Mortality and appropriate and inappropriate therapy in patients with ischaemic heart disease and implanted cardioverter-defibrillators for primary prevention: data from the Danish ICD Register.

AIMS: To evaluate the incidences of and risk factors predisposing to appropriate and inappropriate shocks and mortality in a 'real-world' population of patients with ischaemic heart disease (IHD) and implantable cardioverter defibrillators (ICD) for primary prevention of sudden cardiac death (SCD). METHODS AND RESULTS: In this nationwide cohort, we prospectively followed 1609 patients with IHD and left ventricular dysfunction from the Danish ICD Register who received an ICD for primary prevention of SCD (1 January 2007 to 30 November 2011). Primary study outcomes were appropriate shocks, inappropriate shocks, and all-cause mortality. Secondary study outcomes included the composite endpoints: appropriate therapy and inappropriate therapy (defined as shock or anti-tachycardia pacing). All-cause mortality was 12.1% during a mean follow-up time of 1.9 ± 1.3 years. Inappropriate shocks and therapy occurred in 2.6% and 3.7% during follow-up, respectively. Appropriate shocks and therapy was identified in 7.8% and 13.4%, respectively. Time-dependent multivariable Cox regression analyses were used to identify risk factors of inappropriate/appropriate shock, therapy and mortality. Implantation of a dual-chamber ICD was associated with increased risk of both inappropriate shocks and any inappropriate therapy compared to single-chamber ICD [hazard ratios (HR) = 2.45; confidence intervals (CI):1.16-5.14 and HR = 2.38; CI:1.28-4.42, respectively]. No excess risk of mortality was associated with any device type. CONCLUSION: In this nationwide study of IHD patients with an ICD for primary prevention of SCD, the incidence of appropriate shocks as well as inappropriate shocks were significantly lower than reported in randomized trials. Implantation of a dual-chamber ICD was associated with more inappropriate shocks compared with single chamber devices.

Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing: no association with pacing mode or right ventricular pacing site.

AIMS: Previous studies indicate that ventricular pacing may precipitate heart failure (HF). We investigated occurrence of HF during long-term follow-up among patients with sick sinus syndrome (SSS) randomized to AAIR or DDDR pacing. Furthermore, we investigated effects of percentage of ventricular pacing (%VP) and pacing site in the ventricle. METHODS AND RESULTS: We analysed data from 1415 patients randomized to AAIR (n = 707) or DDDR pacing (n = 708). Ventricular pacing leads were recorded as located in either an apical or a non-apical position. The %VP and HF hospitalizations were recorded during follow-up. Patients were classified with new HF, if in New York Heart Association (NYHA) functional class IV or if presence of ≥2 of: oedema; dyspnoea; NYHA functional class III. Mean follow-up was 5.4 ± 2.4 years. Heart failure hospitalizations did not differ between groups. In the AAIR group, 170 of the 707 (26%) patients developed HF vs. 169 of the 708 (26%) patients in the DDDR group, hazard rate ratio (HR) 1.00, 95% confidence interval (CI) 0.79-1.22, P = 0.87. In DDDR patients, 146 of the 512 patients (29%) with ventricular leads in an apical position developed HF vs. 28 of the 161 patients (17%) with the leads in a non-apical position, HR 0.67, CI 0.45-1.00, P = 0.05. After adjustments this difference was non-significant. The incidence of HF was not associated with %VP (P = 0.57). CONCLUSION: In patients with SSS, HF was not associated with pacing mode, %VP, or ventricular lead localization. This suggests that DDDR pacing is safe in patients with SSS without precipitating HF.

Pneumothorax in cardiac pacing: a population-based cohort study of 28,860 Danish patients.

