Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
1.
J Am Heart Assoc ; 11(10): e024060, 2022 May 17.
Article in English | MEDLINE | ID: mdl-35574957

ABSTRACT

Background Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. Methods and Results In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups incurred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40-7.17] and HR, 9.30 [95% CI, 4.09-21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14-9.52] and subdistribution HR, 9.29 [95% CI, 3.09-27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25-3.55] and subdistribution HR, 3.55 [95% CI, 2.04-6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25-3.55] and HR, 3.55 [95% CI, 2.04-6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, P=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without. Conclusions Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery.

2.
Front Cardiovasc Med ; 9: 804336, 2022.
Article in English | MEDLINE | ID: mdl-35528841

ABSTRACT

Background: Despite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes. Objective: To study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes. Methods: Among 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking. Results: Post-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e', lower LV GLS (0.37, 95%CI 0.04-0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01-0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00-1.07], impaired GLS (aHR 0.87, 95%CI 0.78-0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90-0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69-64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01-3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79-18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well. Conclusion: Menopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further.

3.
Eur J Heart Fail ; 24(4): 681-684, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35060248

ABSTRACT

AIMS: Little information is available on sex differences in coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF). We investigated sex-specific proteomic profiles associated with CMD in patients with HFpEF. METHODS AND RESULTS: Using the prospective multinational PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in HFpEF; n = 182; 54.6% women), we compared clinical and biomarker correlates of CMD (defined as coronary flow reserve [CFR] <2.5) between men and women with HFpEF. We used lasso penalized regression to analyse 242 biomarkers from high-throughput proximity extension assays, adjusting for age, body mass index, creatinine, smoking and study site. The prevalence of CMD was similarly high in men and women with HFpEF (77% vs. 70%; p = 0.27). Proteomic correlates of CFR differed by sex, with 10 versus 16 non-overlapping biomarkers independently associated with CFR in men versus women, respectively. In men, proteomic correlates of CFR included chemokine ligand 20, brain natriuretic peptide, proteinase 3, transglutaminase 2, pregnancy-associated plasma protein A and tumour necrosis factor receptor superfamily member 14. Among women, the strongest proteomic correlates with CFR were insulin-like growth factor-binding protein 1, phage shock protein D, CUB domain-containing protein 1, prostasin, decorin, FMS-like tyrosine kinase 3, ligand growth differentiation factor 15, spondin-1, delta/notch-like epidermal growth factor-related receptor and tumour necrosis factor receptor superfamily member 13B. Pathway analyses suggested that CMD was related to the inflammation-mediated chemokine and cytokine signalling pathway among men with HFpEF, and the P13-kinase and transforming growth factor-beta signalling pathway among women with HFpEF. CONCLUSION: While the prevalence of CMD among men and women with HFpEF is similar, the drivers of microvascular dysfunction may differ by sex. The current inflammatory paradigm of CMD in HFpEF potentially predominates in men, while derangement in ventricular remodelling and fibrosis may play a more important role in women.

4.
Cardiovasc Diabetol ; 20(1): 218, 2021 11 06.
Article in English | MEDLINE | ID: mdl-34740359

ABSTRACT

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Disease Management , Heart Failure/epidemiology , Mass Screening/methods , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Glycated Hemoglobin A/metabolism , Heart Failure/blood , Heart Failure/diagnosis , Humans , Mass Screening/trends , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis
6.
Am Heart J ; 243: 11-14, 2022 01.
Article in English | MEDLINE | ID: mdl-34516969

ABSTRACT

Important racial differences in characteristics, treatment, and outcomes of patients with acute heart failure (AHF) have been described. The objective of this analysis of the International Registry to assess medical Practice with longitudinal observation for Treatment of Heart Failure (REPORT-HF) registry was to investigate racial differences in patients with AHF according to country income level.


