Association of biomarkers and risk scores with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). We sought the extent to which clinical scores (ARIC-HF, WATCH-DM), natriuretic peptides (NTpBNP) and troponin (hs-TnT) were associated with subclinical LV dysfunction (LVD). These associations could inform the ability of these tests to identify which patients should undergo echocardiography. METHODS: Participants with T2DM were prospectively recruited from three community-based populations. ARIC-HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP and hs-TnT were measured using an electro-chemiluminescence assay. All underwent a comprehensive echocardiogram. We calculated the sensitivity and specificity of clinical scores and biomarkers to identify abnormal global longitudinal strain (GLS ≥ -16%)), diastolic function (E/e' ≥ 14 or e' < 8 cm/s), left atrial volume index (LAV > 34 ml/m2) and LV hypertrophy (LV mass index > 88 g/m2 (F) > 102 g/m2(M)). RESULTS: Of 804 participants (median age 69 years [inter-quartile range (IQR) 65-73], 36% female), clinical scores suggested significant HF risk (median ARIC-HF 8% [IQR 4-12]; WATCH-DM 10 points [IQR 8-12]), and the median NTpBNP was 50 pg/mL [IQR 25-101] and hs-TnT 9.6 pg/mL [IQR 6.8-13.6]. Abnormal GLS was present in 126 (17%), elevated E/e' in 114 (15%), impaired e' in 629 (78%), increased LAV in 351 (44%) and LV hypertrophy in 113 (14%). After adjustments for age, body-mass index, and renal function, each standard deviation increase in NTpBNP was associated with a GLS increase of 0.32 (p < 0.001) and hs-TnT increase by 0.26 (p < 0.001). Similar trends were observed with ARIC-HF (standardised ß = 0.22, p < 0.001) and WATCH-DM (standardised ß = 0.22, p < 0.001) in univariable analyses. However, none of the risk assessment tools provided satisfactory discrimination for abnormal GLS (AUC 63%), diastolic indices (e' AUC 54-61%) or LV mass (AUC 59-67%). At a sensitivity of 90%, there was an unacceptably low (< 50%) specificity. CONCLUSION: Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LVD.

Echocardiographic detection of heart valve disease in a community cohort of asymptomatic Australians > 65 years with cardiovascular risk factors.

BACKGROUND: Valvular heart disease is becoming an increasingly prevalent with population ageing. We sought to define the current prevalence of valvular heart disease in Australia. METHODS: The TasELF and VicELF studies prospectively recruited 962 asymptomatic participants ≥65 years, with at least one cardiovascular risk factor, from the Tasmanian and Victorian communities. People were excluded if they had a previous diagnosis of heart failure, or a life expectancy <1 year. All underwent baseline echocardiography. Those with moderate or severe valvular disease were identified. The current prevalence of clinically significant valve disease was applied to the Australian Bureau of Statistics population projections. RESULTS: Echocardiograms were interpretable in 943 participants (98%). Clinically significant valve disease was present in 5% of the population, and mitral regurgitation was the most common overall valvular lesion, present in 36% of the population. The projected numbers of people with clinically significant valvular disease is expected to increase significantly across all age groups by the year 2060. CONCLUSIONS: Clinically significant yet asymptomatic valvular disease was prevalent in a large community cohort of participants with at least one risk factor. The total burden of valvular heart disease is expected to increase dramatically over the coming decades.

Evolution of Myocardial Dysfunction in Asymptomatic Patients at Risk of Heart Failure.

