Exercise-based cardiac rehabilitation in patients with reduced left ventricular ejection fraction: The Cardiac Rehabilitation Outcome Study in Heart Failure (CROS-HF): A systematic review and meta-analysis.

BACKGROUND: In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established. DESIGN: The design of this study involved a structured review and meta-analysis. METHODS: Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later. RESULTS: Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39-1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66-2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26-3.16, seven studies). In addition there was no significant difference between the groups with respect to 'hospitalization-for-any-reason' (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41-1.53, four studies), or 'hospitalization-due-to-heart-failure' (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12-2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07-9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35-3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference -4.19, 95% confidence interval -10.51-2.12, seven studies; six-months follow-up: mean difference -5.97, 95% confidence interval -16.17-4.23, four studies). CONCLUSION: No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

[Development and short-term effects of a standardized patient education program for in-patient cardiologic rehabilitation]. / Entwicklung und kurzfristige Effektivität eines standardisierten Schulungsprogramms für die Rehabilitation bei koronarer Herzkrankheit.

BACKGROUND: Patient education is an essential part in the treatment of coronary heart disease in medical rehabilitation. In the German-speaking area, no standardized and evaluated patient education program for coronary heart disease is available so far. In this paper, we demonstrate the development of a quality assured patient education program based on a health-education program of the German statutory pension insurance scheme. METHODS: In a multi-level approach, an existing program was modified concerning treatment evidence, practical guidelines, theories of health and illness behavior and quality criteria for patient education as well as clinical experience and thereafter manualized. In a formative evaluation, feasibility and patient acceptance of this modified program were assessed using evaluation questionnaires of patients and trainers. Afterwards, effects of the patient education program as compared to a traditional education program were assessed on a short-term (at discharge), medium-term (6-month follow-up) and long-term (12-month follow-up) basis in a multicenter quasi-experimental control group study of patients with coronary heart disease (n=434). RESULTS: Results of the formative evaluation demonstrate an overall good acceptance and a good feasibility of the manualized program. Short-term results show a significant small treatment effect in the primary outcome variable patients' knowledge (p=0.001, η2 =0.028). Furthermore, small effects were also observed among some secondary outcomes, such as attitude towards medication, planning of physical activity, psychological quality of life and satisfaction with the education program. CONCLUSION: A standardized education program for patients with coronary heart disease has been developed in a systematic process based on established quality standards. Depending on the outstanding medium and long-term effects, the program may be recommended for general use in medical rehabilitation. The manual provides the prerequisites allowing for a successful transfer into clinical practice.

Cardio-metabolic characterisation of patients with coronary heart disease: specific consideration of the 1-h postprandial plasma glucose.

Cardiovascular events and type 2 diabetes are closely correlated. The clinical impact of this knowledge still appears improvable, since patients frequently develop macrovascular diseases directly after, or even before reaching the routine criteria for diabetes. Consideration of the 1-h plasma glucose in the oral glucose tolerance test (OGTT) might allow detecting a high cardiovascular and/or diabetes risk earlier. We performed OGTTs in patients with unknown diabetes after acute coronary syndromes and compared data of patients reaching either a 1-h plasma glucose<140 mg/dl (n=151) or≥200 mg/dl (n=125). Patients with a low or high 1-h plasma glucose differed in BMI 26.2±3.7 vs. 28.1±3.6 kg/m², waist circumference 95.3±10.7 vs. 101.5±11.7 cm, hypertension 59.6 vs. 73.6%, HDL-cholesterol 46.2±13.5 vs. 43.2±13.9 mg/dl, triglycerides 118.6±57.9 vs. 135.9±59.3 mg/dl, cardiac septum/posterior wall thickness 12±2 vs. 13±2 mm, respectively, left atrium diameter 42±6 vs. 45±7 mm, diabetes 1.3 vs. 36.0%, impaired glucose tolerance 6.6 vs. 35.2%; p<0.05, respectively. In summary, a 1-h OGTT plasma glucose≥200 mg/dl suggests a high cardiovascular risk and might help to identify such patients independently of reaching the definition criteria for manifest diabetes.

