Hyperkalemia and Renin-Angiotensin-Aldosterone System Inhibitors Dose Therapy in Heart Failure With Reduced Ejection Fraction.

Renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in patients who have heart failure with reduced ejection fraction (HFrEF). To reduce mortality in these patients, RAASi should be uptitrated to the maximally tolerated dose. However, RAASi may also cause hyperkalemia. As a result of this side-effect, doses of RAASi are reduced, discontinued and seldom reinstated. Thus, the therapeutic target needed in these patients is often not reached because of hyperkalemia. Also, submaximal dosing of RAASi may be a result of symptomatic hypotension, syncope, hypoperfusion, reduced kidney function and other factors. The reduction of RAASi dose leads to adverse outcomes, such as an increased risk of mortality. Management of these side-effects is pivotal to maximise the use of RAASi in HFrEF, particularly in high-risk patients

Hypophosphataemia risk associated with ferric carboxymaltose in heart failure: A pooled analysis of clinical trials.

AIMS: Iron deficiency is a common finding among patients with heart failure (HF) and is associated with adverse outcomes, including decreased quality of life, increased risk of hospitalization, and decreased survival. Intravenous ferric carboxymaltose (FCM) has been shown to improve outcomes among patients with HF and concomitant iron deficiency, but FCM is associated with an increased risk of hypophosphataemia. We aimed to better characterize this risk among HF populations. METHODS AND RESULTS: This pooled analysis examined data from 41 studies of adults with iron deficiency across disease states and therapeutic areas. Among the 7931 patients treated with FCM available for analysis, 14% made up the HF subgroup. Additional subgroups included women's health (36%), non-dialysis-dependent chronic kidney disease (NDD-CKD; 27%), haemodialysis-dependent chronic kidney disease (HD-CKD; 1%), gastrointestinal (10%), neurology (3%), and other (10%). The incidence of post-baseline moderate or severe hypophosphataemia (i.e. serum phosphate [PO4 3- ] level 60 mL/min/1.73 m2 vs. <30 mL/min/1.73 m2 ; odds ratio: 12.2). Among patients in the HF subgroup, the incidence of treatment-emergent adverse events potentially related to hypophosphataemia (e.g. cardiac failure, ventricular tachyarrhythmias, fatigue, muscle weakness, bone pain, neurological symptoms, and muscle pain) was lower among FCM-treated patients than among those receiving placebo, and lower among patients with a post-baseline PO4 3- <2 mg/dL vs. those not meeting such criteria. CONCLUSIONS: The risk of laboratory-assessed hypophosphataemia in HF patients treated with FCM was lower than that seen in patients in other therapeutic areas treated with FCM, and clinical events associated with hypophosphataemia are uncommon with FCM therapy in this population. Appropriate monitoring, particularly soon after administration, will allow for further refinement of management strategies

Medical Treatment of Heart Failure with Reduced Ejection Fraction in the Elderly.

The aging population, higher burden of predisposing conditions and comorbidities along with improvements in therapy all contribute to the growing prevalence of heart failure (HF). Although the majority of trials have not demonstrated age-dependent heterogeneity in the efficacy or safety of medical treatment for HF, the latest trials demonstrate that older participants are less likely to receive established drug therapies for HF with reduced ejection fraction. There remains reluctance in real-world clinical practice to prescribe and up-titrate these medications in older people, possibly because of (mis)understanding about lower tolerance and greater propensity for developing adverse drug reactions. This is compounded by difficulties in the management of multiple medications, patient preferences and other non-medical considerations. Future research should provide a more granular analysis on how to approach medical and device therapies in elderly patients, with consideration of biological differences, difficulties in care delivery and issues relevant to patients' values and perspectives. A variety of approaches are needed, with the central principle being to 'add years to life - and life to years'. These include broader representation of elderly HF patients in clinical trials, improved education of healthcare professionals, wider provision of specialised centres for multidisciplinary HF management and stronger implementation of HF medical treatment in vulnerable patient groups

Efficacy and Safety of Novel Aspirin Formulations: A Randomized, Double-Blind, Placebo-Controlled Study.

