ABSTRACT
Background
Ventricular arrhythmias and sudden cardiac death (SCD) are common in adults with congenitally corrected transposition of great arteries (cc-TGA). The purpose of this study was to describe the outcomes after implantable cardioverter-defibrillator (ICD) implantation in adults with cc-TGA.
Method
Retrospective cohort study of adults with cc-TGA who underwent ICD implantation at Mayo Clinic (2003-2024). Indications for ICD implantation were classified as primary versus secondary prevention. Study outcomes were appropriate and inappropriate ICD shocks. Exploratory outcomes were device-related complications and mortality.
Results
Of 278 patients, 87 (31%) underwent ICD implantation (age 45±15 years, 59% males; primary prevention [ N = 67, 77%], secondary prevention [ N = 20, 23%]). Overall, 14 (16%) patients received appropriate ICD shock. The annual incidence of appropriate ICD shock was 3.7% per year and was lower in the primary versus secondary prevention groups (1.9% versus 8.2% per year, P =.006). Overall, 11 (13%) patients received inappropriate ICD shock, yielding annual incidence of 3.5% per year. This was similar between the 2 groups. Apart from ICD implantation for secondary prevention, none of the conventional risk factors were associated with an appropriate ICD shock. All-cause mortality was high (31%) among the cohort, but none of the patients experienced SCD.
Conclusions
We observed a high rate of appropriate ICD shock, especially in the secondary prevention group. However, risk stratification of ICD implantation for primary prevention remains challenging. The absence of SCD (despite a high prevalence of all-cause mortality) suggest that ICD implantation may provide a survival benefit.
Abbreviations
CHD, Congenital heart disease; cc-TGA, Congenitally corrected transposition of great arteries; EF, Ejection fraction; FAC, Fractional area change; FWS, Free wall strain; ICD, Implantable cardioverter-defibrillator; LV, Left ventricle; RV, Right ventricular; PA, Pulmonary artery; SCD, Sudden cardiac death
CLINICAL SUMMARY
Of 278 adults with cc-TGA, 87 (31%) underwent ICD implantation (age 45±15 years, 59% males; primary prevention [ N = 67, 77%], secondary prevention [ N = 20, 23%]). The risk of appropriate ICD shock was high in the overall cohort (prevalence 16% and annual incidence 3.7%) and was significantly higher in secondary prevention group compared to the primary prevention group. The risk of inappropriate shock was comparable between the 2 groups. Although all-cause mortality was highly prevalent (31% of the cohort), none of the patients experienced sudden cardiac death. This suggests that ICD implantation may provide a survival benefit.
Background
There has been a significant improvement in the long-term survival of adults with congenital heart disease (CHD). ,, However, cardiovascular death remains the leading cause of mortality in this population, and the risk factors associated with cardiovascular death include complex CHD, systemic morphologic right ventricle (RV), and systemic ventricular systolic dysfunction. ,, All these risk factors are present in adults with congenitally corrected transposition of great arteries (cc-TGA), and contribute to the reduced life expectancy in this disease group relative to other CHD diagnoses. ,
Among patients with cc-TGA, systemic RV systolic dysfunction and ventricular arrhythmias are highly prevalent (40%-60% and 15%-20%, respectively), and both risk factors are associated with sudden cardiac death (SCD). ,,, While implantable cardioverter-defibrillator (ICD) is a well-established therapy for prevention of SCD in patients with cardiovascular disease, and there are limited data about the clinical benefits (or lack thereof) of ICD therapy in adults with cc-TGA. , The purpose of this study was to address this knowledge gap, by describing outcomes after ICD implantation in adults with cc-TGA.
Methods
Study population
This is a retrospective cohort study of adults (age ≥18 years) with cc-TGA with ICD implantation who received care at the Mayo Clinic Enterprise (Rochester, MN; Jacksonville, FL; Scottsdale, AZ; and the Mayo Clinic Health System) from January 1, 2003 to December 31, 2024. The patient were identified through the Mayo Adult Congenital Heart Disease (MACHD) Registry. The patients were classified as simple cc-TGA versus complex cc-TGA, and complex cc-TGA was defined as having associated lesions such as ventricular septal defect, left ventricular (LV) outflow tract obstruction (subvalvular or valvular pulmonic stenosis, and pulmonary atresia), or any other hemodynamically significant lesion other than an atrial septal defect.
