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Background: Heart transplantation is the most effective treatment for well-selected patients with endstage heart failure. Unfortunately, transplant candidates with pulmonary hypertension (PHT) are often not considered for heart transplantation. This study was performed to assess the value of prostaglandin E1 (PG-E1) for reduction of PHT and to predict the postoperative outcome, compared to patients without PHT. Patients and methods: We studied a group of 151 consecutive heart transplant candidates using right heart catheterization. In patients with PHT (pulmonary vascular resistance, PVR&ges;2.5 Wood-Units (WU) and/or transpulmonary gradient (TPG)&ges;12 mmHg) a short-term treatment protocol with PG-E1 was performed, to achieve PVR<2.5 WU and TPG<12 mmHg. Results: 61 patients (40%) had PHT according to our criteria. Reduction of PHT was successful in 71% of patients (n=43), of these, 18 patients underwent cardiac transplantation and the 1-year mortality rate was 22% (n=4). The 1-year mortality rate in transplanted patients without PHT was 14% (n=3). There was no statistical difference in survival between the PHT and the non-PHT group. Outcome in patients without heart transplantation was similar in both groups, except for patients with non-reducible PHT (1-year mortality 50%). Conclusions: Our study demonstrates the efficacy and safety of PG-E1 in lowering PHT in heart transplant candidates, as well as the need for aggressive evaluation and treatment in these patients. Patients with reversible PHT have comparable post-transplant outcomes and no tendency to higher acute right ventricular failure. [Copyright &y& Elsevier]

Reports on third-generation centrifugal intrapericardial pumps ( Heart Ware International, Inc., Framingham, MA, USA) have shown better survival results than the previous-generation devices. However, outcomes depending on the preoperative level of stability can substantially differ, resulting in a limited analysis of potentialities and drawbacks of a given device. In the present study we sought to compare in our single-center experience the survival results of this third-generation device with previous left ventricular systems taking into account the different preoperative Interagency Registry for Mechanically Assisted Circulatory Support ( INTERMACS) levels. Between February 1993 and March 2012, 287 patients underwent assist device implantation in our university hospital ( INTERMACS Level 1-2 = 158 patients; INTERMACS Level 3-4-5 = 129 patients). Assist devices implanted were: Group A ( HVAD HeartWare, n = 52), group B (previous continuous-flow ventricular assist device [ VAD], InCor [Berlin Heart, Berlin, Germany], n = 37; VentrAssist [VentraCor, Inc., Chatswood, NSW, Australia], n = 7; DeBakey [MicroMed Cardiovascular, Inc., Houston, TX, USA], n = 32), and group C (pulsatile systems, n = 159). After cumulative support duration of 54 436 days and a mean follow-up of 6.21 ± 7.46 months (range 0-45.21 months), log-rank analysis revealed a survival for group A of 82.0%, 70.4%, and 70.4%; for group B of 84.0%, 48.2%, 33.7%; and for group C of 71.6%, 46.1%, 33.8%, at 1, 12, and 24 months respectively, with a significantly ( P = 0.013) better outcome for group A. When stratifying the survival on the basis of INTERMACS level, no significant survival improvement was observed among all patients who underwent VAD implantation in INTERMACS 1-2 ( P = 0.47). However, among patients who underwent elective VAD implantation ( INTERMACS 3-4-5), group A had a significantly better outcome ( P = 0.005) compared with the other INTERMACS-matched groups (B,C) with a survival rate of 88.8% in group A versus 34.2% in group B and 45.6% in group C at 24 months, respectively. Elective HVAD system implantation shows improved survival benefit over the other INTERMACS-matched devices. Moreover, preoperative unstable hemodynamics resulted in a poor prognosis independently from the pump generation. [ABSTRACT FROM AUTHOR]

Aims Ranolazine (RAN) was reported to be effective and safe in converting atrial fibrillation (AF) to sinus rhythm by administration of a single dose (‘pill in the pocket’) to patients with structural heart disease. This study examines the underlying mechanisms for the antiarrhythmic benefit of RAN application in chronic heart failure (CHF). Methods and results In 10 female rabbits, CHF was induced by rapid ventricular pacing, leading to a significant decrease in ejection fraction in the presence of a dilated left ventricle and atrial enlargement. Twelve rabbits were sham-operated and served as controls. Isolated hearts were perfused using the Langendorff method. Burst pacing was used to induce AF. Monophasic action potential recordings showed an increase of atrial action potential duration (aAPD) and effective refractory period (aERP) in CHF hearts compared with sham hearts. Infusion of acetylcholine (1 µM) and isoproterenol (1 µM) led to AF in all failing hearts and in 11 sham hearts. Simultaneous infusion of RAN (10 µM) remarkably reduced inducibility of AF in 50% of sham and 50% of failing hearts. RAN had no effect on aAPD but significantly increased aERP, leading to a marked increase in atrial post-repolarization refractoriness. Moreover, RAN application moderately increased interatrial conduction time. Conclusion RAN has been shown to be effective in reducing the inducibility of AF in an experimental model of AF. The antiarrhythmic effect is mainly due to development of atrial post-repolarization refractoriness and a moderate increase in conduction time. The described electrophysiological mechanisms remain preserved in the setting of CHF. [ABSTRACT FROM PUBLISHER]

