Higher Risk Of Heart Failure Research Articles

Abstract P064: Metabolic Risk Transitions In Obesity With The Incidence Of Heart Failure And Coronary Heart Disease: The Atherosclerosis Risk In Communities (aric) Study

Introduction: Obesity is associated with a varying spectrum of metabolic risk, from the metabolically healthy obesity (MHO) phenotype, to metabolically unhealthy obesity (MUO) with the development of metabolic syndrome (MetS) and diabetes (DM). The longitudinal association of metabolic risk with CVD phenotypes (CHD, HF) has not been well characterized. Hypothesis: Persistent MHO is independently associated with heart failure (HF) but not coronary heart disease (CHD), and regression from MUO to MHO mitigates CVD risk. Methods: We conducted a prospective analysis of 10,011 Visit 4 (1996-98) ARIC participants free of HF and CHD (mean age 63, 21% Black, 56% female). Metabolic risk among those with obesity (BMI ≥ 30 kg/m 2 ) was categorized as MHO (no MetS or DM), MUO (MetS present) and MUO with DM, with same categorizations among those without obesity. We used Cox regression models to estimate associations of cross-categories of metabolic risk status at Visit 2 (1990-92) and Visit 4 with risk of HF and CHD after Visit 4 through 12/21/19. (Reference: persistent metabolically healthy normal weight). Results: Between Visits 2 and 4, 56% of those with MHO transitioned to MUO. There were 2212 HF and 1648 CHD events, median follow-up of 20.5 years. Persistent MHO status was associated with increased risk for HF (HR:1.59, 95% CI: 1.19-2.13) but not CHD (HR: 1.08, 95% CI: 0.74-1.58) (Table). Persistent MUO with DM had the highest risk for HF (HR: 5.30, 95% CI: 4.38-6.41) and CHD (HR: 3.77, 95% CI: 3.00-4.74). Among those with MUO at Visit 2, progression to MUO with DM at Visit 4 was linked to greater risk for HF and CHD, while regression to MHO was associated with an attenuated risk for CVD. Similar patterns were seen for those without obesity (data not shown). Conclusions: Transitions in metabolic risk status are common and associated with divergent patterns of CVD risk. Progression from MHO to MUO and even persistent MHO are linked to HF risk, whereas regression from MUO to MHO may attenuate CVD risk. Primordial prevention of obesity is warranted to stave off HF.

Abstract P127: Differences By Gender In Autopsy-determined Myocardial Characteristics Following Myocardial Infarction

Introduction: Women are at higher risk for heart failure and mortality after myocardial infarction (MI) than men. Differences in tissue-level response to ischemia and MI for women vs. men are incompletely understood and have the potential to contribute to differences in post-MI sequelae such as heart failure and sudden death. Methods: We analyzed clinical data and paired autopsy reports from decedent patients who underwent autopsy at a large urban medical center from 4/6/2002 to 4/1/2021. Using clinical autopsy reports completed by a trained pathologist, we then determined the presence or absence of five specific autopsy-based myocardial characteristics: fibrosis, pathologic evidence of a remote vs. acute myocardial infarction, myocardial inflammation, and/or myocardial infiltrates. Linked clinical data were used to determine demographics, anthropometrics, and presence/absence of clinical diagnoses (the latter of which were based on administrative codes). Our primary analyses compared the presence of autopsy-based diagnoses for men vs. women, stratified by prior clinical diagnoses of MI; we used Chi-square analyses with a p-value of <0.05 to indicate statistical significance. Results: Ages at death of men (N=152) and women (N=103) who had clinical diagnoses of MI preceding death and autopsy were similar (Table), but men with MI diagnoses were more commonly White non-Hispanic (75/152, 49%) whereas women were more commonly Black non-Hispanic (51/103, 50%). Women with clinical diagnoses of MI were significantly less likely to have myocardial fibrosis at autopsy compared with men (68% vs 79%; p=0.048). Conclusions: Among individuals with clinical diagnoses of MI prior to death, we observed that men were more likely to have autopsy-determined myocardial fibrosis compared with women. These data do not suggest increased post-MI myocardial scar among women as a likely cause of higher rates of heart failure following MI; however, our data require validation in other cohorts with linked clinical and pathology data.

