want an LVAD

MedicalResearch.com Interview with:

A left ventricular assist device (LVAD) pumping blood from the left ventricle to the aorta, connected to an externally worn control unit and battery pack. Wikipedia image

A left ventricular assist device (LVAD) pumping blood from the left ventricle to the aorta, connected to an externally worn control unit and battery pack.
Wikipedia image

Larry A. Allen, MD, MHS
Associate Professor, Medicine
Associate Head for Clinical Affairs, Cardiology
Medical Director, Advanced Heart Failure
Aurora, CO 80045

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Deciding whether or not to get a left ventricular assist device (LVAD) is one of the most challenging medical decisions created by modern medicine.

LVADs improve overall survival but also come with serious risks and lifestyle changes. Particularly for older patients with multiple medical problems, this is a complex choice.

Our research group at the University of Colorado spent years systematically developing unbiased pamphlet and video decision aids for patients and caregivers. We also developed a clinician-directed decision support training for LVAD program staff. The DECIDE-LVAD trial studied the implementation and effectiveness of this decision support intervention with patients and their caregivers in 6 hospitals in the U.S. When compared to previously used education materials, the decision aids appeared to improve patients’ decision quality and lowered the total number of patients getting LVADs.

Continue reading

Aggressive Systolic Blood Pressure Control In Older Patients With HFpEF Should Be Avoided

“Doctors” by Tele Jane is licensed under CC BY 2.0MedicalResearch.com Interview with:
Dr. Apostolos Tsimploulis, Chief Medical Resident
Dr. Phillip H. Lam, Chief Cardiology Fellow
The Washington, DC Veterans Affairs Medical Center, Georgetown University, and
MedStar Washington Hospital Center, Washington, DC 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hypertension is a major risk factor for the development of new heart failure (HF). Findings from multiple randomized controlled trials in hypertension have consistently demonstrated that controlling systolic blood pressure (SBP) to normal levels such as to SBP <120 mm Hg reduces the risk of developing new HF.

However, interestingly, once patients develop heart failure, those with a normal SBP value such as SBP <120 mm Hg tend to have poor outcomes. This paradoxical association – also called reverse epidemiology – although poorly understood – has been described with other HF risk factors such as smoking and obesity. Regarding poor outcomes associated with lower SBP in HF patients with reduced ejection fraction (HFrEF – pronounced Hef-ref), it has been suggested that it may be a marker of weak heart muscle that is unable to pump enough blood. However, less is known about this association in patients with HF and preserved ejection fraction (HFpEF – pronounced Hef-pef) –– the heart muscle is not weak in the traditional sense.

This is an important question for a number of reasons: nearly half of all heart failure patients have HFpEF which accounts for about 2.5 to 3 million Americans. These patients have a high mortality similar to those with HFrEF – but unlike in HFrEF few drugs have been shown to improve their outcomes. Thus, there is a great deal of interest in improving their outcomes. One of those approaches is to control . systolic blood pressure and the 2017 ACC/AHA/HFSA Focused Update of the HF guidelines recommend that SBP “should be controlled in patients with HFpEF in accordance with published clinical practice guidelines to prevent morbidity.”

Thus, our study was designed to answer that simple question: do patients with HFpEF and SBP <120 mmHg, which is considered to be normal SBP, have better outcomes than those with SBP ≥120 mmHg.

Using a sophisticated approach called propensity score matching we assembled two groups of patients with HFpEF – one group with SBP <120 mmHg and the other groups had SBP ≥120 mmHg – and patients in both groups were similar in terms of 58 key baseline characteristics. In this population of balanced patients with HFpEF, those with a normal systolic blood pressure had a higher risk of mortality – starting 30 days post-discharge up to about 6 years. Finding from our restricted cubic spline plots suggest that compared with SBP <120 mm Hg, SBP values ≥120 mm Hg (up to 200 mm Hg) was not associated with a higher risk of death.

