Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.

Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status.

Clinical Implications of Pretest Probability of HFpEF on Outcomes in Precapillary Pulmonary Hypertension.

Background: Patients with group 1 pulmonary hypertension (PH) and risk factors for heart failure with preserved ejection fraction (HFpEF) demonstrate worse response to pulmonary vasodilator therapy. The mechanisms and optimal diagnostic approach to identify such patients remain unclear.

Objectives: The purpose of this study was to compare exercise capacity, cardiac function, and hemodynamic responses to provocative maneuvers among patients with group 1 PH based upon pretest probability of HFpEF.

Pulmonary hypertension across the spectrum of left heart and lung disease.

Aims: Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2-3), but this group is not well-characterized.

Sleep-Related Hypoxia, Right Ventricular Dysfunction, and Survival in Patients With Group 1 Pulmonary Arterial Hypertension.

Background: Group 1 pulmonary arterial hypertension (PAH) is a progressive fatal condition characterized by right ventricular (RV) failure with worse outcomes in connective tissue disease (CTD). Obstructive sleep apnea and sleep-related hypoxia may contribute to RV dysfunction, though the relationship remains unclear.

Objectives: The aim of this study was to prospectively evaluate the association of the apnea-hypopnea index (AHI) and sleep-related hypoxia with RV function and survival.

Frequency of acute vasodilator response (AVR) in incident and prevalent patients with pulmonary arterial hypertension: Results from the pulmonary vascular disease phenomics study.

The prevalence of acute vasodilator response (AVR) to inhaled nitric oxide (iNO) during right heart catheterization (RHC) is 12% in idiopathic pulmonary arterial hypertension (IPAH). AVR, however, is reportedly lower in other disease-associated pulmonary arterial hypertension (PAH), such as connective tissue disease (CTD). The prevalence of AVR in patients on PAH therapy (prevalent cases) is unknown.

Prognostic Role of Metabolic Exercise Testing in Heart Failure.

Heart failure is a clinical syndrome with significant heterogeneity in presentation and severity. Serial risk-stratification and prognostication can guide management decisions, particularly in advanced heart failure, when progression toward advanced therapies or end-of-life care is warranted. Each currently utilized prognostic marker carries its own set of challenges in acquisition, reproducibility, accuracy, and significance.

Distinct Impact of Noncardiac Comorbidities on Exercise Capacity and Functional Status in Chronic Heart Failure.

Background: Noncardiac comorbidities (NCCs) are common in patients with heart failure (HF), but how they jointly affect exercise capacity and functional status is relatively unexplored.

Objectives: This study sought to investigate the cumulative effects of NCC on exercise capacity and functional status in chronic HF.

Methods: Baseline NCC-status was assessed in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), IRONOUT-HF (Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure), NEAT-HFpEF (Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction), INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF), and RELAX-HFpEF (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) trials, and relations with peak Vo and 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and all-cause death were determined according to HF type (with reduced vs preserved ejection fraction).

Prognostic Value of Hemodynamic Gain Index in Patients With Heart Failure With Reduced Ejection Fraction.

Background: Assessment of functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) is essential for risk stratification, and it traditionally relied on cardiopulmonary exercise testing (CPET)-derived peak oxygen consumption (peak Vo).

Objectives: This study sought to investigate the prognostic value of alternative nonmetabolic exercise testing parameters in a contemporary cohort with HFrEF.

Methods: Medical records of 1,067 consecutive patients with chronic HFrEF who underwent CPET from December 2012 to September 2020 were reviewed for a primary outcome that was a composite of all-cause mortality, left ventricular assist device implantation, and/or heart transplantation.

Iron deficiency in pulmonary vascular disease: pathophysiological and clinical implications.

Aims: Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear.

Methods And Results: Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores.

Long-term outcomes in nonprogressors to cardiac resynchronization therapy.

Background: Among patients with heart failure undergoing cardiac resynchronization therapy (CRT), patients with a minimal change in left ventricular ejection fraction (LVEF) have recently been defined as "nonprogressors" rather than as "nonresponders." Little is known regarding long-term outcomes of nonprogressors.

Objective: We sought to evaluate outcomes in patients undergoing CRT on the basis of echocardiographically determined response status.

Invasive Hemodynamic and Metabolic Evaluation of HFpEF.

Purpose Of Review: Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous condition of multiple causes, characterized by a clinical syndrome resulting from elevated left ventricular filling pressures, with an apparently unimpaired left ventricular systolic function. Although HFpEF has been long recognized as a distinct entity with significant morbidity for patients, its diagnosis remains challenging to this day. In recent years, few diagnostic algorithms have been postulated to aid in the identification of this condition.

All-cause mortality predicted by peak oxygen uptake differs depending on spirometry pattern in patients with heart failure and reduced ejection fraction.

