Association between left ventricular global longitudinal strain, health-related quality of life and functional capacity in chronic kidney disease patients with preserved ejection fraction.

AIM: Patients with chronic kidney disease (CKD) have a significant burden of dyspnoea and fatigue in spite having normal left ventricular (LV) ejection fraction (EF). Global longitudinal strain (GLS) can detect subtle changes in LV function. This study aimed to evaluate the relationship between LV function, functional capacity and quality of life (QOL) in CKD patients with preserved EF. METHODS: A cross-sectional study of patients with stage 3/4 CKD (n = 108). Clinical characteristics, biochemical data, functional capacity (6-min walk test (6MWT), timed up and go (TUG) test) and QOL (short form-12 (SF-12v2™) ) were measured. Echocardiogram was used to assess GLS, EF and diastolic function (E/A, e' and E/e'). RESULTS: The mean age was 58.1 ± 9.9 years, 55.6% were men, estimated glomerular filtration rate was 44.8 ± 10.6 mL/min/1.73 m(2), GLS was -18.5 ± 3.6% and 19.4% had impaired GLS (>-16%). Patients with impaired GLS had a significantly shorter 6MWT and slower TUG test compared with patients with preserved GLS. Bivariate analysis showed GLS and E/e' correlated with distance walked in 6MWT (GLS (r = -0.24, P = 0.02); E/e'(r = -0.38, P = 0.002) ). Following adjustment for potential confounders, GLS remained independently associated with 6MWT (model R(2) = 0.37, P < 0.001). Mean physical component summary scores (PCS) and mental component summary scores (MCS) were 43.0 ± 10.2 and 50.9 ± 9.5. There was no cardiac parameter that was independently associated with PCS. However women, lower systolic blood pressure and GLS was associated with lower MCS (model R(2) = 0.30, P < 0.001). CONCLUSION: GLS was associated with measures of functional capacity and QOL in CKD patients with preserved EF.

Left ventricular global longitudinal strain is associated with cardiovascular risk factors and arterial stiffness in chronic kidney disease.

BACKGROUND: Global longitudinal strain (GLS) has emerged as a superior method for detecting left ventricular (LV) systolic dysfunction compared to ejection fraction (EF) on the basis that it is less operator dependent and more reproducible. The 2-dimensional strain (2DS) method is easily measured and integrated into a standard echocardiogram. This study aimed to determine the relationship between GLS and traditional and chronic kidney disease (CKD)-related risk factors of cardiovascular disease (CVD) in patients with CKD. METHODS: A cross sectional study of patients with moderate CKD stages 3 and 4 (n = 136). Clinical characteristics, anthropometric, biochemical data including markers of inflammation [C-reactive protein (CRP)], uremic toxins [indoxyl sulphate (IS), p-cresyl sulphate (PCS)], and arterial stiffness [pulse wave velocity (PWV)] were measured. Inducible ischemia was detected using exercise stress echocardiogram. GLS was determined from 3 standard apical views using 2-dimensional speckle tracking and EF was measured using Simpson's rule. Associations between GLS and traditional and CKD-related risk factors were explored using multivariate models. RESULTS: The study population parameters included: age 59.4 ± 9.8 years, 58 % male, estimated glomerular filtration rate (eGFR) 44.4 ± 10.1 ml/min/1.73 m(2), GLS -18.3 ± 3.6 % and EF 65.8 % ± 7.8 %. This study demonstrated that GLS correlated with diabetes (r = 0.21, p = 0.01), history of heart failure (r = 0.20, p = 0.01), free IS (r = 0.24, p = 0.005) free PCS (r = 0.23, p = 0.007), body mass index (BMI) (r = 0.28, p < 0.001), and PWV (r = 0.24, p = 0.009). Following adjustment for demographic, baseline co-morbidities and laboratory parameters, GLS was independently associated with free IS, BMI and arterial stiffness (R(2) for model = .30, p < 0.0001). CONCLUSIONS: In the CKD cohort, LV systolic function assessed using GLS was associated with uremic toxins, obesity and arterial stiffness.

Subclinical LV dysfunction and 10-year outcomes in type 2 diabetes mellitus.

