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Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disorder characterized by ventricular arrhythmias induced by physical or emotional stress. Currently, there are limited data available on the long term prognosis of CPVT. Methods and Results: In this study, which included both retrospective and prospective components, 12 patients with CPVT (7 males and 5 females) under 18 years old were enrolled to gather and evaluate demographic, clinical, and genetic data. The mean age at diagnosis onset was 7.0 ± 3.1 years. All patients experienced syncope. The mean follow up duration was 20.1 years. During the follow-up period, all patients experienced at least one episode of supraventricular tachycardia (SVT). Despite beta-blocker therapy, nine patients experienced syncope (75%), and four patients were noncompliant with their treatment. An implantable cardiac defibrillator (ICD) implantation was performed in 10 patients (83%), and among those 5 (50%) experienced appropriate shocks. Inappropriate shocks were observed in all patients with an ICD. The left cardiac sympathetic denervation was performed in 6 patients (50%). One patient died during the follow-up period. Genetic testing was performed in eight patients, five of whom had RYR2 mutations, one patient had mutations in CASQ2, one in TECRL, and one was gene-elusive. Conclusions: The prevalence of cardiac events, even after the initiation of beta-blocker therapy, was found to be distressingly high during long-term follow-up. SVT, such as atrial fibrillation, were found to be more common than previously thought. Combination therapy with a beta-blocker and an IC antiarrhythmic drug shows promise. An individualized approach to the selection of treatment strategies is essential. [ABSTRACT FROM AUTHOR]

Background: Beta-blocker (BB) therapy plays a central role in the treatment of cardiovascular diseases. An increasing number of patients with cardiovascular diseases undergoe noncardiac surgery, where opioids are an integral part of the anesthesiological management. There is evidence to suggest that short-term intravenous BB therapy may influence perioperative opioid requirements due to an assumed cross-talk between G-protein coupled beta-adrenergic and opioid receptors. Whether chronic BB therapy could also have an influence on perioperative opioid requirements is unclear. Methods: A post hoc analysis of prospectively collected data from a multicenter observational (BioCog) study was performed. Inclusion criteria consisted of elderly patients (≥ 65 years) undergoing elective noncardiac surgery as well as total intravenous general anesthesia without the use of regional anesthesia and duration of anesthesia ≥ 60 min. Two groups were defined: patients with and without BB in their regular preopreative medication. The administered opioids were converted to their respective morphine equivalent doses. Multiple regression analysis was performed using the morphine-index to identify independent predictors. Results: A total of 747 patients were included in the BioCog study in the study center Berlin. 106 patients fulfilled the inclusion criteria. Of these, 37 were on chronic BB. The latter were preoperatively significantly more likely to have arterial hypertension (94.6%), chronic renal failure (27%) and hyperlipoproteinemia (51.4%) compared to patients without BB. Both groups did not differ in terms of cumulative perioperative morphine equivalent dose (230.9 (BB group) vs. 214.8 mg (Non-BB group)). Predictive factors for increased morphine-index were older age, male sex, longer duration of anesthesia and surgery of the trunk. In a model with logarithmised morphine index, only gender (female) and duration of anesthesia remained predictive factors. Conclusions: Chronic BB therapy was not associated with a reduced perioperative opioid consumption. Trial registration: This study was registered at ClinicalTrials.gov (NCT02265263) on the 15.10.2014 with the principal investigator being Univ.-Prof. Dr. med. Claudia Spies. [ABSTRACT FROM AUTHOR]