AIM: To identify risk factors for pneumothorax treated with a chest tube after cardiac pacing device implantation in a population-based cohort. METHODS AND RESULTS: A nationwide cohort study was performed based on data on 28 860 patients from the Danish Pacemaker Register, which included all Danish patients who received their first pacemaker (PM) or cardiac resynchronization device from 1997 to 2008. Multiple logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for the association between risk factors and pneumothorax treated with a chest tube. The median age was 77 years (25th and 75th percentile: 69-84) and 55% were male (n = 15 785). A total of 190 patients (0.66%) were treated for pneumothorax, which was more often in women [aOR 1.9 (1.4-2.6)], and in patients with age >80 years [aOR 1.4 (1.0-1.9)], a prior history of chronic obstructive pulmonary disease [aOR 3.9 (1.6-9.5)], implantation of a dual-chamber PM [aOR 1.5 (1.0-2.2)], venous access with subclavian vein puncture [aOR 7.8 (4.9-12.5)], venous access with both subclavian vein puncture and cephalic vein cut-down [aOR 5.7 (3.0-10.8)], and implantation in a non-university centre [aOR 2.1 (1.6-2.9)]. CONCLUSION: Pneumothorax treated with a chest tube remains a clinically important problem in device therapy. The cephalic vein cut-down technique should be applied whenever possible to avoid this complication.

Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing.

AIMS: In the recently published DANPACE trial, incidence of atrial fibrillation (AF) was significantly higher with single-lead atrial (AAIR) pacing than with dual-chamber (DDDR) pacing. The present analysis aimed to evaluate the importance of baseline PQ-interval and percentage of ventricular pacing (VP) on AF. METHODS AND RESULTS: We analysed data on AF during follow-up in 1415 patients included in the DANPACE trial. In a subgroup of 650 patients with DDDR pacemaker, we studied whether %VP, baseline PQ-interval, and programmed atrio-ventricular interval (AVI) was associated with AF burden measured as time in mode-switch (MS) detected by the pacemaker. In the entire DANPACE study population, the incidence of AF was significantly higher in patients with baseline PQ-interval >180 ms (P< 0.001). Among 650 patients with DDDR pacemaker, telemetry data were available for 1.337 ± 786 days, %VP was 66 ± 33%, AF was detected at planned follow-up in 160 patients (24.6%), MS occurred in 422 patients (64.9%), and AF burden was marginally higher with baseline PQ-interval >180 ms (P= 0.028). No significant association was detected between %VP and %MS (Spearman's ρ 0.056, P= 0.154). %MS was not different between minimal-paced programmed AVI ≤ 100 and >100 ms (median value), respectively (P= 0.60). CONCLUSIONS: The present study indicates that a longer baseline PQ-interval is associated with an increased risk of AF in patients with sick sinus syndrome. Atrial fibrillation burden is not associated with the percentage of VP or the length of the programmed AVI.

Risk factors for lead complications in cardiac pacing: a population-based cohort study of 28,860 Danish patients.

BACKGROUND: Lead complications are the main reason for reoperation after implantation of pacemakers (PM) or cardiac resynchronization therapy (CRT-P) devices. OBJECTIVE: This study sought to describe the incidence of lead complications causing reoperation after device implantation and to identify risk factors for lead complications. METHODS: A nationwide, population-based, historic cohort study was performed based on data from the Danish Pacemaker Register, which includes all Danish patients who received their first PM or CRT-P device from 1997 to 2008. Follow-up occurred 3 months after implantation. RESULTS: The study population consisted of 28,860 patients. The incidence of any lead complication was 3.6%, encompassing right atrial (RA; 2.3%), right ventricular (2.2%), and left ventricular (4.3%) lead complications. The lead complication risk declined during the first part of the study period and remained stable after 2002. Multivariate analysis identified the following significant risk factors: chronic heart failure as indication (adjusted odds ratio (aOR) 3.0; 95% confidence interval [CI] 2.1 to 4.3), implantation in a nonuniversity center (aOR 1.4; 95% CI 1.2 to 1.6), inexperienced operator with <25 implantations (aOR 1.6; 95% CI 1.3 to 2.0), single-lead RA device (aOR 1.4; 95% CI 1.1 to 1.8), dual-chamber pacing device (aOR 1.6; 95% CI 1.4 to 1.9), CRT-P device (aOR 3.3; 95% CI 2.4 to 4.4) and passive-fixation RA lead (aOR 2.2; 95% CI 1.7 to 2.9). CONCLUSION: Lead complications causing reoperation remain a clinically important problem in device therapy. Mainly procedure-related factors were identified as independent risk factors for lead complications.

