The Effectiveness of Lifestyle Interventions in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To perform a network meta-analysis to determine the effectiveness of lifestyle interventions in exercise tolerance and quality of life (QoL) in people with HFpEF. METHODS: Ten databases were searched for randomized controlled trials that evaluated a diet and/or exercise intervention in people with heart failure with preserved ejection fraction until May 2022. The co-primary outcomes were peak oxygen uptake (V̇O2peak) and Quality of Life as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). We synthesized data using network meta-analysis. RESULTS: We identified 13 trials, including a total of 869 participants, and we incorporated 6 different interventions. Improvements in V̇O2peak compared to controls were seen for all exercise interventions (2.88 [95% CI: 1.36; 4.39] mL/kg/min) for high-intensity interval training (HIIT); 2.37 [95% CI: 1.02; 3.71] mL/kg/min for low-intensity exercise (LIT) combined with a hypocaloric diet; 2.05 [95% CI: 0.81; 3.29] mL/kg/min for moderate-intensity continuous training (MICT); 1.94 [95% CI: 0.59; 3.29] mL/kg/min for LIT; 1.85 [95% CI: 0.27; 3.44] mL/kg/min for MICT combined with resistance training) but not a hypocaloric diet alone (1.26 [95%CI: -0.08; 2.61] mL/kg/min). Only HIIT (-14.45 [95%CI: -24.81; -4.10] points) and LIT (95% CI: -11.05 [-20.55; -1.54] mL/kg/min) significantly improved MLHFQ scores. Network meta-analysis indicated that HIIT was the most effective intervention for improving both V̇O2peak (mean improvement 2.88 [95% CI: 1.36; 4.39] mL/kg/min, follow-up range, 4 weeks-3 years) and QoL (-14.45 [95% CI: -24.81; -4.10] points, follow-up range, 12-26 weeks) compared to usual care. CONCLUSIONS: This network meta-analysis indicates that HIIT is the most effective lifestyle intervention studied to improve exercise capacity and QoL, with mean improvements exceeding the minimum clinically meaningful thresholds. HIIT is likely to be an underused management strategy in HFpEF, but further studies are needed to confirm long-term improvements in symptoms and clinical outcomes.

Ethnic differences in cardiac structure and function assessed by MRI in healthy South Asian and White European people: A UK Biobank Study.

BACKGROUND: Echocardiographic studies indicate South Asian people have smaller ventricular volumes, lower mass and more concentric remodelling than White European people, but there are no data using cardiac MRI (CMR). We aimed to compare CMR quantified cardiac structure and function in White European and South Asian people. METHODS: Healthy White European and South Asian participants in the UK Biobank Imaging CMR sub-study were identified by excluding those with a history of cardiovascular disease, hypertension, obesity or diabetes. Ethnic groups were matched by age and sex. Cardiac volumes, mass and feature tracking strain were compared. RESULTS: 121 matched pairs (77 male/44 female, mean age 58 ± 8 years) of South Asian and White European participants were included. South Asian males and females had smaller absolute but not indexed left ventricular (LV) volumes, and smaller absolute and indexed right ventricular volumes, with lower absolute and indexed LV mass and lower LV mass:volume than White European participants. Although there were no differences in ventricular or atrial ejection fractions, LV global longitudinal strain was higher in South Asian females than White European females but not males, and global circumferential strain was higher in both male and South Asian females than White European females. Peak early diastolic strain rates were higher in South Asian versus White European males, but not different between South Asian and White European females. CONCLUSIONS: Contrary to echocardiographic studies, South Asian participants in the UK Biobank study had less concentric remodelling and higher global circumferential strain than White European subjects. These findings emphasise the importance of sex- and ethnic- specific normal ranges for cardiac volumes and function.

Association of ambulatory blood pressure with coronary microvascular and cardiac dysfunction in asymptomatic type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2D) and hypertension commonly coexist and are associated with subclinical myocardial structural and functional changes. We sought to determine the association between blood pressure (BP) and left ventricular (LV) remodeling, systolic/diastolic function, and coronary microvascular function, among individuals with T2D without prevalent cardiovascular disease. METHODS: Participants with T2D and age-, sex-, and ethnicity-matched controls underwent comprehensive cardiovascular phenotyping including fasting bloods, transthoracic echocardiography, cardiovascular magnetic resonance imaging with quantitative adenosine stress/rest perfusion, and office and 24-h ambulatory BP monitoring. Multivariable linear regression was performed to determine independent associations between BP and imaging markers of remodeling and function in T2D. RESULTS: Individuals with T2D (n = 205, mean age 63 ± 7 years) and controls (n = 40, mean age 61 ± 8 years) were recruited. Mean 24-h systolic BP, but not office BP, was significantly greater among those with T2D compared to controls (128.8 ± 11.7 vs 123.0 ± 13.1 mmHg, p = 0.006). Those with T2D had concentric LV remodeling (mass/volume 0.91 ± 0.15 vs 0.82 ± 0.11 g/mL, p < 0.001), decreased myocardial perfusion reserve (2.82 ± 0.83 vs 3.18 ± 0.82, p = 0.020), systolic dysfunction (global longitudinal strain 16.0 ± 2.3 vs 17.2 ± 2.1%, p = 0.004) and diastolic dysfunction (E/e' 9.30 ± 2.43 vs 8.47 ± 1.53, p = 0.044) compared to controls. In multivariable regression models adjusted for 14 clinical variables, mean 24-h systolic BP was independently associated with concentric LV remodeling (ß = 0.165, p = 0.031), diastolic dysfunction (ß = 0.273, p < 0.001) and myocardial perfusion reserve (ß = - 0.218, p = 0.016). Mean 24-h diastolic BP was associated with LV concentric remodeling (ß = 0.201, p = 0.016). CONCLUSION: 24-h ambulatory systolic BP, but not office BP, is independently associated with cardiac remodeling, coronary microvascular dysfunction, and diastolic dysfunction among asymptomatic individuals with T2D. (Clinical trial registration. URL: https://clinicaltrials.gov/ct2/show/NCT03132129 Unique identifier: NCT03132129).

