Implantable cardioverter defibrillators (ICD) are used as standard therapy to prevent sudden cardiac death in heart failure patients. Today, physicians in emergency and intensive care medicine are often confronted with problems of ICD therapy in these patients. We report a case of a patient suffering from recurrent ventricular tachycardia (VT) requiring antiarrhythmia treatment with amiodarone. With an increasing drug loading, the VT cycle length was progressively prolonged resulting in a slow VT undetectable for the ICD. Subsequently, the patient was scheduled for VT ablation after which the patient became free of arrhythmia recurrences.

Die Implantation eines ICD (implantierbarer Cardioverter-Defibrillator) gehört zur Standardtherapie der Prävention des plötzlichen Herztodes herzinsuffizienter Patienten. Notfallmediziner werden zunehmend mit rhythmologischen Ereignissen dieser Patienten konfrontiert. Wir beschreiben in dieser Kasuistik den Verlauf eines Patienten mit einer ventrikulären Tachykardie (VT), die durch das ICD-System nicht korrekt erkannt wurde. Im weiteren Verlauf traten VTs auf, deren Zykluslänge sich unter Amiodarontherapie repetitiv progressiv verlängerte und vom ICD-System nicht detektiert werden konnten. Mittels einer Ablationstherapie konnte die Tachykardie anhaltend beseitigt werden.

Ein überlebter akuter Verschluss des Hauptstammes der linken Koronararterie ist eine Rarität. Die meisten Patienten versterben plötzlich, da es dabei zu einem massiven Myokardinfarkt mit kardiogenem Schock und Arrhythmie kommt. Schnelles Erkennen von Symptomen und umgehende Diagnosestellung eines Myokardinfarktes, rasche perkutane Koronarintervention, Schocktherapie mit intraaortaler Ballongegenpulsationspumpe und notfallmäßige Bypassoperation ermöglichten in dem geschilderten Fall des akuten kompletten Hauptstammverschlusses das Überleben des Patienten.

Background— In patients with chronic heart failure (CHF) and conduction delay, biventricular (BiV) and left ventricular (LV) pacing similarly improve systolic function at resting heart rates. We hypothesized that BiV and univentricular pacing differentially affect contractile function at increasing heart rates. Methods and Results— Twenty-two patients (aged 66±2 years, QRS 179±8 ms, LV ejection fraction 23±1%) underwent cardiac catheterization before device implantation to measure LV hemodynamics at baseline (rate 68±2 bpm; sinus rhythm n=18; atrial fibrillation n=4) and during BiV, LV, and right ventricular (RV) stimulation at 80, 100, 120, and 140 bpm. BiV and LV pacing at 80 bpm equally augmented dP/dtmax as compared with baseline and RV pacing (P<0.001). Stimulation rate significantly interacted with the effect of BiV, LV, and RV pacing on LV end-diastolic pressure (LVEDP), systolic pressure (LVSP), and dP/dtmax. Increasing the rate from 80 to 140 bpm enhanced dP/dtmax from 913±28 to 1119±50 mm Hg/s during BiV stimulation (P<0.001) but had no significant effect on contractility during single-site LV (951±47 versus 1002±54 mm Hg/s) or RV (800±46 versus 881±49 mm Hg/s) pacing. At 140 bpm, LVEDP was lower and LVSP higher during BiV pacing than during RV and LV pacing (LVEDP 12±1 versus 17±1 and 16±1 mm Hg, P<0.001; LVSP 112±5 versus 106±5 and 108±6 mm Hg, P<0.01 and P=0.09; BiV versus RV and LV pacing, respectively). Conclusions— Different modes of ventricular stimulation alter the in vivo force–frequency relation of CHF patients. In contrast to single-site LV and RV pacing, contractile function improves with increasing heart rates during BiV stimulation. This effect may contribute to the enhanced exercise capacity during BiV pacing and could provide a functional benefit over LV-only pacing in patients for whom resynchronization therapy is indicated.

