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.

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.

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.

Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab.

BACKGROUND: Trastuzumab prolongs survival in patients with human epidermal growth factor receptor type 2-positive breast cancer. Sequential left ventricular (LV) ejection fraction (EF) assessment has been mandated to detect myocardial dysfunction because of the risk of heart failure with this treatment. Myocardial deformation imaging is a sensitive means of detecting LV dysfunction, but this technique has not been evaluated in patients treated with trastuzumab. The aim of this study was to investigate whether changes in tissue deformation, assessed by myocardial strain and strain rate (SR), are able to identify LV dysfunction earlier than conventional echocardiographic measures in patients treated with trastuzumab. METHODS: Sequential echocardiograms (n = 152) were performed in 35 female patients (51 +/- 8 years) undergoing trastuzumab therapy for human epidermal growth factor receptor type 2-positive breast cancer. Left ventricular EF was measured by 2- and 3-dimensional (2D and 3D) echocardiography, and myocardial deformation was assessed using tissue Doppler imaging and 2D-based (speckle-tracking) strain and SR. Change over time was compared every 3 months between baseline and 12 months. RESULTS: There was no overall change in 3D-EF, 2D-EF, myocardial E-velocity, or strain. However, there were significant reductions seen in tissue Doppler imaging SR (P < .05), 2D-SR (P < .001), and 2D radial SR (P < .001). A drop > or =1 SD in 2D longitudinal SR was seen in 18 (51%) patients; 13 (37%) had a similar drop in radial SR. Of the 18 patients with reduced longitudinal SR, 3 had a concurrent reduction in EF > or =10%, and another 2 showed a reduction over 20 months follow-up. CONCLUSIONS: Myocardial deformation identifies preclinical myocardial dysfunction earlier than conventional measures in women undergoing treatment with trastuzumab for breast cancer.

Gender differences in systolic tissue velocity: role of left ventricular length.

AIMS: Previous research has described differences in left ventricular (LV) systolic tissue velocity between genders. This study aimed to determine the association between LV tissue velocity and LV size in healthy controls and in those with type 2 diabetes (T2DM). METHODS AND RESULTS: LV tissue velocities were measured in 71 controls and 222 patients with T2DM by pulsed-wave Doppler and colour-coded tissue Doppler (TDI) during systole (S' and S(m)) and diastole (early, E' and E(m), and late, A' and A(m)) at the basal septum and lateral wall. Both systolic tissue velocities were higher in males than in females within controls (S': 7.3 +/- 1.2 vs. 6.6 +/- 1.0 cm/s; P = 0.017, S(m): 6.2 +/- 1.0 vs. 5.5 +/- 0.7 cm/s; P = 0.002) but only by colour-coded TDI in patients with T2DM (S(m): 5.7 +/- 1.7 vs. 4.9 +/- 1.7 cm/s; P = 0.025). Correction for LV length negated the difference between genders in the controls and patients with T2DM (P > 0.05 for all). In controls, LV length was the strongest predictor of S' (beta = 0.393, P = 0.002), whereas height was the strongest predictor of S(m) (beta = 0.394, P = 0.003). CONCLUSION: In controls, systolic tissue velocities are significantly higher in males compared with females, which may be explained by the increased chamber size of men.

Use of body weight and insulin resistance to select obese patients for echocardiographic assessment of subclinical left ventricular dysfunction.