Purpose: In addition to prolonged life and reduced hospitalization rates, it is currently unclear whether beta-blocker (BB) treatment modulates peak oxygen consumption (...O 2peak), a hallmark of exercise capacity, in patients with heart failure (HF). The main aim of this study is to determine the effect of BB treatment on (...O 2peak in HF patients. Methods: We conducted a systematic search of MEDLINE, Scopus, and Web of Science since their inceptions until March 2017 for randomized controlled trials (RCT) assessing the effect of BB treatment on (...O 2peak in chronic HF patients. A meta-analysis was performed to ascertain the standardized mean difference (SMD) between the effects of BB and placebo treatment on (...O 2peak. Secondary outcomes included peak exercise performance and New York Health Association functional class. Subgroup and meta-regression analyses assessed potential moderating factors. Results: Fourteen RCT met the inclusion criteria (overall n = 616). Interventions comprised BB (n = 324) or placebo (n = 292) administration lasting 3 to 24 months. Concomitant reported medication did not differ between HF patients assigned to BB and placebo groups. After data pooling, (...O 2peak was preserved with BB compared with placebo treatment (SMD, -0.04; 95% confidence interval (CI), -0.20 to 0.12; P = 0.61); heterogeneity among studies was not detected (I² = 0%, P = 0.88). Peak exercise performance was not altered (SMD, 0.02; 95% CI, -0.16 to 0.20; P = 0.85), whereas New York Health Association functional class was reduced with BB compared with placebo (SMD, -0.54; 95% CI, -0.90 to -0.18; P = 0.003). Conclusions: According to evidence from RCT, prolonged BB (B1-selective or nonselective) treatment does not affect (...O 2peak but improves functional status in HF patients. [ABSTRACT FROM AUTHOR]

Background A puzzling feature of the long QT syndrome (LQTS) is that family members carrying the same mutation often have divergent symptoms and clinical outcomes. Objectives This study tested the hypothesis that vagal and sympathetic control, as assessed by spectral analysis of spontaneous beat-to-beat variability of RR and QT intervals from standard 24-h electrocardiogram Holter recordings, could modulate the severity of LQTS type 1 (LQT1) in 46 members of a South-African LQT1 founder population carrying the clinically severe KCNQ1 A341V mutation. Methods Nonmutation carriers (NMCs) (n = 14) were compared with mutation carriers (MCs) (n = 32), 22 with and 10 without major symptoms. We assessed the effect of circadian rhythm and beta-blocker therapy over traditional time and frequency domain RR and QT variability indexes. Results The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest. Conclusions The present data identified an additional factor contributing to the differential arrhythmic risk among patients with LQT1 carrying the same mutation. A healthy autonomic control confers a high risk, whereas patients with higher sympathetic control of the QT interval and reduced vagal control of heart rate are at lower risk. This differential “autonomic make-up,” likely under genetic control, will allow refinement of risk stratification within families with LQTS, leading to more targeted management. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of this study was to investigate the effects of chronic treatment with carvedilol in blood pressure (BPV) and heart rate (HRV) variability of rats with myocardial infarction (MI). Methods: MI was produced in male rats by ligature of anterior interventricular branch of left coronary artery. Control rats were submitted to a sham surgery (SO). MI and SO rats were randomized to receive for 30days placebo (Plac 0.5% metilcelulose) or carvedilol (Carv, 2mg/Kg body weight/day, drinking water): SO-Plac (N =10), SO-Carv (N =10), MI-Plac (N =12), MI-Carv (N =13). Blood pressure (BP) was directly recorded in the awake animals and BPV was determined, in time (variance, mmhg2) and frequency domains by the autoregressive method. Statistical significance was set in P <0.05. Data are median and interquartile range. Results: No significant changes in HRV was observed in MI rats, while BPV showed significant decreasing of blood pressure variance (SO-Plac=42.08 (39.21) mmHg2 vs. MI-Plac=21.67 (12.58) mmHg2, P <0.05), reversed by the Carv treatment (MI-Plac=21.67 (12.58) vs. MI-Carv=38.64 (29.25), P <0.05). In the frequency domain analyses, MI reduced absolute and normalized LF component (LF (mmHg2): SO-Plac=8.98 (14.84) vs. MI-Plac=2.08 (4.84), P <0.05; LF(nu): SO-Plac=79.48 (45.03) nu vs. MI-Plac=24.25 (40.67) nu, P <0.05) and increased the normalized HF component of the BPV (SO-Plac=20.51 (39.18) vs. MI-Plac=60.51 (39.73). Carv treatment significantly attenuated the LF component fall. Conclusion: Chronic treatment with carvedilol restored the variance of BPV altered by the MI. [Copyright &y& Elsevier]

