Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Influenza vaccine to reduce adverse vascular events in patients with heart failure: a multinational randomised, double-blind, placebo-controlled trial.

BACKGROUND: Influenza increases the risk of cardiovascular events and deaths. We aimed to see whether influenza vaccination reduces death and vascular events in patients with heart failure. METHODS: We did a pragmatic, randomised, double-blind, placebo-controlled trial in 30 centres (mostly hospitals affliated with universities or a research institute) in ten countries in Asia, the Middle East, and Africa (7 in India, 4 in Philippines, 4 in Nigeria, 6 in China, 1 in Zambia, 2 in Mozambique, 3 in Saudi Arabia, 1 in Kenya, 1 in Uganda, and 1 in Zambia). Participants (aged ≥18 years; 52·1% female; not disaggregated by race or ethnicity) with heart failure (New York Heart Association class II, III, or IV) were randomly assigned (1:1) by a centralised web-based system with block randomisation stratified by site, to receive 0·5 ml intramuscularly once a year for up to 3 years of either inactivated standard dose influenza vaccine or placebo (saline). We excluded people who had received influenza vaccine in 2 of the previous 3 years, and those likely to require valve repair or replacement. Those who administered assigned treatments were not masked and had no further role in the study. Investigators, study coordinators, outcome adjudicators, and participants were masked to group assignment. The first of two co-primary outcomes was a first-event composite for cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, and the second was a recurrent-events composite for cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. Outcomes were assessed every 6 months in the intention-to-treat population. Secondary outcomes were all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, hospitalisation for heart failure, and pneumonia, both overall and during periods of peak influenza exposure. This study is registered with ClinicalTrials.gov, NCT02762851. FINDINGS: Between June 2, 2015, and Nov 21, 2021, we enrolled 5129 participants and randomly assigned (1:1) 2560 (50·0%) to influenza vaccine and 2569 (50·0%) to placebo. The first co-primary outcome occurred in 380 (14·8%) of 2560 participants in the vaccine group and 410 (16·0%) of 2569 participants in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·81-1·07]; p=0·30). The second co-primary outcome occurred in 754 (29·5%) of 2560 participants in the vaccine group and 819 (31·9%) of 2569 participants in the placebo group; HR 0·92 [95% CI 0·84-1·02]; p=0·12). The secondary outcomes of all-cause hospitalisations (HR 0·84 [95% CI 0·74-0·97]; p=0·013) and pneumonia (HR 0·58 [0·42-0·80]; p=0·0006) were significantly reduced in the vaccine group compared with in the placebo group but there was no significant difference between groups for all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. In a prespecified analysis, in which events were limited to periods of peak influenza circulation, the first co-primary outcome, and the secondary outcomes of all-cause death, cardiovasular death, and pneumonia were significantly lower in the vaccinated group than in the placebo group, whereas the second co-primary outcome and the secondary outcomes of non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, and hospitalisation for heart failure were not significantly lower. INTERPRETATION: Although the prespecified co-primary outcomes during the entire period of observation were not statistically significant, the reduction during the peak influenza circulating period suggests that there is likely to be a clinical benefit of giving influenza vaccine, given the clear reduction in pneumonia, a moderate reduction in hospitalisations, and a reduction in cardiovascular events and deaths during periods of peak circulation of influenza. Taken in conjunction with previous trials and the observational studies, the collective data suggest benefit. FUNDING: UK Joint Global Health Trials Scheme and Canadian Institutes for Health Research Foundation.

Impact of Dual versus Single Antiplatelet Therapy on Major Cardiovascular Outcomes in Patients with Acute Coronary Syndrome in the Arabian Gulf.