Continue reading

Majority of Older Adults With Heart Failure Have Hearing Loss

MedicalResearch.com Interview with:
“Handicapped Hearing Impaired” by Mark Morgan is licensed under CC BY 2.0Madeline Sterling M.D., M.P.H.

Fellow, Department of Medicine
Weill Cornell Medical College – New York Presbyterian Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Heart Failure currently affects 5.8 million people in the United States and is becoming increasingly common as the population ages. Because it has no cure and tends to get progressively worse, physicians recommend that patients control their symptoms by taking multiple medications, maintain a diet low in salt, monitor their weight and blood pressure, and watch for changes in their symptoms.

At the most basic level, in order to understand and follow these instructions, heart failure patients must be able to hear them.  Hearing loss, however, had not been studied in heart failure.  There are a lot of chronic diseases in which hearing loss is more common than in the general population, including coronary heart disease, hypertension, and diabetes. And many adults with heart failure also have these conditions. So, we thought it would be important to understand if hearing loss was prevalent among adults with heart failure, especially since so much of heart failure management revolves around effective communication between patients and their healthcare providers. Continue reading

Aging Population, Socio-Economic Disparities Linked To Increase in Heart Failure Incidence

MedicalResearch.com Interview with:

Prof Kazem Rahimi FRCP The George Institute for Global Health Oxford Martin School University of Oxford, Oxford

Prof. Rahimi

Prof Kazem Rahimi FRCP
The George Institute for Global Health
Oxford Martin School
University of Oxford, Oxford

MedicalResearch.com: What is the background for this study?

Response: We decided to investigate this topic because disease incidence data is very important for public health bodies; for example, for the allocation of healthcare resources or for the design and assessment of disease prevention measures.

When we reviewed the literature, we found that estimates of heart failure incidence, temporal trends, and association by patient features were scarce. Studies often referred to restricted populations (such as relatively small cohorts that may or may not be representative of the general population), or limited data sources (for example, only including patients hospitalized for their heart failure and not considering those diagnosed by clinicians outside of hospitals). Few studies reported comparable, age-standardized rates, with the result that the rates reported varied considerably across the literature.

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Eating a Mostly Plant Based Diet Linked To Lower Risk of Heart Failure

MedicalResearch.com Interview with:
“Fresh Food” by Sonny Side Up! is licensed under CC BY 2.0

 

Dr. Kyla M Lara
Icahn School of Medicine at Mount Sinai

 

 

 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This was the first study to evaluate whether dietary patterns of black and white adults living in the United States were associated with developing heart failure. We’re hearing a lot in the news about specific diets like low-fat, high protein, low carb, and other diets that decrease cardiovascular risk. We would love it, as physicians, if we could prescribe a specific diet to limit cardiovascular risk in our patients. I’m really excited about our study because instead of examining patterns of what we already know are healthy, we looked at foods people were regularly consuming in the United States and developed dietary patterns from this. This study is similar to other work we have done with stroke and heart attack.

We used data from the NIH funded REGARDS study, also known as the Reasons for Geographic and Racial Differences in Stroke. More than 30,000 white and African-American adults were recruited from 2003-2007. From this group, we studied over 18,000 adults who successfully completed a dietary assessment called the Food Frequency Questionnaire. This was a really great group to study because people who live in this particular geographic area of the Southeastern United States, also known as the stroke belt, suffer from a higher risk of death from stroke. It’s extremely important for us to better understand the major risk factors that contribute to this and also cardiovascular disease.

We used statistical techniques to derive 5 dietary patterns based on the types of foods participants tended to eat.
• Convenience – Mexican and Chinese food, mixed dishes (both meat and bean)
• Sweets – added fats, bread, chocolate, desserts, sweet breakfast foods
• Southern – added fats, fried food, organ and processed meat, fatty milk
• Alcohol/Salads – beer, wine, liquor, green leafy vegetables, salad dressings, nuts and seeds, coffee
• Plant Based- fruit, vegetables, fruit juice, cereal, fish, poultry

Each participant received a score for each pattern that reflected how closely their diet resembled that dietary pattern. This approach reflects the real world and how people eat.

