Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function.

Some studies have demonstrated that left ventricular (LV) diastolic function is the principal determinant of impaired exercise capacity in hypertrophic cardiomyopathy (HC). In this study we sought the capability of echocardiographic indexes of diastolic function in predicting exercise capacity in patients with HC. We studied 52 patients with HC while they were not on drugs;12 of them had LV tract obstruction at rest. Diastolic function was assessed by M-mode and Doppler echocardiography by measuring: (1) left atrial fractional shortening, and the slope of posterior aortic wall displacement during early atrial emptying on M-mode left atrial tracing; and (2) Doppler-derived transmitral and pulmonary venous flow velocity indexes. Exercise capacity was assessed by maximum oxygen consumption by cardiopulmonary test during cycloergometer upright exercise. Maximum oxygen consumption correlated with the left atrial fractional shortening (r = 0.63, p <0.001), the slope of posterior aortic wall displacement during early atrial emptying (r = 0.55, p <0.001), age (r = -0.50; p <0.001), pulmonary venous diastolic anterograde velocity (r = 0.41, p <0.01), and the systolic filling fraction (r = -0.43; p <0.01). By stepwise multiple linear regression analysis, left atrial fractional shortening and the pulmonary venous systolic filling fraction were the only determinants of the maximum oxygen consumption (multiple r = 0.70; p <0.001). Exercise capacity did not correlate with Doppler-derived transmitral indexes. Thus, in patients with HC, exercise capacity was determined by passive LV diastolic function, as assessed by the left atrial M-mode and Doppler-derived pulmonary venous flow velocities.     

Effect of autonomic blockade, postural changes and isometric exercise on Doppler indexes of diastolic left ventricular function

Previous studies have demonstrated substantial changes in Doppler-derived indexes of left ventricular (LV) diastolic function in response to changes in loading conditions. To assess the influence of autonomic reflexes on these indexes, 2-dimensional and Doppler echophonocardiography were performed in 8 normal male subjects before and during autonomic blockade (0.2 mg/kg of propranolol and 0.04 mg/kg of atropine, intravenously) in the supine, passive upright 80 degree tilt and passive leg-raised positions, and during supine isometric exercise. During autonomic blockade in the supine position, there were significant increases in transmitral peak late filling velocity (A) (mean +/- standard error of the mean +34 +/- 7%) and isovolumic relaxation time (+18 +/- 9%), and significant decreases in transmitral peak early filling velocity (E) (-20 +/- 7%), deceleration time (-35 +/- 7%) and E/A ratio (-40 +/- 5%). E/A ratio decreased from 2.0 +/- 0.1 to 1.2 +/- 0.1 with autonomic blockade. When either upright tilt or isometric handgrip exercise was combined with autonomic blockade, the pattern of diastolic filling became distinctly "abnormal," with E/A ratio decreasing to 0.9 +/- 0.1. The effect of volume loading (increased end-diastolic volume and increased peak E) was seen in the legs-raised position only during autonomic blockade. It is concluded that autonomic blockade substantially alters the Doppler indexes of LV diastolic filling and modifies both hemodynamic response and Doppler indexes produced by positional changes and by isometric exercise.     

Effect of age on left ventricular filling in children of hypertensive parents

Doppler transmitral flow velocity A/E ratio is a useful noninvasive estimate of left ventricular (LV) filling. However, the A/E ratio increases with age. To evaluate the effect of age on LV filling in children, Doppler transmitral flow velocity A/E ratios and echocardiographic measurements were obtained in 51 normal children (mean age 12 +/- 4 years) of hypertensive parents (study children), sex- and age-matched against 28 normal children (mean age 12 +/- 4 years) from normotensive parents (control children). There was a significant correlation between age and LV systolic and diastolic internal dimensions (r = 0.74 and 0.83, respectively, P less than .0001, in study children, and r = 0.70 and 0.79, respectively, P less than .0001, in control children), total wall thickness (r = 0.72, P less than .0001, in study children, and 0.61, P less than .001, in control children), and with LV mass index (r = 0.56, P less than .0001 and r = 0.45, P less than .02, respectively). In contrast, there was no correlation between age and transmitral flow velocity A/E ratio in either group (r = 0.12 and 0.07, respectively). In conclusion, age does not have an effect on LV filling in normal children from either normotensive or hypertensive parents. Therefore, age correction of A/E ration, which is necessary in adults, is not required in children. Because of a strong correlation between age and LV mass as well as LV mass index, age should be taken into account when defining criteria for LV hypertrophy in children.     