Abstract 026: Rurality And Incident Heart Failure Risk In The Southern Community Cohort Study

Background: Rural-urban disparities in cardiovascular mortality are increasing, with higher heart failure (HF) mortality among rural residents. Whether rurality is also associated with an increased risk of HF incidence is not known. Methods: A total of 27,119 Southern Community Cohort Study participants without prevalent HF receiving Centers for Medicare and Medicaid Services (CMS) at cohort enrollment (2002-2009) were included. Rurality at enrollment was classified by Rural-Urban Commuting Area codes based on participant census tract. Incident HF was defined using ICD 9/10 codes (428.x, I50x) via CMS linkage through 2016. The association between rurality and incident HF was tested in Cox models adjusted for age, sex, race, socioeconomic status, cardiovascular risk factors and comorbidities, with addition of a race-sex by rurality interaction term. Results: Overall, 20% (5,556) of participants resided in rural areas. Compared with urban-residing participants, individuals in rural areas were more likely to be older, female, married, less educated, and to have a higher burden of traditional cardiovascular risk factors, but were of similar race and income. Over median 13-years follow-up, 1,865 (33.6%) and 5,677 (26.3%) rural and urban individuals developed HF, respectively; p < 0.001. In adjusted analysis, rurality associated with a 19% greater risk of incident HF (HR 1.19, 95% CI 1.12-1.26). The association between rurality and HF risk varied by race-sex (p-interaction = 0.003), with a marked disparity between Black (HR 1.34, 95% CI 1.19-1.50) and white (HR 0.98, 95% CI 0.82-1.17) men (Figure). Conclusions: In this large biracial Southeastern US population, rural residence associated with a substantial excess risk of HF particularly for women and Black men. These disparities highlight need for further research into underlying determinants and public health interventions.

Abstract P5-18-12: Cardioprotective effects of walnuts against aromatase inhibitor: Pilot study in a zebrafish model

Abstract BACKGROUND: Breast cancer patients on aromatase inhibitor (AI) are at a significantly higher risk of heart failure and cardiovascular disease (CVD) compared with patients on tamoxifen, and trend toward increased risks of myocardial infarction and ischemic stroke. In a clinical setting, AI has been shown to induce endothelial dysfunction that is a predictor of CVD. Further, patients on extended AI therapy exhibit significantly higher number of cardiovascular events when compared with patients who took AI for no longer than 5 years. AI effects on cardiovascular health may reflect the expression of functional estrogen receptors (ERs) in vascular endothelial and smooth muscle cells and cardiomyocytes, especially the membrane bound G-protein coupled ER (GPER). Activation of nuclear ER causes enhanced vasorelaxation and re-endovascularization, whilst GPER has been identified as a mediator of estrogen-induced vasodilation, either acting through nitric oxide (NO) or independent of it. GPER activation also protects against cholesterol-induced endothelial changes and endothelial inflammation. Since walnuts and walnut oil have many cardioprotective properties, we investigated if walnuts might prevent adverse effects of AI on a zebrafish model. Walnuts are rich in plant-derived n-3 PUFA alpha-linolenic acid (ALA).METHODS: Zebrafish embryos are used in cardiotoxicity studies (reduction of heartbeat) to model various human diseases. It has been shown that at 72 hours post fertilization (hpf) the primary and sprout vessels in the zebrafish embryo heart become active, and the blood vessel structure closely resembles of that in the human body. In our study, zebrafish embryos were treated with 4 mL of corn oil, soybean oil, docosahexaenoic acid (DHA) added to soybean oil, walnut oil or walnut powder added to walnut oil when they were 24 hpf. Oils were administered to yolk sac. 10-500 mM letrozole was added to water when fish were 48 hpf, and finally heart beat was measured from 72 hpf embryos. For the heart beat measurements, zebrafish embryos were anesthetized, and recorded to calculate the heart rate. After zebrafish was euthanized, RNA and protein were collected to assess changes in Esr2a, Esr2b, Gper1, Nos1, Nos2a, and Nos2b (shares properties with Nos3/eNOS). RESULTS: Administration of 500 mM letrozole significantly (p<0.001) reduced the heartbeat in zebrafish, indicating that it impaired cardiac function. None of the oils significantly altered the heartbeat, compared with controls. However, both walnut oil (p<0.006) and walnut powder enriched walnut oil (p<0.001) increased heartbeat in letrozole treated zebrafish, compared with zebrafish only given letrozole. Thus, walnuts prevented letrozole induced reduction in heartbeat. RT-qPCR analysis indicated that letrozole significantly reduced Gper (p<0.001) levels. Walnut oil prevented this change. Walnut oil also caused a significant reduction in Nos1 (p=0.014) levels during letrozole treatment. The effect of walnut powder on gene expression has not yet been studied.CONCLUSIONS: Although preliminary, our data suggest that walnuts might be cardioprotective during letrozole treatment. The protective effect may be mediated by prevention of letrozole-induced inhibition of GPER which acts as a vasodilator in the vasculature and cardiomyocytes. Future studies are planned to investigate if feeding adult zebrafish walnut powder and/or walnut oil has cardioprotective effects against chronic letrozole administration, whether GPER is the mediator of these effects, and if GPER acts through activating pathways such as EGFR, ERK, PI3K/Akt and cAMP/PKA. Further, the possibility that walnuts might either adversely or beneficially affect AIs’ effects on breast cancer will be studied. Citation Format: Leena Hilakivi-Clarke, Joas Lucas Da Silva, Anne Blaes, Luke Hoeppner. Cardioprotective effects of walnuts against aromatase inhibitor: Pilot study in a zebrafish model [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-12.