Over the 3135 days (8.6 years) of median follow up, 594 participants were hospitalized for incident HF. Greatest adherence to the plant-based dietary pattern during the study period was associated with a 28% risk reduction of developing heart failure.
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Regardless of Ejection Fraction, Hospitalization for Heart Failure Linked To Increased Risk of Death

MedicalResearch.com Interview with:

Kevin S. Shah, M.D. Cardiology Fellow, University of California, Los Angeles Ronald Reagan UCLA Medical Center

Dr. Shah

Kevin S. Shah, M.D.
Cardiology Fellow, University of California, Los Angeles
Ronald Reagan UCLA Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Heart failure (HF) is a chronic condition and progressive disease which is associated with a high-risk of hospitalization and death. One of the principle ways in which heart function is estimated is the use of ultrasound to calculate the ejection fraction of the heart, an estimate of the heart’s pump function. The ejection fraction can help predict how long patients will live and affects decision-making with regards to what medications may help their condition.

A total of 39,982 patients from 254 hospitals who were admitted for Heart failure between 2005 and 2009 were included. They were followed over time to see if they were admitted to the hospital again or if they died during this period. We compared three subgroups within this large group of patients based on their estimated ejection fraction. Across subgroups, the 5-year risk of hospitalization and death was high when compared with the U.S. population. Furthermore, the survival for patients with a diagnosis of heart failure who have been hospitalized once for this condition have a similarly poor 5-year risk of death and re-hospitalization, regardless of their estimated ejection fraction.
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Going the Wrong Way: ACA’s Readmission Reduction Program Linked To Increased Heart Failure Deaths

MedicalResearch.com Interview with:

Ankur Gupta, MD, PhD Division of Cardiovascular Medicine Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts

Dr. Ankur Gupta

Ankur Gupta, MD, PhD
Division of Cardiovascular Medicine
Brigham and Women’s Hospital Heart & Vascular Center and
Harvard Medical School,
Boston, Massachusetts 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Hospital Readmissions Reduction Program (HRRP), established under the Affordable Care Act, aimed to reduce readmissions from various medical conditions including heart failure – the leading cause of readmissions among Medicare beneficiaries. The program financially penalizes hospitals with high readmission rates. However, there have been concerns of unintended consequences especially on mortality due to this program.

Using American Heart Association’s Get With The Guidelines-Heart Failure (GWTG-HF) data linked to Medicare data, we found that the policy of reducing readmissions after heart failure hospitalizations was associated with reduction in 30-day and 1-year readmissions yet an increase in 30-day and 1-year mortality.

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Anti-Fibrotic Drug May Block Cardiac Scarring That Leads To Heart Failure

MedicalResearch.com Interview with:

Bruno Péault PhD Professor and Chair, Vascular Regeneration Center For Cardiovascular Science MRC Centre for Regenerative Medicine Scientific Director, BHF Laboratories The University of Edinburgh and Professor, David Geffen School of Medicine at UCLA Orthopaedic Hospital Research Center University of California at Los Angeles Los Angeles, CA 90095-7358

Dr. Péault

Bruno Péault PhD
Professor and Chair, Vascular Regeneration
Center For Cardiovascular Science
MRC Centre for Regenerative Medicine
Scientific Director, BHF Laboratories
The University of Edinburgh and
Professor, David Geffen School of Medicine at UCLA
Orthopaedic Hospital Research Center
University of California at Los Angeles
Los Angeles, CA 90095-7358

MedicalResearch.com: What is the background for this study?

Response: Kidney, lung, liver, muscle, heart are among the many organs which can be severely affected by fibrosis, a natural scarring process whereby healthy tissues are replaced by a fibrous non-functional substitute. For instance, the billions of cardiac muscle cells that die after a heart infarct, consequently to blood supply interruption, are replaced by a fibrotic scar that cannot contract, reducing the capacity of the heart to pump blood, and leading often to heart failure. There is currently no efficient treatment of fibrotic scars, the basic cellular component of which is the myofibroblast, a cell of unremarkable appearance and unclear origin. The transforming growth factor β (TGFβ) molecule triggers fibrosis development after being activated, via the extra-cellular matrix, by αv integrins, which are adhesion molecules present at the surface of the target cells.

