Heart Failure with Preserved Ejection Fraction: The Pathophysiological Mechanisms behind the Clinical Phenotypes and the Therapeutic Approach.

Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome with systemic involvement, and it is characterized by multiple cardiac and extracardiac pathophysiological alterations. The increasing prevalence is currently reaching epidemic levels, thereby making HFpEF one of the greatest challenges facing cardiovascular medicine today. Compared to HF with reduced ejection fraction (HFrEF), the medical attitude in the case of HFpEF was a relaxed one towards the disease, despite the fact that it is much more complex, with many problems related to the identification of physiopathogenetic mechanisms and optimal methods of treatment. The current medical challenge is to develop effective therapeutic strategies, because patients suffering from HFpEF have symptoms and quality of life comparable to those with reduced ejection fraction, but the specific medication for HFrEF is ineffective in this situation; for this, we must first understand the pathological mechanisms in detail and correlate them with the clinical presentation. Another important aspect of HFpEF is the diversity of patients that can be identified under the umbrella of this syndrome. Thus, before being able to test and develop effective therapies, we must succeed in grouping patients into several categories, called phenotypes, depending on the pathological pathways and clinical features. This narrative review critiques issues related to the definition, etiology, clinical features, and pathophysiology of HFpEF. We tried to describe in as much detail as possible the clinical and biological phenotypes recognized in the literature in order to better understand the current therapeutic approach and the reason for the limited effectiveness. We have also highlighted possible pathological pathways that can be targeted by the latest research in this field.

Cardiomyopathies and Arrhythmias Induced by Cancer Therapies.

Cardiology and oncology are two fields dedicated to the study of various types of oncological and cardiac diseases, but when they collide, a new specialty is born, i.e., cardio-oncology. Continuous research on cancer therapy has brought into the clinic novel therapeutics that have significantly improved patient survival. However, these therapies have also been associated with adverse effects that can impede the proper management of oncological patients through the necessity of drug discontinuation due to life-threatening or long-term morbidity risks. Cardiovascular toxicity from oncological therapies is the main issue that needs to be solved. Proper knowledge, interpretation, and management of new drugs are key elements for developing the best therapeutic strategies for oncological patients. Upon continuous investigations, the profile of cardiotoxicity events has been enlarged with the inclusion of myocarditis upon administration of immune checkpoint inhibitors and cardiac dysfunction in the context of cytokine release syndrome with chimeric antigen receptor T cell therapy. Affinity enhanced and chimeric antigen receptor T cells have both been associated with hypotension, arrhythmia, and left ventricular dysfunction, typically in the setting of cytokine release syndrome. Therefore, the cardiologist must adhere to the progressing field of cancer therapy and become familiar with the adverse effects of novel drugs, and not only the ones of standard care, such as anthracycline, trastuzumab, and radiation therapy. The present review provides essential information summarized from the latest studies from cardiology, oncology, and hematology to bring together the three specialties and offers proper management options for oncological patients.

Protective Effects of a Discontinuous Treatment with Alpha-Lipoic Acid in Obesity-Related Heart Failure with Preserved Ejection Fraction, in Rats.

Obesity induces hemodynamic and humoral changes that are associated with functional and structural cardiac remodeling, which ultimately result in the development of heart failure (HF) with preserved ejection fraction (HFpEF). In recent years, pharmacological studies in patients with HFpEF were mostly unsatisfactory. In these conditions, alternative new therapeutic approaches are necessary. The aim of our study was (1) to assess the effects of obesity on heart function in an experimental model and (2) to evaluate the efficacy of an alpha-lipoic acid (ALA) antioxidant treatment. Sprague-Dawley rats (7 weeks old) were either included in the control group (n = 6) or subjected to abdominal aortic banding (AAB) and divided into three subgroups, depending on their diet: standard (AAB + SD, n = 8), hypecaloric (AAB + HD, n = 8) and hypercaloric with discontinuous ALA treatment (AAB + HD + ALA, n = 9). Body weight (BW), glycemia, echocardiography parameters and plasma hydroperoxides were monitored throughout the study. After 36 weeks, plasma adiposity (leptin and adiponectin) and inflammation (IL-6 and TNF-alpha) markers, together with B-type natriuretic peptide and oxidative stress markers (end-products of lipid peroxidation and endogenous antioxidant systems) were assessed. Moreover, cardiac fiber diameters were measured. In our experiment, diet-induced obesity generated cardiometabolic disturbances, and in association with pressure-overload induced by AAB, it precipitated the onset of heart failure, cardiac hypertrophy and diastolic dysfunction, while producing a pro-oxidant and pro-inflammatory plasmatic status. In relationship with its antioxidant effects, the chronic ALA-discontinuous treatment prevented BW gain and decreased metabolic and cardiac perturbations, confirming its protective effects on the cardiovascular system.

The Association between Peripheral Blood Cells and the Frailty Syndrome in Patients with Cardiovascular Diseases.

BACKGROUND: Frailty syndrome is characterized by multisystem dysregulation frequently found in older individuals or even in younger patients with chronic disabling diseases such as cardiovascular diseases. OBJECTIVE: To determine whether peripheral blood cell count, and its subpopulations, red blood cell and platelets, morphology and different ratios (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and red blood distribution width-to-platelet ratio) are associated with cardiac frail patients, and through this to improve the prediction of frailty status in patients with cardiovascular diseases. METHODS: An observational, retrospective, cohort study enrolling 179 patients with cardiovascular disease divided into two groups: non-frail group (100 pts) and frail group (79 pts), a cohort detached from the Frail.RO study. The frailty was evaluated based on the Fried criteria; haematological markers, sociodemographic data, and variables related to cardiovascular diseases and comorbidities were also recorded. RESULTS: Lower lymphocytes, platelet count, and neutrophil-to-lymphocyte ratio were significantly associated with a more severe frailty syndrome. Regarding red blood cells, haemoglobin concentration and red cell distribution width significantly correlated with the severity of the frailty syndrome. Receiver operating characteristic curve analysis for these markers associated with the frailty syndrome revealed an acceptable sensitivity of 66 % and specificity of 65% to identify frail individuals. Malnutrition and hypercholesterolemia are relevant predictors for identifying frailty in hospitalized cardiovascular patients. CONCLUSION: The evaluation of peripheral blood cell composition routinely measured in clinical practice can represent a valuable, but limited indicator, to diagnose frailty syndrome and eventually, the effects of interventions in frail patients with cardiovascular diseases.