A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features.

BACKGROUND: Primary carnitine deficiency (PCD) denotes low carnitine levels with an autosomal recessive pattern of inheritance. Cardiomyopathy is the most common cardiac symptom in patients with PCD, and early diagnosis can prevent complications. Next-generation sequencing can identify genetic variants attributable to PCD efficiently. OBJECTIVE: We aimed to detect the genetic cause of the early manifestations of hypertrophic cardiomyopathy and metabolic abnormalities in an Iranian family. METHODS: We herein describe an 8-year-old boy with symptoms of weakness and lethargy diagnosed with PCD through clinical evaluations, lab tests, echocardiography, and cardiac magnetic resonance imaging. The candidate variant was confirmed through whole-exome sequencing, polymerase chain reaction, and direct Sanger sequencing. The binding efficacy of normal and mutant protein-ligand complexes were evaluated via structural modeling and docking studies. RESULTS: Clinical evaluations, echocardiography, and cardiac magnetic resonance imaging findings revealed hypertrophic cardiomyopathy as a clinical presentation of PCD. Whole-exome sequencing identified a new homozygous variant, SLC22A5 (NM_003060.4), c.821G > A: p.Trp274Ter, associated with carnitine transport. Docking analysis highlighted the impact of the variant on carnitine transport, further indicating its potential role in PCD development. CONCLUSIONS: The c.821G > A: p.Trp274Ter variant in SLC22A5 potentially acted as a pathogenic factor by reducing the binding affinity of organic carnitine transporter type 2 proteins for carnitine. So, the c.821G > A variant may be associated with carnitine deficiency, metabolic abnormalities, and cardiomyopathic characteristics.

Pulsed-Field Ablation in Management of Ventricular Tachycardia: A Systematic Review of Case Reports and Clinical Outcomes.

BACKGROUND: Pulsed-field ablation (PFA) is a cutting-edge technique that employs non-thermal energy to cause cell death by inducing irreversible electroporation of cell membranes. This systematic review evaluates the PFA effectiveness as a potential alternative to radiofrequency and cryo-ablation for treating ventricular tachycardia. METHODS: PubMed, Embase, Scopus, and Web of Science were systematically searched using keywords related to ventricular tachycardia and pulsed-field ablation. Eligible Studies evaluating this therapeutic approach for ventricular tachycardia were included in the final analysis. RESULTS: We included six studies (five case reports and one case series) in our systematic review. Eight (88.8%) of procedures were successful with 100% long-term efficacy. No procedural complications or ventricular tachycardia (VT) recurrence were observed in the cases. CONCLUSION: The absence of complications, high effectiveness, and long-term success rate make PFAs a good VT treatment option. However, PFA safety and efficacy studies for VT treatment are scarce. Thus, larger investigations on this topic are urgently needed.

Vitamin D deficiency and atrial fibrillation: A cross sectional single center study.

BACKGROUND: Atrial fibrillation (AF) augments the risk of stroke by 4-5 times. Vitamin D is pivotal in numerous metabolic pathways. A handful of studies have explored the correlation between vitamin D deficiency (VDD) and AF outcomes. Hence, the authors sought to assess the relationship between VDD and AF outcomes. METHODS: From December 2021 to February 2023, 190 patients with AF were incorporated into the authors' study. Given the seasonal fluctuation of vitamin D levels, these levels were examined from the start of December until the end of March. RESULTS: The final analysis comprised 190 patients (55.8% male) with an average age of 46.22±15.03. Vitamin D deficiency, insufficiency, and sufficiency were noted in 77 (40.5%), 46 (24.2%), and 67 (35.3%) patients, respectively. Fatigue and syncope were significantly more prevalent in the VDD group than in other groups. Three-vessel disease was more frequent in the VDD group (p-value=0.04). Mortality was more prevalent in patients with VDD (6.31%) compared to the VDI (2.10%) and VDS (0.05%) groups (p = 0.03). Successful cardioversion was significantly more prevalent in the VDS group (p = 0.03). CONCLUSION: A sufficient level of vitamin D was linked with a better response to cardioversion. However, low vitamin D levels are correlated with higher mortality in AF patients.

Percutaneous versus surgical closure of paravalvular leaks in prosthetic valves: A cross-sectional comparison of clinical outcomes.