Wasted myocardial work may affect left ventricular remodelling occurrence after primary percutaneous coronary revascularization

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Left ventricular function recovery (LV-REC) or left ventricular adverse remodelling (LV-REM) after acute myocardial infarction (AMI) play an important role for identifying patients at risk of heart failure. Purpose In this study we aim to evaluate the usefulness of non-invasive myocardial work (MW), a new index of global and regional myocardial performance, to predict LV-REC or LV-REM after AMI. Methods Fifty patients with AMI (mean age, 63,8 ±13,4 years), treated by primary percutaneous coronary intervention (PCI), were prospectively enrolled. They underwent a baseline transthoracic Doppler echocardiography (TTE) within 48 hours after PCI and a second TTE after a median of 31 days during the follow-up. MW was derived from the strain-pressure loops, integrating in its calculation the non-invasive arterial pressure, according to standard speckle tracking echocardiography recommendations. LV-REC was defined as an absolute improvement of left ventricular ejection fraction (LVEF) ≥ 5% from LVEF at baseline, whereas LV-REM was defined as an increase of ≥ 20% of the LV end diastolic volume (LVEDV) at 1 month follow up. Results We overall found a significant improvement from baseline to one-month follow-up for values of LVEF (49,8 ± 9,5 % vs 52,8 ± 9,3 %, p = 0.001), Global Longitudinal Strain (GLS) (-13,4 ± 3,9 % vs -18,7 ± 5,4 %, p = 0.016), Global Work Index (GWI) (1368,6 ±435,2 vs 1788 ±493 mmHg/%, p = 0.0001), Global Work Efficiency (GWE) (89,96 ± 9,3 % vs 91,3 ± 6,4 %, p = 0.001), Global Constructive Work (GCW) (1619,16 ± 497,9 mmHg/% vs 2008,6 ± 535,3 mmHg/%, p = 0.0001), Global Wasted Work (GWW) (188,8 ± 19,8 mmHg/% vs 149,2 ± 16,5 mmHg/%). However, LV-REC at 1 month of follow-up was observed only in 36 % of the population enrolled, whereas LV-REM was described in 18% of cases. Using ROC curve analysis, we identified a cut off value of 202 mmHg/% for baseline GWW (Sensitivity 75%, Specificity 62%, AUC 0.6667, CI 95%: 0,51618 - 0,81715, p =0.0001) to identify patients with LV-REM at 1 month. With regards to conventional echo parameters, patients with LV-REC showed lower baseline Wall Motion Score Index (WMSI) than those without LV-REC (1,73 vs 1,38, p = 0.007). Conclusions Among standard and advanced TTE parameters, only baseline GWW is able to predict early LV-REM at 1 month after primary PCI. Therefore, it could be used during baseline evaluation of AMI patients for a more accurate stratification of those at higher risk of heart failure. However, further larger scale studies are needed to validate these findings. Abstract table 1 Abstract table 2

Cardiac autonomic neuropathy and risk of incident heart failure among adults with type 2 diabetes.

Community-based data on the association between cardiac autonomic neuropathy (CAN) and incident heart failure (HF) in type 2 diabetes are limited. We evaluated the association of CAN with incident HF in adults with type 2 diabetes. This analysis included participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without HF at baseline. CAN was assessed by electrocardiogram-based measures of heart rate variability (HRV) and QT interval index (QTI). HRV was measured using standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). CAN was defined using composite measures of the lowest quartile of SDNN and highest quartiles of QTI and heart rate. Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) for HF in relation to various CAN measures. A total of 7160 participants (mean age 62.3 [standard deviation 6.4] years, 40.8% women, 61.9% white) were included. Over a median follow-up of 4.9 years (interquartile range 4.0-5.7), 222 participants developed incident HF. After multivariable adjustment for relevant confounders, lower HRV as assessed by SDNN was associated with a higher risk of HF (aHR for the lowest vs highest quartile of SDNN: 1.70, 95% confidence interval [CI] 1.14-2.54). Participants with CAN (defined as lowest quartile of SDNN and highest quartiles of QTI and heart rate) had a 2.7-fold greater risk of HF (aHR 2.65, 95% CI 1.57-4.48). In a large cohort of adults with type 2 diabetes, CAN was independently associated with higher risk of incident HF.

Aortic diastolic pressure decay explains sex-related differences in the subendocardial viability ratio: the Wakuya study.

