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.

Health-Related Quality of Life and Mortality in Heart Failure: The Global Congestive Heart Failure Study of 23 000 Patients From 40 Countries.

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-12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years. RESULTS: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score 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 association in Eastern Europe: HR, 1.31 [95% CI, 1.21-1.42]; interaction P<0.0001). Lower HRQL predicted death in patients with New York Heart Association class I or II and III or 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 New York Heart Association class I or II versus class III or IV (HR 1.15 [95% CI, 1.13-1.17] versus 1.09 [95% CI, [1.07-1.11]; interaction P<0.0001). HR for death was greater in ejection fraction ≥40 versus <40% (HR, 1.23 [95% CI, 1.20-1.26] and HR, 1.15 [95% CI, 1.13-1.17]; interaction P<0.0001). CONCLUSION: 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 patients with preserved and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078166.

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

The other side of the medallion in heart failure: Reverse metabolic syndrome.

BACKGROUND AND AIMS: Lower levels of cardiovascular risk factors are associated with an increase in mortality in H.F. To explain this paradox, the term reverse metabolic syndrome (RMetS) has recently been proposed. We suggest defining these patients with lower levels of three risk factors can be combined under the heading "RMetS." We aimed to investigate the effect of MetS and RMetS on hemodynamic parameters and prognosis in patients with H.F. and reduced ejection fraction (HFrEF). METHODS AND RESULTS: We included 304 patients who were performed right heart catheterization and followed up for a median of 16 (0-48) months. We first grouped patients according to the presence of MetS or not, then we added the RMetS category and stratified patients into three groups as MetS, RMetS, and metabolic healthy. Compared with not MetS group, Pulmonary arterial pressures and VO2 were higher in MetS group. In the second step, LVEF, CI, VO2I, O2 delivery, and LVSWI were lowest in RMetS, pulmonary artery pressures were higher in MetS group. In multivariate Cox regression analysis, being in RMetS group was associated with 2.4 times and 1.8 times increased risk for composite end point (CEP) and all-cause mortality, respectively. In Kaplan Meier analysis, RMetS had the highest all-cause mortality and CEP. CONCLUSIONS: We determined that RMetS patients had the worst prognosis with unfavorable hemodynamic profile. Hence, a better understanding of the pathophysiology of RMetS may help refine the treatment targets of CV risk factors, may yield new interventions targeting catabolic syndrome.

Association of estimated sleep duration and naps with mortality and cardiovascular events: a study of 116 632 people from 21 countries.

AIMS: To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events. METHODS AND RESULTS: We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6-8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99-1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99-1.12), 1.17 (1.09-1.25), and 1.41 (1.30-1.53) for 8-9 h/day, 9-10 h/day, and >10 h/day, Ptrend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h). CONCLUSION: Estimated total sleep duration of 6-8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

Inhaled Iloprost and Oral Sildenafil Combination Therapy: Is it a Chance for Heart Transplant Candidacy?

BACKGROUND: Severe pulmonary hypertension is a risk factor for mortality, due to increased postoperative right ventricular failure, in a heart transplant patient. Elevated pulmonary vascular resistance (PVR) in heart transplant candidates can be reduced using a left ventricular assist device or medical therapy. This study analysed the effect of inhaled iloprost and oral sildenafil combination therapy (ilo-sil) on pulmonary haemodynamic parameters in patients with secondary pulmonary hypertension. METHODS: Between May 2011 and April 2014, 25 patients who were unresponsive to reversibility test and PVR >3.5 Wood units (WU) during right heart catheterisation were included in this study. After 6 months of oral sildenafil (3 × 20 mg/day) and inhaled iloprost (6 × 5 µg/day) combination therapy, second right heart catheterisations were performed and eligibility for heart transplant was evaluated. RESULTS: Repeat right heart catheterisation revealed that there was a significant decrease in the PVR from 5.4 ± 1.6 WU to 3.54 ± 2.5 WU (p<0.001), with trans-pulmonary gradient from 13.7 ± 5.6 to 11.46 ± 6.64 (p=0.042), and mean cardiac index (CI) increasing non-significantly from 1.45 ± 0.51 L/min/m2 to 1.82 ± 0.60 (p=0.157). The mean sPAP was initially 57.54 ± 14.79 mmHg and fell to 52.93 ± 16.83 mm Hg (p=0.03). Twenty (20) (80%) patients were enrolled in the waiting list since their PVR values decreased to <3.5 WU. Of these 20 patients, one had undergone heart transplant and four were bridged to transplant with mechanical circulatory support devices. CONCLUSIONS: After a decrease in PVR with ilo-sil combination therapy for patients with severe pulmonary hypertension, these patients may become candidates for heart transplant without bearing additional risk. Ilo-sil combination therapy could be a viable option with which to evaluate the reversibility of PVR.

