Implantable loop recorder in unexplained syncope: classification, mechanism, transient loss of consciousness and role of major depressive disorder in patients with and without structural heart disease.

OBJECTIVE: To stratify mechanisms and predictors of unexplained syncope documented by an implantable loop recorder (ILR) in patients with and without structural heart disease (SHD). DESIGN AND SETTING: Prospective study in consecutive patients of a university cardiac centre. PATIENTS AND METHODS: An ILR was implanted in 70 patients (34 male/36 female, aged 55 (17) years) in whom syncope remained unexplained after thorough testing. SHD was present in 33 patients (ischaemic cardiomyopathy in 16, dilated cardiomyopathy in 9 and hypertrophic cardiomyopathy in 8) and absent in 37 patients (mean (SD) left ventricular ejection fraction 46 (4)% vs 61 (7)%, respectively). RESULTS: A syncopal recurrence occurred during 16 (8) months in 30 patients (91%) with SHD and in 30 patients (81%) without SHD. Fifteen patients (45%) versus 19 patients (51%), respectively, had an ILR-documented arrhythmia at the time of recurrence which led to specific treatment. The remaining 15 patients (45%) with SHD and 11 patients (30%) without SHD had normal sinus rhythm at the time of the recurrence. On stepwise multivariate analysis only major depressive disorder was predictive for early recurrence during ILR follow-up (p = 0.01, hazard ratio = 3.35, 95% CI 1.1 to 7.1). Fifty seven per cent of patients with major depressive disorder had sinus rhythm during recurrence compared with 31% of patients without the disorder (p = 0.01). Conversely, no patient with major depressive disorder had asystole compared with 33% without (p<0.001). CONCLUSIONS: The presence of SHD has little predictive value for the occurrence or type of arrhythmia in patients with unexplained syncope. Patients with major depressive disorder are prone to early recurrence of symptoms and have no evidence of arrhythmia in most cases. The ILR leads to specific treatment in half of all patients.

Activity-based proteomics: enzymatic activity profiling in complex proteomes.

In the postgenomic era new technologies are emerging for global analysis of protein function. The introduction of active site-directed chemical probes for enzymatic activity profiling in complex mixtures, known as activity-based proteomics has greatly accelerated functional annotation of proteins. Here we review probe design for different enzyme classes including serine hydrolases, cysteine proteases, tyrosine phosphatases, glycosidases, and others. These probes are usually detected by their fluorescent, radioactive or affinity tags and their protein targets are analyzed using established proteomics techniques. Recent developments, such as the design of probes for in vivo analysis of proteomes, as well as microarray technologies for higher throughput screenings of protein specificity and the application of activity-based probes for drug screening are highlighted. We focus on biological applications of activity-based probes for target and inhibitor discovery and discuss challenges for future development of this field.

Prolonged asystole provoked by head-up tilt testing.

We describe a patient with a history of neurocardiogenic syncopes who had a positive headup tilt test that resulted in an lasting asystole lasting 34 seconds. However, the previously carried out Schellong test with a 30-min phase of standing showed a normal result. The patient showed typical orthostatic symptoms while tilted at the angle of 75 degrees. Shortly before asystole occurred, heart rate variability showed high frequency bands, indicating vagal stimulation. The pathophysiology of neurocardiogenic syncope (NCS) in context with heart rate variability is discussed. This patient was successfully treated with propranolol. This case shows the utility of a provocative head-up tilt test in establishing the diagnosis of NCS. If the Schellong test is normal, still further examination by tilt-table test is indispensable.

Bradycardia and sinus arrest during percutaneous ethanol injection therapy for hepatocellular carcinoma.

BACKGROUND: Percutaneous ethanol injection (PEI) is an established method in the treatment of hepatocellular carcinoma (HCC) and considered a safe procedure, with severe complications occurring rarely. Cardiac arrhythmias have not been reported to date. Aim of the study was to investigate the occurrence of dysrhythmias during PEI. PATIENTS AND METHODS: Twenty-six consecutive patients with inoperable HCC were included. During ultrasound-guided PEI with 95% ethanol, electrocardiogram (ECG) monitoring was performed before starting and continuously during PEI. RESULTS: During PEI a significant reduction in mean heart rate (> 20%) was seen in 15 of 26 (58%) patients. In 11 of 26 patients (42%) occurrence of sinuatrial block (SAB) or atrioventricular block (AVB) was observed after a median time of 9 s (range 4-50) from the start of PEI with a median length of 24 s (range 12-480). Clinical symptoms were seen in two patients, including episodes of unconsciousness, seizure-like symptoms in both and a respiratory arrest during PEI in one patient, requiring mechanical ventilation. In four of 12 patients with repeat interventions, dysrhythmias were reproducible during monthly performed procedures. There was a significant association between the occurrence of SAB or AVB and the amount of instilled alcohol (P = 0.03) and post-PEI serum ethanol levels (P = 0.03). CONCLUSIONS: Bradycardia and block formation occur frequently during PEI. These symptoms could be explained by a vasovagal reaction and/or the direct effect of ethanol on the sinus node or the right atrial conduction system. Ethanol dose is an important factor for the occurrence of SAB/AVB. ECG-monitoring seems mandatory during PEI. Prophylactic use of intravenously administered Atropine might be useful.