Subject(s)
Heart Failure , Hospitalization , Acute Disease , Heart Failure/therapy , Humans , Race Factors , Registries
7.
Curr Heart Fail Rep ; 18(5): 284-289, 2021 10.
Article in English | MEDLINE | ID: mdl-34213729

ABSTRACT

PURPOSE OF REVIEW: This narrative review synthesizes sex differences in guideline-directed medical therapy (GDMT) use and response among female patients with heart failure with reduced ejection fraction (HFrEF), discusses female representation in HFrEF clinical trials, and outlines future areas of investigation to reduce sex disparities in HFrEF care globally. RECENT FINDINGS: Observational registries suggest sex-specific disparities persist in GDMT rates, and there may be key sex-specific differences in optimal dosing of GDMT in HFrEF patients. Underrepresentation of female patients in HF clinical trials is a key barrier, and sex disparities in HF clinical trial leadership may influence sex-specific knowledge generation of medical management of HFrEF patients. There are important sex-specific differences in GDMT use and response among female HFrEF patients that warrant further study. Increasing female representation in HFrEF clinical trials, diversifying HF trial leadership, and embedding sex-specific approaches in the lifecycle of research from conception to reporting are essential to decreasing sex disparities in clinical care of all HFrEF patients.


Subject(s)
Heart Failure , Ventricular Dysfunction, Left , Female , Heart Failure/drug therapy , Humans , Male , Registries , Stroke Volume
8.
PLoS Med ; 18(6): e1003661, 2021 06.
Article in English | MEDLINE | ID: mdl-34061848

ABSTRACT

BACKGROUND: Obesity, a known risk factor for cardiovascular disease and heart failure (HF), is associated with adverse cardiac remodeling in the general population. Little is known about how nutritional status modifies the relationship between obesity and outcomes. We aimed to investigate the association of obesity and nutritional status with clinical characteristics, echocardiographic changes, and clinical outcomes in the general community. METHODS AND FINDINGS: We examined 5,300 consecutive asymptomatic Asian participants who were prospectively recruited in a cardiovascular health screening program (mean age 49.6 ± 11.4 years, 64.8% male) between June 2009 to December 2012. Clinical and echocardiographic characteristics were described in participants, stratified by combined subgroups of obesity and nutritional status. Obesity was indexed by body mass index (BMI) (low, ≤25 kg/m2 [lean]; high, >25 kg/m2 [obese]) (WHO-recommended Asian cutoffs). Nutritional status was defined primarily by serum albumin (SA) concentration (low, <45 g/L [malnourished]; high, ≥45 g/L [well-nourished]), and secondarily by the prognostic nutritional index (PNI) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Cox proportional hazard models were used to examine a 1-year composite outcome of hospitalization for HF or all-cause mortality while adjusting for age, sex, and other clinical confounders. Our community-based cohort consisted of 2,096 (39.0%) lean-well-nourished (low BMI, high SA), 1,369 (25.8%) obese-well-nourished (high BMI, high SA), 1,154 (21.8%) lean-malnourished (low BMI, low SA), and 681 (12.8%) obese-malnourished (high BMI, low SA) individuals. Obese-malnourished participants were on average older (54.5 ± 11.4 years) and more often women (41%), with a higher mean waist circumference (91.7 ± 8.8 cm), the highest percentage of body fat (32%), and the highest prevalence of hypertension (32%), diabetes (12%), and history of cardiovascular disease (11%), compared to all other subgroups (all p < 0.001). N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were substantially increased in the malnourished (versus well-nourished) groups, to a similar extent in lean (70.7 ± 177.3 versus 36.8 ± 40.4 pg/mL) and obese (73.1 ± 216.8 versus 33.2 ± 40.8 pg/mL) (p < 0.001 in both) participants. The obese-malnourished (high BMI, low SA) group also had greater left ventricular remodeling (left ventricular mass index, 44.2 ± 1.52 versus 33.8 ± 8.28 gm/m2; relative wall thickness 0.39 ± 0.05 versus 0.38 ± 0.06) and worse diastolic function (TDI-e' 7.97 ± 2.16 versus 9.87 ± 2.47 cm/s; E/e' 9.19 ± 3.01 versus 7.36 ± 2.31; left atrial volume index 19.5 ± 7.66 versus 14.9 ± 5.49 mL/m2) compared to the lean-well-nourished (low BMI, high SA) group, as well as all other subgroups (p < 0.001 for all). Over a median 3.6 years (interquartile range 2.5 to 4.8 years) of follow-up, the obese-malnourished group had the highest multivariable-adjusted risk of the composite outcome (hazard ratio [HR] 2.49, 95% CI 1.43 to 4.34, p = 0.001), followed by the lean-malnourished (HR 1.78, 95% CI 1.04 to 3.04, p = 0.034) and obese-well-nourished (HR 1.41, 95% CI 0.77 to 2.58, p = 0.27) groups (with lean-well-nourished group as reference). Results were similar when indexed by other anthropometric indices (waist circumference and body fat) and other measures of nutritional status (PNI and GLIM criteria). Potential selection bias and residual confounding were the main limitations of the study. CONCLUSIONS: In our cohort study among asymptomatic community-based adults in Taiwan, we found that obese individuals with poor nutritional status have the highest comorbidity burden, the most adverse cardiac remodeling, and the least favorable composite outcome.


