Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.

The giant protein titin (TTN) is a sarcomeric protein that forms the myofibrillar backbone for the components of the contractile machinery which plays a crucial role in muscle disorders and cardiomyopathies. Diagnosing TTN pathogenic variants has important implications for patient management and genetic counseling. Genetic testing for TTN variants can help identify individuals at risk for developing cardiomyopathies, allowing for early intervention and personalized treatment strategies. Furthermore, identifying TTN variants can inform prognosis and guide therapeutic decisions. Deciphering the intricate genotype-phenotype correlations between TTN variants and their pathologic traits in cardiomyopathies is imperative for gene-based diagnosis, risk assessment, and personalized clinical management. With the increasing use of next-generation sequencing (NGS), a high number of variants in the TTN gene have been detected in patients with cardiomyopathies. However, not all TTN variants detected in cardiomyopathy cohorts can be assumed to be disease-causing. The interpretation of TTN variants remains challenging due to high background population variation. This narrative review aimed to comprehensively summarize current evidence on TTN variants identified in published cardiomyopathy studies and determine which specific variants are likely pathogenic contributors to cardiomyopathy development.

Prevalence of contrast-induced nephropathy after primary percutaneous coronary intervention at a tertiary referral hospital.

Objective: This study aimed to quantify the incidence of Contrast-induced nephropathy (CIN) in patients undergoing primary percutaneous coronary intervention (PPCI) due to acute ST-elevation myocardial infarction (STEMI). Methods: From April 2019 to March 2022, a prospective, observational study enrolled 213 consecutive STEMI patients referred to a tertiary hospital for PPCI. Participants were divided into tow groups based on the presence or absence of contrast-induced nephropathy. The chi-square test (χ2) and Student's t-test evaluated the data, with logistic regression identifying CIN's independent predictors. Results: Results: In this study, the incidence of contrast-induced nephropathy was observed at 13.1% (N = 28). Several factors were more prevalent among patients exhibiting contrast-induced nephropathy. These factors encompassed: radial access for coronary angiography over the femoral method (P = 0.021), elevated contrast volume (P = 0.003), smoking (P = 0.009), diabetes (P = 0.04), heart failure (P = 0.049), a history of coronary artery bypass graft (P = 0.006), diminished left ventricular ejection fraction indicating systolic dysfunction (P = 0.012), cardiogenic shock (P = 0.046), increased BUN at the time of admission (P = 0.043), decreased initial GFR (P = 0.004), and prior consumption of medications such as aspirin (P = 0.002), diuretics (P = 0.046), beta blockers (P = 0.04), angiotensin-converting enzyme inhibitors (P = 0.033), angiotensin receptor blockers (P = 0.02). Other relevant conditions included anemia (P = 0.012), leukocytosis (P = 0.011), hypercholesterolemia (P = 0.034), and reduced HDL levels (P = 0.004).Through logistic regression, key predictors for the onset of contrast-induced nephropathy were determined, which included heart failure (OR: 5.52; 95% CI: 1.08-28.24), radial access (OR: 12.71; 95% CI: 1.45-110.9), hypercholesterolemia (OR: 1.02; 95% CI: 1.004-1.04), increased BUN upon admission (OR: 1.11; 95% CI: 1.006-1.24), and leukocytosis (OR: 2.03; 95% CI: 1.18-3.49). Conclusions: While heart failure, radial access, hypercholesterolemia, elevated BUN at admission, and leukocytosis significantly influenced renal filtration deterioration post-PPCI, it's evident that CIN is multifactorial. Further studies are crucial to elucidate the underlying factors.

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.

Aortic Arch Debranching and Thoracic Endovascular Aortic Repair (TEVAR) for Type B Aortic Dissection.

BACKGROUND: Since its introduction, thoracic endovascular aortic repair (TEVAR) has revolutionized the treatment of type B aortic dissections (TBADs). However, the proximal aspect of the aortic pathology treated may infringe on the origin of the left subclavian artery or even more proximally. Hence, to ensure durable outcomes, the origin of these vessels needs to be covered, but an extra-anatomical bypass is required to perfuse vital branches, known as aortic arch debranching. This series aims to describe and delineate the disparities of aortic arch debranching during TEVAR for TBAD. METHODS: A retrospective review and analysis of a multicenter international database was conducted to identify patients with TBAD treated with TEVAR between 2005 and 2021. Data analyzed included patient demographics, disease characteristics, operative characteristics, and postoperative outcomes with follow-up on mortality and reintervention. All statistical analyses were carried out using IBM SPSS 26. Patient survival was calculated using a Kaplan-Meier survival analysis, and a P value of less than 0.05 was considered statistically significant. RESULTS: A total of 58 patients were included in the analysis, of which 27 (46.6%) presented with complicated disease and 31 were uncomplicated, of which 10 (17.2%) were classed as high risk and 21 (36.2%) low risk. Zone 2 was the most common proximal landing zone for the stent graft. Left subclavian artery bypass was performed selectively (26%), with 1 stroke occurring, likely due to embolic reasons. A further 6 underwent more proximal aortic debranching before TEVAR (10%) and was a significant risk factor for mortality and the number of stents deployed. The overall rates of reintervention and mortality were 17.2% (n = 10) and 29.3% (n = 17). CONCLUSIONS: Aortic arch debranching and TEVAR for TBAD is associated with significant mortality. Future developments to treat aortic arch pathology could incorporate branched graft devices, eliminating the need for debranching, improving stroke rates, and reducing future reinterventions.

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.

MicroRNA-143 as a potential tumor suppressor in cancer: An insight into molecular targets and signaling pathways.

MicroRNAs (MiRNAs), which are highly conserved and small noncoding RNAs, negatively regulate gene expression and influence signaling pathways involved in essential biological activities, including cell proliferation, differentiation, apoptosis, and cell invasion. MiRNAs have received much attention in the past decade due to their significant roles in cancer development. In particular, microRNA-143 (miR-143) is recognized as a tumor suppressor and is downregulated in most cancers. However, it seems that miR-143 is upregulated in rare cases, such as prostate cancer stem cells, and acts as an oncogene. The present review will outline the current studies illustrating the impact of miR-143 expression levels on cancer progression and discuss its target genes and their relevant signaling pathways to discover a potential therapeutic way for cancer.