OBJECTIVE: New imaging techniques have permitted the detection of subclinical LV dysfunction (LVD) in up to half of patients with type 2 diabetes mellitus (DM) with a normal EF. However, the connection between early LVD and prognosis is unclear. This study aimed to define the long-term outcome of LVD associated with type 2 DM. METHODS: In this prospective cohort study, 230 asymptomatic patients with type 2 DM underwent measurement of global longitudinal 2D strain (GLS) for detection of LVD and were followed for up to 10 years. All subjects had normal EF (≥50%) and no evidence of coronary artery disease at recruitment. Outcome data were obtained through centralised state-wide death and hospital admission registries. The primary endpoint was all-cause mortality and hospitalisation. RESULTS: On study entry, almost half (45%) of the cohort had evidence of LVD as detected by GLS. Over a median follow-up of 7.4±2.6 years (range 0.6-9.7 years), 68 patients (30%) met the primary endpoint (LVD: 37%; normal LV function: 24%). GLS was independently associated with the primary endpoint (HR=1.10; p=0.04), as was systolic blood pressure (HR=1.02; p<0.001) and levels of glycosylated haemoglobin (HR=1.28; p=0.011). Patients with LVD had significantly worse outcome than those without (χ(2)=4.73; p=0.030). CONCLUSIONS: Subclinical LVD is common in asymptomatic patients with type 2 DM, is readily detectable by GLS imaging and is independently associated with adverse outcome. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ACTRN12612001178831).

Left Ventricular Global Longitudinal Strain (GLS) Is a Superior Predictor of All-Cause and Cardiovascular Mortality When Compared to Ejection Fraction in Advanced Chronic Kidney Disease.

BACKGROUND: Echocardiographic global longitudinal strain (GLS) is increasingly recognised as a more effective technique than conventional ejection fraction (EF) in detecting subtle changes in left ventricular (LV) function. This study investigated the prognostic value of GLS over EF in patients with advanced Chronic Kidney Disease (CKD). METHODS: The study included 183 patients (57% male, 63% on dialysis) with CKD stage 4, 5 and 5Dialysis (D). 112 (61%) of patients died in a follow up of 7.8 ± 4.4 years and 41% of deaths were due to cardiovascular (CV) disease. GLS was calculated using 2-dimensional speckle tracking and EF was measured using Simpson's biplane method. Cox proportional hazard models were used to assess the association of measures of LV function and all- cause and CV mortality. RESULTS: The mean GLS at baseline was -13.6 ± 4.3% and EF was 45 ± 11%. GLS was a significant predictor of all-cause [Hazard Ratio (HR) 1.09 95%; Confidence Interval (CI) 1.02-1.16; p = 0.01] and CV mortality (HR 1.16 95%; CI 1.04-1.30; p = 0.008) following adjustment for relevant clinical variables including LV mass index (LVMI) and EF. GLS also had greater predictive power for both all- cause and CV mortality compared to EF. Impaired GLS (>-16%) was associated with a 5.6-fold increased unadjusted risk of CV mortality in patients with preserved EF. CONCLUSIONS: In this cohort of patients with advanced CKD, GLS is a more sensitive predictor of overall and CV mortality compared to EF. Studies of larger populations in CKD are required to confirm that GLS provides additive prognostic value in patients with preserved EF.

Cardiorespiratory fitness and cardiovascular burden in chronic kidney disease.

OBJECTIVES: Reduced functional capacity is associated with poor prognosis. In patients with chronic kidney disease the factors that contribute to low cardiorespiratory fitness are unclear. The objective of this study was to evaluate the cardiorespiratory and cardiovascular response to exercise in chronic kidney disease patients, and secondly investigate the relationships between cardiorespiratory fitness and cardiovascular burden. DESIGN: Cross-sectional analysis. METHODS: Baseline demographic, anthropometric and biochemical data were examined in 136 patients with moderate chronic kidney disease (age 59.7±9.6yrs, eGFR 40±9ml/min/1.73m(2), 55% male, 39% with a history of cardiovascular disease, 38% diabetic and 17% current smokers). Cardiorespiratory fitness was measured as peak VO2, left ventricular morphology and function using echocardiography, central arterial stiffness by aortic pulse wave velocity and left ventricular afterload using augmentation index. Physical activity levels were assessed using the Active Australia questionnaire. RESULTS: Peak VO2 (22.9±6.5ml/kg/min) and peak heart rate (148±22bpm) were 17% and 12% lower than the age-predicted values, respectively. The low fit group were significantly older, and were more likely to have type II diabetes, cardiovascular disease, a higher BMI and be less active than the high fit group (P<0.05). The independent predictors of peak VO2 were age, type II diabetes, hemoglobin level, physical activity, aortic pulse wave velocity, augmentation index, and global longitudinal strain. CONCLUSIONS: In patients with chronic kidney disease, the peak VO2 and heart rate response is markedly impaired. Reduced cardiorespiratory fitness is independently associated with increased aortic stiffness, increased left ventricle afterload, poor left ventricle function and higher burden of cardiovascular risk.

