BackgroundIncreased activity of single ventricular L-type Ca2+-channels (L-VDCC) is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary β-subunits as a possible explanation.Methods and ResultsBy molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC β-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac β-subunits: Unlike β1 or β3 isoforms, β2a and β2b induce a high-activity channel behavior typical of failing myocytes. In accordance, β2-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac CaV1.2 also reveal increased single-channel activity and sarcolemmal β2 expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing (“Adaptive Phase”), reveal the opposite phenotype, viz : reduced single-channel activity accompanied by lowered β2 expression. Additional evidence for the cause-effect relationship between β2-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive CaV1.2 and inducible β2 cardiac overexpression. Here in non-failing hearts induction of β2-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure.ConclusionsOur study presents evidence of the pathobiochemical relevance of β2-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. The ReninAngiotensin-Aldosterone-System plays a major role for the atrial structural and electrical remodelling. Recently elevated aldosterone levels have been suggested to increase the risk for the development of AF. Methods: Rats were treated with aldosterone by means of an osmotic minipump (0.5µg/h) over a period of 4 weeks. AF was induced by transesophageal burst pacing. Action potentials (AP) were recorded from left atrial preparations with microelectrodes. Atrial collagen was quantified by histological studies. Results: Aldosterone treatment resulted in hypertrophy as indicated by an increased ratio of heart weight/tibia length and doubled the time until the AF converted spontaneously into sinus rhythm (85.8±13.4 s vs.38.3±6.9 s, p<0.01). This was associated with a significant shortening of the AP (APD90 26.2±1.1 vs. 31.2±1.9, p<0.05) and an increased protein expression of Kir2.1 and Kv1.5. Atrial collagen deposition was significantly greater in aldosterone-treated rats. The alterations could be prevented by additional application spironolactone. Conclusions: The results of the present study suggest that in addition to the structural remodelling aldosterone also promotes AF by altering repolarising potassium currents leading to action potential shortening.

Objectives Coronary sinus (CS) based mitral annuloplasty using the Carillon device is effective in reducing functional mitral valve regurgitation (FMR). However, this positive effect might be dependent on the relation between CS and the mitral annulus. Background Computed tomography (CT) assessment prior to mitral valve interventions is an emerging technique to optimize patient selection. Methods In a retrospective analysis 30 patients underwent Carillon device implantation and received CT‐angiography prior to CS based percutaneous mitral valve repair. Patients were assigned to responders or non‐responders according to the 3‐month transthoracic echocardiographic follow‐up including quantitative mitral valve regurgitation assessment. A prototype software for CS reconstruction was used to assess distance and angle of both CS and mitral annulus planes. Results Comparison of the distance and angle of the CS plane and the mitral valve annulus plane showed a significant shorter distance and lower angle in the responder group implicating an impact on procedure success. Our results suggest a CS plane and MV annulus plane with a favorably distance of <7.8 mm and an optimal angle of <14.2° could be considered favorably for mitral annuloplasty using a Carillon device. Conclusions Distance and angle of mitral annulus and CS planes determined by three‐dimensional reconstructions of CT‐angiography might predict a reduction in echocardiographic FMR using Carillon Mitral Contour System.

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Objectives: We aimed to compare indirect mitral annuloplasty using the Carillon Mitral Contour System and edge-to-edge repair via MitraClip in atrial functional mitral regurgitation (aFMR). Background: In patients with left ventricular dilation, both edge-to-edge repair and indirect mitral annuloplasty are effective in reducing mitral regurgitation, while no clinical trial has compared both interventional methods in aFMR. Methods: In a retrospective single-center analysis, 41 patients with aFMR underwent either edge-to-edge mitral valve repair (MitraClip group, n = 20) or indirect annuloplasty (Carillon group, n = 21). Results: Both treatment groups showed high procedural success (100%) and low complication rates. Both treatment groups showed a comparable reduction of New York Heart Association (NYHA) classification postimplantation, after 3-and 12months follow-up. Quantitative reduction in echocardiographic FMR parameters was significantly pronounced in the MitraClip group (reduction in vena contracta