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Implantable cardioverter defibrillators (ICDs) are used for primary or secondary prevention of sudden cardiac death. We sought to clarify prognosis and causes of death after ICD implantation. A total of 2743 patients with ICDs implanted during 1990–2020 were analyzed. Median age was 68.5 (59.6–74.6) years; 21% women, median left ventricular ejection fraction (LVEF) was 30 (23–35), 52% had an ischemic etiology and 77% had a primary preventive indication. Mortality rate after 10 years was 22, 44, 55, and 72% in the 1st, 2nd, 3rd, and 4th age quartile, respectively. The calculated median sex and age adjusted loss of life years compared to the average German population was 9.7 (6.1–14.0) years. Prognosis was independently related to sex, age, LVEF, and glomerular filtration rate. 713 out of 852 deaths could be classified to a specific cause. Congestive heart failure (CHF) accounted for death in 214 (30%) and sudden death (SD) for 144 patients (20%). Postmortem interrogation of devices in 74 patients revealed VT/VF in 39 and no episodes in 35 patients. Cancer was identified as the cause of death in 121 patients (17% of cases), of which 36 were bronchial carcinomas. 73 (10%) of patients died due to infection. 67 patients (9%) died within 24 h of procedures. Compared to other causes, significantly more life years were lost associated with procedures and SD: 9.3 (5.7–12.9) versus 12.1 (7.4–15.2) and 11.9 (7.6–17.8) years. Life expectancy of ICD patients is lower than for the general population. Mortality is predominantly due to CHF, but there is still a considerable rate of SD. The occurrence of cancers, most importantly bronchial carcinomas, and infections, warrants protective measures. Some deaths during procedures are possibly preventable. Patients with ICDs comprise a vulnerable cohort, and treatment has to be optimized in many directions to improve prognosis.

Background Patients with atrial fibrillation (AF) often have sleep apnea (SA), but diagnosis of SA with polysomnography is costly. SA monitoring is a pacemaker feature that measures respiratory disturbance index, the sum of abnormal respiratory events divided by sleep duration. Objective The purpose of this study was to evaluate the incidence and severity of SA and its association with AF in an unselected population fitted with pacemakers. Methods RESPIRE (REgistry of Sleep APnea monItoring and Atrial Fibrillation in pacemakeR patients) was a multicenter, international, observational, open-label study following adult subjects for 18 months after implantation with an SA monitoring–enabled dual-chamber pacemaker. Severe SA was defined as average respiratory disturbance index ≥20 from implantation to follow-up visit. The first co-primary end point was the difference in significant AF (cumulative AF episodes lasting ≥24 hours over 2 consecutive days) between subjects with severe and those nonsevere SA at 12 months in the full analysis set (N = 553). The second co-primary end point was the rate of major serious adverse events at 18 months in the modified intention-to-treat set (N = 1024). Results Severe SA was detected in 31.1% (172 of 553). A higher incidence of significant AF was reported in patients with severe SA than in patients with nonsevere SA (25.0% vs 13.9%; difference 11.1%; 95% confidence interval 3.7%–18.4%; P = .002). Significant AF increased with time in both groups, but at a faster rate in the severe SA group. No intergroup difference in the overall rate of major serious adverse events was observed (P = .065). Conclusion SA screening over 12 months identified severe SA in almost one-third of unselected patients fitted with pacemakers. Severe SA was associated with a higher incidence of significant AF.

A 65-year-old patient received an implantable cardioverter-defibrillator shock that resulted in ventricular tachycardia termination but induction of atrial fibrillation. The possible consequences of this rarely reported event are discussed.Ein 65 jähriger Patient erlitt einen Schock seines implantierten Defibrillators, welcher eine laufende Kammertachykardie terminierte, jedoch gleichzeitig Vorhofflimmern auslöste. Mögliche Konsequenzen dieses selten berichteten Ereignisses werden diskutiert.

Aims: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results: In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 &plusmn, 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed, this was narrowed down to a specified profile of five genes (CPT1, CCL20, CCR5, CCR6, TLR8) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions: Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of a) overcoming the sampling error associated with purely histologic examinations and b) monitoring the effectiveness of therapy.

Background A significant proportion of patients receiving CRT are non-responders. We evaluated the efficacy of Cardiac Contractility Modulation in subjects with reduced LVEF who, despite cardiac resynchronization therapy (CRT), continued to experience clinically significant symptoms. Methods This was a multi-center, open label, treatment-only, feasibility study of 17 CRT non-responders who received CCM therapy. Changes in NYHA class, ejection fraction (EF), Minnesota Living with Heart Failure Questionnaire (MLWHFQ) score, and exercise tolerance (6 minute walk test; 6MWT and peak VO2) were analyzed over 6 months. Mortality and hospitalization rates were determined. Results Patients (82% male) were 69.4 ± 9.6 years of age with baseline EF = 22.8 ± 6.5%. Among primary endpoints, peak VO2 increased 1.1 ± 1.6 ml/kg/min (p = 0.03) and MLWHFQ improved (−16 ± 16 points; p Conclusions Patients with heart failure and reduced ejection fraction who remain moderately to severely symptomatic despite use of CRT, may benefit from CCM therapy with improvement in quality of life and exercise tolerance. A larger prospective study in this population is warranted.