A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome.

AIMS: In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any difference between single-lead atrial pacing (AAIR) and dual-chamber pacing (DDDR). METHODS AND RESULTS: We randomly assigned 1415 patients referred for first pacemaker implantation to AAIR (n = 707) or DDDR (n = 708) pacing and followed them for a mean of 5.4 ± 2.6 years. The primary outcome was death from any cause. Secondary outcomes included paroxysmal and chronic atrial fibrillation, stroke, heart failure, and need for pacemaker reoperation. In the AAIR group, 209 patients (29.6%) died during follow-up vs. 193 patients (27.3%) in the DDDR group, hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.88-1.29, P = 0.53. Paroxysmal atrial fibrillation was observed in 201 patients (28.4%) in the AAIR group vs. 163 patients (23.0%) in the DDDR group, HR 1.27, 95% CI 1.03-1.56, P = 0.024. A total of 240 patients underwent one or more pacemaker reoperations during follow-up, 156 (22.1%) in the AAIR group vs. 84 (11.9%) in the DDDR group (HR 1.99, 95% CI 1.53-2.59, P < 0.001). The incidence of chronic atrial fibrillation, stroke, and heart failure did not differ between treatment groups. CONCLUSION: In patients with sick sinus syndrome, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00236158.

Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients.

AIMS: Infection is a serious complication of pacemaker (PM) systems. Although the rate of infection has been debated, the figures are largely unknown. We therefore studied the incidence of PM infection and its associated risk factors in the Danish population. METHODS AND RESULTS: Since 1982, all PM implantation and removal procedures performed in Denmark have been prospectively recorded in the Danish Pacemaker Register. All patients (n = 46299) who underwent implantation between 1982 and 2007 were included. The total length of surveillance was 236,888 PM-years. The incidence of infection was calculated according to the total number of PM-years. The incidence of surgical site infection (≤ 365 days after PM implantation) was compared with later infection in first implant and replacement procedures. Multiple-record and multiple-event-per-subject proportional hazards analyses were used to identify the independent risk factors of PM infection. Surgical site infection occurred in 192 cases after first implantation (incidence rate 4.82/1000 PM-years), and in 133 cases after replacement (12.12/1000 PM-years). Infections occurring more than 365 days after the first implantation occurred in 153 cases (1.02/1000 PM-years), and in 118 cases after replacement (3.26/1000 PM-years). Independent factors associated with an increased risk of PM infection were a greater number of PM operations (including replacements), male sex, younger age, implantation during the earliest part of the study period, and absence of antibiotics (P< 0.001). CONCLUSION: The overall risk of infection after PM implantation was low. A greater number of operations augmented the risk of infection. This should be taken into account when considering revisions of PM systems.

Attitudes towards implantable cardioverter-defibrillator therapy: a national survey in Danish health-care professionals.