OBJECTIVE: To evaluate the association of dual versus single antiplatelet therapy with major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) in the Arabian Gulf. SUBJECTS AND METHODS: Data were analyzed from 3,559 patients with a diagnosis of ACS admitted to 29 hospitals in 4 Arabian Gulf countries (Bahrain, Kuwait, Oman, and United Arab Emirates) from January 2012 to January 2013. Dual antiplatelet therapy (DAPT), consisting of aspirin and clopidogrel, was compared to aspirin alone. MACE included 12-months cumulative stroke/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and readmissions for cardiac reasons, post discharge. Analyses were performed using multivariable logistic regression. RESULTS: A total of 74% (n = 2,634) of the patients were on DAPT. At 12-month follow-up, patients on DAPT were significantly less likely to experience MACE events (adjusted OR [aOR] 0.73; 95% CI: 0.61-0.86; p < 0.001). Lower cardiovascular (CV) event rates were also consistent across the following MACE components; MI (aOR 0.66; 95% CI: 0.49-0.88; p = 0.005), all-cause mortality (aOR 0.69; 95% CI: 0.51-0.94; p = 0.018), and readmissions for cardiac reasons (aOR 0.79; 95% CI: 0.66-0.95; p = 0.011). Conversely, DAPT was adversely associated with increased risk of stroke/TIA (aOR 1.68; 95% CI: 1.05-2.69; p = 0.030). CONCLUSIONS: DAPT, compared to aspirin therapy alone, was generally associated with better CV outcomes after an ACS event. However, DAPT was adversely associated with increased risk of stroke/TIA in ACS patients in the Arabian Gulf.

Premature Myocardial Infarction in the Middle East and North Africa: Rationale for the Gulf PREVENT Study.

The Middle East and North Africa (MENA) region has a high burden of morbidity and mortality due to premature (≤55 years in men; ≤65 years in women) myocardial infarction (MI) and acute coronary syndrome (ACS). Despite this, the prevalence of risk factors in patients presenting with premature MI or ACS is incompletely described. We compared lifestyle, clinical risk factors, and biomarkers associated with premature MI/ACS in the MENA region with selected non-MENA high-income countries. We identified English-language, peer-reviewed publications through PubMed (up to March 2018). We used the World Bank classification system to categorize countries. Patients with premature MI/ACS in the MENA region had a higher prevalence of smoking than older patients with MI/ACS but a lower prevalence of diabetes, hypertension, and dyslipidemia. Men with premature MI/ACS had a higher prevalence of smoking than women but a lower prevalence of diabetes and hypertension. The MENA region had sparse data on lifestyle, diet, psychological stress, and physical activity. To address these knowledge gaps, we initiated the ongoing Gulf Population Risks and Epidemiology of Vascular Events and Treatment (Gulf PREVENT) case-control study to improve primary and secondary prevention of premature MI in the United Arab Emirates, a high-income country in the MENA region.

Randomized controlled trial of influenza vaccine in patients with heart failure to reduce adverse vascular events (IVVE): Rationale and design.

BACKGROUND: Influenza is associated with an increase in the risk of cardiac and other vascular events. Observational data and small randomized trials suggest that influenza vaccination may reduce such adverse vascular events. RESEARCH DESIGN AND METHODS: In a randomized controlled trial patients with heart failure are randomized to receive either inactivated influenza vaccine or placebo annually for 3 years. Patients aged ≥18 years with a clinical diagnosis of heart failure and NYHA functional class II, III and IV are eligible. Five thousand patients from 10 countries where influenza vaccination is not common (Asia, the Middle East, and Africa) have been enrolled. The primary outcome is a composite of the following: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalizations for heart failure using standardized criteria. Analyses will be based on comparing event rates between influenza vaccine and control groups and will include time to event, rate comparisons using Poisson methods, and logistic regression. The analysis will be conducted by intention to treat i.e. patients will be analyzed in the group in which they were assigned. Multivariable secondary analyses to assess whether variables such as age, sex, seasonality modify the benefits of vaccination are also planned for the primary outcome. CONCLUSION: This is the largest randomized trial to test if influenza vaccine compared to control reduces adverse vascular events in high risk individuals. TRIAL REGISTRATION NUMBER: Clinicaltrials.govNCT02762851.

Association between Peripheral Artery Disease and Major Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome: Findings from the Gulf COAST Registry.