Comparable short-term prognosis in diabetic and non-diabetic patients with acute coronary syndrome after cardiac rehabilitation.

BACKGROUND: Patients with pathological glucometabolism are at increased risk of recurrent cardiovascular events after acute coronary syndrome (ACS). The goal of this study was to investigate the association of glucometabolism and the one-year outcome of cardiac rehabilitation patients. DESIGN: Prospective multicentre registry from four German rehabilitation clinics. METHODS: During 2005-2006, 1614 consecutive patients (85.9% male, mean age 55 ± 10.3 years) were included after the first ACS (mean 18.9 days) and classified into group 1 (apparent diabetes mellitus, n = 268), group 2 (no diabetes, impaired oral glucose tolerance [OGT], n = 185), and group 3 (normal fasting glucose and normal OGT, n = 1161). The mean follow-up was 13.4 months and the follow-up events were analysed by multivariate logistic regression models with backward elimination. RESULTS: The overall mortality was 1.3% (group 1: 1.2%; group 2: 1.8%; group 3: 1.5%; p(Trend) = NS). The target blood pressure values at discharge (<140/90 mmHg) were achieved by 88.7%, 89.1% and 90.8% of patients in groups 1, 2 and 3, respectively (p(Trend) = NS). The target value for LDL cholesterol (<100 mg/dl) was attained by 87.0%, 80.8% and 81.5% of the patients in groups 1, 2 and 3, respectively (p(Trend) = NS). There was a trend of a lower proportion of patients reaching the target values for HDL-C of 46.1%, 51.4% and 60.8% (p(Trend) < 0.001) and triglycerides of 65.1%, 79.9% and 74.6% (p(Trend) = 0.004) for groups 1, 2 and 3, respectively. The strongest multivariate predictors for overall mortality were patients experiencing a previous stroke (OR, 6.29 [95% CI: 1.06-37.19]; p = 0.042) and, with a trend, peripheral arterial disease (OR, 3.60 [95% CI: 0.95-13.68]; p = 0.061). In the multivariate analysis, the diabetic state had no association with poor outcomes (i.e. death or rehospitalization). CONCLUSION: The short-term prognosis for both diabetic and non-diabetic patients was good and was determined by end organ damage rather than by glucometabolic status. Diabetic patients received comparable (and not more aggressive) pharmacotherapy and therefore achieved target values for cardiovascular risk factors to a lesser extent than the non-diabetic and pre-diabetic patients.

[Telemedicine during cardiac rehabilitation after acute myocardial infarction]. / Telemedizin in der Rehabilitation nach Herzinfarkt.

After acute myocardial infarction, cardiac rehabilitation should be an essential part of any therapy aimed at long-term success. Telemedical studies have mostly investigated ECG-monitored exercise training at home and internet-based counseling for lifestyle modification in selected patients. This approach cannot replace the holistic and multidisciplinary approach of cardiac rehabilitation. Telemedicine should be further evaluated, however, as it offers significant opportunities to facilitate access to rehabilitation for those patients who would otherwise not be able to attend for geographical, logistic or psychosocial reasons.

[Cardiovascular rehabilitation]. / Kardiovaskuläre Rehabilitation.

Cardiovascular rehabilitation encompasses the optimization of secondary prevention to reduce morbidity and mortality, the improvement of physical fitness and quality of life as well as the reintegration into social life and employment. This requires a multifactorial intervention on the physical, psychological, educative and social level by a multidisciplinary team. In Germany, cardiac rehabilitation started early after an index event, could demonstrate a significant reduction of total mortality, myocardial infarction and hospitalization during a follow-up of 1-2 years in 4 cohort studies including 10,758 patients with myocardial infarction and bypass surgery. This reduction of clinical events was obtained in addition to rapid revascularization therapy during the acute coronary event and on top of an evidence based secondary preventive medication. By national and international medical societies, cardiac rehabilitation is recommended as well in patients with congestive heart failure, after valve replacement or valve repair, after heart transplantation and cardioverter/defibrillator implantation. In the future, cardiac rehabilitation in Germany should be evaluated by a randomized controlled trial and multifactorial interventions should be tailored individually to specific patient subgroups and medical conditions.

