Determinants of exercise capacity in hypertensive patients

An impaired exercise capacity is common in hypertensive patients (pts) and factors affecting exercise capacity are not completely elucidated. The aim of the study was to investigate factors influencing exercise capacity in hypertensive pts Studied group consisted of 41 pts (18 males, 23 females) mean age 54.2 +/- 11.9 with essential hypertension and without coronary artery disease. Each patient underwent an echocardiographic examination followed by treadmill exercise test. Echocardiographic assessment comprised estimation of left ventricular (LV) mass index (LVMI), pattern of LV geometry, ejection fraction (LVEF), fractional shortening (LVFS), peak and integral velocities of early (E, Ei) and late (A, Ai) transmitral flow, deceleration time of E wave (DT), isovolumic relaxation time (IVRT), duration of A wave (A-dur), total ejection isovolume index (TEI), E (ETT) and A (ATT) wave transit time to the LV outflow tract, flow propagation velocity of E wave (EP), peak and integral velocities of systolic (S, Si), diastolic (D, Di) and atrial reversal (AR, ARi) pulmonary venous flow, duration of AR wave (AR-dur), acceleration (SAT) and deceleration (SDT) of systolic pulmonary venous flow, systolic forward fraction of pulmonary venous flow (SFF). Exercise capacity was assessed by exercise time and total workload expressed in MET. Significant correlations were found for MET and: age (r = -0.49, p < 0.001), A (r = -0.62, p < 0.001), E/A ratio (r = 0.55, p < 0.004), Di (r = 0.55), p < 0.004), ARi (r = -0.38, p < 0.01), SFF (r = 0.46, p < 0.002). Exercise time correlated with A (r = -0.61, p < 0.001), E/A ratio (r = 0.41, p < 0.04), Di (r = 0.51, p < 0.009), ARi (r = -0.35, p < 0.02), SFF (r = -0.51, p < 0.008), S/D ratio (r = -0.47, p < 0.01). Other investigated parameters did not correlate with both MET and exercise time. By stepwise multiple linear regression analysis Di and ARi were the only determinants of MET (multiple r = 0.85, p < 0.0001) whereas A and Di turn out to be the only independent predictors of exercise time (multiple r = 0.76, p < 0.0004). In hypertensive pts: 1. diastolic function of LV is a principle determinant of exercise capacity, 2. integral velocity of diastolic and atrial reversal pulmonary venous flow and peak velocity of late transmitral flow are the best predictors of exercise tolerance.     

Impact of Doppler-derived left ventricular diastolic performance on exercise capacity in normal individuals

BACKGROUND: Doppler-derived left ventricular (LV) diastolic indexes have been shown to correlate with exercise capacity in patients with heart diseases as well as healthy individuals. However, it is uncertain whether they predict exercise capacity independent of noncardiac factors. METHODS: To clarify the impact of the LV diastolic index on exercise capacity, 160 healthy individuals were investigated. All underwent Bruce protocol treadmill stress testing and 2-dimensional and Doppler echocardiography. Estimated metabolic equivalent was calculated from exercise time (metabolic equivalent = 1.11 + 0.016 x exercise time). Diastolic performance was assessed by Doppler transmitral flow velocity pattern. Pulmonary function tests and complete blood cell count were also performed. RESULTS: LV diastolic indexes correlated well with metabolic equivalent (peak transmitral filling velocity (A): r = -0.51, P <.0001; ratio of early and late transmitral filling velocities (E/A): r = 0.58, P <. 0001). However, there was no significant correlation between LV systolic indexes and metabolic equivalent. Independent predictors for a higher metabolic equivalent by multivariate analysis were higher E/A (P <.0001), higher vital capacity (P =.001), smaller body mass index (P =.0003), younger age (P =.0050), and higher hemoglobin concentration (P =.0026). CONCLUSION: Doppler-derived LV diastolic index may help in predicting exercise capacity in normal individuals independent of other cardiac and extracardiac factors.     

Determinants and clinical significance of natriuretic peptides and hypertrophic cardiomyopathy.

