Genotype-Phenotype Insights of Inherited Cardiomyopathies-A Review.

Background: Cardiomyopathies (CMs) represent a heterogeneous group of primary myocardial diseases characterized by structural and functional abnormalities. They represent one of the leading causes of cardiac transplantations and cardiac death in young individuals. Clinically they vary from asymptomatic to symptomatic heart failure, with a high risk of sudden cardiac death due to malignant arrhythmias. With the increasing availability of genetic testing, a significant number of affected people are found to have an underlying genetic etiology. However, the awareness of the benefits of incorporating genetic test results into the care of these patients is relatively low. Aim: The focus of this review is to summarize the current basis of genetic CMs, including the most encountered genes associated with the main types of cardiomyopathies: hypertrophic, dilated, restrictive arrhythmogenic, and non-compaction. Materials and Methods: For this narrative review, we performed a search of multiple electronic databases, to select and evaluate relevant manuscripts. Results: Advances in genetic diagnosis led to better diagnosis precision and prognosis prediction, especially with regard to the risk of developing arrhythmias in certain subtypes of cardiomyopathies. Conclusions: Implementing the genomic information to benefit future patient care, better risk stratification and management, promises a better future for genotype-based treatment.

Short-Term Changes in Weather Conditions and the Risk of Acute Coronary Syndrome Hospitalization with and without ST-Segment Elevation: A Focus on Vulnerable Subgroups.

Background and Objectives: Acute coronary syndrome (ACS), a prevalent global cardiovascular disease and leading cause of mortality, is significantly correlated with meteorological factors. This study aims to analyze the impact of short-term changes in meteorological factors on the risk of ACS, both with and without ST-segment elevation, and to identify vulnerable subgroups. Materials and Methods: Daily ACS admissions and meteorological variables were collected from October 2016 to December 2021. A generalized linear model (GLM) with a Poisson distribution was employed to examine how short-term fluctuations in meteorological parameters influence ACS hospitalizations. Subgroup analyses were conducted to identify the populations most vulnerable to climate change. Results: Multiple regression analyses showed that short-term fluctuations in atmospheric pressure (≥10 mbar) and air temperature (≥5 °C) seven days prior increased the number of ACS hospitalizations by 58.7% (RR: 1.587; 95% CI: 1.501-1.679) and 55.2% (RR: 1.552; 95% CI: 1.465-1.644), respectively, notably impacting ST-segment elevation myocardial infarctions (STEMIs). The least pronounced association was observed between the daily count of ACS and the variation in relative air humidity (≥20%), resulting in an 18.4% (RR: 1.184; 95% CI: 1.091-1.286) increase in the risk of hospitalization. Subgroup analysis revealed an increased susceptibility among men and older adults to short-term variations in weather parameters. Conclusions: The findings indicate that short-term changes in weather conditions are associated with an increased risk of ACS hospitalizations, particularly STEMIs. Male and older adult patients exhibit heightened susceptibility to variations in climatic factors. Developing effective preventive strategies is imperative to alleviate the adverse consequences of these environmental risk factors.

Assessing the Relationship between Indexed Epicardial Adipose Tissue Thickness, Oxidative Stress in Adipocytes, and Coronary Artery Disease Complexity in Open-Heart Surgery Patients.

Background and Objectives: This cross-sectional study conducted at the Timișoara Institute of Cardiovascular Diseases, Romania, and the Centre for Translational Research and Systems Medicine from "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Romania, investigated the relationship between indexed epicardial adipose tissue thickness (EATTi) and oxidative stress in epicardial adipose tissue (EAT) adipocytes in the context of coronary artery disease (CAD) among open-heart surgery patients. The objective was to elucidate the contribution of EATTi as an additional marker for complexity prediction in patients with CAD, potentially influencing clinical decision-making in surgical settings. Materials and Methods: The study included 25 patients undergoing cardiac surgery, with a mean age of 65.16 years and a body mass index of 27.61 kg/m2. Oxidative stress in EAT was assessed using the ferrous iron xylenol orange oxidation spectrophotometric assay. The patients were divided into three groups: those with valvular heart disease without CAD, patients with CAD without diabetes mellitus (DM), and patients with both CAD and DM. The CAD complexity was evaluated using the SYNTAX score. Results: The EATTi showed statistically significant elevations in the patients with both CAD and DM (mean 5.27 ± 0.67 mm/m2) compared to the CAD without DM group (mean 3.78 ± 1.05 mm/m2, p = 0.024) and the valvular disease without CAD group (mean 2.67 ± 0.83 mm/m2, p = 0.001). Patients with SYNTAX scores over 32 had significantly higher EATTi (5.27 ± 0.66 mm/m2) compared to those with lower scores. An EATTi greater than 4.15 mm/m2 predicted more complex CAD (SYNTAX score >22) with 80% sensitivity and 86% specificity. The intra- and interobserver reproducibility for the EATTi measurement were excellent (intra-class correlation coefficient 0.911, inter-class correlation coefficient 0.895). Conclusions: EATTi is significantly associated with CAD complexity in patients undergoing open-heart surgery. It serves as a reliable indicator of more intricate CAD forms, as reflected by higher SYNTAX scores. These findings highlight the clinical relevance of EATTi in pre-operative assessment, suggesting its potential utility as a prognostic marker in cardiac surgical patients.