Subject(s)
Cardiovascular Diseases/epidemiology , Malnutrition/epidemiology , Nutritional Status , Obesity/epidemiology , Ventricular Function, Left , Ventricular Remodeling , Aged , Body Composition , Body Mass Index , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/mortality , Cardiovascular Diseases/physiopathology , Cause of Death , Comorbidity , Echocardiography, Doppler , Female , Hospitalization , Humans , Male , Malnutrition/diagnosis , Malnutrition/mortality , Malnutrition/physiopathology , Middle Aged , Nutrition Assessment , Obesity/diagnosis , Obesity/mortality , Obesity/physiopathology , Prevalence , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , Taiwan/epidemiology , Time Factors
9.
Circ Cardiovasc Qual Outcomes ; 14(4): e006962, 2021 04.
Article in English | MEDLINE | ID: mdl-33757307

ABSTRACT

BACKGROUND: Little is known regarding the impact of socioeconomic factors on the use of evidence-based therapies and outcomes in patients with heart failure with reduced ejection fraction across Asia. METHODS: We investigated the association of both patient-level (household income, education levels) and country-level (regional income level by World Bank classification, income disparity by Gini index) socioeconomic indicators on use of guideline-directed therapy and clinical outcomes (composite of 1-year mortality or HF hospitalization, quality of life) in the prospective multinational ASIAN-HF study (Asian Sudden Cardiac Death in Heart Failure). RESULTS: Among 4540 patients (mean age: 60±13 years, 23% women) with heart failure with reduced ejection fraction, 39% lived in low-income regions; 34% in regions with high-income disparity (Gini ≥42.8%); 64.4% had low monthly household income (

Subject(s)
Heart Failure , Quality of Life , Asia/epidemiology , Female , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/therapy , Humans , Male , Middle Aged , Prospective Studies , Social Class , Stroke Volume
10.
Circulation ; 141(7): 540-548, 2020 02 18.
Article in English | MEDLINE | ID: mdl-32065763