The prognostic value of positive T wave in lead aVR: A novel marker of adverse cardiac outcomes in peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an uncommon complication of pregnancy. Clinical courses of PPCM are markedly heterogeneous. Positive T waves in lead aVR (TaVR) are shown to be associated with adverse cardiac events in several cardiovascular diseases. We aimed to investigate the prevalence and prognostic role of positive TaVR in patients with PPCM. METHODS: A total of 82 patients (mean age 29.1 ± 6.3 years) with the diagnosis of PPCM were enrolled. Presentation electrocardiogram (ECG) was investigated for presence of a positive TaVR. The median follow-up duration was 67.0 months. The primary endpoint was defined as composite cardiac events, including cardiac death, arrhythmic events, or persistent left ventricular systolic dysfunction. RESULTS: Patients with positive T wave in lead aVR showed higher rates for persistent left ventricular systolic dysfunction, arrhythmic events, and cardiac death compared to patients without it. In multivariate logistic regression analysis, after adjusting for other confounding factors, the presence of positive TaVR was found to be as an independent and strong predictor of primary composite endpoint (odds ratio 6.21, 95% CI 1.45-26.51; p = 0.014). In Kaplan-Meier survival analysis, both primary and secondary endpoints occurred more frequently in the positive TaVR group. Using the cut-off level of 0.25 mV, T-wave amplitude in lead aVR predicted primary endpoint with a sensitivity of 100% and specificity of 100%. CONCLUSION: Positive T wave in lead aVR, as a simple and feasible electrocardiographic marker, seems to be a novel predictor of adverse cardiovascular outcomes in patients with PPCM.

Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data.

BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability. METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, ß blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry. FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55). INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Relationship between Serum Albumin Level and Monocyte-to-High-Density Lipoprotein Cholesterol Ratio with Saphenous Vein Graft Disease in Coronary Bypass.

Background Previous studies proposed that inflammation, oxidative stress, and impaired endothelial dysfunction have a crucial role in occurrence of saphenous vein graft (SVG) disease (SVGD). The aim of this study was to assess the relationship between monocyte-to-high-density lipoprotein cholesterol (HDL-C) ratio (MHR) and serum albumin (SA) level as readily available inflammatory and oxidative stress markers with the presence of SVGD in patients with a coronary bypass. Methods In this retrospective cross-sectional study, a total of 257 patients (n = 112 SVGD [+] [mean age was 65.3 ± 8.4 years, 75.0% males] and n = 145 SVGD [-] [mean age was 66.5 ± 10.1 years, 74.5% males]) were enrolled. At least one SVG with ≥ 50% stenosis was defined as SVGD. Independent predictors of SVGD were determined by logistic regression analysis. Results White blood cell, neutrophil, monocyte, the age of SVG, and MHR were significantly higher, whereas SA level was significantly lower in patients with SVGD. In regression analysis, neutrophil, age of SVG, SA (odds ratio [OR]: 0.232 [0.156-0.370], p < 0.001), and MHR (OR: 1.122 [1.072-1.174], p < 0.001) remained as independent predictors of SVGD. Moreover, age of SVG showed a significant negative correlation with SA (r = - 0.343, p < 0.001) and a positive correlation with MHR (r = 0.238, p < 0.001). In the receiver-operating characteristic curve analysis, the cutoff value of ≤ 3.75 g/dL for SA has a 73.2% sensitivity and 64.8% specificity and the cutoff value of ≥ 12.1 for MHR has a 71.4% sensitivity and 60.0% specificity for prediction of SVGD. Conclusion Consequently, to the best of our knowledge, this is the first study showing a significant and independent association between SA and MHR with SVGD.