Diastolic stress echocardiography: hemodynamic validation and clinical significance of estimation of ventricular filling pressure with exercise.

OBJECTIVES: Our study attempted to validate a Doppler index of diastolic filling (E/E') during exercise with simultaneously measured left ventricular diastolic pressure (LVDP), investigate its association with exercise capacity, and understand which patients to select for testing. BACKGROUND: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity approximates LVDP at rest, but there is limited validation of exercise E/E' with invasive hemodynamic measurement, and its clinical implications are unclear. METHODS: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity was measured at rest and during supine cycle ergometry in 37 patients undergoing left heart catheterization. In addition to correlation between invasive and estimated LVDP, the accuracy of different cutoffs for identification of elevated LVDP (>15 mm Hg) was determined at both rest and exercise. Doppler index of diastolic filling was also measured at rest and immediately after maximal treadmill exercise in 166 patients to investigate the association between exercise E/E' and exercise capacity (<8 metabolic equivalents [METs]). RESULTS: In patients undergoing invasive measurement, nine (24%) had elevation of LVDP only during exercise. There was a good correlation between E/E' and LVDP at rest (r = 0.67) and during exercise (r = 0.59), and the regressions at rest and exercise corresponded closely. Receiver-operator curve analysis indicated that a cutoff value of 13 for exercise E/E' identified patients with an elevated LVDP during exercise. A post-exercise E/E' >13 was highly specific (90%) for reduced exercise capacity, and even after classification of resting E/E', exercise E/E' permitted classification of patients with exercise capacity <8 METs or > or =8 METs. CONCLUSIONS: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity correlates with invasively measured LVDP during exercise. It can be used to reliably identify patients with elevated LVDP during exercise and reduced exercise capacity.     

Improvement of exercise capacity and left ventricular diastolic function with metoprolol XL after acute myocardial infarction

BACKGROUND: Left ventricular (LV) diastolic function predicts and correlates with exercise capacity. Beta-blockers improve exercise capacity and LV diastolic function in patients with severe LV systolic dysfunction in dilated cardiomyopathy. However, information on the effect of metoprolol XL on exercise capacity in relation to LV diastolic function in patients with mild to moderate LV systolic dysfunction after acute myocardial infarction is limited. METHODS: In a randomized, double-blind, placebo-controlled study of 77 patients, a subgroup of 59 patients with mild to moderate LV systolic dysfunction after acute myocardial infarction were given metoprolol XL (n = 29) or placebo (n = 30). The effects of metoprolol XL on exercise capacity in relation to effects on LV diastolic filling were studied. Two-dimensional Doppler echocardiography and maximal symptom limited bicycle test were performed on days 5 through 7 and after 3 months. RESULTS: Maximal exercise capacity increased in the metoprolol XL group (124 +/- 30 W vs 135 +/- 29 W) compared with placebo (125 +/- 31 W vs 126 +/- 34 W) (P <.01). E/A ratio decreased, A peak velocity increased, reverse pulmonary flow decreased, and deceleration time was significantly prolonged in the metoprolol XL group. A significant correlation was found between the changes of deceleration time (metoprolol XL: rho = 0.69, P <.0001; placebo: rho = 0.31, P = not significant) and A peak velocity (metoprolol XL: rho = 0.71, P <.0001; placebo: rho = -0.15, not significant) in relation to changes of exercise capacity. CONCLUSION: Metoprolol XL increases exercise capacity after 3 months, and this change seems related to improvement of LV diastolic filling after acute myocardial infarction.     

