Search

Background: Variants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13-25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family., Methods: Molecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases., Results: Seventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late‑gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall., Conclusion: This large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Endomyocardial biopsy (EMB) is a diagnostic tool for evaluating various cardiac conditions, such as myocarditis and myocardial infiltrative diseases. It is also the gold standard screening technique for detecting allograft rejection after heart transplantation. Despite advances in noninvasive imaging modalities for myocardial tissue characterization, EMB is still necessary for making a definitive diagnosis and determining treatment for certain conditions. Herein, we report our recent experience using EMB and its diagnostic yield., Methods and Results: We retrospectively reviewed EMBs performed at our institution from March 2018 through March 2023. Clinical data, including patient characteristics, indication and diagnostic yield of EMB, and procedure-related complications, were collected. Histopathological findings of the biopsies were recorded and classified based on the degree to which they matched the clinical diagnosis and cardiac magnetic resonance imaging (CMR) findings. A total of 212 EMBs obtained in 178 consecutive patients were retrospectively analyzed, with 42 biopsies performed for allograft rejection surveillance (10 patients) and the remaining performed for presumptive diagnosis of acute myocarditis or unexplained cardiomyopathy. Among the non-heart transplant cases, 54.7% of EMBs provided a clear diagnosis. The most common diagnosis was myocarditis (69%), followed by cardiac amyloidosis (CA) (26%). EMB was also helpful in detecting several rare cardiac conditions, such as eosinophilic granulomatosis with polyangiitis (EGPA), Fabry disease, and cardiac sarcoidosis. In a cohort of 101 patients who underwent both CMR and EMB, the results were concordant in 66% of cases. However, in 24.7% of patients, EMB was able to identify pathological conditions where CMR results were inconclusive, highlighting its complementary role in determining an accurate diagnosis. No complications were reported in any of the 212 EMBs performed., Conclusions: With advances in cardiac imaging modalities, EMB is not routinely indicated for the diagnosis of cardiomyopathy. However, EMB is still an important tool for diagnosing specific cardiac diseases and could be crucial for confirming the diagnosis. EMB is generally safe if performed at experienced centers., Competing Interests: Conflicts of interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Introduction: Lipoprotein(a) [Lp(a)] is composed of 2 major protein components, a low-density lipoprotein (LDL) cholesterol-like particle containing apolipoprotein B (apo B) that is covalently bound to apolipoprotein(a). Its level is predominantly genetically determined, and it is estimated that 20% to 25% of the population have Lp(a) levels that are associated with increased cardiovascular risk. Elevated Lp(a) is related to increased vascular inflammation, calcification, atherogenesis and thrombosis, and is considered an independent and potentially causal risk factor for atherosclerotic cardiovascular diseases and calcified aortic valve stenosis. Recent data demonstrate that Lp(a) testing has the potential to reclassify patients' risk and improve cardiovascular risk prediction, and therefore could inform clinical decision-making regarding risk management. Statins and ezetimibe are ineffective in lowering Lp(a) levels, whereas proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have a modest effect on Lp(a) reduction. Nevertheless, RNA interference-based therapies with potent Lp(a)-lowering effects are in advanced stages of development, and clinical trials are underway to confirm their benefit in reducing cardiovascular events. This scientific consensus document was developed by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, and the Israeli Society for Clinical Laboratory Sciences, in order to create uniformity in Lp(a) measurement methods, indications for testing and reporting of the results, aiming to improve the diagnosis and management of elevated Lp(a) in clinical practice.

