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Aims Cardiac involvement in Fabry disease (FD) occurs prior to left ventricular hypertrophy (LVH) and is characterized by low myocardial native T1 with sphingolipid storage reflected by cardiovascular magnetic resonance (CMR) and electrocardiogram (ECG) changes. We hypothesize that a pre-storage myocardial phenotype might occur even earlier, prior to T1 lowering. Methods and results FD patients and age-, sex-, and heart rate-matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR [cines, global longitudinal strain (GLS), T1 and T2 mapping, stress perfusion (myocardial blood flow, MBF), and late gadolinium enhancement (LGE)]. One hundred and fourteen Fabry patients (46 ± 13 years, 61% female) and 76 controls (49 ± 15 years, 50% female) were included. In pre-LVH FD (n = 72, 63%), a low T1 (n = 32/72, 44%) was associated with a constellation of ECG and functional abnormalities compared to normal T1 FD patients and controls. However, pre-LVH FD with normal T1 (n = 40/72, 56%) also had abnormalities compared to controls: reduced GLS (−18 ± 2 vs. −20 ± 2%, P < 0.001), microvascular changes (lower MBF 2.5 ± 0.7 vs. 3.0 ± 0.8 mL/g/min, P = 0.028), subtle T2 elevation (50 ± 4 vs. 48 ± 2 ms, P = 0.027), and limited LGE (%LGE 0.3 ± 1.1 vs. 0%, P = 0.004). ECG abnormalities included shorter P-wave duration (88 ± 12 vs. 94 ± 15 ms, P = 0.010) and T-wave peak time (Tonset – Tpeak; 104 ± 28 vs. 115 ± 20 ms, P = 0.015), resulting in a more symmetric T wave with lower T-wave time ratio (Tonset – Tpeak)/(Tpeak – Tend) (1.5 ± 0.4 vs. 1.8 ± 0.4, P < 0.001) compared to controls. Conclusion FD has a measurable myocardial phenotype pre-LVH and pre-detectable myocyte storage with microvascular dysfunction, subtly impaired GLS and altered atrial depolarization and ventricular repolarization intervals.

Alterations of normal intra- and interatrial conduction are a common outcome of multiple cardiovascular conditions. They arise most commonly in the context of advanced age, cardiovascular risk factors, organic heart disease, atrial fibrosis, and left atrial enlargement. Interatrial block (IAB), the most frequent and extensively studied atrial conduction disorder, affects up to 20% of the general primary care population. IAB can be partial (P wave duration ≥ 120 ms on any of the 12 ECG leads) or advanced (P wave ≥ 120 ms and biphasic morphology (positive-negative) in inferior leads). Advanced IAB is an independent risk factor for supraventricular tachyarrhythmias and embolic stroke in a variety of clinical settings. Advanced IAB is a cause of left atrial electromechanical dysfunction and left atrioventricular dyssynchrony and has been associated with left ventricular diastolic dysfunction. P wave duration is associated with cardiovascular and all-cause mortality in the general population. Atrial conduction abnormalities should be identified as markers of atrial remodeling, prognostic indicators, and, in the case of advanced IAB, a true arrhythmologic syndrome. IAB and other P wave abnormalities should prompt the search for associated conditions, the treatment of which may partially reverse atrial remodeling or prevent it if administered upstream. Future studies will help define the role of preventive therapeutic interventions in high-risk patients, including antiarrhythmic drug therapy and oral anticoagulation. Implications for the treatment of heart failure and for pacing should also be further investigated.

Pulmonary vein isolation (PVI) is the cornerstone of AF ablation, but studies have reported improved efficacy with high rates of repeat procedures. Because of the large interindividual variability in the underlying electrical and anatomical substrate, achieving optimal outcomes requires an individualised approach. This includes optimal candidate selection as well as defined ablation strategies with objective procedure endpoints beyond PVI. Candidate selection is traditionally based on coarse and sometimes arbitrary clinical stratification such as AF type, but finer predictors of treatment efficacy including biomarkers, advanced imaging and electrocardiographic parameters have shown promise. Numerous ancillary ablation strategies beyond PVI have been investigated, but the absence of a clear mechanistic and evidence-based endpoint, unlike in other arrhythmias, has remained a universal limitation. Potential endpoints include functional ones such as AF termination or non-inducibility and substrate-based endpoints such as isolation of low-voltage areas. This review summarises the relevant literature and proposes guidance for clinical practice and future research.