Obesity is associated with heart failure. Recognition of subclinical left ventricular (LV) dysfunction may permit the initiation of therapy to prevent the development of heart failure. In this study of anthropometric, biochemical, and echocardiographic measurements in 295 healthy overweight subjects, we sought to investigate the effect of insulin resistance and severity of obesity on LV function and to establish a strategy for detection of LV dysfunction using metabolic and echocardiographic measurements. Correlates of subclinical dysfunction (defined from myocardial deformation in a matched group of 98 slim controls) were sought, and receiver operator characteristic curves for clinical and laboratory parameters were performed to identify optimal cutoffs to permit an effective diagnostic strategy. Subclinical impairment of LV function (average strain<18%) was present in 124 subjects (42%), and 52% of severely obese patients (body mass index [BMI]>35 kg/m2). Independent correlates of strain were BMI (beta=-0.25, p<0.0001), fasting insulin (beta=-0.22, p<0.001), and age (beta=-0.18, p<0.003). In patients with a BMI<35 kg/m2, subclinical impairment was uncommon in the absence of hyperinsulinemia. Using a BMI<35 kg/m2 and an insulin level<13 mIU/L to select patients for further testing allowed echocardiography to be avoided in 35% of subjects in whom the prevalence of LV dysfunction was low. In conclusion, obesity and insulin resistance are important contributors to LV dysfunction, a deleterious effect of hyperinsulinemia on LV performance is particularly seen in overweight and moderately obese subjects, and the combination of BMI, fasting insulin, and echocardiography appears optimal for efficient identification of subclinical LV dysfunction in overweight and obese subjects.

Patients with type 2 diabetes have exaggerated brachial and central exercise blood pressure: relation to left ventricular relative wall thickness.

BACKGROUND: A hypertensive response to exercise has prognostic significance. Patients with type 2 diabetes have vascular abnormalities which may predispose to exaggerated brachial and central blood pressure (BP) during exercise. This study aimed to test this hypothesis and to determine the clinical significance of high exercise BP by examining its relation to left ventricular (LV) mass. METHODS: Brachial and central BP were recorded at rest and in response to maximal exercise in 73 diabetic patients (aged 54 +/- 10 years) and 73 controls (aged 53 +/- 12 years). Brachial BP was recorded using mercury sphygmomanometry and LV mass using 2D-echocardiography. Central BP was estimated by radial tonometry using an exercise-validated generalized transfer function. RESULTS: At rest there were no significant (P > 0.05) differences between groups in brachial or central BP. The diabetic patients had significantly increased exercise brachial systolic BP (SBP: 199 +/- 25 mm Hg vs. 185 +/- 21 mm Hg; P = 0.002) and central SBP (158 +/- 17 mm Hg vs. 149 +/- 15 mm Hg; P = 0.002). There was a significantly higher prevalence of an exaggerated exercise BP response (> or =210/105 mm Hg; men and > or =190/105 mm Hg; women) in the diabetic patients (51% vs. 22%; P < 0.01). Compared with those with normal exercise BP, LV relative wall thickness (RWT) was significantly higher (0.41 +/- 0.09 vs. 0.36 +/- 0.08; P < 0.05) and LV hypertrophy was more prevalent (35% vs. 16%; P < 0.05) in those with a hypertensive response. After accounting for other confounding variables, exercise central SBP remained independently associated with LV RWT (beta = 0.22; P = 0.006). CONCLUSION: Diabetic patients are more likely to exhibit exaggerated exercise BP. Regardless of disease status, high exercise central SBP may contribute to cardiovascular risk via adverse cardiac remodeling.

Prognostic role of subclinical left ventricular abnormalities and impact of transplantation in chronic kidney disease.

OBJECTIVE: The outcome of patients with chronic kidney disease (CKD) is influenced by overt left ventricular (LV) abnormalities. We sought the predictive value and treatment response of subclinical LV dysfunction in CKD. METHOD: Resting and dobutamine stress echocardiography were used to identify LV enlargement, dysfunction, or ischemia in 176 patients with CKD. In 129 patients who had normal dobutamine stress echocardiography, myocardial tissue characterization was performed using tissue Doppler imaging and integrated backscatter. Clinical, biochemical, and echocardiographic parameters were recorded at baseline, and patients were followed up for cardiac events and all-cause mortality over 2.4 years. Follow-up echocardiographic and tissue characterization parameters were performed in 80 patients. RESULTS: Previous cardiac history (HR 5.2, P = .002) and serum phosphate (HR 6.2, P = .001) were independent clinical predictors of events (model chi2 = 20.9). Diastolic tissue velocity (HR 0.8, P = .05) was an independent predictor of outcome, and its addition to clinical assessment added incremental prognostic information (model chi2 = 24.8, P < .001). Patients who underwent transplantation (n = 45) showed reduction of wall thickness (P < .001) and LV volumes (P < .001) and increases in diastolic tissue velocity (P = .007) and strain (P = .001), whereas these measurements worsened in those who remained on dialysis. CONCLUSION: In patients with CKD, subclinical LV dysfunction is associated with adverse outcome. Subclinical disease can be improved by transplantation but progresses in patients who continue on dialysis.