Aims Life-threatening arrhythmias are a major problem in chronic heart failure (CHF). The aim of the present study was to investigate the mechanism underlying the low proarrhythmic potential of amiodarone in a model of pacing-induced heart failure. Methods and results Heart failure was induced in 35 female rabbits by rapid ventricular pacing, resulting in a significant decrease of ejection fraction. Thirty-four rabbits were sham-operated. In 17 of 35 CHF-rabbits and 20 of 34 ‘sham’-rabbits, amiodarone (50 mg/kg/day) was fed for 6 weeks. Eight monophasic action potentials and a simultaneously recorded 12-lead electrocardiogram showed prolongation of QT-interval and action potential duration (APD90) in all failing hearts (P< 0.05). Amiodarone pre-treatment led to a prolongation of APD90 (+19 ms) as compared with sham-controlled hearts but showed only a marginal effect on APD90 in failing hearts. Infusion of sotalol (50–100 µM) led to a significant prolongation of APD90 in sham and a further prolongation of APD90 in failing hearts [+55 ms (50 µM); +70 ms (100 µM); P< 0.01 as compared with sham hearts]. Sotalol led to a triangular action potential configuration in sham and failing hearts, whereas amiodarone did not cause triangularization but caused a rapid phase-III repolarization. Moreover, amiodarone did not increase dispersion of repolarization either in sham or in failing hearts. Infusion of sotalol led to a significant increase in dispersion of repolarization in sham (+29 ms) and a further increase in failing hearts (+67 ms; P< 0.05). Conclusion Chronic amiodarone results in a rapid phase-III-repolarization and does not increase dispersion of repolarization. These electrophysiological findings are present in healthy hearts and are preserved in heart failure. This contributes to the low proarrhythmic potential of amiodarone in heart failure. [ABSTRACT FROM AUTHOR]

Background: Numerous noncardiovascular drugs prolong repolarization and thereby increase the risk for patients to develop life-threatening tachyarrhythmias of the torsade de pointes (TdP) type. The development of TdP is an individual, patient-specific response to a repolarization-prolonging drug, depending on the repolarization reserve. The aim of the present study was to analyze the underlying mechanisms that discriminate hearts that will develop TdP from hearts that will not develop TdP. We therefore investigated the group of quinolone antibiotics that reduce repolarization reserve via IKr blockade in an intact heart model of proarrhythmia. Methods and Results: In 47 Langendorff-perfused, AV-blocked rabbit hearts, ciprofloxacin (n = 10), ofloxacin (n = 14), levofloxacin (n = 10), and moxifloxacin (n = 13) in concentrations from 100 μM to 1,000 μM were infused. Eight monophasic action potentials (MAPs) and an ECG were recorded simultaneously. After incremental pacing at cycle lengths from 900 ms to 300 ms to compare the action potential duration, potassium concentration was lowered to provoke TdP. All antibiotics led to a significant increase in QT interval and MAP duration, and exhibited reverse-use dependence. Eight simultaneously recorded MAPs demonstrated an increase in dispersion of repolarization in the presence of all antibiotics. MAP triangulation (ratio: MAP90/50) and fluctuation of consecutive action potentials were increased for all tested drugs at high concentrations. In the presence of low potassium concentration, all quinolones led to TdP: ciprofloxacin, 4 out of 10 (40%); ofloxacin, 3 out of 14 (21%); moxifloxacin, 9 out of 13 (69%); and levofloxacin, 2 out of 10 (20%). Hearts that developed TdP demonstrated a significant greater influence on dispersion of repolarization and on triangulation as compared with hearts without TdP. Conclusion: Quinolone antibiotics may be proarrhythmic due to a significant effect on myocardial repolarization. The individual response of a heart to develop TdP in this experimental model is characterized by a greater effect on dispersion of repolarization and on triangulation of action potential as compared with hearts that do not develop TdP. [ABSTRACT FROM AUTHOR]

Assessment of replenishment kinetics (RK) following ultrasound-induced destruction of contrast microbubbles allows quantification of myocardial blood flow reserve (MBFR) applying the model , with parameter β describing mean flow velocity and parameter A representing blood volume. However, few data on the variability and reproducibility of RK in a clinical setting are available. Therefore, we examined 30 patients in a rest—adenosine protocol in one center. Off-line quantification of real-time perfusion imaging (RTPI) and triggered replenishment imaging (TRI) was performed at two sites and compared with coronary angiography and flow reserve measurements. Parameter A was found to be robust in all investigated segments (coefficient of variation (CV) < 7.2%± 5.1). Variability was lowest for parameter β using TRI in apical segments (CV 6.5%± 5.2, P < 0.01). Highest CV was found with RTPI in lateral segments (CV β: 39.8%± 40.6). Concerning day-to-day reproducibility both methods revealed similar results within range of heterogeneity of myocardial blood flow. Both sites obtained significantly lower MBFR in patients with flow-limiting CAD, compared to subjects without (P < 0.01). Correlation of both sites showed close relationship (y = 0.88x + 0.45, r = 0.83, P < 0.0001), without systematic bias. TRI significantly reduces variability of RK in quantitative MCE. Assessment of MBFR allows investigator-independent evaluation of CAD. [ABSTRACT FROM AUTHOR]

