Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome

Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome

Chiriac A, Riley DC, Russell M, Moore JP, Padmanabhan D, Hodge DO, Spiegel MR, Vargas ER, Phillips SD, Ammash NM, Madhavan M, Asirvatham SJ, McLeod CJ.

J Am Heart Assoc. 2020 Mar 17;9(6):e014554. doi: 10.1161/JAHA.119.014554. Epub 2020 Mar 15.

PMID: 32174228 Free Article

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Take Home Points:

  • This is a large contemporary longitudinal study of Eisenmenger patients at 2 large US Academic centers
  • Predictors of sudden cardiac death in this cohort were (on univariate analysis):
    • Older age HR 1.03
    • LVEF <40% HR 3.38
    • Right Atrial Pressure > 10mmHg HR 2.49
    • Atrial fibrillation HR 6.36
    • Complete Heart block HR 27.49
    • QRS duration >120ms HR 2.34
    • Presence of a pacemaker HR 2.75
    • Advanced pulmonary hypertensive drugs – protective HR 0.21
  • On multivariate analysis, only AF and QRS duration >120ms remained as adverse predictors, the use of advanced pulmonary hypertensive drugs remained protective.


Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch: In patients with Eisenmenger syndrome, little is known about the risk factors for sudden cardiac death (SCD). Previously recognized predictors for all-cause mortality in this population included oxygen saturations, arrythmias and type of defect (pre-vs post-tricuspid). In this retrospective review, 2 tertiary centers in the USA followed up patients with Eisenmenger syndrome to help elucidate the predictive factors for SCD.
The review was conducted at The Mayo Adult Congenital Heart Disease Clinic and the Ahmanson/UCLA Adult Congenital Heart Disease Center for the period 1987 to 2015. A total of 246 patients were reviewed. Sixty-five percent were women and the mean age was 37.3 years. The median follow-up period was 7.1 years.
The defect distribution was as follows: ventricular septal defect (42%, n=104), atrial septal defect (24.4%, n=48 secundum, 11 sinus venosus, 1 coronary sinus ASD), PDA (12%, n=30). Atrioventricular canal defects were present in 17% (n=42), and 13% (n=32) had characteristics of single ventricle physiology. Of these patients, 15.4% (n=38) have in fact had a palliative procedure in the past. A total of 42 patients (17%) had Downs syndrome, with atrioventricular canal defects being the most common defect in this group.
Heart failure was seen in 42.3% of patients. Only 3.7% had documented coronary artery disease. Syncope was documented in 20 patients (8.1%). Nineteen patients were listed for transplant – 7 (3%) had received a combined heart/double lung transplant.
Two-hundred and eighteen patients had a systemic LV – with a mean LVEF of 52%. More than 60% of patients had RV enlargement and moderate to severe RV dysfunction was present in 55.3%. The RA pressure was elevated in 92 patients (49.7%). The estimated RVSP was >80mmHg in 83.4% of cases
Most patients were in sinus rhythm at first consultation, but many exhibited intermittent atrial arrythmias. After complete follow up, atrial fibrillation was noted in up to 16.7% (n=41) of patients. Both atrial and other supraventricular tachycardias were seen in an additional 20% of patients on follow-up. Only 3.7% had sustained ventricular arrythmias. Thirty percent of patients were on anti-arrhythmic drugs..
Thirteen patients had pacemakers (5.3%) – 7 epicardial and 6 transvenous systems. Four had intra-cardiac defibrillators (ICD’s). The indications for pacing were complete heart block, sinus node dysfunction, sinoatrial exit block. Anticoagulation was prescribed in 22.4% (n=55), mainly for atrial fibrillation or atrial flutter. Forty-three percent (n=105) were treated with advanced pulmonary hypertension therapies.
Clinical outcomes in patient with Eisenmenger syndrome.
A total of 136 patients died during follow-up. In 40 patients (16.3%), the cause was sudden cardiac death (see figure 1 above). The patients with non-sudden cardiac death was mainly due to heart failure.
Clinical Parameters and Total Mortality
On univariate analysis – table 3 above, age (p<0.001), male sex (p=0.02), clinical heart failure (p<0.001) and atrial fibrillation at presentation (p=0.022) were significant independent predictors of total mortality. Advanced pulmonary hypertensive therapies were protective (p<0.001). Combined ASD and VSD was associated with a higher mortality (HR 4.34, 95% CI 1.72-10.95, p=0.002).
Clinical Parameters and SCD
For sudden cardiac death, age (p=0.011) and atrial fibrillation (p<0.011) remain independent predictors. The presence of a pacemaker increases risk of SCD – HR 2.75 (95% CI 1.07 – 7.06). There was no association between type of anatomical defect and risk of SCD. Downs syndrome also did not confer increased risk (HR 1.24, p=0.582)
Once again, advanced therapies for pulmonary hypertension was strongly protective, reducing the risk 5-fold (HR 0.21, 95% CI 0.1-0.44, p<0.001).
Echocardionagphy and Outcomes
Independent echo predictors of mortality for sudden cardiac death were: Reduced LVEF (<40% – for these the overall mortality was 83% – HR 3.38, 95%CI 1.71-6.66, p<0.001), increased RA pressure >10mmHg (HR 2.49, 95%CI 1.13-5.48, p=0.024), RV index for myocardial performance (RIMP)(HR 6.16, 95%CI 1.92-19.61, p=0.002).
Findings on the Initial ECG and  Subsequent Risk of Death
Please refer to the table 6 above for the ECG predictors of sudden cardiac death: Atrial fibrillation (HR 6.35), Complete Heart block (HR 27.49), QRS duration >120ms (HR 2.34), Right atrial enlargement (HR 2.11), RBBB (HR 2.4). Arrythmia surveillance was not part of a protocol, and screening was done at the discretion of the attending clinician. There was no significant association between anti-arrhythmic medication use or ablation in the prevention of SCD – these numbers were small though so it’s unlikely that meaningful conclusions could be drawn.
The presence of a pacemaker was significantly associated with an increased risk of SCD (HR 2.75, 95%CI 1.07-7.06, p=0.036). Of the 13 with pacemakers, 5 had SCD. Those with a high ventricular pacing burden were more likely to suffer SCD compared to those with atrial only pacing.
Figure 3: Survival free of sudden cardiac death on the basis of the presence of atrial fibrillation.
On multivariate analysis, atrial fibrillation, QRS duration>120ms, and advanced therapies for pulmonary hypertension remained significant – Figure 3 above shows the survival curves for these 3 groups:
A: Atrial fibrillation (HR 11.45, p<0.0001)
B: QRS duration >120ms (HR 2.51, p=0.0072)
C: Advanced ongoing therapies for pulmonary hypertension conferred benefit (HR 0.14, p<0.0001)
This is obviously a retrospective review and subject to the same limitations and biases.