Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450 ms in males and greater than 470 ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G > A, p. Arg594Gln; c.532G > A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A, KCNJ5, AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning.

Lipoprotein(a) and the risk of recurrent events in patients with acute myocardial infarction treated by percutaneous coronary intervention.

BACKGROUND: The role of lipoprotein(a) (Lp[a]) in risk stratification following an acute myocardial infarction (AMI) is still debated. We aimed to investigate whether elevated Lp(a) levels in patients with AMI treated by percutaneous coronary intervention (PCI) are associated with worse outcomes. METHODS: We designed a retrospective registry including patients with AMI undergoing PCI. The occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as death from cardiovascular causes, recurrent myocardial infarction, unplanned coronary revascularization and stroke, was assessed at follow-up and compared between patients with high (≥30 mg/dL) and low (<30 mg/dL) Lp(a) levels. Cox proportional hazard analysis was performed in order to assess independent predictors of MACCE. RESULTS: During a 3-year period (2018-2020) we identified 634 patients with AMI treated by PCI and known Lp(a) blood levels; follow-up visits were performed in 414 patients (median length 29 months [19-38]). Median Lp(a) level was 18 mg/dL [8-42]. The incidence of MACCE was significantly higher in high as compared to low Lp(a) group (log-rank P=0.018). The following independent predictors were identified at multivariate Cox regression: Lp(a) ≥30 mg/dL (HR 1.82 [95% CI 1.04-3.19], peripheral artery disease (HR 4.62 [95% CI 2.50-8.54]), number of diseased coronary vessels (HR 1.51 [95% 1.03-2.24] and presence of a coronary chronic total occlusion at coronary angiography (HR 3.46 [95% CI 1.77-6.76]). CONCLUSIONS: in this study, Lp(a) values ≥30 mg/dL were associated to worse outcomes in patients with AMI receiving PCI. Lp(a) could represent a useful tool to identify patients at high risk of recurrent events.

Glycoprotein IIb/IIIa Inhibitors May Modulate the Clinical Benefit of Radial Access as Compared to Femoral Access in Primary Percutaneous Coronary Intervention: A Meta-Regression and Meta-Analysis of Randomized Trials.

OBJECTIVES: Several randomized controlled trials (RCTs) consistently reported better clinical outcomes with radial as compared to femoral access for primary percutaneous coronary intervention (PCI). Nevertheless, heterogeneous use of potent antiplatelet drugs, such as Gp IIb/IIIa inhibitors (GPI), across different studies could have biased the results in favor of radial access. We performed an updated meta-analysis and meta-regression of RCTs in order to appraise whether the use of GPI had an impact on pooled estimates of clinical outcomes according to vascular access. METHODS: We computed pooled estimates by the random-effects model for the following outcomes: mortality, major adverse cardiovascular events (death, myocardial infarction, stroke, and target vessel revascularization), and major bleedings. Additionally, we performed meta-regression analysis to investigate the impact of GPI use on pooled estimates of clinical outcomes. RESULTS: We analyzed 14 randomized controlled trials and 11090 patients who were treated by radial (5497) and femoral access (5593), respectively. Radial access was associated with better outcomes for mortality (risk difference 0.01 (0.00, 0.01), p=0.03), MACE (risk difference 0.01 (0.00, 0.02), p=0.003), and major bleedings (risk difference 0.01 (0.00, 0.02), p=0.02). At meta-regression, we observed a significant correlation of mortality with both GPI use (p=0.011) and year of publication (p=0.0073), whereas no correlation was observed with major bleedings. CONCLUSIONS: In this meta-analysis, the use of radial access for primary PCI was associated with better clinical outcomes as compared to femoral access. However, the effect size on mortality was modulated by GPI rate, with greater benefit of radial access in studies with larger use of these drugs.

Left Ventricular Remodeling in Hypertrophic Cardiomyopathy: An Overview of Current Knowledge.

While most patients with hypertrophic cardiomyopathy (HCM) show a relatively stable morphologic and clinical phenotype, in some others, progressive changes in the left ventricular (LV) wall thickness, cavity size, and function, defined, overall, as "LV remodeling", may occur. The interplay of multiple pathophysiologic mechanisms, from genetic background to myocardial ischemia and fibrosis, is implicated in this process. Different patterns of LV remodeling have been recognized and are associated with a specific impact on the clinical course and management of the disease. These findings underline the need for and the importance of serial multimodal clinical and instrumental evaluations to identify and further characterize the LV remodeling phenomenon. A more complete definition of the stages of the disease may present a chance to improve the management of HCM patients.

TNNI3 and KCNQ1 co-inherited variants in a family with hypertrophic cardiomyopathy and long QT phenotypes: A case report.

QTc prolongation is reported in patients with hypertrophic cardiomyopathy (HCM). However, the causes of the QTc interval increase remain unclear. The main contribution to QTc prolongation in HCM is attributed to the myocardial hypertrophy and related structural damage. In a 24-year-old male proband, affected by HCM and long QTc, we identified by Next Generation Sequencing a pathogenic variant in gene TNNI3 co-inherited with a damaging variant in KCNQ1 gene. This evidence suggests the possibility that QTc interval prolongation and its dispersion in HCM could be associated not only to the severity of left ventricular hypertrophy but also to the co-inheritance of pathogenic variants related to both long QT Syndrome (LQTS) and HCM. Although the simultaneous presence of pathogenic variants in genes related to different heart diseases is extremely rare, counseling and genetic testing appear crucial for the clinical diagnosis. Screening of LQTS genes should be considered in HCM patients to clarify the origin of long QTc, to provide more information about the clinical presentation and to evaluate the incidence of the co-existence of LQTS/HCM gene variants that could occur more frequently than so far reported.

[Benign thyroid nodules: diagnostic and therapeutic approach]. / Noduli tiroidei benigni: guida ad una razionale scelta diagnostico-terapeutica.

In the last years an increase in thyroid nodules detection has been reported from several epidemiological studies. This trend is largely due to the routine use of diagnostic sonography procedures in clinical practice. Thyroid nodules, both palpable or not palpable, rarely turn out to be malignant. Fine-needle aspiration cytology (FNAc) plays a central role in establishing the nature of the nodule. Excluded the presence of malignant lesions, which are generally treated with surgery, physicians are faced with a variety of therapeutic options, and choosing the optimal approach can be a difficult task. These include a periodic follow-up alone without treatment, the iodine supplementation, the thyroid-hormone suppressive therapy, the radioiodine administration, the percutaneous ethanol injections, and the new technique of laser photocoagulation. In all cases, decisions on the management of benign thyroid nodules should always be based on clinical target and a careful analysis of benefits and risks to the patient.