Zeliha Koyak

Sudden Cardiac Death in Adult Congenital Heart Disease

Background— Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. Methods and Results— We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5–7.9; P=0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.4; P=0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.2; P=0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10–1.34; P=0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22–1.48; P=0.008). Conclusions— The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort

Objective Patients with repaired tetralogy of Fallot (TOF) experience increased rates of mortality and morbidity in adulthood. This study was designed to identify risk factors for death and ventricular tachycardia (VT) in a large contemporary cohort of patients with repaired TOF. Methods Subjects with repaired TOF from four large congenital heart centres in the USA, Canada and Europe were enrolled. Clinical, ECG, exercise, cardiac magnetic resonance (CMR) and outcome data were analysed. Results Of the 873 patients (median age 24.4 years), 32 (3.7%) reached the primary outcome (28 deaths, 4 sustained VT; median age at outcome 38 years; median time from CMR to outcome 1.9 years). Cox proportional-hazards regression identified RV mass-to-volume ratio ≥0.3 g/mL (HR, 5.04; 95% CI 2.3 to 11.0; p<0.001), LV EF z score<−2.0 (HR, 3.34; 95% CI 1.59 to 7.01; p=0.001), and history of atrial tachyarrhythmia (HR, 3.65; 95% CI 1.75 to 7.62; p=0.001) as outcome predictors. RV dysfunction was predictive of the outcome similar to LV dysfunction. In subgroup analysis of 315 subjects with echocardiographic assessment of RV systolic pressure, higher pressure (HR 1.39; 95% CI 1.19 to 1.62; p<0.001) was associated with death and sustained VT independent of RV hypertrophy and LV dysfunction. Conclusions RV hypertrophy, ventricular dysfunction and atrial tachyarrhythmias are predictive of death and sustained VT in adults with repaired TOF. These findings may inform risk stratification and the design of future therapeutic trials.

Implantable cardioverter defibrillator therapy in adults with congenital heart disease: who is at risk of shocks?

Background— The value of implantable cardioverter defibrillators (ICDs) in adults with congenital heart disease (CHD) is unknown. We investigated the long-term outcome after ICD implantation and developed a simple risk stratification score for ICD therapy. Methods and Results— A total of 136 adults with CHD and ICD (mean age±SD, 41±13 years; 67% male) were identified from 10 tertiary referral centers in the Netherlands and Belgium. The indication for ICD implantation was primary prevention in 50% of patients. Diagnoses included tetralogy of Fallot (51%), septal defects (20%), (congenitally corrected) transposition of the great arteries (13%), and other (16%). Thirty-nine patients (29%) received appropriate ICD shocks during a median follow-up of 4.6 years. Secondary prevention indication (hazard ratio [HR], 3.6; 95% CI, 1.3–9.5; P=0.009), coronary artery disease (HR, 2.7; 95% CI, 1.0–7.2; P=0.042), and symptomatic nonsustained ventricular tachycardia (NSVT; HR, 9.1; 95% CI, 2.8–29.2; P=0.001) were associated with appropriate ICD shocks. A risk score was developed to evaluate the likelihood of appropriate ICD shocks. The 8-year survival curve to first appropriate shocks was 94%, 57%, and 26% for low-, intermediate-, and high-risk patients, respectively. In primary prevention, symptomatic NSVTs (HR, 8.0; 95% CI, 2.3–27.1; P=0.001) and subpulmonary ventricular dysfunction (HR, 3.0; 95% CI, 1.2–12.6; P=0.02) were associated with appropriate shocks in univariable analysis. Inappropriate shocks occurred in 41 patients (30%). In addition, 40 patients (29%) experienced 45 implantation-related complications. Conclusions— Adults with CHD and ICDs receive high rates of appropriate and effective shocks. Patients with secondary prevention indication, coronary artery disease, and symptomatic NSVT are at highest risk of receiving appropriate ICD shocks. ICD implantation is accompanied by considerable morbidity, including inappropriate shocks and procedure- related complications.

