Why has positive inotropy failed in chronic heart failure? Lessons from prior inotrope trials

Current pharmacological therapies for heart failure with reduced ejection fraction are largely either repurposed anti ‐hypertensives that blunt overactivation of the neurohormonal system or diuretics that decrease congestion. However, they do not address the symptoms of heart failure that result from reductions in cardiac output and reserve. Over the last few decades, numerous attempts have been made to develop a nd test positive cardiac inotropes that improve cardiac haemodynamics. However, definitive clinical trials have failed to show a survival benefit. As a result, no positive inotrope is currently approved for long‐term use in heart failure. The focus of this state‐of‐the‐art review is to revis it prior clinical trials and to understand the causes for their findings. Using the learnings from those experiences, we propose a framework for future trials of such agents that maximizes their potential for success. This includes enriching the trials with patients who are most likely to derive ben efit, using biomarkers and imaging in trial design and execution, evaluating efficacy based on a wider range of intermediate phenotypes, and collecting detailed data on functional status and quality of life. With a rapidly growing population of patients with advanced heart failure, the epidemiologic insignificance of heart transplantation as a therapeutic intervention, and both the cost and morbidity associated with ventricular assist devices, there is an enormous potential ...
Source: European Journal of Heart Failure - Category: Cardiology Authors: Tags: Review Source Type: research

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Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Improved understanding of the clinical course of ambulatory advanced chronic systolic heart failure may improve the provision of appropriate care and is central to the design of clinical trials in this population.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: Original Clinical Science Source Type: research
Heart transplantation is still the primary surgical treatment for end-stage heart failure. Due to limited donor heart availability, alternative and improved strategies are required. The tremendous developments in the field of active left ventricular assist devices (LVADs) have resulted in increased usage of LVADs as a bridge to transplant strategy and pose a technical challenge for LVAD preparation and removal during heart transplantation. The HeartMate 3 is the latest generation of fully magnetically levitated centrifugal left ventricular assist device and can be completely intrapericardially implanted in many different configurations.
Source: Operative Techniques in Cardiac and Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Transplant Source Type: research
Induced pluripotent stem cells (iPSC) [1] have been applied to clinical regenerative cell therapies such as the macular degeneration of the retina [2], spinal cord injury [3] and heart failure [4] et al. As use in autologous settings is hampered by the high time and cost requirements of the individual production of iPSC, an iPSC banking system which collects HLA typed cells from cord blood banks, marrow donor registries and HLA matched platelet donor registries has been proposed [5-8], and tissue transplantation generated from iPSC through banking in allogeneic settings has just been performed [8].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Small children with end-stage heart failure who require left ventricular assist device (LVAD) support to heart transplant have limited device options leading to high morbidity and mortality and chronic hospitalization until transplant.1,2 The only FDA-approved durable LVAD for children is a paracorporeal pulsatile device that carries a high stroke risk and lacks portability precluding hospital discharge.1 Temporary paracorporeal continuous flow (CF) devices have also been used off-label for bridge-to-transplant but carry higher mortality, require lengthy paracorporeal cannulas prone to circuit thrombus, and typically requi...
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: Case Anecdotes, Comments and Opinions Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
We report our experience using catheter ablation to treat recurrent arrhythmia in patients with CHD or CMP considered for transplantation.
Source: International Journal of Cardiology - Category: Cardiology Authors: Source Type: research
AbstractPurpose of reviewA multidisciplinary approach is vital to reduce mortality and hospitalizations in patients with heart failure. As members of the multidisciplinary team, pharmacists are uniquely positioned to care for patients across the spectrum of heart failure. This comprehensive review explores the different facets in which pharmacists can be utilized to impact the care for patients with heart failure, including those with cardiac transplant and left ventricular assist devices (LVADs), in the outpatient setting.Recent findingsPharmacists can see heart failure patients in a variety of settings to reduce drug the...
Source: Current Treatment Options in Cardiovascular Medicine - Category: Cardiology Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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