The association between left ventricular global longitudinal strain, renal impairment and all-cause mortality.

BACKGROUND: Left ventricular (LV) systolic dysfunction is an important predictor of cardiovascular death. Global longitudinal strain (GLS) is a widely available echocardiographic technique proven to be more sensitive than conventional ejection fraction (EF) in detecting subtle changes in LV function. However, the prognostic value of GLS in patients with chronic kidney disease (CKD) is unknown. METHODS: We studied 447 patients from a single center who were stratified according to estimated glomerular filtration rate (eGFR). GLS was calculated using two-dimensional speckle tracking and EF was measured using Simpson's biplane. Cox proportional hazard model was used to identify independent predictors of survival and measures of discrimination and reclassification were used to assess the predictive value of GLS. Multivariable regression models were used to evaluate clinical and laboratory factors associated with GLS. RESULTS: The mean EF was 58 ± 11% and GLS was -16.6 ± 4.2%. eGFR correlated negatively with GLS (r = -0.14, P = 0.004). Factors that were independently associated with GLS include gender, previous myocardial infarction, eGFR and phosphate (R(2) = 0.16, P < 0.001). Sixty-four patients died in a follow-up of 5.2 ± 1.4 years. GLS remained a significant predictor of all-cause mortality [hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.01-1.15] following adjustment for age, diabetes mellitus, hypertension, eGFR and left ventricular mass index (LVMI). The strength of association between demographic data, eGFR, LVMI and mortality increased following addition of GLS [c-statistic 0.68 (95% CI 0.61-0.74) to 0.71 (95% CI 0.64-0.77), P = 0.04]. Addition of GLS also demonstrated a 21% net reclassification improvement in risk prediction for all-cause mortality over clinical factors. CONCLUSIONS: GLS is an important predictor of all-cause mortality in CKD patients. Traditional and non-traditional risk factors such as phosphate are important determinants of GLS. Strain assessment in CKD patients may provide greater cardiovascular risk stratification.

Hemodynamic benefit of rest and exercise optimization of cardiac resynchronization therapy.

The optimal method of cardiac resynchronization therapy (CRT) optimization is as yet unknown. We sought to investigate the responses of optimization at rest and on exercise. This 2 stage study involved 59 patients (age 65 ± 10, 75% male), who had all recently undergone successful CRT implantation. In the first stage, the 6-month response was compared between 30 individuals who underwent resting echocardiographic optimization of CRT [atrioventricular (AV delay) plus ventriculo-ventricular delays (VV delay)], compared with the 29 who did not. In the second stage, a subset of 37 patients from the original cohort were randomized (double-blind) to either resting echocardiographic optimization (n = 20) or exercise echocardiographic optimization (n = 17) and followed for a further 6 months. Clinical and echocardiographic data were collected at each stage. Patients undergoing rest optimization demonstrated improvement in almost all variables and significantly in B-type natriuretic peptide (BNP) in contrast to those without optimization. In a linear regression model, the only significant predictor of BNP change was whether an individual underwent resting optimization or not (ß = 0.38, P = 0.04). In those undergoing resting optimization, the degree of change in AV delay was correlated with improvement in left ventricle (LV) end-diastolic volume (r(2)  = 0.33, P < 0.01). Optimization on exercise was associated with a significant decrease in 6-minute walk test compared to those randomized to rest optimization possibly due to inducing nonoptimization at rest. In conclusion, echocardiographic optimization of CRT at rest is superior to no optimization or optimization on exercise. Patients with the greatest change in AV delay to reach optimal may undergo greater LV remodeling.

Effects of exercise and lifestyle intervention on cardiovascular function in CKD.

