Sex Differences and Long-Term Outcome in Patients With Pacemakers.

Introduction: Evidence of sex-related differences in patients with pacemakers regarding comorbidities is insufficiently investigated. The aim of this study was to determine the relationship of cardiovascular comorbidities and sex category with properties of pacemaker implantation, pacemaker follow-up, and long-term survival. Methods: This retrospective, single-center cohort study consisted of 6,362 pacemaker-patients (39.7% female) enrolled between May 2000 and April 2015. Functional pacemaker parameters were registered at regular pacemaker controls. Survival status and cause of death were analyzed in relation to comorbidities, implanted pacing devices, and echocardiography. Survival analyses were plotted for a 10-year follow-up. Results: Patients with hypertension or hyperlipidemia had higher rates of implantations due to sick sinus syndrome (28.6 vs. 25.5% without hypertension, P < 0.001; 30.7 vs. 25.7% without hyperlipidemia, P < 0.001), while endocarditis was associated with higher rates of implantations due to AV block (46.7 vs. 33.4%, P < 0.001). Patients with valvular heart disease had higher rates of pacemaker implantation due to bradycardic atrial fibrillation (24.9 vs. 21.0% without valvular heart disease, P < 0.001). Ventricular pacing threshold increased in both sexes during the follow-up and was higher in women in the final follow-up (0.94 vs. 0.91 V in men, P = 0.002). During the 10-years follow-up, 6.1% of women and 8.6% of men underwent lead replacement (P = 0.054). Device and lead replacement rates were increased if the comorbidities coronary artery disease, heart failure, hypertension, hyperlipidemia, valvular heart disease, previous stroke/TIA, atrial arrhythmias, chronic kidney disease, or endocarditis were present. Diabetes and previous CABG increase the rates of device replacement, but not the rate of lead replacement. Severe tricuspid regurgitation after implantation of pacemaker was present in more men than women (14.4 vs. 6.1%, P < 0.001). In a multivariate COX regression, the following variables were associated with independent decrease of 10-year survival: hypertension (HR 1.34, 95% CI 1.09-1.64), chronic kidney disease (HR 1.83, 95% CI 1.53-2.19), tricuspid regurgitation after pacemaker implantation (HR 1.48, 95% CI 1.26-1.74). Survival was independently increased in female sex (HR 0.83, 95% CI 0.70-0.99) and hyperlipidemia (HR 0.81, 95% CI 0.67-0.97). Conclusions: Cardiovascular comorbidities influenced significantly pacemaker implantations and long-term outcome. Trial Registration: ClinicalTrials.gov Unique identifier: NCT03388281.

Appropriate and inappropriate therapy in patients with single- or multi-chamber implantable cardioverter-defibrillators.

BACKGROUND: Inappropriate ICD therapy is associated with adverse outcome. Previous studies indicated that patients with a cardiac resynchronization therapy-defibrillator (CRT-D) might have a lower risk for inappropriate device activations than patients with a single (VVI) or dual chamber (DDD) ICD. METHODS: All ICD recipients from a university cardiac center between 2000 - 2015 were included in this analysis. Outcome parameters were incidence of appropriate and inappropriate therapy and overall mortality. RESULTS: A total of 1471 patients were analyzed: 629 (43%) patients with a VVI-ICD, 486 (33%) patients with a DDD-ICD and 356 (24%) with a CRT-D device. During an average follow-up of 4.1 ± 3.6 years, CRT-D patients had the lowest risk to receive at least one inappropriate shock therapy (p < 0.001). Rates of appropriate (RR (Rate Ratio) = 0.45, p = 0.019) and inappropriate shock therapy (RR = 0.38, p = 0.021) were significantly lower in CRT-D patients compared to VVI-patients. CRT-D recipients had a lower rate of appropriate shock therapy (RR = 0.323, p = 0.043) compared to DDD patients, but not of inappropriate shock therapy (p = 0.371). Kaplan Meier Analysis did not reveal a significant difference in overall survival (p = 0.396). However, after adjustment for relevant confounding factors, VVI-patients had a higher risk for overall-death (HR = 1.28, p = 0.030). CONCLUSIONS: CRT-D recipients have a significantly lower rate of appropriate shock therapy and a lower rate of inappropriate shock therapy. More frequent inappropriate therapies in VVI-ICD recipients may account for their higher overall mortality.