Comparison of two-dimensional speckle and tissue velocity based strain and validation with harmonic phase magnetic resonance imaging.

Two-dimensional (2-D) strain (epsilon2-D) on the basis of speckle tracking is a new technique for strain measurement. This study sought to validate epsilon2-D and tissue velocity imaging (TVI)-based strain (epsilonTVI) with tagged harmonic-phase (HARP) magnetic resonance imaging (MRI). Thirty patients (mean age 62 +/- 11 years) with known or suspected ischemic heart disease were evaluated. Wall motion (wall motion score index 1.55 +/- 0.46) was assessed by an expert observer. Three apical images were obtained for longitudinal strain (16 segments) and 3 short-axis images for radial and circumferential strain (18 segments). Radial epsilonTVI was obtained in the posterior wall. HARP MRI was used to measure principal strain, expressed as maximal length change in each direction. Values for epsilon2-D, epsilonTVI, and HARP MRI were comparable for all 3 strain directions and were reduced in dysfunctional segments. The mean difference and correlation between longitudinal epsilon2-D and HARP MRI (2.1 +/- 5.5%, r = 0.51, p <0.001) were similar to those between longitudinal epsilonTVI and HARP MRI (1.1 +/- 6.7%, r = 0.40, p <0.001). The mean difference and correlation were more favorable between radial epsilon2-D and HARP MRI (0.4 +/- 10.2%, r = 0.60, p <0.001) than between radial epsilonTVI and HARP MRI (3.4 +/- 10.5%, r = 0.47, p <0.001). For circumferential strain, the mean difference and correlation between epsilon2-D and HARP MRI were 0.7 +/- 5.4% and r = 0.51 (p <0.001), respectively. In conclusion, the modest correlations of echocardiographic and HARP MRI strain reflect the technical challenges of the 2 techniques. Nonetheless, epsilon2-D provides a reliable tool to quantify regional function, with radial measurements being more accurate and feasible than with TVI. Unlike epsilonTVI, epsilon2-D provides circumferential measurements.

Alterations of left ventricular myocardial characteristics associated with obesity.

BACKGROUND: Obesity is associated with heart failure, but an effect of weight, independent of comorbidities, on cardiac structure and function is not well established. We sought whether body mass index (BMI) and insulin levels were associated with subclinical myocardial disturbances. METHODS AND RESULTS: Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and early diastolic velocity (em), strain and strain rate imaging and tissue characterization with cyclic variation (CVIB), and calibrated integrated backscatter (cIB) were obtained in 109 overweight or obese subjects and 33 referents (BMI <25 kg/m2). BMI correlated with left ventricular (LV) mass and wall thickness (P<0.001). Severely obese subjects (BMI >35) had reduced LV systolic and diastolic function and increased myocardial reflectivity compared with referents, evidenced by lower average long-axis strain, sm, cIB, lower CVIB, and reduced em, whereas LV ejection fraction remained normal. Differences in regional or global strain, sm, and em were identified between the severely obese (BMI >35) and the referent patients (P<0.001). Similar but lesser degrees of reduced function by sm, em, and basal septal strain and increased reflectivity by cIB were present in overweight (BMI, 25 to 29.9) and mildly obese (BMI, 30 to 35) groups (P<0.05). Although tissue Doppler measures were not associated with duration of obesity, they did correlate with fasting insulin levels and reduced exercise capacity. BMI was independently related to average LV strain (beta=0.40, P=0.02), sm (beta=-0.36, P=0.002), and em (beta=-0.41, P<0.001). CONCLUSIONS: Overweight subjects without overt heart disease have subclinical changes of LV structure and function even after adjustment for mean arterial pressure, age, gender, and LV mass.

Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure.

BACKGROUND: Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study. METHODS AND RESULTS: Thirty medically treated ambulatory hypertensive patients (19 women, age 62+/-6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A <1, E deceleration time >250 m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31+/-5 kg/m2) with reduced treadmill exercise capacity (6.7+/-2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133+/-17/80+/-7 mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: -1.57+/-0.46 s(-1) versus 6-months: -1.91+/-0.36 s(-1), P<0.01), peak systolic strain (-20.3+/-5.0% versus -26.9+/-4.3%, P<0.001), and CVIB (7.4+/-1.7 dB versus 8.6+/-1.7 dB, P=0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P=0.05, P=0.02, and P=0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P=0.04) and a trend to reduced left atrial area (P=0.09). CONCLUSIONS: Aldosterone antagonism improves myocardial function in hypertensive heart disease.

Evidence for abnormal left ventricular structure and function in normotensive individuals with familial hyperaldosteronism type I.

OBJECTIVES: To explore whether aldosterone excess can induce adverse cardiovascular effects independently of effects on blood pressure (BP), we sought evidence of disturbed cardiovascular structure or function in normotensive individuals with primary aldosteronism. METHODS: Eight normotensive subjects with genetically proven familial hyperaldosteronism type I (FH-I) were compared with 24 age- and sex-matched normotensive controls in terms of BP, biochemical parameters, pulse wave velocity, and echocardiographic characteristics. RESULTS: Subjects with FH-I demonstrated higher serum aldosterone levels and aldosterone/renin ratios than controls, as expected. Despite having similar 24-h ambulatory BPs, subjects with FH-I demonstrated evidence of concentric remodeling with greater septal (mean +/- sd, 9.4 +/- 1.1 vs. 7.9 +/- 0.9 mm; P < 0.001), posterior wall (9.2 +/- 1.7 vs. 7.7 +/- 1.0 mm; P < 0.01), and relative wall (0.29 +/- 0.03 vs. 0.24 +/- 0.02; P < 0.001) thicknesses, and lower mitral early peak velocities (0.74 +/- 0.10 vs. 0.90 +/- 0.16 m/sec; P < 0.05), ratios of early to late peak diastolic transmitral flow velocity (1.56 +/- 0.24 vs. 2.06 +/- 0.41; P < 0.01), and myocardial early peak velocities (8.3 +/- 1.8 vs. 10.3 +/- 2.6 cm/sec; P < 0.05). There were no significant differences in pulse wave velocity or left ventricular ejection fraction, long axis strain rate, peak systolic strain, cyclic variation of integrated backscatter, or posterior wall calibrated integrated backscatter. CONCLUSIONS: Aldosterone excess is associated with increased left ventricular wall thicknesses and reduced diastolic function, even in the absence of hypertension.

Patients with a hypertensive response to exercise have impaired systolic function without diastolic dysfunction or left ventricular hypertrophy.