OBJECTIVE: To evaluate the association between peripheral artery disease (PAD) and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) in the Arabian Gulf. METHODS: Data from 4,044 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 were analyzed. PAD was defined as any of the following: claudication, amputation for arterial vascular insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention in the extremities, documented aortic aneurysm or an ankle brachial index of <0.8 in any of the legs. MACE included stroke/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and readmissions for cardiac reasons diagnosed between hospital admission and at 1-year post discharge. Analyses were performed using univariate and multivariate statistical techniques. RESULTS: The overall mean age of the cohort was 60 ± 13 years and 66% (n = 2,686) were males. A total of 3.3% (n = 132) of the patients had PAD. Patients with PAD were more likely to be associated with smoking, prior MI, hypertension, diabetes mellitus, and stroke/TIA. At the 1-year follow-up, patients with PAD were significantly more likely to have MACE (adjusted OR [aOR], 2.07; 95% confidence interval [CI]: 1.41-3.06; p< 0.001). The higher rates of events were also observed across all MACE components; stroke/TIA (aOR, 3.22; 95% CI: 1.80-5.75; p< 0.001), MI (aOR, 2.15; 95% CI: 1.29-3.59; p =0.003), all-cause mortality (aOR, 2.21; 95% CI: 1.33-3.69; p =0.002), and readmissions for cardiac reasons (aOR, 1.83; 95% CI: 1.24-2.70; p =0.003). CONCLUSIONS: PAD was significantly associated with MACE in ACS patients in the Arabian Gulf.

Congenital aneurysmal right coronary artery with a fistula to the left atrium in an adult.

BACKGROUND: Congenital coronary artery fistula in association with aneurysm of the involved coronary artery in adults is rare. Moreover, the right coronary artery- left atrial fistula is also uncommon. Most of the cases are asymptomatic. However, symptomatic patients need therapeutic interventions. The potential complications associated with this anomaly are life-threatening, therefore, there is a need to explore more on differential diagnosis, investigations, management strategies and prevention of complications. CASE PRESENTATION: We present herewith a 26-year-old male patient with symptoms of chest pain and dyspnea. He was diagnosed with aneurysmal dilatation of the right coronary artery in its entire course which terminated as a fistulous communication into the left atrium. The closure of the fistula was done using autologous pericardial patch under cardiopulmonary bypass. Currently, the patient is being followed up after surgery and receiving anticoagulants. CONCLUSION: The advancement in the diagnostic imaging modalities have made it possible to find similar abnormalities more frequently. Due to rare nature of this anomaly, there is a need to explore and discuss management strategies that include medical management, surgical intervention or percutaneous interventions for a successful outcome.

Design and Rationale of Gulf Documentation of Ambulatory Sick Patients with Heart Failure (Gulf DYSPNEA) Registry.

AIM: The aim of this study is to describe the clinical characteristics of ambulatory patients with chronic heart failure (HF) in the Arabian Gulf and to examine several aspects including types of HF, causes, and adherence to management guidelines. METHODS: Gulf documentation of ambulatory sick patients with HF (Gulf DYSPNEA) registry is a multicenter, cross-sectional study, recruiting adult ambulatory HF patients from 24 hospitals in five Arabian Gulf countries. Consecutive patients are recruited prospectively from participating clinics with no follow-up data collection. Recruitment started on November 07, 2016 and will stop when 3,500 patients are enrolled in this study. Collected data explore demographics, baseline patient characteristics, symptoms, previous medical history, comorbidities, physical signs, presenting electrocardiogram, echocardiographic findings, types of HF, and management. CONCLUSION: This registry is expected to provide useful data on several important aspects and features of ambulatory patients with chronic HF in Arabian Gulf countries. The trial registration number is "ClinicalTrials.gov number, NCT02793180".

Disparity in ST-segment Elevation Myocardial Infarction Practices and Outcomes in Arabian Gulf Countries (Gulf COAST Registry).