Sex difference in inappropriate therapy and survival among 1471 implantable cardioverter-defibrillator recipients.

INTRODUCTION: To assess a potential relationship between sex and outcome in recipients of an implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: All 1471 ICD recipients between 2000 and 2015 were sex-related analyzed with the following outcome parameters: overall survival (OS), the occurrence of inappropriate and appropriate antitachycardia pacing (ATP), and shock therapy. We followed 1206 (82%) male and 265 (18%) female ICD recipients during 4.1 ± 3.6 and 4.3 ± 3.8 years, respectively, (P = .369). Kaplan-Meier analysis revealed that there was no significant difference in OS between female and male patients (P = .132). After adjustment for relevant confounding factors in a multivariate model, sex remained a nonsignificant predictor of overall mortality (hazard ratio [male] = 1.11; P = .493). Negative binomial regression analysis revealed that women received less appropriate ATP therapy (rate ratio [RR] = 0.37; P = .043), whereas rates of appropriate shock therapy (RR = 1.95; P = .369) did not differ between women and men. No significant differences were observed in the occurrence of inappropriate ATP (RR = 1.22; P = .715) and inappropriate shock therapy (RR = 0.64; P = .121). CONCLUSION: Female and male patients equally benefit from ICD therapy in terms of OS. Women are less likely to receive appropriate ATP therapy, whereas appropriate shock and inappropriate ATP and shock therapy are independent of sex.

Defensive Implantable Cardioverter-Defibrillator Programming Is Safe and Reduces Inappropriate Therapy　- Comparison of 3 Programming Strategies in 1,471 Patients.

BACKGROUND: Careful device programming is necessary to reduce inappropriate antitachycardia pacing (ATP) and shock therapy in recipients of implantable cardioverter-defibrillators (ICD). This retrospective study investigated the safety and efficacy of a therapy-reducing programming strategy in comparison with conventional strategies in consecutive ICD recipients of a university cardiac center. Methods and Results: All 1,471 ICD recipients from 2000 to 2015 were analyzed. Individual ICD programming (IND) was used from 2000 to 2005 followed by standard-three-zone programming (STD) until 2010. From 2010 to 2015 therapy-reducing long detection time programming (RED) was established. The mean follow-up was 2.4±1.6, 2.3±1.6 and 1.7±1.2 years in the IND, STD and RED groups, respectively. Switchover from IND to STD revealed a significant reduction in inappropriate ATP (P=0.024) and shock therapy (P<0.001). Further reduction of 58% (RR=0.42, 95% confidence interval [CI]: 0.17-1.04; P=0.061) in inappropriate ATP and 29% (RR=0.71, 95% CI: 0.29-1.72; P=0.452) in inappropriate shock therapy was achieved by switchover from STD to RED. Kaplan-Meier analysis revealed a significant difference in time until first inappropriate ATP and shock therapy among the 3 groups, being lowest in the RED group (P≤0.001). There was no difference in overall mortality (P=0.416). CONCLUSIONS: Defensive ICD programming with prolonged detection times is safe and significantly reduced inappropriate ICD therapies.

Pacemaker-Mediated Programmable Hypertension Control Therapy.

