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Povzetek: Hypertrophic cardiomyopathy is often caused by pathogenic MYBPC3 variants. The study of Italian patients with HCM and MYBPC3(NM_000256.3):c.913_914del showed a higher disease penetrance in males and a higher frequency of arrhythmias compared to patients with other likely pathogenic and pathogenic (LP/P) MYBPC3 variants. We investigated the clinical outcomes of Slovenian probands with MYBPC3 LP/P variants, estimated the variant penetrance and compared the results with an Italian study. We identified 31 haplotype-matched individuals with MYBPC3:c.913_914del and 34 individuals with other LP/P MYBPC3 variants. We observed some significant differences in clinical and echocardiographic characteristics and frequency of adverse cardiac events between Slovenian and Italian probands with MYBPC3:c913_914del. We were unable to replicate previous findings for MYBPC3:c.913_914del, highlighting the complexity of genotype–phenotype associations.
Ključne besede: cardiogenetics, cardiology, MYBPC3, hypertrophic cardiomyopathy
Objavljeno v DiRROS: 16.03.2026; Ogledov: 56; Prenosov: 37
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Povzetek: Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) improve outcomes in heart failure; however, data in left ventricular non-compaction cardiomyopathy (LVNC) patients are limited. We sought to analyze the clinical effects of the SGLT2is dapagliflozin and empagliflozin in patients with LVNC. Methods: Thirty consecutive LVNC patients diagnosed by CMR were prospectively enrolled. Clinical, biochemical and echocardiography data were obtained at the initiation of the SGLT2is and at the 12-month follow-up. All patients were on stable guideline-directed medical therapy. A response to SGLT2i therapy was defined as an improvement in LVEF ≥ 5% at 12 months. Results: Of the 30 enrolled patients, 25 were male, with a mean age of 49 ± 16 years and few comorbidities. Dapagliflozin 10 mg was prescribed to 23 patients and empagliflozin 10 mg to 7 patients. Five patients experiened an adverse event during follow-up (one sudden cardiac death; four heart transplantations or LVAD implantations). During follow-up, significant improvements were observed in LVEF (32.1 ± 6.9% vs. 43.5 ± 9.7%; p = 0.003), LVOT VTI (14.8 ± 6.5 cm vs. 17.6 ± 3.3 cm; p = 0.008), E/e′ (14.8 ± 4.7 vs. 10.0 ± 4.1; p < 0.001), and TAPSE (2.0 ± 0.4 cm vs. 2.3 ± 0.4 cm; p = 0.012). NT-proBNP levels decreased significantly (2025 ± 2198 pg/mL vs. 582 ± 803 pg/mL; p = 0.005). Eighteen patients responded favorably to SGLT2i therapy (Group A), whereas seven showed no significant LVEF improvement (Group B). The groups did not differ significantly in age, sex, baseline creatinine, or bilirubin. Compared to Group B, Group A had a smaller baseline LV end-diastolic diameter (6.3 ± 0.8 cm vs. 7.1 ± 0.9 cm; p = 0.025) and lower NT-proBNP levels (1720 ± 1662 pg/mL vs. 4527 ± 4397 pg/mL; p = 0.02). Conclusions: In patients with LVNC, SGLT2i therapy is associated with significant reverse remodeling and functional improvement. Benefits may be greater in those with less advanced disease.
Ključne besede: non-compaction cardiomyopathy, guideline-directed heart failure medical therapy, myocardial recovery
Objavljeno v DiRROS: 15.12.2025; Ogledov: 316; Prenosov: 158
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Povzetek: Background Titin truncating variants (TTNtv-s) are the most common genetic cause of dilated cardiomyopathy (DCM). Only rare TTNtv-s in the constitutively expressed exons of the A-band of the protein titin are associated with DCM according to the guidelines, however, studies in large cohorts of patients with DCM suggest that the region where TTNtv-s are associated with DCM is wider, extending at least into the I-band. The aim of this study was to describe the molecular pathology of TTNtv-s in Slovenian patients with cardiomyopathy and to clinically characterise the most recurrent TTNtv. Results We collected all TTNtv-s identified in patients with cardiomyopathy using next-generation sequencing genetic testing between 2010 and July 2024, resulting in 42 unique variants identified in 54 patients. The TTN:c.12478del variant, affecting not the A-band but the proximal I-band, specifically the cardiac-specific N2Bus region, was found to be the most recurrent variant, present in seven (11.6%) probands with DCM. Genetic characterisation revealed a probable founder origin of the variant. Clinical characterisation of these probands revealed a phenotype consistent with DCM and severely reduced left ventricular ejection fraction in all probands. Three (43%) of the probands had atrial fibrillation and/or non-sustained ventricular tachycardia. Based on literature reports and evidence supporting the pathogenicity of the TTN:c.12478del variant affecting the proximal I-band, we classified all rare TTNtv-s in constitutively expressed exons of the I-band as (likely) pathogenic. Therefore, 33 (78.6%) TTNtv-s were classified as (likely) pathogenic (13 in the I-band, affecting 19 probands and 20 in the A-band affecting 25 probands), meaning that TTNtv-s were identified in 44 genotype-positive Slovenian probands with DCM, explaining 73.3% of the molecular pathology of DCM. Conclusion We report an almost threefold higher diagnostic yield of TTNtv-s in probands with DCM compared to previously reported findings in cohorts of patients with DCM from other populations. We also highlight the need for screening for rare TTNtv-s in the constitutively expressed exons of the I-band and for TTN:c.12478del in patients with DCM in this geographical region.
Ključne besede: Titin, TTNtv, I-band, TTN:c.12478del, dilated cardiomyopathy, DCM
Objavljeno v DiRROS: 02.12.2025; Ogledov: 785; Prenosov: 164
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