Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial.

BACKGROUND: Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. METHODS: Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. RESULTS: We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531-0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116-0.343, p < 0.0001) lower SCD risk. CONCLUSIONS: There was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02099721.

The mortality analysis of primary prevention patients receiving a cardiac resynchronization defibrillator (CRT-D) or implantable cardioverter-defibrillator (ICD) according to guideline indications in the improve SCA study.

BACKGROUND: In primary prevention (PP) patients the utilization of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy-defibrillators (CRT-D) remains low in many geographies, despite the proven mortality benefit. PURPOSE: The objective of this analysis was to examine the mortality benefit in PP patients by guideline-indicated device type: ICD and CRT-D. METHODS: Improve sudden cardiac arrest was a prospective, nonrandomized, nonblinded multicenter trial that enrolled patients from regions where ICD utilization is low. PP patient's CRT-D or ICD eligibility was based upon the 2008 ACC/AHA/HRS and 2006 ESC guidelines. Mortality was assessed according to guideline-indicated device type comparing implanted and nonimplanted patients. Cox proportional hazards methods were used, adjusting for known factors affecting mortality risk. RESULTS: Among 2618 PP patients followed for a mean of 20.8 ± 10.8 months, 1073 were indicated for a CRT-D, and 1545 were indicated for an ICD. PP CRT-D-indicated patients who received CRT-D therapy had a 58% risk reduction in mortality compared with those without implant (adjusted hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.28-0.61, p < .0001). PP patients with an ICD indication had a 43% risk reduction in mortality with an ICD implant compared with no implant (adjusted HR: 0.57, 95% CI: 0.41-0.81, p = .002). CONCLUSIONS: This analysis confirms the mortality benefit of adherence to guideline-indicated implantable defibrillation therapy for PP patients in geographies where ICD therapy was underutilized. These results affirm that medical practice should follow clinical guidelines when choosing therapy for PP patients who meet the respective defibrillator device implant indication.

Risk factors for mortality in post-myocardial infarction patients: insights from the improve SCA bridge study.

BACKGROUND: Underutilization of implantable cardioverter defibrillators (ICD) to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients remains an issue across several geographies. A better understanding of risk factors for SCD in post-MI patients from regions with low ICD adoption rates will help identify those who will benefit from an ICD. This analysis assessed risk factors for all-cause and cardiovascular-related mortality in post-MI patients from the Improve Sudden Cardiac Arrest (SCA) Bridge Trial. RESULTS: For the entire cohort, the overall 1-year mortality rate was 5.9% (88/1491) and 3.4% (51/1491) for all-cause and cardiovascular mortality, respectively, with 76.5% of all cardiac deaths being from SCD. A multivariate model determined increased age, reduced left ventricular ejection fraction (LVEF), increased time from myocardial infarction to hospital admission, being female, being from Southeast Asia (SEA), and having coronary artery disease to be significant risk factors for all-cause mortality. The risk factors for cardiovascular-related mortality revealed increased age, reduced LVEF, and being from SEA as significant risk factors. CONCLUSIONS: We show several characteristics as being predictors of cardiovascular-related mortality in post-MI patients from the Improve SCA Bridge study. Patients who experience an MI and present with these characteristics would benefit from a referral to an electrophysiologist for further SCD risk stratification and management and possible subsequent ICD implantation to reduce unnecessary death.

Personalized Intervention Strategy Based on a Risk Score Generated From Subcutaneous Insertable Cardiac Monitor: Results From Phase 1 of ALLEVIATE-HF.