Aims: In patients with heart failure and reduced ejection fraction (HFrEF), it remains unclear how exacerbated impairments in peak exercise oxygen uptake (V̇O ) caused by coexistent obstructive or restrictive ventilatory defects affect mortality risk. We evaluated in patients with HFrEF, whether demonstrating either an obstructive or restrictive-patterned ventilatory defect on spirometry affects V̇O to yield all-cause mortality risk predicted by V̇O that is spirometry pattern specific.

Methods And Results: We retrospectively analysed resting spirometry and treadmill cardiopulmonary exercise testing data of patients with HFrEF (left ventricular ejection fraction ≤ 40%).

Temporal Trends of Cardiac Outcomes and Impact on Survival in Patients With Cancer.

To evaluate the temporal relations of cardiovascular disease in oncology patients referred to cardio-oncology and describe the impact of cardiovascular disease and cardiovascular risk factors on outcomes. All adult oncology patients referred to the cardio-oncology service at the Cleveland Clinic from January 2011 to June 2018 were included in the study. Comprehensive clinical information were collected.

Calcium/calmodulin-dependent protein kinase II causes atrial structural remodeling associated with atrial fibrillation and heart failure.

Background: Atrial fibrillation (AF) is sustained by reentrant mechanisms that depend, in part, on atrial structural remodeling. Increased Ca/calmodulin-dependent protein kinase II (CaMKII) activity occurs in persistent AF. A general consensus has been that electrophysiological actions of CaMKII must be the contributing factor, but electrical remodeling in AF differs considerably with electrophysiological effects of CaMKII.

Protecting the heart in cancer therapy.

Recent advances in cancer prevention and management have led to an exponential increase of cancer survivors worldwide. Regrettably, cardiovascular disease has risen in the aftermath as one of the most devastating consequences of cancer therapies. In this work, we define cancer therapeutics-induced cardiotoxicity as the direct or indirect cardiovascular injury or injurious effect caused by cancer therapies.

Pharmacologic Management of Cancer Therapeutics-Induced Cardiomyopathy in Adult Cancer Survivors.

Purpose Of Review: The number of cancer survivors is exponentially increasing worldwide, due to both advances in cancer detection and treatment strategies, as well as the aging and growth of the population. This decrease in cancer mortality has brought forth a concurrent increase of non-ischemic (toxic) dilated cardiomyopathy in the survivor population, also known as cancer therapeutics-induced cardiomyopathy (CTIC). The optimal pharmacological management for this condition is still elusive, and hence, the focus of this work.

Fusion of Anthopleurin-B to AAV2 increases specificity of cardiac gene transfer.

AAV-mediated gene therapy has become a promising therapeutic strategy for chronic diseases. Its clinical utilization, however, is limited by the potential risk of off-target effects. In this work we attempt to overcome this challenge, hypothesizing that cardiac ion channel-specific ligands could be fused onto the AAV capsid, and narrow its tropism to cardiac myocytes.

Management of Heart Failure in Cancer Patients and Cancer Survivors.

The number of cancer survivors increases annually, because of advances in detection and treatment, and the aging and growth of the population. This increase has brought a concomitant increase in morbidity and mortality from other conditions related to the adverse effects of cancer treatments. Cardiovascular diseases, and in particular left ventricular dysfunction and heart failure, are among the most significant of these.

Increasing the impact of medical image computing using community-based open-access hackathons: The NA-MIC and 3D Slicer experience.

The National Alliance for Medical Image Computing (NA-MIC) was launched in 2004 with the goal of investigating and developing an open source software infrastructure for the extraction of information and knowledge from medical images using computational methods. Several leading research and engineering groups participated in this effort that was funded by the US National Institutes of Health through a variety of infrastructure grants. This effort transformed 3D Slicer from an internal, Boston-based, academic research software application into a professionally maintained, robust, open source platform with an international leadership and developer and user communities.

Cardio-Oncology Training: A Proposal From the International Cardioncology Society and Canadian Cardiac Oncology Network for a New Multidisciplinary Specialty.

There is an increasing awareness and clinical interest in cardiac safety during cancer therapy as well as in optimally addressing cardiac issues in cancer survivors. Although there is an emerging expertise in this area, known as cardio-oncology, there is a lack of organization in the essential components of contemporary training. This proposal, an international consensus statement organized by the International Cardioncology Society and the Canadian Cardiac Oncology Network, attempts to marshal the important ongoing efforts for training the next generation of cardio-oncologists.

Efficacy and durability of central oversewing for treatment of aortic insufficiency in patients with continuous-flow left ventricular assist devices.

Background: Aortic insufficiency (AI) in patients supported with continuous-flow left ventricular assist devices (CF-LVAD) results in regurgitant volume returning from the aorta to the left ventricle, increased LVAD pump volume and reduced systemic cardiac output. One common strategy to address AI during CF-LVAD support is central oversewing of the aortic valve, which allows some opening between the valve leaflets laterally. However, the long-term durability of this technique has not been extensively described.