Unexplained syncope in patients with structural heart disease and no documented ventricular arrhythmias: value of electrophysiologically guided implantable cardioverter defibrillator therapy.

AIMS: To evaluate electrophysiologically guided implantable cardioverter defibrillator (ICD) therapy in patients with syncope, structural heart disease and no documented sustained ventricular tachycardia (sVT). METHODS AND RESULTS: Programmed ventricular stimulation (PVS) was performed in 52 patients (age 62+/-10 years): 40 patients had ischaemic and 12 patients had idiopathic dilated cardiomyopathy. On PVS sVT and ventricular fibrillation were induced in seven and four patients, respectively, and two patients spontaneously experienced symptomatic sVT. These patients received an ICD (ICD group, n=13). Non-inducible patients were left on conventional therapy (non-ICD group, n=39). During 5+/-2.8 years five ICD patients received therapies, all appropriate. There were seven non-sudden deaths and overall survival analysis revealed no significant difference. Recurrent syncope occurred in five ICD and four non-ICD patients and did not correlate well with sVT. The positive and negative predictive values of PVS for tachyarrhythmias or sudden death were 36 and 98%, respectively. CONCLUSION: Syncope per se does not necessarily herald a bad prognosis. PVS identifies high-risk patients. Induction of ventricular fibrillation with double or triple extrastimuli is of limited value. Patients with poor left ventricular function and bad clinical condition benefit most from an ICD. Syncope and sVT are not necessarily correlated during follow-up, which may merit consideration.

Survival benefit of the implantable cardioverter-defibrillator in patients on the waiting list for cardiac transplantation.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) effectively reduces sudden cardiac death in patients with severe LV dysfunction. Effect of ICD therapy on total mortality in patients on the waiting list for cardiac transplantation is still uncertain. METHODS AND RESULTS: We retrospectively analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the waiting list for cardiac transplantation between January 1992 and March 2000. Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan-Meier analysis revealed improved survival for ICD (total mortality, 13.2%) compared with non-ICD (total mortality, 25.8%) patients (log rank, P=0.03). No event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12-month sudden death rate was 20.1% (P=0.0001). Nonsudden death rates did not differ between ICD and non-ICD patients (P=0.16). A Cox proportional hazards model demonstrated that absence of an ICD was a powerful independent predictor of total mortality (P=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to 4.17) and sudden cardiac death (P<0.0001; infinite relative risk) on the waiting list. CONCLUSIONS: ICD therapy, because it prevents sudden cardiac death, significantly improves survival on the waiting list for cardiac transplantation. The present study supports the use of ICDs as a bridge to transplantation in patients who are at risk of sudden cardiac death. Prospective randomized trials are needed to evaluate the potential benefit of prophylactic ICD therapy as a bridge to transplantation in all patients on cardiac transplant waiting lists.

Spatial and temporal heterogeneity of depolarization and repolarization may complicate implantable cardioverter defibrillator therapy in Brugada syndrome.

INTRODUCTION: Dynamic variations in electrophysiologic phenomena inherent to the Brugada syndrome may complicate therapy with implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: Between 1997 and 1999, 3 of 7 patients with Brugada syndrome (1 man and 2 women, mean age 42 years) received an ICD. During follow-up, 2 patients experienced multiple inappropriate shocks. Simultaneously with dynamic changes in the surface ECG, endocardial ECGs revealed a dynamic decrease in the right ventricular R wave and an increase in the corresponding T wave, resulting in T wave oversensing. With ajmaline administration, these dynamic changes in endocardial signals were reproducible at different right ventricular sites, whereas left ventricular epicardial signals remained stable. Incremental AAI pacing and exercise stress testing resulted in similar changes in right ventricular endocardial signals, but normalization of the surface ECG apart from progressively increasing S waves in leads II, V5, and V6. Orciprenaline administration had no effect on ECG phenomena. After implantation of a left ventricular epicardial lead for sensing and pacing, no inappropriate tachycardia detection recurred. CONCLUSION: These findings demonstrate that, in Brugada syndrome, spontaneous or ajmaline-induced changes in the surface ECG may be paralleled by significant variations in the right ventricular endocardial electrogram that may result in ICD malfunction. Implantation of a left ventricular epicardial lead for sensing and pacing may be the ultimate successful approach in certain patients. To assure proper ICD function, ajmaline testing during ICD implantation appears to be helpful.