BACKGROUND: Many patients requiring a pacemaker have persistent hypertension with systolic blood pressures above recommended levels. We evaluated a pacemaker-based Programmable Hypertension Control (PHC) therapy that uses a sequence of variably timed shorter and longer atrioventricular intervals. METHODS AND RESULTS: Patients indicated for dual-chamber pacing with office systolic blood pressure (oSBP) >150 mm Hg despite stable medical therapy were implanted with a Moderato™ pulse generator that delivers PHC therapy. Patients were followed for 1 month (Run-In period) with conventional pacing; those with persistent oSBP >140 mm Hg were included in the study and had PHC therapy activated. The co-primary efficacy end points were changes in 24-hour ambulatory systolic blood pressure and oSBP between baseline and 3 months. Safety was assessed by tracking adverse events. Thirty-five patients met the initial inclusion criteria and underwent Moderato implantation. At 1 month, oSBP was <140 mm Hg in 7 patients who were excluded. PHC was activated in the remaining 27 patients with baseline office blood pressure 166±11/80±10 mm Hg despite an average of 3.2 antihypertensive medications. During the Run-In period, oSBP and 24-hour ambulatory systolic blood pressure decreased by 8±13 and 5±12 mm Hg (P<0.002), respectively. Compared with pre-PHC activation measurements, oSBP decreased by another 16±15 mm Hg and 24-hour ambulatory systolic blood pressure decreased by an additional 10±13 mm Hg (both P<0.01) at 3 months. No device-related serious adverse effects were noted. CONCLUSIONS: In pacemaker patients with persistent hypertension despite medical therapy, oSBP and 24-hour ambulatory systolic blood pressure are decreased by PHC therapy. Initial indications are that this therapy is a safe and promising therapy for such patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02282033.

Risk of arrhythmic death in ischemic heart disease: a prospective, controlled, observer-blind risk stratification over 10 years.

BACKGROUND: Risk of arrhythmic death is considered highest in ischemic heart disease with severe left ventricular ejection fraction (LVEF) reduction. Non-invasive testing should improve decision-making of prophylactic defibrillator (ICD) implantation. DESIGN: We enrolled 120 patients with ischemic heart disease and LVEF < 50% and 30 control subjects without ischemic heart disease and normal LVEF. An initial assessment, a second assessment after 3 years and a final follow-up comprised of pharmacological baroreflex testing (BRS), short-term spectral [low-frequency (LF) to high-frequency (HF) ratio] and long-term time-domain analysis of heart rate variability (SDNN), exercise Microvolt T-wave alternans (MTWA) and others. RESULTS: The median follow-up was 7·5 years. Resuscitated cardiac arrest and arrhythmic death due to ventricular arrhythmias ≥ 240/min was observed in 18% and 15% of patients, respectively. Cardiac death was observed in 28% of patients. The incidence of arrhythmic death and resuscitated cardiac arrest was identical in patients with ischemic heart disease with LVEF < 30% and ≥ 30%. No significant difference between subgroups with LVEF of < 30%, 30-39% and ≥ 40% was found either. MTWA, BRS, SDNN and LF to HF ratio failed to identify patients at risk of arrhythmic death in a multiple regression model. CONCLUSIONS: Ischemic heart disease patients with LVEF < 30% and ≥ 30% face the same risk of arrhythmic death. Stratification techniques fail to identify high-risk patients. Therefore, the current practice to constrain prophylactic ICDs to patients with severely reduced LVEF seems to be insufficient.

Health-related quality of life changes in patients undergoing repeated catheter ablation for atrial fibrillation.

OBJECTIVE: Pulmonary vein isolation (PVI) for paroxysmal or non-paroxysmal atrial fibrillation (AF) should increase health-related quality of life (QOL). DESIGN: Retrospective cohort study of consecutive patients scheduled for PVI. SETTING: University Medical Center. MAIN OUTCOME MEASURES: QOL was assessed using the physical (PCS) and mental (MCS) component summary scores from the SF-12v2 in patients undergoing PVI (mean 50, range 0-100, with higher scores indicating greater QOL). SF-12v2 was obtained at initial presentation (3-months) before PVI and after PVI at the end of follow-up (mean 1.7 ± 1.4 years) which included: (1) Clinical status, ECG, and 24-h ECG every 3 months, (2) trans-telephonic ECGs for 4 weeks every 3 months, or (3) continuous ECG via implanted devices. A recurrence was any atrial arrhythmia >30 s. RESULTS: Out of 229 patients (73% males; 58 ± 11 years), 72% returned SF-12v2 regarding 187 PVI procedures: 56% for 1st PVI, 48% for 2nd PVI, 71% for 3rd PVI, and 44% for 4th PVI. The mean difference between before and after PVI was 10 for PCS and 9 for MCS. History of paroxysmal or non-paroxysmal AF did not influence QOL (p = 0.724). Patients with an estimated PCS improvement ≥ 10 or an estimated MCS improvement ≥ 9 had the best outcome after repeated PVI. Success rates were 72 or 82% after 1 year compared to 20 and 22% in patients not achieving this improvement, respectively (p < 0.0001). CONCLUSION: Improvement in QOL correlates with success of AF ablation after single and repeated PVI. Assessment of QOL pre- and post-PVI can complement ECG techniques for PVI success monitoring.