Patients receiving dual-chamber implantable cardioverter-defibrillator (DR-ICD) therapy are at risk of developing atrial arrhythmia because of the increased rate of ventricular pacing and the progression of heart failure. Remote monitoring (RM) may identify the patients at highest risk of adverse events such as atrial arrhythmias. A total of 283 patients with 91,632 remote transmissions during a 15-month follow-up (FU) period enrolled in the LION registry were analysed. The parameters retrieved included the pacing mode, lower rate limit, percentage of atrial (%AP) and ventricular pacing (%VP), and percentage of atrial arrhythmia burden (%AB). In 92.7% of patients, the devices were initially programmed in DDD(R) or DDI(R), with changes of the pacing mode in 19.3% only. The lower rate limit remained stable in 80.4% of patients. At the first transmission, 8.7% of patients suffered from RM-detected atrial arrhythmia, which reached 36% during FU. The %AP was not associated with increased AB (p = 0.67), but the %VP was different in patients developing RM-detected atrial arrhythmia (26.9% vs. 13.7%, p < 0.00001). The %VP increased in 105 patients (significance level of α = 0.05), and 11 patients crossed the border of 50% VP. The LION substudy supports the concept of using RM in a real-world DR-ICD population. Remote monitoring of DR-ICDs allows for the quantification of the course of the pacing parameters and AB. Based on these observations, device parameters can be adjusted and optimized.

Sensing of left ventricular (LV) activity in some devices used for cardiac resynchronization therapy (CRT) was designed primarily to prevent the delivery of an LV stimulus into the LV vulnerable period. Such a sensing function of the LV channel is not universally available in contemporary CRT devices. Recordings of LV electrograms may provide special diagnostic data unavailable solely from the standard right ventricular electrogram and corresponding marker channel. We used the LV sensing function of Biotronik CRT defibrillators to find 3 cases of dissimilar ventricular rhythms or tachyarrhythmias. Such arrhythmias are potentially important because concomitant slower right ventricular activity may prevent or delay implantable cardioverter-defibrillator therapy for a life-threatening situation involving a faster and more serious LV tachyarrhythmia. Dissimilar ventricular rhythms may not be rare and may account for cases of unexplained sudden death with a normally functioning implantable cardioverter-defibrillator and no recorded terminal arrhythmia.

Aims One option to improve cardiac resynchronization therapy (CRT) responder rates lies in the optimization of pacing intervals. A haemodynamic sensor embedded in the SonRtip atrial lead measures cardiac contractility and provides a systematic automatic atrioventricular and interventricular delays optimization. This multi-centre study evaluated the safety and performance of the lead, up to 1 year. Methods and results A total of 99 patients were implanted with the system composed of the lead and a CRT-Defibrillator device. Patients were followed at 1, 3, 6, and 12 months post-implant. The primary safety objective was to demonstrate that the atrial lead complication free rate was superior to 90% at 3-months follow-up visit. A lead handling questionnaire was filled by implanting investigators. Lead electrical performances and the performance of the system to compute AV and VV delays were evaluated at each study visit over 1 year. The complication free rate at 3 months post-implant was 99.0% [95%CI 94.5–100.0%], P < 0.001. Electrical performances of the lead were adequate whatever the atrial lead position and remained stable over the study period. The optimization algorithm was able to compute AV and VV delays in 97% of patients, during >75% of the weeks. Conclusion The atrial lead is safe to implant and shows stable electrical performance over time. It therefore offers a promising tool for automatic CRT optimization to further improve responder rates to CRT.

The authors wanted to investigate whether the heart failure survival score (HFSS) is useful for sudden cardiac arrest (SCA) risk stratification and whether there is a difference with regard to congestive heart failure (CHF) etiology. Data of 712 severe CHF patients (New York Heart Association III/IV 58%/42%, mean age 62+/-8 years, mean left ventricular ejection fraction 26%+/-11%) during the period from 1993-2003 were analyzed. The HFSS was calculated using the Aaronson formula. SCA-free survival was calculated using Kaplan-Meier analysis according to the etiology of CHF: coronary artery disease (CAD) (n=317) vs no CAD (n=395). In regard to SCA risk, the authors found no significant overall difference between patients with or without CAD. Non-CAD HFSS high-risk patients had a significantly higher risk for SCA than all the other groups ( P.001). The HFSS is useful for the detection of a subgroup of non-CAD severe CHF patients at very high risk for SCA.

A. Castel Hospital Clinic Thorax Institute Villarroel 17008036 Barcelona, Spain Tel.: +34 /932275722 Fax: +34 /932279868 E-Mail: acastel@gmx.de Sirs: Brugada syndrome is defined as a typical ECG pattern that predisposes individuals with structurally normal hearts to ventricular arrhythmias and sudden cardiac death. It is an inheritable arrhythmia syndrome first described in 1992 by Brugada & Brugada [1] that can be linked to mutations in myocardial ion channel mutations in 20% of patients. Typical electrocardiograms show ST segment elevation in the precordial leads V1 to V3, with morphology of the QRS complex resembling a right bundle branch block [2]. We report on a case with underlying coronary artery disease, presenting with a defibrillator shock due to ventricular tachycardia under amiodarone and beta-blocker therapy and a Brugada type ECG pattern. Possible interferences by these drugs and suitable therapeutic actions are discussed.