Association of epicardial adipose tissue with early structural and functional cardiac changes in Type 2 diabetes.

BACKGROUND: Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical cardiac dysfunction in people with T2D and no prevalent cardiovascular disease. METHODS: Prospective case-control study enrolling participants with and without T2D and no known cardiovascular disease. Two hundred and fifteen people with T2D (median age 63 years, 60 % male) and thirty-nine non-diabetics (median age 59 years, 62 % male) were included. Using computed tomography (CT), total EAT volume and mean CT attenuation, as well as, low attenuation (Hounsfield unit range -190 to -90) EAT volume were quantified by a deep learning method and volumes indexed to body surface area. Associations with cardiac magnetic resonance-derived left ventricular (LV) volumes and strain indices were assessed using linear regression. RESULTS: T2D participants had higher LV mass/volume ratio (median 0.89 g/mL [0.82-0.99] vs 0.79 g/mL [0.75-0.89]) and lower global longitudinal strain (GLS; 16.1 ± 2.3 % vs 17.2 ± 2.2 %). Total indexed EAT volume correlated inversely with mean CT attenuation. Low attenuation indexed EAT volume was 2-fold higher (18.8 cm3/m2 vs. 9.4 cm3/m2, p < 0.001) in T2D and independently associated with LV mass/volume ratio (ß = 0.002, p = 0.01) and GLS (ß = -0.03, p = 0.03). CONCLUSIONS: Higher EAT volumes seen in T2D are associated with a lower mean CT attenuation. Low attenuation indexed EAT volume is independently, but only weakly, associated with markers of subclinical cardiac dysfunction in T2D.

Impact of the Remission of Type 2 Diabetes on Cardiovascular Structure and Function, Exercise Capacity and Risk Profile: A Propensity Matched Analysis.

Type 2 diabetes (T2D) confers a high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The impact of the remission of T2D, beyond weight loss and glycaemia, on cardiovascular structure and function and exercise capacity is described. Adults with T2D without cardiovascular disease underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing and cardiometabolic profiling. T2D remission cases (Glycated hemoglobin (HbA1c) < 6.5% without glucose-lowering therapy, ≥3 months) were propensity score matched 1:4 based on age, sex, ethnicity and time of exposure to those with active T2D (n = 100) with the nearest-neighbour method and 1:1 with non-T2D controls (n = 25). T2D remission was associated with a lower leptin-adiponectin ratio, hepatic steatosis and triglycerides, a trend towards greater exercise capacity and significantly lower minute ventilation/carbon dioxide production (VE/VCO2 slope) vs. active T2D (27.74 ± 3.95 vs. 30.52 ± 5.46, p < 0.0025). Evidence of concentric remodeling remained in T2D remission vs. controls (left ventricular mass/volume ratio 0.88 ± 0.10 vs. 0.80 ± 0.10, p < 0.025). T2D remission is associated with an improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.

Impact of diabetes on remodelling, microvascular function and exercise capacity in aortic stenosis.

OBJECTIVE: To characterise cardiac remodelling, exercise capacity and fibroinflammatory biomarkers in patients with aortic stenosis (AS) with and without diabetes, and assess the impact of diabetes on outcomes. METHODS: Patients with moderate or severe AS with and without diabetes underwent echocardiography, stress cardiovascular magnetic resonance (CMR), cardiopulmonary exercise testing and plasma biomarker analysis. Primary endpoint for survival analysis was a composite of cardiovascular mortality, myocardial infarction, hospitalisation with heart failure, syncope or arrhythmia. Secondary endpoint was all-cause death. RESULTS: Diabetes (n=56) and non-diabetes groups (n=198) were well matched for age, sex, ethnicity, blood pressure and severity of AS. The diabetes group had higher body mass index, lower estimated glomerular filtration rate and higher rates of hypertension, hyperlipidaemia and symptoms of AS. Biventricular volumes and systolic function were similar, but the diabetes group had higher extracellular volume fraction (25.9%±3.1% vs 24.8%±2.4%, p=0.020), lower myocardial perfusion reserve (2.02±0.75 vs 2.34±0.68, p=0.046) and lower percentage predicted peak oxygen consumption (68%±21% vs 77%±17%, p=0.002) compared with the non-diabetes group. Higher levels of renin (log10renin: 3.27±0.59 vs 2.82±0.69 pg/mL, p<0.001) were found in diabetes. Multivariable Cox regression analysis showed diabetes was not associated with cardiovascular outcomes, but was independently associated with all-cause mortality (HR 2.04, 95% CI 1.05 to 4.00; p=0.037). CONCLUSIONS: In patients with moderate-to-severe AS, diabetes is associated with reduced exercise capacity, increased diffuse myocardial fibrosis and microvascular dysfunction, but not cardiovascular events despite a small increase in mortality.