Coronary heart disease is the leading cause of mortality in women. Despite a higher risk of heart failure after the first myocardial infarction in women compared with men, the sex-specific mechanisms are unknown. We hypothesized that myocardial ischemia is attributable to sex-related diastolic alterations in the central hemodynamics. We investigated the subendocardial viability ratio (myocardial oxygen supply/demand) and aortic diastolic pressure decay index in 962 apparently healthy adults (mean age, 56 ± 10 years). Using noninvasive applanation tonometry, the subendocardial viability ratio, aortic diastolic pressure decay index, and aortic augmentation index were estimated in all participants. The aortic diastolic pressure decay index was quantified by fitting an exponential curve: P(t) = P0e-λt (λ, decay index; P0, end-systolic pressure; t, time from end-systole). Women showed a significantly higher aortic diastolic pressure decay index, even after adjusting for age, hypercholesterolemia, and diabetes, and a significantly lower subendocardial viability ratio than men (P < 0.001). Analysis demonstrated a mediating effect of the aortic decay index on the sex-related differences in the subendocardial viability ratio (71%), despite different effects of the augmentation index (5%). These results suggest that the predisposition of women to coronary heart disease is more likely attributable to impaired myocardial perfusion caused by accelerated aortic diastolic pressure decay, rather than increased myocardial load due to augmented aortic systolic pressure.

Race- and Gender-Based Differences in Cardiac Structure and Function and Risk of Heart Failure

BackgroundAlthough heart failure (HF) risk and cardiac structure/function reportedly differ according to race and gender, limited data exist in late life when risk of HF is highest. ObjectivesThe goal of this study was to evaluate race/gender–based differences in HF risk factors, cardiac structure/function, and incident HF in late life. MethodsThis analysis included 5,149 HF-free participants from ARIC (Atherosclerosis Risk In Communities), a prospective epidemiologic cohort study, who attended visit 5 (2011-2013) and underwent echocardiography. Participants were subsequently followed up for a median 5.5 years for incident HF/death. ResultsPatients’ mean age was 75 ± 5 years, 59% were women, and 20% were Black. Male gender and Black race were associated with lower mean left ventricular ejection fraction. Black race was also associated with greater left ventricular wall thickness and concentricity, differences that persisted after adjusting for cardiovascular comorbidities. After adjusting for cardiovascular comorbidities, men were at higher risk for HF and heart failure with reduced ejection fraction (HFrEF) in Black participants compared with White participants (HF: HR of 2.36 [95% CI: 1.37-4.08] vs 1.16 [95% CI: 0.89-1.51], interaction P = 0.016; HFrEF: HR of 3.70 [95% CI: 1.72-7.95] vs 1.55 [95% CI: 1.01-2.37] respectively, interaction P = 0.039). Black race was associated with a higher incidence of HF overall and HFrEF in men only (HF: 1.65 [95% CI: 1.07-2.53] vs 0.76 [95% CI: 0.49-1.17]; HFrEF: HR of 2.55 [95% CI: 1.46-4.44] vs 0.91 [95% CI: 0.46-1.83]). No race/gender–based differences were observed in risk of incident heart failure with preserved ejection fraction. ConclusionsAmong older persons free of HF, men and Black participants exhibit worse systolic performance and are at heightened risk for HFrEF, whereas the risk of heart failure with preserved ejection fraction is similar across gender and race groups.

Unstable Angina Pectoris With Myocardial Injury Versus Myocardial Infarction in the Era of High-Sensitivity Cardiac Troponin

It is unknown whether outcomes in patients with unstable angina pectoris (UAP) and myocardial injury are different from outcomes in patients with non-ST-segment myocardial infarction (NSTEMI) with low peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT). This study aimed to compare the prognosis in patients with UAP and evidence of myocardial injury, with prognosis in patients with NSTEMI and different peak hs-cTnT concentrations. All visits to 7 different emergency departments in Sweden from December 9, 2009 to December 31, 2016 were identified (n=5,225,075). We included all hospitalized patients with hs-cTnT >14ng/L and a diagnosis of UAP or NSTEMI, with ≥2hours-cTnT measurements. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for all-cause mortality and cardiovascular events, in patients with NSTEMI categorized according to peak hs-cTnT concentrations, compared with patients with UAP. Altogether, 11,944 patients were included, of whom 1,253 (10%) received a diagnosis of UAP. During a median follow-up of 3.0 years (interquartile [IQR] 1.6 to 4.7), 3,297 patients died. There was no difference comparing patients with NSTEMI with peak hs-cTnT of 15 to 49ng/L to patients with UAP, with regards to long-term cardiovascular mortality (HR 1.15; 95% CI, 0.85 to 1.56), but the risk of recurrent myocardial infarction was higher in patients with NSTEMI (HR, 1.61; 95% CI, 1.29 to 2.00), and the risk of heart failure hospitalization slightly lower (HR 0.80, 95% CI, 0.64 to 0.99). In conclusion, patients with UAP and myocardial injury have a similar risk of death after discharge, but a lower risk of recurrent myocardial infarction and a marginally higher risk of heart failure, compared with patients with NSTEMI with moderately elevated hs-cTnT levels.