Cardiac magnetic resonance markers of progressive RV dilation and dysfunction after tetralogy of Fallot repair

Objective Patients with repaired tetralogy of Fallot (TOF) are followed serially by cardiac magnetic resonance (CMR) for surveillance of RV dilation and dysfunction. We sought to define the prevalence of progressive RV disease and the optimal time interval between CMR evaluations. Methods Candidates were selected from a multicentre TOF registry and were included if ≥2 CMR studies performed ≥6 months apart were available without interval cardiovascular interventions. Patients with ‘disease progression’ (defined as increase in RV end-diastolic volume index (RVEDVi) ≥30 mL/m2, decrease in RVEF ≥10% or decrease in LVEF ≥10%) were compared with those with ‘disease non-progression’ (defined as RVEDVi increase ≤5 mL/m2, RVEF decrease ≤3% and LVEF decrease ≤3%). Results A total of 849 CMR studies in 339 patients (median age at first CMR 23.6 years) were analysed. Over a median interval of 2.2 years between CMR pairs, RVEDVi increased 4±18 mL/m2 (p<0.001), RV end-systolic volume index increased 3±13 mL/m2 (p<0.001), RVEF decreased 1%±6% (p=0.02) and LVEF decreased 1%±6% (p=0.001). Disease progression was observed in 15% (n=76) and non-progression in 26% (n=133). There were no significant differences between those with and without progression in baseline demographic, anatomic, ECG, exercise or baseline CMR characteristics. The optimal time interval between CMR studies for detection of progression was a 3-year interval (63% sensitivity, 65% specificity, area under the receiver operating characteristic curve 0.65). Conclusions Although progressive RV dilation and decline in biventricular systolic function occur at a slow pace in the majority of adults with repaired TOF, 15% of patients experience rapid disease progression. The results of this study support the practice of serial CMR examinations to identify progressive disease at a time interval of up to 3 years.

Symptomatic but not asymptomatic non-sustained ventricular tachycardia is associated with appropriate implantable cardioverter therapy in tetralogy of Fallot

BACKGROUND A recently developed risk score model aims to predict appropriate implantable cardioverter defibrillator (ICD) therapy for primary prevention of sudden cardiac death in tetralogy of Fallot (TOF). We assessed the validity of the proposed risk score model. METHODS Patients included in a retrospective international cohort were stratified according to the risk score system. Risk factors were prior shunt, inducible sustained ventricular tachycardia, QRS ≥ 180 ms, ventriculotomy incision, nonsustained ventricular tachycardia (NSVT) and left ventricular end-diastolic pressure ≥ 12 mmHg (LVEDP). Left ventricular ejection fraction ≤ 35% measured by means of echocardiography was used because LVEDP values were incomplete in our cohort. RESULTS Thirty-six adults had TOF and ICD for primary prevention (72% male, mean age 37 ± 12). Seven patients (19%) received appropriate shocks during a median follow-up of 5.5 years. Of the proposed risk factors only NSVT was associated with appropriate shocks (HR 2.6, CI 1.1-6.0, P=0.02). Patients with asymptomatic NSVT did not receive any appropriate shocks. The 8-year Kaplan-Meier estimate from the first appropriate shock was 86%, 78% and 75% for low, intermediate and high risk patients, respectively. In this study, the annual rate of appropriate shocks was 4.1% in the high risk group which was considerably lower than that reported by Khairy and colleagues (17.5%). CONCLUSIONS The risk score model of Khairy and colleagues was capable of identifying low versus intermediate/high risk patients. However, event rates of lethal arrhythmias were lower in our cohort than previously reported. Symptomatic but not asymptomatic NSVT was the sole clinical variable associated with appropriate ICD therapy in TOF.