Reduced Left Ventricular Twist Early after Acute ST-Segment Elevation Myocardial Infarction as a Predictor of Left Ventricular Adverse Remodelling.

BACKGROUND: The left ventricular (LV) remodelling process represents the main cause of heart failure after a ST-segment elevation myocardial infarction (STEMI). Speckle-tracking echocardiography (STE) can detect early deformation impairment, while also predicting LV remodelling during follow-up. The aim of this study was to investigate the STE parameters in predicting cardiac remodelling following a percutaneous coronary intervention (PCI) in STEMI patients. METHODS: The study population consisted of 60 patients with acute STEMI and no history of prior myocardial infarction treated with PCI. The patients were assessed both by conventional transthoracic and ST echocardiography in the first 12 h after admission and 6 months after the acute phase. Adverse remodelling was defined as an increase in LVEDV and/or LVESV by 15%. RESULTS: Adverse remodelling occurred in 26 patients (43.33%). By multivariate regression equation, the risk of adverse remodelling increases with age (by 1.1-fold), triglyceride level (by 1.009-fold), and midmyocardial radial strain (mid-RS) (1.06-fold). Increased initial twist decreases the chances of adverse remodelling (0.847-fold). The LV twist presented the largest area under the receiver operating characteristic (ROC) curve to predict adverse remodelling (AUROC = 0.648; 95% CI [0.506;0.789], p = 0.04). A twist value higher than 11° has a 76.9% specificity and a 72.7% positive predictive value for reverse remodelling at 6 months.

Contribution of Global and Regional Longitudinal Strain for Clinical Assessment of HFpEF in Coronary and Hypertensive Patients.

Background: Contribution of global and regional longitudinal strain (GLS) for clinical assessment of patients with heart failure with preserved ejection fraction (HFpEF) is not well established. We sought to evaluate subclinical left ventricular dysfunction secondary to coronary artery disease (CAD) in HFpEF patients compared with hypertensive patients and age-matched healthy subjects. Material and methods: This was a retrospective study that included 148 patients (group 1 = 62 patients with HFpEF, group 2 = 46 hypertensive patients, and group 3 = 40 age-matched control subjects). Peak systolic segmental, regional (basal, mid, and apical), and global longitudinal strain were assessed for each study group using two-dimensional speckle-tracking echocardiography (2D-STE). Results: GLS values presented statistically significant differences between the three groups (p < 0.001); markedly increased values (more negative) were observed in the control group (-20.2 ± 1.4%) compared with HTN group values (-18.4 ± 3.0%, p = 0.031) and with HFpEF group values (-17.6 ± 2.3%, p < 0.001). The correlation between GLS values and HTN stages was significant, direct, and average (Spearman coefficient rho = 0.423, p < 0.001). GLS had the greatest ability to detect patients with HFpEF when HFpEF + CAD + HTN diastolic dysfunction (n = 30) + CON diastolic dysfunction (n = 2) from HFpEF + CAD + HTN + CON was analyzed. (optimal GLS limit of -19.35%, area under curve = 0.833, p < 0.001). Conclusions: Global longitudinal strain can be used for clinical assessment in differentiating coronary and hypertensive patients at higher risk for development of systolic dysfunction.

Assessment of the Impact of Alcohol Consumption Patterns on Heart Rate Variability by Machine Learning in Healthy Young Adults.

