Right ventricular failure in left heart disease: from pathophysiology to clinical manifestations and prognosis

Right heart failure (RHF) is a clinical syndrome in which symptoms and signs are caused by dysfunction and/or overload of the right heart structures, predominantly the right ventricle (RV), resulting in systemic venous hypertension, peripheral oedema and finally, the impaired ability of the right heart to provide tissue perfusion. Pathogenesis of RHF includes the incompetence of the right heart to maintain systemic venous pressure sufficiently low to guarantee an optimal venous return and to preserve renal function. Virtually, all myocardial diseases involving the left heart may be responsible for RHF. This may result from coronary artery disease, hypertension, valvular heart disease, cardiomyopathies and myocarditis. The most prominent clinical signs of RHF comprise swelling of the neck veins with an elevation of jugular venous pressure and ankle oedema. As the situation worsens, fluid accumulation becomes generalised with extensive oedema of the legs, congestive hepatomegaly and eventually ascites. Diagnosis of RHF requires the presence of signs of elevated right atrial and venous pressures, including dilation of neck veins, with at least one of the following criteria: (1) compromised RV function; (2) pulmonary hypertension; (3) peripheral oedema and congestive hepatomegaly. Early recognition of RHF and identifying the underlying aetiology as well as triggering factors are crucial to treating patients and possibly reversing the clinical manifestations effectively and improving prognosis

Age over 50 does not predict results in anterior cruciate ligament reconstruction

Grown in the worldwide population of over 50 of age individuals who remain in good health and continue to engage in sports has led to an increase of anterior cruciate ligament (ACL) tears in this aged population. ACL reconstruction was reserved for young and active athletes, but seems to produce good outcomes also in over 50s

Monitoring of cardiovascular risk factors in competitive athletes

It is well known that physical activity can improve cardiovascular risk factors, but it is also true that strenuous activity may result detrimental for the athlete health. Among the emerging markers of cardiovascular risk, plasma homocysteine (Hcy) plays a prominent role, since it has been shown its significant increase in competitive athletes. Some research has concluded that Hcy levels may be influenced by the duration, intensity and type of exercise, whereas other studies have identified lifestyle factors, such as smoking, eating habits, alcohol consumption, age, elevated blood pressure and genetic factors, as factors that contribute to increased plasma concentrations of Hcy. Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) (677C/T, 1298A/C) are reported to modulate homocysteine levels. The aim of this work was to identify a genetic profile of risk for cardiovascular disease in two populations of competitive athletes, football players (n = 19) and those engaged in athletics (n=37). The distribution of MTHFR A1298C and C677T polymorphisms was examined by Real-time PCR allelic discrimination on genomic DNA isolated from lymphocytes of whole peripheral blood. The serum levels of Hcy were determined by HPLC method, while vitamin B12 and folate by RIA technique. The data showed that 50% of the subjects in both groups are carrier of MTHFR C677T polymorphism either in heterozygous or homozygous state. In addition, all subjects had mild hyperhomocysteinemia (13-27 micromol/L). The highest mean levels of Hcy were recorded in the football players, and the differences compared to those engaged in athletics were very significant (21.8 ± 11.6 vs. 13.5 ± 6.6, p <0.05). The increase of Hcy could be ascribed mainly to the diet style of the recruited subjects, characterized by a high consumption of red meat and very low intake of B vitamins. Moreover, this increase may also be explained in relation to the type of exercise required in football, that is considered an intermittent intensity sport. The preliminary results of this study suggest that screening for the MTHFR variants C677T and A1298C should be included in the panel of screening for cardiovascular risk in competitive athletes

Heart Failure and Cancer: Mechanisms of Old and New Cardiotoxic Drugs in Cancer Patients

Although there have been many improvements in prognosis for patients with cancer, anticancer therapies are burdened by the risk of cardiovascular toxicity. Heart failure is one of the most dramatic clinical expressions of cardiotoxicity, and it may occur acutely or appear years after treatment. This article reviews the main mechanisms and clinical presentations of left ventricular dysfunction induced by some old and new cardiotoxic drugs in cancer patients, referring to the most recent advances in the field. The authors describe the mechanisms of cardiotoxicity induced by anthracyclines, which can lead to cardiovascular problems in up to 48% of patients who take them. The authors also describe mechanisms of cardiotoxicity induced by biological drugs that produce left ventricular dysfunction through secondary mechanisms. They outline the recent advances in immunotherapies, which have revolutionised anticancer therapies

Echocardiographically defined haemodynamic categorization predicts prognosis in ambulatory heart failure patients treated with sacubitril/valsartan

Aim: Echo-derived haemodynamic classification, based on forward-flow and left ventricular (LV) filling pressure (LVFP) correlates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prognostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan. Methods and results: In our multicentre, open-label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m2 ) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e': ≥ or <15): Profile-A: normal-flow, normal-pressure; Profile-B: low-flow, normal-pressure; Profile-C: normal-flow, high-pressure; Profile-D: low-flow, high-pressure. Patients were started on sacubitril/valsartan and followed-up for 12.3 months (median). Rates of the composite of death/HF-hospitalization were assessed by multivariable Cox proportional-hazards models. Twelve sites enrolled 727 patients (64 ± 12 year old; LVEF: 29.8 ± 6.2%). Profile-D had more comorbidities and worse renal and LV function. Target dose of sacubitril/valsartan (97/103 mg BID) was more likely reached in Profile-A (34%) than other profiles (B: 32%, C: 24%, D: 28%, P < 0.001). Event-rate (per 100 patients per year) progressively increased from Profile-A to Profile-D (12.0%, 16.4%, 22.9%, and 35.2%, respectively, P < 0.0001). By covariate-adjusted Cox model, profiles with low forward-flow (B and D) remained associated with poor outcome (P < 0.01). Adding this categorization to MAGGIC-score and natriuretic peptides, provided significant continuous net reclassification improvement (0.329; P < 0.001). Intermediate and high-dose sacubitril/valsartan reduced the event's risk independently of haemodynamic profile. Conclusions: Echocardiographically-derived haemodynamic classification identifies ambulatory HFrEF patients with different risk profiles. In real-world HFrEF outpatients, sacubitril/valsartan is effective in improving outcome across different haemodynamic profiles