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Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries. Methods: We used the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 to record HRQL in 23,291 HF patients from 40 countries in 8 different world regions in the Global Congestive Heart Failure study (G-CHF). We compared standardized KCCQ-12-summary scores (SS; adjusted for age, sex and markers of HF severity) between regions (0-100, higher=better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12-SS and the composite of all-cause death, of HF hospitalization and each component over a median follow-up of 1.6 years. Results: The mean age was 65 years, 61% were men, 40% had NYHA class III-IV symptoms, and 46% had left ventricular ejection fraction (EF) ≥40%. Average HRQL differed between regions (lowest in Africa [39.5 SE±0.3], highest in Western Europe [62.5±0.4]). There were 4,460 (19%) deaths, 3,885 (17%) HF hospitalizations and 6,949 (30%) had either event. Lower KCCQ-12-SS was associated with higher risk of all outcomes, the adjusted hazard ratio (HR) for each 10-unit KCCQ-12-SS decrement was 1.18 (95% CI 1.17-1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America and Africa (weakest association in South Asia, HR 1.08 [95% CI 1.03-1.14], strongest in Eastern Europe HR 1.31 [95% CI [1.21-1.42], interaction p<0.0001). Lower HRQL predicted death in both those with NYHA class I-II and III-IV symptoms (HR 1.17 [95% CI 1.14-1.19] and HR 1.14 [95% CI [1.12-1.17], interaction p=0.13) and was a stronger predictor for the composite outcome in NYHA class I-II vs. III-IV (HR 1.15 [95% CI 1.13-1.17] vs. 1.09 [95% CI [1.07-1.11], interaction p<0.0001). HR for death was greater in EF ≥40 vs. <40% (HR 1.23 [95% CI 1.20-1.26] and HR 1.15 [95% 1.13-1.17], interaction p<0.0001). Conclusions: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF and among those with preserved and reduced EF. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03078166

Stemming the tide of noncommunicable diseases (NCDs) worldwide requires a multi-pronged approach. Although much attention has been paid to disease control measures, there is relatively little consideration of the importance of training the next generation of health-related researchers to play their important role in this global epidemic. The lack of support for early stage investigators in low- and middle-income countries interested in the global NCD field has resulted in inadequate funding opportunities for research, insufficient training in advanced research methodology and data analysis, lack of mentorship in manuscript and grant writing and meager institutional support for developing, submitting and administering research applications and awards. To address this unmet need, the NHLBI-UnitedHealth Collaborating Centers of Excellence initiative created a Training Subcommittee that coordinated and developed an intensive, mentored health-related research experience for a number of early stage investigators from the 11 Centers of Excellence around the world. We describe the challenges faced by early stage investigators in low- and middle-income countries, the organization and scope of the Training Subcommittee, training activities, early outcomes of the early stage investigators (foreign and domestic) and training materials that have been developed by this program that are available to the public. By investing in the careers of individuals in a supportive global NCD network, we demonstrate the impact that an investment in training individuals from low- and middle-income countries can have on the preferred future of or current efforts to combat NCDs.

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