Predictors of mortality and ICD shock therapy in primary prophylactic ICD patients-A systematic review and meta-analysis

Abstract

Background: There is evidence that the benefit of a primary prophylactic ICD therapy is not equal in all patients.

Purpose: To evaluate risk factors of appropriate shocks and all- cause mortality in patients with a primary prophylactic ICD regarding contemporary studies.

Data source: PubMed, LIVIVO, Cochrane CENTRAL between 2010 and 2016.

Study selection: Studies were eligible if at least one of the endpoints of interest were reported.

Data extraction: All abstracts were independently reviewed by at least two authors. The full text of all selected studies was then analysed in detail.

Data synthesis: Our search strategy retrieved 608 abstracts. After exclusion of unsuitable studies, 36 papers with a total patient number of 47282 were included in our analysis. All-cause mortality was significantly associated with increasing age (HR 1.41, CI 1.29-1.53), left ventricular function (LVEF; HR 1.21, CI 1.14-1.29), ischemic cardiomyopathy (ICM; HR 1.37, CI 1.14-1.66) and co-morbidities such as impaired renal function (HR 2.30, CI 1.97-2.69). Although, younger age (HR 0.96, CI 0.85-1.09), impaired LVEF (HR 1.26, CI 0.89-1.78) and ischemic cardiomyopathy (HR 2.22, CI 0.83-5.93) were associated with a higher risk of appropriate shocks, none of these factors reached statistical significance.

Limitations: Individual patient data were not available for most studies.

Conclusion: In this meta-analysis of contemporary clinical studies, all-cause mortality is predicted by a variety of clinical characteristics including LVEF. On the other hand, the risk of appropriate shocks might be associated with impaired LVEF and ischemic cardiomyopathy. Further prospective studies are required to verify risk factors for appropriate shocks other than LVEF to help select appropriate patients for primary prophylactic ICD-therapy.

Fig 1. Flow chart showing the results of the literature search and the number of available studies regarding the chosen end-points and the considered factors.

HR stands for hazard ratio and PP for primary prevention.

Fig 2. Visualization of the risk of bias assessments of the 36 identified studies.

The unclear risk of bias regarding patients‘ selection is due to secondary analyses of a randomized controlled trial and studies with some specific inclusion criteria on the consecutive patients. In case of the missing values and the measurement of covariates, a high risk is associated with omitted reporting. The risk evaluation regarding confounders reflects the number of studies supplying only univariate results (high risk), both univariate and multivariate results (unclear risk), and only multivariate results (low risk) for our analyses.

Fig 3. Forest plot showing pooled hazard ratios for the effect of age at implantation on instantaneous risk (Cox PH model) and cumulative incidence (Fine & Gray model) of the first appropriate shocks.

HR of 1 corresponds to no age effect. PP indicates re-analysis of the primary prevention subgroup. Reported are the pooled results obtained by the Bayesian (Bayes) and the standard (DL) approach. DL stands for DerSimonian-Laird (for details see the section Methods).

Fig 4. Forest plot showing pooled hazard ratios for the effect of age at implantation on the risk of death.

Univariable models are denoted with *. HR of 1 corresponds to no age effect. Reported are the pooled results obtained by the Bayesian approach (Bayes) and the standard (DL: DerSimonian-Laird) approach (for details see the section Methods).

Fig 5. Forest plot showing pooled hazard ratio for the effect of LVEF at implantation on instantaneous risk (Cox PH model) of the first appropriate shock.

HR of 1 corresponds to no LVEF effect. PP denotes re-analysis for primary prevention subgroup. Reported are the pooled results obtained by the Bayesian (Bayes) and the standard (DL) approach. DL stands for DerSimonian-Laird (for details see the section Methods).

Fig 6. Forest plot showing pooled hazard ratios for the effect of LVEF at implantation on the risk of all-cause mortality.

HRs coming from univariable models are denoted with *. HR of 1 corresponds to no LVEF effect. PP denotes re-analysis of primary prevention subgroup. Reported are the pooled results obtained by the Bayesian (Bayes) procedure and the standard (DL: DerSimonian-Laird) approach (for details see the section Methods).

Fig 7. Forest plot showing pooled hazard ratio for the effect of NYHA class on the risk of all-cause mortality.

HRs coming from univariable models are denoted with *. HR of 1 corresponds to no difference between NYHA classes >II and ≤ II. Reported are the pooled results obtained by the Bayesian (Bayes) and the standard (DL: DerSimonian-Laird) approach (for details see the section Methods).

Fig 8. Forest plot showing pooled hazard ratio comparing the risk of all-cause mortality for CRT-D patients and those with ICD only.

HRs coming from univariable models are denoted with *. HR of 1 corresponds to no difference between the groups. Reported are the pooled results obtained by Bayesian (Bayes) and the standard (DL: DerSimonian-Laird) approach (for details see the section Methods).

Fig 9. Forest plot showing pooled hazard ratio comparing instantaneous risks of the first appropriate shock for patients with ICM and those without this condition.

HR of 1 corresponds to no difference between the groups. PP indicates a re-analysis for the primary prevention subgroup. Reported are the pooled results obtained by the Bayesian (Bayes) and the standard (DL) approach. DL stands for DerSimonian-Laird (for details see the section Methods).

Fig 10. Forest plot showing pooled hazard ratios comparing the risk of all-cause mortality for patients with comorbidities and those without.

HRs coming from univariable models are denoted with *. HR of 1 corresponds to no difference between the groups. Reported are the pooled results obtained by the Bayesian (Bayes) and the standard (DL: DerSimonian-Laird) approach (for details see the section Methods).

Fig 11. Forest plot showing pooled hazard ratios capturing the effect of a decreasing eGFR on the risk of all-cause mortality.

HRs coming from univariable models are denoted with *. eGFR is measured in mL/min/1.73 m2 and calculated by the Cockroft-Gault formula (22) or the MDRD (Modification of Diet in Renal Disease) formula (all other studies). HR of 1 corresponds to no effect of decreasing eGFR. PP indicates re-analysis for primary prevention subgroup. Reported are the pooled results obtained by the Bayesian (Bayes) procedure and the standard (DL: DerSimonian-Laird) approach (for details see the section Methods).

Fig 12. Forest plot showing hazard ratios comparing cumulative incidences of the first appropriate shock for patients with prescribed Amiodarone and those without.

HR of 1 corresponds to no difference between the patient groups. PP indicates re-analysis for the primary prevention subgroup.

Fig 13. Forest plot showing pooled hazard ratios comparing the risk of all-cause mortality for patients with medication prescribed at baseline and those without.

HRs coming from univariable models are denoted with *. HR of 1 corresponds to no difference between the groups. PP indicates a re-analysis for the primary prevention subgroup. Reported are the pooled results obtained by the Bayesian (Bayes) and the standard (DL: DerSimonian-Laird) approach (for details see the section Methods).