Color, power, spectral, and tissue Doppler have been applied to mice. Due to the noninvasive nature of the technique, serial intraindividual Doppler measurements of cardiovascular function are feasible in wild-type and genetically altered mice before and after microsurgical procedures or to follow age-related changes. Fifty-megahertz ultrasound biomicroscopy allows to record the first beats of the embryonic mouse heart at somite stage 5, and the first Doppler-flow signals can be recorded after the onset of intrauterine cardiovascular function at somite stage 7. Using 10- to 20-MHz ultrasound transducers in the mouse embryo, cardiac, and circulatory function can be studied as early as 7.5 days after postcoital mucous plug. Postnatal Doppler ultrasound examinations in mice are possible from birth to senescent age. Several strain-, age-, and gender-related differences of Doppler ultrasound findings have been reported in mice. Results of Doppler examinations are influenced by the experimental settings as stress testing or different forms of anesthesia. This review summarizes the present status of Doppler ultrasound examinations in mice and animal handling in the framework of a comprehensive phenotype characterization of cardiac contractile and circulatory function. [ABSTRACT FROM AUTHOR]

Phytanic Acid Causes Cardiac Conduction Block. Introduction: The sterol carrier protein-2 gene encodes two functionally distinct proteins: sterol carrier protein-2 (SCP2, a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx, a peroxisomal thiolase known as peroxisomal thiolase-2), which is involved in peroxisomal metabolism of bile acids and branched-chain fatty acids. We show in this study that mice deficient in SCP2 and SCPx (SCP2 null) develop a cardiac phenotype leading to a high sudden cardiac death rate if mice are maintained on diets enriched for phytol (a metabolic precursor of branched-chain fatty acids). Methods and Results: in 210 surface and 305 telemetric ECGs recorded in wild-type (C57BL/6; wt; n = 40) and SCP2 null mice (n = 40), no difference was observed at baseline. However, on diet, cycle lengths were prolonged in SCP2 null mice (262.9 ± 190 vs 146.3±43 msec), AV conduction was prolonged (58.3 ± 17 vs 42.6 ± 4 ms), and QRS complexes were wider (19.1 ± 5 vs 14.0 ± 4 ms). in 11 gene-targeted Langendorff-perfused hearts isolated from SCP2 null mice after dietary challenge, complete AV blocks (n = 5/11) or impaired AV conduction (Wenckebach point 132 ± 27 vs 92 ± 10 msec; P < 0.05) could be confirmed. Monophasic action potentials were not different between the two genotypes. Left ventricular function studied by echocardiography was similar in both strains. Phytanic acid but not pristanic acid accumulated in the phospholipid fraction of myocardial membranes isolated from SCP2 null mice. Conclusion: Accumulation of phytanic acid in myocardial phospholipid membranes is associated with bradycardia and impaired AV nodal and intraventricular impulse conduction, which could provide an explanation for sudden cardiac death in this model. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the value of epicardial mapping immediately before CABG in the differentiation of hibernating from scarred myocardium in correlation to the noninvasive gold standard (18)F-FDG PET.Methods and Results: In 35 patients with CAD, myocardial perfusion ((99m)Tc-Tetrofosmin-SPECT), viability ((18)F-FDG-PET), and function (LVangiography) were assessed before CABG. 102 bipolar epicardial electrograms per patient (n = 3570 electrograms) were recorded simultaneously with a ventricular jacket array. Based on the scintigraphic and LV angiographic data at the site of each electrode with good myocardial contact (n = 1963), segments (n = 492, 14.1 +/- 5.6 per patient; mean +/- SD) were classified into three groups: hibernating (n = 139), scarred (n = 104), and control (n = 249). Regional mean bipolar voltage values were calculated for Receiver Operating Characteristic (ROC) analysis. Mean bipolar voltage was significantly lower in scarred when compared to hibernating myocardium. ROC curve analysis (area under the curve of 0.92 +/- 0.47, mean +/- SE) for mean bipolar voltage to discriminate between hibernating and scarred myocardium revealed a sensitivity of 94% with a specificity of 83% at a cut-off value of 8.75 mV.Conclusion: Hibernating myocardium can be differentiated correctly from scarred myocardium by direct epicardial mapping. In the future, hibernating myocardium may be detectable by body surface mapping techniques using inverse solutions. [ABSTRACT FROM AUTHOR]

Presents the summary of a research on the lysosomal, cytoskeletal and metabolic alterations in cardiomyopathy of cathepsin L (CTSL) knockout mice. Findings on the morphology and functional impairment of CTSL-deficient hearts; Development of fibrosis and ultrastructural alterations in CTSL-deficient myocardium; Observations on the alterations of the acidic cellular compartment of CTSL-deficient myocardium and cell death, cell proliferation and its vascular structure.