Both diabetes and low magnesium-containing food intake may increase the risk of heart failure (HF). However, the effect of nonprescription magnesium supplements on the risk of HF or major adverse cardiac events in patients with diabetes is unknown.

Using a target-trial-emulation approach, we assembled a national cohort of 94 239 veterans ≥40 years with diabetes, without prior HF or magnesium use, who received ambulatory care in the US veterans-health care system documented by electronic clinic notes between January 1, 2006 and December 31, 2020. A natural language processing approach was used to detect self-reported magnesium-supplement use from clinic notes, n=17 619 were identified as users versus n=76 620 as nonusers. Using inverse probability treatment weighting, we constructed a cohort balanced in 88 baseline characteristics between users and nonusers. The primary outcome was incident HF. Secondary outcomes were major adverse cardiac events (myocardial infarction, stroke, HF hospitalization, or death). Hazard ratios (HRs) associated with magnesium-supplement use and outcomes were estimated in the inverse probability treatment weighting weighted cohort using Cox regression. The inverse probability treatment weighting weighted cohort had a mean age of 67.4±10.3 years; 18.4% were Black, and 5.1% were women. The mean duration of magnesium-supplement use was 3.5±3.1 (interquartile range, 1.1-5.1) years. Incident HF occurred in 8.0% of users and 9.7% of nonusers of magnesium supplements (HR, 0.94 [95% CI, 0.89-0.99]). Magnesium-supplement use was also associated with a reduced risk of major adverse cardiac events (HR, 0.94 [95% CI, 0.90-0.97]).

Long-term nonprescription magnesium supplement use was associated with a lower risk of incident HF and major adverse cardiac events in patients with diabetes. These findings should be replicated in randomized controlled trials.

Hypertension is a major risk factor of various cardiac complications, including hypertensive heart disease (HHD). This condition can lead to a number of structural and functional changes in the heart, such as left ventricular hypertrophy, diastolic dysfunction, and, eventually, systolic dysfunction. In the management of hypertensive heart disease, early diagnosis and appropriate treatment are crucial for preventing the progression to congestive heart failure. One potential diagnostic marker that has gained attention in recent years is the N-terminal pro-brain natriuretic peptide (NT-proBNP). The natriuretic peptides, including the brain natriuretic peptide (BNP) and its inactive N-terminal fragment, are secreted by the myocardium in response to increased wall stress and volume overload. In patients with hypertensive heart disease, increased NT-proBNP levels may reflect the structural and functional changes occurring in the myocardium as a result of chronic pressure overload. Several studies have investigated the diagnostic utility of NT-proBNP in hypertensive heart disease. NT-proBNP levels can be a useful adjunct in the diagnosis of hypertensive heart disease, particularly in the assessment of diastolic dysfunction and left ventricular hypertrophy. This review paper explores the role of NT-proBNP levels in the diagnosis of hypertensive heart disease.

Both aging and high blood pressure (BP) are associated with a risk of left ventricular concentricity and hypertrophy. We hypothesized that optimal BP management improves left ventricular remodeling beyond aging. Among 558 hypertensive patients on continuous antihypertensive treatment and without concurrent heart disease who were referred to a cardiology clinic with echocardiography and ambulatory BP monitoring data, 142 patients' echocardiographic data was available after 10 years. Baseline BP and changes in left ventricular geometry were evaluated. Mean age at baseline was 71.0 years old. Baseline daytime BP was 129.9/72.4 ± 17.1/10.2 mmHg and nighttime BP was 122.5/67.1 ± 16.9/9.1 mmHg. After 10 years, left ventricular mass index (LVMI) and relative wall thickness (RWT) significantly decreased from 104.5 ± 26.3 to 97.9 ± 26.4 g/m2, p = 0.003 and 0.51 ± 0.09 to 0.47 ± 0.09, p < 0.001, consecutively. Among patients with hypertrophic geometry at baseline, 17.2% reverted to normal geometry at follow-up. Daytime systolic BP (136.9 ± 18.5 mmHg vs 126.2 ± 16.5 mmHg, p = 0.03), nighttime systolic BP (126.2 ± 17.7 mmHg vs 116.3 ± 16.0 mmHg, p = 0.038) and daytime pulse pressure (63.5 ± 17.3 mmHg vs 53.1 ± 14.9 mmHg, p = 0.022) at baseline were higher in patients who remained hypertrophic than those without hypertrophy at follow-up. On logistic regression analysis, daytime, nighttime systolic BP, and daytime pulse pressure were significantly related to the regression of hypertrophy adjusted for age, sex, eGFR, BMI, LVMI, and RWT at baseline. For conclusion, antihypertensive treatment for 10 years improved LV geometry despite aging. Ambulatory BP and pulse pressure at baseline predicted the change of LV geometry after 10 years.

Hypertension, a worldwide cardiovascular issue, is known to result in significant damage to the left ventricle. Left ventricular hypertrophy refers to an increase in ventricular mass, which is not only the primary independent risk factor for cardiovascular disease onset but also independently related to the risk of death.

We sought to synthesize the existing literature on the occurrence and correlation between hypertension and left ventricular hypertrophy and the progress.

A scoping review was performed based on the methodological framework developed by Arksey & O'Malley. Search in the Pubmed database with no language restrictions, as of September 1, 2024.

Of the 8110 articles retrieved, 110 were finally included. The selected articles were published between 1987 and 2024, with 55.5% (61/110) of the studies in the last five years and 14.5% (16/110) of 2024. The studies covered diagnosis, epidemiology, pathophysiology, prognosis, and treatment of hypertension with left ventricular hypertrophy.