Stored electrograms or marker channels are available in most of modern cardiac pacemaker models. We sought to analyse these information to uncover terminal events of pacemaker patients dying suddenly. Method and results We made post-mortem pacemaker (PM) interrogations in 19 patients dying suddenly out of hospital between the years 1997 and 2005 (mean age 59 +/- 13 years, 90% males). The systems had activated arrhythmia monitoring algorithms. Indications of pacing were sick sinus syndrome in seven, AV-block in five, and heart failure due to asynchrony in seven cases. The interrogated pacemakers were CHORUS 7034 (n = 12), CONTAK TR (n = 2), and INSYNC III (n = 5). For interpretation stored marker channels and electrograms were analysed. The mean observation time after PM implantation prior death was 2.11 +/- 1.44 years, the mean left ventricular ejection fraction from the last available echo examination in the year prior death was 27.5 +/- 8%, mean age was 63 +/- 12 years. In 17/19 cases (89%), a tachycardia (most likely ventricular tachycardia) was found correlating to the time of death. The mean cycle length of the terminal arrhythmia was 307 +/- 144 (250-344) ms, corresponding to a heart rate of 195 +/- 95 (174-240) bpm. We found no evidence of specific pacemaker-related problems such as electronic failure, battery depletion, or undersensing.Post-mortem analysis of arrhythmia monitoring of pacemaker patients revealed tachycardias (most likely ventricular tachycardia) to be related to sudden death. These findings give some insight in mechanisms of terminal events in this group.

Aims Coronary sinus (CS) lead implantation is a technically challenging procedure owing to variable vein anatomies and a high dislocation rate. Therefore, CS lead technology has undergone evolutionary changes during the last 10 years. The mode of fixation has been a passive one up to now. We want to describe our first clinical experience with the newly available active fixation lead 4195 in terms of dislocation rate and stability of thresholds compared with conventional models. Methods and results From 1999 to February 2007, we implanted 403 CS leads in 368 patients. Leads were categorized into three different groups on the basis of their fixation mechanism: straight (Easytrak I and Situs OTW; n ¼ 54), curved (Attain 4193 and 4194, Corox, Aescula, Situs ULD; n ¼ 308), and active (Attain 4195; n ¼ 41). Operative and follow-up data were prospectively noted and checked for significance between groups during the first 3 months after implantation. Kaplan–Meier analysis of long-term lead function was also performed. Straight and curved CS leads suffered from significantly more dislocations compared with active fixation (P , 0.001). The active fixation lead (4195) has a stable threshold over time compared with a significant rise after 24 h and thereafter in straight (62%) and curved leads (20%). However, retraction of an active fixation CS lead may be a difficult issue as outlined in two cases requiring pullback of a 4195 lead owing to phrenic nerve stimulation (one unsuccessful despite vigorous traction). Conclusion The active fixation lead 4195 using retention lobes yielded stable thresholds over time and seems to be superior to conventional leads in terms of dislocation. However, extraction may be a difficult or even impossible task.

Aims To evaluate the utility of intrathoracic impedance monitoring for detecting heart failure (HF) deterioration in patients with an implanted cardiac resynchronization/defibrillation device. Methods and results Patients enrolled in the European InSync Sentry Observational Study were audibly alerted by a device algorithm if a decrease in intrathoracic impedance suggested fluid accumulation. Clinical HF status and device data were assessed at enrolment, during regular follow-up, and if patients presented with an alert or HF deterioration. Data from 373 subjects were analysed. Fifty-three alert events and a total of 53 clinical events (HF deterioration defined by worsening of HF signs and symptoms) were reported during a median of 4.2 months. Adjusted for multiple events per patient, the alert detected clinical HF deterioration with 60% sensitivity (95% CI 46–73) and with a positive predictive value of 60% (95% CI 46–73). Higher NYHA class at baseline was predictive for adequate alert events during follow-up (P , 0.05). In 11 of 20 HF deteriorations without preceding alert, an upstroke of the fluid index occurred without reaching the programmed alert threshold. Conclusion A device-based algorithm that alerts patients in case of decreasing intrathoracic impedance facilitates the detection of HF deterioration. Future randomized, controlled trials are needed to test whether the tailored use of intrathoracic impedance monitoring can improve the ambulatory management of patients with chronic HF and an implanted device.

Aims Intracardiac electrograms (IEGMs) are essential for the assessment of implantable cardioverter-defibrillator (ICD) function. The Biotronik Home Monitoring systems transmit an ‘IEGM Online’ that is shorter than the full-length programmer IEGM due to technical constrains. The aim of this study was to evaluate the accuracy of the physician's classification of the underlying rhythm based on the second-generation IEGM Online. Methods and results In total, 1533 patients treated with single- and dual-chamber ICDs and cardiac resynchronization therapy defibrillators were enrolled at 67 investigational sites and followed for 15 months. The investigators classified the rhythm shown in IEGM Online as ventricular tachycardia, ventricular fibrillation, atrial fibrillation, other supraventricular tachyarrhythmia, oversensing due to lead failure, T-wave oversensing, or other rhythm. At the next in-office follow-up, the investigators classified independently the rhythm seen in the corresponding programmer IEGM. The two rhythm classifications were compared thereafter. Both IEGM Online and programmer IEGM were available in 2099 arrhythmic or oversensing events, of which 146 (7.0%) were classified as other rhythm or artefacts and were excluded as inconclusive or atypical. The remaining 1953 events, affecting 352 patients (23.0%), were classified correctly in 1803 cases (92.3%). The accuracy of rough rhythm classification as ventricular, supraventricular, or oversensing was 97.2%. Conclusion The Lumax and IEGM Online HD Evaluation study demonstrates that remote IEGM analysis is reasonably accurate in a remote monitoring system that transmits shorter IEGM than the full-length programmer IEGM for the sake of frequent, fully automatic data transmission.