To gain further insight into the cells that drive fibrosis in the heart and skeletal muscle, and explore ways to control this deleterious process, mice were used in which cells expressing the β receptor for PDGF (platelet derived growth factor) have been genetically tagged with a green fluorescent protein, a system previously used by Prof. Neil Henderson to trace fibrosis in the diseased liver (cells naturally expressing PDGFRβ are, in their vast majority, perivascular cells surrounding small blood vessels, as well as some interstitial fibroblasts). Skeletal muscle was injured by a small incision or with a targeted injection of cardiotoxin, a snake venom compound that locally kills myofibers, while the heart was damaged by prolonged infusion of angiotensin II. In both settings, progression of fibrosis was followed over time and contribution of green fluorescent cells – i.e. those expressing PDGFRβ – was assessed.

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Hip and Knee Replacements More Common In Patients With Transthryretin Cardiac Amyloidosis

MedicalResearch.com Interview with:

Dr. Mathew Maurer, Medical Director The Hypertrophic Cardiomyopathy Center NewYork-Presbyterian/Columbia University Medical Center.

Dr. Maurer

Dr. Mathew Maurer, Medical Director
The Hypertrophic Cardiomyopathy Center
NewYork-Presbyterian/Columbia University Medical Center.

MedicalResearch.com: What is the background for this study?

Response: Transthryretin cardiac amyloidosis (TTR-CA) is an underdiagnosed type of cardiomyopathy in which TTR (transthyretin, also known as prealbumin), a protein that forms amyloid fibrils, deposits in the heart. The deposits cause thickening of the ventricular wall and diastolic as well as systolic dysfunction. It is usually discovered around age 75 and presents more commonly in men than in women. With advances in non-invasive diagnostic modalities and growing awareness, TTR-CA is being diagnosed increasingly more frequently. Additionally, there are several emerging treatments that are under active investigation. Most of these therapies prevent disease progression and don’t address the amyloid already deposited in the heart. Accordingly, it is imperative that we diagnose TTR-CA before patients develop significant amyloid heart disease. However, this presents a great challenge since there are few known clinical predictors that might alert even the most astute physician that a patient is at such risk. With identification of predictors that may appropriately raise the index of clinical suspicion, clinicians may begin to pick up more subtle (and perhaps not yet clinically significant) forms of TTR-CA and initiate treatment before significant damage occurs.

The few known clinical predictors of TTR-CA include bilateral carpal tunnel syndrome and lumbar spinal stenosis, and numerous studies found TTR on biopsies and autopsies of other musculoskeletal sites, particularly in hip and knee joints. (Just last week, and also discussed here on MedicalResearch.com, biceps tendon rupture was also shown to occur more frequently in TTR-CA!) We suspected that patients who ultimately develop TTR-CA may first develop clinically significant hip and knee disease, enough to even warrant a hip (THA) or knee (TKA) replacement.

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Ruptured Biceps Tendon and Wild-type Transthyretin Amyloidosis

MedicalResearch.com Interview with:

Avinainder Singh, M.B.B.S. Research Fellow Cardiovascular Medicine Brigham & Women's Hospital Harvard Medical School Boston, MA

Dr. Singh

Avinainder Singh, M.B.B.S.
Research Fellow
Cardiovascular Medicine
Brigham & Women’s Hospital
Harvard Medical School
Boston, MA

MedicalResearch.com: What is the background for this study?

Response: Amyloidosis due to aberrant folding of proteins. These misfolded proteins can deposit in various parts of the body and lead to organ dysfunction. The two most common types of amyloidosis affecting the heart include transthyretin and light chain amyloidosis. Transthyretin is a protein produced by the liver which supports the transport of thyroxine and retinol.

