Carolyn Su Ping Lam

This article details a correction to: Prabhakaran D, Singh K, Kondal D, Raspail L, Mohan B, Kato T, et al. Cardiovascular Risk Factors and Clinical Outcomes among Patients Hospitalized with COVID-19: Findings from the World Heart Federation COVID-19 Study. Global Heart. 2022; 17(1): 40. DOI: http://doi.org/10.5334/gh.1128.

Background and aims: Limited data exist on the cardiovascular manifestations and risk factors in people hospitalized with COVID-19 from low- and middle-income countries. This study aims to describe cardiovascular risk factors, clinical manifestations, and outcomes among patients hospitalized with COVID-19 in low, lower-middle, upper-middle- and high-income countries (LIC, LMIC, UMIC, HIC).Methods: Through a prospective cohort study, data on demographics and pre-existing conditions at hospital admission, clinical outcomes at hospital discharge (death, major adverse cardiovascular events (MACE), renal failure, neurological events, and pulmonary outcomes), 30-day vital status, and re-hospitalization were collected. Descriptive analyses and multivariable log-binomial regression models, adjusted for age, sex, ethnicity/income groups, and clinical characteristics, were performed.Results: Forty hospitals from 23 countries recruited 5,313 patients with COVID-19 (LIC = 7.1%, LMIC = 47.5%, UMIC = 19.6%, HIC = 25.7%). Mean age was 57.0 (±16.1) years, male 59.4%, pre-existing conditions included: hypertension 47.3%, diabetes 32.0%, coronary heart disease 10.9%, and heart failure 5.5%. The most frequently reported cardiovascular discharge diagnoses were cardiac arrest (5.5%), acute heart failure (3.8%), and myocardial infarction (1.6%). The rate of in-hospital deaths was 12.9% (N = 683), and post-discharge 30 days deaths was 2.6% (N = 118) (overall death rate 15.1%). The most common causes of death were respiratory failure (39.3%) and sudden cardiac death (20.0%). The predictors of overall mortality included older age (≥60 years), male sex, pre-existing coronary heart disease, renal disease, diabetes, ICU admission, oxygen therapy, and higher respiratory rates (p < 0.001 for each). Compared to Caucasians, Asians, Blacks, and Hispanics had almost 2–4 times higher risk of death. Further, patients from LIC, LMIC, UMIC versus. HIC had 2–3 times increased risk of death.Conclusions: The LIC, LMIC, and UMIC’s have sparse data on COVID-19. We provide robust evidence on COVID-19 outcomes in these countries. This study can help guide future health care planning for the pandemic globally.

Background Heart failure with preserved ejection fraction (HFpEF) is a global public health problem. Unfortunately, little is known about HFpEF across Asia. Methods and results We prospectively studied clinical characteristics, echocardiographic parameters and outcomes in 1204 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions, grouped as Northeast Asia (Hong Kong, Taiwan, China, Japan, Korea, n = 543), South Asia (India, n = 252), and Southeast Asia (Malaysia, Thailand, Singapore, Indonesia, Philippines, n = 409). Mean age was 68 ±12 years (37% were < 65 years) and 50% were women. Seventy per cent of patients had ≥2 co‐morbidities, most commonly hypertension (71%), followed by anaemia (57%), chronic kidney disease (50%), diabetes (45%), coronary artery disease (29%), atrial fibrillation (29%) and obesity (26%). Southeast Asian patients had the highest prevalence of all co‐morbidities except atrial fibrillation, South Asians had the lowest prevalence of all co‐morbidities except anaemia and obesity, and Northeast Asians had more atrial fibrillation. Left ventricular hypertrophy and concentric remodelling were most prominent among Southeast and South Asians, respectively (P < 0.001). Overall, 12.1% of patients died or were hospitalized for heart failure within 1 year. Southeast Asians were at higher risk for adverse outcomes, independent of co‐morbidity burden and cardiac geometry. Conclusion These first prospective multinational data from Asia show that HFpEF affects relatively young patients with a high burden of co‐morbidities. Regional differences in types of co‐morbidities, cardiac remodelling and outcomes of HFpEF across Asia have important implications for public health measures and global HFpEF trial design.

Background: QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. Methods: We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. Results: Compared with whites, Asian patients with HF were younger (62 vs 74 years, pinteraction120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity. Conclusion: We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study.