AIMS: The aim of this study was to examine health-care professionals attitudes towards implantable cardioverter-defibrillator (ICD) therapy and issues discussed with patients. METHODS AND RESULTS: Survey of 209 health-care professionals providing specialized treatment and care of ICD patients at the five implanting centres in Denmark. Questions pertained to gender, age, years of experience within the field, knowledge of the ongoing critical debate on ICD therapy, and personal experience with ICD treatment, and/or sudden cardiac arrest within family and/or friends. Of all participants, 185 (88.5%) completed the survey. Physicians spent less time informing patients about ICD treatment prior to implantation (mean min = 17.7 ± 11.2 vs. 28.6 ± 19.4; P < 0.001). They were more likely to discuss clinical issues but less likely to discuss psychosocial issues with patients compared with non-physicians. Physicians were less likely to believe that their personal attitude towards ICD treatment has no influence on how they deal professionally with patients (27.8 vs. 43.6%; P = 0.04). Physicians and non-physicians were equally positive towards ICD therapy as primary prophylaxis in ischaemic cardiomyopathy (87.6 vs. 82.1%; P = 0.40) but not in non-ischaemic cardiomyopathy (57.3 vs. 83.9%; P < 0.001). Physicians were more positive towards ICD therapy as secondary prophylaxis (98.9 vs. 84.2%; P = 0.001) compared with non-physicians. CONCLUSIONS: Physicians focus on clinical rather than psychosocial issues when discussing ICD treatment with candidate patients. At the same time, physicians are more aware that their attitude towards ICD treatment may influence how they deal professionally with patients compared with non-physicians.

Twins with implanted pacemakers: Is there an increased mortality risk for the co-twin? A follow-up study based on the Danish Twin Registry and the Danish Pacemaker Register.

BACKGROUND: The main indications for implanting a cardiac pacemaker are either acquired atrio-ventricular block (AVB) or sick sinus syndrome (SSS). In general, the exact aetiology of these conditions is unknown. Genetic factors may play a role. Untreated AVB is associated with increased mortality but SSS seems to have a good prognosis. The present study was designed to assess whether first-degree relatives of these patients have an increased mortality risk. METHODS: We investigated the survival pattern of the co-twins of twins who have had a cardiac pacemaker implanted, by linking two nationwide registries in Denmark: the Danish Pacemaker Register and the Danish Twin Registry. For each "pacemaker-twin" four control-twins matched with respect to age, sex, and zygosity were selected among the twins who were alive at the time of the pacemaker implantation. A total of 159 twins with a pacemaker treated bradycardia of unknown aetiology were identified of which 73 had AVB and 64 had SSS. A total of 622 matched control-twins could be identified. The survival from age six of the co-twins of the "pacemaker-twins" was compared with that of the co-twins of the control-twins. The follow-up period ended January 1st, 2000. FINDINGS: The survival curves for the co-twins of the "pacemaker-twins" were virtually identical to those of the co-twins of the control-twins. This finding was consistent for both AVB and SSS and for monozygotic as well as dizygotic twins. CONCLUSION: No increased mortality risk could be demonstrated for first-degree relatives--including monozygotic twins--of patients with a cardiac pacemaker implanted due to either acquired AVB or SSS.

QT interval dynamics predict mortality in high-risk patients after myocardial infarction.

OBJECTIVE: The purpose of this study was to evaluate the prognostic properties of the QT/RR relationship in survivors of myocardial infarction with severe left ventricular dysfunction. DESIGN: The QT/RR interval slope was assessed from 24-h electrocardiographic recordings obtained from 241 patients representative of survivors of an acute myocardial infarction with an ejection fraction < or =35%. During a median follow-up of 752 days, 63 patients died. RESULTS: In a multivariate analysis QT/RR at night-time was an independent predictor of all-cause mortality. A linear all-cause mortality predictor score was calculated from age, ejection fraction, QRS duration and QT/RR night, allowing identification of a high-risk one-third of the patients with a relative risk of death at 4.0. CONCLUSION: This study demonstrates independent prognostic information of night-time QT/RR dynamics in patients at high risk after myocardial infarction. A linear predictor score calculated from age, ejection fraction, QRS duration and QT/RR night identifies a high-risk one-third of the patients with a 1-year mortality of 36% vs 9% in the remaining patients.

Improvement of risk-stratification by use of a new combination of Holter variables in survivors of myocardial infarction.

