Comparison of ventricular tachyarrhythmia recurrence between ischemic cardiomyopathy and dilated cardiomyopathy: a retrospective study

Database

The protocol was set according to our previous work examining predictors for recurrent VT/VF in secondary prevention ICD recipients (Lee et al., 2016). The type of data collected was also similar to that in the above study. Specifically, the study extended to the follow-up period and enrolled more patients in our hospital. In addition, the study focused on the comparison of recurrent VT/VF between the ICM and the DCM groups. Recurrent VT/VF was defined as a sustained VT (duration longer than 30 s) and VF. Baseline characteristics such as general demographics, heart diseases, comorbidities, the LV function, the functional class of HF, QRS length, primary presenting rhythm, systolic blood pressure (SBP), renal function, medication, VT/VF detection zone, and VT ablation were compared between the two groups. According to the chart review, data on cardiovascular death and all-cause death were collected and compared between the groups. All patients who received ICD implantation had regular out-patient department follow-ups and underwent ICD record follow-up every three months in our hospital.

Patient population (inclusion and exclusion criteria)

From May 2004 to December 2015, 132 consecutive patients, who had survived sudden death related to VT/VF events, were diagnosed with ICM or DCM, and received ICD implantation for secondary prevention were enrolled in this study in Kaohsiung Chang Gung Memorial Hospital. We excluded the patients who received implantable cardiac resynchronization therapy defibrillator implantation and those with other etiologies, such as Brugada syndrome, idiopathic VF or arrhythmogenic right ventricular cardiomyopathy receiving ICD implantation. The ICM group comprised 94 patients, and the non-ischemic DCM group comprised 38 patients. In the DCM group, all patients underwent coronary angiography to exclude obstructive coronary lesions. Only seven patients had focal 50% stenotic lesions in the coronary artery that did not involve the left anterior descending artery. All patients received the echocardiography evaluation at the registry inclusion prior to ICD implantation. All patients were also administered guideline-base treatments for ventricular tachyarrhythmia and HF if the patient could tolerate without decrease of renal function. All information from ICD integgoration during follow-up or anti-tachycardia events were reviewed and validated with the occurrences of VT/VF and anti-tachycardia therapy (anti-tachycardia pacing or shock) by two different electrophysiologists independently.

Echocardiography

Echocardiographic parameters, including LV diastolic dysfunction, LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV), were measured using a Philips IE33 or GE’s Vivid 9. LVEDV and LVESV were quantified by M-mode and corrected by the two-dimensional guided biplane Simpson’s method of disc measurements by echocardiography (Crawford et al., 1980; Lang et al., 2005).

Study endpoints

The primary study endpoints included the recurrence of sustained VT/VF (longer than 30 s) which needed anti-tachycardia pacing therapy or ICD shock therapy. The secondary endpoints included cardiovascular death (death related to HF and arrhythmic death) and all-cause mortality from any cause (including cardiovascular death, sepsis, hepatic failure, and brain hemorrhage).

Ethics statement

The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Committee for Human Research (201701405B0) of our institution. The raw data were from the ICD registry of Kaohsiung Chang Gung Memorial Hospital. The accession number for the KCGMH ICD registry was 104-8143B, and it was deposited at the Kaohsiung Chang Gung Memorial Hospital.

Statistical analysis

Data are presented as mean ± standard deviation or percentages; median and interquartile range were used for non-normally distributed parameters. The clinical characteristics of the study groups were compared by the t-test or Mann–Whitney U test for continuous variables or chi-square test or Kruskal–Wallis test for categorical variables. The significant predictors for the recurrence of VT/VF after ICD implantation were identified by the univariate and multivariate Cox regression analyses. Each independent variable was based on previous studies and conventional risk factors, and predictors for the recurrence of VT/VF were expressed as hazard ratios with 95% confidence intervals. Receiver operating characteristic (ROC) curves were used to determine the optimal values in terms of sensitivity and specificity. The Kaplan–Meier method and log-rank test were used to compare the event-free survival of the recurrence of VT/VF, cardiovascular mortality, and all-cause mortality during follow-up. Statistical analysis was carried out using statistical software (SPSS for Windows, Version 22; SPSS, Inc., Chicago, IL, USA). A two-sided p-value of 0.05 was considered statistically significant.

Receiver operating characteristic curves

Receiver operating characteristic curves for LVEDV were constructed, and they revealed that the cut-off point for the LVEDV was 158 mL. This resulted in the best sensitivities and specificities of recurrent VT/VF in the ICM group; the areas under these curves was 0.694 (p = 0.002). In the DCM group, ROC curves for LVEDV did not have significant values for recurrent VT/VF.