BACKGROUND AND OBJECTIVES: CKD is associated with poor cardiorespiratory fitness (CRF). This predefined substudy determined the effect of exercise training and lifestyle intervention on CRF and explored the effect on cardiovascular risk factors and cardiac and vascular function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between February 2008 and March 2010, 90 patients with stage 3-4 CKD were screened with an exercise stress echocardiogram before enrollment. Patients (n=83) were randomized to standard care (control) or lifestyle intervention. The lifestyle intervention included multidisciplinary care (CKD clinic), a lifestyle program, and aerobic and resistance exercise training for 12 months. CRF (peak Vo2), left ventricular function, arterial stiffness, anthropometric, and biochemical data were collected at baseline and 12 months. RESULTS: Ten percent of randomized patients had subclinical myocardial ischemia at screening and completed the study without incident. There was no baseline difference among 72 patients who completed follow-up (36 in the lifestyle intervention group and 36 in the control group). The intervention increased peak Vo2 (2.8±0.7 ml/kg per minute versus -0.3±0.9 ml/kg per minute; P=0.004). There was small weight loss (-1.8±4.2 kg versus 0.7±3.7 kg; P=0.02) but no change in BP or lipids. Diastolic function improved (increased e' of 0.75±1.16 cm/s versus -0.47±1.0 cm/s; P=0.001) but systolic function was well preserved and did not change. The change in arterial elastance was attenuated (0.11±0.76 mmHg/ml versus 0.76±0.96 mmHg/ml; P=0.01). Δ peak Vo2 was associated with group allocation and improved body composition. CONCLUSIONS: Exercise training and lifestyle intervention in patients with CKD produces improvements in CRF, body composition, and diastolic function.

Impact of spironolactone on vascular, myocardial, and functional parameters in untreated patients with a hypertensive response to exercise.

BACKGROUND: Although a hypertensive response to exercise (HRE) is associated with cardiac risk and masked hypertension (MHT), its mechanisms and appropriate treatment remain unclear. We investigated spironolactone as a treatment for abnormal vascular and myocardial stiffness in HRE. METHODS: In this randomized, double-blind, placebo-controlled study of 115 patients (54 ± 9 years, 57% men) with an HRE (≥210/105 mm Hg in men; ≥190/105 mm Hg in women) but no prior history of hypertension or myocardial ischemia, MHT prevalence was 40%. Patients were randomized to spironolactone 25mg daily (n = 58) or placebo (n = 57) and underwent evaluation at baseline and 3 months with exercise echocardiography, VO2max, pulse wave velocity (PWV), exercise and central blood pressure (BP), and 24-hour ambulatory BP. Changes in left ventricular mass index (LVMI), Doppler-derived E/em ratio (LV filling pressure), and myocardial strain were assessed. RESULTS: Baseline 24-hour systolic BP (SBP) was 133 ± 10 mm Hg and peak-exercise SBP was 219 ± 16 mm Hg. Peak systolic strain (0.3 ± 3.6% vs. -0.1 ± 3.2, P = 0.56), E/em (-1.1 ± 2.3 vs. -0.6 ± 1.7, P = 0.30), VO(2max) (0.4 ± 4.9 vs. -0.9 ± 4.1 ml/kg/min, P = 0.15), and adjusted PWV did not significantly change with treatment, despite reduction in exercise SBP, 24-hour SBP, and LVMI. The change in exercise E/em was of borderline significance (-0.3 ± 2.4 vs. 0.8 ± 2.8, P = 0.06) and became significant after adjustment for baseline differences (P = 0.01). Patients with higher LVMI significantly increased VO(2max) (1.1 ± 5.6 vs. -2.4 ± 4.4 ml/kg/min, P < 0.05) and reduced exercise E/e(m) (-0.7 ± 2.7 vs. 1.9 ± 2.8, P < 0.05). CONCLUSIONS: In HRE patients without previous hypertension, short-term spironolactone reduced exercise BP, 24-hour ambulatory BP, LVMI, and E/e(m) but did not significantly alter exercise capacity or myocardial strain.

Acute elevation of lipids does not alter exercise hemodynamics in healthy men: A randomized controlled study.

OBJECTIVE: Exaggerated exercise blood pressure (BP) predicts mortality. Some studies suggest this could be explained by chronic hyperlipidemia, but whether acute-hyperlipidemia effects exercise BP has never been tested, and was the aim of this study. METHODS: Intravenous infusion of saline (control) and Intralipid were administered over 60 min in 15 healthy men by double-blind, randomized, cross-over design. Brachial and central BP (including, pulse pressure, augmentation pressure and augmentation index), cardiac output and systemic vascular resistance were recorded at rest and during exercise. RESULTS: Compared with control, Intralipid caused significant increases in serum triglycerides, very low density lipoproteins and free fatty acids (p < 0.001 for all). However, there was no significant difference for any exercise hemodynamic variable (p > 0.05 for all). CONCLUSION: Acute-hyperlipidemia does not significantly change exercise hemodynamics in healthy males. Therefore, the association between raised lipids and increased exercise BP is likely due to the chronic effects of hyperlipidemia.