BACKGROUND: Diagnostic variables from insertable cardiac monitors may be useful in identifying patients at increased risk of heart failure (HF) events. High-risk alerts must be coupled with interventions to improve outcomes. We aim to assess the safety of a predefined protocolized intervention pathway activated by insertable cardiac monitor high-risk alerts. METHODS AND RESULTS: ALLEVIATE-HF (Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure) Phase 1 was a randomized interventional study enrolling patients with New York Heart Association class II/III and a recent HF event. A HF risk score based on insertable cardiac monitor diagnostics, including impedance, respiration rate, atrial fibrillation burden, heart rate during atrial fibrillation, heart rate variability, and activity duration, was calculated. A protocolized intervention pathway was activated when high-risk scores were detected that involved physician-prescribed nurse-implemented uptitration of diuretic for 4 days, unless safety rule-out conditions were met. Interventions could be repeated if high-risk scores persisted and did not require worsening symptoms. In total, 59 patients were randomized (mean age 68.2±11.8 years; 59.3% male); 67.8% with ejection fraction ≥50%. The mean follow-up was 11.8±8.1 months. Overall, 146 high-risk scores were recorded in 33 patients and 118 interventions occurred in 75 (51.4%) high-risk alerts that did not meet safety rule-out criteria. There were no serious adverse events and 13 adverse events related to interventions. In patients with symptoms at intervention initiation, symptoms resolved in 37 interventions (80%) and worsened in 8 (17%). In asymptomatic patients, symptoms developed in 3 interventions (7%). CONCLUSIONS: A personalized medication intervention based on insertable cardiac monitor risk score can be safely instituted in patients with HF, irrespective of symptoms. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04452149.

Cardioverter-defibrillator reduces mortality risk in eligible ischemic and non-ischemic cardiomyopathy patients: Sub-analysis of the multi-center Improve SCA study.

BACKGROUND & OBJECTIVE: Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA trial demonstrated that primary prevention (PP) patients in these regions benefit from an ICD or a cardiac resynchronization therapy defibrillator (CRT-D). We aimed to compare the rate of device therapy and mortality among ischemic and non-ischemic cardiomyopathy (ICM and NICM) PP patients who met guideline indications for ICD therapy and had an ICD/CRT-D implanted. METHODS: Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from the above-mentioned regions. All-cause mortality and device therapy were examined by cardiomyopathy (ICM vs NICM) and implantation status. Cox proportional hazards methods were used, adjusting for factors affecting mortality risk. RESULTS: Of 1848 PP NICM patients, 1007 (54.5%) received ICD/CRT-D, while 303 of 581 (52.1%) PP ICM patients received an ICD/CRT-D. The all-cause mortality rate at 3 years for NICM patients with and without an ICD/CRT-D was 13.1% and 18.3%, respectively (HR 0.51, 95% CI 0.38-0.68, p < 0.001). Similarly, all-cause mortality at 3 years in ICM patients was 13.8% in those with a device and 19.9% in those without an ICD/CRT-D (HR 0.54, 95% CI 0.33-.0.88, p = 0.011). The time to first device therapy, time to first shock, and time to first antitachycardia pacing (ATP) therapy were not significantly different between groups (p ≥ 0.263). CONCLUSIONS: In this large data set of patients with a guideline-based PP ICD indication, defibrillator device implantation conferred a significant mortality benefit in both NICM and ICM patients. The rate of appropriate device therapy was also similar in both groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02099721.

Improve the Prevention of Sudden Cardiac Arrest in Patients With Post-Acute Myocardial Infarction.

Background: Implantable cardioverter-defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients varies by geography but remains low in many regions despite guideline recommendations. Objectives: This study aimed to characterize the care pathway of post-MI patients and understand barriers to referral for further SCD risk stratification and management in patients meeting referral criteria. Methods: This prospective, nonrandomized, multi-nation study included patients ≥18 years of age, with an acute MI ≤30 days and left ventricular ejection fraction <50% ≤14 days post-MI. The primary endpoint was defined as the physician's decision to refer a patient for SCD stratification and management. Results: In total, 1,491 post-MI patients were enrolled (60.2 ± 12.0 years of age, 82.4% male). During the study, 26.7% (n = 398) of patients met criteria for further SCD risk stratification; however, only 59.3% of those meeting criteria (n = 236; 95% CI: 54.4%-64.0%) were referred for a visit. Of patients referred for SCD risk stratification and management, 94.9% (n = 224) attended the visit of which 56.7% (n =127; 95% CI: 50.1%-63.0%) met ICD indication criteria. Of patients who met ICD indication criteria, 14.2% (n = 18) were implanted. Conclusions: We found that ∼40% of patients meeting criteria were not referred for further SCD risk stratification and management and ∼85% of patients who met ICD indications did not receive a guideline-directed ICD. Physician and patient reasons for refusing referral to SCD risk stratification and management or ICD implant varied by geography suggesting that improvement will require both physician- and patient-focused approaches. (Improve Sudden Cardiac Arrest [SCA] Bridge Study; NCT03715790).