Selection for atrial fibrillation ablation: Importance of diastolic function grading.

BACKGROUND: Pulmonary vein isolation (PVI) has become an accepted therapy for patients with atrial fibrillation (AF) and the indications have widened to include non-paroxysmal AF-patients. Maintenance of sinus rhythm after PVI can be adversely affected by clinical or echocardiographic parameters, which should be clearly identified. METHODS AND RESULTS: After baseline clinical and echocardiographic evaluations, PVI was performed in patients with paroxysmal or non-paroxysmal AF. The follow-up strategy after PVI included: (1) clinical follow up, 12-lead electrocardiography (ECG) and 24-h ECG every 3 months, (2) trans-telephonic ECGs twice daily and when symptomatic (over 4 weeks) every 3 months, or (3) continuous monitoring via implanted devices. A recurrence was an atrial arrhythmia lasting >30s. All 340 PVI procedures of 229 patients were analyzed. On average, 1.5 PVI procedures per patient (range, 1-6 PVI) were performed. The mean age was 58±11 years (73% male) with 109 paroxysmal and 120 non-paroxysmal AF cases. Clinical follow-up with 12-lead ECGs, 24-h ECGs, trans-telephonic ECGs, and implanted devices was complete in 100%, 63%, 51%, and 16% of cases, respectively. The overall one-year recurrence rate of 59% (range, 24-82%) was dependent on grades of diastolic function (normal - dysfunction grade III) in a multivariable analysis model. Patients with normal diastolic function had the lowest recurrence rates of 24% and 49% after 1 and 3 years of follow-up, respectively (p<0.0001). CONCLUSION: Diastolic function could serve as a simple summary predictor for AF recurrence, and would facilitate clinical decision-making in AF treatment.

Primary preventive cardioverter-defibrillator implantation (Pro-ICD) in patients awaiting heart transplantation. A prospective, randomized, controlled 12-year follow-up study.

The aim of this study was to evaluate whether short-term primary preventive cardioverter-defibrillator (ICD) implantation as bridge to heart transplantation (HTX) provides any survival benefit. Thirty-three patients awaiting HTX were randomized to either conventional therapy (control group) or primary preventive ICD implantation (ICD group). Fourteen patients had ischemic cardiomyopathy (ICM) and 19 patients had dilated cardiomyopathy (DCM). Sixteen patients were randomized to the ICD group and 17 patients were randomized to the control group. Twenty patients (61%) were transplanted after a waiting time of 10 ± 9 months. The remaining 13 patients (39%) were not transplanted because of clinical improvement (n = 5), cerebral hemorrhage (n = 3), or death (n = 5). On the waiting list, 3 ICD patients with DCM developed slow VTs without ICD intervention, two patients with ICM (6%) had fast VT terminated by the ICD, and no arrhythmic death was observed. After 11.9 years (median), 13 of 20 HTX patients (65%) and 5 of 13 non-HTX patients (38%) were alive. Survivors had a higher LVEF (22 ± 6 vs. 17 ± 4%, P = 0.0092) and a better exercise capacity (75 ± 29 vs. 57 ± 24 Watt, P = 0.0566) at baseline as compared to nonsurvivors. This study may not support the general use of primary preventive ICDs as a short-term bridge to heart transplantation.

T-wave variability for the prediction of fast ventricular arrhythmias ­ prospective, observer-blind study.