Background and Aims: Paravalvular leak (PVL) is a serious complication of prosthetic valve replacement. Both surgical and percutaneous closure techniques are used for PVL closure, but optimal strategies and comparative outcomes are uncertain. This study aimed to compare the efficacy and safety of percutaneous versus surgical PVL closure by analyzing changes in leak severity, functional status, echocardiographic parameters, and clinical outcomes. Methods: A total of 72 patients were included in this retrospective cross-sectional single-center study comparing percutaneous (n = 25) and surgical (n = 47) PVL closure from 2015 to 2022. Demographics, medical history, echocardiograms, laboratory data, complications, and mortality data were extracted from the records. Changes in leak severity, NYHA class, echocardiographic parameters, and clinical outcomes were compared between the percutaneous and surgical groups. Results: Both percutaneous and surgical PVL closure significantly reduced leak severity and improved NYHA class (both p < 0.01), with no difference between the quantity of changes in each group. The 30-day mortality was 4% after percutaneous and 6.4% after surgical closure (p = 0.65). At 90 days, mortality was 24% percutaneous versus 17% surgical (p = 0.48). The length of stay in the hospital and post-procedural decrease in hemoglobin were considerably lower in the percutaneous group. The rate of complication rates was similar between the groups. Echocardiographic changes were also comparable. Conclusion: Percutaneous and surgical PVL closure had similar efficacy in reducing leaks and improving symptoms, with no significant difference in early outcomes. Both options should be considered viable for PVL repair after heart team evaluation.

Hypertension in Cardio-Oncology Clinic: an update on etiology, assessment, and management.

Hypertension is one of the most common comorbidity and the leading cause of cancer-related death in cancer patients. The prevalence of hypertension in cancer patients is much higher than that of the general population. In the older population of cancer patients, specific cancer treatments such as new tyrosine kinase inhibitors and Vascular endothelial growth factor inhibitor drugs give rise to hypertension in cancer patients; The aim of present study is to provide a detailed discussion etiologies of cancer treatment-induced hypertension and explore the most innovative diagnostic and management approaches. This review will address the optimal approach to hypertension treatment, covering treatment initiation thresholds, targets, and the selection of anti-hypertensive agents. The lack of evidence in recent guidelines for managing cardiovascular toxicities in cancer patients can create uncertainty in clinicians' therapeutic and clinical decisions. This review aims to enhance our understanding of hypertension etiology in cancer patients and provide a practical guide to current treatment approaches.

Arrhythmogenic left ventricular cardiomyopathy caused by a novel likely pathogenic DSP mutation, p.K1165Rfs*8, in a family with sudden cardiac death.

OBJECTIVE: We conducted an investigation into the clinical and molecular characteristics of Arrhythmogenic left ventricular cardiomyopathy (ALVC) caused by a novel likely pathogenic mutation in an Iranian pedigree with sudden cardiac death (SCD). BACKGROUND: ALVC is a genetically inherited myocardial disease characterized by the substitution of fibro-fatty tissue in the left ventricular myocardium, predominantly inherited in an autosomal dominant pattern and is commonly associated with genes involved in encoding desmosomal proteins, specifically Desmoplakin (DSP). METHODS: The patient and available family members underwent a comprehensive clinical assessment, including Cardiac magnetic resonance (CMR) imaging, along with Whole-exome sequencing (WES). The identified variant was confirmed and segregated by Polymerase chain reaction (PCR) and Sanger sequencing in the family members. RESULTS: A novel likely pathogenic heterozygous variant, DSP (NM_004415.4), c.3492_3498del, p.K1165Rfs*8 was discovered in the proband. This variant is likely to be the primary reason for ALVC in this specific family. This variant was confirmed by Sanger sequencing and segregated in other affected members of the family. CONCLUSION: We identified a novel likely pathogenic variant in the DSP gene, which has been identified as the cause of ALVC in an Iranian family. Our investigation underscores the importance of genetic testing, specifically WES, for individuals suspected of ALVC and have a family history of SCD.

The predictive value of cardiac MRI strain parameters in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction and a low fibrosis burden: a retrospective cohort study.

Background: Prompt interventions prevent adverse events (AE) in hypertrophic cardiomyopathy (HCM). We evaluated the pattern and the predictive role of feature tracking (FT)-cardiac magnetic resonance (CMR) imaging parameters in an HCM population with a normal left ventricular ejection fraction (LVEF) and a low fibrosis burden. Methods: The CMR and clinical data of 170 patients, consisting of 142 HCM (45 ± 15.7 years, 62.7% male) and 28 healthy (42.2 ± 11.26 years, 50% male) subjects, who were enrolled from 2015 to 2020, were evaluated. HCM patients had a normal LVEF with a late gadolinium enhancement (LGE) percentage below 15%. Between-group differences were described, and the potent predictors of AE were determined. A P-value below 0.05 was considered significant. Results: LV global longitudinal, circumferential, and radial strains (GLS, GCS, and GRS, respectively) and the LV myocardial mass index (MMI) were different between the healthy and HCM cases (all Ps < 0.05). Strains were significantly impaired in the HCM patients with a normal MMI. A progressive decrease in LVGLS and a distinct fall in LVGCS were noted with a rise in MMI. AE were predicted by LVGLS, LVGCS, and the LGE percentage, and LVGCS was the single robust predictor (HR, 1.144; 95% CI, 1.080-1.212; P = 0.001). An LVGCS below 16.2% predicted AE with 77% specificity and 58% sensitivity. Conclusions: LV strains were impaired in HCM patients with a normal EF and a low fibrosis burden, even in the presence of a normal MMI. CMR parameters, especially FT-CMR values, predicted AE in our HCM patients.