Heart rate dynamics at the onset of ventricular tachyarrhythmias as retrieved from implantable cardioverter-defibrillators in patients with coronary artery disease.

BACKGROUND: The recent availability of implantable cardioverter-defibrillators (ICDs) that record 1024 R-R intervals preceding a ventricular tachyarrhythmia (VTA) provides a unique opportunity to analyze heart rate variability (HRV) before the onset of VTA. METHODS AND RESULTS: Fifty-eight post-myocardial infarction patients with an implanted ICD for recurrent VTA provided 2 sets of 98 heart rate recordings in sinus rhythm: (1) before a VTA and (2) during control conditions. Three subgroups were considered according to the antiarrhythmic (AA) drug regimen. A state of sympathoexcitation was suggested by the significant reduction in HRV before VTA onset compared with control conditions. beta-Blockers and dl-sotalol enhanced HRV in control recordings; nevertheless, HRV declined before VTA independent of AA drugs. A gradual increase in heart rate and decrease in sinus arrhythmia at VTA onset were specific findings of patients who received dl-sotalol. CONCLUSIONS: The peculiar heart rate dynamics observed before VTA onset are suggestive of a state of sympathoexcitation that is independent of AA drugs.

Local anaesthesia versus general anaesthesia for cardioverter-defibrillator implantation.

AIMS: Cardioverter-defibrillators are conventionally implanted under general anaesthesia. However, implantation under conscious sedation is being increasingly used. It has been shown that cardioverter-defibrillators can be implanted in a more pacemaker-like approach: under local anaesthesia for the surgical procedure, and with mild sedation for defibrillation threshold testing only. The aim of the present study was to compare local and general anaesthesia in defibrillation threshold testing and implantation of cardioverter-defibrillators. METHODS AND RESULTS: Forty patients were assigned to two groups: in the first 20 consecutive patients the cardioverter-defibrillator was implanted under general anaesthesia (GA), and in the subsequent 20 patients under local anaesthesia (LA). There was no significant difference between the two groups in regard of age, body weight, underlying disease, left ventricular ejection fraction, and NYHA classification. The defibrillation threshold was 13.7 +/- 5.5 J under local anaesthesia versus 10.7 +/- 4.7 J under general anaesthesia (n.s.). For defibrillation threshold testing 7.9 +/- 3.6 shocks had to be applied in patients under general anaesthesia versus 6.2 +/- 1.3 shocks under local anaesthesia (n.s.). Mean heart rate, arterial oxygen saturation and mean arterial blood pressure remained stable throughout defibrillation threshold testing, irrespective of the type of anaesthesia used. The duration of the surgical procedure was 62 +/- 16 min under GA and 60 +/- 14 min under LA (n.s.), however, the entire implantation procedure was significantly longer in patients under general anaesthesia than in those under local anaesthesia (124 +/- 24 min and 97 +/- 22 min, respectively, p < 0.005). There were no complications in either group and the procedure was well tolerated. With the use of local anaesthesia the cost of anaesthesia were reduced by 72%. CONCLUSION: Local anaesthesia in combination with mild sedation is as safe and well tolerated as general anaesthesia in cardioverter-defibrillator implantation. Lidocaine used for local anaesthesia does not adversely affect the defibrillation threshold. Device implantation in a pacemaker-like approach results in a significant reduction in total procedure time and costs, and facilitates scheduling of the procedure.

The implantable cardioverter defibrillator as a "bridge to transplant": a viable clinical strategy?