Right Ventricular Dysfunction Complicates Time in Therapeutic Range in Heart Failure Patients Receiving Warfarin.

AIM: We aimed to evaluate the effect of echocardiographically demonstrated right ventricular dysfunction (RVD) on time in therapeutic range (TTR) in heart failure (HF) patients receiving warfarin therapy. METHODS: A total of 893 consecutive HF patients were included and classified into 4 different subgroups: HF with preserved ejection fraction (HFpEF) without RVD (n = 373), HF with reduced EF (HFrEF) without RVD (n = 215), HFpEF with RVD (n = 106) and HFrEF with RVD (n = 199). Groups were compared according to baseline, demographic and clinical data and the characteristics of warfarin therapy. RESULTS: Presence of RVD yielded lower median TTR values both in HFpEF and HFrEF patients. RVD, current smoking, New York Heart Association functional class III/IV, hypertension, diabetes mellitus, pulmonary disease, prior transient ischemic attack or stroke, chronic kidney disease (CKD) stage 4/5 and CKD stage 3 were found to be independent predictors of poor anticoagulation control in multivariate logistic regression analysis. CONCLUSIONS: The present study demonstrated that presence of RVD in HF increases the risk for poor anticoagulation.

Fragmented QRS Complex Predicts In-Hospital Adverse Events and Long-Term Mortality in Patients with Acute Pulmonary Embolism.

BACKGROUND: Electrocardiographic (ECG) abnormalities in pulmonary embolism (PE) are increasingly reported, and mounting data have recommended that ECG plays a crucial role in the prognostic assessment of PE patient population. However, there is scarce data on the prognostic importance of fragmented QRS (fQRS) on short- and long-term outcomes in patients with PE. Therefore, we aimed to investigate the prognostic role of fQRS in predicting in-hospital and long-term adverse outcomes in PE patients. METHODS: A total of 249 patients (155 female, 66.2%; mean age, 66.0 ± 16.0) with the diagnosis of acute PE were enrolled and followed-up during median 24.8 months. RESULTS: Compared with the fQRS (-) patient group, patients with fQRS showed higher rates of in-hospital adverse events including cardiogenic shock, the necessity of thrombolytic therapy, and in-hospital mortality as well as long-term all-cause mortality. In Kaplan-Meier survival analysis, during follow-up, all-cause mortality occurred more frequently in the fQRS (+) group (log-rank, P = 0.002). In multivariate Cox regression analysis, adjusted with other relevant parameters, the presence of fQRS were determined as an independent predictor of in-hospital adverse events (HR: 2.743, 95% CI: 1.267-5.937, P = 0.003) and long-term all-cause mortality (HR: 3.137, 95% CI: 1.824-6.840, P = 0.001). CONCLUSIONS: The presence of fQRS complex, as a simple and feasible ECG marker, seems to be a novel predictor of in-hospital adverse events and long-term all-cause mortality in PE patient population. This parameter may utilize the identification of patients whom at higher risk for mortality and individualization of therapy.

Monocyte to HDL Cholesterol Ratio Predicts Coronary Artery Disease Severity and Future Major Cardiovascular Adverse Events in Acute Coronary Syndrome.