Background and Objectives: Autonomic nervous system (ANS) dysfunction is present in early stages of alcohol abuse and increases the likelihood of cardiovascular events. Given the nonlinear pattern of dynamic interaction between sympathetic nervous system (SNS) and para sympathetic nervous system (PNS) and the complex relationship with lifestyle factors, machine learning (ML) algorithms are best suited for analyzing alcohol impact over heart rate variability (HRV), because they allow the analysis of complex interactions between multiple variables. This study aimed to characterize autonomic nervous system dysfunction by analysis of HRV correlated with cardiovascular risk factors in young individuals by using machine learning. Materials and Methods: Total of 142 young adults (28.4 ± 4.34 years) agreed to participate in the study. Alcohol intake and drinking patterns were assessed by the AUDIT (Alcohol Use Disorders Identification Test) questionnaire and the YAI (Yearly Alcohol Intake) index. A short 5-min HRV evaluation was performed. Post-hoc analysis and machine learning algorithms were used to assess the impact of alcohol intake on HRV. Results: Binge drinkers presented slight modification in the frequency domain. Heavy drinkers had significantly lower time-domain values: standard deviation of RR intervals (SDNN) and root mean square of the successive differences (RMSSD), compared to casual and binge drinkers. High frequency (HF) values were significantly lower in heavy drinkers (p = 0.002). The higher low-to-high frequency ratio (LF/HF) that we found in heavy drinkers was interpreted as parasympathetic inhibition. Gradient boosting machine learner regression showed that age and alcohol consumption had the biggest scaled impact on the analyzed HRV parameters, followed by smoking, anxiety, depression, and body mass index. Gender and physical activity had the lowest impact on HRV. Conclusions: In healthy young adults, high alcohol intake has a negative impact on HRV in both time and frequency-domains. In parameters like HRV, where a multitude of risk factors can influence measurements, artificial intelligence algorithms seem to be a viable alternative for correct assessment.

MicroRNAs-The Heart of Post-Myocardial Infarction Remodeling.

Myocardial infarction (MI) is one of the most frequent cardiac emergencies, with significant potential for mortality. One of the major challenges of the post-MI healing response is that replacement fibrosis could lead to left ventricular remodeling (LVR) and heart failure (HF). This process involves canonical and non-canonical transforming growth factor-beta (TGF-ß) signaling pathways translating into an intricate activation of cardiac fibroblasts and disproportionate collagen synthesis. Accumulating evidence has indicated that microRNAs (miRNAs) significantly contribute to the modulation of these signaling pathways. This review summarizes the recent updates regarding the molecular mechanisms underlying the role of the over 30 miRNAs involved in post-MI LVR. In addition, we compare the contradictory roles of several multifunctional miRNAs and highlight their potential use in pressure overload and ischemia-induced fibrosis. Finally, we discuss their attractive role as prognostic biomarkers for HF, highlighting the most relevant human trials involving these miRNAs.

Single-Pass VDD Pacing Lead for Cardiac Resynchronization Therapy: A Reliable Alternative.

(1) Background: Cardiac resynchronization therapy (CRT) systems can be simplified by excluding the atrial lead and using a Ventricular-Dual-Dual (VDD) pacing lead. Possible disadvantages might include atrial undersensing and Ventricular-Ventricular-Inhibition (VVI) pacing. Because literature data concerning these systems are scarce, we analyzed their benefits and technical safety. (2) Methods: this retrospective study compared 50 patients implanted with VDD-CRT systems (group A), mainly because of unfavorable venous anatomy concerning the complication rate, with 103 subjects with Dual-Dual-Dual (DDD)-CRT systems (group B) implanted during 2000-2016 and 49 (group C) during 2016-2020. To analyze the functional parameters of the devices, we selected subgroups of 27 patients (subgroup A) and 47 (subgroup B) patients with VDD-CRT in 2000-2016, and 36 subjects (subgroup C) with DDD-CRT implanted were selected in 2017-2020. (3) Results: There was a trend of a lower complication rate with VDD-CRT systems, especially concerning infections during 2000-2016 (p = 0.0048), but similar results were obtained after rigorous selection of patients and employment of an upgraded design of devices/leads. With a proper device programing, CRT pacing had similar results, atrial undersensing being minimal (p = 0.65). For VDD-systems, VVI pacing was recorded only 1.7 ± 2.24% of the time. (4) Conclusions: In patients with a less favorable venous anatomy, VDD-CRT systems may represent a safe alternative regarding complications rates and functional parameters.

Echocardiographic Parameters as Predictors for the Efficiency of Resynchronization Therapy in Patients with Dilated Cardiomyopathy and HFrEF.