Assessment of left ventricular global longitudinal strain in patients with type 2 diabetes: Relationship with microvascular damage and glycemic control

Background and aimsType 2 Diabetes mellitus (T2DM) is associated with a higher risk of Heart Failure; Left Ventricular (LV) diastolic dysfunction is often considered the first marker of Diabetic cardiomyopathy; however, early preclinical LV systolic dysfunction has also been observed by means of echocardiographic measurement of strain. This study is aimed at assessing determinants of impaired strain and diastolic ventricular dysfunction in patients with T2DM. Methods and resultsCross-sectional study, performed on a consecutive series of patients with T2DM aged 30–80 years, BMI<40 kg/m2, free of cardiovascular disease, assessing metabolic control, microvascular complications, echocardiographic measures.Out of 206 patients, 19.6% had GLS lower than 18. GLS showed a significant inverse correlation with HBA1c, (p = 0.016), BMI (p = 0.002), waist (p < 0.0001), and mean L:H Ratio (p = 0.019). In a multivariate regression for LV GLS including HbA1c, age, sex, BMI and mean RR SDNN index, only HbA1c retained statistical significance: (B = −0.050 [−0.091; −0.009], p = 0.01. Among markers of LV diastolic function, only the E/E’ ratio was associated with HbA1c at a univariate analysis, and it retained statistical significance in a multivariate regression including HbA1c, age, sex and disease duration (B = 0.038 [0.03; −0.073], p = 0.032). No significant difference in any parameter of systolic or diastolic function was observed between patients with or without microalbuminuria or diabetic retinopathy. ConclusionIn patients with T2DM, a reduced left ventricular global longitudinal strain appears to be independently associated with impaired glucose control and autonomic neuropathy, regardless of microvascular complications.

Diastolic Dysfunction With Preserved Ejection Fraction After the Fontan Procedure.

BackgroundHeart failure phenotyping in single‐ventricle Fontan patients is challenging, particularly in patients with normal ejection fraction (EF). The objective of this study was to identify Fontan patients with abnormal diastolic function, who are high risk for heart failure with preserved ejection fraction (HFpEF), and characterize their cardiac mechanics, exercise function, and functional health status.Methods and ResultsData were obtained from the Pediatric Heart Network Fontan Cross‐sectional Study database. EF was considered abnormal if <50%. Diastolic function was defined as abnormal if the diastolic pressure:volume quotient (lateral E:e’/end‐diastolic volume) was >90th percentile (≥0.26 mL‐1). Patients were divided into: controls=normal EF and diastolic function; systolic dysfunction (SD) = abnormal EF with normal diastolic function; diastolic dysfunction (DD) = normal EF with abnormal diastolic pressure:volume quotient. Exercise function was quantified as percent predicted peak VO2. Physical Functioning Summary Score (FSS) was reported from the Child Health Questionnaire. A total of 239 patients were included, 177 (74%) control, 36 (15%) SD, and 26 (11%) DD. Median age was 12.2 (5.4) years. Arterial elastance, a measure of arterial stiffness, was higher in DD (3.6±1.1 mm Hg/mL) compared with controls (2.5±0.8 mm Hg/mL), P<0.01. DD patients had lower predicted peak VO2 compared with controls (52% [20] versus 67% [23], P<0.01). Physical FSS was lower in DD (45±13) and SD (44±13) compared with controls (50±7), P<0.01.ConclusionsFontan patients with abnormal diastolic function and normal EF have decreased exercise tolerance, decreased functional health status, and elevated arterial stiffness. Identification of patients at high risk for HFpEF is feasible and should be considered when evaluating Fontan patients.

Discriminative Utility of Apelin-to-NT-Pro-Brain Natriuretic Peptide Ratio for Heart Failure with Preserved Ejection Fraction among Type 2 Diabetes Mellitus Patients.

Background: Apelin is a regulatory vasoactive peptide, which plays a pivotal role in adverse cardiac remodeling and heart failure (HF) with reduced ejection fraction. The purpose of the study was to investigate whether serum levels of apelin is associated with HF with preserved election fraction (HFpEF) in patients with T2DM. Methods: The study retrospectively involved 101 T2DM patients aged 41 to 62 years (48 patients with HFpEF and 28 non-HFpEF patients). The healthy control group consisted of 25 individuals with matched age and sex. Data collection included demographic and anthropometric information, hemodynamic performances and biomarkers of the disease. Transthoracic B-mode echocardiography, Doppler and TDI were performed at baseline. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and apelin were measured by ELISA in all patients at the study entry. Results: Unadjusted multivariate logistic model yielded the only apelin to NT-proBNP ratio (OR = 1.44; p = 0.001), BMI > 34 кг/м2 (OR = 1.07; p = 0.036), NT-proBNP > 458 pmol/mL (OR = 1.17; p = 0.042), LAVI > 34 mL/m2 (OR = 1.06; p = 0.042) and E/e’ > 11 (OR = 1.04; p = 0.044) remained to be strong predictors for HFpEF. After obesity adjustment, multivariate logistic regression showed that the apelin to NT-proBNP ratio < 0.82 × 10−2 units remained sole independent predictor for HFpEF (OR = 1.44; 95% CI: 1.18–2.77; p = 0.001) HFpEF in T2DM patients. In conclusion, we found that apelin to NT-proBNP ratio < 0.82 × 10−2 units better predicted HFpEF in T2DM patients than apelin and NT-proBNP alone. This finding could open new approach for CV risk stratification of T2DM at higher risk of HF.