Left ventricular Doppler characteristics in first-degree relatives of patients with hypertrophic cardiomyopathy

Left ventricular (LV) diastolic function may be affected early in patients with hypertrophic cardiomyopathy (HCM), regardless of the phenotypic expression of the disease. The aim of the present study was to detect whether LV diastolic performance, evaluated by conventional Doppler echocardiography, is impaired in first-degree relatives of patients with phenotypically expressed HCM, who had no clinical, electrocardiographic, or echocardiographic signs of the disease. Twenty-two young adults having the previously described characteristics comprised the study population and 22 sex- and age-matched healthy individuals served as controls. The 2 groups were compared according to several echocardiographic parameters and the following diastolic function indices: peak velocity of E wave, representing early filling; peak velocity of A wave, representing late filling; ratio of peak early to peak late velocity (E/A); deceleration time of E wave; and LV isovolumic relaxation time. Slower deceleration time of transmitral early filling in first-degree relatives of patients with HCM (192 +/- 31 vs 149 +/- 31 msec, p < 0.001) was the only variable that significantly differentiated the 2 groups. This study shows that in healthy persons with a family history of HCM, Doppler-derived mitral filling pattern shifted toward that observed in HCM and the slower deceleration time may serve as an early sign of disease development.     

Value of Doppler index combining systolic and diastolic myocardial performance in predicting cardiopulmonary exercise capacity in patients with congestive heart failure: effects of dobutamine

STUDY OBJECTIVE: Doppler-derived myocardial performance index (MPI), a measure of combined systolic and diastolic myocardial performance, was assessed at rest and after low-dose dobutamine administration in patients with idiopathic or ischemic dilated cardiomyopathy. MPI also was correlated with other conventional echocardiographic indexes of left ventricular (LV) function, and its ability to assess cardiopulmonary exercise capacity in those patients was investigated. SETTINGS: A tertiary-care, university heart failure clinic. PATIENTS: Forty-two consecutive patients (27 men; mean [+/- SD] age, 57 +/- 10 years) with heart failure (New York Heart Association [NYHA] class, II to IV) who had received echocardiographic diagnoses of dilated cardiomyopathy. Coronary angiography distinguished the cause of dilated cardiomyopathy. INTERVENTIONS: Low-dose IV dobutamine was infused after patients underwent a baseline echocardiographic study. All patients also underwent a cardiopulmonary exercise test using a modified Naughton protocol. RESULTS: Advanced NYHA class and restrictive LV filling pattern were associated with higher index values. A negative correlation was found between MPI and LV stroke volume, cardiac output, early filling/late filling velocity ratio, and late LV filling velocity, as well as oxygen uptake at peak exercise (r = -0.550; p < 0.001) and at the anaerobic threshold (r = -0.490; p = 0.002). Dobutamine administration produced an improvement in MPI, reducing its value and decreasing the isovolumic relaxation and contraction times. Stepwise regression analysis revealed that the rest index and the late LV filling velocity were the only independent predictors of cardiopulmonary exercise capacity. CONCLUSION: MPI correlates inversely with LV performance, reflects disease severity, and is a useful complimentary variable in the assessment of cardiopulmonary exercise performance in patients with heart failure.     

Impact of diastolic Doppler indices on exercise capacity in hypertensive patients with electrocardiographic left ventricular hypertrophy (a LIFE substudy)