Importance: Limited data describe attendance to pelvic floor physical therapy (PFPT) in a postpartum patient population., Objectives: The objective was describe attendance to PFPT in a cohort of postpartum women at high-risk of pelvic floor concerns. We secondarily compared attendance between patients with and without evaluation in a postpartum pelvic floor healing clinic (PPFHC)., Study Design: This was a retrospective cohort study of 2 convenience samples from an academic hospital. The PPFHC cohort comprised all postpartum vaginal delivery patients evaluated in the PPFHC from July 2021 to July 2022. The historical pre-PPFHC cohort comprised patients with third/fourth-degree obstetrical lacerations from December 2019 to January 2021. We abstracted attendance to PFPT, number of visits, Pelvic Floor Distress Inventory-20 (PFDI-20) scores, Pelvic Floor Impact Questionnaire (PFIQ) scores, and discharge status., Results: Our cohort contained 464 patients, 195 (42.0%) from pre-PPFHC and 269 (58.0%) from PPFHC. Among all patients 302 (65.1%) were referred to PFPT and 170 (56.3%) attended at least 1 visit, 82 (48.2%) were discharged from PFPT with goals met, and the median number of visits was 6 (3-10). The majority of patients (97.0%, n = 261) seen in the PPFHC were referred to PFPT, compared with 22.0% (n = 41) of pre-PPFHC patients (P < 0.01). More patients in the pre-PPFHC cohort attended PFPT than in those the PPFHC cohort (75.6% vs 53.5%, P ≤ 0.01). Most patients exhibited improved PFDI and PFIQ scores after PFPT (n = 88, 80.0%, and n = 89, 81.7% respectively)., Conclusions: Patients attending postpartum PFPT demonstrated high therapy completion rates. A dedicated PPFHC had more referrals, however, lower PFPT attendance rates, when compared with a historical cohort., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Competing Interests: Disclosures None.

Background: Homozygous familial hypercholesterolemia is a genetic disease characterized by extremely high levels of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular events. The proof-of-concept study ORION-2 (A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia) showed that inclisiran, a small interfering RNA that prevents production of the hepatic PCSK9 protein (proprotein convertase subtilisin/kexin type 9), could lead to durable reductions in LDL-C levels when added to statins and ezetimibe in patients with homozygous familial hypercholesterolemia., Methods: ORION-5 was a phase 3, 2-part, multicenter study in 56 patients with homozygous familial hypercholesterolemia and elevated LDL-C levels despite maximum tolerated doses of LDL-C-lowering therapies with or without lipoprotein apheresis. Patients eligible for part 1 (double-blind, 6 months) were randomized 2:1 to receive either 300 mg of inclisiran sodium (equivalent to 284 mg of inclisiran) or placebo. Placebo-treated patients from part 1 were transitioned to inclisiran in part 2 (open-label, 18 months). The primary end point was the percentage change in LDL-C levels from baseline to day 150., Results: The mean age of the patients was 42.7 years, and 60.7% were women. The mean baseline LDL-C levels were 294.0 mg/dL and 356.7 mg/dL in the inclisiran and placebo groups, respectively. The placebo-corrected percentage change in LDL-C level from baseline to day 150 was -1.68% (95% CI, -29.19% to 25.83%; P =0.90), and the difference was not statistically significant between the inclisiran and placebo groups. The placebo-corrected percentage change in PCSK9 levels from baseline to day 150 was -60.6% with inclisiran treatment ( P <0.0001); this was sustained throughout the study, confirming the effect of inclisiran on its biological target of PCSK9. No statistically significant differences between the inclisiran and placebo groups were observed in the levels of other lipids and lipoproteins (apolipoprotein B, total cholesterol, and non-high-density lipoprotein cholesterol). Adverse events and serious adverse events did not differ between the inclisiran and placebo groups throughout the study., Conclusions: Inclisiran treatment did not reduce LDL-C levels in patients with homozygous familial hypercholesterolemia despite substantial lowering of PCSK9 levels. Inclisiran was well-tolerated, and the safety findings were consistent with previously reported studies and the overall safety profile., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03851705., Competing Interests: Disclosures Dr Raal received consulting fees and honoraria from Amgen, Novartis Pharmaceuticals, Regeneron Pharmaceuticals, and LIB Therapeutics. Dr Durst received consulting fees and honoraria from Novartis and Sanofi, lecturing fees from Novartis, and honoraria from Medison. Drs Bi, Talloczy, Maheux, and Lesogor are full-time employees of Novartis and have Novartis stocks or stock options. Dr Kastelein received consulting fees from 89Bio, Esperion Therapeutics, Madrigal, CiVi Therapeutics, North Sea Therapeutics, CSL-Behring, Novartis, Inversago, Draupnir, CinCor, and Scribe Therapeutics; is a board member of North Sea and Staten Biotech; is Chief Scientific Officer of New Amsterdam Pharma; is acting Chief Medical Officer of Staten Biotech; and holds stock and stock options in New Amsterdam.