ABSTRACT

BACKGROUND: Cardiovascular disease is the leading cause of death among women worldwide, yet, women have historically been underrepresented in cardiovascular trials. METHODS: We systematically assessed the participation of women in completed cardiovascular trials registered in ClinicalTrials.gov between 2010 and 2017, and extracted publicly available information including disease type, sponsor type, country, trial size, intervention type, and the demographic characteristics of trial participants. We calculated the female-to-male ratio for each trial and determined the prevalence-adjusted estimates for participation of women by dividing the percentage of women among trial participants by the percentage of women in the disease population (participation prevalence ratio; a ratio of 0.8 to 1.2 suggests comparable prevalence and good representation). RESULTS: We identified 740 completed cardiovascular trials including a total of 862 652 adults, of whom 38.2% were women. The median female-to-male ratio of each trial was 0.51 (25th quartile, 0.32; 75th quartile, 0.90) overall and varied by age group (1.02 in ≤55 year old group versus 0.40 in the 61- to 65-year-old group), type of intervention (0.44 for procedural trials versus 0.78 for lifestyle intervention trials), disease type (0.34 for acute coronary syndrome versus 3.20 for pulmonary hypertension), region (0.45 for Western Pacific versus 0.55 for the Americas), funding/sponsor type (0.14 for government-funded versus 0.73 for multiple sponsors), and trial size (0.56 for smaller [n≤47] versus 0.49 for larger [n≥399] trials). Relative to their prevalence in the disease population, participation prevalence ratio was higher than 0.8 for hypertension, pulmonary arterial hypertension and lower (participation prevalence ratio 0.48 to 0.78) for arrhythmia, coronary heart disease, acute coronary syndrome, and heart failure trials. The most recent time period (2013 to 2017) saw significant increases in participation prevalence ratios for stroke (P=0.007) and heart failure (P=0.01) trials compared with previous periods. CONCLUSIONS: Among cardiovascular trials in the current decade, men still predominate overall, but the representation of women varies with disease and trial characteristics, and has improved in stroke and heart failure trials.


Subject(s)
Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Patient Participation , Sex Characteristics , Adult , Aged , Clinical Trials as Topic , Female , Humans , Male , Middle Aged , Patient Selection , Prevalence
11.
Eur Heart J ; 40(47): 3859-3868c, 2019 12 14.
Article in English | MEDLINE | ID: mdl-31800034

ABSTRACT

The overall lifetime risk of heart failure (HF) is similar between men and women, however, there are marked sex differences in the landscape of this condition that are both important and under-recognized. Men are predisposed to HF with reduced ejection fraction (HFrEF), whereas women predominate in HF with preserved ejection fraction (HFpEF). Sex differences are also notable in the penetrance of genetic cardiomyopathies, risk factors, e.g. breast cancer which may be associated with cancer treatment-induced cardiomyopathy, as well as sex-specific conditions such as peripartum cardiomyopathy (PPCM). This review outlines the key sex differences with respect to clinical characteristics, pathophysiology, and therapeutic responses to HF treatments. Finally, we address important differences in the prognosis of HF. A central hypothesis is that the higher risk of HFrEF in men compared to women may be attributable to their predisposition to macrovascular coronary artery disease and myocardial infarction, whereas coronary microvascular dysfunction/endothelial inflammation has been postulated to play a key role in HFpEF and maybe the common link among HF syndromes that women are predisposed to Takotsubo cardiomyopathy, PPCM, and breast cancer radiotherapy-induced cardiomyopathy. Under-pinning current sex disparities in HF, there is a paucity of women recruited to HF clinical trials (20-25% of cohorts) and thus treatment guidelines are predominantly based on male-derived data. Large gaps in knowledge exist in sex-specific mechanisms, optimal drug doses for women and sex-specific criteria for device therapy.


Subject(s)
Heart Failure/epidemiology , Risk Assessment/methods , Stroke Volume/physiology , Ventricular Function, Left/physiology , Female , Global Health , Heart Failure/physiopathology , Humans , Male , Morbidity/trends , Risk Factors , Sex Distribution , Sex Factors , Survival Rate/trends
13.
PLoS Med ; 16(9): e1002916, 2019 09.
Article in English | MEDLINE | ID: mdl-31550265

ABSTRACT

BACKGROUND: Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia. METHODS AND FINDINGS: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries. CONCLUSIONS: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF. TRIAL REGISTRATION: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398.


Subject(s)
Heart Failure/epidemiology , Obesity/epidemiology , Adiposity , Aged , Asia/epidemiology , Body Mass Index , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Male , Middle Aged , Obesity/diagnosis , Obesity/physiopathology , Prospective Studies , Registries , Risk Assessment , Risk Factors , Stroke Volume , Ventricular Function , Waist-Hip Ratio
14.
J Am Heart Assoc ; 8(17): e013114, 2019 09 03.
Article in English | MEDLINE | ID: mdl-31431116