The literature reviewed suggests that studies on hypertension combined with left ventricular hypertrophy covered a variety of clinical progress, especially the clinical trial results of some new drugs that may bring great hope for treatment.

Metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in the presence of liver fibrosis, increases the risk of cardiovascular morbidity and mortality, but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus (T2DM) is not fully understood.

To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis.

T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle, anthropometric measurements, vital signs, an extensive laboratory panel, and a standard echocardiography. Liver fibrosis was evaluated using two scores [Fibrosis-4 (FIB4) and Non-alcoholic fatty liver disease-Fibrosis Score (NFS)], and subjects were classified as having advanced fibrosis, no fibrosis, or an indeterminate risk. The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses. Statistical significance was set at P < 0.05.

Data from 267 T2DM-MASLD subjects with complete assessment was analyzed. Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular (LV) posterior wall thickness, atrial diameters, LV end-systolic volume, LV mass index (LVMi), and epicardial adipose tissue thickness (EATT). Their mean ejection fraction (EF) was significantly lower (49.19% ± 5.62% vs 50.87% ± 5.14% vs 52.00% ± 3.25%; P = 0.003), and a smaller proportion had an EF ≥ 50% (49.40% vs 68.90% vs 84.21%; P = 0.0017). Their total and mid LV wall motion score indexes were higher (P < 0.05). Additionally, they had markers of diastolic dysfunction, with a higher E/e' ratio [9.64 ± 4.10 vs 8.44 (2.43-26.33) vs 7.35 ± 2.62; P = 0.026], and over 70% had lateral e' values < 10 cm/second, though without significant differences between groups. In multiple regression analyses, FIB4 correlated with left atrium diameter (LAD; β = 0.044; P < 0.05), and NFS with both LAD (β = 0.039; P < 0.05) and right atrium diameter (β = 0.041; P < 0.01), Moreover, LVMi correlated positively with age and EATT (β = 1.997; P = 0.0008), and negatively with serum sex-hormone binding protein (SHBP) concentrations (β = -0.280; P = 0.004). SHBP also correlated negatively with LAD (β = -0.036; P < 0.05).

T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy. Additionally, LVMi and LAD correlated negatively with serum SHBP concentrations.

Type 2 diabetes mellitus (T2DM) is a major risk factor for heart failure with preserved ejection fraction and cardiac arrhythmias. Precursors of these complications, such as diabetic cardiomyopathy, remain incompletely understood and underdiagnosed. Detection of early signs of cardiac deterioration in T2DM patients is critical for prevention. Our goal is to quantify T2DM-driven abnormalities in ECG and cardiac imaging biomarkers leading to cardiovascular disease.

We quantified ECG and cardiac magnetic resonance imaging biomarkers in two matched cohorts of 1781 UK Biobank participants, with and without T2DM, and no diagnosed cardiovascular disease at the time of assessment. We performed a pair-matched cross-sectional study to compare cardiac biomarkers in both cohorts, and examined the association between T2DM and these biomarkers. We built multivariate multiple linear regression models sequentially adjusted for socio-demographic, lifestyle, and clinical covariates.

Participants with T2DM had a higher resting heart rate (66 vs. 61 beats per minute, p < 0.001), longer QTc interval (424 vs. 420ms, p < 0.001), reduced T wave amplitude (0.33 vs. 0.37mV, p < 0.001), lower stroke volume (72 vs. 78ml, p < 0.001) and thicker left ventricular wall (6.1 vs. 5.9mm, p < 0.001) despite a decreased Sokolow-Lyon index (19.1 vs. 20.2mm, p < 0.001). T2DM was independently associated with higher heart rate (beta = 3.11, 95% CI = [2.11,4.10], p < 0.001), lower stroke volume (beta = -4.11, 95% CI = [-6.03, -2.19], p < 0.001) and higher left ventricular wall thickness (beta = 0.133, 95% CI = [0.081,0.186], p < 0.001). Trends were consistent in subgroups of different sex, age and body mass index. Fewer significant differences were observed in participants of non-white ethnic background. QRS duration and Sokolow-Lyon index showed a positive association with the development of cardiovascular disease in cohorts with and without T2DM, respectively. A higher left ventricular mass and wall thickness were associated with cardiovascular outcomes in both groups.

T2DM prior to cardiovascular disease was linked with a higher heart rate, QTc prolongation, T wave amplitude reduction, as well as lower stroke volume and increased left ventricular wall thickness. Increased QRS duration and left ventricular wall thickness and mass were most strongly associated with future cardiovascular disease. Although subclinical, these changes may indicate the presence of autonomic dysfunction and diabetic cardiomyopathy.

Current knowledge about non-acute myocardial infarction-associated cardiogenic shock (nAMI-CS) by ethnicity is limited. This study compares clinical features and outcomes of nAMI-CS in Hispanic versus non-Hispanic patients in the U.S.

Hospitalizations with nAMI-CS from 2018 to 2020 were identified using the National Inpatient Sample (NIS) database. Patients were classified by ethnicity (Hispanic vs. non-Hispanic). Statistical analysis, including Chi-square and t-tests, was conducted using STATA version 18.