[Telemedicine in cardiac rehabilitation--a literature review and critical appraisement]. / Telemedizin in der kardiologischen Rehabilitation--Eine Literaturübersicht mit kritischer Wertung.

The propagation of telemedicine has influenced the development of cardiac rehabilitation as well. Especially on an outpatient basis, there is an increasing number of publications about exercise training at home controlled by telemedical ECG. These trials, however, are predominantly feasibility studies including only few patients. In addition, most of the patients were male, classified as uncomplicated low-risk patients, and the vast majority was not included until weeks and months after the acute event. So far, there is no randomized controlled trial about telemedicine in cardiac rehabilitation in a large representative population. Furthermore, in most of the studies, only telemedically conducted exercise training was evaluated, and education classes as well as psychosocial interaction with the multidisciplinary team were not considered. The argument most often cited for the further spread of telemedicine, i.e. that its use will reduce the costs of medical care, has been proven so far neither. In conclusion, telemedical supervision of exercise training at home is technically feasible. As controlled data are lacking, risks and benefits of telemedical interventions in cardiac rehabilitation are not well evaluated yet. By no means may the sole telemedically supervised exercise training at home replace the multidisciplinary cardiac rehabilitation on an in- or outpatient basis. However, as there is the great opportunity to facilitate access to cardiac rehabilitation programmes for patients living in rural areas as well, the application of telemedical techniques should be further evaluated scientifically in this setting giving special attention to cost-effectiveness in times of limited financial resources.

Can serum NT-proBNP detect changes of functional capacity in patients with chronic heart failure?

Recently, in a cross-sectional study, a correlation of moderate degree was documented between serum BNP (brain natriuretic peptide) and exercise capacity in patients with chronic heart failure (CHF). However, it remains unknown if BNP, which increases in response to high myocardial wall stress, is sufficiently sensitive for changes in exercise capacity during clinical follow-up. To elucidate this, 42 CHF patients were recruited and randomized into a training (T; 58 +/- 10 years; n = 14 NYHA II; n = 5 NYHA III) and a control group (CO; 54 +/- 9, n = 17 NYHA II; n = 6 NYHA III). T carried out 12 weeks of endurance training on a cycle ergometer (4 sessions per week, 45 min duration). Venous blood sampling and cycle ergometry with simultaneous gas exchange measurements were carried out prior to and after the experimental phase. Due to its superior stability during laboratory procedures, NTproBNP was determined instead of BNP. Both proteins are secreted in equimolar amounts and share an identical diagnostic meaning. In both groups, NT-proBNP decreased slightly (T: from 1092 +/- 980 to 805 +/- 724 pg x ml(-1); CO: from 1075 +/- 1068 to 857 +/- 1138 pg x ml(-1); T vs CO: p = 0.65). Anaerobic threshold (AT) as a measure of exercise capacity went up in T (from 0.96 +/- 0.17 to 1.10 +/- 0.22 l x min(-1)) but remained almost constant in CO (pre: 1.02 +/- 0.27; post: 1.00 +/- 0.27 l x min(-1); T vs CO: p < 0.001). The correlation between changes in NT-proBNP and changes in AT remained insignificant (r = 0.02, p = 0.89)-even if only T was considered (r = 0.09, p = 0.72). Improved exercise capacity in CHF patients due to 3 months of endurance training is not reflected in the course of NT-proBNP. These findings are inconsistent with a sufficient sensitivity of this parameter to detect changes in exercise capacity during clinical follow-up. Changes in NT-proBNP beyond its spontaneous variability are more likely to be detected following therapeutical interventions which aim more clearly at the myocardium. In determining alterations of functional capacity ergometric testing cannot be replaced by serial determinations of NT-proBNP.