OBJECTIVES: The objective of this study is to describe contemporary management and 1-year outcomes of patients hospitalized with ST-segment elevation myocardial infarction (STEMI) in Arabian Gulf countries. METHODS: Data of patients admitted to 29 hospitals in four Gulf countries [Bahrain, Kuwait, Oman, United Arab Emirates (UAE)] with the diagnosis of STEMI were analyzed from Gulf locals with acute coronary syndrome (ACS) events (Gulf COAST) registry. This was a longitudinal, observational registry of consecutive citizens, admitted with ACS from January 2012 to January 2013. Patient management and outcomes were analyzed and compared between the four countries. RESULTS: A total of 1039 STEMI patients were enrolled in Gulf COAST Registry. The mean age was 58 years, and there was a high prevalence of diabetes (47%). With respect to reperfusion, 10% were reperfused with primary percutaneous coronary intervention, 66% with fibrinolytic therapy and 24% were not reperfused. Only one-third of patients who received fibrinolytic therapy had a door-to-needle time of 30 min or less. The in-hospital mortality rate was 7.4%. However, we noted a significant regional variability in mortality rate (3.8%-11.9%). In adjusted analysis, patients from Oman were 4 times more likely to die in hospital as compared to patients from Kuwait. CONCLUSIONS: In the Gulf countries, fibrinolytic therapy is the main reperfusion strategy used in STEMI patients. Most patients do not receive this therapy according to timelines outlined in recent practice guidelines. There is a significant discrepancy in outcomes between the countries. Quality improvement initiatives are needed to achieve better adherence to management guidelines and close the gap in outcomes.

Opportunistic Screening for CVD Risk Factors: The Dubai Shopping for Cardiovascular Risk Study (DISCOVERY).

BACKGROUND: Comprehensive cardiovascular disease risk factor (CVDRF) screening programs are limited in the developing world. Simplifying screening can increase its utility. OBJECTIVES: The present study aims to estimate the burden of CVDRF in volunteers and the yield of newly discovered CVDRF comparing different sites and nationalities using this screening method. METHODS: Voluntary point-of-care CVDRF screening was conducted in 4 shopping malls, 9 health care facilities, and 3 labor camps in 5 cities in the United Arab Emirates. Follow-up for newly diagnosed diabetes mellitus, hypertension, and dyslipidemia was made 1 month after screening to inquire about physician consultation, confirmation of diagnosis, and lifestyle changes. RESULTS: A total of 4,128 subjects were screened (43% at malls, 36% at health care facilities, and 22% at labor camps). Subjects were relatively young (38 ± 11 years), predominantly male (75%), and of diverse nationalities (United Arab Emirates: 7%, other Arabs: 10%, South Asians: 74%, other Asians: 5%, and other nationalities: 5%). CVDRF were frequent (diabetes mellitus: 32%, hypertension: 31%, dyslipidemia: 69%, current smokers: 21%, obesity: 20%, and central obesity: 24%). Most subjects (85%) had ≥1 CVDRF, and many (17%) had ≥3 CVDRF. A new diagnosis of diabetes mellitus, hypertension, or dyslipidemia was uncovered in 61.5%, with the highest yield (74.0%) in labor camps. At follow-up of those with new CVDRF, positive lifestyle changes were reported in 60%, but only 33% had consulted a doctor; of these, diagnosis was confirmed in 63% for diabetes mellitus, 93% for hypertension, and 87% for dyslipidemia. CONCLUSIONS: In this relatively young and ethnically diverse cohort, CVDRF burden and yield of screening was high. Screening in these settings is pertinent and can be simplified.

Design and Rationale of Gulf locals with Acute Coronary Syndrome Events (Gulf Coast) Registry.

OBJECTIVES: To describe the risk profile, management and one-year outcomes of patients hospitalized with acute coronary syndrome (ACS) in the Gulf region of the Middle East. SUBJECTS AND METHODS: The Gulf locals with acute coronary syndrome events (Gulf COAST) registry is a prospective, multinational, longitudinal, observational, cohort-based registry of consecutive citizens, from the Gulf region of the Middle East, admitted from January 2012 to January 2013 to 29 hospitals with a diagnosis of ACS. Data entered online included patient demographics, cardiovascular risk profiles, past medical history, physical findings on admission, in-hospital diagnostic tests and therapeutic management, as well as one year outcomes. RESULTS: 3188 patients were recruited. The mean age was 60.4 ± 12.6years (range: 22-112), 2104 (66%) were males and 1084 (34%) females. The discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 741 (23.2%), new-onset left bundle branch block myocardial infarction (LBBBMI) in 30 (0.9%), non-ST-segment elevation myocardial infarction (NSTEMI) in 1486 (46.6%) and unstable angina in 931 (29.2%). At hospital presentation, 2105 (66%), 1779 (55.8%), 1703 (53.4%) and 740 (23.2%) had history of hypertension, dyslipidemia, diabetes mellitus and active smoking, respectively. CONCLUSION: Patients with ACS in our region are young with very high risk profile. The Gulf COAST registry is an example of successful regional collaboration and will provide information on contemporary management of ACS in the region.

