Daily Cardiology Research Analysis

BACKGROUND: Detection of monoclonal components (MCs) using serum and urine immunofixation (IFE) and free light chain measurement is a critical early step in diagnosing cardiac amyloidosis. Patients with MCs are referred for biopsy-based diagnostic work-up. New reference ranges for the free light chain ratio (FLCR), adjusted for age and estimated glomerular filtration rate, have been proposed. OBJECTIVES: The aim of this study was to compare the diagnostic performance of the new vs the conventional FLCR in patients with light chain (AL) amyloidosis and wild-type transthyretin (ATTRwt) amyloidosis. METHODS: The analysis included 1,705 patients with AL amyloidosis and 675 with ATTRwt amyloidosis. RESULTS: In the AL cohort, 44 patients (3%) had negative results on serum and urine IFE at diagnosis. Among these, 13 patients had normal conventional FLCRs and 15 had normal new FLCRs, with no significant difference in diagnostic sensitivity (70.4% [95% CI: 55.8%-82.5%] vs 65.9% [95% CI: 50.0%-79.5%]; P = 0.82). Overall diagnostic sensitivity for MC detection was similar between the new and conventional FLCRs (99.2% vs 99.1%). Among patients with ATTRwt amyloidosis and negative serum and urine IFE results, 156 (26.5%) had abnormal FLCRs using the conventional cutoff, compared with only 12 (2%) using the new FLCR. At hematologic response assessment in AL amyloidosis, concordance in the definition of complete response between the 2 FLCR methods was 94.9% (95% CI: 93.4%-95.9%). CONCLUSIONS: The new FLCR demonstrates equivalent diagnostic sensitivity in AL amyloidosis and can be integrated into complete response criteria. In patients with suspected ATTRwt amyloidosis, it significantly reduces the proportion of FLCR-only abnormalities, thereby limiting the need for biopsy confirmation.

AIMS: Dilated cardiomyopathy (DCM) has a monogenic aetiology in up to 40% of patients. Understanding the spectrum of genotype-phenotype associations in DCM is crucial for risk stratification and personalized treatment. We aimed to (i) characterize genotype-specific features, (ii) evaluate whether phenotype-based clustering reflects underlying genotype, and (iii) compare the prognostic value of genotype- versus phenotype-based approaches. METHODS AND RESULTS: A multicentre cohort of 534 DCM patients with a (likely) pathogenic variant were grouped by genotype (genotype-first approach) and clustered by clinical phenotype (phenotype-first approach). We compared clinical characteristics, identified genotype-phenotype associations, and evaluated outcomes, including all-cause mortality, heart failure hospitalization, heart transplantation, and malignant ventricular arrhythmias. Using the genotype-first approach, significant genotype-phenotype associations were found for 10 genes. FLNC, LMNA, DSP, and PLN variants were linked to arrhythmias. BAG3, TNNT2, DMD, and TTN were associated with increased cardiac volumes and decreased left ventricular ejection fraction (LVEF). Clustering identified four phenotypic clusters: (1) young, moderately reduced LVEF; (2) arrhythmias, moderate reduced LVEF; (3) low LVEF; (4) arrhythmias, low LVEF. There were no clear correlations between phenotypic clusters and genotype. The genotype-first approach showed that LMNA, FLNC, and BAG3 variants had the highest risk for heart failure and arrhythmogenic adverse outcomes. The phenotype-first approach indicated that clusters 3 and 4 were associated with the worst prognosis. Overall, genotype was the strongest predictor of outcome. CONCLUSIONS: Patients with a genetic form of DCM exhibit clinical and genetic heterogeneity. Genotype-based risk stratification is more accurate compared to a phenotype-first approach, highlighting the importance of broad genetic screening among patients with DCM. Additionally, gene-specific risk prediction should become more prominent in current guidelines on management of genetic DCM patients.

BACKGROUND: Percutaneous left ventricular assist devices (pLVADs) are often used in critically ill patients undergoing scar-related ventricular tachycardia (VT) ablation. However, there are no randomized controlled trials evaluating their benefits. OBJECTIVES: The goal of this study was to compare outcomes between pLVAD- and non-pLVAD-supported VT ablation using a propensity score matching analysis. METHODS: This retrospective analysis comprised 481 scar-related VT patients who underwent catheter ablation (175 pLVAD and 306 non-pLVAD). A 1:1 propensity score matching was conducted to balance baseline characteristics for comparison of procedural and long-term outcomes. RESULTS: A propensity score analysis generated 115 matched pairs in each group. Baseline characteristics of the matched cohorts were comparable (mean left ventricular ejection fraction 27%, 40% NYHA functional class ≥III, and 36% electrical storm). Compared with the non-pLVAD, more patients in the pLVAD group had at least 1 VT termination during ablation. Despite including a higher use of advanced ablation strategies and a longer procedure time, the pLVAD group had a postprocedural VT inducibility similar to that of the non-pLVAD group. The incidence of periprocedural major complications was higher among pLVAD patients (29.6% vs 13.9%; P = 0.004), largely driven by vascular complications requiring intervention and periprocedural heart failure. During a median follow-up of 326 days, Kaplan-Meier curves showed no statistically significant differences in composite outcome (hospitalization for VT or worsening heart failure requiring hospitalization, LVAD implantation, orthotopic heart transplantation, and all-cause mortality), and VT recurrence. CONCLUSIONS: The use of pLVADs during VT ablation is associated with longer procedures and higher procedural complications without any benefit in acute or long-term outcomes.