BACKGROUND: We aimed to investigate the usefulness of monocyte to HDL cholesterol ratio (MHR) in predicting coronary artery disease severity and future major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). METHODS: 2661 patient with ACS were enrolled and followed up during median 31.6 months. RESULTS: MHR were significantly positively correlated with neutrophil to lymphocyte ratio (r=0.438), CRP (r=0.394), Gensini (r=0.407), and SYNTAX score (r=0.333). During in-hospital and long-term follow-up, MACE, stent thrombosis, non-fatal MI, and mortality occurred more frequently in the third tertile group. Kaplan-Meier analysis revealed the higher occurrence of MACE in the third tertile group compared with other tertiles. Adjusting for other factors, a MHR value in the third tertile group was determined as an independent predictor of in-hospital and long-term MACE. CONCLUSIONS: MHR as a novel inflammation-based marker seemed to be an independent predictor of severity of coronary artery disease and future cardiovascular events in patients with ACS. MHR may utilise the identification of patients who are at higher risk for MACE and individualisation of targeted therapy.

Epicardial adipose tissue is related to coronary collateral vessel formation in patients with acute coronary syndrome.

OBJECTIVES: Epicardial adipose tissue (EAT) is the ectopic fat surrounding the heart, and it may contribute to coronary collateral vessel (CCV) formation. We aimed to evaluate the association of EAT with the presence of CCV in patients with acute coronary syndrome (ACS). DESIGN: A total of 230 patients with ACS were included. The CCVs were graded according to the Rentrop scoring system, and a Rentrop grade 0-1 was accepted as low-grade CCV group, Rentrop grade 2-3 was accepted as high-grade CCV group. RESULTS: According to angiography, 70 (30%) patients constituted the high-grade CCV group and 160 (70%) constituted the low-grade CCV group. The high-grade CCV group had thicker EAT than the low-grade CCV group (6.1 ± 1.4 vs. 5.3 ± 1.4 mm; p = 0.001). Multivariate logistic regression analysis showed that presence of CCV was independently associated with EAT thickness, ejection fraction, presenting with ST-segment elevation myocardial infarction, and presence of angina on admission. EAT thickness of > 5.7 mm can independently predict high-grade CCV with 73% sensitivity and 69% specificity (area under the curve or AUC: 0.65; 95% confidence interval or CI: 0.57-0.72). CONCLUSIONS: EAT thickness on admission was associated with the presence of CCVs in patients with ACS.

Lymphocytopenia is associated with poor NYHA functional class in chronic heart failure patients with reduced ejection fraction.

OBJECTIVE: In heart failure (HF) patients, functional capacity has been demonstrated to be a marker of poor prognosis, independent of left ventricular ejection fraction (EF). Lymphocyte count is currently recognized in certain risk stratification scores for chronic HF, and severe HF is associated with lymphocytopenia. However, no data exists on the association between lymphocyte count and functional capacity in patients with stable HF. This study aimed to assess the relationship between lymphocyte count and New York Heart Association (NYHA) functional capacity in systolic HF outpatients. METHODS: The Turkish Research Team-HF (TREAT-HF) is a network which undertakes multi-center observational studies in HF. Data on 392 HF reduced ejection fraction (HFREF) patients from 8 HF centers are presented here. The patients were divided into two groups and compared: Group 1 comprised stable HFREF patients with mild symptoms (NYHA Class I-II), while Group 2 consisted of patients with NYHA Class III-IV symptoms. RESULTS: Patient mean age was 60±14 years. Lymphocyte count was lower in patients with NYHA functional classes III and IV than in patients with NYHA functional classes I and II, (0.9 [0.6-1.5]x1000 versus 1.5 [0.7-2.2]x1000, p<0.001). In multivariate logistic regression analysis, lymphocyte count (OR: 0.602, 95% CI: 0.375-0.967, p=0.036), advanced age, male gender, presence of hypertension, EF, left atrium size, systolic pulmonary artery pressure, neutrophil and basophil counts, creatinine level, and diuretic usage were associated with poor NYHA functional class in systolic HF outpatients. CONCLUSION: The present study demonstrated that in stable HFREF outpatients, lymphocytopenia was strongly associated with poor NYHA function, independent of coronary heart disease risk factors.

Risk factors for recognized and unrecognized SARS-CoV-2 infection: a seroepidemiologic analysis of the Prospective Urban Rural Epidemiology (PURE) study.