OBJECTIVE: Holter monitoring is one option in risk-stratification after acute myocardial infarction (MI). Measurements of heart rate variability (HRV), ventricular tachycardia (VT) and ST-segment elevation (ST upward arrow ) have been useful in predicting clinical outcome. We investigated if a combination of different Holter variables could optimize risk-stratification. DESIGN: One hundred and twenty-one men < 70 years old with a first MI were studied. Holter monitoring for 24 h was started 11 +/- 5 days after MI and analysed for HRV, VT and ST. Follow-up was 10-12 years with cardiac death as endpoint. RESULTS: Thirty-six patients were positive for > or = 1 Holter variable (HRV in 15, VT in 16, ST in 10). At follow-up 22 cardiac deaths had occurred. The prognostic sensitivity of individual Holter variables ranged from 23 to 36%, but increased to 64% if combined. The cardiac death rate in Holter positive patients (39%) was significantly higher than in Holter negative patients (9%) (p < 0.0001). CONCLUSION: By combining measurements of HRV, VT and ST the prognostic importance of Holter monitoring can be significantly improved. The patients can be stratified in a low-risk group with an annual mortality < 1% vs a high-risk group with a cardiac death rate around 40% over the following decade.

Risk of severe cardiac arrhythmia in male utility workers: a nationwide danish cohort study.

To address concern about the potential cardiovascular effects of occupational exposure to electromagnetic fields in the 50- to 60-Hz frequency band, the authors launched an epidemiologic study of the incidence of severe cardiac arrhythmia, as indicated by the need for a pacemaker, in a nationwide cohort of Danish utility workers. The cohort of 24,056 men employed at utility companies between 1900 and 1993 was linked to the nationwide, population-based Danish Pacemaker Register, and the numbers of persons who had undergone pacemaker implantation between 1982 and 2000 were compared with corresponding numbers in the general population. In addition, the data on the utility workers were fitted to a multiplicative Poisson regression model in relation to estimated levels of exposure to 50-Hz electromagnetic fields. Overall, based on 135 men with pacemakers (140 expected), there was no increased risk of severe cardiac arrhythmia among the utility employees; the risk estimate was 0.96 (95% confidence interval: 0.81, 1.14). No clear dose-response pattern emerged with increasing levels of exposure to electromagnetic fields or with duration of employment. These results are largely reassuring, since they do not support the hypothesis of a link between occupational exposure to electromagnetic fields and an excess risk of severe cardiovascular arrhythmia leading to permanent implantation of a pacemaker.

Cancer risk among pacemaker recipients in Denmark, 1982-1996.

To address concerns about the potential carcinogenicity of pacemakers, we launched the first epidemiologic study of cancer incidence among pacemaker recipients. A nationwide cohort of 16,357 pacemaker recipients in Denmark from 1982 through 1996 was identified. The Danish Cancer Registry was used to identify all incident cancers within the cohort, with almost 75,000 person-years of observation. The cohort had a slight excess of cancer overall (SIR = 1.19, 95% confidence interval [95% CI, 1.1-1.2]). This was largely caused by an elevated SIR for multiple myeloma among men (SIR = 1.78,95% CI, 1.1-2.8), which increased to 2.60 (95% CI, 0.9-5.7) 5-9 years after implantation, and to a similarly increased SIR for kidney cancer among women (SIR = 2.05, 95% CI, 1.3-3.0), which increased to 3.39 (95% CI, 1.6-6.2) after a latency period of 5-9 years. An excess of urinary bladder cancer was also seen after 10 years. No excess risk was observed for breast cancer or sarcomas, although the SIRs for sarcomas tended to increase over time, based on small numbers. Our results are largely reassuring but, as pacemakers become more common and are implanted at earlier ages and as survival following implantation improves, the excesses of bladder cancer, multiple myeloma among men, and kidney cancer among women with long-term followup warrant further investigation.