Sex- and age-specific normal values for automated quantitative pixel-wise myocardial perfusion cardiovascular magnetic resonance.

AIMS: Recently developed in-line automated cardiovascular magnetic resonance (CMR) myocardial perfusion mapping has been shown to be reproducible and comparable with positron emission tomography (PET), and can be easily integrated into clinical workflows. Bringing quantitative myocardial perfusion CMR into routine clinical care requires knowledge of sex- and age-specific normal values in order to define thresholds for disease detection. This study aimed to establish sex- and age-specific normal values for stress and rest CMR myocardial blood flow (MBF) in healthy volunteers. METHODS AND RESULTS: A total of 151 healthy volunteers recruited from two centres underwent adenosine stress and rest myocardial perfusion CMR. In-line automatic reconstruction and post processing of perfusion data were implemented within the Gadgetron software framework, creating pixel-wise perfusion maps. Rest and stress MBF were measured, deriving myocardial perfusion reserve (MPR) and were subdivided by sex and age. Mean MBF in all subjects was 0.62 ± 0.13 mL/g/min at rest and 2.24 ± 0.53 mL/g/min during stress. Mean MPR was 3.74 ± 1.00. Compared with males, females had higher rest (0.69 ± 0.13 vs. 0.58 ± 0.12 mL/g/min, P < 0.01) and stress MBF (2.41 ± 0.47 vs. 2.13 ± 0.54 mL/g/min, P = 0.001). Stress MBF and MPR showed significant negative correlations with increasing age (r = -0.43, P < 0.001 and r = -0.34, P < 0.001, respectively). CONCLUSION: Fully automated in-line CMR myocardial perfusion mapping produces similar normal values to the published CMR and PET literature. There is a significant increase in rest and stress MBF, but not MPR, in females and a reduction of stress MBF and MPR with advancing age, advocating the use of sex- and age-specific reference ranges for diagnostic use.

Role of inflammation in diabetic cardiomyopathy.

The prevalence of type 2 diabetes (T2D) has reached a pandemic scale. Systemic chronic inflammation dominates the diabetes pathophysiology and has been implicated as a causal factor for the development of vascular complications. Heart failure (HF) is regarded as the most common cardiovascular complication of T2D and the diabetic diagnosis is an independent risk factor for HF development. Key molecular mechanisms pivotal to the development of diabetic cardiomyopathy include the NF-κB pathway and renin-angiotensin-aldosterone system, in addition to advanced glycation end product accumulation and inflammatory interleukin overexpression. Chronic myocardial inflammation in T2D mediates structural and metabolic changes, including cardiomyocyte apoptosis, impaired calcium handling, myocardial hypertrophy and fibrosis, all of which contribute to the diabetic HF phenotype. Advanced cardiovascular magnetic resonance imaging (CMR) has emerged as a gold standard non-invasive tool to delineate myocardial structural and functional changes. This review explores the role of chronic inflammation in diabetic cardiomyopathy and the ability of CMR to identify inflammation-mediated myocardial sequelae, such as oedema and diffuse fibrosis.

Sex and ethnic differences in the cardiovascular complications of type 2 diabetes.

Diabetes mellitus represents a global health concern affecting 463 million adults and is projected to rapidly rise to 700 million people by 2045. Amongst those with type 2 diabetes (T2D), there are recognised differences in the impact of the disease on different sex and ethnic groups. The relative risk of cardiovascular complications between individuals with and without T2D is higher in females than males. People of South Asian heritage are two to four times more likely to develop T2D than white people, but conversely not more likely to experience cardiovascular complications. Differences in the pathophysiological responses in these groups may identify potential areas for intervention beyond glycaemic control. In this review, we highlight key differences of diabetes-associated cardiovascular complications by sex and ethnic background, with a particular emphasis on South Asians. Evidence assessing therapeutic efficacy of new glucose lowering drugs in minority groups is limited and many major cardiovascular outcomes trials do not report ethnic specific data. Conversely, lifestyle intervention and bariatric surgery appear to have similar benefits regardless of sex and ethnic groups. We encourage future studies with better representation of women and ethnic minorities that will provide valuable data to allow better risk stratification and tailored prevention and management strategies to improve cardiovascular outcomes in T2D.