ABSTRACT

Background Diabetes mellitus frequently coexists with heart failure (HF), but few studies have compared the associations between diabetes mellitus and cardiac remodeling, quality of life, and clinical outcomes, according to HF phenotype. Methods and Results We compared echocardiographic parameters, quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire), and outcomes (1-year all-cause mortality, cardiovascular mortality, and HF hospitalization) between HF patients with and without type 2 diabetes mellitus in the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, as well as community-based controls without HF. Adjusted Cox proportional hazards models were used to assess the association of diabetes mellitus with clinical outcomes. Among 5028 patients with HF and reduced ejection fraction (HFrEF; EF <40%) and 1139 patients with HF and preserved EF (HFpEF; EF ≥50%), the prevalences of type 2 diabetes mellitus were 40.2% and 45.0%, respectively (P=0.003). In both HFrEF and HFpEF cohorts, diabetes mellitus (versus no diabetes mellitus) was associated with smaller indexed left ventricular diastolic volumes and higher mitral E/e' ratio. There was a predominance of eccentric hypertrophy in HFrEF and concentric hypertrophy in HFpEF. Patients with diabetes mellitus had lower Kansas City Cardiomyopathy Questionnaire scores in both HFpEF and HFrEF, with more prominent differences in HFpEF (Pinteraction<0.05). In both HFpEF and HFrEF, patients with diabetes mellitus had more HF rehospitalizations (adjusted hazard ratio, 1.27; 95% CI, 1.05-1.54; P=0.014) and higher 1-year rates of the composite of all-cause mortality/HF hospitalization (adjusted hazard ratio, 1.22; 95% CI, 1.05-1.41; P=0.011), with no differences between HF phenotypes (Pinteraction>0.05). Conclusions In HFpEF and HFrEF, type 2 diabetes mellitus is associated with smaller left ventricular volumes, higher mitral E/e' ratio, poorer quality of life, and worse outcomes, with several differences noted between HF phenotypes. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01633398.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Diabetic Cardiomyopathies/physiopathology , Heart Failure/physiopathology , Quality of Life , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling , Aged , Aged, 80 and over , Asia/epidemiology , Cause of Death , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/therapy , Diabetic Cardiomyopathies/diagnostic imaging , Diabetic Cardiomyopathies/mortality , Diabetic Cardiomyopathies/therapy , Echocardiography , Female , Heart Failure/diagnostic imaging , Heart Failure/mortality , Heart Failure/therapy , Hospitalization , Humans , Male , Middle Aged , Prevalence , Prognosis , Prospective Studies , Registries , Risk Assessment , Risk Factors , Surveys and Questionnaires , Time Factors
15.
Diabetes Care ; 42(9): 1792-1799, 2019 09.
Article in English | MEDLINE | ID: mdl-31292141

ABSTRACT

OBJECTIVE: Microvascular complications are common among patients with diabetes mellitus (DM). The presence of heart failure (HF) is presumed to be due to macrovascular disease (typically HF with reduced ejection fraction [HFrEF] following myocardial infarction). We hypothesized that HF with preserved ejection fraction (HFpEF) in patients with DM may be a manifestation of microvascular disease compared with HFrEF. The objective of this study was to examine the prevalence and association with clinical outcome of microvascular complications in patients with HF and DM. RESEARCH DESIGN AND METHODS: We investigated the prevalence, association with clinical outcome, and cardiac structure and function of microvascular (neuropathy, nephropathy, and retinopathy) complications of DM in 2,800 prospectively enrolled participants with HF and DM (561 with HFpEF) from the Asian Sudden Cardiac Death In Heart Failure (ASIAN-HF) registry. RESULTS: A total of 601 (21.5%) participants with DM had microvascular complications. Participants with DM and any (one or more) microvascular complications were more likely to have HFpEF (odds ratio 1.70 [95% CI 1.15-2.50]; P = 0.008). Furthermore, the likelihood of having HFpEF increased with an increasing number of microvascular complications (P trend < 0.001). Microvascular complications were associated with more left ventricular (LV) hypertrophy and a greater reduction in quality of life in HFpEF than HFrEF (P interaction < 0.001 for all). Compared with participants with DM and without microvascular complications, the adjusted hazard ratio for the composite outcome of all-cause death or HF hospitalization was 1.35 (95% CI 1.04-1.76) for participants with DM and microvascular complications regardless of HF type (P interaction = 0.112). CONCLUSIONS: Diabetic microvascular disease is more common, and related to greater LV remodeling, more impairment of quality in life, and similar adverse outcomes, in participants with HFpEF compared with HFrEF. HFpEF may be a clinical manifestation of microvascular disease in DM.