Postoperative arrhythmias in adults with congenital heart disease: Incidence and risk factors

BACKGROUND Little is known about the clinical impact of arrhythmias after surgery for congenital heart disease (CHD) in adults. Therefore, we investigated the prevalence of in-hospital arrhythmias after CHD surgery and their impact on clinical outcome. METHODS This was a multicenter retrospective study and included adults who underwent congenital cardiac surgery between January 2009 and December 2011. Clinical events were defined as all cause mortality, heart failure (HF) requiring medical treatment, thrombo-embolic event, major infections and permanent pacemaker (PM) implantation. RESULTS Overall, 419 patients were included (mean age 38 ± 14 years, 55% male). Arrhythmias occurred in 134 patients (32%) and included supraventricular tachycardia (SVT, n = 100), bradycardias (n = 47) and ventricular tachycardia (VT, n = 19). In multivariate analysis age ≥40 years at surgery (OR 2.48, 95% Cl 1.40-4.60, P = 0.003), NYHA class ≥ II (OR 2.42, 95% Cl 1.18-4.67, P = 0.009), significant subpulmonary AV-valve regurgitation (OR 2.84, 95% Cl 1.19-6.72, P = 0.018), coronary bypass time (OR 1.35/60 minute increase, 95% Cl 1.06-1.82, P = 0.019) and CK-MB (OR 1.05 per 10 U/L increase, 95% Cl 1.01-1.09, P = 0.021) were associated with in-hospital arrhythmias. Overall, 58 clinical events occurred in 55 patients (13%) and included in the majority of the cases permanent PM implantation (5%), HF (4%) and death (2%). In-hospital arrhythmias were independently associated with clinical events (OR 7.80, 95% CI 2.41-25.54, P = 0.001). CONCLUSION Arrhythmias are highly prevalent after congenital heart surgery in adults and are associated with worse clinical outcome. Older and symptomatic patients with significant valvular heart disease at baseline are at risk of in-hospital arrhythmias.

Interventional and surgical treatment of cardiac arrhythmias in adults with congenital heart disease.

Arrhythmias are a major cause of morbidity, mortality and hospital admission in adults with congenital heart disease (CHD). The etiology of arrhythmias in this population is often multifactorial and includes electrical disturbances as part of the underlying defect, surgical intervention or hemodynamic abnormalities. Despite the numerous existing arrhythmia management tools including drug therapy, pacing and ablation, management of arrhythmias in adults with CHD remains difficult and challenging. Owing to improvement in mapping and ablation techniques, ablation and arrhythmia surgery are being performed more frequently in adults with CHD. However, there is little information on the long-term results of these treatment strategies. The purpose of this article is therefore to review the available data on nonpharmacological treatment of cardiac arrhythmias in adult patients with CHD and to give an overview of the available data on the early and late outcomes of these treatment strategies.

Sudden cardiac death in adult congenital heart disease: can the unpredictable be foreseen?

Aims Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). Several risk factors for SCD including conduction disturbances and ventricular dysfunction have been described previously. However, electrocardiogram (ECG) and echocardiographic parameters may change over time, and the predictive value of such temporal changes, rather than their point estimates, for SCD remains unknown. Methods and results This was a retrospective case-control study in adults with CHD and proven or presumed SCD and matched controls. Data were obtained from three databases including 25 000 adults with CHD. Sequential measurements were performed on electrocardiograms and echocardiograms. Ventricular function was assessed by echocardiography and graded on a four-point ordinal scale: 1, normal [ejection fraction (EF) ≥50%]; 2, mildly impaired (EF 40-49%); 3, moderately impaired (EF 30-39%); and 4, severely impaired (EF < 30%). Overall, 131 SCDs (mean age 36 ± 14 years, 67% male) and 260 controls (mean age 37 ± 13 years, 63% male) were included. At baseline, median QRS duration was 108 ms (range 58-168 ms) in SCDs and 97 ms (range 50-168 ms) in controls and increased over time at a rate of 1.6 ± 0.5 vs. 0.5 ± 0.2 ms/year in SCDs and controls, respectively (P = 0.011). QT dispersion at baseline was 61 ms (range 31-168 ms) in SCDs and 50 ms (range 21-129 ms) in controls. QT dispersion increased at a rate of 1.1 ± 0.4 ms/year in SCD victims and decreased at a rate of 0.2 ± 0.2 ms/year in controls (P = 0.004). Increase of QRS duration ≥5 ms/year was associated with an increased risk of SCD [OR 1.9, 95% confidence interval (CI) 1.1-3.3, P = 0.013]. Change from any baseline systemic ventricular function (normal, mild, or moderately impaired) to severe ventricular dysfunction over time was associated with the highest risk of SCD (OR 16.9, 95% CI 1.8-120.1, P = 0.008). Conclusion In adults with CHD, QRS duration and ventricular dysfunction progress over time. Progression of QRS duration and the rate of impairment of ventricular function served to identify those at increased risk of SCD.