Cardiac dimensions are largely determined by dietary salt in patients with primary aldosteronism: results of a case-control study.

CONTEXT: Animal studies have demonstrated that dietary sodium intake is a major influence in the pathogenesis of aldosterone-induced effects in the heart such as left ventricular (LV) hypertrophy and fibrosis. LV hypertrophy is an important predictor for cardiovascular morbidity and mortality. OBJECTIVE: We aimed to investigate the relationships between aldosterone and dietary salt and LV dimensions in patients with primary aldosteronism (PA). DESIGN AND PARTICIPANTS: This case-control study included 21 patients with confirmed PA and 21 control patients with essential hypertension matched for age, gender, duration of hypertension, and 24-h systolic and diastolic blood pressure. MAIN OUTCOME MEASURES: Patients were evaluated by echocardiography and 24-h urinary sodium (UNa) excretion while consuming their usual diets. RESULTS: Patients with PA had significantly greater mean LV end-diastolic diameter, interventricular septum and posterior wall thicknesses, LV mass (LVM) and LV mass index, and end systolic and diastolic volumes than control patients. UNa significantly positively correlated with interventricular septum, posterior wall thicknesses, and LVM in the patients with PA but not in control patients. In a multivariate analysis, UNa was an independent predictor for LV wall thickness and LV mass among the patients with PA but not in patients with essential hypertension. CONCLUSIONS: These findings emphasize the importance of dietary sodium in determining the degree of cardiac damage in those patients with PA, and we suggest that aldosterone excess may play a permissive role. In patients with PA, because a high-salt diet is associated with greater LVM, dietary salt restriction might reduce cardiovascular risk.

Contribution of abnormal central blood pressure to left ventricular filling pressure during exercise in patients with heart failure and preserved ejection fraction.

BACKGROUND: Hypertension is ubiquitous in patients with heart failure and preserved ejection fraction (HFpEF) and contributes to arterial and ventricular stiffening. Exertional dyspnea may result from diastolic dysfunction with exercise; however, the association of central blood pressure (BP) to left ventricular filling pressure during exercise has not been assessed in this population and was the aim of this study. METHODS: Fifteen patients with HFpEF and 15 age-matched and sex-matched controls were studied at rest, during submaximal and immediately after maximal exercise. Simultaneous echocardiography and radial tonometry was performed to measure E/e' and central BP, defined by central augmented pressure (C_AP) and augmentation index (AIx). RESULTS: Patients with HFpEF had higher E/e' (P = 0.020) and peripheral and central BP (P < 0.001) at rest, yet similar C_AP and AIx to controls (P > 0.05). There was a large increase in E/e' with exercise in patients (P = 0.012) but no change in C_AP or AIx. Importantly, the change in E/e' from rest to submaximal exercise was significantly and independently associated with ΔC_AP (r = 0.559; P = 0.030) and ΔAIx (r = 0.654; P = 0.008) in patients with HFpEF. In contrast with the controls, E/e', C_AP and AIx decreased with exercise and there were no associations between exercise E/e' and central or peripheral BP (P > 0.05 for all). CONCLUSION: Indices of central BP are associated with the left ventricular diastolic response to exercise in patients with HFpEF. Arterial function and central hemodynamics may be important targets for treating symptoms associated with raised left ventricular filling pressure with exertion.

Application of an exercise intervention on the evolution of diastolic dysfunction in patients with diabetes mellitus: efficacy and effectiveness.

BACKGROUND: Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes. We studied the impact of an exercise-based lifestyle intervention on the evolution of DD in patients with type 2 diabetes mellitus (T2DM) and prospectively investigated the clinical correlates of DD progression. METHODS AND RESULTS: A total of 223 outpatients with T2DM were randomized to supervised exercise-based lifestyle intervention (initial gym-based program and lifestyle and diet advice followed by telephone-guided supervision) or usual care. Patients underwent echocardiographic assessment of diastolic function and metabolic and clinical evaluation at baseline and 3 years. Changes in prevalence and evolution of DD were assessed and correlations sought with clinical and metabolic variables. DD was present in 50% of patients at baseline and 54% at 3 years, with no difference between the usual care and intervention groups (60% versus 48%, P=0.10). Abnormal DD at the final visit was independently associated with older age and a decrease in peak oxygen consumption over time (P<0.05). There was no impact on glycemic control or exercise capacity. In a subanalysis restricted to patients who finished the full 3-year follow-up, control subjects were independently associated with DD at 3 years (ß=0.90; odds ratio, 2.46; P=0.034), with the only other independent correlate being older age (ß=0.05; odds ratio, 1.06; P=0.019). CONCLUSIONS: Despite being efficacious in the subgroup who completed 3 years of exercise-based lifestyle intervention, randomization to this program was not effective in reducing progression of subclinical DD in patients with T2DM, which may reflect the recognized difficulty of adherence to prolonged exercise intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12607000060448.

Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction.

Acute elevation of circulating lipids, such as the postprandial state, contributes to increased cardiovascular risk. However, the effect of acutely elevated triglycerides on arterial and left ventricular function is not completely understood. We aimed to assess whether an acute increase in triglycerides affects ventricular-vascular interaction. Fifteen healthy men (age, 49 ± 8 yr) underwent blinded, randomized infusion of saline and intravenous fat emulsion to acutely raise plasma triglycerides. All subjects underwent both randomization trials, in random order on two separate days. Ventricular-vascular interaction measures were recorded by tonometry (central blood pressure) and echocardiography (left ventricular volumes, strain, and strain rate) at baseline and after 1 h infusion. Net ventricular-vascular interaction was defined by the effective arterial elastance (E(A))-to-left ventricular end-systolic elastance (E(LV)) ratio (E(A)/E(LV)). When compared with saline, the infusion of intravenous fat emulsion increased triglycerides and free fatty acids (ΔP < 0.001 for both) and improved left ventricular contractility (ΔE(LV), end-systolic volume and strain rate; P < 0.05 for all). However, arterial function was unchanged (ΔE(A), brachial and central blood pressure; P > 0.05 for all). Overall, E(A)/E(LV) was decreased by an infusion of intravenous fat emulsion (P = 0.004) but not saline (P > 0.05, P = 0.001 for Δ between trials). We conclude that intravenous fat emulsion and acute elevation of blood lipids (including triglycerides and free fatty acids) alter ventricular-vascular interaction by increasing left ventricular contractility without affecting arterial load. These findings may have implications for cardiovascular responses to parenteral nutrition.

Association of masked hypertension and left ventricular remodeling with the hypertensive response to exercise.

BACKGROUND: A hypertensive response to exercise (HRE; defined as normal clinic blood pressure (BP) and exercise systolic BP (SBP) ≥210 mm Hg in men or ≥190 mm Hg in women, or diastolic BP (DBP) ≥105 mm Hg) independently predicts mortality. The mechanisms remain unclear but may be related to masked hypertension. This study aimed to assess the prevalence of masked hypertension and its association with cardiovascular risk factors, including left ventricular (LV) mass, in patients with a HRE. METHODS: Comprehensive clinical and echocardiographic evaluation (including central BP, aortic pulse wave velocity by tonometry) and 24-h ambulatory BP monitoring (ABPM) were performed in 72 untreated patients with HRE (aged 54 ± 9 years; 60% male; free from coronary artery disease confirmed by exercise stress echocardiography). Masked hypertension was defined according to guidelines as daytime ABPM ≥135/85 mm Hg and clinic BP <140/90 mm Hg. RESULTS: Masked hypertension was present in 42 patients (58%). These patients had higher LV mass index (41.5 ± 8.7 g/m(2.7) vs. 35.9 ± 8.5 g/m(2.7); P = 0.01), LV relative wall thickness (RWT; 0.42 ± 0.09 vs. 0.37 ± 0.06; P = 0.004) and exercise SBP (222 ± 17 mm Hg vs. 212 ± 14 mm Hg; P = 0.01), but no significant difference in aortic pulse wave velocity or central pulse pressure (P > 0.05 for both). The strongest independent determinant of LV mass index was the presence of masked hypertension (unstandardized ß = 5.6; P = 0.007), which was also independently related to LV RWT (unstandardized ß = 0.04; P = 0.03). CONCLUSIONS: Masked hypertension is highly prevalent in HRE patients with a normal resting office BP and is associated with increased LV mass index and RWT. Clinicians should consider measuring ABPM or home BP in HRE patients.

Effects of myocardial ischaemia on left ventricular untwist and filling pressure.