The epinephrine test has been shown to be a powerful tool to predict the genotype of congenital long QT syndrome (LQTS). The aim of this study was to evaluate its role in the diagnosis and management of LQTS in children. The test (using the Shimizu protocol) was conducted in patients with some evidence of LQTS but in whom clinical and management decisions were challenging ( n = 41, age 9.6 ± 3.9 years, 19 female). LQT1, LQT2, and negative responses to epinephrine were obtained in 16, 5, and 20 subjects, respectively. LQTS gene positivity was obtained in two subjects. Beta-blocker therapy was started in all subjects with a positive epinephrine response ( n = 21) and in some negative responders because of their strong LQTS phenotype ( n = 10). No therapy was given to the subset with less convincing features of LQTS who had also responded negatively to epinephrine ( n = 10). Follow-up for 3.0 ± 2 years was uneventful in both management groups. Due to the discordance with genotyping, the epinephrine test cannot be used to diagnose genotype-positive LQTS but when used in combination with phenotype assessment and genetic screening, it could enable better management decisions. [ABSTRACT FROM AUTHOR]

Abstract: Background: Peak oxygen uptake (pVO2) is used for risk stratification in chronic heart failure (CHF), but little is known about the prognostic impact of pVO2-changes in patients on chronic beta-blocker (BBL) therapy. We therefore prospectively evaluated individual pVO2-changes at a 6-month interval in patients all receiving BBL. Methods: 194 patients with stable CHF on stable medication were included (V1) and underwent clinical evaluation and exercise testing. Testing was repeated (V2) at 5.7±1.5 months after V1 and patients were followed >12 months after V2. Death or hospitalisation due to cardiac reasons was the predefined EP (EPP, end-point positive; n =62; EPN, end-point negative; n =113). Results: Initial characteristics did not differ between EPP and EPN. Multivariate cox regression analysis revealed that change of pVO2 (EPP: −0.6±2.6 ml/kg min; EPN: +2.5±3.3 ml/kg min; p <0.001) was independent to pVO2, LVEF, NTproBNP and NYHA at V2 for prediction of the combined end-point during follow-up. An increase of pVO2 by 10% was identified as an adequate cut-off value for risk stratification and ROC-analysis showed the significant incremental prognostic value of the determination of pVO2 changes in combination with pVO2. Conclusions: Serial measurements of pVO2 yield additional information for risk stratification in clinically homogenous CHF patients receiving BBL. This is the first study demonstrating this fact within a narrow predefined interval with all patients on BBL. [Copyright &y& Elsevier]

Abstract: Adrenergic beta-blockade is the most potent pharmacological therapy for the improvement of global left ventricular (LV) function in heart failure. A substantial portion of patients responds poorly to beta-blockers, but there is scarce information about LV regional function and recovery. We intended to evaluate the effects of beta-blockade on LV regional function and recovery, contractile reserve (CR) and response to long-term treatment. Methods: Twenty-two patients with heart failure were investigated at rest and during dobutamine stress echocardiography (DSE), before and after 6 months of metoprolol treatment. LV function was evaluated by global ejection fraction (EF), and by regional function in basal, mid and apical segments. Results: Recovery of LV global function (increase in EF >5%) after metoprolol treatment was significantly and best correlated to CR in basal segments of the ventricle (r =0.79, p <0.001), in comparison with function of mid and apical segments. The correlation between global recovery and global CR was r =0.55, p =0.007. In a multivariate logistic regression, including global and regional CR, age, gender, etiology of heart failure, ACE-inhibitor treatment, heart rate, and baseline EF, only basal CR was independently associated with recovery, OR 1.07 [95% CI, 1.01–1.21], p =0.019. Conclusion: The strongest association for prediction of LV recovery after metoprolol treatment was found regarding function of basal segments of the ventricle. Patients that responded favourably to beta-blockade had a significantly better CR, and treatment effect, in these segments. This gives further evidence for the importance of myocardial function in basal segments to the contribution of recovery and LV global function. [Copyright &y& Elsevier]