OBJECTIVES: We sought to determine if a hypertensive response to exercise (HRE) is associated with myocardial changes consistent with early hypertensive heart disease. BACKGROUND: An HRE predicts the development of chronic hypertension (HT) and may reflect a preclinical stage of HT. METHODS: Patients with a normal left ventricular (LV) ejection fraction and a negative stress test were recruited into three matched groups: 41 patients (age 56 +/- 10 years) with HRE (>210/105 mm Hg in men; >190/105 in women), comprising 22 patients with (HT+) and 19 without resting hypertension (HT-); and 17 matched control subjects without HRE. Long-axis function was determined by measurement of the strain rate (SR), peak systolic strain, and cyclic variation (CV) of integrated backscatter in three apical views. RESULTS: An HRE was not associated with significant differences in LV mass index. Exercise performance and diastolic function were reduced in HRE(HT+) patients, but similar in HRE(HT-) patients and controls. Systolic dysfunction (peak systolic strain, SR, and CV) was significantly reduced in HRE patients (p < 0.001 for all). These reductions were equally apparent in patients with and without a history of resting HT (p = NS) and were independent of LV mass index and blood pressure (p < 0.01). CONCLUSIONS: An HRE is associated with subtle systolic dysfunction, even in the absence of resting HT. These changes occur before the development of LV hypertrophy or detectable diastolic dysfunction and likely represent early hypertensive heart disease.

Patients with early diabetic heart disease demonstrate a normal myocardial response to dobutamine.

OBJECTIVES: We sought to use quantitative markers of the regional left ventricular (LV) response to stress to infer whether diabetic cardiomyopathy is associated with ischemia. BACKGROUND: Diabetic cardiomyopathy has been identified in clinical and experimental studies, but its cause remains unclear. METHODS: We studied 41 diabetic patients with normal resting LV function and a normal dobutamine echo and 41 control subjects with a low probability of coronary disease. Peak myocardial systolic velocity (Sm) and early diastolic velocity (Em) in each segment were averaged, and mean Sm and Em were compared between diabetic patients and controls and among different stages of dobutamine stress. RESULTS: Both Sm and Em progressively increased from rest to peak dobutamine stress. In the diabetic group, Sm was significantly lower than in control subjects at baseline (4.2 +/- 0.9 cm/s vs. 4.7 +/- 0.9 cm/s, p = 0.012). However, Sm at a low dose (6.0 +/- 1.3), before peak (8.4 +/- 1.8), and at peak stress (8.9 +/- 1.8) in diabetic patients was not significantly different from that of controls (6.3 +/- 1.4, 8.9 +/- 1.6, and 9.6 +/- 2.1 cm/s, respectively). The Em (cm/s) in the diabetic group (rest: 4.2 +/- 1.2; low dose: 5.0 +/- 1.4; pre-peak: 5.3 +/- 1.1; peak: 5.9 +/- 1.5) was significantly lower than that of controls (rest: 5.8 +/- 1.5; low dose: 6.6 +/- 1.5; pre-peak: 6.9 +/- 1.3; peak: 7.3 +/- 1.7; all p < 0.001). However, the absolute and relative increases in Sm or Em from rest to peak stress were similar in diabetic and control groups. CONCLUSIONS: Subtle LV dysfunction is present in diabetic patients without overt cardiac disease. The normal response to stress suggests that ischemia due to small-vessel disease may not be important in early diabetic heart muscle disease.

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography: a comparison with contrast-enhanced magnetic resonance imaging.

OBJECTIVES: We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). BACKGROUND: Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. METHODS: Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, <25%, 26% to 50%, 51% to 75%, and >75% of the wall thickness replaced by scar. RESULTS: As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (<25% TES), >50% were viable by SPECT. CONCLUSIONS: Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar.

Determinants of functional capacity in patients with chronic heart failure: role of filling pressure and systolic and diastolic function.