OBJECTIVE: To link ischaemia, left ventricular (LV) untwisting and changes in filling pressure during dobutamine stress echocardiography (DSE). DESIGN: Cross-sectional study at rest and at peak dobutamine stress. SETTING: Academic medical centre. PATIENTS: Patients who had undergone routine DSE between January and September 2009. METHODS: Routine DSE was combined with measurement of transmitral pulsed-wave Doppler, myocardial tissue Doppler and speckle-tracking echocardiography at baseline and peak dose in 110 patients (51 women, 62±12 years). Untwisting rates (proto-diastolic and during isovolumic relaxation time (IVRT)) were measured by speckle tracking. Raised filling pressure was defined as E/e'>15. DSE studies were classified into normal, ischaemic or scar responses, independent of E/e'. MAIN OUTCOMES: Echocardiographic outcomes. RESULTS: Patients were categorised in three groups: group 1 (n=44), normal resting and peak E/e'; group 2 (n=33), normal resting E/e' but raised peak E/e'; group 3 (n=33), abnormal resting E/e'. Risk factors and resting ejection fraction were similar in each group. Proto-diastolic untwisting rate was an independent predictor of raised filling pressure at peak stress (r(2)=0.3, p=0.03). An abnormal filling response during DSE was independently predicted by resting untwisting rate (UTR)-IVRT (p=0.003), and resting E/a (p=0.0001) (model pseudo-r(2)=0.76). Proto-diastolic UTR was lower in the ischaemic and scar groups at peak. CONCLUSION: Patients with abnormal filling pressure response have an impaired LV untwisting rate during isovolumic relaxation. This phenomenon supports the role of impaired LV suction as the mediator of the effect of myocardial ischaemia during DSE on filling pressure response to stress.

Usefulness of at rest and exercise hemodynamics to detect subclinical myocardial disease in type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (T2DM) might have subclinical myocardial dysfunction identified at rest or unmasked during exercise. We examined the correlates of the myocardial exercise response in patients with T2DM. Myocardial dysfunction was sought during at rest and exercise echocardiography in 167 healthy patients with T2DM (97 men, 55 ± 10 years). Myocardial ischemia was excluded using stress echocardiography. Standard echocardiography and color tissue Doppler imaging measures (early diastolic tissue velocity [Em], strain, and strain rate) were acquired at baseline and peak stress. The calibrated integrated backscatter was calculated from the at rest parasternal long-axis view. The longitudinal diastolic functional reserve index after exercise was defined as ΔEm [1 - (1/Em(base))]. The clinical, anthropometric, and metabolic data were collected at rest and stress. Subclinical myocardial dysfunction at baseline (n = 24) was independently associated with weight (odds ratio [OR] 1.02, p = 0.04) and hemoglobin A1c (OR 1.36, p = 0.03). This group displayed an impaired exercise response that was independently associated with a reduced exercise capacity (OR 0.84, p = 0.034) and longitudinal diastolic functional reserve index (OR 0.69, p = 0.001). Inducible myocardial dysfunction (stress Em <-9.9 cm/s) was identified after exercise in 70 of the remaining 143 subjects. This finding was associated with calibrated integrated backscatter (OR 1.08, p = 0.04) and lower peak heart rate (OR 0.97, p = 0.002) but not metabolic control. The intensity of the metabolic derangement in patients with T2DM was associated with subclinical at rest myocardial dysfunction, but not with the myocardial exercise response. In conclusion, the association of an abnormal stress response with nonmetabolic factors, including backscatter and blunted peak heart rate, suggests potential roles for myocardial fibrosis and cardiac autonomic neuropathy in patients with nonischemic diabetic heart disease.

Lifestyle change diminishes a hypertensive response to exercise in type 2 diabetes.

PURPOSE: A hypertensive response to exercise (HRE) is common in patients with type 2 diabetes and is associated with increased left ventricular (LV) mass and mortality. This study aimed to determine whether lifestyle modification would improve exercise blood pressure (BP) and reduce LV mass in patients with type 2 diabetes. METHODS: One hundred and eighty-five patients with type 2 diabetes were randomized to 1 yr of lifestyle intervention (n=97, mean ± SD age=54.7 ± 11.3 yr, 51% men) or usual care (control; n=88, age=53.8 ± 8.1 yr, 61% men). Brachial BP was measured at rest and during a graded maximal exercise test at baseline and 1 yr. Patients also underwent two-dimensional echocardiography to determine LV dimensions. A subgroup of 61 patients had resting and exercise central BP estimated from radial tonometry. An HRE was defined as a maximal exercise systolic BP of ≥210 mm Hg for men and ≥190 mm Hg for women. RESULTS: At study entry, there were 101 patients (55%) with an HRE (n=51 controls). Compared with controls, lifestyle intervention significantly reduced the propensity to develop an HRE in those participants who did not have HRE at baseline (29.8% vs 59.5%, P=0.006). However, absolute values of exercise and resting (brachial and central) BP and LV mass were not significantly changed (all P values >0.05). There were significant (all P values <0.05) improvements in V˙O2max, body mass index, plasma glucose, insulin resistance, and HDL cholesterol after lifestyle intervention compared with control. CONCLUSIONS: Lifestyle intervention significantly attenuates the development of an HRE but does not reduce cardiac size after 1 yr in patients with type 2 diabetes.