BACKGROUND: The clinical value of T-wave variability (T-var) for ventricular arrhythmia (VA) risk prediction was evaluated. METHODS AND RESULTS: Three 20-min Holter-ECG-based T-var measurements (I1 at baseline, I2 after 6.5 ± 1.6 months and I3 after 13.1 ± 2.0 months) were done in 121 patients. T-var was defined as the amplitude variability of the T-wave with the maximum of T-wave oscillation. The endpoint was a fast, potentially fatal VA (>240 beats/min). During follow-up (20 ± 4 months) 20/121 patients (55% ischemic heart disease, 15% preserved left ventricular ejection fraction [LVEF]) had fast VA terminated by ICD or external shock. Although T-var did not differ between patients with vs. without fast VA at baseline (I1: 10.7 ± 7.3 µV vs. 7.8 ± 4.1 µV, P=0.170), patients with fast VA had higher T-var compared to those without fast VA at 2 subsequent measurements (I2: 14.0 ± 6.5 µV vs. 8.2 ± 3.6 µV, P=0.030; I3: 17.0 ± 5.4 µV vs. 8.8 ± 4.6 µV, P=0.004). The increase in T-var between I1 and I2 was higher in patients with fast VA (∆T-var=7.0 ± 9.3 µV), as compared to patients without (∆T-var=0.4 ± 4.3 µV). After adjustment for LVEF in a multiple logistic regression model, the odds ratio for developing fast VA was 1.1 (P=0.056) for each 1-µV increment in T-var at I1. CONCLUSIONS: T-var is elevated in patients with fast VA, and both elevation of T-var and increase in T-var may complement LVEF in VA risk stratification.

Multiple autonomic and repolarization investigation of sudden cardiac death in dilated cardiomyopathy and controls.

BACKGROUND: Prophylactic defibrillator implantation is recommended in dilated, nonischemic heart disease and left ventricular ejection fraction of ≤0.30 to 0.35. Noninvasive testing should improve accuracy in decision making of prophylactic defibrillator implantation. METHODS AND RESULTS: We enrolled 60 patients (median age, 57 years) with dilated cardiomyopathy and left ventricular ejection fraction ≤0.50, and 30 control subjects (median age, 59 years) with left ventricular ejection fraction >0.50. The protocol included an initial assessment, a second assessment after 3 years, and a final follow-up: pharmacological baroreflex testing (baroreceptor reflex sensitivity), short-term spectral analysis of heart rate variability (low frequency/high frequency), and long-term time domain analysis (SD of all normal-to-normal R-R intervals), exercise microvolt T wave alternans, and signal-averaged ECG, and corrected QT-time. The median follow-up was 7 years. End points were cardiac death, resuscitated cardiac arrest, and arrhythmic death. Cardiac death was observed in 21 patients. Resuscitated cardiac arrest and arrhythmic death caused by ventricular tachyarrhythmias ≥240 per minute was observed in 7 and 10 patients, respectively. In the single time point analysis, microvolt T wave alternans, baroreceptor reflex sensitivity, and SD of all normal-to-normal R-R intervals at initial testing added significant information regarding cardiac death. Microvolt T wave alternans added information on resuscitated cardiac arrest or arrhythmic death at multiple time points (P<0.001). False-negative microvolt T wave alternans results were seen in 8% of patients. CONCLUSIONS: Noninvasive testing and left ventricular ejection fraction could not reliably identify patients with dilated cardiomyopathy at risk of fatal ventricular tachyarrhythmias. Therefore, the strategy to confine prophylactic implantable cardioverter-defibrillator implantation to patients with dilated cardiomyopathy and severely reduced LV function should be reconsidered.

Single, remote-magnetic catheter approach for pulmonary vein isolation in patients with paroxysmal and non-paroxysmal atrial fibrillation.

BACKGROUND: The aim of the study was to investigate the safety and efficacy of a single, remote-magnetic catheter navigation system (MNS) for pulmonary vein isolation (PVI). METHODS: A total of 107 PVI procedures in 71 patients with paroxysmal (32%), persistent (38%) and longstanding-persistent (30%) atrial fibrillation (AF) were analyzed. A wide area circumferential radiofrequency ablation PVI was performed with either an 8mm MNS (first 35 procedures) or an irrigated MNS (last 36 procedures) catheter. Electrical isolation was confirmed with circular pacing/sensing using the MNS catheter and a coronary sinus catheter. Our follow-up strategy in the first year and upon symptoms thereafter was: clinical check plus 12-lead ECG (100%) and 24 h-ECG recordings (76%) at 3 month intervals, trans-telephonic ECG (79%) twice daily and upon symptoms (4 weeks every 3 months), or ECG monitoring via implanted devices (9%). RESULTS: The mean procedure time at 1st PVI was 247±61 min, and mean fluoroscopy time was 44±18 min. The overall complication rate was 2%. Success rates did not differ at the 1st PVI regarding catheter type (p=0.931) but were dependent on history of AF: patients with paroxysmal AF had the highest success rates of 58% and 29% after 1 and 3 years of follow-up, respectively (p=0.0084). CONCLUSION: PVI with a single MNS catheter is safe and is associated with short fluoroscopy exposition. Despite a rigorous follow-up strategy success rates favorably compare with recently published data on hand-held PVI. Thus, multipolar catheters or a 2nd trans-septal puncture may not be mandatory.

