Rajalakshmi Santhanakrishnan

Growth differentiation factor 15, ST2, high‐sensitivity troponin T, and N‐terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction

Growth differentiation factor 15 (GDF15), ST2, high‐sensitivity troponin T (hsTnT), and N‐terminal pro brain natriuretic peptide (NT‐proBNP) are biomarkers of distinct mechanisms that may contribute to the pathophysiology of heart failure (HF) [inflammation (GDF15); ventricular remodelling (ST2); myonecrosis (hsTnT); and wall stress (NT‐proBNP)].

Iron deficiency in a multi-ethnic Asian population with and without heart failure: prevalence, clinical correlates, functional significance and prognosis

Current heart failure (HF) guidelines highlight the importance of iron deficiency (ID) in HF. Whether HF itself or age‐related comorbidities contribute to ID is uncertain, and previous data were limited to Western populations. We aimed to study the prevalence, clinical correlates, functional significance and prognosis of ID in HF patients, compared with community‐based controls in a multi‐ethnic Southeast Asian population.

The Singapore Heart Failure Outcomes and Phenotypes (SHOP) Study and Prospective Evaluation of Outcome in Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PEOPLE) Study: Rationale and Design

BACKGROUND Heart failure (HF) with preserved ejection fraction (EF) accounts for a substantial proportion of cases of HF, and to date no treatments have clearly improved outcome. There are also little data comparing HF cohorts of differing ethnicity within the Asia-Pacific region. METHODS The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study are parallel prospective studies using identical protocols to enroll patients with HF across 6 centers in Singapore and 4 in New Zealand. The objectives are to determine the relative prevalence, characteristics, and outcomes of patients with HF and preserved EF (EF ≥50%) compared with those with HF and reduced EF, and to determine initial data on ethnic differences within and between New Zealand and Singapore. Case subjects (n = 2,500) are patients hospitalized with a primary diagnosis of HF or attending outpatient clinics for management of HF within 6 months of HF decompensation. Control subjects are age- and gender-matched community-based adults without HF from Singapore (n = 1,250) and New Zealand (n = 1,073). All participants undergo detailed clinical assessment, echocardiography, and blood biomarker measurements at baseline, 6 weeks, and 6 months, and are followed over 2 years for death or hospitalization. Substudies include vascular assessment, cardiopulmonary exercise testing, retinal imaging, and cardiac magnetic resonance imaging. CONCLUSIONS The SHOP and PEOPLE studies are the first prospective multicenter studies defining the epidemiology and interethnic differences among patients with HF in the Asia-Oceanic region, and will provide unique insights into the pathophysiology and outcomes for these patients.

PT015 Association of Ethnicity, Age and Body Size with Electrocardiographic Values in the Community

Existing reference values for electrocardiography (ECG) were derived in Caucasian adults. We studied the association of ethnicity, age and body size with ECG measurements in a multi-ethnic community-based cohort of Asian adults. Adults without cardiovascular disease or bundle branch block were

Predicting Heart Failure With Preserved and Reduced Ejection FractionCLINICAL PERSPECTIVE: The International Collaboration on Heart Failure Subtypes

Background—Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF). Methods and Results—Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2:1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c-statistic 0.80; 95% confidence interval [CI], 0.78–0.82) and validation samples (internal: 0.79; 95% CI, 0.77–0.82 and external: 0.76; 95% CI: 0.71–0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80–0.84) and validation samples (internal: 0.80; 95% CI, 0.78–0.83 and external: 0.76; 95% CI, 0.71–0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF (P value for each comparison ⩽0.02). Conclusions—We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes.Background— Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF). Methods and Results— Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2:1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c-statistic 0.80; 95% confidence interval [CI], 0.78–0.82) and validation samples (internal: 0.79; 95% CI, 0.77–0.82 and external: 0.76; 95% CI: 0.71–0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80–0.84) and validation samples (internal: 0.80; 95% CI, 0.78–0.83 and external: 0.76; 95% CI, 0.71–0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF ( P value for each comparison ≤0.02). Conclusions— We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes.

Predicting Heart Failure With Preserved and Reduced Ejection FractionCLINICAL PERSPECTIVE

Background—Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF). Methods and Results—Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2:1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c-statistic 0.80; 95% confidence interval [CI], 0.78–0.82) and validation samples (internal: 0.79; 95% CI, 0.77–0.82 and external: 0.76; 95% CI: 0.71–0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80–0.84) and validation samples (internal: 0.80; 95% CI, 0.78–0.83 and external: 0.76; 95% CI, 0.71–0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF (P value for each comparison ⩽0.02). Conclusions—We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes.Background— Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF). Methods and Results— Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2:1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c-statistic 0.80; 95% confidence interval [CI], 0.78–0.82) and validation samples (internal: 0.79; 95% CI, 0.77–0.82 and external: 0.76; 95% CI: 0.71–0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80–0.84) and validation samples (internal: 0.80; 95% CI, 0.78–0.83 and external: 0.76; 95% CI, 0.71–0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF ( P value for each comparison ≤0.02). Conclusions— We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes.