OBJECTIVE : To assess whether Doppler evidence of impaired early diastolic relaxation during exercise is associated with lesser exercise capacity in hypertensive patients. DESIGN : Single center addition to the echocardiographic substudy in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. SETTING : University hospital out-patient clinic. METHODS: A total of 60 patients (29 women and 31 men) with essential hypertension and electrocardiographic LV hypertrophy. INTERVENTIONS : Assessment of Doppler echocardiography and ergospirometry during semi-upright bicycling. MAIN OUTCOME MEASURE : Exercise capacity and its relation to diastolic Doppler indices at rest and during exercise. RESULTS : Average resting blood pressure was 181/97 +/- 18/9 mmHg, LV mass/body surface area 127 +/- 26 g/m2, midwall shortening 16 +/- 2%, and isovolumic relaxation time (IVRT) and transmitral early to atrial filling velocity (E/A) ratio 121 ms and 0.80, respectively. Exercise capacity, assessed as peak oxygen uptake and exercise load at exhaustion in all patients, were 20 and 25% higher, respectively, in men than women (both P < 0.01). In multivariate analysis, higher peak exercise load was related to male gender, higher E/A ratio at rest, greater reduction in IVRT during exercise and higher peak exercise heart rate (multiple R2 = 0.59, P < 0.01). Younger age, greater reduction in IVRT during exercise, higher midwall shortening and peak exercise heart rate were associated with higher peak oxygen uptake (multiple R2 = 0.47, P < 0.01). CONCLUSION : Diastolic LV performance significantly influences exercise capacity in hypertensive patients with LV hypertrophy. Impaired exercise capacity is more strongly associated with blunted reduction in IVRT during exercise than with lower E/A ratio at rest.     

Prevalence and determinants of left ventricular diastolic filling abnormalities in an unselected hypertensive population

The independent contribution of age, sex, duration of hypertension, heart rate, clinic and ambulatory blood pressure and echocardiographic left ventricular mass to left ventricular diastolic filling abnormalities in essential hypertension was investigated in 250 subjects (145 untreated and unselected hypertensives and 105 healthy normotensive controls) undergoing Doppler and standard echocardiography and non-invasive 24-h ambulatory blood pressure monitoring. Late and early diastolic transmitral peak flow velocities and their ratio (all P less than 0.01), the rate of deceleration of early diastolic mitral flow (P less than 0.01) and the time of deceleration of early diastolic mitral flow (P = 0.018) were abnormal in the hypertensive group vs controls. None of these parameters significantly varied in the presence vs absence of LV hypertrophy. In the hypertensive group, the prevalence of abnormal age-corrected Doppler values varied up to 46% (up to 45.4% and 50% in the absence and presence of left ventricular hypertrophy, respectively; P = n.s.). In a stepwise multivariate regression analysis, age and average daytime or night-time ambulatory blood pressure showed a significant independent relationship with each of these Doppler indexes of left ventricular diastolic filling. Late transmitral peak flow velocity and the ratio of late to early peak flow velocity were also independently affected by the heart rate. Sex, duration of hypertension, clinic systolic and diastolic blood pressure and left ventricular mass index did not show any independent relationship to these Doppler parameters of left ventricular filling. In conclusion, Doppler abnormalities of diastolic transmitral blood flow were detected in up to 46% of patients in an unselected hypertensive population with a low prevalence (14.5%) of left ventricular hypertrophy. Age and ambulatory blood pressure, but not sex, duration of hypertension, clinic blood pressure and left ventricular mass itself, were the major independent determinants of these abnormalities.     

Factors of Importance to Doppler Indexes of Left Ventricular Filling in 50-Year-Old Hypertensive Persons

Altered left ventricular (LV) diastolic filling has been shown in subjects with hypertension. Age is a major determinant of Doppler indexes of LV diastolic filling; therefore, a group of subjects of uniform age should preferably be chosen, if other determinants of diastolic LV filling are to be studied. A limited body of data is available regarding Doppler indexes of LV filling in hypertensive persons of a similar age. We therefore evaluated 26 hypertensive subjects (13 women and 13 men) 50 years old by Doppler echocardiography. The peak velocity of early diastolic filling (E wave), the peak velocity of atrial filling (A wave), the early-to-atrial peak velocity (E/A) ratio, and the deceleration time of early velocity were measured. The peak E wave velocity was 0.76 ± 0.11 versus 0.62 ± 0.13 m/s (P < 0.005), and the E/A ratio was 1.11 ± 0.24 versus 0.93 ± 0.23 (P < 0.05) in hypertensive women and men, respectively. The peak A wave velocity was increased and the E/A ratio was decreased in both hypertensive women and men compared with healthy 50-year-old subjects. In multivariate analyses, LV diameter, body mass index, and gender correlated with the E/A ratio in hypertensive persons. It is concluded that there is a significant difference in Doppler LV filling indexes between 50-year-old hypertensive women and men. LV diameter, gender, and body mass index are independent determinants of LV diastolic inflow in similarly aged hypertensive persons.     

Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension Relationship to tissue Doppler indices of diastolic relaxation

BACKGROUND: Hypertension, hypertensive heart disease, and left ventricular (LV) hypertrophy are integral to symptomatic diastolic heart failure. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is linked to extracellular matrix fibrosis and is elevated in hypertension. We hypothesized a link between circulating TIMP-1, matrix metalloproteinase-9 (MMP-9), and resting echocardiographic LV filling parameters using tissue Doppler parameters of diastolic (dys)function. METHODS: Circulating MMP-9 and TIMP-1 levels were measured in citrated plasma by ELISA in 74 patients with hypertension (58 men, mean age 58 +/- 11 years) and 34 controls (23 men, mean age 53 +/- 13 years). All had confirmed normal short axis systolic contractility, with no significant wall motion abnormalities; the LV mass and standard resting tissue Doppler echocardiographic indices of diastolic function were also recorded. RESULTS: Both MMP-9 and TIMP-1 levels were higher in the hypertensive group (P =.0039 and P =.0054, respectively). When compared to controls, hypertensive patients had a greater LV mass (P =.0054), and differences in many of the parameters reflecting diastolic dysfunction (controls versus hypertensives: E: 0.71 +/- 0.15 v 0.81 +/- 0.15 m/sec, P =.004; A: 0.66 +/- 0.12 v 0.81 +/- 0.16 m/sec, P <.0001; e': 0.12 (0.09-0.14) v 0.09 (0.07-0.10) m/sec, P =.0017; e'/a': 1.20 (1.00-1.80) v 0.88 (0.71-1.05), P <.0001; E/e': 6.54 (4.75-7.14) v 8.89 (7.55-10.75), P <.0001, respectively). Within the hypertensive cohort, only TIMP-1 levels correlated with LV mass (r = 0.271, P =.024), LV mass index (r = 0.323, P =.007), and tissue Doppler parameters of diastolic dysfunction, including e' (r = -0.338, P =.005), a' (r = -0.350, P =.005), and E/e' (r = 0.334, P =.005). CONCLUSIONS: TIMP-1 is thought to increase tissue concentrations of collagen type I by preventing its breakdown by MMPs. Our findings therefore add weight to a hypothesis suggesting that TIMP-1 may be a key mediator of LV diastolic dysfunction through definition of ventricular matrix composition.     

Longitudinal myocardial dysfunction in healthy older subjects as a manifestation of cardiac ageing

BACKGROUND: Abnormalities of longitudinal left ventricular (LV) contraction and relaxation may be early markers of cardiac disease. This study was designed to assess the relationship between long-axis LV function and age in healthy subjects. METHODS: 118 healthy individuals aged 57 +/-19 years (range 20-90 years) with no evidence of cardiovascular disease under-went echocardiography with Doppler examination of transmitral flow. To assess longitudinal LV function, systolic (S(m)), early diastolic (E(m)) and late diastolic (A(m)) mitral annular velocities were measured using colour-coded tissue Doppler imaging. RESULTS: The left atrium was enlarged (P<0.001) in subjects >/=60 years of age compared to those <60 years, but there were no differences in LV volumetric indices and ejection fraction. Peak E velocity was lower (P<0.001) and peak A velocity of transmitral flow was higher in older subjects (P<0.001) with a higher E/A ratio (P<0.001) and longer isovolumic relaxation time (P= 0.001) indicative of impaired ventricular relaxation. S m and E m mitral annular velocities decreased (P<0.001) and A m velocity increased (P=0.002) in the older group. E m velocity and E m /A m ratio showed a strong negative correlation with age (r= -0.80, P<0.001 and r=-0.78, P<0.001, respectively). CONCLUSIONS: Global LV systolic function is preserved but the velocity of long-axis systolic shortening is depressed in older individuals, indicating selective impairment of the longitudinal component of systolic contraction. The decline in the velocity of early diastolic long-axis LV lengthening and the changes in the pattern of transmitral flow suggest impaired ventricular relaxation. These measures of cardiac function may be a useful index of normal cardiac ageing.     