Die Implantation (eigentlich Transplantation) frischer oder kryokonservierter menschlicher Herzklappen (Homografts) in Aortenposition gehort seit uber 30 Jahren zum herzchirurgischen Repertoire. Homografts sind attraktive Alternativen zu mechanischen oder xenobiologischen Klappen, da eine Antikoagulation vermieden und eine nahezu normale Anatomie hergestellt werden kann. Behandelnde Arzte sollten uber die verfugbaren Implantate, die Operationsmethoden und die zu erwartenden Ergebnisse informiert sein, um Patienten mit Klappenvitien entsprechend beraten zu konnen und individuelle Komplikationsmoglichkeiten in der Nachsorge fruh zu erfassen. Dargelegt wird eine Literaturubersicht zum Thema Homograftklappen. Es erfolgt eine Schilderung des Verfahrens der Graftgewinnung, der Herstellung und der Konservierung. Die Einsatzgebiete von Homografts werden erlautert und die Operationstechniken (subkoronar, Miniroot, Wurzelersatz) sowie die Ross-Operation diskutiert. Erwahnung findet auch der Einsatz von Homograftklappen bei fruhkindlichen Herzfehlern. Komplikationen und wichtige Aspekte der Nachsorge werden kommentiert. Homografts eignen sich zum Aorten- und Pulmonalklappenersatz bei speziellen Indikationen (jugendlicher Patient, Kontraindikation zur Antikoagulation, Endokarditis). Angaben zu Langzeitergebnissen schwanken je nach Zentrum, eingesetzter Operationsmethode und Klappentyp. Pulmonale Homografts in Aortenposition sind im Gegensatz zu aortalen Homografts negativ zu beurteilen. Der Stellenwert von Homografts und der Ross-Operation im Vergleich zu ungestutzten Xenografts sollte durch weitere moglichst multizentrische Langzeitstudien uberpruft werden. Im Bereich der Kinderherzchirurgie haben sich Homografts bewahrt, vor allem zur Rekonstruktion der rechtsventrikularen Ausflussbahn. Homograftimplantate in Mitralposition gehoren noch nicht zur klinischen Routine und zeigen bislang enttauschende Resultate. Die wesentliche Limitation im Einsatz von Homografts ist ihre geringe Verfugbarkeit; deshalb konnen Homografts nur begrenzt fur die oben erwahnten speziellen Indikationen zur Verfugung gestellt werden.

Background: Because the risk of developing malignant tumors after heart transplantation is approximately 100-fold higher, methods for rapid diagnosis must be developed to allow early and aggressive treatment in these patients. Although tumor markers have been used frequently for surveying already detected cancer, we studied their value in screening for tumors in heart transplant patients. Methods The levels of the tumor markers CEA, CA19-9, CA125, CA72-4, TPA, TPS, and CYFRA 21-1 were determined prospectively in 3-month intervals in 91 heart transplant patients between 1993 and 1998. Results In eight patients a definite diagnosis of cancer was made during the marker survey (mean observation time 2.85 ± 1.3 years), including bronchogenic carcinoma in six, renal carcinoma in one, and colon cancer in one. All patients with bronchogenic carcinoma were smokers. The markers had a sensitivity below 60% to detect cancer. Given a 2-fold cutoff level (10 ng/mL), the CEA was the only marker with sufficient specificity (93.8%, only one false-positive result). Two patients were symptom-free even though they had elevated CEA levels. In one of those patients, disseminated intractable cancer was diagnosed at first evaluation, whereas no tumor was found in the other case at first evaluation. Subsequently, by means of fluorodeoxyglucose positron emission tomography, a hypermetabolic region was found in the right upper mediastinum. Control computed tomographic scan 4 weeks after the first investigation showed disseminated intractable disease also in this patient. Another heart transplant patient with colon cancer showed a normalization of the CEA after hemicolectomy and an increase in the CEA when liver dissemination developed. There was a relationship between cardiac death and CA125 and TPS in some heart transplant patients. Conclusions We conclude that the CEA is the only tumor marker with adequate sensitivity and specificity to detect subclinical malignancies in the follow-up of heart transplant patients. However, because of several limitations (limited diagnostic and therapeutic possibilities and enormous costs), we cannot recommend screening by tumor markers on a regular basis. Because of the elevated risk of cancer in patients who had organ transplantation, further prophylactic measures, especially smoking cessation programs, must be developed. Once a malignancy is diagnosed, tumor markers can help target clinical decisions. Additionally, nonspecific increases in CA125 and TPS levels might be related to nonmalignant circulatory disturbances and cardiac death.

CA 125, known as a marker for ovarian cancer with hypothetical but hitherto uncharacterized biologic functions, was reported to be elevated in some not-well-defined benign conditions. There are no reports on fluctuations of CA 125 related to cardiac function, especially the failing heart and neurohumoral factors such as norepinephrine or atrial natriuretic peptid/e.CA 125 blood levels were determined in patients with heart failure before and after heart transplantation (HTx). In 71 patients, parallel determinations of norepinephrine, atrial natriuretic peptide, pulmonary capillary wedge pressure, and right atrial filling pressure were done. CA 125 levels also were prospectively studied in patients with heart failure with stabilization (n = 25) or worsening of the clinical status (n = 9) and after HTx (n = 25). Parallel determinations of the tumor markers CEA, CA 199, CA 153, TPS, and TPA were also done. The results were grouped according to the clinical status (New York Heart Association class) of the patients. CA 125 was significantly correlated with neurohormones and filling pressures. Follow-up investigations revealed a decrease of CA 125 levels after HTx (401 +/- 259 U/L vs 33 +/- 22 U/L, P.001, n = 25) or stabilization (429 +/- 188 U/L vs 78 +/- 35 U/L, P.001, n = 25) and an increase during worsening of heart failure (42 +/- 25 U/L vs 89 +/- 32 U/L, P.01, n = 9). In 4 patients after HTx, unexpected death was preceded by rising CA 125 levels. CEA, CA 199, CA 153, TPS, or TPA did not correlate with heart failure status or clinical events.CA 125 is a marker of the clinical and hemodynamic status and the course of patients with heart failure before and after heart transplantation. The determination of CA 125 serum levels may be an additional tool in the management of these patients. In patients with cancer, these "nonspecific" changes must be considered when CA 125 levels are determined. Whether CA 125 has a specific biologic role in heart failure deserves further studies.