[Feasibility and reliability of a transtelephonic 12 leads ECG]. / Zur Praktikabilität und Reliabilität des selbst abgeleiteten und telefonisch übertragenen 12-Kanal-EKG.

Feasibility and reliability of a 12 lead electrocardiogram (ECG), recorded by the patient himself and transmitted via telephone are mandatory for prehospital diagnosis of myocardial ischemia in patients with coronary heart disease. In this study, a 12-lead ECG recorded by patients and transmitted to the cardiology call center via telephone (Tele-ECG; model CG-7100; Card Guard) was compared with the conventional 12-lead ECG from the same patient recorded at the same time in 128 cases. The Tele-ECGs received by the call center were compared with conventional ECG by two cardiologists and one internist independently and blindly. In relation to the conventional ECG, reproducibility of PQ, QRS and QT-durations [ms] as measured in the Tele-ECG was 85%. Concordance between Tele-ECG and conventional ECG in the detection of negative T-waves was very high (Kappa value (kappa) 0.94, 0.96 and 0.97), respectively, depending on the physician. ST-segment changes were diagnosed correctly in most of the cases in Tele-ECG (kappa=0.98-0.99), as compared with the conventional ECG by all physicians. Concordance between Tele- and conventional ECG concerning the pattern of old myocardial infarction was very high (kappa=0.99) for all infarct localization. The limitations of Tele-ECG were of technical nature. In 14 cases, the peripheral electrodes were displaced; in 12 cases, there were baseline artifacts. These technical errors could be corrected in 126/128 patients (98.4%) by transtelephonic verbal communication. In conclusion, the reliability and feasibility of the 12-lead Tele-ECG-recorder used in this pilot study could be demonstrated. In an ongoing randomized controlled multicenter study, it is being investigated whether the strategy of prehospital diagnosis of acute coronary syndromes by Tele-ECG in combination with verbal communication is able to reduce pre- and in-hospital time delay, to avoid unnecessary hospital admissions and to reduce the economic burden of coronary heart disease.

Defining the optimum upper heart rate limit during exercise: a study in pacemaker patients with heart failure.

AIMS: There is no non-invasive method to determine the individual optimum of maximum exercise heart rate. Knowledge of this value is of particular interest in patients with structural heart disease who are prone to tachycardia intolerance. The purpose of this study was to define the optimal maximum heart rate using cardiopulmonary exercise testing and exercise Doppler echocardiography and to compare the results of both approaches. METHODS AND RESULTS: In 49 pacemaker patients with chronotropic incompetence, the optimum upper heart rate limit was determined using cardiopulmonary exercise testing and exercise Doppler echocardiography. The optimum upper rate limit was given by the highest pacing rate which still produced an increase in oxygen consumption, or by that pacing rate which was linked to the lowest value for the Doppler-derived myocardial performance index. In patients with normal left ventricular ejection fraction (>or=55%) the optimum upper rate limit was 86% of age-predicted maximum heart rate, in patients with left ventriuclar dysfunction (ejection fraction

Longevity of dual chamber pacemakers: device and patient related determinants.

In 382 patients with three different dual chamber pulse generators, the median time interval to battery depletion was 98.3 months. Cox regression analysis revealed the following variables as significant predictors of battery longevity: programmed pacing rate, energy of the stimulation output, mode of stimulation (i.e., proportion of paced cycles in one or two chambers), battery capacity, and internal sensing current of the pacemaker. Although 27% of all patients died before the service life of the pacemaker was over and despite a rate of premature reoperations of 8.6%, the majority of pacemaker patients (55%) fully used the expected battery life span of the pulse generator. Patients who died before the pacemaker had reached its end of service were significantly older at implantation than patients who survived until pacemaker replacement. The vast majority (92%) of patients received another dual chamber pulse generator when replacement was required. These data underline the need for long-lasting dual chamber devices.