Elevated Brain Natriuretic Peptide and High Brachial Pulse Pressure in Patients With Diabetes.

Heart failure (HF) is frequent in patients with diabetes mellitus (DM), and early detection improves prognosis. We investigated whether analysis of brachial blood pressure (BP) in daily practice can identify patients with DM and high risk for subsequent HF, as defined by brain natriuretic peptide (BNP) >50 pg/ml. 3,367 outpatients with DM without a history of cardiovascular disease were enrolled in a prospective study. Age (mean ± SD) was 56 ± 14 years, 57% were male, 78% had type 2 DM, and HbA1C was 7.4 ± 1.4%. A history of hypertension was recorded in 43% of patients and uncontrolled BP was observed in 13%. BNP concentration (mean ± SD) was 21 ± 21 ng/l and 9% of patients had high risk of incident HF. Brachial pulse pressure (PP) was the best BP parameter associated with high risk of incident HF compared with diastolic, systolic, or mean BP (area under the receiver operating characteristic curve: 0.70, 0.65, 0.57, and 0.57, respectively). A multivariate analysis demonstrated that elevated PP was independently associated with high risk of incident HF (odds ratio [95% confidence interval, CI]: 2.1 [1.5-2.8] for PP ≥65 mm Hg). Study of central aortic BP and pulse wave velocity on 117 patients demonstrated that high risk of incident HF was associated with increased arterial stiffness and subendocardial ischemia. After a mean follow-up of 811 days, elevated PP was associated with increased all-cause mortality (hazard ratio [95% CI]: 1.7 [1.1-2.8]). Brachial PP is powerful and independent "easy to record" BP parameter associated with high risk of incident HF in diabetic patients.

Obesity Duration, Severity, and Distribution Trajectories and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study.

BackgroundResearch examining the role of obesity in cardiovascular disease (CVD) often fails to adequately consider heterogeneity in obesity severity, distribution, and duration.Methods and ResultsWe here use multivariate latent class mixed models in the biracial Atherosclerosis Risk in Communities study (N=14 514; mean age=54 years; 55% female) to associate obesity subclasses (derived from body mass index, waist circumference, self‐reported weight at age 25, tricep skinfold, and calf circumference across up to four triennial visits) with total mortality, incident CVD, and CVD risk factors. We identified four obesity subclasses, summarized by their body mass index and waist circumference slope as decline (4.1%), stable/slow decline (67.8%), moderate increase (24.6%), and rapid increase (3.6%) subclasses. Compared with participants in the stable/slow decline subclass, the decline subclass was associated with elevated mortality (hazard ratio [HR] 1.45, 95% CI 1.31, 1.60, P<0.0001) and with heart failure (HR 1.41, 95% CI 1.22, 1.63, P<0.0001), stroke (HR 1.53, 95% CI 1.22, 1.92, P=0.0002), and coronary heart disease (HR 1.36, 95% CI 1.14, 1.63, P=0.0008), adjusting for baseline body mass index and CVD risk factor profile. The moderate increase latent class was not associated with any significant differences in CVD risk as compared to the stable/slow decline latent class and was associated with a lower overall risk of mortality (HR 0.85, 95% CI 0.80, 0.90, P<0.0001), despite higher body mass index at baseline. The rapid increase latent class was associated with a higher risk of heart failure versus the stable/slow decline latent class (HR 1.34, 95% CI 1.10, 1.62, P=0.004).ConclusionsConsideration of heterogeneity and longitudinal changes in obesity measures is needed in clinical care for a more precision‐oriented view of CVD risk.

709 Non-invasive assessment of myocardial work: an useful tool for predicting LV remodelling after myocardial infarction?