Out of 8607 nAMI-CS hospitalizations, 832 (9.6 %) were Hispanic. Hispanic patients were younger (62.3 ± 15.2 vs. 66.2 ± 15.3 years) and had higher incidences of smoking (2.4 % vs. 2.1 %), coronary artery disease (45.4 % vs. 44.1 %), myocardial infarction (2.9 % vs. 1.9 %), heart failure (10.1 % vs. 9.2 %), and diabetes mellitus (18.9 % vs. 18.1 %). They had lower incidences of hypertension (32.9 % vs. 34.3 %), valve disease (1.9 % vs. 2.1 %), and cerebrovascular disease (6.5 % vs. 8.5 %, all p < 0.005). Hispanic patients had slightly higher in-hospital mortality rates (18.6 % vs. 17 %, p < 0.001), with an adjusted odds ratio (aOR) of 1.20 (95 % CI: 1.01-1.50, p = 0.01). Their hospital stays were longer (17.7 ± 1.87 vs. 13.2 ± 0.31 days, p = 0.03) and costlier ($409,280 ± 591,582 vs. $291,298 ± 461,920, p = 0.03).

Hispanic nAMI-CS patients are younger, have more co-morbid conditions, longer hospital stays, higher costs, and higher in-hospital mortality rates than non-Hispanic patients. Further research is needed to understand the mechanisms behind these disparities.

To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D).

A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes.

One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (β 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (β 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (β ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (β ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only.

Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

Cardiovascular-kidney-metabolic (CKM) multimorbidity is prevalent among individuals with heart failure (HF), but whether cardiac structure and function, clinical outcomes, and treatment response to sacubitril/valsartan vary in relation to CKM status is unknown.

In this PARAGON-HF post-hoc analysis, we evaluated the impact of CKM multimorbidity (atherosclerotic cardiovascular [CV] disease, chronic kidney disease, and type 2 diabetes) on cardiac structure and function, clinical outcomes, and treatment effects of sacubitril/valsartan versus valsartan. The primary outcome was a composite of total HF hospitalizations and CV death. Secondary outcomes included the individual components of the primary outcome and a composite kidney outcome (sustained estimated glomerular filtration rate reduction of ≥50%, end-stage kidney disease, or kidney-related death). At baseline, 35.2% had one CKM condition, 33.3% had two, 15.9% had three, and only 15.6% had HF alone. CKM multimorbidity was associated with higher septal and posterior wall thickness, lower global longitudinal strain, higher E/e', and worse right ventricular function. Total HF hospitalizations or CV death increased with greater CKM multimorbidity, with the highest relative risk observed with three CKM conditions (rate ratio 3.06, 95% confidence interval 2.33-4.03), compared with HF alone. Treatment effects of sacubitril/valsartan were consistent irrespective of the number of CKM conditions for the primary endpoint (pinteraction = 0.75), CV death (pinteraction = 0.82), total HF hospitalizations (pinteraction = 0.67), and the composite kidney endpoint (pinteraction = 0.99).

Cardiovascular-kidney-metabolic multimorbidity was common in PARAGON-HF and associated with adverse changes in cardiac structure and function and with a stepwise increase in risk of clinical outcomes. Treatment effects of sacubitril/valsartan were consistent irrespective of CKM burden.

ClinicalTrials.gov NCT01920711.

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD-induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin-angiotensin-aldosterone system inhibitors, beta-blockers, diuretics and sodium-glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end-diastolic/end-systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre-clinical evaluation.

African Americans (AAs) have been underrepresented in polygenic risk score (PRS) studies. Here, we integrated genome-wide data from multiple observational studies on type 2 diabetes (T2D), encompassing a total of 101,987 AAs, to train and optimize an AA-focused T2D PRS (PRSAA), using a Bayesian polygenic modeling method. We further tested the score in three independent studies with a total of 7,275 AAs and compared the PRSAA with other published scores. Results show that a 1-SD increase in the PRSAA was associated with 40-60% increase in the odds of T2D (odds ratio [OR] 1.60, 95% CI 1.37-1.88; OR 1.40, 95% CI 1.16-1.70; and OR 1.45, 95% CI 1.30-1.62) across three testing cohorts. These models captured 1.0-2.6% of the variance (R2) in T2D on the liability scale. The positive predictive values for three calculated score thresholds (the top 2%, 5%, and 10%) ranged from 14 to 35%. The PRSAA, in general, performed similarly to existing T2D PRS. The need remains for larger data sets to continue to evaluate the utility of within-ancestry scores in the AA population.

Several studies investigated the association between nighttime blood pressure (BP) and left ventricular hypertrophy (LVH) in diabetes, but since most of these studies were conducted in diabetes populations only, they did not compare differences in the impact of nighttime BP on LVH in subjects without diabetes. Moreover, data about the impact of glucose control in diabetes on the relationship between nighttime BP and LVH are sparse. We classified 1277 adults (age 64.7 ± 11.8 years) performing ambulatory BP monitoring while enrolled as part of the Japan Morning Surge Home Blood Pressure (J-HOP) study into groups according to the control status of daytime BP (systolic BP [SBP] < 135 mmHg or ≥135 mmHg), nighttime BP (SBP < 120 mmHg or ≥120 mmHg), and diabetes (HbA1c < 7.0% or ≥7.0%). LVH was assessed by echocardiography. LVH according to echocardiographic criteria was identified in 33.7% of the participants. The group with poorly controlled diabetes plus uncontrolled nighttime BP (n = 90) had a 2.1-fold higher risk of LVH compared to the group with controlled nighttime BP and non-diabetes (n = 505) (odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.29-3.44). No association was observed between uncontrolled daytime BP and diabetes for LVH. In the participants with poorly controlled diabetes (n = 146), uncontrolled nighttime BP posed a 3.1-fold higher risk of LVH compared to controlled nighttime BP (OR 3.12, 95%CI: 1.47-6.62). This association was not found in controlled diabetes. Uncontrolled nighttime BP was associated with a risk of LVH, especially among individuals with poorly controlled diabetes.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Diabetes may identify an essential phenotype that significantly affects the prognosis of these patients. The WATCH-DM risk score has been validated for predicting the risk of heart failure in outpatients with type 2 diabetes mellitus (T2DM), but its ability to predict clinical outcomes in HFpEF patients with T2DM is unknown. We aimed to assess whether this risk score could predict the prognosis of diabetic phenotype patients with heart failure and preserved ejection fraction.