Background : Because of donor shortage, heart transplantation (HTx) as therapy for end-stage heart failure is limited by a mortality rate of 25% on waiting lists, and lists are steadily increasing. Aim : To analyse whether an intensive medical therapeutic regimen for heart failure (based on the results of frequent haemodynamic studies) can delay or even prevent the need for HTx. Methods : Data analysis of 517 patients who were referred to our institution for HTx from 1984 to 1996 is presented. Characteristics and management of 359 non-emergency, New York Heart Association (NYHA) III or IV heart transplant candidates, without contraindications (and with sufficient compliance) are described. All candidates receiving conventional therapy with ACE inhibitors, digitalis and diuretics at entry were evaluated. Drug therapy was intensified as follows: a further reduction of preload; a further reduction of afterload; individualised diuresis; and amiodarone therapy. Results : Under this regimen, clinical and haemodynamic parameters improved in many patients. Only 95 patients (26%) were primary non-responders to intensified medical therapy and had to be listed for HTx early (during the first year of follow-up). Actuarial survival rates of the early listed versus the early responding HTx candidates, at 1 and 5 years, were 68.3%/87% and 41%/59%, respectively (p=0.02). An additional benefit of co-therapy with amiodarone and calcium antagonists was found. The most important mode of cardiac death was sudden (32% at 5 years), whereas mortality due to pump failure was much lower (13% at 5 years). Only 38 patients (16%):had to be listed for HTx in further follow-up. Conclusions : Intensive medical therapy in heart transplant candidates may be an alternative to immediate HTx, especially in times of donor shortage or in countries without a transplantation program. Responders to therapy showed a similar or even better prognosis than HTx patients. This conservative approach may allow available donor hearts to be saved for those patients most needing a transplant.

Background A novel method to estimate cardiac volumes based on impedance measurements using the leads of a resynchronization device has been developed. This study investigated the method in patients with ischemic cardiomyopathy and documented wall motion abnormalities. Method and Results Fifteen postinfarction patients (age 68 ± 8 years, ejection fraction 27 ± 5%) with symptomatic heart failure and ≥1 akinetic or dyskinetic segment were included. During the implantation of a cardiac resynchronization therapy (CRT) device, acute impedance curves were recorded along with stroke volume determined by the arterial pulse contour method. In an overdrive protocol, the impedance parameter “stroke impedance” decreased in significant correlation with stroke volume in all patients. The median correlation coefficient between stroke volume and stroke impedance was 0.83 (interquartile range 0.70–0.89). Furthermore, the atrioventricular delay was optimized based on impedance and reference stroke volume. After optimization by the impedance method, it differed by 18 ± 15 ms from the figure after optimization by the invasive reference. Compared with a standard atrioventricular delay of 120 ms, stroke volume was improved by 8.6 ± 9.8% with the use of invasive optimization and by 6.4 ± 10.8% with the use of impedance-based optimization. Conclusions In CRT patients with chronic infarction and wall motion abnormalities, impedance is a valid parameter to estimate stroke volume and to guide optimization of CRT timing.

Aim To investigate whether diagnostic data from implanted cardiac resynchronization therapy defibrillators (CRT-Ds) retrieved automatically at 24 h intervals via a Home Monitoring function can enable dynamic prediction of cardiovascular hospitalization and death. Methods and results Three hundred and seventy-seven heart failure patients received CRT-Ds with Home Monitoring option. Data on all deaths and hospitalizations due to cardiovascular reasons and Home Monitoring data were collected prospectively during 1-year follow-up to develop a predictive algorithm with a predefined specificity of 99.5%. Seven parameters were included in the algorithm: mean heart rate over 24 h, heart rate at rest, patient activity, frequency of ventricular extrasystoles, atrial–atrial intervals (heart rate variability), right ventricular pacing impedance, and painless shock impedance. The algorithm was developed using a 25-day monitoring window ending 3 days before hospitalization or death. While the retrospective sensitivities of the individual parameters ranged from 23.6 to 50.0%, the combination of all parameters was 65.4% sensitive in detecting cardiovascular hospitalizations and deaths with 99.5% specificity (corresponding to 1.83 false-positive detections per patient-year of follow-up). The estimated relative risk of an event was 7.15-fold higher after a positive predictor finding than after a negative predictor finding. Conclusion We developed an automated algorithm for dynamic prediction of cardiovascular events in patients treated with CRT-D devices capable of daily transmission of their diagnostic data via Home Monitoring. This tool may increase patients’ quality of life and reduce morbidity, mortality, and health economic burden, it now warrants prospective studies. ClinicalTrials.gov NCT00376116.