Role of left atrial booster pump function in a worsening course of congestive heart failure.

We evaluated changes in left ventricular (LV) preload and the Doppler-derived transmitral late to early diastolic peak velocity ratio (A/E ratio) during the exercise in 27 patients with ischemic heart disease. After the exercise, A/E ratio decreased in 16 patients with a remarkable elevation in LV preload, and increased in 11 with a mild elevation. Further, Doppler transmitral flow in conjunction with pulmonary venous flow and hemodynamic parameters were analyzed in 11 dogs during a worsening course of heart failure induced by dextran infusion. The relationship of A/E ratio to LV end-diastolic pressure showed a quadratic curve concave to the pressure axis. A/E ratio, an index expressing left atrial (LA) contribution to LV filling, returned to that seen before volume loading under the condition of cardiac dysfunction. Pulmonary venous reflux fraction determined as the ratio of peak velocity of pulmonary venous reflux during LA systole to the sum of systolic and diastolic peak velocities of pulmonary venous antegrade flow, did not increase here. In this situation, blood could not be ejected from the left atrium into the left ventricle and even into the pulmonary veins during LA contraction. Finally, LV filling was not compensated by the left atrium, and LA booster pump function itself was deteriorated.     

Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension

OBJECTIVES: The purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH). BACKGROUND: Bosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH. METHODS: Patients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment. RESULTS: Baseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m(2) (p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm(2) (p = 0.003), LV systolic eccentricity index = -0.12 (p = 0.047), RV end-systolic area = -2.3 cm(2) (p = 0.057), RV:LV diastolic areas ratio = -0.64 (p = 0.007), Doppler RV index = -0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05). CONCLUSIONS: Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.     

Effect of preload alterations by hemodialysis on the time interval between the onsets of early diastolic mitral inflow and annular waveforms

BACKGROUND: The T(Ea-E), which is defined as the time interval between the peak of the R-wave and the onset of early diastolic mitral annular waveform (T(Ea)) minus the time interval between the peak of the R-wave and the onset of early diastolic mitral inflow waveform (T(E)), is recently proposed as a useful index of left ventricular (LV) relaxation. The aim of this study is to determine whether the T(Ea-E) is preload-independent. METHODS: Twenty hemodialysis (HD) patients (9 men; age 64 +/- 9 years) underwent echocardiography 1 hour before and 1 hour after HD was studied. RESULTS: After HD, the body weight (P < 0.001), early transmitral filling wave peak velocity (E) (P < 0.001), the ratio of E to late transmitral filling wave peak velocity (P = 0.011), the early diastolic mitral anuular velocity (Ea) (P = 0.002), E/Ea (P = 0.026), and T(Ea-E) (P < 0.001) decreased significantly, and the T(Ea) (P = 0.047) and T(E) (P = 0.005) increased significantly. In addition, T(Ea-E) had a significant negative correlation with Ea either before (r =-0.457, P = 0.043) or after HD (r =-0.637, P = 0.003). CONCLUSIONS: T(Ea-E), as well as Ea, was a preload-dependent relaxation index. The preload dependence of this newer Doppler parameter limited its utility in evaluating LV diastolic function in HD patients.     

Tissue Doppler-derived indices predict exercise capacity in patients with apical hypertrophic cardiomyopathy