Atrial Fibrillation Begets Heart Failure and Vice VersaCLINICAL PERSPECTIVE: Temporal Associations and Differences in Preserved Versus Reduced Ejection Fraction

Background— Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction. Methods and Results— We studied Framingham Heart Study participants with new-onset AF or HF between 1980 and 2012. Among 1737 individuals with new AF (mean age, 75±12 years; 48% women), more than one third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79±11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HF with preserved ejection fraction (multivariable-adjusted hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.48–3.70; no AF as referent) versus HF with reduced ejection fraction (HR, 1.32; 95% CI, 0.83–2.10), with a trend toward difference between HF subtypes ( P for difference=0.06). Prevalent HF was associated with incident AF (HR, 2.18; 95% CI, 1.26–3.76; no HF as referent). The presence of both AF and HF portended greater mortality risk compared with neither condition, particularly among individuals with new HF with reduced ejection fraction and prevalent AF (HR, 2.72; 95% CI, 2.12–3.48) compared with new HF with preserved ejection fraction and prevalent AF (HR, 1.83; 95% CI, 1.41–2.37; P for difference=0.02). Conclusions— AF occurs in more than half of individuals with HF, and HF occurs in more than one third of individuals with AF. AF precedes and follows HF with both preserved and reduced ejection fraction, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted. # CLINICAL PERSPECTIVE {#article-title-46}Background— Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction. Methods and Results— We studied Framingham Heart Study participants with new-onset AF or HF between 1980 and 2012. Among 1737 individuals with new AF (mean age, 75±12 years; 48% women), more than one third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79±11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HF with preserved ejection fraction (multivariable-adjusted hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.48–3.70; no AF as referent) versus HF with reduced ejection fraction (HR, 1.32; 95% CI, 0.83–2.10), with a trend toward difference between HF subtypes (P for difference=0.06). Prevalent HF was associated with incident AF (HR, 2.18; 95% CI, 1.26–3.76; no HF as referent). The presence of both AF and HF portended greater mortality risk compared with neither condition, particularly among individuals with new HF with reduced ejection fraction and prevalent AF (HR, 2.72; 95% CI, 2.12–3.48) compared with new HF with preserved ejection fraction and prevalent AF (HR, 1.83; 95% CI, 1.41–2.37; P for difference=0.02). Conclusions— AF occurs in more than half of individuals with HF, and HF occurs in more than one third of individuals with AF. AF precedes and follows HF with both preserved and reduced ejection fraction, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted.

Atrial Fibrillation Begets Heart Failure and Vice VersaCLINICAL PERSPECTIVE

Background— Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction. Methods and Results— We studied Framingham Heart Study participants with new-onset AF or HF between 1980 and 2012. Among 1737 individuals with new AF (mean age, 75±12 years; 48% women), more than one third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79±11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HF with preserved ejection fraction (multivariable-adjusted hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.48–3.70; no AF as referent) versus HF with reduced ejection fraction (HR, 1.32; 95% CI, 0.83–2.10), with a trend toward difference between HF subtypes ( P for difference=0.06). Prevalent HF was associated with incident AF (HR, 2.18; 95% CI, 1.26–3.76; no HF as referent). The presence of both AF and HF portended greater mortality risk compared with neither condition, particularly among individuals with new HF with reduced ejection fraction and prevalent AF (HR, 2.72; 95% CI, 2.12–3.48) compared with new HF with preserved ejection fraction and prevalent AF (HR, 1.83; 95% CI, 1.41–2.37; P for difference=0.02). Conclusions— AF occurs in more than half of individuals with HF, and HF occurs in more than one third of individuals with AF. AF precedes and follows HF with both preserved and reduced ejection fraction, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted. # CLINICAL PERSPECTIVE {#article-title-46}Background— Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction. Methods and Results— We studied Framingham Heart Study participants with new-onset AF or HF between 1980 and 2012. Among 1737 individuals with new AF (mean age, 75±12 years; 48% women), more than one third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79±11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HF with preserved ejection fraction (multivariable-adjusted hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.48–3.70; no AF as referent) versus HF with reduced ejection fraction (HR, 1.32; 95% CI, 0.83–2.10), with a trend toward difference between HF subtypes (P for difference=0.06). Prevalent HF was associated with incident AF (HR, 2.18; 95% CI, 1.26–3.76; no HF as referent). The presence of both AF and HF portended greater mortality risk compared with neither condition, particularly among individuals with new HF with reduced ejection fraction and prevalent AF (HR, 2.72; 95% CI, 2.12–3.48) compared with new HF with preserved ejection fraction and prevalent AF (HR, 1.83; 95% CI, 1.41–2.37; P for difference=0.02). Conclusions— AF occurs in more than half of individuals with HF, and HF occurs in more than one third of individuals with AF. AF precedes and follows HF with both preserved and reduced ejection fraction, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted.

ETHNICITY AND SEX-SPECIFIC ECHOCARDIOGRAPHIC AND ELECTROCARDIOGRAPHIC CRITERIA FOR LEFT VENTRICULAR HYPERTROPHY: COMMUNITY-BASED DATA FROM AN ASIAN POPULATION

Current electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH), such as the Cornell criteria, were derived in Western populations. We assessed the utility of Cornell criteria for the diagnosis of echocardiographic LVH, and if alternative ECG cut-offs may improve the diagnostic