Heart failure with preserved ejection fraction (HFPEF) is a global health problem of considerable socioeconomic burden. It is projected to worsen with the aging population worldwide. The lack of effective therapies underscores our incomplete understanding of this complex heterogeneous syndrome. A novel paradigm has recently emerged, in which central roles are ascribed to systemic inflammation and generalized endothelial dysfunction in the pathophysiology of HFPEF. In this review, we discuss the role of the endothelium in cardiovascular homeostasis and how deranged endothelial-related signaling pathways contribute to the development of HFPEF. We also review the novel therapies in various stages of research and development that target different components of this signaling pathway.

Aims: Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) worldwide regardless of haemoglobin levels. Results from therapeutic trials of intermittently dosed intravenous (i.v.) iron are promising in the ambulatory Caucasian population with HF with reduced left ventricular ejection fraction, although evidence is scarce in Asia. The Pilot Randomized Controlled Trial to Assess the Role of Intravenous Ferric Carboxymaltose in Asian Patients with Heart Failure aims to assess the effect of single-dose i.v. ferric carboxymaltose (FCM) in a multi-ethnic Asian population with HF and ID. Methods and results: This is an open-label, randomized, placebo-controlled trial recruiting stabilized inpatients with decompensated HF (regardless of left ventricular ejection fraction), ID [defined as serum ferritin <300 ng/mL if transferrin saturation <20%] and haemoglobin ≤14 g/dL. Patients from two tertiary institutions were randomized in a 1:1 ratio to receive a single dose of either i.v. FCM (Ferinject®) 1000 mg or i.v. normal saline. The primary endpoint is the change in 6-min walk distance at Weeks 4 and 12, and secondary endpoints are changes at Weeks 4 and 12 in (i) quality of life as measured by the Kansas City Cardiomyopathy Questionnaire and Visual Analogue Scale scores and (ii) New York Heart Association functional class. Conclusions: Preliminary efficacy data on i.v. FCM therapy in Asian HF are expected from this pilot study to support larger-scale multicentre therapeutic i.v. FCM trials within Asia.

Aim Growth differentiation factor 15 (GDF15) is a cytokine highly expressed in states of inflammatory stress. We aimed to study the clinical correlates and prognostic significance of plasma GDF15 in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction(HFrEF), compared with N-terminal pro-brain natriuretic peptide (NT-proBNP), an indicator of haemodynamic wall stress. Methods Plasma GDF15 and NT-proBNP were prospectively measured in 916 consecutive patients with HFrEF (EF n = 730) and HFpEF (EF ≥50%; n = 186), and measured again at 6 months in 488 patients. Patients were followed up for a composite outcome of death or first HF rehospitalization. Results Median GDF15_baseline values were similarly elevated in HFpEF [2862 (1812 represent the 25th percentile and 4176 represent the 75th percentile) ng/L] and HFrEF [2517 (1555, 4030) ng/L] (P = 0.184), whereas NT-proBNP was significantly lower in HFpEF than HFrEF (1119 ng/L vs. 2335 ng/L, P < 0.001). Independent correlates of GDF15_baseline were age, systolic blood pressure, New York Heart Association (NYHA) class, diabetes, atrial fibrillation, sodium, haemoglobin, creatinine, diuretic therapy, high sensitivity troponin T (hsTnT) and NT-proBNP (all P < 0.05). During a median follow-up of 23 months, there were 379 events (307 HFrEF, 72 HFpEF). GDF15 remained a significant independent predictor for composite outcome even after adjusting for important clinical predictors including hsTnT and NT-proBNP (adjusted hazard ratio 1.76 per 1 Ln U, 95% confidence interval 1.39–2.21; P < 0.001), regardless of HF group (P_interaction = 0.275). GDF15_baseline provided incremental prognostic value when added to clinical predictors, hsTnT and NT-proBNP (area under receiver operating characteristic curve increased from 0.720 to 0.740, P < 0.019), with a net reclassification improvement of 0.183 (P = 0.004). Patients with ≥20% GDF15_6months increase had higher risk for composite outcome (adjusted hazard ratio 1.68, 95% confidence interval 1.15–2.45; P = 0.007) compared with those with GDF15_6months within ± 20% of baseline. Conclusions The similarly elevated levels and independent prognostic utility of GDF15 in HFrEF and HFpEF suggest that beyond haemodynamic stress (NT-proBNP), inflammatory injury (GDF15) may play an important role in both HF syndromes.