BACKGROUND
In approximately 5-10% of cases, hypertrophic cardiomyopathy (HCM) presents left ventricular remodeling with hypokinesia and dilatation, defined "end-stage" phase (ES) of the disease, typically associated with development of advanced heart failure (HF). Prescription of conventional medical treatments for HF with a reduced ejection fraction (HFrEF) have never been investigated in ES-HCM.
METHODS
ES-HCM patients from 11 Italian referral centres were retrospectively evaluated. We included only patients with a last clinical evaluation after 2019, to ensure all patients were potentially evaluated in the era of the "4 HFrEF pillars" (beta blockers [BB], renin-angiotensin system inhibitors [RASi], mineralocorticoid receptor antagonists [MRA], and sodium-glucose cotransporter-2 inhibitors [SGLT2i]). For all patients we collected clinical information, with a focus on medical therapy at last clinical evaluation.
RESULTS
The study population included 274 ES-HCM patients (59% males, mean age 60 ± 15 years). All 4 HFrEF pillars were prescribed in 26%. Specifically, 90% were treated with BB, 75% with RASi, 66% with MRA, 46% with SGLT2i. Few differences emerged when comparing patients taking versus not taking BB or RASi. Patients taking versus not taking MRA and SGLT2i more commonly had atrial fibrillation and showed worse echocardiographic features. SGLT2i use was significantly higher among ES-HCM patients with LVEF <40%.
CONCLUSIONS
While BB and RASi are commonly used in ES-HCM, MRA and SGLT2i are prescribed less frequently and in patients with a worse clinical profile. Combination of all classes is not common, suggesting both clinical inertia and limitations inherent to the disease pathophysiology.
G. Tini, Isabella Perlati, S. Palma et al.· International Journal of Car...· 0 citations
BACKGROUND
Periodic reinterpretation of variants associated with hypertrophic cardiomyopathy (HCM) is recommended in the light of evolving knowledge, but it requires considerable resources, and its clinical impact is unresolved.
OBJECTIVES
We here report the results of a systematic variant reclassification of HCM-associated variants identified at a national referral center, and the impact on clinical profiling.
METHODS
A total of 805 consecutive probands with a definite HCM diagnosis genotyped in 1998-2023 (overall 276 variants: 162 pathogenic/likely pathogenic -P/LP-, 109 variants of uncertain significance -VUS-, and 5 benign/likely benign - B/LB) underwent variant reclassification. All were analyzed for all-cause death, ventricular arrhythmia composite (sudden death, cardiac arrest, appropriate implantable cardioverter-defibrillator therapy), atrial fibrillation or cerebrovascular events, heart failure composite (NYHA class III/IV, left ventricular ejection fraction <35%, cardiac transplantation).
RESULTS
After a median follow-up of 8.8 [6.1-11.8] years, among the 276 variants, 61 (22.1%) were reclassified: 29 variants from P/LP to VUS or B/LB, 21 from VUS to P/LP, and 11 from VUS to B/LB, affecting 69 patients overall. The overall yield of genetic testing (% with P/LP) changed from 58.7 to 55.4%. At survival analysis, HRs associated with P/LP status improved after reclassification for both all-cause death and ventricular arrhythmia. No changes were observed for the other outcomes.
CONCLUSION
Systematic reclassification of genetic variants led to a refinement of variant classification accuracy due to downgrading of 5.5% of P/LP variants, although 18.3%VUS/B/LB were upgraded to P/LP. Reclassification more accurately identified risks associated with P/LP status, compared to the initial adjudication.
A. Del Franco, Valeria Setti, Federica Colio et al.· International Journal of Car...· 0 citations
The results indicate that pangenome-based workflows aid improved detection of large variants from targeted sequencing data in the clinical context and suggest that they may contribute to more unified variant detection frameworks for all-size genetic variants in the future.
F. Mazzarotto, Özem Kalay, E. Arslan et al.· Genome Medicine· 0 citations
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