Heart transplantation is an accepted therapeutic option for patients with end-stage heart disease. However, because the availability of heart donors fails to keep pace with the growing demand, increasing numbers of potential recipients are placed on the waiting list, resulting in longer waiting times. About 20% of patients die while awaiting heart transplantation. The majority die from progressive pump failure (46%), whereas about 30% of all deaths occur suddenly. Monitored terminal cardiac electrical activity in patients dying while awaiting transplantation reveals that bradyarrhythmias and/or electromechanical dissociation are involved in 68% of cases and ventricular tachyarrhythmias in 32% of cases. Patients with a history of aborted cardiac arrest are at highest risk for recurrent malignant arrhythmias. The implantable cardioverter defibrillator (ICD) is the most effective therapy for preventing sudden cardiac death from ventricular tachyarrhythmias. Pooled data from a total of 75 sudden death survivors listed for cardiac transplantation demonstrate that ICD therapy can be applied with low mortality, low morbidity, and high efficacy, with up to 94% of the patients receiving appropriate shocks during the waiting period. However, there is considerable concern that this early survival benefit conferred by the ICD may be nullified by the competing risk of death due to terminal pump failure, as the waiting list and waiting time to transplantation lengthens. In advanced heart failure, risk stratification for sudden tachyarrhythmic death is only of limited value. Therefore, although sudden tachyarrhythmic death appears to constitute only a minor fraction of total cardiac death in patients awaiting heart transplantation, prophylactic ICD implantation as on electronic bridge to transplant may be considered. To define conclusively the role of prophylactic ICD therapy in this setting, prospective randomized studies are needed.

Recurrent cardiac tamponade as first manifestation of gastric cancer.

Malignant pericardial effusion is an uncommon disorder and is usually caused by far advanced lung cancer, breast cancer, lymphoma and leukaemia. Pericardial effusion in recurrent gastric cancer has been reported in only three patients. We report the case of a 53-year-old male with sudden onset of dyspnoea, pericardial effusion and cardiac tamponade and the unexpected and the asymptomatic concurrence of gastric cancer. Recurrent haemorrhagic pericardial effusion with physical signs of cardiac tamponade as the initial and only clinical manifestation of gastric cancer has not been described previously.

Transjugular intrahepatic portosystemic shunt and cardiac arrhythmias.

The approach to the liver for a transjugular intrahepatic porto-systemic shunt (TIPS) is through the venous system. Because catheter and guidewire system traverses the heart, cardiac arrhythmias may be expected during the procedure. We have prospectively investigated the incidence of such dysrhythmias during TIPS implantation. Twelve consecutive patients, 4 women and 8 men aged 26 to 75 years (mean, 58 +/- 13 years), were studied. Before and on the day of TIPS implantation, a 24-hour Holter recording was performed. Transjugular intrahepatic portosystemic shunt implantation was performed under local anesthesia (lidocaine) and sedoanalgesia (midazolam and fentanyl). None of the patients had concomitant cardiac disease or electrolyte disturbances. In all patients except one, TIPS implantation was successful without any technical complications. A mean of 43 +/- 5.3 hours of Holter recording was performed before and after TIPS implantation. All recordings obtained during this control period were considered inconspicuous. The mean heart rate was significantly higher during the implantation procedure of 136 +/- 37 minutes' duration (83 +/- 20 beats per minute vs 70 +/- 19 beats per minute; p < 0.01). Nine of the 12 patients experienced episodes of nonsustained supraventricular tachycardias, and one patient had two sustained supraventricular tachycardias. Frequent episodes of nonsustained ventricular tachycardias developed in 75% of the patients. It seems clear that TIPS implantation is frequently associated with supraventricular and ventricular tachyarrhythmias even in patients with apparently good cardiac condition at the beginning of the procedure. Thus close cardiac monitoring with resuscitation equipment immediately available throughout the procedure is mandatory.

Predictors of outcome in patients with implantable cardioverter defibrillators.

UNLABELLED: This study determined the impact of clinical characteristics on shock occurrence and survival in patients with implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: During a follow-up of 27 +/- 18 months, the actuarial incidence of appropriate shocks in 200 consecutive patients was 18, 36 and 72% at 1, 3, and 5 years, respectively. Coronary artery disease was the only significant predictor for shock occurrence (relative risk 1.32, p = 0.03). The actuarial incidence of total mortality was 10, 17 and 33% at 1, 3, and 5 years, respectively. The most powerful predictors for total mortality were: New York Heart Association functional class (NYHA) III (relative risk 4.8, p = 0.001) and a history of congestive cardiac failure (relative risk 3.6, p = 0.01). CONCLUSION: During long-term follow-up, the majority of patients receive appropriate shocks. No strong predictors for shock occurrence can be identified from the data analyzed. A history of congestive cardiac failure and the NYHA III are the most powerful predictors for total mortality. These clinical factors may provide valuable criteria to identify patients who will benefit from the implantation of ICD.