Impact of accelerated ventricular tachyarrhythmias on mortality in patients with implantable cardioverter-defibrillator therapy.

BACKGROUND: Anti-tachycardia pacing (ATP) and shock delivery may induce or accelerate tachyarrhythmias in patients with implantable cardioverter-defibrillator (ICD). We investigated the incidence, triggers and impact on mortality of accelerated ventricular tachyarrhythmias. METHODS: Database analysis concerning ventricular tachyarrhythmias accelerated by ATP or shock in 1275 ICD patients (age at implantation 59.7 ± 14.0 years; 81% male). RESULTS: Within a mean follow-up period of 5.3 ± 4.0 years, intracardiac electrograms were available in 1170 patients (91.8%). Overall 157 episodes of accelerated ventricular tachyarrhythmias were found in 100 of 1170 patients (8.5%). Termination of tachyarrhythmias was achieved by shock delivery in 153 episodes (96.8%). Triggers of accelerated tachyarrhythmias were appropriate ATP in 139 (88.5%) and inappropriate ATP in 14 (8.9%), as well as appropriate and inappropriate shocks in 2 (1.3%) episodes, respectively. Chronic heart failure was significantly correlated with the occurrence and recurrence of acceleration (p<0.001). Patients with accelerated ventricular tachyarrhythmia and subsequent shock therapy revealed higher all-cause mortality (HR 1.760; 95% CI 1.286-2.410; p<0.001) as well as higher cardiac mortality (HR 2.555; 95% CI 1.446-4.513; p=0.001). The correlation between acceleration and all-cause mortality was independent of left ventricular function (HR 2.076; 95% CI 1.633-2.639; p<0.001). CONCLUSIONS: Ventricular ATP with arrhythmia acceleration and subsequent shock delivery is a frequent and serious complication of ICD therapy that predominantly occurs in patients with reduced left ventricular function. Finally, occurrence of accelerated ventricular tachyarrhythmias was associated with increased all-cause mortality.

The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure.

PURPOSE: Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO(2)) in patients with chronic heart failure using (11)C-acetate positron emission tomography (PET). METHODS: We prospectively enrolled 21 patients with severe heart failure. (11)C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. RESULTS: Under resting conditions, the values of myocardial blood flow (MBF), MVO(2) and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min(-1) g(-1) with the device off and 0.80 ± 0.15 ml min(-1) g(-1) with the device on (p = 0.818), MVO(2) was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m(2) with the device off and 5.21 ± 1.36 mmHg ml/m(2) with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO(2) and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. CONCLUSION: These results indicate that CCM does not induce increased MVO(2), even under stress conditions.

Regional prevalence and clinical benefit of implantable cardioverter defibrillators in Brugada syndrome.