Baseline characteristics of study patients

A total of 94 patients with a mean age of 66.7 ± 10 years were in the ICM group, and the majority was male (77.7%). A total of 38 patients with a mean age of 59.7 ± 12 years were in the non-ischemic DCM group and the majority was male (78.9%). The ICM group contained a statistically significant number of older patients and had a significantly higher prevalence of coronary artery disease, hypertension, diabetes mellitus, and hyperlipidemia than did the ICM group (Table 1). The HF functional class was similar between the two groups. The majority of primary presenting rhythm was VT in the ICM group, and the majority of the primary presented rhythm was VT plus VF in the DCM group (p < 0.001). SBP was well controlled in both groups and was higher in the DCM group. The prevalence of the use of angiotensin-converting-enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was significantly lower and the prevalence of the use of statin, and anti-platelet agents was significantly higher in the ICM group compared to the DCM group. Only eight (8.5%) patients in the ICM group and six (15.8%) patients in the DCM group received VT ablation (p = 0.226). The DCM group had a lower LVEF (37.46 ± 14.57% vs. 44.40 ± 15.32%; p = 0.019), a larger LVEDV (209.0 (167.0–264.0) vs. 167.0 (124.0–201.0) mL; p = 0.001), higher prevalence of LVEDV >158 mL (78.4% vs. 53.2%; p = 0.010), and a larger LVESV (121.0 (74.8–168.5) vs. 85.5 (59.0–130.0) mL; p = 0.010) than the ICM group.

Differences in the incidence of recurrent VT/VF, cardiovascular mortality, and all-cause mortality during follow-up between ICM and DCM patients

The median number of follow-up years was similar between the two groups (3.03 (1.33–5.70) years vs. 3.01 (1.01–6.06) years; p = 0.966). The DCM group had a significantly higher incidence of recurrent VT/VF (57.9% vs. 36.2%; p = 0.032) than the ICM group. The difference in event-free survival from VT/VF occurrence between the ICM and DCM patients began to separate at the 3-year follow-up and became significant at the 5-year follow-up (57.7% vs. 84.6%; p = 0.022) (Fig. 1).

There were no significant differences in cardiovascular mortality and all-cause mortality between the two groups at the 1-year and 3-year follow-ups (Table 1). Five patients in the ICM group had cardiovascular deaths due to refractory VT/VF, and three patients in the DCM group experienced cardiovascular death (two patients because of severe HF with cardiogenic shock and one patient because of refractory VT/VF) at the 1-year follow-up (Table 1).

Clinical predictors of recurrence of VT/VF in patients with ICM

On univariate Cox regression analyses, larger LVEDV, LVEDV >158 mL, non-use of ACEI/ARB, and use of spironolactone were found to be statistically significant predictors of recurrence of VT/VF in patients with ICM (Table 2). By multivariate Cox regression analyses of LVEDV >158 mL, no use of ACEI/ARB, and the use of spironolactone, LVEDV >158 mL and no use of ACEI/ARB were independent predictors of recurrence of VT/VF in patients with ICM (Table 2).

Clinical predictors of recurrence of VT/VF in patients with DCM

By univariate Cox regression analyses, age, gender, atrial fibrillation, LV function, LV volume, clinical HF functional class, QRS length, and medications (ACEI/ARB, ß-blocker, amiodarone, spironolactone) were not predictors of recurrence of VT/VF in patients with DCM (Table 3).

Comparison of the recurrent rate of VT/VF between DCM patients and ICM patients with LV volume and function like DCM patients

A total of 50 ICM patients had LVEDV >158 mL and the mean LV function and volume like the 38 DCM patients. These 50 ICM patients were older and had less use of ACEI/ARB than the 38 DCM patients (Table 4) and there was no difference in the clinical functional class of HF, QRS length, the prevalence of use of ß-blocker, diuretics, spironolactone, and amiodarone between the 50 ICM patients and 38 DCM patients. The 1-year recurrence rate of VT/VF (34.0% vs. 35.3%; p = 1.000), 1-year cardiovascular mortality, and 1-year all-cause mortality did not differ between these 50 ICM patients and the 38 DCM patients (Table 4; Fig. 2).

The incidence of recurrent ventricular tachyarrhythmia in the patients with improving LVEDV or LVEF at 1-year follow-up period

After excluding the expired patients and the patients who did not receive the follow-up echocardiography between the half-year and 1-year follow-up period, a total the 101 patients received follow-up echocardiography after at least half a year of medical treatment. LVEDV regressed ≥10% with less prevalence of recurrent ventricular tachyarrhythmia but did not reach significance (Table 5). LVEDV still greater than 158 mL had a significantly higher prevalence of recurrent ventricular tachyarrhythmia (LVEDV >158 vs. ≤158 mL; 54.2% vs. 31.0%; p = 0.026) (Table 5). The patients with improving LVEF greater than 5% did not have a lesser prevalence of recurrent ventricular tachyarrhythmia (Table 5).

Study limitations

This retrospective analysis had several limitations. First, this study population was relatively small. However, we provided important information in terms of the difference in clinical predictors for recurrent VT/VF, after receiving ICD for secondary prevention, between patients with ICM and patients with non-ischemic DCM. Second, electrocardiographic variability and biomarkers were not included in the analysis, and this study included only conventional clinical parameters.