Andrew E. Epstein

Background: Inherited cardiomyopathies cause ventricular tachycardia (VT) and heart failure, yet genotype‐based substrate characterization is limited. Methods: Patients with inherited cardiomyopathy undergoing VT (n=80) or premature ventricular complex (n=25) ablation between 2010 and 2024 were evaluated for arrhythmia substrate, ablation, and heart failure outcomes. Results: Among 105 patients, the median age was 51 years, 72% were men, and the cohort comprised desmosomal (desmoplakin [DSP], 11%; non‐DSP, 24%), titin (22%), lamin A/C (LMNA; 20%), sarcomeric (14%), ion‐channel (5%), and cytoskeletal/Z‐disk (4%) genotype groups. In the VT cohort, low‐voltage substrate was predominantly septal in the LMNA (55%), titin (67%), and sarcomeric (75%) groups; both septal (75%) and lateral left ventricle (75%) in the cytoskeletal/Z‐disk group; perimitral (71%) and lateral left ventricle (57%) in the DSP desmosomal group; and right ventricular free wall (91%) in the non‐DSP desmosomal group. Ablation eliminated clinical VT in 90%, with noninducibility of any VT in 52 of 80 (65%) cases. VT‐free survival was 51% during 3 years (1.8–6.3 years). Among recurrences, 11 of 39 (28%) patients had a single VT episode. VT‐free survival was highest in the non‐DSP desmosomal group and lowest in the LMNA group (66% versus 20%, P =0.03). Residual VT inducibility (hazard ratio [HR], 2 [95% CI, 1.05–3.77]) and LMNA variant (HR, 2.25 [95% CI, 1.1–4.57]) predicted recurrence. In the premature ventricular complex cohort, the burden decreased from 12% (interquartile range [IQR]=Q3–Q1, 21–8) to 3.75% (IQR 3–1, 6–1), and 17 of 25 (68%) had ≤5% burden. End‐stage heart failure outcome (left ventricular assist device, transplant, or death) occurred in 29% overall and 52% in the LMNA group. Conclusions: Genotype correlates with VT substrate. Ablation successfully reduced VT and premature ventricular complex burden; however, long‐term VT recurrence was common except in non‐DSP desmosomal variants. LMNA variants portend worse outcomes.

BACKGROUND: The subcutaneous implantable cardioverter defibrillator (S-ICD) offers protection from sudden cardiac death without transvenous leads. Although contemporary techniques and programming have reduced inappropriate shocks, high rates persist in certain populations. The objective of this study was to evaluate the impact of a novel quantitative vector screening (QVS) protocol on the incidence of sensing-related complications and inappropriate shocks in patients undergoing S-ICD implantation. METHODS: We analyzed 223 consecutive patients who underwent S-ICD implantation at the Hospital of the University of Pennsylvania from December 2018 to July 2025. Traditional vector screening was used before 2023. In 2023, we implemented QVS, which incorporated quantitative sensing scores for each candidate and raised the threshold for S-ICD implantation. The primary end point was time to first inappropriate shock or under-sensed ventricular arrhythmia. Secondary outcomes included SMART Pass deactivation and need for device revision. Outcomes were reported as survival analyses. RESULTS: During preimplant screening, the QVS protocol reduced patient eligibility from 96% to 83%. The median follow-up after implant was 42 months (interquartile range, 48) in the traditional vector screening arm and 18 months (interquartile range, 15) in the QVS arm. The primary end point of time to first inappropriate shock or under-sensed ventricular arrhythmia was longer in the QVS arm (log-rank, P =0.02). There were 23 primary end point events among 145 patients in the traditional vector screening arm (5.2 per 100 patient-years [95% CI, 3.1–7.4]) and 2 primary end point events among 78 patients in the QVS arm (1.8 per 100 patient-years [95% CI, 0.01–4.38]). CONCLUSIONS: Implementation of a novel S-ICD screening protocol with stricter eligibility thresholds reduced sensing-related complications, particularly inappropriate shocks.

BACKGROUND: The intramural site of origin is a major cause of ablation failure of ventricular arrhythmias, and the optimal strategy is unclear. This study investigated the efficacy of a stepwise ablation approach for intramural outflow tract (OT) premature ventricular complexes (PVCs) guided by mapping of the septal coronary venous system. METHODS: Consecutive patients with OT PVCs were included, in whom an intramural origin was confirmed by demonstration of earliest activation in a septal coronary vein. Radiofrequency ablation was performed from the closest endocardial site in the left ventricular OT or right ventricular OT independent of the local activation time. If there was no suppression by endocardial ablation, then retrograde transvenous ethanol infusion with a single- or double-balloon technique was performed, targeting the earliest septal coronary vein. If venous anatomy was not suitable for ethanol ablation or if this failed, then bipolar ablation was performed. RESULTS: Sixty patients (age 61±12 years; 78% men) were included. The mean QRS duration of the PVC was 150.8±17.6 ms with a maximum deflection index of 0.51±0.11, and the most common ECG pattern was a left bundle branch block with inferior axis and V3 transition (63%), followed by a right bundle branch block with inferior axis and no transition (27%). Earliest ventricular activation (28.6±11.2 ms before QRS) was recorded in the left ventricular annular vein in 15 cases and a septal perforator vein in 45 cases. Acute PVC suppression at the end of the procedure was achieved in all cases. In 87% of cases (n=52), endocardial ablation from the endocardial left ventricular OT, right ventricular OT, or both was successful in eliminating the PVC. In the remaining 8 patients, the PVC was eliminated with ethanol infusion (n=7) and bipolar ablation (n=1). Complications included one case of pericardial effusion related to venous mapping. During follow-up (17±24 months), the PVC burden was reduced from 28±12% to 2.3±4.7%, and long-term success (≥80% burden reduction) was 88%. CONCLUSIONS: Most intramural OT PVCs can be successfully eliminated with endocardial ablation adjacent to the earliest intramural activation site. A high success rate is achieved when following a stepwise approach, with bailout ablation strategies required in a minority of cases.

Technological advances have made diagnosis of heart rhythm disturbances much easier, with a wide variety of options, including single-lead portable devices, smartphones/watches to sophisticated implantable cardiac monitors, allowing accurate data to be collected over different time periods depending on symptoms frequency. This review provides an overview of the novel and existing heart rhythm testing options, including a description of the supporting evidence for their use. A description of each of the tests is provided, along with discussion of their advantages and limitations. This is intended to help clinicians towards choosing the most appropriate test, thus improving diagnostic yield management of patients with suspected arrhythmias.