There are limited data on individual risk factors for SARS-CoV-2 infection (including unrecognized infection). In this seroepidemiologic substudy of an ongoing prospective cohort study of community-dwelling adults, participants were thoroughly characterized pre-pandemic. The SARS-CoV-2 infection was ascertained by serology. Among 8,719 participants from 11 high-, middle-, and low-income countries, 3,009 (35%) were seropositive for SARS-CoV-2. Characteristics independently associated with seropositivity were younger age (odds ratio, OR; 95% confidence interval, CI, per five-year increase: 0.95; 0.91-0.98) and body mass index >25 kg/m2 (OR, 95% CI: 1.16, 1.01-1.34). Smoking (as compared with never smoking, OR, 95% CI: 0.83, 0.70-0.97) and COVID-19 vaccination (OR, 95% CI: 0.70, 0.60-0.82) were associated with a reduced risk of seropositivity. Among seropositive participants, 83% were unaware of having been infected with SARS-CoV-2. Seropositivity and a lack of awareness of infection were more common in lower-income countries. The COVID-19 vaccination reduces the risk of SARS-CoV-2 infection (including recognized and unrecognized infections). Overweight or obesity is an independent risk factor for SARS-CoV-2 infection. Infection and lack of infection awareness are more common in lower-income countries.IMPORTANCEIn this large, international study, evidence of SARS-CoV-2 infection was obtained by testing blood specimens from 8,719 community-dwelling adults from 11 countries. The key findings are that (i) the large majority (83%) of community-dwelling adults from several high-, middle-, and low-income countries with blood test evidence of SARS-CoV-2 infection were unaware of this infection-especially in lower-income countries; and (ii) overweight/obesity predisposes to SARS-CoV-2 infection, while COVID-19 vaccination is associated with a reduced risk of SARS-CoV-2 infection. These observations are not attributable to other individual characteristics, highlighting the importance of the COVID-19 vaccination to prevent not only severe infection but possibly any infection. Further research is needed to understand the mechanisms by which overweight/obesity might increase the risk of SARS-CoV-2 infection.

Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries.

IMPORTANCE: Hypertension is the most important preventable cause of morbidity and mortality globally, yet there are relatively few data collected using standardized methods. OBJECTIVE: To examine hypertension prevalence, awareness, treatment, and control in participants at baseline in the Prospective Urban Rural Epidemiology (PURE) study. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study of 153,996 adults (complete data for this analysis on 142,042) aged 35 to 70 years, recruited between January 2003 and December 2009. Participants were from 628 communities in 3 high-income countries (HIC), 10 upper-middle-income and low-middle-income countries (UMIC and LMIC), and 4 low-income countries (LIC). MAIN OUTCOMES AND MEASURES: Hypertension was defined as individuals with self-reported treated hypertension or with an average of 2 blood pressure measurements of at least 140/90 mm Hg using an automated digital device. Awareness was based on self-reports, treatment was based on the regular use of blood pressure-lowering medications, and control was defined as individuals with blood pressure lower than 140/90 mm Hg. RESULTS: Among the 142,042 participants, 57,840 (40.8%; 95% CI, 40.5%-41.0%) had hypertension and 26,877 (46.5%; 95% CI, 46.1%-46.9%) were aware of the diagnosis. Of those who were aware of the diagnosis, the majority (23,510 [87.5%; 95% CI, 87.1%-87.9%] of those who were aware) were receiving pharmacological treatments, but only a minority of those receiving treatment were controlled (7634 [32.5%; 95% CI, 31.9%-33.1%]). Overall, 30.8%, 95% CI, 30.2%-31.4% of treated patients were taking 2 or more types of blood pressure-lowering medications. The percentages aware (49.0% [95% CI, 47.8%-50.3%] in HICs, 52.5% [95% CI, 51.8%-53.2%] in UMICs, 43.6% [95% CI, 42.9%-44.2%] in LMICs, and 40.8% [95% CI, 39.9%-41.8%] in LICs) and treated (46.7% [95% CI, 45.5%-47.9%] in HICs, 48.3%, [95% CI, 47.6%-49.1%] in UMICs, 36.9%, [95% CI, 36.3%-37.6%] in LMICs, and 31.7% [95% CI, 30.8%-32.6%] in LICs) were lower in LICs compared with all other countries for awareness (P <.001) and treatment (P <.001). Awareness, treatment, and control of hypertension were higher in urban communities compared with rural ones in LICs (urban vs rural, P <.001) and LMICs (urban vs rural, P <.001), but similar for other countries. Low education was associated with lower rates of awareness, treatment, and control in LICs, but not in other countries. CONCLUSIONS AND RELEVANCE: Among a multinational study population, 46.5% of participants with hypertension were aware of the diagnosis, with blood pressure control among 32.5% of those being treated. These findings suggest substantial room for improvement in hypertension diagnosis and treatment.