We enrolled retrospectively 414 patients with HFpEF (70.03 ± 8.654 years, 58.70% female), including 203 (49.03%) type 2 diabetics. Diabetic HFpEF patients were stratified by baseline WATCH-DM risk score.

Diabetic HFpEF patients exhibited a trend toward more concentric remodeling/hypertrophy than nondiabetic HFpEF patients. When analyzed as a continuous variable, per 1-point increase in the WATCH-DM risk score was associated with increased risks of all-cause death (HR 1.181), cardiovascular death (HR 1.239), any hospitalization (HR 1.082), and HF hospitalization (HR 1.097). The AUC for the WATCH-DM risk score in predicting incident cardiovascular death (0.7061, 95% CI 0.6329-0.7792) was higher than that of all-cause death, any hospitalization, or HF hospitalization.

As a high-risk phenotype for heart failure, diabetic HFpEF necessitates early risk stratification and specific treatment. To the best of our knowledge, the current study is the first to demonstrate that the WATCH-DM score predicts poor outcomes in diabetic HFpEF patients. Its convenience may allow for quick risk assessments in busy clinical settings.

The duration of type 2 diabetes mellitus (T2DM) is an important determinant of diabetes severity. The EMPA-HEART CardioLink-6 trial reported significant left ventricular (LV) mass indexed to body surface area (LVMi) regression in patients treated with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin for 6 months. This exploratory sub-analysis of the same trial investigated the association between T2DM duration and LVMi regression.

A total of 97 individuals with T2DM and coronary artery disease (CAD) were randomly assigned to receive empagliflozin 10 mg daily or placebo. LVMi was measured at the baseline and 6 month visit using cardiac magnetic resonance imaging. The study population was divided into those with a baseline T2DM duration <10 years (n = 40) or ≥10 years (n = 57). A linear model adjusting for baseline values in each of the subgroups (ANCOVA) was used to assess the treatment effect of 6 month change in LVMi, LV end systolic volume indexed to body surface area, LV end diastolic volume indexed to body surface area and LV ejection fraction. Patients in the T2DM duration <10 years group (38 males [95.0%], median age 63 [IQR: 55 years to 70 years]) had a median T2DM duration of 4 years (IQR: 2.0 years to 7.0 years). Those in the T2DM duration ≥10 years group (52 males [91.2%], median age 65 [IQR: 57 years to 71 years]) had a median duration of 15 years (IQR: 12 years to 20 years). There was no significant difference in baseline LVMi according to T2DM duration (median 62 g/m² [IQR: 53.1 g/m² to 70.0 g/m² ] for T2DM duration <10 years; median 57.5 g/m² [IQR: 52.1 g/m² to 66.2 g/m² ] for T2DM duration ≥10 years; P = 0.11). Empagliflozin was associated with reductions in LVMi irrespective of duration of T2DM above and below 10 years (T2DM duration <10 years group, mean adjusted difference -2.90 g/m² [95% CI: -6.64 g/m² to 0.84 g/m² ]; T2DM duration ≥10 years group, mean adjusted difference -3.69 g/m² [95% CI: -0.14 g/m² to -7.24 g/m² ]; P_interaction  = 0.07).

In the EMPA-HEART CardioLink-6 trial, empagliflozin treatment was associated with reductions in LVMi in people with T2DM and CAD irrespective of the duration of diabetes assessed categorically above and below 10 years.

Background Diabetes and hypertension have been associated with adverse left ventricular (LV) remodeling. While they often occur concurrently, their individual effects are understudied. We aimed to assess the independent effects of diabetes and hypertension on LV remodeling in Black adults. Methods and Results The JHS (Jackson Heart Study) participants (n=4143 Black adults) with echocardiographic measures from baseline exam were stratified into 4 groups: neither diabetes nor hypertension (n=1643), only diabetes (n=152), only hypertension (n=1669), or both diabetes and hypertension (n=679). Echocardiographic measures of LV structure and function among these groups were evaluated by multivariable regression adjusting for covariates. Mean age of the participants was 52±1 years, and 63.7% were women. LV mass index was not different in participants with only diabetes compared with participants with neither diabetes nor hypertension (P=0.8). LV mass index was 7.9% (6.0 g/m2) higher in participants with only hypertension and 10.8% (8.1 g/m2) higher in participants with both diabetes and hypertension compared with those with neither (P<0.001). LV wall thickness (relative, posterior, and septal) and brain natriuretic peptide levels in participants with only diabetes were not significantly higher than participants with neither (P>0.05). However, participants with both diabetes and hypertension demonstrated higher LV wall thickness and brain natriuretic peptide levels than participants with neither (P<0.05). Conclusions In this cross-sectional analysis, diabetes was not associated with altered LV structure or function in Black adults unless participants also had hypertension. Our findings suggest hypertension is the main contributor to cardiac structural and functional changes in Black adults with diabetes.