Introduction: Left bundle brunch block (LBBB) and right ventricular stimulation (RVS) may be associated with asynchrony and heart failure. Differences between these two entities and their response to cardiac resynchronization therapy (CRT) are not well defined. Methods: Patients receiving CRT from 1999 to 2006 were analyzed for cardiac events and prognosis separated between primary implants for LBBB (n = 221) and upgrades from RVS (n = 107). A subgroup of 105 patients (LBBB = 69; RVS = 36) was studied in more detail (New York Heart Association [NYHA], quality of life, brain natriuretic peptide, peakVO2, left ventricular ejection fraction [LVEF], wedge pressure, Cardiac Index, QRS, left-right preejection period using pulsed wave doppler, septum-lateral wall motion delay using tissue doppler imaging) at baseline and after 1 year. Results: Age (68.4 ± 11 years vs 68.7 ± 15 years, n. s.), NYHA class (3.1 vs 3.1, n. s.), LVEF (26.4 vs 28.1, n. s.), and clinical parameters were comparable between LBBB and RVS. The latter group consisted of more patients with chronic atrial fibrillation (14% vs 37%, P = 0.03). After 1 year, NYHA class (−0.8 ± 0.8 vs −0.6 ± 0.8, n. s.), LVEF (+13.7 ± 14% vs +8.7 ± 10%, n. s.), and clinical parameters improved similarly. After a median follow-up of 2.33 ± 1.8 years in the LBBB versus 2.43 ± 1.9 years in the RVS group, there was no difference in long-term prognosis or cardiac events in the total cohort (5-year event rate, 53% vs 55%, P = n. s.). Conclusion: Upgrade patients showed similar baseline parameters and response to CRT as to primary implants. No difference in events or long-term prognosis could be observed. (PACE 2008; 31:1265‐1271)

Aims Chronotropic incompetence (CI) in patients with congestive heart failure (CHF) develops frequently under b-blocker and amiodarone therapy. It can be corrected by pacing. We performed a randomized study to test whether pacing is beneficial in CHF patients with CI. Methods and results Congestive heart failure patients under combined beta-blocker and amiodarone therapy (n ¼ 77) were randomly assigned to inhibited pacing (INH; basal rate 40 bpm/hysteresis 30 bpm; n ¼ 38) or to DDDR pacing with optimized atrioventricular delay (OPT; stimulation rate 65–120 bpm, n ¼ 39). Groups showed similar baseline values in NYHA class, heart rate, and ejection fraction (EF) and were followed up to 10 years. The resting and mean 24 h heart rate after 1 year decreased by 22.6/25 bpm in INH, but increased by þ3.6/þ6.0 bpm in the OPT group (P , 0.001). The QRS interval after 1 year increased by 12 + 23 ms in the INH group, but þ32 + 36 ms in the OPT group (P , 0.01). Patients with INH developed a greater left ventricular EF (LVEF) when compared with OPT patients (þ10.6 + 8 vs. þ2 + 10%, respectively; P ¼ 0.04). Changes in LVEF were negatively correlated with heart rate, but not with QRS width changes. Prognosis and the event rate were better in the INH group. Conclusion In the long-term follow-up, single-site ventricular pacing in patients with CHF and low LVEF is associated with significant clinical events and a poor prognosis.

Background: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM. Aims: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD). Methods: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing. Results: Three different LMNA mutations (Arg377His, c.1397delA, c.424_425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure. Conclusions: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as “presymptomatic” because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.

A 66-year-old patient with terminal heart insufficiency (NYHA IV) received maximum medical therapy, but was also in need of an implantable-cardioverter-defibrillator (ICD). The ICD functioned flawlessly for the whole duration of implantation. It reverted several ventricular tachycardias with anti-tachycardial pacing alone, whereas some needed cardioversion as well. The patient died on the fourth day of hospitalization for a routine check of his ICD. The post-mortem examination revealed, that the ICD was deactivated and that the data had been erased after the patient's death. By reading off the raw data still stored within the ICD, the erased information could be restored. The stored EGMs showed traces of old ICD interventions as well as a permanent deactivation provoked by exposition to a magnetic field just hours before the patient's death. The problem of archiving and documenting the volatile electronic data inside the ICD is discussed. The need of a full autopsy after telemetric reading of the ICD data, including the explantation of the ICD aggregate and electrodes, as a means of quality assurance and under forensic aspects is emphasized.

Carvedilol and at least in some studies, amiodarone have been shown to improve symptoms and prognosis of patients with heart failure. There are no reports on the outcome of combined treatment with both drugs on top of angiotensin-converting enzyme inhibitors (ACEI), diuretics and digitalis.In 109 patients with severe heart failure submitted for heart transplantation at one single center between the years 1996 and 1998 [left ventricular ejection fraction (LVEF) 24.6+/-11%, 85% males, 52% idiopathic dilated cardiomyopathy (DCM), mean observation time 1. 9+/-0.4 years] a therapy with low-dose amiodarone (1000 mg/week) plus titrated doses of carvedilol (target 50 mg/day) was instituted. In addition, patients received a prophylactic dual chamber pacemaker (PM) in order to protect from bradycardia and for continuous holter monitoring. The devices were programmed in back-up mode with a basal rate of 40 i.p.m. with a hysteresis of 25%. Significantly, more patients were in sinus rhythm after 1 year than at study entry (85% vs. 63%, P0.01). In 47 patients, under therapy over at least 1 year, the resting heart rate fell from 90+/-19 to 59+/-5 b.p.m. (P0.001). Ventricular premature contractions in 24-h holter ECGs were suppressed from 1.0+/-3 to 0.1+/-0.3%/24 h (P167 b.p.m. detected by the pacemaker (1.2+/-2.8 episodes/patient/3 months vs. 0.3+/-0.8 episodes/patient/3 months after 1 year (P0.01). The LVEF increased from 26+/-10 to 39+/-13% (P0.001). NYHA class improved from 3. 17+/-0.3 to 1.8+/-0.6 (P0.001) as well as right heart catheterization data. From the total cohort, seven patients (6%) developed symptomatic documented bradycardic rhythm disturbances requiring reprogramming of their pacemakers to DDD(R)/VVI(R) mode with higher basic rates. Two of these patients developed AV block, four sinu-atrial blocks or sinus bradycardia and one patient had bradycardic atrial fibrillation. During the observation period five patients died (3 sudden, 1 due to heart failure and 1 due to mesenteric infarction). Two patients had undergone heart transplants. The 1-year survival rate (Kaplan-Meier) without transplantation was 89%. Compared to historic control patients with amiodarone only (n=154) or without either agent (n=283) this rate was 64 and 57% (P0.01).Heart failure patients benefit from a combined therapy with carvedilol and amiodarone resulting in a markedly improved NYHA stage, an increase in LV ejection fraction, a stabilization of sinus rhythm, a significant reduction in heart rate, a delay of electrical signal conduction and a suppression of ventricular ectopies. Approximately 6% of patients under such a regime became pacemaker-dependent in the first year. Compared to historic controls prognosis was better and the need for heart transplantation was lower. The exact role of either agent in combination or alone should be clarified in larger randomized studies.