Hospitalized heart failure patients with preserved vs. reduced ejection fraction in Dubai, United Arab Emirates: a prospective study.

AIMS: To compare the baseline characteristics, pharmacological treatment, and in-hospital outcomes across hospitalized heart failure (HF) patients with preserved LVEF (HF-PEF) and those with reduced LVEF (HF-REF). METHOD AND RESULTS: This was a prospective analysis of consecutive patients admitted with decompensated HF at two government hospitals in the United Arab Emirates, from 1 December 2011 to 30 November 2012. Multivariate factors of HF-PEF vs. HF-REF included elevated systolic blood pressure [odds ratio (OR) 1.02; 95% confidence interval (CI) 1.01­1.03], heart rate (OR 0.98; 95% CI 0.97­0.99), age (OR 1.02; 95% CI 1.01­1.04), female sex (OR 2.38; 95% CI 1.41­4.03), angina or myocardial infarction (OR 0.42; 95% CI 0.25­0.71), AF (OR 1.82; 95% CI 1.05­3.15), COPD or asthma (OR 2.80; 95% CI 1.47­5.35), Charlson Comorbidity Index score (OR 0.75; 95% CI 0.64­0.88), and anaemia (OR 2.97; 95% CI 1.64­5.38). In-hospital outcomes were similar between the two groups. However, patients with HF-PEF were less likely to be prescribed HF medication, and used more anticoagulants and fewer antiplatelet medications. CONCLUSION: These results suggest that patients with HF-PEF are older, more often female, and have higher prevalence of respiratory diseases and AF. Compared with developed countries, hospitalized HF patients in the Middle East are 10 years younger and have a higher prevalence of diabetes mellitus, and the majority have HF-REF.

Short-term effects of ivabradine in patients with chronic stable ischemic heart disease.

INTRODUCTION: Ivabradine is a novel selective If current inhibitor with anti-ischemic and antianginal activity. OBJECTIVES: To assess the effect of the selective If current inhibitor ivabradine on heart rate, angina pectoris, and functional capacity in stable patients with chronic coronary artery disease on maximally tolerated medical therapy. MATERIALS AND METHODS: Consecutive patients from the out-patient cardiology clinic with stable coronary artery disease documented by coronary angiography were included. Patients had to be on maximally tolerated medical therapy with ß-blockers, angiotensin-converting enzyme inhibitors or receptor blockers (ACE-I or ARB), antiplatelets, statins, nitrates, and anti-metabolics with a baseline heart rate of at least 70 beats per minute. All patients underwent assessment of angina (Canadian Cardiovascular Society Angina Class: CCS I to IV) and functional capacity (using a validated self-administered questionnaire), at baseline and after 4 months of ivabradine therapy. RESULTS: Twenty patients were enrolled (mean age 47 ± 7 years, all male, 60% with hypertension, 30% with diabetes mellitus). Patients were on optimal medical regimen of aspirin (100%), ß-blocker (100%), statins (100%), clopidogrel (90%), nitrates (35%), anti-metabolics (90%), and ACE-I or ARB (95%). At baseline, the majority of patients (90%) were in CCS class II-IV. All patients were started on ivabradine 5 mg twice daily, and in 12 patients the dose was increased to 7.5 mg twice daily. After 4 months of treatment, the heart rate was significantly reduced from an average of 82 ± 8 to 68 ± 6 bpm (P < 0.001). The reduction in heart rate was accompanied by a significant improvement in functional capacity (score 3.5 ± 0.9 to 4.7 ± 0.7, P < 0.001) and angina classification; at baseline 10% of the patients were in CCS class I compared to 50% after 4 months of therapy (P = 0.01). No symptomatic bradycardia was reported with ivabradine. CONCLUSION: The addition of ivabradine to optimal medical therapy in patients with stable coronary artery disease is associated with significant improvement in anginal symptoms and functional capacity.