BACKGROUND: Although impaired left ventricular (LV) diastolic function is a prominent feature of hypertrophic cardiomyopathy (HCM), diastolic function and its relation to exercise capacity in apical HCM (ApHCM) has not been explored previously. This study was sought to determine the relationship between diastolic mitral annular velocities combined with conventional Doppler indexes and exercise capacity in patients with ApHCM. PATIENTS: Twenty-nine patients with ApHCM (24 men; mean age +/- SD, 57 +/- 10 years) underwent supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. RESULTS: The mitral inflow velocities (early filling [E], late filling, and deceleration time) were traced and measured. Early diastolic mitral annular velocity (E') was measured at the septal corner of mitral annulus by Doppler tissue imaging (DTI) from the apical four-chamber view. Pro-brain natriuretic peptide (proBNP) was measured at the time of echocardiography using a quantitative electrochemiluminescence immunoassay. E/E' ratio correlated inversely with maximal oxygen uptake (Vo(2)max) [r = - 0.47, p = 0.0106]. There was a significant positive correlation between E' and Vo(2)max (r = 0.41, p = 0.024). However, no correlation was found between conventional two-dimensional, Doppler indices, and proBNP and Vo(2)max). Of all the echocardiographic and clinical parameters assessed, E/E' ratio had the best correlation with exercise capacity (r - 0.47) and was the strongest independent predictor of Vo(2)max by multivariate analysis (p = 0.0106). CONCLUSIONS: DTI-derived indexes (E', E/E' ratio), an estimate of myocardial relaxation and LV filling pressures, correlate with exercise capacity in patients with ApHCM, suggesting that abnormal diastolic function may be a factor limiting exercise capacity.     

Independent association of plasma leptin levels and left ventricular isovolumic relaxation in uncomplicated hypertension.

BACKGROUND: On the basis of evidence of plasma leptin (LE) effects on cardiovascular system, we assessed possible association of LE and Doppler-derived left ventricular (LV) diastolic function in arterial hypertension. METHODS: Doppler echocardiography, blood sample for fasting plasma LE levels, and euglycemic hyperinsulinemic glucose clamp were performed on 15 healthy insulin-sensitive men and 40 newly diagnosed hypertensive men, who were divided into two groups according to insulin sensitivity degree: 15 insulin sensitive (IS) and 25 insulin resistant (IR) individuals (whole body glucose disposal >33.3 and <33.3 micromol/kg, respectively). RESULTS: The IR hypertensives had significantly higher body mass index (BMI), waist/hip ratio, LE and LV mass index than the other two groups. IR hypertensives had lower LE (even after adjusting for BMI and waist/hip ratio) and among LV diastolic indexes, lower E peak velocity (P < .05) and longer isovolumic relaxation time (IVRT) (P < .001) in comparison to IR hypertensives. IR hypertensives had the lowest E/A ratio (0.88 +/- 0.2) compared to IS patients (1.03 +/- 0.1 P < .05) and controls (1.31 +/- 10.2 P < .001). By multiple linear regression analyses performed both in the overall population and hypertensives, LV mass index and LE were independently associated to IVRT (R2 = 0.41 in overall population, R2 = 0.42 in hypertensives, both P < .0001), whereas age, heart rate, diastolic and systolic blood pressure (BP), BMI, waist/hip ratio, and insulin action were not significant. CONCLUSIONS: Our study underscores an independent association of increased plasma LE and lengthening of isovolumic relaxation in uncomplicated hypertension. Further studies will need to understand the conditions underlying both these phenomena.     

Cold exposure and left ventricular diastolic performance in coronary artery disease

It is known that cold exposure is accompanied by coronary artery vasoconstriction and ischemia in patients with coronary artery disease (CAD). The aim of the present study was to evaluate the response of left ventricular (LV) diastolic and systolic functions, estimated by means of Doppler echocardiography, to cold pressor test (CPT) in patients with CAD. Twenty-five male patients (mean age 50.8 +/- 8.1 years) with documented CAD underwent CPT with Doppler echocardiographic assessment of LV diastolic and systolic functions. According to the development of ischemic response to CPT, all patients were divided into 2 groups: group 1, 10 patients with ischemia and group 2, 15 patients without ischemia during CPT. Cold exposure caused significant increase in blood pressure with no changes in heart rate in all CAD patients. Patients with signs of ischemia during cold exposure had lower transmitral flow velocity during early filling (p < 0.001), prolonged isovolumic relaxation time (p < 0.04), shortened deceleration time of early transmitral flow velocity (p < 0.001), and higher values of Doppler-derived index of myocardial performance (p < 0.0001) than those without ischemic response to CPT. Cold exposure in CAD patients through stimulating of vasoconstriction and ischemia was associated with derangements in LV myocardial performance, manifested by delayed relaxation, impaired stiffness, and reduced contractility.     