BACKGROUND: Previous work suggesting a better correlation of diastolic than systolic function with exercise capacity in heart failure may reflect the relative insensitivity and load-dependence of ejection fraction (EF). We sought the correlation of new and more sensitive methods of quantifying systolic and diastolic function and filling pressure with functional capacity. METHODS: We studied 155 consecutive exercise tests on 95 patients with congestive heart failure (81 male, aged 62 +/- 10 years), who underwent resting 2-dimensional echocardiography and tissue Doppler imaging before and after measurement of maximum oxygen uptake (peak VO2). RESULTS: The resting EF was 31% +/- 10% and a peak VO2 was 13 +/- 5 mL/kg.min; the majority of these patients (80%) had an ischemic cardiomyopathy. Resting EF (r = 0.14, P = .09) correlated poorly with peak VO2 and mean systolic (r = 0.23, P = .004) and diastolic tissue velocities (r = 0.18, P = .02). Peak EF was weakly correlated with the mean systolic (r = 0.18, P = .02) and diastolic velocities (r = 0.16, P < .04). The mean sum of systolic and diastolic velocities in both annuli (r = 0.30, P < .001) and E/Ea ratio (r = -0.31, P < .001) were better correlated with peak VO2 . Prediction of peak VO2 was similar with models based on models of filling pressure (R = 0.61), systolic factors (R = 0.63), and diastolic factors (R = 0.59), although a composite model of filling pressure, systolic and diastolic function was a superior predictor of peak VO2 (R = 0.69; all P < .001). CONCLUSIONS: The reported association of diastolic rather than systolic function with functional capacity may have reflected the limitations of EF. Functional capacity appears related not only to diastolic function, but also to systolic function and filling pressure, and is most closely associated with a combination of these factors.

Screening for heart disease in diabetic subjects.

BACKGROUND: The prevalence of left ventricular hypertrophy (LVH), coronary artery disease, and subclinical cardiomyopathy in diabetic patients without known cardiac disease is unclear. We sought the frequency of these findings to determine whether plasma brain natriuretic peptide (BNP) could be used as an alternative screening tool to identify subclinical LV dysfunction. METHODS: Asymptomatic patients with diabetes mellitus without known cardiac disease (n = 101) underwent clinical evaluation, measurement of BNP, exercise stress testing, and detailed echocardiographic assessment. After exclusion of overt dysfunction or ischemia, subclinical myocardial function was sought on the basis of myocardial systolic (Sm) and diastolic velocity (Em). Association was sought between subclinical dysfunction and clinical, biochemical, exercise, and echocardiographic variables. RESULTS; Of 101 patients, 22 had LVH and 16 had ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients had abnormal BNP levels; BNP was significantly increased in patients with LVH. After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy was identified in 24 of 66 patients. Subclinical disease could not be predicted by BNP. CONCLUSIONS: Even after exclusion of asymptomatic ischemia and hypertrophy, subclinical systolic and diastolic dysfunction occurs in a significant number of patients with type 2 diabetes. However, screening approaches, including BNP, do not appear to be sufficiently sensitive to identify subclinical dysfunction, which requires sophisticated echocardiographic analysis.

Myocardial and vascular dysfunction and exercise capacity in the metabolic syndrome.

The metabolic syndrome (MS) is associated with cardiovascular risk exceeding that expected from atherosclerotic risk factors, but the mechanism of this association is unclear. We sought to determine the effects of the MS on myocardial and vascular function and cardiorespiratory fitness in 393 subjects with significant risk factors but no cardiovascular disease and negative stress echocardiographic findings. Myocardial function was assessed by global strain rate, strain, and regional systolic velocity (s(m)) and diastolic velocity (e(m)) using tissue Doppler imaging. Arterial compliance was assessed using the pulse pressure method, involving simultaneous radial applanation tonometry and echocardiographic measurement of stroke volume. Exercise capacity was measured by expired gas analysis. Significant and incremental variations in left ventricular systolic (s(m), global strain, and strain rate) and diastolic (e(m)) function were found according to the number of components of MS (p <0.001). MS contributed to reduced systolic and diastolic function even in those without left ventricular hypertrophy (p <0.01). A similar dose-response association was present between the number of components of the MS and exercise capacity (p <0.001) and arterial compliance. The global strain rate and e(m) were independent predictors of exercise capacity. In conclusion, subclinical left ventricular dysfunction corresponded to the degree of metabolic burden, and these myocardial changes were associated with reduced cardiorespiratory fitness. Subjects with MS who also have subclinical myocardial abnormalities and reduced cardiorespiratory fitness may have a higher risk of cardiovascular disease events and heart failure.