We detected markedly decreased cyclosporin blood levels in a heart-transplanted patient after the gastrointestinal lipase inhibitor orlistat was accidentally added to the treatment program to control for his obesity. Therefore, we determined cyclosporin plasma concentration time kinetics with and without orlistat reexposition in this patient.Plasma concentration time kinetics of whole blood cyclosporin levels in an obese heart-transplant patient were measured using a standard monoclonal fluorescence polarisation immunoassay. Results were obtained in hourly intervals up to 12 h without and with co-therapy of 3 x 120 mg orlistat (Xenical, Roche Ltd., Switzerland). The orlistat re-exposition was started the day before taking blood samples.Cyclosporin trough levels (98 ng/ml vs 52 ng/ml), maximum concentrations (532 ng/ml vs 74 ng/ml) and the area under the blood drug concentration-time curve (2832 ng h ml-1 vs 700 ng h ml-1) were greatly reduced with orlistat.Orlistat markedly decreased blood cyclosporin concentrations, possibly due to an interference with its absorption in the small intestine. To avoid potential dangerous under-immunosuppression, orlistat should not be used in patients taking cyclosporin.

Due to the shortage of donor organs there is a long waiting time for heart transplantation. As a consequence, a high mortality rate on the waiting list diminishes the potential benefit of the procedure. Tailored medical therapy optimized according to the individual patients demands was introduced to select responding HTx candidates for continued management without transplantation. The development of modes of death over time (heart failure, sudden arrhythmic) in this population is unknown.In 434 elective candidates for heart transplantation, submitted to our institution in the years 1984-1997 (50% coronary artery disease, mean age 51.6 +/- 12 years, 86% males) medical therapy was adjusted according to the results of repeated right heart catherizations. Adjuncts to conventional therapy with ACE inhibitors, digitalis and diuretics were amiodarone, beta-blockers, spironolactone, oral anticogulants, molsidomine or nitrates. Only patients not responding to these measures were processed to HTx. Clinical events (death, mode of death, HTx, resuscitation) were noted and analyzed by the Kaplan-Meier method and related to patients characteristics by multivariance analysis.During the mean follow-up of 2.36 +/- 2.4 years only 113 patients (25%) received a donor heart. One hundred-sixteen patients (26%) died without transplantation. Eighty-three (72%) of the deaths were sudden, 24 (20%) due to progression of heart failure and 9 (8%) due to other reasons. A shift from heart failure to sudden death was observed. Including 8 successful resuscitations due to documented VT/VF, there is a 20% risk of having a major arrhythmic event during the first two years of observation. Long-term (1 year) medical responders had better hemodynamics at entry. Patients who died suddenly had similar clinical and hemodynamic data at entry than patients who needed an early transplant, but were in a comparable NYHA stage before death than long-term medical responders (2.15 +/- 0.8 vs 1.82 +/- 0.6, NS). Patients dying suddenly had significant more ventricular premature beats (1.6 +/- 2.9%/24 hours vs 1.06 +/- 2.8%/24 hours, p.01) and complex ventricular arrhythmias (7.3 +/- 2.7/24 hours vs 1.98 +/- 5.6/24 hours, p.01) than long-term responders. Seventy-five percent of all sudden death occurred during the first 2 observation years.The rate of heart failure death in elective candidates for heart transplantation under optimized medical therapy is low when patients are followed closely and transplant can be done rapidly after deterioration is recognized. Sudden death represents the highest risk for most patients. This event occurred predominantly in stable patients under tailored medical therapy without indication for HTx at that time. Our results strongly demand strategies for risk stratification and the investigation of prophylactic measures in this population.

This report describes the reversal of a cardiac resynchronization therapy non-responder status in a patient with a surgically placed left ventricular lead by the use of a newly available active fixation coronary sinus lead.

Cardiac Resynchronization therapy (CRT) using coronary sinus (CS) leads is an established method for the therapy of congestive heart failure (CHF) in the case of inter- and intraventricular conduction delays. However implantation of CS leads is somewhat challenging due to a high number of peri- or postoperative dislocations at a rate of about 10%. The retained guidewire technique has been proposed for the implantation of coronary sinus leads for stabilization in case of repetitive intraoperative dislocations. This report describes CS lead and guidewire fracture 2 years after such an implant.