Left ventricular mass is a risk marker for cardiovascular events, and may indicate an underlying cardiomyopathy. Cardiac magnetic resonance is the gold-standard for left ventricular mass estimation, but is challenging to obtain at scale. Here, we use deep learning to enable genome-wide association study of cardiac magnetic resonance-derived left ventricular mass indexed to body surface area within 43,230 UK Biobank participants. We identify 12 genome-wide associations (1 known at TTN and 11 novel for left ventricular mass), implicating genes previously associated with cardiac contractility and cardiomyopathy. Cardiac magnetic resonance-derived indexed left ventricular mass is associated with incident dilated and hypertrophic cardiomyopathies, and implantable cardioverter-defibrillator implant. An indexed left ventricular mass polygenic risk score ≥90th percentile is also associated with incident implantable cardioverter-defibrillator implant in separate UK Biobank (hazard ratio 1.22, 95% CI 1.05-1.44) and Mass General Brigham (hazard ratio 1.75, 95% CI 1.12-2.74) samples. Here, we perform a genome-wide association study of cardiac magnetic resonance-derived indexed left ventricular mass to identify 11 novel variants and demonstrate that cardiac magnetic resonance-derived and genetically predicted indexed left ventricular mass are associated with incident cardiomyopathy.

The aim of this study was to investigate cardiomyocyte Ca2+ handling and contractile function in freshly excised human atrial tissue from diabetic and non-diabetic patients undergoing routine surgery. Multicellular trabeculae (283 ± 20 μm in diameter) were dissected from the endocardial surface of freshly obtained right atrial appendage samples from consenting surgical patients. Trabeculae were mounted in a force transducer at optimal length, electrically stimulated to contract, and loaded with fura-2/AM for intracellular Ca2+ measurements. The response to stimulation frequencies encompassing the physiological range was recorded at 37°C. Myofilament Ca2+ sensitivity was assessed from phase plots and high potassium contractures of force against [Ca2+ ]i . Trabeculae from diabetic patients (n = 12) had increased diastolic (resting) [Ca2+ ]i (p = 0.03) and reduced Ca2+ transient amplitude (p = 0.04) when compared to non-diabetic patients (n = 11), with no difference in the Ca2+ transient time course. Diastolic stress was increased (p = 0.008) in trabeculae from diabetic patients, and peak developed stress decreased (p ≤ 0.001), which were not accounted for by reduction in the cardiomyocyte, or contractile protein, content of trabeculae. Trabeculae from diabetic patients also displayed diminished myofilament Ca2+ sensitivity (p = 0.018) compared to non-diabetic patients. Our data provides evidence of impaired calcium handling during excitation-contraction coupling with resulting contractile dysfunction in atrial tissue from patients with type 2 diabetes in comparison to the non-diabetic. This highlights the importance of targeting cardiomyocyte Ca2+ homeostasis in developing more effective treatment options for diabetic heart disease in the future.

Cardiometabolic diseases still represent a major cause of mortality worldwide. In addition to pharmacological approaches, lifestyle interventions can also be adopted for the prevention of these morbid conditions. Lifestyle changes include exercise and dietary restriction protocols, such as calorie restriction and intermittent fasting, which were shown to delay cardiovascular ageing and elicit health-promoting effects in preclinical models of cardiometabolic diseases. Beneficial effects are mediated by the restoration of multiple molecular mechanisms in heart and vessels that are compromised by metabolic stress. Exercise and dietary restriction rescue mitochondrial dysfunction, oxidative stress and inflammation. They also improve autophagy. The result of these effects is a marked improvement of vascular and heart function. In this review, we provide a comprehensive overview of the molecular mechanisms involved in the beneficial effects of exercise and dietary restriction in models of diabetes and obesity. We also discuss clinical studies and gap in animal-to-human translation.

Diabetic cardiomyopathy (DCM) is one of the common complications of diabetic patients, which can induce myocardial hypertrophy, cardiac fibrosis, and heart failure. Growing evidence has shown that the occurrence and development of DCM are accompanied by pyroptosis which is an NLRP3-mediated intense inflammatory cell death. Cyclovirobuxine D (CVB-D) has been shown to significantly ameliorate DCM and anti-inflammatory effects associated with cardiomyopathy, but it is unclear whether it has an effect on cardiomyocyte pyroptosis accompanying DCM. Therefore, the purpose of the present study was to explore the ameliorating effect of CVB-D on cardiomyocyte pyroptosis associated with DCM and its molecular regulation mechanism. Type 2 diabetes in C57BL/6 mice was reproduced by the high-fat and high-glucose diet (HFD) combined with low-dose streptozotocin (STZ). The characteristics of DCM were evaluated by cardiac ultrasonography, serum detection, and histopathological staining. The results suggested that CVB-D could significantly alleviate the cardiac pathology of DCM. Then, we explored the mechanism of CVB-D on primary neonatal rat cardiomyocyte (PNRCM) injury with high glucose (HG) in vitro to simulate the physiological environment of DCM. Preincubation with CVB-D could significantly increase cell viability, attenuate cytopathological changes and inhibit the expression levels of pyroptosis-related proteins. Further research found that the myocardial improvement effect of CVB-D was related to its inhibition of NLRP3 expression. In conclusion, our data suggest that CVB-D can ameliorate DCM by inhibiting cardiomyocyte pyroptosis via NLRP3, providing a novel molecular target for CVB-D clinical application.

