Rationale and design of the Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure: BEGIN-HF study.

AIMS: Sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) represent a unique class of anti-hyperglycaemic agents for type 2 diabetes mellitus that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT-2i in patients with heart failure (HF), unrelated to its glucosuric effect. It is unclear whether the benefits of SGLT-2i therapy also rely on the improvement of left ventricular (LV) and/or right ventricular (RV) function in patients with HF. This study aimed to evaluate the effect of SGLT-2i on LV and RV function through conventional and advanced echocardiographic parameters with a special focus on RV function in patients with HF. METHODS AND RESULTS: The Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure (BEGIN-HF) study is an international multicentre, prospective study that will evaluate the effect of SGLT-2i on echocardiographic parameters of myocardial function in patients with chronic stable HF across the left ventricular ejection fraction (LVEF) spectrum. Patients with New York Heart Association Class II/III symptoms, estimated glomerular filtration rate > 25 mL/min/1.73 m2 , age > 18 years, and those who were not previously treated with SGLT-2i will be included. All patients will undergo conventional, tissue-derived imaging (TDI), and strain echocardiography in an ambulatory setting, at time of enrolment and after 6 months of SGLT-2i therapy. The primary endpoint is the change in LV function as assessed by conventional, TDI, and myocardial deformation speckle tracking parameters. Secondary outcomes include changes in RV and left atrial function as assessed by conventional and deformation speckle tracking echocardiography. Univariate and multivariate analyses will be performed to identify predictors associated with primary and secondary endpoints. CONCLUSIONS: The BEGIN-HF will determine whether SGLT-2i therapy improves LV and/or RV function by conventional and advanced echocardiography in patients with HF irrespective of LVEF.

A Rare Case of Isolated Right Ventricular Loeffler's Endocarditis in Primary Hypereosinophilic Syndrome.

Hypereosinophilic syndrome (HES) is a systemic disorder with various manifestations, characterized by hypereosinophilia and caused by primary or secondary conditions. Loeffler's endocarditis (LE) represents a frequent cardiac manifestation of HES, caused by infiltration of the myocardium by eosinophilic cells, which determines endocardial damage, with subsequent inflammation, thrombosis, and fibrosis of either one or both ventricles. The diagnosis of cardiac involvement is based on a multimodality approach (i.e., two-dimensional transthoracic echocardiography [2D-TTE], speckle-tracking echocardiography [STE], and cardiac magnetic resonance [CMR]), with different findings depending on the stage of disease. STE may be useful in the initial phase when traditional imaging techniques may result negative, whereas CMR allows myocardial tissue characterization along with a better definition of the right ventricle. We present a rare case of LE with isolated right ventricular involvement in a patient with HES caused by chronic eosinophilic leukemia with constitutively activated fusion tyrosine kinase on chromosome 4q12, successfully treated with imatinib mesylate.

Nonbacterial Thrombotic Endocarditis with Multiple Systemic Emboli in a Patient with Primary Lung Cancer.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that refers to a spectrum of noninfectious lesions of cardiac valves that is most commonly seen in advanced malignancy. We describe a case report of a 63-year-old male with NBTE and multiple embolizations (encephalic, coronary, splenic, and renal). The patient was admitted to the emergency department for stroke. During hospitalization, the patient complained of left leg pain and a venous echo color Doppler of the lower limbs was performed, showing bilateral distal deep-vein thrombosis. A thoracoabdominal computed tomography scan, which was performed to rule out pulmonary embolism, revealed a primary lung cancer and subcarinal lymphadenopathy. As collateral findings, multiple ischemic lesions in the spleen and in both kidneys were identified. In addition, areas of subendocardial hypodensity compatible with ischemia were also highlighted. An electrocardiogram showed acute myocardial infarction and focused echocardiographic evaluation displayed hypokinesis of the lateral and posterior in the mid- and distal segments and aortic and mitral valve vegetations, confirmed by a transesophageal echocardiography. Empiric antimicrobial therapy was started; all blood culture sets were negative and the patient was apyretic throughout the hospitalization. These findings supported the hypothesis of NBTE with multiple embolizations during a hypercoagulable state associated with advanced lung cancer.

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.

OBJECTIVES: CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. METHODS: We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). RESULTS: During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. CONCLUSIONS: Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

Association Between Layer-Specific Longitudinal Strain and Risk Factors of Heart Failure and Dyspnea: A Population-Based Study.

BACKGROUND: Global longitudinal strain (GLS), derived from speckle-tracking echocardiography (STE), is a widely used and reproducible left ventricular deformation parameter; assessment of multilayer strain components has also become possible. However, its association with comorbidities/symptoms in low-risk populations without cardiac disease remains understudied. We report reference ranges for longitudinal deformation and their association with cardiovascular risk factors and dyspnea in a large population-based cohort. METHODS: We studied 1,243 subjects without cardiac disease (47 ± 14 years, 47.4% men; 13.8% with dyspnea) enrolled at the fourth visit of the STANISLAS Cohort (Lorraine, France). Clinical evaluation included a comprehensive dyspnea questionnaire. Multilayer GLS (full-wall, subendocardial, and subepicardial) and strain rate (systolic, early, and late diastolic) were evaluated by GLS STE acquisition and measurement protocols as per recommendations by the European Association of Cardiovascular Imaging, American Society of Echocardiography, and Industry Task Force. RESULTS: Full-wall GLS was 23.4% ± 2.7% (mean ± SD) with a subendocardial/subepicardial ratio of 1.2 ± 0.1. Age, gender, smoking status, and body mass index were significantly associated with strain variables, whereas diabetes, dyslipidemia, and hypertension/systolic blood pressure were not. Specifically, there were reductions in diastolic strain rate with aging but no differences in GLS. After propensity score matching, subjects with dyspnea had lower global endocardial strain (-23.48 ± 2.70 vs -23.02 ± 2.81; P = .043) and lower global subendocardial/subepicardial strain ratio (P = .034), whereas transmural strain and classical echocardiographic measurements were unrelated to dyspnea. CONCLUSIONS: Higher body mass index was found to be significantly associated with impaired strain variables in a low-risk population without cardiac disease. In addition, lower global endocardial strain and lower global subendocardial/subepicardial strain ratio were significantly associated with dyspnea contrary to other echocardiographic variables.