Differentiation of left ventricular diastolic dysfunction, identification of pseudonormal/restrictive mitral inflow pattern and determination of left ventricular filling pressure by Tei index obtained from tissue Doppler echocardiography

BACKGROUND: Tei index obtained from tissue Doppler echocardiography (TDE-Tei index) has an inherent advantage of recording its systolic and diastolic components simultaneously on the same cardiac cycle. The aims of this study are to evaluate whether TDE-Tei index also exerts a correlation with left ventricular (LV) systolic and diastolic function and filling pressure and to see whether it can effectively identify the pseudonormal/restrictive mitral filling pattern. METHODS: Echocardiographic examination was performed in 243 consecutive patients. These patients were classified into three groups as normal, abnormal relaxation, and pseudonormal/restrictive groups according to the transmitral E/A-wave velocity (E/A), early diastolic velocity of lateral mitral annulus (Ea) and E/Ea. RESULTS: Standard Doppler indices of LV filling such as E, A, E/A, and E-wave deceleration time had a bimodal distribution, but Ea decreased and E/Ea and TDE-Tei index increased progressively with worsening of LV diastolic function. The sensitivity and specificity of TDE-Tei index>0.51 in the discrimination of pseudonormal/restrictive filling pattern were 85% and 96%, respectively. After stepwise multiple linear regression analysis, TDE-Tei index had a significant negative correlation with Ea (beta=-0.296, P<0.001) and ejection fraction (beta=-0.293, P<0.001) and positive correlation with E/Ea (beta=0.235, P=0.001). CONCLUSIONS: TDE-Tei index increased with worsening of LV diastolic function and can effectively identify the pseudonormal/restrictive mitral inflow pattern. It also correlated with the echocardiographic parameters of LV systolic and diastolic function and filling pressure. It suggests that TDE-Tei index is a simple and feasible marker in assessing global LV function.     

Doppler-derived mitral deceleration time as an early predictor of left ventricular thrombus after first anterior acute myocardial infarction

BACKGROUND: The relation between left ventricular (LV) diastolic function and LV thrombus has not yet been fully investigated. The aim of this study was to determine whether early assessment of Doppler-derived mitral deceleration time (DT), a measure of LV compliance and filling, may predict LV thrombus formation after acute myocardial infarction. METHODS AND RESULTS: Two-dimensional and Doppler echocardiographic examinations were performed in 98 consecutive patients (aged 57 +/- 12 years; 8 women) with first acute myocardial infarction. The patients were studied within 24 hours and at days 3, 7, 15, and 30 after arrival to the coronary care unit. Mitral flow velocities were obtained from the apical 4-chamber view with pulsed Doppler. LV thrombus was detected in 20 of 98 patients. Patients were divided into 2 groups according to LV thrombus formation: group 1 (n = 20) with thrombus and group 2 (n = 78) without thrombus. Mitral E-wave DT was significantly shorter in group 1 than group 2 (134 ms vs 175 ms; P <.001). Patients in group 1 had significantly larger LV end-diastolic and end-systolic volumes and a higher wall motion score index than patients in group 2 (133 +/- 39 mL vs 112 +/- 41 mL, P =.03; 83 +/- 34 mL vs 59 +/- 30 mL, P =.003; and 1.8 +/- 0.3 mL vs 1.5 +/- 0.3 mL, P =.007, respectively). The LV ejection fraction was significantly lower in group 1 than in group 2 (39% +/- 13% vs 48% +/- 12%; P =.004). In a multivariate regression analysis, mitral E-wave DT was identified as an independent variable related to development of LV thrombus (P =.04). CONCLUSIONS: Doppler-derived mitral DT is superior to conventional clinical and 2-dimensional echocardiographic assessment in estimating the risk of left ventricular thrombosis after myocardial infarction.