Determining the etiologies of left ventricular hypertrophy (LVH) can be challenging due to the similarities of the different manifestations in clinical presentation and morphological features. Depending on the underlying cause, not only left ventricular mass but also left ventricular cavity size, or both, may increase. Patients with LVH remain asymptomatic for a few years, but disease progression will lead to the development of systolic or diastolic dysfunction and end-stage heart failure. As hypertrophied cardiac muscle disrupts normal conduction, LVH predisposes to arrhythmias. Distinguishing individuals with treatable causes of LVH is important for prevention of cardiovascular events and mortality. Athletic's heart with physiological LVH does not require treatment. Frequent causes of hypertrophy include etiologies due to pressure/volume overload, such as systemic hypertension, hypertrophic cardiomyopathy, or infiltrative cardiac processes such as amyloidosis, Fabry disease, and sarcoidosis. Hypertension and aortic valve stenosis are the most common causes of LVH. Management of LVH involves lifestyle changes, medications, surgery, and implantable devices. In this review we systematically summarize treatments for the different patterns of cardiac hypertrophy and their impacts on outcomes while informing clinicians on advances in the treatment of LVH due to Fabry disease, cardiac amyloidosis, and hypertrophic cardiomyopathy.

Objective: The coexistence of type 2 diabetes (T2D) and heart failure (HF) has obvious consequences during cardiovascular diagnosis. This study evaluated the relationship between T2D and clinical and echocardiographic features of patients with HF. Methods & results: 121 patients with HF were clinically evaluated by echocardiography in this case-control study. They were divided into two groups based on the presence of T2D. Patients with diabetes were subdivided and compared via an HbA1c control. Significant differences between T2D and non-T2D groups were detected by comparing the left atrial diameter, E/E' and left ventricular end-diastolic diameter. When comparing patients with diabetes, differences in acute heart failure episodes, left ventricular ejection fraction, left atrial diameter and E/E' were evaluated. Conclusion: T2D was associated with important cardiac alterations and more severe HF. Poor control of diabetes resulted in worse cardiovascular outcomes.

Young adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics for these cardiovascular risk factors.

Non-athletic non-smoking asymptomatic adults aged 18-45 years were prospectively recruited and underwent 3Tesla cardiac MRI. Multivariate linear regression was performed to investigate independent associations of risk factor-related parameters with cardiac MRI values.

We included 311 adults (age, 32 ± 7 years; men, 49%). Of them, 220 subjects had one or multiple risk factors, while 91 subjects were free of risk factors. For overweight, increased body mass index (per SD = 5.3 kg/m2) was associated with increased left ventricular (LV) mass (+7.3 g), biventricular higher end-diastolic (LV, +8.6 ml), and stroke volumes (SV; +5.0 ml), higher native T1 (+7.3 ms), and lower extracellular volume (ECV, -0.38%), whereas the higher waist-hip ratio was associated with lower biventricular volumes. Regarding hypertension, increased systolic blood pressure (per SD = 14 mmHg) was associated with increased LV mass (+6.9 g), higher LV ejection fraction (EF; +1.0%), and lower ECV (-0.48%), whereas increased diastolic blood pressure was associated with lower LV EF. In T2D, increased HbA1c (per SD = 9.0 mmol/mol) was associated with increased LV mass (+2.2 g), higher right ventricular end-diastolic volume (+3.2 ml), and higher ECV (+0.27%). Increased heart rate was linked with decreased LV mass, lower biventricular volumes, and lower T2 values.

Young asymptomatic adults with overweight, hypertension, and T2D show subclinical alterations in cardiac morphology, function, and tissue characteristics. These alterations should be considered in cardiac MRI-based clinical decision making.

Recent evidence indicates that mildly increased fasting and post-oral load blood glucose concentrations contribute to development of organ damage in nondiabetic patients with hypertension. In previous studies, vitamin D deficiency was associated with decreased glucose tolerance. The aim of this study was to examine the relationships between serum 25(OH)D levels and glucose tolerance and insulin sensitivity in hypertension. In 187 nondiabetic essential hypertensive patients free of cardiovascular or renal complications, we measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) and performed a standard oral glucose tolerance test (OGTT). Patients with 25(OH)D deficiency/insufficiency were older and had significantly higher blood pressure, fasting and post-OGTT (G-AUC) glucose levels, post-OGTT insulin (I-AUC), PTH levels, and prevalence of metabolic syndrome than patients with normal serum 25(OH)D. 25(OH)D levels were inversely correlated with age, blood pressure, fasting glucose, G-AUC, triglycerides, and serum calcium and PTH, while no significant relationships were found with body mass index (BMI), fasting insulin, I-AUC, HOMA index, and renal function. In a multivariate regression model, greater G-AUC was associated with lower 25(OH)D levels independently of BMI and seasonal vitamin D variations. Thus, in nondiabetic hypertensive patients, 25(OH)D deficiency/insufficiency could contribute to impaired glucose tolerance without directly affecting insulin sensitivity.

There has been great interest in genetic risk prediction using risk scores in recent years, however, the utility of scores developed in European populations and later applied to non-European populations has not been successful. The goal of this study was to create a methylation risk score (MRS) for metabolic syndrome (MetS), demonstrating the utility of MRS across race groups using cross-sectional data from the Hypertension Genetic Epidemiology Network (HyperGEN, N = 614 African Americans (AA)) and the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, N = 995 European Americans (EA)). To demonstrate this, we first selected cytosine-guanine dinucleotides (CpG) sites measured on Illumina Methyl450 arrays previously reported to be significantly associated with MetS and/or component conditions in more than one race/ethnic group (CPT1A cg00574958, PHOSPHO1 cg02650017, ABCG1 cg06500161, SREBF1 cg11024682, SOCS3 cg18181703, TXNIP cg19693031). Second, we calculated the parameter estimates for the 6 CpGs in the HyperGEN data (AA) and used the beta estimates as weights to construct a MRS in HyperGEN (AA), which was validated in GOLDN (EA). We performed association analyses using logistic mixed models to test the association between the MRS and MetS, adjusting for covariates. Results showed the MRS was significantly associated with MetS in both populations. In summary, a MRS for MetS was a strong predictor for the condition across two race groups, suggesting MRS may be useful to examine metabolic disease risk or related complications across race/ethnic groups.