Subject(s)
Diabetic Angiopathies/physiopathology , Diabetic Cardiomyopathies/physiopathology , Heart Failure/physiopathology , Microvessels/physiopathology , Stroke Volume/physiology , Aged , Cause of Death , Diabetic Angiopathies/etiology , Diabetic Angiopathies/mortality , Diabetic Cardiomyopathies/etiology , Diabetic Cardiomyopathies/mortality , Female , Heart Failure/etiology , Heart Failure/mortality , Humans , Male , Middle Aged , Prevalence , Prognosis , Proportional Hazards Models , Prospective Studies , Quality of Life , Registries
17.
Eur J Heart Fail ; 21(3): 297-307, 2019 03.
Article in English | MEDLINE | ID: mdl-30548089

ABSTRACT

AIMS: To examine sex differences in clinical characteristics, echocardiographic features, quality of life and 1-year death or heart failure (HF) hospitalization outcomes in patients with/without diabetes mellitus (DM). METHODS AND RESULTS: Utilizing the Asian Sudden Cardiac Death in HF (ASIAN-HF) registry, 5255 patients (mean age 59.6 ± 13.1, 78% men) with symptomatic HF with reduced ejection fraction (HFrEF) were stratified by DM status to address the research aims. Despite similar prevalence of DM between Asian men (43%) and women (42%), the odds of DM increased at lower body mass index in women vs. men (≥ 23 vs. ≥ 27.5 kg/m2 , Pinteraction = 0.014). DM was more strongly related to chronic kidney disease in women vs. men [adjusted odds ratio (OR) 1.85, 95% confidence interval (CI) 1.33-2.57 vs. OR 1.32, 95% CI 1.11-1.56, Pinteraction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (Pinteraction = 0.003), whereby DM was associated with a more concentric left ventricular geometry in women than men. Women had lower quality of life than men (P < 0.001), in both DM and non-DM groups. DM was associated with worse composite outcomes at 1 year in women vs. men [hazard ratio (HR) 1.79, 95% CI 1.24-2.60 vs. HR 1.32, 95% CI 1.12-1.56; Pinteraction = 0.005). CONCLUSIONS: Asian women with HFrEF were more likely to have DM despite a lean body mass index, a greater burden of chronic kidney disease and more concentric left ventricular geometry, compared to men. Furthermore, DM confers worse quality of life, irrespective of sex, and a greater risk of adverse outcomes in women than men. These data underscore the need for sex-specific approaches to diabetes in patients with HF.


Subject(s)
Death, Sudden, Cardiac , Diabetes Mellitus/epidemiology , Heart Failure , Hospitalization/statistics & numerical data , Quality of Life , Sex Factors , Aged , Asia/epidemiology , Comorbidity , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Echocardiography/methods , Echocardiography/statistics & numerical data , Female , Heart Failure/mortality , Heart Failure/physiopathology , Heart Failure/psychology , Heart Failure/therapy , Humans , Male , Middle Aged , Prevalence , Risk Factors , Stroke Volume
18.
JACC Heart Fail ; 6(8): 710-713, 2018 08.
Article in English | MEDLINE | ID: mdl-30078394
19.
J Am Heart Assoc ; 7(11)2018 06 01.
Article in English | MEDLINE | ID: mdl-29858360