The effect of weight reduction on the surface electrocardiogram: a prospective trial in obese children and adolescents.

OBJECTIVE: Controversial data exist on the effect of obesity and weight reduction on surface electrocardiographic parameters. The purpose of this study was to analyze electrocardiograms of obese children in the course of short-term weight reduction. DESIGN: Prospective trial over a period of three weeks with a conventional low calorie diet containing a mean of 525 +/- 109 kcal. SUBJECTS: Thirty-three children, 17 girls and 16 boys with a mean age of 12.2 +/- 1.7 y and an overweight of 25.4-102%, mean 54.2 +/- 15.6%. MEASUREMENTS: Before the onset of therapy and thereafter, body weight, blood chemistry and 12 lead electrocardiographic evaluations were performed. RESULTS: The mean loss of body weight was 5.7 +/- 1.6 kg resulting in a mean decrease in overweight of 13.5 +/- 3.4%. Blood chemistry analyses revealed no significant changes except for cholesterol, triglycerides and uric acid. All electrocardiograms were within normal limits, however, a change in the electrocardiographic pattern was noted after weight loss. Heart rate (84 +/- 14 vs 64 +/- 11 beats per min, P < 0.0001) and QT interval (418 +/- 20 msec vs 391 +/- 22 msec, P < 0.0001) decreased and there was a tendency towards a rightward shift of the frontal plane QRS axis and a leftward shift of the horizontal plane QRS axis. CONCLUSION: Weight reduction in obese children and adolescents is associated with significant changes in the electrocardiographic pattern. These changes may only be detected by intraindividual comparison. Reduction of heart rate and shortening of the QT interval in the course of weight reduction may be of clinical significance by reducing the cardiovascular risk profile, including the risk of potentially fatal arrhythmias in obese subjects.

Effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy requirements in isolated rabbit heart.

The majority of patients with implanted cardioverter defibrillators (ICD) require antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements. This study investigated the effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and 80% successful defibrillation energy (ED50, ED80) was calculated in four phases: predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n = 6) with only Tyrode's solution infusion indicated that the preparation was stable over time. Defibrillation energy requirements significantly (p < 0.05) increased with all ARs. Low, medium, and high lidocaine concentrations increased ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively. Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%, respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158, 212, and 286%, respectively. The results of this study demonstrate a dose-dependent increase in defibrillation energy requirements by using lidocaine, diltiazem, and ajmaline. In patients with ICDs, administration of these drugs might cause a critical increase in defibrillation energy requirements, resulting in device failure.

Comparison of three cardioverter defibrillator implantation techniques: initial results with transvenous pectoral implantation.

A total of 121 patients underwent epicardial (n = 32), transvenous abdominal (n = 30), and transvenous pectoral (n = 59) ICD implants. Perioperative complications were defined as those occurring within 30 days after surgery. Hospital costs were calculated with $750 per day as a fixed charge. Duration of surgery was the time between the first skin incision and the last skin suture. Severe perioperative complications that were life-threatening or required surgical intervention occurred in the epicardial (6%) and transvenous (10%) abdominal groups, but not in the pectoral group. Perioperative mortality occurred only in the epicardial abdominal group, predominantly in patients with concomitant surgery (18%), and in 5% of patients without concomitant surgery. The duration of surgery was significantly shorter for transvenous pectoral implantation (58 +/- 15 min, P < 0.05) compared to transvenous abdominal implantation (115 +/- 38 min). Epicardial abdominal ICD implantation had the longest procedure time (154 +/- 31 min). The postimplant hospital length of stay was significantly shorter for pectoral implantation (5 +/- 3 days, P < 0.05) compared to transvenous (13 +/- 5) and epicardial (19 +/- 5) abdominal implantation. Total hospitalization costs significantly decreased in the pectoral implantation group ($4,068 +/- $2,099 for the pectoral group vs $14,887 +/- $4,415 and $9,975 +/- $3,657 for the epicardial and the transvenous abdominal group, respectively, P < 0.05). These initial results demonstrate the advantage of transvenous pectoral ICD implantation in terms of perioperative complications, procedure time, hospital length of stay, and hospitalization costs.

Implantation of a unipolar cardioverter/defibrillator system under local anaesthesia.