Abstract Aims Left ventricular function recovery (LV-REC) or left ventricular adverse remodelling (LV-REM) after acute myocardial infarction (AMI) play an important role for identifying patients at risk of heart failure. In this study we aim to evaluate the usefulness of non-invasive myocardial work (MW), a new index of global and regional myocardial performance, to predict LV-REC or LV-REM after AMI. Methods and results Fifty patients with AMI (mean age, 63.8 ± 13.4 years), treated by primary percutaneous coronary intervention (PCI), were prospectively enrolled. They underwent a baseline transthoracic Doppler echocardiography (TTE) within 48 h after PCI and a second TTE after a median of 31 days during the follow-up. MW was derived from the strain-pressure loops, integrating in its calculation the non-invasive arterial pressure, according to standard speckle tracking echocardiography recommendations. LV-REC was defined as an absolute improvement of left ventricular ejection fraction (LVEF) ≥ 5% from LVEF at baseline, whereas LV-REM was defined as an increase of ≥ 20% of the LV end diastolic volume (LVEDV) at 1 month follow-up. We overall found a significant improvement from baseline to one-month follow-up for values of LVEF (49.8 ± 9.5% vs. 52.8 ± 9.3%, P = 0.001), global longitudinal strain (GLS) (−13.4 ± 3.9% vs. −18.7 ± 5.4%, P = 0.016), global work index (GWI) (1368.6 ± 435.2 vs. 1788 ± 493 mmHg/%, P = 0.0001), global work efficiency (GWE) (89.96 ± 9.3% vs. 91.3 ± 6.4%, P = 0.001), global constructive work (GCW) (1619.16 ± 497.9 mmHg/% vs. 2008.6 ± 535.3 mmHg/%, P = 0.0001), global wasted work (GWW) (188.8 ± 19.8 mmHg/% vs. 149.2 ± 16.5 mmHg/%). However, LV-REC at 1 month of follow-up was observed only in 36% of the population enrolled, whereas LV-REM was described in 18% of cases. Using ROC curve analysis, we identified a cut off value of 202 mmHg/% for baseline GWW (sensitivity 75%, specificity 62%, AUC 0.6667, CI 95%: 0.51618–0.81715, P = 0.0001) to identify patients with LV-REM at 1 month. With regards to conventional echo parameters, patients with LV-REC showed lower baseline wall motion score index (WMSI) than those without LV-REC (1.73 vs. 1.38, P = 0.007). Conclusions Among standard and advanced TTE parameters, only baseline GWW is able to predict early LV-REM at 1 month after primary PCI. Therefore, it could be used during baseline evaluation of AMI patients for a more accurate stratification of those at higher risk of heart failure. However, further larger scale studies are needed to validate these findings.

Diabetes Status Modifies the Association Between Different Measures of Obesity and Heart Failure Risk Among Older Adults: A Pooled Analysis of Community-Based NHLBI Cohorts.

Obesity and diabetes are associated with a higher risk of heart failure (HF). The interrelationships between different measures of adiposity-overall obesity, central obesity, fat mass (FM)-and diabetes status for HF risk are not well-established. Participant-level data from the ARIC study (Atherosclerosis Risk in Communities; visit 5) and the CHS (Cardiovascular Health Study; visit 1) cohorts were obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with versus without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m2), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes. The study included 10 387 participants (52.9% ARIC; 25.1% diabetes; median age, 74 years). The correlation between predicted and bioelectrical impedance-based FM was high (R2=0.90; n=5038). During a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (hazard ratio [95% CI] per 1 SD higher BMI=1.15 [1.05, 1.27], WC=1.22 [1.10, 1.36]; FM=1.13 [1.02, 1.25]). A significant interaction was noted between diabetes status and measures of BMI (P interaction=0.04) and WC (P interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (hazard ratio [95% CI] per 1 SD higher BMI=1.29 [1.14-1.47]; WC=1.48 [1.29-1.70]; FM=1.25 [1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, and 13.7%, respectively) versus those without diabetes (≤1% for each). Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.

ELABELA acts as a protective biomarker in patients with atrial fibrillation.

BackgroundAtrial fibrillation (AF) is the most common type of clinical arrhythmia. An early diagnosis can be beneficial in the prevention of complications, such as heart failure (HF) and stroke. In this study, we revealed that ELABELA (ELA) acts as a protective factor in patients with arrhythmia and could serve as a prognostic marker for AF and its associated complication of HF.MethodsWe tested the expression level of potential biomarkers including matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and ELA with enzyme-linked immunosorbent assay (ELISA) in serum derived from 131 patients (patients with AF =103; patients with paroxysmal supraventricular tachycardia =28). The impact of clinical risk factors and biomarkers on AF occurrence was evaluated using binary logistic analysis.ResultsThe ELA expression level was lower in AF patients than in the negative controls (P<0.0001). Expression of ELA was negatively correlated with brain natriuretic peptide (BNP) expression in all the samples. In the binary logistic analysis, high levels of BNP and lower levels of ELA were significantly associated with an increased risk of AF (P<0.0001) and could be used as prognostic markers for patients with AF.ConclusionsExpression of ELA showed a protective role in AF patients. The ELA level was negatively correlated with BNP levels, which has been shown to predict a high risk of HF independently and consistently. Additionally, lower levels of ELA were associated with a high risk of AF and HF in patients with arrhythmia.KeywordsELABELA (ELA); matrix metalloproteinase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1); atrial fibrillation (AF); brain natriuretic peptide (BNP)

Changes in Thyroid Hormone Signaling Mediate Cardiac Dysfunction in the Tg197 Mouse Model of Arthritis: Potential Therapeutic Implications.

