Brian Haluska

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 >250m/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±7mm 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±1.7dB 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.

Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women

OBJECTIVES This study compared the accuracy and cost implications of using exercise echocardiography and exercise electrocardiography for detection of coronary artery disease in women. BACKGROUND The specificity of exercise electrocardiography in women is lower than in men. Exercise echocardiography accurately identifies coronary artery disease in women, but its utility in place of exercise electrocardiography is unclear. METHODS One hundred sixty-one women without a previous Q wave infarction underwent exercise echocardiography and coronary angiography. Positive findings were a new or worsening wall motion abnormality on the exercise echocardiogram and ST segment depression > 0.1 mV at 0.08 s after the J point on the exercise electrocardiogram (ECG). RESULTS Coronary artery stenosis > 50% diameter narrowing was present in 59 patients; the sensitivity (mean +/- SD) of exercise echocardiography was 80 +/- 3%. In 48 patients with an interpretable ECG, the sensitivity of exercise echocardiography was 81 +/- 4%, and that of the exercise ECG was 77 +/- 3% (p = 0.50). In 102 patients without coronary artery disease, the overall specificity of exercise echocardiography was 81 +/- 4%. In 70 patients with an interpretable ECG, the specificity of exercise echocardiography (80 +/- 3%) exceeded that of the exercise ECG (56 +/- 4%, p < 0.0004). The accuracy of exercise echocardiography was also greater than exercise electrocardiography (81 +/- 5% vs. 64 +/- 6%, p < 0.005). Exercise echocardiography stratified significantly more patients of intermediate (20% to 80%) pretest disease probability into the high (> 80%) or low (< 20%) posttest probability group. In women without a previous exercise ECG, the specificity of exercise echocardiography continued to exceed that of exercise electrocardiography (80 +/- 3% vs. 64 +/- 3%, p = 0.05). Exercise echocardiography had the best balance between accuracy and cost for the diagnosis of coronary artery disease in women. CONCLUSIONS Exercise echocardiography is more specific than exercise electrocardiography for diagnosis of coronary artery disease in women and is a cost-effective approach to the diagnosis of coronary artery disease because of the avoidance of inappropriate angiography.

Left ventricular volume measurement with echocardiography: a comparison of left ventricular opacification, three-dimensional echocardiography, or both with magnetic resonance imaging

AIMS Both contrast enhanced (CE) two-dimensional echocardiography (2DE) and three-dimensional echocardiography (3DE) have been proposed as techniques to improve the accuracy of left ventricular (LV) volume measurements. We sought to examine the accuracy of non-contrast (NC) and CE-2DE and 3DE for calculation of LV volumes and ejection fraction (EF), relative to cardiac magnetic resonance imaging (MRI). METHODS AND RESULTS We studied 50 patients (46 men, age 63 +/- 10 year) with past myocardial infarction who underwent echocardiographic assessment of LV volume and function. All patients sequentially underwent NC-2DE followed by NC-3DE. CE-2DE and CE-3DE were acquired during contrast infusion. Resting echocardiographic image quality was evaluated on the basis of NC-2DE. The mean LV end-diastolic volume (LVEDV) of the group by MRI was 207 +/- 79 mL and was underestimated by 2DE (125 +/- 54 mL, P = 0.005), and less by CE-2DE (172 +/- 58 mL, P = 0.02) or 3DE (177 +/- 64 mL, P = 0.08), but EDV was comparable by CE-3DE (196 +/- 69 mL, P = 0.16). Limits of agreement with MRI were similar for NC-3DE and CE-2DE, with the best results for CE-3D. Results were similar for calculation of LVESV. Patients were categorized into groups of EF (< or =35, 35-50, >50%) by MRI. NC-2DE demonstrated a 68% agreement (kappa 0.45, P = 0.001), CE-2DE a 62% agreement (kappa 0.20, P = 136), NC-3DE a 74% agreement (kappa 0.39, P = 0.005) and CE-3DE an 80% agreement (kappa 0.56, P < 0.001). CONCLUSION CE-2DE is analogous to NC-3DE in accurate categorization of LV function. However, CE-3DE is feasible and superior to other NC- and CE-techniques in patients with previous infarction.

Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease

Objectives: To examine the relation of arterial compliance to diastolic dysfunction in hypertensive patients with suspected diastolic heart failure (HF). Patients: 70 medically treated hypertensive patients with exertional dyspnoea (40 women, mean (SD) age 58 (8) years) and 15 normotensive controls. Main outcome measures: Mitral annular early diastolic velocity with tissue Doppler imaging and flow propagation velocity were used as linear measures of diastolic function. Arterial compliance was determined by the pulse pressure method. Results: According to conventional Doppler echocardiography of transmitral and pulmonary venous flow, diastolic function was classified as normal in 33 patients and abnormal in 37 patients. Of those with diastolic dysfunction, 28 had mild (impaired relaxation) and nine had advanced (pseudonormal filling) dysfunction. Arterial compliance was highest in controls (mean (SD) 1.32 (0.58) ml/mm Hg) and became progressively lower in patients with hypertension and normal function (1.04 (0.37) ml/mm Hg), impaired relaxation (0.89 (0.42) ml/mm Hg), and pseudonormal filling (0.80 (0.45) ml/mm Hg, p  =  0.011). In patients with diastolic dysfunction, arterial compliance was inversely related to age (p  =  0.02), blood pressure (p < 0.001), and estimated filling pressures (p < 0.01) and directly related to diastolic function (p < 0.01). After adjustment for age, sex, body size, blood pressure, and ventricular hypertrophy, arterial compliance was independently predictive of diastolic dysfunction. Conclusions: In hypertensive patients with exertional dyspnoea, progressively abnormal diastolic function is associated with reduced arterial compliance. Arterial compliance is an independent predictor of diastolic dysfunction in patients with hypertensive heart disease and should be considered a potential target for intervention in diastolic HF.

Feasibility and Accuracy of Different Techniques of Two-Dimensional Speckle Based Strain and Validation With Harmonic Phase Magnetic Resonance Imaging

BACKGROUND Different 2-dimensional speckle-based strain techniques have been developed to overcome the problem of angle dependency with Doppler-based strain. However, their relative accuracy has not been assessed. The aim of this study was to determine the feasibility and accuracy of 2 such techniques (velocity vector imaging [VVI] and automated function imaging [AFI]), using tagged harmonic phase (HARP) magnetic resonance imaging (MRI) as a reference standard. METHODS Thirty patients with known or suspected ischemic heart disease underwent measurement of peak systolic longitudinal, radial, and circumferential Lagrangian strain with all 3 techniques using a 16-segment model. The extent of scar tissue in each segment was determined using contrast-enhanced MRI. RESULTS The measurement of myocardial strain in all 3 directions was highly feasible with both VVI and AFI. Longitudinal strain was underestimated by both VVI (-11 +/- 8%; P < .01) and AFI (-12 +/- 6%; P < .01) in comparison with HARP MRI (-14 +/- 5%), and radial strain was underestimated by VVI (14 +/- 18% vs 23 +/- 7%; P < .01). All strain measurements with AFI showed better correlation and agreement with HARP MRI compared with VVI. Circumferential strain with AFI had the greatest accuracy (area under the receiver operating characteristic curve = 0.74, P < .001) for the prediction of scar tissue on MRI. CONCLUSIONS Two-dimensional strain measured with AFI has significantly better accuracy than VVI. Circumferential strain with AFI has the best discriminative ability for the detection of regional myocardial dysfunction.

Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation

Objective: To evaluate contractile reserve (CR) determined by exercise echocardiography in predicting clinical outcome and left ventricular (LV) function in asymptomatic severe mitral regurgitation (MR). Design: Cohort study. Setting: Regional cardiac centre. Patients and outcome measures: LV volumes and ejection fraction (EF) were measured at rest and after stress in 71 patients with isolated MR. During follow up (mean (SD) 3 (1) years), EF and functional capacity were serially assessed and cardiac events (cardiac death, heart failure, and new atrial fibrillation) were documented. Results: CR was present in 45 patients (CR+) and absent in 26 patients (CR−). Age, resting LV dimensions, EF, and MR severity were similar in both groups. Mitral surgery was performed in 19 of 45 (42%) CR+ patients and 22 of 26 (85%) CR− patients. In patients undergoing surgery, CR was an independent predictor of follow up EF (p  =  0.006) and postoperative LV dysfunction (EF < 50%) persisted in five patients, all in the CR− group. Event-free survival was lower in surgically treated patients without CR (p  =  0.03). In medically treated patients, follow up EF was preserved in those with intact CR but progressively deteriorated in patients without CR, in whom functional capacity also deteriorated. Conclusions: Evaluation of CR by exercise echocardiography may be useful for risk stratification and may help to optimise the timing of surgery in asymptomatic severe MR.

Atherosclerotic disease is increased in recent-onset rheumatoid arthritis: a critical role for inflammation

Rheumatoid arthritis (RA) patients have increased mortality and morbidity as a result of cardiovascular and cerebrovascular disease. What is not clear, however, is either how early accelerated atherosclerosis begins in RA or how soon risk factors must be rigorously controlled. Furthermore, given the strong relationship of vascular disease to RA mortality and of inflammation to the accelerated atherosclerosis associated with RA, it is important to evaluate indices that could serially and noninvasively quantify atherosclerotic disease in RA patients. The carotid intima-media thickness (cIMT) and plaque, measured by ultrasound, correlate closely with direct measurement of the local and systemic atherosclerotic burden. To investigate the presence of subclinical atherosclerosis in the early stages of RA, the cIMT and plaque were measured using carotid duplex scanning in 40 RA patients with disease duration < 12 months and in 40 control subjects matched for age, sex and established cardiovascular risk factors. Patients with RA had significantly higher average cIMT values and more plaque than the control group (cIMT 0.64 ± 0.13 mm versus 0.58 ± 0.09 mm, respectively; P = 0.03). In RA patients, the cIMT was predicted by age and C-reactive protein level at first presentation to the clinic (R2 = 0.64). C-reactive protein was associated with age of disease onset and history of smoking. Since inflammation has been shown to predate onset of clinical RA, the accelerated atherogenic process related to inflammation may precede RA symptom onset.

Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection

AIMS The variability of ejection fraction (EF) poses a problem in the assessment of left ventricular (LV) function in patients receiving potentially cardiotoxic chemotherapy. We sought to use global longitudinal strain (GLS) to compare LV responses to various cardiotoxic chemotherapy regimens and to examine the response to cardioprotection with beta-blockers (BB) in patients showing subclinical myocardial damage. METHODS AND RESULTS We studied 159 patients (49 ± 14 year, 127 women) receiving anthracycline (group A, n = 53, 46 ± 17 year), trastuzumab (group T, n = 61, 53 ± 12 year), or trastuzumab after anthracyclines (group AT, n = 45, 46 ± 9 year). LV indices [ejection fraction (EF), mitral annular systolic velocity, and GLS] were measured at baseline and follow-up (7 ± 7 months). Patients who decreased GLS by ≥11% were followed for another 6 months; initiation of BB was at the discretion of the clinician. Anthracycline dose was similar between group A and group AT (213 ± 118 vs. 216 ± 47 mg/m(2), P = 0.85). Although ΔEF was similar among the groups, attenuation of GLS was the greatest in group AT (group A, 0.7 ± 2.8% shortening; T, 1.1 ± 2.7%; and AT, 2.0 ± 2.3%; P = 0.003, after adjustment). Of 52 patients who decreased GLS by ≥-11%, 24 were treated with BB and 28 were not. GLS improved in BB groups (from -17.6 ± 2.3 to -19.8 ± 2.6%, P < 0.001) but not in non-BB groups (from -18.0 ± 2.0 to -19.0 ± 3.0%, P = 0.08). Effects of BB were similar with all regimens. CONCLUSIONS GLS is an effective parameter for identifying systolic dysfunction (which appears worst with combined anthracycline and trastuzumab therapy) and responds to cardioprotection in patients administered beta-blockers.

Incremental benefit of myocardial contrast to combined dipyridamole–exercise stress echocardiography for the assessment of coronary artery disease

Background—Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results—MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions—The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.

Association of imaging markers of myocardial fibrosis with metabolic and functional disturbances in early diabetic cardiomyopathy

Background— Metabolic and vascular disturbances contribute to diabetic cardiomyopathy, but the role of interstitial fibrosis in early disease is unproven. We sought to assess the relationship between imaging markers of diffuse fibrosis and myocardial dysfunction and to link this to possible causes of early diabetic cardiomyopathy. Methods and Results— Hemodynamic and metabolic data were measured in 67 subjects with type 2 diabetes mellitus (age 60±10 years) with no cardiac symptoms. Myocardial function was evaluated with standard echocardiography and myocardial deformation; ischemia was excluded by exercise echocardiography. Calibrated integrated backscatter was calculated from parasternal long-axis views. T1 mapping was performed after contrast with a modified Look-Locker technique using saturation recovery images. Amino-terminal propeptides of procollagens type I and III, as well as the carboxy-terminal propeptide of procollagen type I, were assayed to determine collagen turnover. Subjects with abnormal early diastolic tissue velocity (Em) had shorter postcontrast T1 values (P=0.042) and higher calibrated integrated backscatter (P=0.007). They were heavier (P=0.003) and had worse exercise capacity (P<0.001), lower insulin sensitivity (P=0.003), and blunted systolic tissue velocity (P=0.05). Postcontrast T1 was associated with diastolic dysfunction (Em r=0.28, P=0.020; E/Em r=−0.24, P=0.049), impaired exercise capacity (r=0.30, P=0.016), central adiposity (r=−0.26, P=0.046), blood pressure (systolic r=−0.30, P=0.012; diastolic r=−0.49, P<0.001), and insulin sensitivity (r=0.30, P=0.037). The association of T1 with E/Em (&bgr;=−0.31, P=0.017) was independent of blood pressure and metabolic disturbance. Amino-terminal propeptide of procollagens type III was linked to diastolic dysfunction (Em r=−0.32, P=0.008) and calibrated integrated backscatter (r=0.30, P=0.015) but not T1 values. Conclusions— The association between myocardial diastolic dysfunction, postcontrast T1 values, and metabolic disturbance supports that diffuse myocardial fibrosis is an underlying contributor to early diabetic cardiomyopathy.