Data collection
Baseline characteristics
The first clinical encounter in the adult CHD clinic after January 1, 2003 was considered the baseline encounter, and clinical data (echocardiogram, electrocardiogram, ambulatory rhythm monitor, laboratory indices, and cardiac catheterization) obtained within 6 months from the baseline encounter were used to define the baseline clinical characteristics of the cohort. For the patients who underwent ICD implantation after the baseline encounter, the clinical data obtained within 6 months prior to ICD implantation were used to describe the baseline characteristics of the cohort.
ICD implantation
Indications for ICD implantation were classified as primary versus secondary prevention based on criteria stipulated in the guidelines. , Primary prevention was defined as ICD implantation for any of the following indications: (1) nonsustained ventricular tachycardia defined as wide QRS complex (≥120 milliseconds) arrhythmia originating from the ventricle consisting of ≥4 consecutive beats with rate >100 beats per minute and lasting ≤30 seconds. ,, (2) Severe systemic RV systolic dysfunction was defined as systemic RV ejection fraction (RVEF) <35%. , (3) Unexplained syncope. Secondary prevention was defined as ICD implantation for the following indications: (1) Resuscitated/aborted SCD (2) Sustained ventricular tachycardia defined as wide QRS complex (≥120 milliseconds) arrhythmia originating from the ventricle with rate >100 beats per minute and lasting >30 seconds. ,,
The ICD leads were classified as: endocardial, epicardial, and subcutaneous lead, respectively. , ICD implantation was considered de novo device implantation in patients without previous pacemaker implantation, or as device upgrade when an ICD was implanted in a patient with a preexisting pacemaker. ,
Echocardiography
Comprehensive 2-dimensional, Doppler, and speckle tracking echocardiography were performed according to contemporary guidelines. Offline imaging analyses were performed in all patients using a standardized imaging protocol in the MACHD Registry Imaging Core Laboratory. RV end-diastolic volume and end-systolic volume were traced in end-diastole and end-systole, respectively, using images acquired from the apical 4-chamber window, and RVEF was calculated using monoplane volumetric analysis. , In addition to RVEF, we assessed RV systolic function using RV free wall strain (RVFWS) and RV fractional area (RVFAC), and both indices were assessed using images obtained from the apical 4-chamber window. , RV systolic dysfunction as RVEF <50%, and moderate/severe RV systolic dysfunction was defined as RVEF <35%. , Similarly, nonsystemic LV end-diastolic volume, end-systolic volume, and LVEF were assessed using images obtained from apical 4-chamber window as described above. The severity of valve regurgitation was assessed using Doppler echocardiography.
Outcomes
The primary outcome was appropriate ICD shock, defined as ICD shocks triggered by sustained ventricular tachycardia or ventricular fibrillation. , The secondary outcome was inappropriate ICD shock defined as ICD shock triggered by lead dysfunction, atrial arrhythmias, ventricular arrhythmias not meeting criteria for appropriate shock, or misclassification of electrical signals such as T-wave oversensing. , The occurrence of ICD shocks was determined by reviewing the device interrogation reports from the time of device implantation or baseline encounter. The patients without primary or secondary outcomes were censored at the time of death or heart transplant, or December 31, 2024.
Exploratory outcomes were device-related complications (defined as the composite outcome of lead dysfunction or device-related infection) and all-cause mortality. Lead dysfunction was defined as the failure to accurately sense, pace, or deliver therapy due to electrical abnormalities such as increase in sensing or pacing threshold, or mechanical abnormalities such as lead fracture or noise. All-cause mortality was subclassified as cardiovascular death (defined as death due to heart failure, SCD, or postoperative death after cardiac surgery), noncardiovascular death, or unknown etiology. SCD was defined as death meeting any of these criteria: (1) death within 1 hour of cardiac manifestation in the absence of proceeding hemodynamic deterioration, (2) death during sleep, or (3) death within 24 hours after patient was last seen alive and apparently clinically stable.
Statistical analysis
Data were presented as mean ± standard deviation, median (Q1, Q3), and count (%). Between-group comparisons were performed using an independent t-test, and Fisher’s exact test, as appropriate. The annual incidence of ICD shock was calculated as the quotient of total number of ICD shocks and the total duration of follow-up for the entire cohort (patient-years). The correlates of appropriate ICD shocks were assessed using univariable Cox regression analysis. The variables included in the Cox regression model were chosen based on clinical relevance, as well as published studies. All statistical analyses were performed with BlueSky Statistics software (version. 7.10; BlueSky Statistics LLC, Chicago, IL, USA), and JMP statistical software (version 17.1.0, JMP Statistical Discovery LLC, NC). P value <.05 was considered to be statistically significant for all analyses.