Cardiac resynchronization therapy (CRT) represents an increasingly recommended solution to alleviate symptomatology and improve the quality of life in individuals with dilated cardiomyopathy (DCM) and heart failure (HF) with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy (OMT). However, this therapy does have the desired results all cases, in that sometimes low sensing and high voltage stimulation are needed to obtain some degree of resynchronization, even in the case of perfectly placed cardiac pacing leads. Our study aims to identify whether there is a relationship between several transthoracic echocardiographic (TTE) parameters characterizing left ventricular (LV) performance, especially strain results, and sensing and pacing parameters. Between 2020-2021, CRT was performed to treat persistent symptoms in 48 patients with a mean age of 64 (53.25-70) years, who were diagnosed with DCM and HFrEF, and who were still symptomatic despite OMT. We documented statistically significant correlations between global longitudinal strain, posterolateral strain, and ejection fraction and LV sensing (r = 0.65, 0.469, and 0.534, respectively, p < 0.001) and LV pacing parameters (r = -0.567, -0.555, and -0.363, respectively, p < 0.001). Modern imaging techniques, such as TTE with cardiac strain, are contributing to the evaluation of patients with HFrEF, increasing the chances of CRT success, and allowing physicians to anticipate and plan for case management.

MTHFR Gene Polymorphisms Prevalence and Cardiovascular Risk Factors Involved in Cardioembolic Stroke Type and Severity.

BACKGROUND: Cardioembolic stroke (CES), generally known as the most severe subtype of ischemic stroke, is related to many factors, including diabetes mellitus (DM), hypertension (HTN), smoking, hyperlipidemia and atrial fibrillation (AF). Genetic mutations of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C have been recently associated with ischemic stroke. The purpose of this study was to analyze the prevalence of MTHFR gene polymorphisms correlated with cardiovascular risk factors in a selected population of patients with CES due to non-valvular AF (NVAF). METHODS: This cross-sectional study was performed on 67 consecutive patients with acute cardioembolic stroke admitted to our hospital. The protocol included general physical examination, neurological clinical status and stroke severity evaluation, imagistic evaluation and genetic testing of MTHFRC677T and A1298C polymorphisms. RESULTS: The prevalence of MTHFR polymorphisms in the study population was 38.2% for C677T and 40.3% for A1298C. The C677T mutation was significantly correlated with increased diastolic blood pressure (DBP) values (p = 0.007), higher total cholesterol (TC) (p = 0.003), low-density lipoprotein cholesterol (LDLc) (p = 0.003) and triglycerides (TGL) (p = 0.001), increased high-sensitive C-reactive protein (hsCRP) values (p = 0.015), HbA1c (p = 0.004) and left ventricle ejection fraction (LVEF) (p = 0.047) and lower high-density lipoprotein cholesterol (HDLc) (p < 0.001) compared to patients without this genetic variant. This genetic profile also included significantly higher CHA2DS2VASC (p = 0.029) and HASBLED (Hypertension, Abnormal liver/renal function, Stroke, Bleeding, Labile INR, Elderly age(>65 years), Drug/Alcohol usage history/Medication usage with bleeding predisposition) (p = 0.025) scores. Stroke severity in patients with MTHFRA1298C mutation was significantly increased when applying National Institutes of Health Stroke Scale (NIHSS) (p = 0.006) and modified Rankin scale (mRS) (p = 0.020) scores. The presence of A1298C mutation as a dependent variable was associated with significantly higher TGL values (odds ratio (OR) = 2.983, 95%CI = (1.972, 7.994)). CONCLUSIONS: The results obtained in this study demonstrate that MTHFR gene polymorphisms have a high prevalence in an NVAF cardioembolic stroke population. Moreover, an association between C677T mutation and stroke severity was highlighted. The C677T mutation in patients with NVAF was correlated with a higher incidence of cardiovascular comorbidities (hypertension HTN, heart failure (HF), dyslipidemia, type II diabetes mellitus (T2DM) with high HbA1c and increased inflammatory state). The A1298CMTHFR gene mutation was associated with a higher incidence of previous lacunar stroke and stroke recurrence rate, while dyslipidemia was the main cardiovascular comorbidity in this category.

Chameleonic appearance of caseous calcification of the mitral valve - still a problem for its appropriate management.

According to the research literature, the caseous calcification of the mitral annulus (CCMA) is a rare variant of the mitral annulus calcification (MAC) entity, described mostly in elderly women. The aim of this study was to present the case of a 53-year-old female patient with caseous calcification of the mitral valve annulus and posterior cusp, which was diagnosed as papillary fibroelastoma. An echo-dense and quasi-homogeneous tumoral mass, measuring 1.6∕1.4 cm, at the level of the posterior mitral ring was detected by echocardiographic examination, as well as by cardiac magnetic resonance imaging (MRI). Histopathological analysis revealed fibrous connective tissue with myxoid areas, hyaline degeneration with unstructured necrosis and dystrophic calcifications, which was consisting with the operative findings of a "toothpaste tumor", or caseous calcification of the mitral valve. Differential diagnosis with other cardiac tumors, abscesses, thrombi or fibroelastomas is emphasized.