It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol-rich low-density lipoprotein (LDL) particles. In a prospective study of 25 patients with colorectal carcinoma, we measured intraindividual shifts in serum cholesterol levels after surgery, and the expression of LDL-receptor mRNA in surgically removed specimens. A significant rise in plasma cholesterol levels was observed in patients 3 and 12 months after curative surgery, but not after non-curative surgery. In human colon carcinoma tissues LDL receptor mRNA expression, as determined by competitive reverse-transcriptase-polymerase-chain reaction, was found to be significantly increased when compared to tissues from the tumour-free margin (median values, 1.2 x 10(6) vs. 2.0 x 10(5) molecules/micrograms total cellular RNA, respectively, n = 17). The extent of LDL-receptor mRNA expression positively correlated to the percentage rise of plasma cholesterol levels 3 months (n = 7, r = 0.8763) and 12 months (n = 6, r = 0.9181) after curative surgery. This finding provides in vivo evidence that the tumour tissue itself contributes to decreased plasma cholesterol levels in patients suffering from colorectal carcinomas. It supports the hypothesis that low cholesterol levels in cancer patients are a consequence, and not the cause, of the malignancy.

This editorial refers to ‘Midterm experience with implantable cardioverter-defibrillators in children and young adults’ by A. Celiker et al ., on page 1732 The article by Celiker et al .1 adds a further experience to a very challenging clinical problem: the primary and secondary prevention of sudden cardiac death in children and adolescents with implantable cardioverter defibrillators (ICDs). As no randomized ICD trials in this population are available, treatment protocols have to be extrapolated from the results of ICD studies in adults. However, children differ from adults in many ways and make this therapy … *Corresponding author. Tel: +49 407 280 5158, Email: herbert_naegele{at}yahoo.de

Twenty-two patients with acute myeloblastic leukaemia (AML) were studied to investigate disease-associated changes in lipid metabolism. Lipoprotein (a) [Lp(a)] levels were found to be elevated at the time of diagnosis (median 23 mg/dl; 41% of patient group had levels greater than 25 mg/dl) and diminished after successful chemotherapeutic treatment in 9 of 10 cases, with a maximum decrease from 56 to 10 mg/dl. In contrast, reduced levels of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) (medians 137, 87 and 20 mg/dl, respectively) were observed at the time of diagnosis. Cholesterol and HDL levels increased in all 10 and LDL in 9 cases in which complete remission was achieved. These data suggest that the catabolism of LDL-cholesterol might be even more enhanced than assumed to date. Furthermore, it indicates that the Lp(a) level in acute myeloblastic leukaemia is influenced either directly or indirectly by the leukaemic blasts.

There is good epidemiologic evidence that hypertension is associated with a high risk of cardiovascular disease. However, primary intervention trials have failed to demonstrate that a reduction in blood pressure in hypertensive patients reduces morbidity and mortality from cardiac events. Since various antihypertensive drugs adversely affect lipoprotein metabolism, these drugs may increase associated coronary risk and offset the beneficial effects of lowering blood pressure. This article reviews the effects of various antihypertensive drugs on plasma lipids, lipoproteins, and apolipoproteins. They can be summarized as follows: thiazide-type diuretics cause a marked elevation of plasma triglycerides and very low-density lipoprotein (VLDL) and minor increases in total cholesterol and low-density lipoprotein (LDL), but have little effects on high-density lipoprotein (HDL). The nonselective beta-blockers do not significantly affect total cholesterol and LDL, but increase total triglycerides and VLDL and decrease HDL. The changes in plasma lipids and lipoproteins caused by cardioselective beta-blockers and beta-blockers with intrinsic sympathomimetic activity are qualitatively similar but less pronounced. Calcium antagonists and angiotensin-converting enzyme inhibitors appear to have no significant effects on plasma lipids. alpha 1-Inhibitors reduce total triglycerides, total cholesterol, VLDL, and LDL and increase HDL. The possible mechanisms by which antihypertensive drugs affect cellular lipid metabolism (e.g., LDL receptor, lipid synthesis, lipoprotein lipase, lecithin cholesteryl acyltransferase, acylcholesteryl acyltransferase, and cholesteryl ester hydrolase) are described. The clinical significance of changes in blood lipids and cellular lipid metabolism caused by antihypertensive drugs is not yet totally clear. Nevertheless, before antihypertensive drug treatment is initiated, blood lipid levels should be measured to identify preexisting hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium antagonists and antihypertensive alpha-adrenergic and beta-adrenergic drugs may cause changes in plasma lipoprotein levels. Different mechanisms by which these antihypertensive agents effect cellular lipid metabolism have been proposed. The activity of lipoprotein lipase that determines the catabolism of very low density lipoproteins (VLDL) is decreased by the beta-blocker propranolol and increased by alpha 1-antagonists. The plasma cholesterol or low density lipoprotein (LDL) level is inversely associated with the number of LDL receptors. Catecholamines suppress the LDL receptor activity, thus leading to an increase in plasma cholesterol concentration. The calcium antagonist verapamil and the beta-blocker propranolol may increase LDL receptor activity either per se or by its antagonizing effect on the catecholamine action. The metabolism of high density lipoproteins (HDL) may be affected directly by catecholamines, which might increase HDL binding activity, thereby enhancing efflux of cholesterol from cells. Catecholamines inhibit cholesterol biosynthesis in extrahepatic cells. The effects are mediated by alpha 2- and beta 2-adrenergic receptors. Accordingly, the alpha 2-agonists clonidine and alpha-methyldopa mimicked and propranolol opposed the catecholamine action. In contrast, the alpha 1 antagonists indoramin, prazosin, and urapidil had no effect on cholesterol synthesis. The results provide evidence that calcium antagonists and various antihypertensive drugs, depending upon their action on beta- or alpha-adrenergic receptors, affect lipid metabolism differently. The metabolic effect may play a role in atherogenesis and may be of clinical importance when antihypertensive treatment is considered.