BACKGROUND: Brugada syndrome (BS) is associated with an increased risk of sudden cardiac death (SCD) caused by ventricular tachyarrhythmia. Thus, implantable cardioverter defibrillators (ICD) became the main therapeutic option in these patients. We aimed to investigate the prevalence of BS in the Eastern Alps as well as the benefit of ICD therapy in this collective. METHODS: During physical examination before military service, 47,606 Austrian men were screened for Brugada ECG pattern. Furthermore, we followed 4491 patients with arrhythmia during the last two decades, of which 26 patients (20 male; age at diagnosis: 43.2 ± 11.6 years) revealed BS. Diagnosis was based on characteristic ECG either at rest (11 patients) or after provocation with Ajmaline (15 patients). RESULTS: The nationwide screening revealed one individual with Brugada ECG (prevalence of 2.10/100,000 inhabitants). Prior to diagnosis of BS, syncope and SCD survival were observed in 7 and 4 patients, respectively; the remaining 15 patients were asymptomatic. ICD were implanted in 17 patients (15 male). Three asymptomatic patients received no ICD because no tachyarrhythmia was inducible on programmed stimulation. Six asymptomatic patients without family history of sudden death refused further evaluation. Mean ICD follow-up period was 57.0 ± 32.2 months. Two patients (11.7%) needed defibrillation therapy. Four patients (23.5%) received exclusively inappropriate shocks (three due to T-wave oversensing, one due to atrial fibrillation). CONCLUSIONS: Brugada syndrome has a low prevalence in the Eastern alpine region. Patients with BS benefit from ICD implantation, but less frequently than anticipated. The problem of inappropriate ICD discharges is still of major concern.

Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma.

PURPOSE: Sunitinib and sorafenib are tyrosine kinase inhibitors (TKIs) that have considerable efficacy in metastatic renal cell carcinoma. TKI-associated cardiotoxicity was reported in approximately 10% of the patients. Detailed cardiovascular monitoring during TKI treatment may reveal early signs of myocardial damage. PATIENTS AND METHODS: In this observational, single-center study, all patients intended for TKI treatment were analyzed for coronary artery disease (CAD) risk factors, history or evidence of CAD, hypertension, rhythm disturbances, and heart failure. Monitoring included assessment of symptoms, ECGs, and biochemical markers (ie, creatine kinase-MB, troponin T). Echocardiography was performed at baseline in selected patients and in all patients who experienced a cardiac event. A cardiac event was defined as the occurrence of increased enzymes if normal at baseline, symptomatic arrhythmia that required treatment, new left ventricular dysfunction, or acute coronary syndrome. RESULTS: A total of 86 patients were treated with either sunitinib or sorafenib. Among 74 eligible patients, 33.8% experienced a cardiac event, 40.5% had ECG changes, and 18% were symptomatic. Seven patients (9.4%) were seriously compromised and required intermediate care and/or intensive care admission. All patients recovered after cardiovascular management (ie, medication, coronary angiography, pacemaker implantation, heart surgery) and were considered eligible for TKI continuation. Statistically, there was no significant survival difference between patients who experienced a cardiac event and those who did not experience a cardiac event. CONCLUSION: Our observations indicate that cardiac damage from TKI treatment is a largely underestimated phenomenon but is manageable if patients have careful cardiovascular monitoring and cardiac treatment at the first signs of myocardial damage.

Cardiac sarcoidosis mimicking Takotsubo syndrome.

An unusual case of cardiac sarcoidosis is described. A woman with biopsy proven lung sarcoidosis was presented on admission in hospital as ventricular tachycardia and non Q myocardial infarction. Ultrasound of the heart and coronarography examination presented Takotsubo syndrome, "ballooning heart", and normal blood vessels. Cardiac sarcoidosis and Takotsubo syndrome are diseases where definitive etiological factor was not found. This case report suggests the existence of their similar pathogenesis. As far as we know, this is the first described connection between Takotsubo syndrome and cardiac sarcoidosis.

Automatic home monitoring of implantable cardioverter defibrillators.

AIMS: With the expanding indications for implantable cardioverter defibrillator (ICD) and reports of unexpected ICD failures, home monitoring (HM) was proposed to decrease follow-up workload and increase patient safety. Home monitoring implantable cardioverter defibrillators offer wireless, everyday transfer of ICD status and therapy data to a central HM Service Center, which notifies the attending physician of relevant HM events. We evaluated functionality and safety of HM ICDs. METHODS AND RESULTS: A total of 260 patients with HM ICDs were monitored for a mean of 10 +/- 5 months. Time to HM events [medical (ventricular tachycardia/ventricular fibrillation) and technical (ICD system integrity)] since ICD implantation and since the latest in-clinic follow-up was analysed. Mean number of HM events per 100 patients per day was calculated, without and with a 2-day blanking period for re-notifying the same type of event. About 41.2% of the patients had HM events (38.1% medical, 0.8% technical, and 2.3% both types). Probability of any HM event after 1.5 years was 0.50 (95% confidence interval: 0.42-0.58). More than 60% of new HM event types occurred within the first month after follow-up. A mean of 0.86 event notifications was received per 100 patients per day or 0.45 with the 2-day blanking period. CONCLUSION: Home monitoring is feasible and associated with an early detection of medical and technical events.

Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure.

AIMS: We performed a randomized, double blind, crossover study of cardiac contractility modulation (CCM) signals in heart failure patients. METHODS AND RESULTS: One hundred and sixty-four subjects with ejection fraction (EF) < 35% and NYHA Class II (24%) or III (76%) symptoms received a CCM pulse generator. Patients were randomly assigned to Group 1 (n = 80, CCM treatment 3 months, sham treatment second 3 months) or Group 2 (n = 84, sham treatment 3 months, CCM treatment second 3 months). The co-primary endpoints were changes in peak oxygen consumption (VO2,peak) and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Baseline EF (29.3 +/- 6.7% vs. 29.8 +/- 7.8%), VO2,peak (14.1 +/- 3.0 vs. 13.6 +/- 2.7 mL/kg/min), and MLWHFQ (38.9 +/- 27.4 vs. 36.5 +/- 27.1) were similar between the groups. VO2,peak increased similarly in both groups during the first 3 months (0.40 +/- 3.0 vs. 0.37 +/- 3.3 mL/kg/min, placebo effect). During the next 3 months, VO2,peak decreased in the group switched to sham (-0.86 +/- 3.06 mL/kg/min) and increased in patients switched to active treatment (0.16 +/- 2.50 mL/kg/min). MLWHFQ trended better with treatment (-12.06 +/- 15.33 vs. -9.70 +/- 16.71) during the first 3 months, increased during the second 3 months in the group switched to sham (+4.70 +/- 16.57), and decreased further in patients switched to active treatment (-0.70 +/- 15.13). A comparison of values at the end of active treatment periods vs. end of sham treatment periods indicates statistically significantly improved VO2,peak and MLWHFQ (P = 0.03 for each parameter). CONCLUSION: In patients with heart failure and left ventricular dysfunction, CCM signals appear safe; exercise tolerance and quality of life (MLWHFQ) were significantly better while patients were receiving active treatment with CCM for a 3-month period.

Ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical presentation, risk stratification and results of long-term follow-up.

BACKGROUND: Not all patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are at risk for sudden cardiac death. The aim of the study was to evaluate the risk stratification in patients with ARVD/C. METHODS AND RESULTS: Programmed ventricular stimulation (PVS) was performed in 34 ARVD/C patients. Twenty-two, 7 and 4 patients had documented sustained monomorphic ventricular tachycardia (smVT), non-smVT and ventricular fibrillation, respectively. One patient experienced syncope only. An implantable cardioverter defibrillator (ICD) was implanted in 11 patients inducible in smVT with hemodynamic compromise, in 4 patients with documented ventricular fibrillation and in one patient with non-smVT (194 ms tachycardia cycle length) (ICD group, n = 16). Ten patients were left without any antiarrhythmic therapy, 5 patients received antiarrhythmic drugs and 3 patients underwent successful VT ablation (non-ICD group, n = 18). Thirteen patients had an abnormal signal averaged ECG. During 6.5 +/- 2.4 years 69% of ICD patients received appropriate discharges and one non-ICD patient had a hemodynamically tolerated smVT recurrence (no sudden cardiac death in both groups). Comparison between the cycle lengths of clinical VT, induced VT and follow-up VT revealed a strong relationship (R = 0.62-0.88). On multivariate analysis abnormal signal averaged ECG and decreased left ventricular ejection fraction were statistically significant predictors for VT recurrence. CONCLUSIONS: In ARVD/C the tachycardia cycle length of clinical VT, PVS-induced VT and follow-up VT correlate well implicating that a PVS-guided approach does not provide additional information. Spontaneous arrhythmia in combination with clinical presentation allows identification of patients in need for an ICD.