Results
Baseline characteristics
Of 278 adults with cc-TGA in the MACHD Registry, 87 (31%) underwent ICD implantation. Supplementary Table SI compares baseline characteristics of patients with versus without ICD implantation. Compared to patients without ICD implantation, those with ICD implantation had more comorbidities and also had worse RV systolic function (RVEF 31±14% versus 38±115, P =.03; RVFWS −17±6% versus −20±5%, P =.007) and invasive hemodynamic indices (pulmonary artery [PA] wedge pressure 17 [13, 24] versus 13 [10, 18] mmHg, P <.001; PA mean pressure 29 [20, 38] versus 21 [14, 30] mmHg, p <.001).
Among 87 patients with ICD implantation, the mean age at ICD implantation was 45±15 years, 51 (59%) were males, and 44 (51%) had complex cc-TGA. Tables I and II show the baseline characteristics and hemodynamic indices of the cohort. The mean systemic RVEF was 31±14%, and all 87 (100%) patients had systemic RV systolic dysfunction (RVEF <50%), while 59 (68%) had moderate/severe systemic RV systolic dysfunction (RVEF <35%). The mean systemic RVFWS and RVFAC were −17±6% and −25±10%, respectively, and 31 (37%) patients had ≥moderate systemic tricuspid regurgitation. Of the 87 patients, 52 (60%) underwent cardiac catheterization prior to ICD implantation, and the RA pressure was 10 (8,15) mmHg, PA mean pressure was 29 (20, 38) mmHg, and PA wedge pressure was 17 (13, 24) mmHg.
Table I
Baseline characteristics ( N = 87)
| Demographic indices | |
| Age, years | 45±15 |
| Male sex | 51 (59%) |
| Body mass index, kg/m 2 | 27±6 |
| Complex cc-TGA | 44 (51%) |
| Heart rate, bpm | 63±14 |
| Prior cardiac procedures | |
| Tricuspid valve replacement | 22 (25%) |
| Ventricular septal defect closure | 39 (45%) |
| PVR/LV-PA conduit placement | 6 (7%) |
| Comorbidities | |
| Hypertension | 25 (29%) |
| Diabetes | 12 (14%) |
| Chronic kidney disease | 13 (15%) |
| Atrial fibrillation | 49 (56%) |
| Laboratory indices | |
| Estimated GFR, ml/min/1.73 m 2 | 80±24 |
| MELD-XI score | 11.5 (9.5,13.3) |
| NT-proBNP, pg/ml | 573 (159, 1196) |
| Medications | |
| Loop diuretics | 43 (49%) |
| ACEI/ARB | 64 (74%) |
| ARNI | 25 (29%) |
| MRA | 28 (32%) |
| Beta blockers | 56 (64%) |
| Class III AAD | 41 (47%) |
AAD , antiarrhythmic drug; ACEI , angiotensin converting enzyme inhibitor; ARB , angiotensin-II receptor blocker; ARNI , angiotensin receptor/neprilysin inhibitor; cc-TGA , congenitally corrected transposition of great arteries; PVR , pulmonary valve replacement; LV-PA , left ventricular to pulmonary artery; MRA , mineralocorticoid receptor antagonist; MELD-XI , model for end-stage liver disease excluding international normalized ratio; NT-proBNP , N-terminal pro-B-type natriuretic peptide; GFR , glomerular filtration rate.
Data with presented as mean ± standard deviation, median (Q1; Q3), or count (%).