Diabetes was regarded as an independent risk factor for abnormal left heart remodeling. However, there was lacking population-based data on the relationship of glucose status with left ventricular hypertrophy (LVH) or left atrial enlargement (LAE). This study intended to clarify the influence of diabetes and prediabetes on the prevalence and incidence of LVH and LAE based on a northeast rural population of China.

We analyzed clinical, laboratory and echocardiographic data of a total of 2824 participants aged over 35 years from a population-based prospective cohort NCRCHS study with 2 years of follow-up, which was carried out in rural areas of northeast China. All measurements were performed according to standardized protocols.

There were 2179 controls, 342 subjects with prediabetes and 303 ones with diabetes. The baseline distribution of LAD, IVSd, LVIDd, LVIDs, LVMI, E wave, A wave, E/A, E/e', diastolic dysfunction, LVEDV, LVESV and SV was significantly different among three groups (all P_trend<0.05). After the adjustment for age, gender, BMI, waist circumference, heart rate, hypertension and dyslipidemia, glucose status remained associated with LVIDd and E/e' (all P < 0.05). At baseline, diabetes was independently related to the prevalence of LVH (OR = 1.53; 95%CI = 1.12-2.10; P < 0.01) and LAE (OR = 1.71; 95%CI = 1.19-2.43; P < 0.01) in the overall population, and the same significant results were also found in gender specific subgroups. During the 2-year follow-up, Cox regression models revealed that baseline diabetes had an independent association with the incidence of LAE in the total subjects (HR = 1.83; 95%CI = 1.10-3.06; P = 0.02) and females (HR = 1.90; 95%CI = 1.05-3.46; P = 0.04) after adjusting the potential confounders.

Diabetes, but not prediabetes, is an independent predictor for the prevalence of LVH and LAE, and for the new-onset LAE, it should be considered in the assessment of diabetes and cardiac structural remodeling.

Despite diabetes being an independent risk for HF, only some DM patients develop HF and hence our aim was to compare the clinical features of DM with and without HF and non-DM with and without HF.

A retrospective observational study was conducted among 397 individuals who visited two tertiary care centres. They were classified into 4 groups - DM with HF(DM-HF), DM without HF, non-DM with HF(non-DM-HF) and non-DM without HF. We assessed and compared the clinical profile of DM with HF vs. DM without HF and non-DM with HF groups respectively.

The parameters such as age, BMI, BP, eGFR showed significant difference between the groups. People with DM-HF were older compared to DM without HF group(58.9 ± 9.2vs.49.5 ± 9.3; p < 0.001). An increasing trend was observed in HF prevalence with increasing duration of DM among the DM-HF group. DM-HF showed a higher prevalence of hypertension and coronary artery disease(CAD) by history than DM without HF group. DM-HF group(91.2%) had HF with preserved left ventricular ejection fraction(HFpEF) whereas a high proportion(43.5%) of non-DM-HF group had HF with reduced LV ejection fraction(HFrEF).

The DM-HF group differed from other groups significantly in age, diabetes duration, HbA1c level, prevalence of hypertension, CAD and HFpEF.

Echocardiography is suggested in the diagnostic work-up of patients with Type 2 diabetes (T2D). We investigated which echocardiographic parameters that best predicted cardiovascular disease (CVD) and whether this was persistent in both genders in a large cohort of outpatients with T2D.

We performed comprehensive echocardiography in 933 patients with T2D followed at specialized out-patients clinics in Copenhagen, Denmark. Follow-up was performed using national registries and included admission with future CVD events and non-CVD death as competing risk. Median follow-up was 4.8 years and 138 CVD events occurred. In univariable and multivariable analyses, a wide range of structural, diastolic, and systolic measurements predicted CVD including mean E/e' [hazard ratio (HR) 1.06, 95% confidence interval: (1.03-1.10), P < 0.001, C-statistics 0.74 (0.70-0.78)] and global longitudinal strain (GLS) [1.10 (1.01-1.20), P = 0.03, C-statistics 0.73 (0.69-0.77)]. However, this was modified by gender. In men, mean E/e' remained the strongest predictor in multivariable analyses and performed best measured by highest C-statistics [HR 1.15, 95% confidence interval: (1.08-1.21), P < 0.001, C-statistics 0.75 (0.71-0.80)] whereas in women this was GLS [1.39 (1.14-1.70), P = 0.001, C-statistics 0.79 (0.70-0.87)]. These findings persisted when excluding patients with known heart disease and when regarding all-cause mortality as a competing risk.

A range of echocardiographic parameters predicted CVD in patients with Type 2 diabetes, however, in multivariable analyses, mean E/e' was the strongest predictor and had the highest model performance. Importantly, this study identifies a hitherto undescribed gender interaction as mean E/e' performed best in men, whereas in women this was GLS.

We aimed to comprehensively determine the effects of hypertension on left ventricular (LV) structure, microcirculation, tissue characteristics, and deformation in type 2 diabetes mellitus (T2DM) using multiparametric cardiac magnetic resonance (CMR) imaging.

We prospectively enrolled 138 asymptomatic patients with T2DM (80 normotensive and 58 hypertensive individuals) and 42 normal glucose-tolerant and normotensive controls and performed multiparametric CMR examination to assess cardiac geometry, microvascular perfusion, extracellular volume (ECV), and strain. Univariable and multivariable linear analysis was performed to analyze the effect of hypertension on LV deformation in patients with T2DM.