Safety and efficiency of pulse charge multiplication for chronic ventricular output programming.

Fifty-one patients with Intermedics pacemakers and different chronic (> or = 12 months) ventricular lead models were investigated. Ventricular charge thresholds (microC) were measured telemetrically at 1.0, 2.0, 2.5, and 3.5 V, respectively. Then pulse duration was increased until charge per pulse (microC) was twice the threshold value in patients not being pacemaker dependent (n = 39) and three times the threshold in pacemaker dependent patients (n = 12), thus giving a 2:1 or 3:1 safety factor in terms of charge ("safety charge"). At safety charge settings, the battery current was measured telemetrically for all four pulse amplitudes (PA) in VVI mode at 70 beats/min. For safety purposes, only pulse amplitudes were considered that fulfilled two conditions: (1) pulse duration threshold (PDT) < or = 0.30 ms at PA and (2) PDT < or = 1.00 ms at a pulse amplitude of (PA-0.5 V). The combination of pulse amplitude and pulse duration that yielded the safety charge at the lowest battery current was defined as optimized ventricular output (Copt). It was found at 1.0 V in 27 patients and at 2.0 V in 24 patients. The safety pulse duration (SPD) that yielded a 2:1 safety charge in patients who were not pacemaker dependent was 0.32 +/- 0.12 ms for both, 1.0 V (n = 23) and 2.0 V (n = 16), respectively. In pacemaker dependent patients, the SPD for the 3:1 safety charge was 0.61 +/- 0.25 ms (at 1.0 V, n = 4) and 0.47 +/- 0.11 ms (at 2.0 V, n = 8), respectively. The safety factor for conversion of PDT into SPD was 3.15 (range 3.00-3.38) for pacemaker dependent patients and 2.04 (range 2.00-2.43) for patients who were not pacemaker dependent, respectively. Charge thresholds measured at study entrance, after 24 hours, and again after 6 months showed a median variation of 14% and a maximum individual variation of 55%. On day 0 and 180, 24-hour Holter recordings were obtained from all patients and revealed constant ventricular capture at output settings Copt. When the output was changed from a fixed setting (2.5 V at 0.50 ms) to Copt, the battery current decreased by 17.5% (P < 0.0001). In conclusion, pacing thresholds in patients with chronic ventricular leads are stable enough to permit programming battery-saving low output settings, if pacemakers are followed on a regular basis. Titration of a 2:1 safety charge (a 3:1 safety charge in pacemaker dependent patients) by prolongation of pulse duration is safe, provided that pulse amplitude is chosen carefully. Using this approach, current consumption can significantly be reduced without jeopardizing patient's life.

Septal lead implantation for the reduction of paced QRS duration using passive-fixation leads.

In 120 consecutive patients with standard pacing indications, we tested the feasibility of RV septal lead implantation technique guided by surface ECG and the degree to which this technique reduces paced QRS duration compared to RV apical stimulation when passive-fixation leads are used. During implantation, an ECG was recorded with a paper speed of 100 mm/s using the orthogonal Frank leads, and QRS was measured from the earliest to the latest deflection in any of the Frank leads. Pace-mapping of the septum was performed until QRS was minimal. The lead was attached, where QRS, pacing threshold, lead impedance, and EGM amplitude provided the best compromise. An average of 3.7 +/- 2.5 attempts (range 1-18, median 7) was needed until a final implantation site was found. There were no technical problems during implantation. QRS could be reduced by 5-55 ms (mean delta QRS 19 +/- 11 ms) in 83 (69%) of 120 patients. In 22 (18%) patients, QRS was identical with apical and septal pacing, and in 15 (13%) patients, QRS was 5-20 ms (10 +/- 4) longer despite septal stimulation. Average QRS was significantly shorter during septal pacing compared with apical pacing (151 +/- 20 vs 162 +/- 23 ms, P < 0.001). There was a tendency towards greatest QRS reduction when the high septum was stimulated (22 +/- 11 ms reduction) as compared with mid- (18 +/- 11 ms) or apical parts of the RV septum (16 +/- 10 ms). QRS reduction was most likely if apical QRS width was > 170 ms (P = 0.0002), and there was an inverse correlation between apical QRS and delta QRS (r = 0.53, P < 10(-7)). During a mean follow-up of 14 months, there was no pacing or sensing problem and no lead dislodgment occurred.