Reduced end-systolic pressure-volume ratio response to exercise: a marker of subclinical myocardial disease in type 2 diabetes.

BACKGROUND: Limitations in the predictive value of negative exercise echocardiography in type 2 diabetes mellitus has been linked to a reduced end-systolic pressure-volume response (ESPVR). We sought whether abnormal ESPVR reflected subclinical diabetic heart disease by examining the association between the ESPVR and markers of myocardial dysfunction and to establish if the change (Delta) or peak systolic blood pressure/end-systolic left ventricular volume ratio (SP/ESV) is a better marker of contractile reserve in type 2 diabetes mellitus. METHODS AND RESULTS: Resting and exercise echocardiography was performed in 167 apparently healthy patients with type 2 diabetes mellitus (97 men; age, 55+/-10 years) without ischemia, other cardiac disease, or noncardiac complications of diabetes. Standard echocardiographic and color tissue Doppler measures (early diastolic tissue velocity, strain, and strain rate) were acquired at baseline and peak stress in apical long-axis views. Calibrated integrated backscatter was calculated from a resting parasternal long-axis view. DeltaSP/ESV was calculated as [(peak stress SP/ESV)-(rest SP/ESV)]. The 83 subjects who demonstrated a DeltaSP/ESV < or =12 mm Hg/mL/m(2) after exercise were older and had lower peak heart rate, resting diastolic and stress systolic tissue velocity, stress ejection fraction, and exercise capacity than the remainder. There was no significant association between DeltaSP/ESV and metabolic derangement or echocardiographic measures of deformation or backscatter. Change in Sm and stress ejection fraction were independent correlates of DeltaSP/ESV. CONCLUSIONS: DeltaSP/ESV ratio is associated with established features of subclinical diabetic heart disease as well as determinants of contractile reserve (peak hemodynamic response and stress systolic function). Peak ESPVR is poorly associated with markers of myocardial dysfunction.

Assessment of myocardial viability at dobutamine echocardiography by deformation analysis using tissue velocity and speckle-tracking.

OBJECTIVES: Comparison of myocardial tissue-velocity imaging (TVI) and speckle-tracking echocardiography (STE) for prediction of viability at dobutamine echocardiography (DbE). BACKGROUND: Use of TVI-based strain imaging during DbE may facilitate the prediction of myocardial viability but has technical limitations. STE overcomes these but requires evaluation for prediction of viability. METHODS: We studied 55 patients with ischemic heart disease and left ventricular systolic dysfunction (left ventricular ejection fraction <0.45) who were undergoing DbE for assessment of myocardial viability and who subsequently underwent myocardial revascularization. TVI was used to measure longitudinal end-systolic strain (longS) and peak systolic strain rate (SR) at rest and at low-dose dobutamine (LDD). Longitudinal, radial, and circumferential strain and strain rate were measured with STE. Segmental functional recovery was defined by improved wall-motion score on side-by-side comparison of echocardiographic images before and 9 months after revascularization and areas under the receiver operator characteristic curves were used to compare methods. RESULTS: Of the 375 segments with abnormal resting function, 154 (41%) showed functional recovery. Only circumferential resting and low-dose STE strain and low-dose longitudinal strain and SR predicted functional recovery independent of wall-motion analysis. Among different strain parameters, only TVI-based longitudinal end-systolic strain and peak systolic SR at LDD had incremental value over wall-motion analysis (areas under the receiver operator characteristic curves of 0.79, 0.79, and 0.74, respectively). STE measurements of strain and SR identified viability only in the anterior circulation, whereas TVI strain and SR accurately identified viability in both anterior and posterior circulations. CONCLUSIONS: Combination of TVI or STE methods with DbE can predict viability, with TVI strain and SR at LDD being the most accurate. TVI measures can predict viability in both anterior and posterior circulations, but STE measurements predict viability only in the anterior circulation.