ABSTRACT

BACKGROUND: Among the growing numbers of patients with heart failure, up to one half have heart failure with preserved ejection fraction (HFpEF). The lack of effective treatments for HFpEF is a substantial and escalating unmet clinical need-and the lack of HFpEF-specific animal models represents a major preclinical barrier in advancing understanding of HFpEF. As established treatments for heart failure with reduced ejection fraction (HFrEF) have proven ineffective for HFpEF, the contention that the intrinsic cardiomyocyte phenotype is distinct in these 2 conditions requires consideration. Our goal was to validate and characterize a new rodent model of HFpEF, undertaking longitudinal investigations to delineate the associated cardiac and cardiomyocyte pathophysiology. METHODS AND RESULTS: The selectively inbred Hypertrophic Heart Rat (HHR) strain exhibits adult cardiac enlargement (without hypertension) and premature death (40% mortality at 50 weeks) compared to its control strain, the normal heart rat. Hypertrophy was characterized in vivo by maintained systolic parameters (ejection fraction at 85%-90% control) with marked diastolic dysfunction (increased E/E'). Surprisingly, HHR cardiomyocytes were hypercontractile, exhibiting high Ca2+ operational levels and markedly increased L-type Ca2+ channel current. In HHR, prominent regions of reparative fibrosis in the left ventricle free wall adjacent to the interventricular septum were observed. CONCLUSIONS: Thus, the cardiomyocyte remodeling process in the etiology of this HFpEF model contrasts dramatically with the suppressed Ca2+ cycling state that typifies heart failure with reduced ejection fraction. These findings may explain clinical observations, that treatments considered appropriate for heart failure with reduced ejection fraction are of little benefit for HFpEF-and suggest a basis for new therapeutic strategies.


Subject(s)
Calcium/metabolism , Heart Failure/physiopathology , Heart Ventricles/diagnostic imaging , Myocardial Contraction/physiology , Myocytes, Cardiac/pathology , Stroke Volume/physiology , Animals , Disease Models, Animal , Echocardiography, Doppler , Electrocardiography , Heart Failure/diagnosis , Heart Ventricles/physiopathology , Immunoblotting , Myocytes, Cardiac/metabolism , Patch-Clamp Techniques , Rats, Inbred F344
20.
Sci Rep ; 8(1): 2346, 2018 02 05.
Article in English | MEDLINE | ID: mdl-29402990

ABSTRACT

Diabetic cardiomyopathy is a distinct pathology characterized by early emergence of diastolic dysfunction. Increased cardiovascular risk associated with diabetes is more marked for women, but an understanding of the role of diastolic dysfunction in female susceptibility to diabetic cardiomyopathy is lacking. To investigate the sex-specific relationship between systemic diabetic status and in vivo occurrence of diastolic dysfunction, diabetes was induced in male and female mice by streptozotocin (5x daily i.p. 55 mg/kg). Echocardiography was performed at 7 weeks post-diabetes induction, cardiac collagen content assessed by picrosirius red staining, and gene expression measured using qPCR. The extent of diabetes-associated hyperglycemia was more marked in males than females (males: 25.8 ± 1.2 vs 9.1 ± 0.4 mM; females: 13.5 ± 1.5 vs 8.4 ± 0.4 mM, p < 0.05) yet in vivo diastolic dysfunction was evident in female (E/E' 54% increase, p < 0.05) but not male diabetic mice. Cardiac structural abnormalities (left ventricular wall thinning, collagen deposition) were similar in male and female diabetic mice. Female-specific gene expression changes in glucose metabolic and autophagy-related genes were evident. This study demonstrates that STZ-induced diabetic female mice exhibit a heightened susceptibility to diastolic dysfunction, despite exhibiting a lower extent of hyperglycemia than male mice. These findings highlight the importance of early echocardiographic screening of asymptomatic prediabetic at-risk patients.


Subject(s)
Blood Pressure , Diabetes Mellitus, Experimental/physiopathology , Diabetic Cardiomyopathies/physiopathology , Hyperglycemia/physiopathology , Animals , Autophagy , Diabetes Mellitus, Experimental/complications , Female , Glucose/metabolism , Hyperglycemia/etiology , Male , Mice, Inbred C57BL , Sex Characteristics , Streptozocin/administration & dosage , Ventricular Remodeling
SELECTION OF CITATIONS
SEARCH DETAIL