Table II
Hemodynamic indices
| Echocardiography | N = 87 |
|---|---|
| Systemic indices | |
| LA volume index, ml/m 2 | 66±47 |
| LA reservoir strain, % | 18±8 |
| RV end-diastolic volume index, ml/m 2 | 84±26 |
| RV end-systolic volume index, ml/m 2 | 66±19 |
| RV ejection fraction, % | 31±14 |
| RV end-diastolic area index, cm 2/m 2 | 43±12 |
| RV end-systolic area index, cm 2/m 2 | 33±12 |
| RV fractional area change, % | 25±10 |
| RV free wall strain, % | −17±6 |
| RV cardiac index, l/min/m 2 | 2.81±0.62 |
| ≥Mod tricuspid regurgitation | 31 (37%) |
| ≥Mod aortic regurgitation | 8 (9%) |
| Aortic valve mean gradient, mmHg | 6 ± 3 |
| Nonsystemic indices | |
| RA volume index, ml/m 2 | 27±12 |
| RA reservoir strain, % | 28±11 |
| RA pressure, mmHg | 9 ± 5 |
| LV end-diastolic volume index, ml/m 2 | 52±21 |
| LV end-systolic volume index, ml/m 2 | 21±13 |
| LV ejection fraction, % | 60±12 |
| LV longitudinal strain, % | −23±5 |
| LV systolic pressure, mmHg | 46 (34, 68) |
| Pulmonary valve mean gradient, mmHg | 5 (3, 20) |
| ≥Mod tricuspid regurgitation | 11 (13%) |
| ≥Mod pulmonary regurgitation | 10 (11%) |
| Cardiac catheterization | N = 52 |
|---|---|
| RA mean pressure, mmHg | 10 (8,15) |
| RV systolic pressure, mmHg | 71 (48,101) |
| PA systolic pressure, mmHg | 46 (34, 59) |
| PA mean pressure, mmHg | 29 (20, 38) |
| PA wedge pressure, mmHg | 17 (13, 24) |
| PVR index, wu*m | 3.89 (2.17, 5.13) |
| Cardiac index, l/min/m 2 | 2.22 (1.57, 2.52) |
RA , right atrium; RV, right ventricle; LV , left ventricle; LA , left atrium; PA , pulmonary artery; PVR , pulmonary vascular resistance.
Data with presented as mean ± standard deviation, median (Q1; Q3), or count (%).
Procedural data
Table III shows ICD data for the overall cohort. Of the 87 patients, 79 (91%) received endocardial ICD leads, 5 (6%) received epicardial ICD leads, and 3 (3%) received subcutaneous ICD leads. ICDs were implanted as de novo device implantation in 68 (78%) patients, and as device upgrade in 19 (12%) patients. Twenty-six (30%) patients underwent ICD implantation prior to baseline encounter, while 61 (70%) underwent ICD implantation after baseline encounter. Compared to patients who received ICD implantation prior to baseline encounter, those who received ICD implantation after baseline encounter were older at the time of ICD implantation (48±14 versus 39±15 years, P =.01) and less likely to have complex cc-TGA (27 [43%] versus 18 [69%], P =.02) ( Table III ).
Table III
ICD data
| Variables | All ( N = 87) | ICD implanted prior to baseline ( N = 26, 30%) | ICD implanted after baseline ( N = 61, 70%) | P |
|---|---|---|---|---|
| Demographic indices | ||||
| Age, years | 45±15 | 39±15 | 48±14 | .01 |
| Male sex | 51 (59%) | 15 (58%) | 36 (59%) | .91 |
| Complex cc-TGA | 45 (51%) | 18 (69%) | 27 (43%) | .02 |
| Systemic RV EF, % | 31±14 | 29±12 | 33±13 | .11 |
| Device data | ||||
| Endocardial lead | 79 (91%) | 23 (89%) | 56 (92%) | .87 |
| Epicardial lead | 5 (6%) | 2 (8%) | 3 (5%) | |
| Subcutaneous lead | 3 (3%) | 1 (4%) | 2 (3%) | |
| # of leads | ||||
| Single (LV) lead | 9 (10%) | 3 (12%) | 6 (10%) | .83 |
| Atrial and LV lead | 38 (44%) | 12 (46%) | 26 (43%) | |
| Biventricular lead | 40 (46%) | 11 (42%) | 29 (48%) | |
| Device implantation | ||||
| De novo implantation | 68 (78%) | 23 (89%) | 45 (74%) | .12 |
| Device upgrade | 19 (12%) | 3 (11%) | 16 (26%) | |
| Indication for ICD | ||||
| Primary prevention* | 67 (77%) | (69%) | 12 (80%) | .42 |
| Nonsustained VT | 17 (20%) | 7 (27%) | 10 (16%) | |
| RV EF <35% | 46 (53%) | 10 (39%) | 36 (59%) | |
| Unexplained syncope | 5 (9%) | 1 (4%) | 4 (7%) | |
| Secondary prevention | 20 (23%) | 8 (31%) | 12 (20%) | .42 |
| Aborted SCD | 11 (13%) | 3 (12%) | 8 (13%) | |
| Sustained VT | 9 (11%) | 5 (19%) | 4 (7%) |
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