OBJECTIVE: To evaluate prospectively the safety and feasibility of the implantation of cardioverter/defibrillator systems under local anaesthesia. Conventionally, cardioverter/defibrillator systems are implanted under general anaesthesia. With the development of single-lead transvenous unipolar cardioverter/defibrillator systems for subpectoral implantation a pacemaker-like approach for device implantation appears applicable. METHODS: Implantation of a single-lead transvenous unipolar cardioverter/defibrillator under local anaesthesia with sedation for defibrillation threshold testing was performed in 37 consecutive patients. The presenting arrhythmia was ventricular fibrillation in 13 patients, and monomorphic ventricular tachycardia in 24 patients. A 1% lidocaine solution was used for local anaesthesia, and midazolam was applied for sedation to perform defibrillation threshold testing. Arterial blood pressure, arterial oxygen saturation and heart rate were monitored throughout the procedure. The patient's tolerance of the implantation procedure was evaluated with a standardized questionnaire. RESULTS: The unipolar transvenous cardioverter/defibrillator system was implanted successfully in all patients under local anaesthesia. During defibrillation threshold testing, sufficient sedation was achieved with 12.5 +/- 3.7 mg midazolam. For determination of the defibrillation threshold 5.9 +/- 1.4 episodes of ventricular fibrillation were induced. The mean defibrillation threshold was 13.1 +/- 5.5 J, and the mean duration of the implantation procedure was 68 +/- 30 min. Mean heart rate, mean arterial blood pressure and arterial oxygen saturation were not significantly different before and after defibrillation threshold testing. Twenty-six patients (70%) were symptom-free throughout the implantation procedure; most of the remaining patients reported minor symptoms. There were no complications, and patients were discharged 2.2 +/- 0.7 days after implantation. In 12 patients, post-implant testing of the implantable cardioverter/defibrillators was performed successfully, without sedation, 2.8 +/- 1.4 days after as an outpatient procedure. CONCLUSION: Single-lead unipolar transvenous implantable cardioverter/defibrillator systems can be safely implanted under local anaesthesia with mild sedation for defibrillation threshold testing. The procedure is well tolerated.

The impact of implantable cardioverter-defibrillators on mortality among patients on the waiting list for heart transplantation.

Implantable cardioverter-defibrillators were investigated for their impact on mortality in 228 consecutive heart transplant candidates on the waiting list for transplantation (207 patients without and 21 with implantable cardioverter-defibrillator therapy). The mortality rate in 207 patients without implantable cardioverter-defibrillator therapy was 23.2% and in 21 patients with implantable cardioverter-defibrillator therapy was 4.7%. In a Cox proportional hazards model for all 228 study patients (mortality while on the waiting list: 21.5%; transplantation rate: 54.8%), the absence of an implantable cardioverter-defibrillator was only a marginally significant predictor of mortality (p = 0.079). However, the absence of an implantable cardioverter-defibrillator was a powerful predictor of mortality for a subgroup of 134 patients with high-grade ventricular arrhythmias on Holter electrocardiography (mortality while on the waiting list: 26.1%; transplantation rate: 54.5%; p = 0.022) and for a subgroup of 58 survivors of sudden cardiac death (mortality while on the waiting list: 22.4%; transplantation rate: 56.9%; p = 0.018). Implantable cardioverter-defibrillator therapy can be strongly recommended in transplant candidates with a history of sudden cardiac death. Recommendations for an expanded, prophylactic use of implantable cardioverter-defibrillator therapy in heart transplant candidates cannot be given.

Diurnal variation of ventricular response to atrial fibrillation in patients with advanced heart failure.

Variability of ventricular rate was quantified by two measures of heart rate variability: the SD of the mean R-R interval (SDNN) and the SD of the 5-minute mean R-R interval (SDANN). In 35 patients with atrial fibrillation and advanced heart failure (left ventricular ejection fraction 20% +/- 9%, cardiac index 2.4 +/- 0.7 L/min/m2), SDNN and SDANN were compared to 13 preselected clinical and hemodynamic variables for prediction of outcome. During a 12-month follow-up period, 8 (23%) patients deteriorated clinically; 3 (9%) died, and 5 (14%) underwent heart transplantation. SDNN and SDANN correlated to the difference of the mean R-R interval between night (2 AM to 3 PM) and day (11 AM to noon) with r values of 0.62 and 0.77, respectively. From 15 preselected variables, only SDANN (chi 2 = 6.7, p = 0.01) was independently associated with survival on multivariate analysis. Dichotomized SDANN at 100 msec accurately predicted 12-month survival in 28 (80%) patients (relative risk = 9.77, p = 0.001). In conclusion, analysis of heart rate variability is useful in quantifying diurnal variation of ventricular rate in atrial fibrillation and might be useful in predicting survival in patients with advanced heart failure.