Hasegawa, Kanae

BACKGROUND: Sustained ventricular tachycardia (VT) in cardiac amyloidosis is uncommon, and the substrate and outcomes of catheter ablation are not defined. METHODS: We included 22 consecutive patients (mean age, 68±10 years; male sex, 91%) with cardiac amyloidosis (ATTR [transthyretin], n=16; light chain, n=6) undergoing catheter ablation for VT/ventricular fibrillation (VF) between 2013 and 2023 in a retrospective, observational, international study. The primary efficacy outcome was recurrent VT/VF during follow-up, while the primary safety end point included major procedure-related adverse events. RESULTS: The indication for ablation was drug-refractory VT in 17 patients (77%), and premature ventricular complex–initiated polymorphic VT/VF in 5 patients (23%). Catheter ablation was performed using endocardial (n=17.77%) or endo-epicardial approaches (n=5.23%). Complete endocardial electroanatomical voltage maps of the left and right ventricles were obtained in 17 (77%) and 10 (45%) patients, respectively. Each patient had evidence of low-voltage areas, most commonly involving the interventricular septum (n=16); late potentials were recorded in 16 patients (73%). A median of 1 (1–2) VT was inducible per patient; 12 of the 26 mappable VTs (46%) originated from the interventricular septum. Complete procedural success was achieved in 16 patients (73%), with 4 (18%) major procedure-related adverse events. After a median follow-up of 32 (14–42) months, sustained VT/VF recurrence was observed in 9 patients (41%); survival free from VT/VF recurrence was 56% (95% CI, 36%–86%) at 36-month follow-up, and most patients remained on antiarrhythmic drugs. A significant reduction in per patient implantable cardioverter defibrillator therapies was noted in the 6-month period after ablation (before: 6 [4–9] versus after: 0 [0–0]; P <0.001). In multivariable analysis, complete procedural success was associated with reduced risk of recurrent VT/VF (hazard ratio, 0.002; P =0.034). CONCLUSIONS: Catheter ablation can achieve control of recurrent VT/VF in more than half of patients with cardiac amyloidosis, and the reduction in VT/VF burden post-ablation may be relevant for quality of life. Septal substrate and risk of procedure-related complications challenge successful management of patients with cardiac amyloidosis and VT/VF.

Abstract Background the electrophysiological substrate underpinning ventricular tachycardia (VT) in cardiac amyloidosis (CA) remains elusive, and outcomes of catheter ablation in this peculiar population are currently unknown. Purpose we sought to describe the electrophysiological substrate and clinical outcomes of VT ablation in a cohort of patients with CA. Methods we included 19 consecutive patients (mean age, 69±10 years; male sex, 89%) with CA (ATTR, n=13; AL, n=6) undergoing catheter ablation for VT/ventricular fibrillation (VF) between 2013 and 2023 in a retrospective, observational, international study, involving 7 referral European and North American electrophysiology units. The primary efficacy outcome was recurrent VT/VF during follow-up, while the primary safety outcome included major procedure-related adverse events. Results the indication for ablation was drug-refractory VT in 16 patients (84%), and PVC-initiated polymorphic VT/VF in 3 (16%). Catheter ablation was performed using endocardial (n=14, 74%) or endo-epicardial approaches (n=5, 26%). Complete endocardial electroanatomical voltage maps of the left and right ventricles were obtained in 14 (74%) and 6 (32%) patients, respectively. Each patient had evidence of low-voltage areas, most commonly involving the interventricular septum (n=12); late potentials were recorded in 13 patients (68%). A median of 1 (1-2) VTs were inducible per patient; in 10 subjects (43% of mappable VTs), activation mapping was consistent with septal VT origin. Complete procedural success was obtained in 13 patients (68%), at the expense of 4 (21%) major procedure-related adverse events. After a median follow-up of 36 (18-54) months, sustained VT/VF recurrence was observed in 9 patients (47%); survival free from VT/VF recurrence was 74% (95%CI, 56-96%) at 12 months, and 53% (95%CI, 34-94%) at 36-month follow-up; the majority of patients remained on antiarrhythmic drugs (Figure). Low-voltage QRS (HR,21.96; p=0.022) and complete procedural success (HR,0.08; p=0.029) were associated with recurrent VT/VF at multivariable analysis (Figure). Conclusions catheter ablation of VT/VF is associated with favorable acute and mid-term arrhythmia control, yet with substantial risk of procedure-related complications and long-term recurrences. Septal substrate and frailty challenge successful management of patients with CA and VT/VF.Multimodality evaluation of LV substrateMain Study Outcomes

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance ( P <5×10 −8 ) near NOS1AP , KCNQ1 , and KLF12 , and 1 missense variant in KCNE1 (p.Asp85Asn) at the suggestive threshold ( P <10 −6 ). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation ( h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r g =0.40; P =3.2×10 −3 ). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls ( P <10−13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive ( P <0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.