Compared with controls, patients with T2DM exhibited decreased strain, decreased microvascular perfusion, increased LV remodeling index, and increased ECV. Hypertension lead to greater deterioration of LV strain (peak strain-radial, P = 0.002; peak strain-longitudinal, P = 0.006) and LV remodeling index (P = 0.005) in patients with T2DM after adjustment for covariates; however, it did not affect microvascular perfusion (perfusion index, P = 0.469) and ECV (P = 0.375). In multivariable analysis, hypertension and diabetes were independent predictors of reduced LV strain, whereas hypertension is associated with greater impairment of diastolic function (P = 0.009) but not systolic function (P = 0.125) in the context of diabetes, independent of clinical factors and myocardial disorder.

Hypertension in the context of diabetes is significantly associated with LV diastolic function and concentric remodeling; however, it has little effect on systolic function, myocardial microcirculation, or fibrosis independent of covariates, which provide clinical evidence for understanding the pathogenesis of comorbidities and explaining the development of distinct heart failure phenotypes.

Heart failure is a prominent complication of type 2 diabetes mellitus (T2D). The goal of this study was to provide longitudinal data on cardiac structure and function (and cross-sectional comparison to normal-weight and obese controls without T2D) in individuals followed from adolescence with youth-onset T2D.

In the TODAY study (Treatment Options for Type 2 Diabetes Mellitus in Adolescents and Youth), echocardiograms were performed at study years 4 to 5 and 9 to 10. Echocardiograms were also obtained at years 8 to 9 in a control population of age, race/ethnicity, and sex-matched normal-weight and obese individuals without diabetes mellitus. Study outcomes were measures of left ventricular structure and function. The cohort included 411 participants with T2D, 194 obese controls, and 51 normal-weight controls.

At follow-up, mean participant age was 23 years, 65% women, 20% non-Hispanic white, 35% non-Hispanic black, and 39% Hispanic. Ejection fraction was <52% in 11.7% of male participants with T2D. Diastolic function declined during follow-up in participants with T2D (mitral valve lateral E/Em increased 0.72±0.12 in women and 0.50±0.17 in men; P<0.01) and was significantly higher than obese controls (women, 6.65±1.89 versus 5.66±1.37; men, 6.15±1.90 versus 5.26±1.31; P<0.0001). Predictors of adverse changes included hypertension, obesity, female sex, Hispanic and non-Hispanic black ethnicity, worse glycemic control, and elevated heart rate. Cardiac structural abnormalities, left ventricular hypertrophy, or concentric geometry, were highest in those with T2D (15.8% versus 5.7% obese versus 0% normal weight).

Adverse changes in cardiac structure and function changed significantly from adolescence to early adulthood in participants with youth-onset T2D. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00081328.

There is conflicting data on early left ventricle (LV) remodeling in diabetes mellitus (DM) and hypertension (HTN). This study examines the feasibility of cardiac computed tomography angiography (CCTA) to detect early LV geometric changes in patients with DM and HTN.

Consecutive patients (n = 5,992) who underwent prospective electrocardiography (ECG)-triggered (mid-diastolic) CCTA were screened. Patients with known structural heart disease or known LV dysfunction were excluded. Left ventricular mass (LVM), left ventricular mid-diastolic volume (LVMDV), and LV concentricity (LVM/LVMDV) were measured and indexed to body surface area.

A total of 4,283 patients were analyzed (mean age 57 ± 10.69 years, female 46.7%). DM, HTN, and HTN + DM were present in 4.1%, 35.8% and 10.6% of patients, respectively. Compared to normal patients, HTN and HTN + DM patients had increased LVM indexed to body surface area (LVMi) (56.87 ± 17.24, 59.26 ± 13.62, and 58.56 ± 13.09, respectively; P < 0.05). There was no difference in LVMi between normal subjects and patients with DM (56.39 ± 11.50, P = 0.617).Concentricity indices were higher in patient with HTN (1.0456 ± 0.417; P < 0.001), DM (1.109 ± 0.638; P = 0.004), and HTN + DM (1.083 ± 0.311, P < 0.001) than normal individuals (0.9671 ± 0.361). There was no overlap of the 95% confidence intervals in the composite of concentricity indices and LVMi between the different groups.

CCTA measures of LVM and concentricity index may discriminate patients with HTN and DM before overt structural heart disease.

Diabetic cardiomyopathy (DCM) is the principal cause of death in people with diabetes. However, there is currently no effective strategy to prevent the development of DCM. Although cyclovirobuxine D (CVB-D) has been widely used to treat multiple cardiovascular diseases, the possible beneficial effects of CVB-D on DCM remained unknown. The present aim was to explore the potential effects and underlying mechanisms of CVB-D on DCM. We explored the effects of CVB-D in DCM by using high fat high sucrose diet and streptozotocin-induced rat DCM model. Cardiac function and survival in rats with DCM were improved via the amelioration of oxidative damage after CVB-D treatment. Our data also demonstrated that pre-treatment with CVB-D exerted a remarkable cytoprotective effect against high glucose -or H2O2 -induced neonatal rat cardiomyocyte damage via the suppression of reactive oxygen species accumulation and restoration of mitochondrial membrane potential; this effect was associated with promotion of Nrf2 nuclear translocation and its downstream antioxidative stress signals (NQO-1, Prdx1). Overall, the present data has provided the first evidence that CVB-D has potential therapeutic in DCM, mainly by activation of the Nrf2 signalling pathway to suppress oxidative stress. Our findings also have positive implications on the novel promising clinical applications of CVB-D.