The genetic basis of apparently idiopathic ventricular fibrillation: a retrospective overview.

AIMS: During the diagnostic work-up of patients with idiopathic ventricular fibrillation (VF), next-generation sequencing panels can be considered to identify genotypes associated with arrhythmias. However, consensus for gene panel testing is still lacking, and variants of uncertain significance (VUS) are often identified. The aim of this study was to evaluate genetic testing and its results in idiopathic VF patients. METHODS AND RESULTS: We investigated 419 patients with available medical records from the Dutch Idiopathic VF Registry. Genetic testing was performed in 379 (91%) patients [median age at event 39 years (27-51), 60% male]. Single-gene testing was performed in 87 patients (23%) and was initiated more often in patients with idiopathic VF before 2010. Panel testing was performed in 292 patients (77%). The majority of causal (likely) pathogenic variants (LP/P, n = 56, 15%) entailed the DPP6 risk haplotype (n = 39, 70%). Moreover, 10 LP/P variants were found in cardiomyopathy genes (FLNC, MYL2, MYH7, PLN (two), TTN (four), RBM20), and 7 LP/P variants were identified in genes associated with cardiac arrhythmias (KCNQ1, SCN5A (2), RYR2 (four)). For eight patients (2%), identification of an LP/P variant resulted in a change of diagnosis. In 113 patients (30%), a VUS was identified. Broad panel testing resulted in a higher incidence of VUS in comparison to single-gene testing (38% vs. 3%, P < 0.001). CONCLUSION: Almost all patients from the registry underwent, albeit not broad, genetic testing. The genetic yield of causal LP/P variants in idiopathic VF patients is 5%, increasing to 15% when including DPP6. In specific cases, the LP/P variant is the underlying diagnosis. A gene panel specifically for idiopathic VF patients is proposed.

Reassessing noninducibility as ablation endpoint of post-infarction ventricular tachycardia: the impact of left ventricular function.

BACKGROUND: Noninducibility is frequently used as procedural end point of ventricular tachycardia (VT) ablation after myocardial infarction. We investigated the influence of left ventricular (LV) function on the predictive value of noninducibility for VT recurrence and cardiac mortality. METHODS AND RESULTS: Ninety-one patients (82 men, 67±10 years) with post-myocardial infarction VT underwent ablation between 2009 and 2012. Fifty-nine (65%) had an LV ejection fraction (EF) >30% (mean 41±7) and 32 (35%) an LVEF≤30% (mean 20±5). Thirty patients (51%) with EF>30% and 13 (41%) with EF≤30% were noninducible after ablation (P=0.386). During a median follow-up of 23 (Q1-Q3 16-36) months, 35 patients (38%) experienced VT recurrences and 17 (18%) cardiac death. At 1 year follow-up, survival free from VT recurrence and cardiac death for patients with LVEF>30% was 80% (95% confidence interval [CI], 70-90) compared with 42% (95% CI, 33-51) for those with LVEF≤30% (P=0.001). Noninducible patients with LVEF>30% had a recurrence-free survival from cardiac death of 90% (95% CI, 71-100) compared with 65% (95% CI, 47-83) for inducible patients (P=0.015). In the subgroup of patients with LVEF≤30%, the survival free from VT recurrence and cardiac death was 31% (95% CI, 0%-60%) for noninducible compared with 39% (95% CI, 27-52) for those who remained inducible (P=0.842). CONCLUSIONS: Noninducible patients with moderately depressed LV function have a favorable outcome compared with patients who remained inducible after ablation. On the contrary, patients with severely depressed LV function have a poor prognosis independent of the acute procedural outcome.

Diagnosis and mortality prediction in pulmonary hypertension: the value of the electrocardiogram-derived ventricular gradient.

PURPOSE: The aim of this study was to investigate the use of the electrocardiogram-derived ventricular gradient, projected on the x-axis (VGx), for detection of pulmonary hypertension (PH) and for prediction of all-cause mortality in PH patients. METHODS: In patients referred for PH screening (n = 216), the VGx was calculated semiautomatically from the electrocardiogram and was defined as abnormal when less than 24 mV · ms. The VGx of PH patients was compared with the VGx of patients without PH. The association between a reduced VGx and mortality was investigated in PH patients. RESULTS: Patients with PH (n = 117) had a significantly reduced VGx: 14 ± 27 vs 45 ± 23 mV · ms, P < .001. Furthermore, a severely reduced VGx (<0 mV · ms) was associated with increased mortality in PH patients: hazard ratio, 1.025 (95% confidence interval, 1.006-1.045; P = .012) per mV·ms VGx decrease. CONCLUSION: Reduced VGx is associated with the presence of PH and, more importantly, within PH patients, a severely reduced VGx predicts mortality.