Background Rheumatoid Arthritis (RA) patients show a higher risk of heart failure. The present study investigated possible causes of cardiac dysfunction related to thyroid hormone (TH) signaling in a RA mouse model. Methods A TNF-driven mouse model of RA[TghuTNF (Tg197)] was used. Cardiac function was evaluated by echocardiography. SERCA2a and phospholamban protein levels in left ventricle (LV) tissue, thyroid hormone levels in serum, TH receptors in LV and TH-related kinase signaling pathways were measured. T3 hormone was administered in female Tg197 mice. Results We show LV and atrial dilatation with systolic dysfunction in Tg197 animals, accompanied by downregulated SERCA2a. We suggest an interaction of pro-inflammatory and thyroid hormone signaling indicated by increased p38 MAPK and downregulation of TRβ1 receptor in Tg197 hearts. Interestingly, female Tg197 mice showed a worse cardiac phenotype related to reduced T3 levels and Akt activation. T3 supplementation increased Akt activation, restored SERCA2a expression and improved cardiac function in female Tg197 mice. Conclusions TNF overexpression of Tg197 mice results in cardiac dysfunction via p38 MAPK activation and downregulation of TRβ1. Gender-specific reduction in T3 levels could cause the worse cardiac phenotype observed in female mice, while T3 administration improves cardiac function and calcium handling via modified Akt activation.

Overlap phenotypes of the left ventricular noncompaction and hypertrophic cardiomyopathy with complex arrhythmias and heart failure induced by the novel truncated DSC2 mutation

BackgroundThe left ventricular noncompaction cardiomyopathy (LVNC) is a rare subtype of cardiomyopathy associated with a high risk of heart failure (HF), thromboembolism, arrhythmia, and sudden cardiac death.MethodsThe proband with overlap phenotypes of LVNC and hypertrophic cardiomyopathy (HCM) complicates atrial fibrillation (AF), ventricular tachycardia (VT), and HF due to the diffuse myocardial lesion, which were diagnosed by electrocardiogram, echocardiogram and cardiac magnetic resonance imaging. Peripheral blood was collected from the proband and his relatives. DNA was extracted from the peripheral blood of proband for high-throughput target capture sequencing. The Sanger sequence verified the variants. The protein was extracted from the skin of the proband and healthy volunteer. The expression difference of desmocollin2 was detected by Western blot.ResultsThe novel heterozygous truncated mutation (p.K47Rfs*2) of the DSC2 gene encoding an important component of desmosomes was detected by targeted capture sequencing. The western blots showed that the expressing level of functional desmocollin2 protein (~ 94kd) was lower in the proband than that in the healthy volunteer, indicating that DSC2 p.K47Rfs*2 obviously reduced the functional desmocollin2 protein expression in the proband.ConclusionThe heterozygous DSC2 p.K47Rfs*2 remarkably and abnormally reduced the functional desmocollin2 expression, which may potentially induce the overlap phenotypes of LVNC and HCM, complicating AF, VT, and HF.

Abstract 13083: Circulating Androgen Levels and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study (CHS)

Introduction: Circulating androgen levels in men decline with advancing age and have been linked to diabetes and atherosclerotic cardiovascular disease (ASCVD). A similar relationship has been reported for low total testosterone (T) and incident heart failure (HF), but whether this differs for free T or the more potent androgen, dihydrotestosterone (DHT), remains unknown. Methods: We hypothesized that total and free T are inversely related and SHBG positively related to incident HF in older men, whereas, based on earlier data on ASCVD in CHS, total DHT bears a U-shaped relationship with this outcome. In a male sample from CHS without prevalent ASCVD or HF, serum T and DHT concentration were measured by liquid chromatography tandem mass spectrometry, and sex hormone-binding globulin (SHBG) by immunoassay. Free T was calculated from total T, SHBG and albumin. We used Cox regression to estimate relative risks of HF, adjusting for age, race, BMI, smoking, alcohol, physical activity, systolic BP, antihypertensive use, total and HDL cholesterol, and eGFR. Results: In 1061 men (age 76±5) followed for a median of 9.6 years, there were 368 HF events. Restricted cubic splines showed no meaningful departure from linearity, and relationships were expressed per SD decrement in androgen levels. After adjustment, lower free T was significantly associated with higher risk of HF (HR 1.14 [95% CI 1.01, 1.28]), p=0.03). Risk estimates for total T (HR 1.12 [0.99, 1.26], p=0.07), DHT (HR 1.10 [0.97, 1.24], p=0.14) and SHBG (HR 1.07 [0.95, 1.21], p=0.25) were directionally similar, but not statistically significant. The association of lower free T and HF was not altered after further adjustment for diabetes or atrial fibrillation. In a sensitivity analysis excluding participants with history of prostate cancer, findings were similar. Conclusion: Total T, free T, DHT and SHBG were inversely associated with incident HF, but only the association of free T was statistically significant. These findings suggest a contribution of androgen deficiency to HF incidence among men late in life, the segment of the population at highest risk of both conditions. Additional research is needed to determine whether androgen replacement therapy is an effective strategy to lower HF risk in older men.