Increased All-Cause Mortality Risk in Ischemic vs Nonischemic Cardiomyopathy

implantable cardiac device, ICD, pacemaker
This study examined outcomes in patients with ischemic vs nonischemic cardiomyopathy who are treated with ICD therapy for the primary prevention of sudden cardiac death.

Patients with ischemic cardiomyopathy (ICM) have a similar risk of life-threatening ventricular arrhythmic events and an increased risk of all-cause mortality compared with patients with nonischemic cardiomyopathy (NICM), according to research results published in JACC: Clinical Electrophysiology.

Using a combined database of 5 landmark implantable cardioverter-defibrillator (ICD) trials, researchers set out to evaluate the differences in outcomes in patients with ischemic vs nonischemic cardiomyopathy who are treated with ICD therapy for the primary prevention of sudden cardiac death (SCD).

The current study included data from patients enrolled in the MADIT, MADIT-II, M2Risk, MADIT-CRT, MADIT-RIT, and RAID clinical trials, conducted between July 1997 and January 2017.

The primary study endpoint was the first incidence of sustained ventricular tachycardia (VT) with a heart rate of ≥200 beats per minute or ventricular fibrillation (VF), both treated and monitored. Investigators considered VT sustained if it persisted for at least 30 seconds or required termination. The prespecified study endpoints included all-cause mortality, any sustained VT ≥170 beats per minute, or VF, as well as appropriate ICD therapy for VT/VF.

Exploratory endpoints included the combined endpoint of heart failure (HF) or mortality, inappropriate defibrillator therapy, including shocks or antitachycardia pacing, and atrial fibrillation, or supraventricular tachycardia.

The participants across all studies included 4803 adults who had an ICD placed for the primary prevention of SCD. Patients with ICM were older, more likely to be men, more likely to be White, and more likely to have comorbid conditions like hypertension, diabetes, renal insufficiency, and tobacco use compared with patients with NICM. These patients were also more likely to be taking antiplatelet or statin therapy.

Conversely, those with NICM were significantly more likely to have advanced symptoms of HF (NYHA Class II or III), to be taking HF medications like antiangiotensin drugs, aldosterone, beta-blockers, or diuretic agents, and were more likely to have a cardiac resynchronization therapy plus defibrillator (CRT-D) device in place.

Observed cumulative incidence of the primary endpoint of life-threatening VT or VF at 3.5 years follow-up was similar in both patient populations (ICM 15% vs NICM 16%). Findings for secondary endpoints were similar: 23% vs 22% for any VT ≥170 beats per minute and 24% vs 23% for appropriate ICD therapy.

Results of multivariate analyses demonstrated that the risk of all ventricular arrhythmic events were similar between groups.

Investigators also performed subgroup analyses exploring the relationship between VT and VD in the ICM vs NICM group; the interaction between subgroups and ICM status was also evaluated. No subgroups and interactions were associated with significant difference in the likelihood of ventricular arrhythmia between groups.

Patients with NICM were significantly more likely to experience supraventricular arrhythmias, including atrial fibrillation or supraventricular tachycardia, vs patients with IC. This difference, however, was not statistically significant. Inappropriate ICD shocks were also more common in the NICM group, but the difference was nonsignificant after adjustment for baseline variables.

At 3.5 years, cumulative probability of death in the ICM group was 16%, vs 7% in the NICM group. Results of a multivariate Cox proportional hazards regression analysis showed that patients with ICM maintained a 1.8-fold higher all-cause mortality vs the NICM group (hazard ratio [HR], 1.84; 95% CI, 1.42-2.38). The risk of HF or mortality was also significantly higher in this group.

As CRT-D was significantly more likely to be present at study enrollment in the NICM group, researchers further investigated the interaction between CRT-D and cardiomyopathy type. Investigators found that the significant association between ICM and all-cause mortality was persistent in patients with and without CRT-D at enrollment. At 3.5 years, unadjusted cumulative probability of non-sudden cardiac mortality in the ICM vs NICM group was 7% vs 3%, respectively for the entire population, 7% vs 3% for patients without CRT-D at enrollment, and 6% vs 2% for patients with CRT-D.

Mortality due to cardiac and noncardiac causes was significantly more frequent in the ICM group vs the NICM group. At 3.5 years, unadjusted cumulative probability of cardiac mortality was 9% vs 4%, respectively, and 6% vs 2% due to noncardiac causes.

In further evaluation of cardiac mortality by cause, SCD at 3.5 years was noted in 3% vs 1% of ICM and NICM patients, respectively; non-sudden cardiac mortality was seen in 7% and 3% of each group.

Study limitations include the use of data over a 20-year period “during which medical treatment of HF and ICD programming have evolved,” according to researchers, as well as the substantial use of pharmacological therapies in the study population and the limited generalizability outside of the study population due to the specific inclusion and exclusion criteria.

“The present study identified significant differences in clinical outcomes between patients with ICM vs NICM,” the researchers concluded. “These findings provide support for ongoing research aimed at further delineating which individuals with ICM and NICM are most likely to benefit from ICD therapy.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Narins CR, Aktas MK, Chen AY, et al. Arrhythmic and mortality outcomes among ischemic versus nonischemic cardiomyopathy patients receiving primary implantable cardioverter-defibrillator therapy. JACC Clin Electrophysiol. Published online August 13, 2021. doi:10.1016/j.jacep.2021.06.020