The association of hemodynamic markers of right ventricular dysfunction with SII index and clinical outcomes in reduced ejection fraction heart failure.

Heart failure (HF) is a clinical syndrome with various etiologies and presentations. The role of the inflammatory pathway in HF prognosis is not fully understood. We investigated the association between the systemic immune-inflammation index (SII) and HF complicated by right ventricular dysfunction (RVD) and whether the SII is related to compromised hemodynamic volume status. A total of 235 patients with HF with reduced ejection fraction (HFrEF) were enrolled and divided into 2 groups according to the presence of RVD. The relationship between the SII score, hemodynamic parameters, and clinical endpoints was evaluated. Higher SII scores and neutrophil counts (P < .001 and P = .017, respectively) were observed in the RVD group (n = 120). In the high SII score group (≥590.4), hospitalization and the need for positive inotrope treatment were significantly higher (P = .026 and P = .009, respectively), and left ventricular ejection fraction (LVEF) was significantly lower (P = .015). In addition, in the high SII score group, right heart catheterization values, including cardiac output and index, were significantly impaired compared with those in the lower SII score group. There was a significant negative correlation between the SII score and the LVEF, cardiac output, and cardiac index in the correlation analyses. A significant relationship was observed between indirect inflammation and RVD in patients with HFrEF. The hemodynamic volume status and functional capacity were impaired in patients with high SII scores. These results indicated that advanced HF with worse outcomes may be related to the inflammatory process.

Effect of renal function on the prognostic importance of chloride in patients with heart failure.

Hypochloremia has recently gained interest as a potential marker of outcomes in patients with heart failure (HF). The exact pathophysiologic mechanism linking hypochloremia to HF is unclear but is thought to be mediated by chloride-sensitive proteins and channels located in kidneys. This analysis aimed to understand whether renal dysfunction (RD) affects the association of hypochloremia with mortality in patients with HF. Using data from a nationwide registry, 438 cases with complete data on serum chloride concentration and 1-year survival were included in the analysis. Patients with an estimated glomerular filtration rate of <60 mL/min/m2 at baseline were accepted as having RD. Hypochloremia was defined as a chloride concentration <96 mEq/L at baseline. For HF patients without RD at baseline, patients with hypochloremia had a significantly higher 1-year all-cause mortality than those without hypochloremia (41.6% vs 13.0%, log-rank p < 0.001) and the association remained significant after multivariate adjustment (odds ratio (OR): 2.55, 95% confidence interval (CI): 1.25-5.21). The evidence supporting the association was very strong in this subgroup (Bayesian Factor (BF)10: 48.25, log OR: 1.56, 95% CI: 0.69-2.43). For patients with RD at baseline, there was no statistically significant difference for 1-year mortality for patients with or without hypochloremia (36.3% vs 29.7, log-rank p = 0.35) and there was no evidence to support an association between hypochloremia and mortality (BF10: 1.18, log OR :0.66, 95% CI: -0.02 to 1.35). In patients with HF, the association between low chloride concentration and mortality is limited to those without RD at baseline.