Cardiac resynchronization therapy in adults with congenital heart disease

Aims In adults with congenital heart disease (CHD) heart failure is one of the leading causes of morbidity and mortality but experience with and reported outcome of cardiac resynchronization therapy (CRT) is limited. We investigated the efficacy of CRT in adults with CHD. Methods and results This was a retrospective study including 48 adults with CHD who received CRT since 2003 in four tertiary referral centres. Responders were defined as patients who showed improvement in NYHA functional class and/or systemic ventricular ejection fraction by at least one category. Ventricular function was assessed by echocardiography and graded on a four point ordinal scale. Median age at CRT was 47 years (range 18-74 years) and 77% was male. Cardiac diagnosis included tetralogy of Fallot in 29%, (congenitally corrected) transposition of great arteries in 23%, septal defects in 25%, left sided lesions in 21%, and Marfan syndrome in 2% of the patients. The median follow-up duration after CRT was 2.6 years (range 0.1-8.8). Overall, 37 out of 48 patients (77%) responded to CRT either by improvement of NYHA functional class and/or systemic ventricular function. There were 11 non-responders to CRT. Of these, three patients died and four underwent heart transplantation. Conclusion In this cohort of older CHD patients, CRT was accomplished with a success rate comparable to those with acquired heart disease despite the complex anatomy and technical challenges frequently encountered in this population. Further studies are needed to establish appropriate guidelines for patient selection and long term outcome.

Prevention of Sudden Cardiac Death in Adults With Congenital Heart Disease: Do the Guidelines Fall Short?

Background— Sudden cardiac death (SCD) is a major cause of mortality in adult congenital heart disease (ACHD) patients. SCD may be prevented by implantable cardioverter-defibrillator (ICD) implantation, but patient stratification remains troublesome. The 2014 Consensus Statement on Arrhythmias in ACHD patients and the 2015 European Society of Cardiology Guidelines specified recommendations for ICD implantation in ACHD patients for the first time. We assess the discriminative ability of these ICD recommendations for SCD in ACHD patients. Methods and Results— Of 25 790 ACHD patients in an international multicenter registry, we identified all SCD cases, matched to living controls by age, sex, congenital defect, and surgical repair. We assessed all primary prevention ICD recommendations listed in both documents. We used conditional logistic regression models to calculate odds ratios and receiver operating characteristic curves with area under the curve. Consensus Statement: One hundred twenty-four cases (median age at death, 33 years [26–44]; 67% men) and 230 controls were studied. In total, 41% of SCD cases and 17% of controls had an ICD recommendation (odds ratio, 5.9; P<0.001). European Society of Cardiology Guidelines: Of one hundred fifty-seven cases (median age at death, 33 years [26–48]; 64% men) and 292 controls, 35% and 14% had an ICD recommendation, respectively (odds ratio, 4.8; P<0.001). Conclusions— A minority of SCD cases had an ICD recommendation according to these guidelines, whereas the majority of SCD victims remained unrecognized. With an area under the curve of 0.6 to 0.7, the discriminative ability of both guidelines was mediocre. Critical clinical reasoning when deciding on ICD implantation in ACHD patients, therefore, remains vital.