Background —Increasing sarcoplasmic/endoplasmic reticulum (SR) Ca 2 (cid:1) -ATPase (SERCA) uptake activity is a promising therapeutic approach for heart failure. We investigated the effects of different levels of SERCA1a expression on contractility and Ca 2 (cid:1) cycling. We tested whether increased SERCA1a expression levels enhance myocyte contractility in a gene-dose–dependent manner. Methods and Results —Rabbit isolated cardiomyocytes were transfected at different multiplicities of infection (MOIs) with adenoviruses encoding SERCA1a (or (cid:1) -galactosidase as control). Myocyte relaxation half-time was decreased by 10% ( P (cid:2) 0.052) at SERCA1a MOI 10 and by 28% at MOI 50 ( P (cid:3) 0.05). Myocyte fractional shortening was increased by 12% at MOI 10 ( P (cid:3) 0.05) but surprisingly decreased at MOI 50 ( (cid:4) 22%, P (cid:3) 0.05) versus control. SR Ca 2 (cid:1) uptake (in permeabilized myocytes) demonstrated a gene-dose–dependent decrease in K m by 29% and 46% and an increase in V max by 37% and 72% at MOI 10 and MOI 50, respectively (all P (cid:3) 0.05 versus control). Ca 2 (cid:1) transient amplitude was increased in Ad-SERCA1a–infected myocytes at MOI 10 (by 121%, P (cid:3) 0.05), but at MOI 50, the Ca 2 (cid:1) transient amplitude was not significantly changed. Caffeine-induced Ca 2 (cid:1) transients indicated significantly increased SR Ca 2 (cid:1) content in Ad-SERCA1a–infected cells, by 72% at MOI 10 and by 87% at MOI 50. Mathematical simulations demonstrate that the functional increase in SR Ca 2 (cid:1) -ATPase uptake activity at MOI 50 (and increased cytosolic Ca 2 (cid:1) buffering) is sufficient to curtail the Ca 2 (cid:1) transient amplitude and explain the reduced contraction. Conclusions —Moderate SERCA1a gene transfer and expression improve contractility and Ca 2 (cid:1) cycling. However, higher SERCA1a expression levels can impair myocyte shortening because of higher SERCA activity and Ca 2 (cid:1) buffering. Circulation 2004;110:3553-3559.) Data are presented as mean (cid:7) SEM based on the number of animals (ie, number of transfections) to allow the comparison of the Ca 2 (cid:1) uptake characteristics from cell aggregates. The number of cells was used to compare contractility and [Ca 2 (cid:1) ] i measurements; the number of animals (ie, transfections) is also reported. Statistical analysis used paired Student t test or Wilcoxon signed-rank test as appropriate. A value of P (cid:3) 0.05 was considered significant. Details of all aspects of the techniques used in this study are given in the online-only Data Supplement.

Treatment with monocrotaline causes pulmonary hypertension in rats. This results in severe pressure overload-induced hypertrophy of the right ventricles, whilst the normally loaded left ventricles do not hypertrophy. Both ventricles are affected by enhanced neuroendocrine stimulation in this model. We analyzed in this model load-induced and catecholamine-induced changes of right and left ventricular proteome by two-dimensional gel electrophoresis, tryptic in-gel digest, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry All analyzed animals showed right ventricular hypertrophy without signs of heart failure. Changes of 27 proteins in the right and 21 proteins in the left ventricular myocardium were found. Given the hemodynamic features of this animal model, proteome changes restricted to the right ventricle are caused by pressure overload. We describe for the first time a potentially novel pathway (BRAP2/BRCA1) that is involved in myocardial hypertrophy. Furthermore, we demonstrate that increased afterload-induced hypertrophy leads to striking changes in the energy metabolism with down-regulation of pyruvate dehydrogenase (subunit beta El), isocitrate dehydrogenase, succinyl coenzyme A ligase, NADH dehydrogenase, ubiquinol-cytochrome C reductase, and propionyl coenzyme A carboxylase. These changes go in parallel with alterations of the thin filament proteome (troponin T, tropomyosin), probably associated with Ca2+ sensitization of the myofilaments. In contrast, neurohumoral stimulation of the left ventricle increases the abundance of proteins relevant for energy metabolism. This study represents the first in-depth analysis of global proteome alterations in a controlled animal model of pressure overload-induced myocardial hypertrophy.

Background - Increasing sarcoplasmic/endoplasmic reticulum (SR) Ca2+-ATPase (SERCA) uptake activity is a promising therapeutic approach for heart failure. We investigated the effects of different levels of SERCA1a expression on contractility and Ca2+ cycling. We tested whether increased SERCA1a expression levels enhance myocyte contractility in a gene-dose - dependent manner.Methods and Results - Rabbit isolated cardiomyocytes were transfected at different multiplicities of infection (MOIs) with adenoviruses encoding SERCA1a (or beta-galactosidase as control). Myocyte relaxation half-time was decreased by 10% (P = 0.052) at SERCA1a MOI 10 and by 28% at MOI 50 (P < 0.05). Myocyte fractional shortening was increased by 12% at MOI 10 (P < 0.05) but surprisingly decreased at MOI 50 (-22%, P < 0.05) versus control. SR Ca2+ uptake (in permeabilized myocytes) demonstrated a gene-dose - dependent decrease in Km by 29% and 46% and an increase in V-max by 37% and 72% at MOI 10 and MOI 50, respectively (all P < 0.05 versus control). Ca2+ transient amplitude was increased in Ad-SERCA1a- infected myocytes at MOI 10 (by 121%, P < 0.05), but at MOI 50, the Ca2+ transient amplitude was not significantly changed. Caffeine-induced Ca2+ transients indicated significantly increased SR Ca2+ content in Ad-SERCA1a- infected cells, by 72% at MOI 10 and by 87% at MOI 50. Mathematical simulations demonstrate that the functional increase in SR Ca2+-ATPase uptake activity at MOI 50 (and increased cytosolic Ca2+ buffering) is sufficient to curtail the Ca2+ transient amplitude and explain the reduced contraction.Conclusions - Moderate SERCA1a gene transfer and expression improve contractility and Ca2+ cycling. However, higher SERCA1a expression levels can impair myocyte shortening because of higher SERCA activity and Ca2+ buffering.