Usefulness of Age, Creatinine and Ejection Fraction - Modification of Diet in Renal Disease Score for Predicting Survival in Patients with Heart Failure. / Utilidade da Idade, Creatinina e Fração de Ejeção - Modificação da Dieta no Escore de Doença Renal para Prever a Sobrevivência em Pacientes com Insuficiência Cardíaca.

BACKGROUND: Central Illustration: Usefulness of Age, Creatinine and Ejection Fraction - Modification of Diet in Renal Disease Score for Predicting Survival in Patients with Heart Failure Summary of the study design and key findings. ACEF: Age, creatinine and ejection fraction, MDRD: Modified Diet in Renal Disease. While many risk models have been developed to predict prognosis in heart failure (HF), these models are rarely useful for the clinical practitioner as they include multiple variables that might be time-consuming to obtain, they are usually difficult to calculate, and they may suffer from statistical overfitting. OBJECTIVES: To investigate whether a simpler model, namely the ACEF-MDRD score, could be used for predicting one-year mortality in HF patients. METHODS: 748 cases within the SELFIE-HF registry had complete data to calculate the ACEF-MDRD score. Patients were grouped into tertiles for analyses. For all tests, a p-value <0.05 was accepted as significant. RESULTS: Significantly more patients within the ACEF-MDRD high tertile (30.0%) died within one year, as compared to other tertiles (10.8% and 16.1%, respectively, for ACEF-MDRD low and ACEF-MDRD med , p<0.001 for both comparisons). There was a stepwise decrease in one-year survival as the ACEF-MDRD score increased (log-rank p<0.001). ACEF-MDRD was an independent predictor of survival after adjusting for other variables (OR: 1.14, 95%CI:1.04 - 1.24, p=0.006). ACEF-MDRD score offered similar accuracy to the GWTG-HF score for predicting one-year mortality (p=0.14). CONCLUSIONS: ACEF-MDRD is a predictor of mortality in patients with HF, and its usefulness is comparable to similar yet more complicated models.

FUNDAMENTO: Figura Central: Utilidade da Idade, Creatinina e Fração de Ejeção - Modificação da Dieta no Escore de Doença Renal para Prever a Sobrevivência em Pacientes com Insuficiência Cardíaca Resumo do desenho do estudo e principais conclusões. ACEF: Idade, creatinina e fração de ejeção (Age, creatinine and ejection fraction) MDRD: Dieta Modificada em Doença Renal (Modified Diet in Renal Disease). Embora muitos modelos de risco tenham sido desenvolvidos para prever o prognóstico na insuficiência cardíaca (IC), esses modelos raramente são úteis para o clínico, pois incluem múltiplas variáveis que podem ser demoradas para serem obtidas, são geralmente difíceis de calcular e podem sofrer de overfitting estatístico. OBJETIVOS: Investigar se um modelo mais simples, nomeadamente o escore ACEF-MDRD, poderia ser usado para prever a mortalidade em um ano em pacientes com IC. MÉTODOS: 748 casos do registro SELFIE-HF tinham dados completos para calcular o escore ACEF-MDRD. Os pacientes foram agrupados em tercis para análise. Para todos os testes, um valor de p <0,05 foi aceito como significativo. RESULTADOS: Significativamente mais pacientes dentro do tercil ACEF-MDRD alto (30,0%) morreram dentro de um ano, em comparação com outros tercis (10,8% e 16,1%, respectivamente, para ACEF-MDRD baixo e ACEF-MDRD med , p<0,001 para ambas as comparações). Houve uma diminuição gradual na sobrevida em um ano à medida que o escore ACEF-MDRD aumentou (log-rank p<0,001). ACEF-MDRD foi preditor independente de sobrevida após ajuste para outras variáveis (OR: 1,14, IC95%:1,04 ­ 1,24, p=0,006). O escore ACEF-MDRD ofereceu precisão semelhante ao escore GWTG-HF para prever a mortalidade em um ano (p=0,14). CONCLUSÕES: ACEF-MDRD é um preditor de mortalidade em pacientes com IC e sua utilidade é comparável a modelos semelhantes, porém mais complicados.