Wild-type transthyretin amyloidosis (ATTRwt, previously known as senile amyloidosis) occurs due to deposition of misfolded fibrils derived from transthyretin and primarily affects elderly men. Once considered a rare disease, it is now reported to be responsible for nearly 13% of heart failure with preserved ejected fraction and increased wall thickness.

Rupture of the biceps tendon is a rare occurrence in the general population (<1 per 1000). We noticed a ruptured biceps tendon in several patients with wild-type transthyretin amyloidosis and performed this study to further evaluate this finding in a group of patients with wild-type transthyretin amyloidosis and in a control group of age-matched patients with non-amyloid heart failure.

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Does Spironolactone Work In Acute Heart Failure?

MedicalResearch.com Interview with:

Javed Butler, MD, PhD Chief of the Cardiology Division Dr. Vincent Yang, Simons Chair in Internal Medicine Stony Brook University

Dr. Butler

Javed Butler, MD, PhD
Chief of the Cardiology Division
Dr. Vincent Yang, Simons Chair in Internal Medicine
Stony Brook University

 MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. We therefore studies high dose spironolactone in patients with AHF. Unfortunately all of our primary and secondary endpoints were not different between spironolactone and placebo arms.

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Survival Benefit from Primary Prevention Implantable Cardioverter Defibrillators

MedicalResearch.com Interview with:

Daniel J. Friedman, MD Duke University Hospital Duke Clinical Research Institute Durham, NC

Dr. Friedman

Daniel J. Friedman, MD
Duke University Hospital
Duke Clinical Research Institute
Durham, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although primary prevention ICDs have saved countless lives among patients with heart failure and a reduced ejection fraction, the use of primary prevention ICDs in patients with more advanced heart failure [defined by New York Heart Association Class (NYHA)] is controversial.

Specifically, there are conflicting data from the pivotal primary prevention ICD trials regarding whether primary prevention ICDs reduce all-cause mortality among patients with a severely reduced ejection fraction (≤35%) and NYHA III heart failure.

We performed a patient level meta-analysis using data from 4 pivotal primary prevention ICD trials (MADIT-I, MADIT-II, SCD-HeFT, and DEFINITE) to assess whether primary prevention ICD efficacy varied by NYHA class (II vs. III). Overall, the ICD reduced all-cause mortality among the overall population of patients (NYHA II and III). We subsequently assessed ICD efficacy after stratification by NYHA class.

Among NYHA II patients, the ICD significantly reduced all-cause mortality by reducing sudden cardiac death. Although NYHA III patients randomized to an ICD experienced a significantly lower rate of sudden cardiac death, this did not translate into a reduction in all-cause mortality, due to competing causes of non-sudden death (which an ICD cannot treat). Based on relatively wide confidence intervals associated with the estimate for ICD effect in NYHA III patients, there appears to be substantial heterogeneity in outcomes among these patients. This suggests that many NYHA III patients can benefit from a primary prevention ICD, but further study is necessary to determine which NYHA III patients are poised to benefit.

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60 Foot Walk Test Correlates With Heart Failure Symptoms

MedicalResearch.com Interview with:

Kristie Harris, M.S. Doctoral Candidate, Department of Psychology Psychology Trainee, OSUWMC Department of Psychiatry Columbus, OH 43210

Ms. Harris

Kristie Harris, M.S.
Doctoral Candidate, Department of Psychology
Psychology Trainee, OSUWMC Department of Psychiatry
Columbus, OH 43210

MedicalResearch.com: What is the background for this study?

Response: In patients with chronic diseases such as heart failure, treatment strategies and medical management often rely on clinician’s assessment of symptoms and impairments in functional status. The six-minute walk test (6MWT) is a validated and commonly-used measure for assessing functional status in this patient population and has the advantage of being self-paced and easily administered.

However, its clinical utility may be limited because it is time consuming, not suitable for patients with comorbidities that interfere with walking, and requires a long continuous hallway course. In this this study we report the development of an alternative measure of objective functional status, the sixty-foot walk test (60ftWT). For this task, patients are simply asked to walk four laps of 15 feet and the total time taken to walk the 60ft is recorded in seconds.

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