Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and has a strong association with heart failure (HF). It often remains unclear if HF is the cause or consequence of AF due to the complexity of the processes that are involved in both the perpetuation of AF and the development of HF. To date, two therapeutic strategies are accepted as the standard of care in AF patients with heart failure. Rhythm control aims to permanently restore sinus rhythm, whereas a rate-control strategy aims to slow ventricular rate without the termination of AF. In the last 5 years a tremendous number of important studies have been published investigating the optimal therapeutic strategy in HF patients. This review highlights the important studies with respect to the involvement of AF in promoting left-ventricular dysfunction and discusses the optimal strategy in HF patients suffering from AF.

An interplay between Ca²⁺/calmodulin-dependent protein kinase IIδc (CaMKIIδc) and late Na⁺ current (I_NaL) is known to induce arrhythmias in the failing heart. Here, we elucidate the role of the sodium channel isoform Na_V1.8 for CaMKIIδc-dependent proarrhythmia. In a CRISPR-Cas9-generated human iPSC-cardiomyocyte homozygous knock-out of Na_V1.8, we demonstrate that Na_V1.8 contributes to I_NaL formation. In addition, we reveal a direct interaction between Na_V1.8 and CaMKIIδc in cardiomyocytes isolated from patients with heart failure (HF). Using specific blockers of Na_V1.8 and CaMKIIδc, we show that Na_V1.8-driven I_NaL is CaMKIIδc-dependent and that Na_V1.8-inhibtion reduces diastolic SR-Ca²⁺ leak in human failing cardiomyocytes. Moreover, increased mortality of CaMKIIδc-overexpressing HF mice is reduced when a Na_V1.8 knock-out is introduced. Cellular and in vivo experiments reveal reduced ventricular arrhythmias without changes in HF progression. Our work therefore identifies a proarrhythmic CaMKIIδc downstream target which may constitute a prognostic and antiarrhythmic strategy.

Severe aortic stenosis (AS) is a common pathological condition in an ageing population imposing significant morbidity and mortality. Based on distinct hemodynamic features, i.e., ejection fraction (EF), transvalvular gradient and stroke volume, four different AS subtypes can be distinguished: (i) normal EF and high gradient, (ii) reduced EF and high gradient, (iii) reduced EF and low gradient, and (iv) normal EF and low gradient. These subtypes differ with respect to pathophysiological mechanisms, cardiac remodeling, and prognosis. However, little is known about metabolic changes in these different hemodynamic conditions of AS. Thus, we carried out metabolomic analyses in serum samples of 40 AS patients (n = 10 per subtype) and 10 healthy blood donors (controls) using ultrahigh-performance liquid chromatography–tandem mass spectroscopy. A total of 1293 biochemicals could be identified. Principal component analysis revealed different metabolic profiles in all of the subgroups of AS (All-AS) vs. controls. Out of the determined biochemicals, 48% (n = 620) were altered in All-AS vs. controls (p < 0.05). In this regard, levels of various acylcarnitines (e.g., myristoylcarnitine, fold-change 1.85, p < 0.05), ketone bodies (e.g., 3-hydroxybutyrate, fold-change 11.14, p < 0.05) as well as sugar metabolites (e.g., glucose, fold-change 1.22, p < 0.05) were predominantly increased, whereas amino acids (e.g., leucine, fold-change 0.8, p < 0.05) were mainly reduced in All-AS. Interestingly, these changes appeared to be consistent amongst all AS subtypes. Distinct differences between AS subtypes were found for metabolites belonging to hemoglobin metabolism, diacylglycerols, and dihydrosphingomyelins. These findings indicate that relevant changes in substrate utilization appear to be consistent for different hemodynamic subtypes of AS and may therefore reflect common mechanisms during AS-induced heart failure. Additionally, distinct metabolites could be identified to significantly differ between certain AS subtypes. Future studies need to define their pathophysiological implications.

Automatic electrocardiogram (ECG) analysis has been one of the very early use cases for computer assisted diagnosis (CAD). Most ECG devices provide some level of automatic ECG analysis. In the recent years, Deep Learning (DL) is increasingly used for this task, with the first models that claim to perform better than human physicians. In this manuscript, a pilot study is conducted to evaluate the added value of such a DL model to existing built-in analysis with respect to clinical relevance. 29 12-lead ECGs have been analyzed with a published DL model and results are compared to build-in analysis and clinical diagnosis. We could not reproduce the results of the test data exactly, presumably due to a different runtime environment. However, the errors were in the order of rounding errors and did not affect the final classification. The excellent performance in detection of left bundle branch block and atrial fibrillation that was reported in the publication could be reproduced. The DL method and the built-in method performed similarly good for the chosen cases regarding clinical relevance. While benefit of the DL method for research can be attested and usage in training can be envisioned, evaluation of added value in clinical practice would require a more comprehensive study with further and more complex cases.

During cryoballon pulmonary vein isolation (PVI) complete occlusion of the pulmonary vein ostia during the freeze cycles is mandatory. Typically, PV occlusion is assessed by contrast injection under fluoroscopy. Using an update for the Cryo Console it is possible to directly visualize occlusion pressure as an indicator of complete PV occlusion during cryoballoon procedures. In this study, we compared PV pressure monitoring during cryoballoon PVI to a conventional approach regarding procedural outcomes. We retrospectively analysed the procedural data of 50 patients (25 patients with pressure-guided PVI and 25 patients with contrast-guided PVI) treated with cryoballoon PVI in our centre. Complete PV occlusion in the pressure-guided group was defined as an abrupt change in the pressure waveform with a loss of the a-wave after advancing the cryoballoon to the PV ostium. We observed comparable results regarding procedural time, left atrial dwell time or fluoroscopy time when comparing the pressure guided to our conventional approach. Moreover, there were no differences regarding acute procedural effectivity or freeze cycle characteristics. As expected, a significant reduction of contrast use was achieved in the pressure measurement group (10.4 vs. 25.5 ml, p < 0.0001). Monitoring complete PV occlusion by visualizing the occlusion pressure is feasible. Acute procedural outcome was comparable to our standard approach using contrast injection to verify complete PV occlusion. Most importantly, a significant reduction in contrast use could be achieved which has to be confirmed in larger patient cohorts.

We report the findings of a 57-year-old patient who was referred to our hospital with recurrent episodes of symptomatic persistent atrial fibrillation (AF). An electrocardiogram-triggered contrast-enhanced cardiac computer tomography (SOMATOM^® Definition Flash, Siemens) was performed before the procedure to integrate left atrial anatomy into the electroanatomic mapping system (CARTO^®3 Merge, Biosense Webster, USA). The computed tomography (CT) revealed a highly unusual, previously unreported pulmonary vein (PV) variant consisting of a large left common PV (LCPV) joining a large right common PV trunk which separates into a right superior pulmonary vein (RSPV) and right inferior pulmonary vein (RIPV), as well as an accessory right PV (Figure 1 and Supplementary material ).