AAIR versus DDDR pacing in the bradycardia tachycardia syndrome: a prospective, randomized, double-blind, crossover trial.

In 19 patients paced and medicated for bradycardia tachycardia syndrome (BTS), AAIR and DDDR pacing were compared with regard to quality of life (QoL), atrial tachyarrhythmia (AFib), exercise tolerance, and left ventricular (LV)function. Patients had a PQ interval < or = 240 ms during sinus rhythm, no second or third degree AV block, no bundle branch block, or bifascicular block. In DDDR mode, AV delay was optimized using the aortic time velocity integral. After 3 months, QoL was assessed by questionnaires, patients were investigated by 24-hour Holter, cardiopulmonary exercise testing (CPX) was performed, and LV function was determined by echocardiography. QoL was similar in all dimensions, except dizziness, showing a significantly lower prevalence in AAIR mode. The incidence of AFib was 12 episodes in 2 patients with AAIR versus 22 episodes in 7 patients with DDDR pacing (P = 0.072). In AAIR mode, 164 events of second and third degree AV block were detected in 7 patients (37%) with pauses between 1 and 4 seconds. During CPX, exercise duration and work load were higher in AAIR than in DDDR mode (423+/-127 vs 402+/-102 s and 103+/-31 vs 96+/-27 Watt, P < 0.05). Oxygen consumption (VO2), was similar in both modes. During echocardiography, only deceleration of early diastolic flow velocity and early diastolic closure rate of the anterior mitral valve leaflet were higher in DDD than in AAI pacing (5.16+/-1.35 vs 3.56+/-0.95 m/s2 and 69.2+/-23 vs 54.1+/-26 mm/s, P < 0.05). As preferred pacing mode, 11 patients chose DDDR, 8 patients chose AAIR. Hence, AAIR and DDDR pacing seem to be equally effective in BTS patients. In view of a considerable rate of high degree AV block during AAIR pacing, DDDR mode should be preferred for safety reasons.

[Pharmacotherapeutical approaches to insomnia patients with cardiac diseases and after heart transplantation]. / Pharmakotherapeutische Behandlungsstrategien der Insomnie bei Patienten mit kardialen Erkrankungen und nach Herztransplantation.

Insomnia in patients with heart transplantation and cardiac disease is a common problem. Organic factors, immunodepressant medication (e.g. ciclosporine and steroids) and psychological factors may account for this symptom. The article reviews different hypnotic drugs and their value in the treatment of insomnia. For short-time treatment, medication with benzodiazepine hypnotics may be useful. If the problems of drug dependence and rebound insomnia are taken into consideration, treatment with non-benzodiazepine hypnotics offers more safety and comfort. If insomnia is part of a depressive syndrome, pharmacotherapeutical intervention with antidepressive sedative medication is required. With regard to cardiac disease, treatment with mirtazapine, nefazodone or trazodone should be preferred because of the chinidine-like effect of tricyclic antidepressants (TCA). Sedative neuroleptic medication (e.g. melperone) is commonly given to geriatric patients; nevertheless, patients with chronic insomnia may also benefit from this medication. The risks and benefits of hypnotic drugs are discussed especially in relation to pharmacological interaction (cytochrome system) and cardiac disease.