Low-dose aspirin represents the best option in the secondary prevention of coronary artery disease, but its extensive use in primary prevention is limited by the occurrence of gastric mucosal lesions and increased risk of bleeding. We investigated the safety profile of a novel sublingual aspirin formulation in 200 healthy volunteers, randomly assigned to ten (n = 20 each) different 7-day once-daily treatment regimens. Gastric mucosal injury based on the modified Lanza score (MLS), the histopathology of gastric mucosa and the serum determination of thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 levels were evaluated at basal as well as after 7 days of each placebo or aspirin treatment regimen. In Groups A and B (placebo-oral and sublingual, respectively), no changes in MLS and in gastric mucosal micro-vessel diameter were found at day 7. In contrast, in Groups C and D (oral standard aspirin-100 and 50 mg daily, respectively), the median MLS was significantly increased. Very few changes were found in Groups E and F (standard sublingual aspirin-100 and 50 mg, respectively). Groups G and H (oral administration of micronized collagen-cogrinded aspirin) showed gastric protection compared to Groups C and D. Moreover, Groups I and L (sublingual collagen-cogrinded aspirin-100 and 50 mg, respectively) showed a significant reduction (Group I) or total abolition (Group L) of gastric mucosal lesions and no difference compared to the standard one in serum TXB2 and urinary 11-dehydro-TXB2 levels. In conclusion, our data show that the new formulation leads to a better safety profile compared to standard aspirin, representing a better therapeutic option for extended use in primary and secondary prevention of cardiovascular diseases

Cardiovascular care of patients with stroke and high risk of stroke: The need for interdisciplinary action: A consensus report from the European Society of Cardiology Cardiovascular Round Table.

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention. Treatment of stroke generally is led by stroke physicians, yet cardiologists need to be integrated care providers in stroke units to address all cardiovascular aspects of acute stroke care, including arrhythmia management, blood pressure control, elevated levels of cardiac troponins, valvular disease/endocarditis, and the general management of cardiovascular comorbidities. Despite substantial progress in stroke research and clinical care has been achieved, relevant gaps in clinical evidence remain and cause uncertainties in best practice for treatment and prevention of stroke. The Cardiovascular Round Table of the European Society of Cardiology together with the European Society of Cardiology Council on Stroke in cooperation with the European Stroke Organisation and partners from related scientific societies, regulatory authorities and industry conveyed a two-day workshop to discuss current and emerging concepts and apparent gaps in stroke care, including risk factor management, acute diagnostics, treatments and complications, and operational/logistic issues for health care systems and integrated networks. Joint initiatives of cardiologists and stroke physicians are needed in research and clinical care to target unresolved interdisciplinary problems and to promote the best possible outcomes for patients with stroke

Welcoming low testosterone as a cardiovascular risk factor

Male hypogonadism now has a new spectrum of complications. They are mainly cardiometabolic in nature. Low serum testosterone levels are a risk factor for diabetes, metabolic syndrome, inflammation and dyslipidemia. These metabolic and inflammatory complications are not without consequences. Recent studies have shown low serum testosterone levels to be an independent risk factor of cardiovascular and all-cause mortality. It is time to welcome low serum testosterone levels as a cardiovascular risk factor

Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors

The phosphodiesterase type 5 (PDE-5) inhibitors are effective in treating erectile dysfunction (ED). ED and heart failure (HF) share similar risk factors, and commonly present together. This association has led to questions ranging from the safety and efficacy of PDE-5 inhibitors in HF patients to a possible role for this class of medication to treat HF patients with or without ED. In addition to endothelial dysfunction, there are causes of ED specific to patients with HF including low exercise tolerance, depression and HF medications. Before treating HF patients with PDE-5 inhibitors, patients should be assessed for their risk of a cardiac event during sexual activity. PDE-5 inhibitors are safe and effective in treating ED in HF patients. An improvement in erectile function by PDE-5 inhibitors was associated with an improvement in quality of life and reduction in depression. Several studies demonstrated the effect of PDE-5 inhibitors on HF per se. PDE-5 inhibitors improved endothelial dysfunction, increased exercise tolerance, decreased pulmonary vascular resistance and pulmonary artery pressure, and increased cardiac index. Several mechanisms whereby PDE-5 inhibitors improve HF have been proposed. PDE-5 inhibitors already have a role in treating primary pulmonary hypertension; however additional studies are needed to determine if they will become a standard therapy for HF patients

Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research

Rationale and design of the ESC Heart Failure III Registry - Implementation and discovery.

AIMS: Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline-recommended therapy in Europe and other ESC affiliated countries. METHODS: Between 1 November 2018 and 31 December 2020, 10 162 patients with chronic or acute/worsening HF with reduced, mildly reduced, or preserved ejection fraction were enrolled from 220 centres in 41 European or ESC affiliated countries. The ESC HF III Registry collected data on baseline characteristics (hospital or clinic presentation), hospital course, diagnostic and therapeutic decisions in hospital and at the clinic visit; and on outcomes at 12-month follow-up. These data include demographics, medical history, physical examination, biomarkers and imaging, quality of life, treatments, and interventions - including drug doses and reasons for non-use, and cause-specific outcomes. CONCLUSION: The ESC HF III Registry will provide comprehensive and unique insight into contemporary HF characteristics, treatment implementation, and outcomes, and may impact implementation strategies, clinical discovery, trial design, and public policy

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC

2016 ESC on Acute and Chronic H