Risk stratification in patients with heart failure: the value of considering both global longitudinal left ventricular strain and mechanical dispersion.

In previous studies, mechanical dispersion (MD) predicted ventricular arrhythmias independently of left ventricular ejection fraction (LVEF). Moreover, the combination of MD and global longitudinal strain (GLS) increased the prediction of arrhythmic events. We investigated the prognostic value of a new 2-dimensional strain index, GLS/MD, in patients with heart failure (HF). We analyzed 340 consecutive HF outpatients in sinus rhythm. Echocardiography was performed at 1.6 ± 0.4 months after hospital discharge. The end point included sudden cardiac death, ventricular fibrillation, and sustained ventricular tachycardia (SCD/VA). During the follow-up period (36 ± 9 months), SCD/VA occurred in 48 patients (14.1%). A multivariate Cox regression analysis, which included LVEF, early diastolic transmitral / mitral annular velocity ratio (E/E'), GLS, MD, and GLS/MD in the model, revealed that GLS/MD was the best independent predictor of SCD/VA (HR = 3.22, 95% confidence interval = 1.72-6.15, p = 0.03). Separate inclusion of LVEF, systolic mitral annular velocity, E/E', GLS, and MD together with GLS/MD showed that GLS/MD remained the best predictor of SCD/VA (each p < 0.05). The optimal GLS/MD cutoff value to predict SCA/VA was -0.20%/ms (80% sensitivity, 76% specificity). Irrespective of LVEF, free survival was significantly better in patients with GLS/MD ≤ -0.2%/ms (log-rank test, p < 0.001). In conclusion, GLS/MD may improve cardiovascular risk stratification in subjects with HF.

Endocardial left ventricular pacing after accidental aortic wall perforation.

Inadvertent endocardial placement of a pacing lead in the left ventricle through the aortic valve is a rare complication with an unknown incidence because of inadequate reporting. Reported cases are usually the result of lead insertion via the subclavian artery. A possible but very unusual situation is endocardial lead insertion in the left ventricle after aortic arch perforation. We report the case of a 72-year-old woman in whom a screw-in pacing lead accidentally perforated the aortic arch and continued its way through the ascending aorta, aortic valve and left ventricle, after insertion through the left subclavian vein. We describe how this complication was diagnosed, the predisposing factors, the risks it carries and the ways in which devastating consequences have so far been avoided, as the patient refused any surgical intervention including lead removal.

Safety and feasibility of biventricular devices reuse in general and elderly population--a single-center retrospective cohort study.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is known to have very important beneficial effects on heart failure patients. Unfortunately, biventricular implantable cardiac devices (CRT devices), through which this therapy is implemented, are very expensive and sometimes hard to achieve, especially in underdeveloped/developing economies, making this an important problem of public health. As a possible solution, CRT reuse is of great interest nowadays, but unlike simple devices, data in the literature are scarce about biventricular device reuse. AIM: To address safety concerns, we aimed to analyze infection burden in the general and elderly population and also early battery depletion and generator malfunction of resterilized biventricular devices compared to new devices. METHODS: A cohort of 261 CRT patients (286 devices), who underwent implantation between 2000 and 2014, was retrospectively analyzed. The study group included 115 patients and 127 resterilized devices, that was divided into a subgroup of 69 elderly patients (≥60 years) and 74 devices and a subgroup of 47 younger patients (<60 years) and 53 devices, and the control group included 146 patients and 159 new devices. The groups were compared using a multivariate logistic regression model. RESULTS: A number of 12 (4.2%) infectious complications were encountered, five (3.9%) in the study group and seven (4.4%) in the control group (odds ratio, 2.83 [0.59-13.44], P=0.189), one (1.3%) in the elderly and four (7.5%) in the younger subgroup (odds ratio, 3.80 [0.36-40.30], P=0.266), with no statistically significant difference between them. There was only one case of early battery depletion, after 17 months, in one study group patient. No generator malfunction was detected. CONCLUSION: Reuse of biventricular cardiac implantable electronics seems feasible and safe in both the general population and the elderly population, and it could be a promising alternative when new devices cannot be obtained in a safe period of time.