AIM: To evaluate the potential of laparoscopy in the diagnosis of cirrhosis and outcome of interferon treatment in HCV-infected patients.METHODS: In this retrospective study, diagnostic laparoscopy with laparoscopic liver biopsy was performed in 72 consecutive patients with chronic HCV infection. The presence or absence of cirrhosis was analyzed macroscopically by laparoscopy and microscopically by liver biopsy specimens. Clinical and laboratory data and outcome of interferon-alfa treatment were compared between cirrhotic and noncirrhotic patients.RESULTS: Laparoscopically, cirrhosis was seen in 29.2% (21/72) and non-cirrhosis in 70.8% (51/72) of patients. Cirrhotic patients were significantly older with a significant longer duration of HCV infection than noncirrhotic patients. Laboratory parameters (AST, y-GT, y-globulin fraction) were measured significantly higher as well as significantly lower (prothrombin index, platelet count) in cirrhotic patients than in non-cirrhotic patients. Histologically, cirrhosis was confirmed in 11.1% (8/72) and non cirrhosis in 88.9% (64/72). Patients with macroscopically confirmed cirrhosis (n = 21) showed histologically cirrhosis in 38.1% (8/21) and histologically non-cirrhosis in 61.9% (13/21). In contrast, patients with macroscopically non-cirrhosis (n = 51) showed histologically non cirrhosis in all cases (51/51). Thirty-nine of 72 patients were treated with interferon-alfa, resulting in 35.9% (14/39) patients with sustained response and 64.1% (25/39) with non response. Non-responders showed significantly more macroscopically cirrhosis than sustained responders. In contrast, there were no significant histological differences between non-responders and sustained responders.CONCLUSION: Diagnostic laparoscopy is more accurate than liver biopsy in recognizing cirrhosis in patients with chronic HCV infection. Liver biopsy is the best way to assess inflammatory grade and fibrotic stage. The invasive marker for staging, prognosis and management, and treatment outcome of chronic HCV-infected patients need further research and clinical trials. Laparoscopy should be performed for recognition of cirrhosis if this parameter is found to be of prognostic and therapeutic relevance in patients with chronic HCV infection.

Rats treated with monocrotaline (MCT) develop pulmonary hypertension. Their right ventricles (RVs) exhibit severe pressure overload - induced hypertrophy, whereas the left ventricles (LVs) are normally loaded. In contrast, enhanced neuroendocrine stimulation during the transition to heart failure affects both ventricles. We assessed gene expression levels of Ca2+-regulating proteins in RVs and LVs of control and MCT rats in transition to heart failure to identify biomechanical load - regulated genes. In MCT RVs, both mRNA and protein levels of the Ca2+-ATPase of the sarcoplasmic/endoplasmic reticulum (SERCA2a) were reduced by 36% ( P = 0.001) and 17% ( P = 0.016), respectively, compared with control RVs. Phospholamban and ryanodine receptor mRNA levels likewise were reduced ( by 27% [ P = 0.05] and 21% [ P = 0.011], respectively) in MCT RVs, whereas sarcolemmal Na+-Ca2+ exchanger expression was not altered. MCT LVs exhibited no significant expression changes compared with control LVs. Isometrically contracting MCT intact RV trabeculae showed enhanced baseline force development. Although control RV preparations exhibited a positive force-frequency relationship, MCT RVs showed a negative force-frequency relationship and blunted postrest potentiation. Contractile function of MCT LV trabeculae was normal. Maximum Ca2+-activated tension was enhanced by 64% in permeabilized RV MCT preparations ( P = 0.013). beta-Myosin heavy chain protein was upregulated in MCT RVs ( P < 0.001) but unaltered in MCT LVs. Degradation of troponin T was prominent in MCT RVs, a phenomenon not observed in the LV. Enhanced biomechanical load is necessary to induce the gene expression changes associated with the hypertrophic phenotype of the pressure-overloaded RV. Neuroendocrine factors, which equally affect both chambers, are not sufficient to alter the expression of Ca2+-cycling proteins.