OBJECTIVES: The determinants of changes in systolic and diastolic parameters in patients age >65 years, at risk of heart failure (HF), and with and without asymptomatic type 2 diabetes mellitus (T2DM) was assessed by echocardiography. The association between metformin and myocardial function was also assessed. BACKGROUND: The increasing prevalence of T2DM will likely further fuel the epidemic of HF. Understanding the development or progression of left ventricular (LV) dysfunction may inform effective measures for HF prevention. METHODS: A total of 982 patients with at least one HF risk factor (hypertension, obesity, or T2DM) were recruited from 2 community-based populations and divided into 2 groups: T2DM (n = 431, age 71 ± 4 years) and non-T2DM (n = 551, age 71 ± 5 years). Associations of metformin therapy were evaluated in the T2DM group. All underwent a comprehensive echocardiogram, including global longitudinal strain (GLS) and diastolic function (transmitral flow [E], annular velocity [e']) at baseline and follow-up (median 19 months [interquartile range: 17 to 26 months]). Comparisons were facilitated by propensity matching. RESULTS: A reduction in GLS was observed in the T2DM group (baseline -17.8 ± 2.6% vs. follow-up -17.4 ± 2.8%; p = 0.003), but not in the non-T2DM group (-18.7 ± 2.7% vs. -18.6 ± 3.0%; p = 0.41). Estimated LV filling pressures increased in both the T2DM group (p = 0.001) and the non-T2DM group (p = 0.04). Metformin-treated patients with T2DM did not increase estimated LV filling pressure (E/e' baseline 8.9 ± 2.7 vs. follow-up 9.1 ± 2.7; p = 0.485) or change e' (7.6 ± 1.5 cm/s vs. 7.6 ± 1.8 cm/s; p = 0.88). After propensity matching, metformin was associated with a smaller change in e' (ß = 0.58 [95% CI: 0.13 to 1.03]; p = 0.013) and E/e' (ß = -0.96 [95% CI: -1.66 to -0.26]; p = 0.007) but was not associated with a change in GLS (p = 0.46). CONCLUSIONS: Over 2 years, there is a worsening of GLS and LV filling pressures in asymptomatic diabetic patients with HF risk factors. Metformin use is associated with less deterioration of LV filling pressures and myocardial relaxation but had no association with systolic function.

Impact of left ventricular diastolic dysfunction on left atrial volume and function: a volumetric analysis.

AIMS: Diastolic dysfunction may result in elevation of left ventricular (LV) and atrial pressures, resulting in left atrial (LA) remodelling. We examined the effects of LV diastolic dysfunction on LA volume and function. METHODS AND RESULTS: We measured LA volume and function in 83 patients with normal LV systolic function. The LV diastolic function grade was defined using traditional Doppler measures of diastolic function. LA volumes were measured using the ellipsoid method. Maximum LA volume (Vol(max)) was indexed to the body surface area(.) The passive filling, conduit and active emptying volumes were estimated and corrected for indexed LA Vol(max). Indexed LA Vol(max) was strongly associated with LV diastolic function grade (Spearman P < 0.01, r(s) = 0.79). An indexed LA Vol(max) > 19.7 mL/m(2) predicted diastolic dysfunction with 97% sensitivity and 96% specificity. Compared with normal controls, corrected passive filling and conduit volumes were lower, and corrected active emptying volume was higher in patients with Grade I diastolic dysfunction (0.38 vs. 0.51, P = 0.02; 1.65 vs. 3.29, P < 0.001; 0.59 vs. 0.44, P = 0.001), resulting in a similar corrected total emptying volume (0.97 vs. 0.96, P= ns). Patients with higher grades of diastolic dysfunction, however, had lower corrected passive filling, conduit, active, and total emptying volumes. CONCLUSION: LA remodelling occurs in patients with LV diastolic dysfunction and LA volume expressed the severity of diastolic dysfunction. Initially, the LA compensates for changes in LV diastolic properties by augmenting active atrial contraction. As the severity of diastolic dysfunction increases, this compensatory mechanism fails as atrial mechanical dysfunction sets in, resulting in lower total atrial emptying volume.

Association of Reduced Apical Untwisting With Incident HF in Asymptomatic Patients With HF Risk Factors.

OBJECTIVES: This study investigated the prognostic utility of left ventricular (LV) untwisting (UT) in the elderly patients at risk of heart failure (HF). BACKGROUND: LV UT mechanics represent a unique combination of LV filling linking ventricular relaxation and suction. The value of this parameter in the prediction of outcomes in patients at risk of HF is unclear. METHODS: A group of 465 asymptomatic subjects ≥65 years of age with ≥1 HF risk factor (hypertension, diabetes, obesity), recruited from the community, underwent clinical evaluation and echocardiography including measurement of LV apical and basal peak UT velocities. Cox regression analysis was used to identify predictors of new-onset HF and cardiovascular death after a mean follow-up of 18.2 ± 7.5 months. RESULTS: A composite of both of the study endpoints occurred in 54 patients (11.6%). Adverse outcome was significantly associated with apical (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.96 to 0.99; p = 0.006) UT but not with basal (p = 0.18) UT. The prognostic value of apical UT was independent of and incremental to clinical data, as expressed by the ARIC (Atherosclerosis Risk In Communities) study risk score, left atrial volume index (LAVI), and LV global longitudinal strain (GLS). The addition of apical UT to the model including ARIC risk score, LAVI, and GLS was associated with a 41% improvement in reclassification (p = 0.006). CONCLUSIONS: Echocardiographic assessment of apical UT provides incremental value in predicting adverse outcome in asymptomatic patients with HF risk factors. The inclusion of apical UT to the diagnostic algorithm may improve the prognostication process in this population.