To examine the ability of myocardial contractile reserve (MCR) assessment to predict the improvement of left ventricular ejection fraction with treatment by carvedilol, a prospective study was undertaken in 85 patients with chronic heart failure and left ventricular ejection fraction <45%. Low dose dobutamine echocardiography (DSE), a 6-min walk test and measured brain natriuretic peptide (BNP) were assessed in all the patients. Patients were separated into two groups. Group A were patients without any myocardial reserve and group B patients with a myocardial contractile reserve defined as an increment of more than 20% of the resting left ventricular ejection fraction during dobutamine infusion. The two groups differed for percentage of ischemic cardiomyopathy (67.8 in group A vs. 29.7% in group B P=0.028), 6-min walk test performance (respectively, 343 vs. 415 meters P<0.05) and BNP plasma levels (respectively, 184.5 vs. 70.1 P<0.02) but not for left ventricular ejection fraction or NYHA class. During DSE, MCR and heart rate variation was higher in group B than in group A. At the end of the follow up, LVEF increased and NYHA class decreased in group B but not in group A. In multivariate analysis the existence of MCR could predict the improvement of LVEF with treatment by carvedilol. In our study, studying MCR could help to predict patients who will improve their LVEF with carvedilol prior to the administration of the treatment. [Copyright &y& Elsevier]

Important new studies relevant to the field of heart failure reported at the annual congress of the European Society of Cardiology (ESC), held in Amsterdam in August 2000, are reviewed. The IMPROVEMENT of Heart Failure survey investigated the knowledge and perceptions of over 1300 primary care physicians from 14 ESC member nations and the actual practice in over 11000 of their patients. Guidelines and clinical practice were compared. The survey suggested, in this large sample, that the quality of care was higher than previous smaller surveys have suggested but have also identified important deficiencies in knowledge and management that should be rectified. The COPERNICUS study demonstrated that carvedilol was remarkably well tolerated even in patients with very severe heart failure and that treatment was associated with a substantial reduction in mortality even among patients that would conventionally not be considered, by many, for beta-blocker therapy. The MUSTIC trial suggested that cardiac resynchronisation using biventricular pacing improved patients symptomatically whether or not the patient was in atrial fibrillation. Morbidity and mortality studies of cardiac resynchronisation are now underway. The ASPECT-II and APRICOT-II studies investigated the role of warfarin, aspirin and their combination for the long-term management of myocardial infarction. One interpretation of the data from these studies is that the combination of aspirin and warfarin is about as effective as warfarin alone but with a much higher incidence of side effects. Warfarin alone appeared superior to aspirin alone. In summary, the annual congress of the ESC provided important new information for clinical practice and, to date, was, by far, the most important cardiology congress in the world this year. [ABSTRACT FROM AUTHOR]

Propranolol in slow-release form has been the first-line treatment in long QT (LQT) until it was withdrawn from the market. We describe two cases where a switch to bisoprolol resulted in worsening of arrhythmia control: A man with LQT2, asymptomatic on propranolol, experienced syncope after switching to bisoprolol 5 mg daily. He switched back to propranolol and has remained asymptomatic during subsequent 12 months. A man with classical Jervell Lange-Nielsen syndrome, previous gangliectomy, and ICD implantation, switched to bisoprolol 5 mg daily. Four months later he experienced a tachycardia storm. He switched back to propranolol and has remained free from arrhythmias during subsequent 12 months. [ABSTRACT FROM AUTHOR]

Abstract: PR-segment changes of ECG can help differentiate acute myocardial infarct from pericarditis preventing the patient from an unnecessary coronarography. Here we present a case where beta-blocker therapy masked PR-segment changes. [Copyright &y& Elsevier]