The aim of this study was to assess the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting late cardiotoxicity in patients treated with not-high-dose chemotherapy (NHDC), and to compare the predictive value of NT-proBNP and cardiac troponin I (cTnI). In 71 patients undergoing NHDC with anthracyclines, NT-proBNP and cTnI levels were measured before and 24 h after each NHDC cycle. Left ventricular (LV) function was assessed by echocardiography at baseline, every two NHDC cycles, at the end of chemotherapy, and at 3-, 6- and 12-month follow-up. During NHDC, only NT-proBNP showed abnormal values. According to NT-proBNP behaviour, patients were divided into two groups: group A (n=50) with normal (n=23) or transiently elevated NT-proBNP levels (n=27), and group B (n=21) with persistently elevated NT-proBNP levels. At follow-up, LV impairment was significantly worse in group B than in group A. %Δ (baseline–peak) NT-proBNP was predictive of LV impairment at 3-, 6- and 12-month follow-up, with a cutoff of 36%. Serial measurements of NT-proBNP may be a useful tool for the early detection of patients treated with NHDC at high risk of developing cardiotoxicity.
Research in Chlamydia trachomatis and Chlamydia pneumoniae has gained new traction due to recent advances in molecular biology, namely the widespread use of the metagenomic analysis and the development of a stable genomic transformation system, resulting in a better understanding of Chlamydia pathogenesis. C. trachomatis, the leading cause of bacterial sexually transmitted diseases, is responsible of cervicitis and urethritis, and C. pneumoniae, a widespread respiratory pathogen, has long been associated with several chronic inflammatory diseases with great impact on public health. The present review summarizes the current evidence regarding the complex interplay between C. trachomatis and host defense factors in the genital micro-environment as well as the key findings in chronic inflammatory diseases associated to C. pneumoniae.
22 October 2019 in Journal of Clinical Investigation
Myocardin (MYOCD) is the founding member of a class of transcriptional coactivators that bind the serum-response factor to activate gene expression programs critical in smooth muscle (SM) and cardiac muscle development. Insights into the molecular functions of MYOCD have been obtained from cell culture studies, and to date, knowledge about in vivo roles of MYOCD comes exclusively from experimental animals. Here, we defined an often lethal congenital human disease associated with inheritance of pathogenic MYOCD variants. This disease manifested as a massively dilated urinary bladder, or megabladder, with disrupted SM in its wall. We provided evidence that monoallelic loss-of-function variants in MYOCD caused congenital megabladder in males only, whereas biallelic variants were associated with disease in both sexes, with a phenotype additionally involving the cardiovascular system. These results were supported by cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity. In conclusion, we have demonstrated that variants in MYOCD result in human disease, and the collective findings highlight a vital role for MYOCD in mammalian organogenesis.
The aim of the present study was to verify whether BNP might detect pre-clinical diastolic dysfunction (LVDD) in type-2 diabetic patients. One-hundred and twenty-seven consecutive outpatients with type-2 diabetes mellitus were enrolled into the study. Subjects with overt heart failure or NYHA class > 1, history of coronary artery disease, severe valvulopathy or chronic atrial fibrillation were excluded from the study. All patients underwent clinical evaluation, laboratory assessment of brain natriuretic peptide (BNP) and echocardiographic examination. No patients showed systolic impairment of left ventricular function, whereas diastolic dysfunction was detected in 53 (42%) cases (all impaired relaxation). Median BNP was 27 pg/ml without any significant difference between 76 patients with normal left ventricular function and 53 with diastolic dysfunction; in 54 (43%) patients showing HBA1C≥8 (uncontrolled diabetes) normal function was found in 32 and diastolic dysfunction in 22, with a significant difference of BNP at multivariate analysis (OR = 1.02, 95%CI = 1.05-1.09, p = 0.003). In uncontrolled diabetic cohort, BNP was a strong predictor for LVDD (OR = 2.7, 95%CI = 1.3-5.6, p = 0.006) along with the duration of diabetes (OR = 1.6, 95%CI = 1.1-2.9, p = 0.046). BNP > 25 pg/ml was a cut-off value with high accuracy to detect a LVDD. Early screening of high-risk patients for diabetic cardiomyopathy development might be useful to better control glycemic profile in order to reduce heart disease progression or even to reverse it BNP could be a cheap, easy and useful tool to screen those ones with preclinical ventricular diastolic dysfunction in a subset of patients particularly prone to develop cardiovascular complications, like uncontrolled diabetic patients.
The aim of this review article is to summarize current knowledge of the pathophysiology underlying right ventricular failure (RVF), focusing, in particular, on right ventricular assessment and prognosis. The right ventricle (RV) can tolerate volume overload well, but is not able to sustain pressure overload. Right ventricular hypertrophy (RVH), as a response to increased afterload, can be adaptive or maladaptive. The easiest and most common way to assess the RV is by two-dimensional (2D) trans-thoracic echocardiography measuring surrogate indexes, such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and tissue Doppler velocity of the lateral aspect of the tricuspid valvular plane. However, both volumes and function are better estimated by 3D echocardiography and cardiac magnetic resonance (CMR). The prognostic role of the RV in heart failure (HF), pulmonary hypertension (PH), acute myocardial infarction (AMI), and cardiac surgery has been overlooked for many years. However, several recent studies have placed much greater importance on the RV in prognostic assessments. In conclusion, RV dimensions and function should be routinely assessed in cardiovascular disease, as RVF has a significant impact on disease prognosis. In the presence of RVF, different therapeutic approaches, either pharmacological or surgical, may be beneficial.