Takotsubo syndrome: a neurocardiac syndrome inside the autonomic nervous system

Levels of angiotensin peptides in healthy and cardiovascular/renal-diseased paediatric population—an investigative review Abstract The renin-angiotensin-aldosterone system (RAAS) plays a major role in the regulation of blood pressure and homeostasis. Therefore, it is a commonly used target for pharmacotherapy of cardiovascular diseases in adults. However, the efficacy of this pharmacotherapy can only be limitedly derived into children. Comprehensive knowledge of the humoral parameters acting in the paediatric RAAS (e.g. angiotensin I, angiotensin II, angiotensin 1–7, angiotensin III, and angiotensin IV) might facilitate a more effective and rational pharmacotherapy in children. Therefore, this review aims to provide an overview of the maturing RAAS. Out of 925 identified records, 35 publications were classified as relevant. Physiological and pathophysiological concentrations of angiotensin peptides were compiled and categorised according to European Medicines Agency age groups. Age has a major impact on circulating angiotensin I, angiotensin II, and angiotensin 1–7, which is reflected in an age-dependent decrease during childhood. In contrast to data obtained in adults, no gender-related differences in angiotensin levels were identified. The observed increase in peptide concentrations regarding cardiac- and renal-diseased children is influenced by surgical repair, while evidence for a pharmacological impact is conflicting. A comprehensive set of angiotensin I, angiotensin II, and angiotensin 1–7 values from neonates up to adolescents was compiled. Indicating age as a strong effector. However, evidence about potential promising targets of the RAAS like angiotensin III and angiotensin IV is still lacking in children.

Invasive therapies for patients with concomitant heart failure and atrial fibrillation Abstract Atrial fibrillation (AF) and heart failure (HF) are two clinical entities that can present either separately or concurrently. One entity can lead to the other and vice versa as AF can not only be the underlying etiology of HF but also exacerbate HF due to other cardiac diseases. Besides prevention of cerebral and systemic embolism and elimination of AF-related symptoms, restoration of sinus rhythm for AF patients helps to avoid or reduce HF, irrespective of their underlying heart disease. Successful rates of medical therapy for AF are low in persistent AF, and much lower in long-standing AF, while invasive procedures for AF yield promising results. In this review, the authors evaluate the value of invasive therapies for HF patients complicated with non-valvular AF. We examine this clinical problem by interpreting the relationships between these two entities: the mechanism of tachycardia-induced cardiomyopathy (TIC), past opinions about rhythm control and rate control of AF, discrimination of HF-related AF and AF-induced HF, how to identify the AF patients that could benefit from invasive therapies, and how to select invasive therapies for different AF patients and peri-operative treatments.

Surgical and physiological challenges in the development of left and right heart failure in rat models Abstract Rodent surgical animal models of heart failure (HF) are critically important for understanding the proof of principle of the cellular alterations underlying the development of the disease as well as evaluating therapeutics. Robust, reproducible rodent models are a prerequisite to the development of pharmacological and molecular strategies for the treatment of HF in patients. Due to the absence of standardized guidelines regarding surgical technique and clear criteria for HF progression in rats, objectivity is compromised. Scientific publications in rats rarely fully disclose the actual surgical details, and technical and physiological challenges. This lack of reporting is one of the main reasons that the outcomes specified in similar studies are highly variable and associated with unnecessary loss of animals, compromising scientific assessment. This review details rat circulatory and coronary arteries anatomy, the surgical details of rat models that recreate the HF phenotype of myocardial infarction, ischemia/reperfusion, left and right ventricular pressure, and volume overload states, and summarizes the technical and physiological challenges of creating HF. The purpose of this article is to help investigators understand the underlying issues of current HF models in order to reduce variable results and ensure successful, reproducible models of HF.

Influence of mitochondrial and systemic iron levels in heart failure pathology Abstract Iron deficiency or overload poses an increasingly complex issue in cardiovascular disease, especially heart failure. The potential benefits and side effects of iron supplementation are still a matter of concern, even though current guidelines suggest therapeutic management of iron deficiency. In this review, we sought to examine the iron metabolism and to identify the rationale behind iron supplementation and iron chelation. Cardiovascular disease is increasingly linked with iron dysmetabolism, with an increased proportion of heart failure patients being affected by decreased plasma iron levels and in turn, by the decreased quality of life. Multiple studies have concluded on a benefit of iron administration, even if just for symptomatic relief. However, new studies field evidence for negative effects of dysregulated non-bound iron and its reactive oxygen species production, with concern to heart diseases. The molecular targets of iron usage, such as the mitochondria, are prone to deleterious effects of the polyvalent metal, added by the scarcely described processes of iron elimination. Iron supplementation and iron chelation show promise of therapeutic benefit in heart failure, with the extent and mechanisms of both prospects not being entirely understood. It may be that a state of decreased systemic and increased mitochondrial iron levels proves to be a useful frame for future advancements in understanding the interconnection of heart failure and iron metabolism.

Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials Abstract The efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF) are controversial. To explore the role of MRAs in HF patients with an ejection fraction of no more than 45%, we conducted a network meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, the Cochrane Library, and Clinicaltrials. RCTs involving the efficacy and/or safety of the use of MRAs in patients with HF were included. Outputs are presented as the surface under the cumulative ranking area (SUCRA) probabilities. Thirteen RCTs involving a total of 13,597 participants were included. Finerenone 10 mg was associated with the lowest probability of achieving at cardiovascular mortality (SUCRA, 5.0%), followed by finerenone 7.5 mg (SUCRA, 31.6%). In reducing N-terminal pro-B-type natriuretic peptide, finerenone 15 mg and finerenone 7.5 mg ranked the best and second best (SUCRA 68.1% and 63.8%, respectively), followed by finerenone 10 mg (SUCRA 59.2%). Spironolactone and canrenone have a higher risk of hyperkalemia and renal deterioration. Regarding the prevention of worsening renal function, finerenone 7.5 mg (SUCRA 14.3%) was the best treatment, followed by finerenone 2.5 mg (SUCRA 16.3%) and finerenone 10 mg (SUCRA 25.6%). Compared with spironolactone and eplerenone, finerenone 10 mg was associated with low risk in the occurrence of cardiovascular mortality, hospitalization, and adverse events (P < 0.01). This network meta-analysis is the first to find that finerenone 7.5–10 mg has the highest probability of being the optimal alternative among MRAs in the treatment of HF patients with an ejection fraction of no more than 45%.

Advanced heart failure: non-pharmacological approach Abstract Patients with advanced heart failure have poor prognosis despite traditional pharmacological therapies. The early identification of these subjects would allow them to be addressed on time in dedicated centers to select patients eligible for heart transplantation or ventricular assistance. In this article we will report the current management of these patients based on latest international guidelines, underlining some critical aspects, with reference to future perspectives.

Clinical significance of nutritional status in patients with chronic heart failure—a systematic review Abstract Chronic heart failure (CHF) and nutritional disorders are recognized as major challenges for contemporary medicine. This study aims to estimate the role of nutritional disorders as risk factors for CHF development and prognostic factors for CHF patients and the outcome of nutritional intervention in CHF. Full-text English articles published between January 2013 and February 2019 available in the PubMed and Scopus databases were considered. Seventy-five prospective, retrospective, and cross-sectional studies as well as meta-analyses on patients with CHF, reporting correlation of their nutritional status with the risk and prognosis of CHF and the outcome of nutritional interventions in CHF were all included. Higher BMI increases the risk of CHF by 15–70%, especially when associated with severe, long-lasting and abdominal obesity. Overweight and obesity are associated with the reduction of mortality in CHF by 24–59% and 15–65%, respectively, and do not affect the outcome of invasive CHF treatment. Malnutrition increases the risk of mortality (by 2- to 10-fold) and the risk of hospitalization (by 1.2- to 1.7-fold). Favorable outcome of nutritional support in CHF patients was reported in a few studies. Nutritional disorders are prevalent in patients with CHF and play a significant role in the incidence, course, and prognosis of the disease. The existence of an “obesity paradox” in patients with CHF was confirmed. Further studies on the effect of nutritional support and body weight reduction in patients with CHF are necessary.

Pharmacological management of cardiac cachexia: a review of potential therapy options Abstract Cardiac cachexia is a syndrome of progressive skeletal muscle and fat loss affecting a significant number of congestive heart failure patients. With the potential detrimental effects of cardiac muscle wasting, greater attention is needed to understanding the prevention and treatment of the condition. Potential therapeutic approaches are aimed at the various mechanisms for the pathogenesis of cardiac cachexia including neurohormonal abnormalities, immune activation and inflammation, metabolic hormonal imbalance, and gastrointestinal abnormalities. While there are no current guideline-recommended treatments for the prevention of cardiac cachexia, targeting an imbalance of the renin-angiotensin-aldosterone system with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers appears to be the most well-studied therapeutic approaches. Treatment of inflammation with monoclonal antibodies, hormonal imbalance with testosterone, and nutritional deficiencies with appetite stimulants has also been suggested. Proposed therapies may prove beneficial in heart failure patients; however, further studies specifically focusing on the cardiac component of cachexia are needed before definitive therapy options can be established.

The left atrium and the right ventricle: two supporting chambers to the failing left ventricle Abstract Heart failure (HF) is mainly caused by left ventricular (LV) impairment of function, hence detailed assessment of its structure and function is a clinical priority. The frequent involvement of the left atrium (LA) and the right ventricle (RV) in the overall cardiac performance has recently gained significant interest with specific markers predicting exercise intolerance and prognosis being proposed. The LA and RV are not anatomically separated from the LV, while the LA controls the inlet the RV shares the interventricular septum with the LV. Likewise, the function of the two chambers is not entirely independent from that of the LV, with the LA enlarging to accommodate any rise in filling pressures, which could get transferred to the RV via the pulmonary circulation. In the absence of pulmonary disease, LA and RV function may become impaired in patients with moderate-severe LV disease and raised filling pressures. These changes can often occur irrespective of the severity of systolic dysfunction, thus highlighting the important need for critical assessment of the function of the two chambers. This review evaluates the pivotal role of the left atrium and right ventricle in the management of HF patients based on the available evidence.