AIMS: Atrial and brain natriuretic peptide levels closely reflect impaired left ventricular function in patients with heart failure. In the present study we assessed the determinants and the clinical significance of atrial and brain natriuretic peptide plasma levels in hypertrophic cardiomyopathy. METHODS AND RESULTS: In 44 patients with hypertrophic cardiomyopathy (40+/-15 years) we evaluated: (a) atrial and brain natriuretic peptide plasma levels; (b) left ventricular hypertrophy; (c) left ventricular ejection fraction; (d) transmitral and pulmonary venous flow velocity patterns, and left atrial fractional shortening; (e) left ventricular outflow tract gradient; (f) maximal oxygen consumption. Left ventricular hypertrophy influenced only brain natriuretic peptide levels (r=0.32;P<0.05). Atrial and brain natriuretic peptide plasma levels did not correlate with left ventricular ejection fraction, but correlated with left ventricular outflow tract gradient (r=0.35;P<0.05; and r=0.40, P=0.022, respectively) and left atrial fractional shortening (r=-0.57;P<0.001, and r=-0.35;P<0.05, respectively). Atrial but not brain natriuretic peptide plasma levels were inversely related to maximal oxygen consumption (r=-0.35;P<0.05). By stepwise multiple regression analysis, left atrial fractional shortening and left ventricular outflow tract gradient were the only predictors of atrial and brain natriuretic peptide plasma levels, respectively. CONCLUSIONS: In hypertrophic cardiomyopathy, atrial natriuretic peptide plasma levels are mainly determined by diastolic function: this explains the relationship with exercise tolerance. In contrast, brain natriuretic peptide plasma levels are mainly determined by left ventricular outflow tract gradient.     

Relation of exercise capacity to left ventricular systolic function and diastolic filling in idiopathic or ischemic dilated cardiomyopathy

Although exercise intolerance is a cardinal symptom of patients with dilated cardiomyopathy (DC) and heart failure, the factors that limit exercise capacity in these patients remain a matter of debate. To assess the contribution of left ventricular (LV) diastolic filling to the variable exercise capacity of patients with DC, we studied 47 patients (60 +/- 12 years) with DC in stable mild-to-moderate heart failure with a mean LV ejection fraction of 28%. Exercise capacity was measured as total body peak oxygen consumption (VO2) during symptom-limited bicycle (10 W/min) and treadmill (modified Bruce protocol) exercise. LV systolic function and diastolic filling were assessed at rest before each exercise by M-mode, Doppler echocardiography, and radionuclide ventriculography. As expected, treadmill exercise always yielded higher peak VO2 than bicycle exercise (21 +/- 6 vs 18 +/- 5 ml/kg/min, range 12 to 35 and 7 to 30 ml/kg/min, respectively, p <0.001). Both of these VO2 measurements were highly reproducible (R = 0.98). With univariate analysis, close correlations were found between peak VO2 (with either exercise modalities) and Doppler indexes of LV diastolic filling, as well as with the radionuclide LV ejection fraction. Stepwise multiple regression analysis identified 3 nonexercise variables as independent correlates of peak VO2, of which the most powerful was the E/A ratio (multiple r2 = 0.38, p <0.0001), followed by peak A velocity (r2 = 0.54, p <0.0001) and mitral regurgitation grade (r2 = 0.58, p = 0.024). In conclusion, our data indicate that in patients with DC, peak VO2 is better correlated to diastolic filling rather than systolic LV function.     

Left ventricular structure and function by echocardiography in ultraendurance athletes

To determine left ventricular (LV) structural and functional changes induced by ultraendurance exercise training, M-mode LV echograms and Doppler recordings of LV inflow velocity in 26 triathletes and 17 normal subjects were studied. All triathletes trained 20 to 40 hours/week in swimming, cycling and running for more than 2 years. Structurally, triathletes had normal LV systolic and diastolic cavity dimensions, but increased wall thickness (1.05 +/- 0.26 vs 0.80 +/- 0.27 cm in normal subjects, p less than 0.001), increased relative wall thickness, or h/R ratio (0.41 +/- 0.10 cm vs 0.33 +/- 0.11 cm in normal subjects, p less than 0.001), and increased LV mass (226 +/- 60 vs 143 +/- 54 g in normal subjects, p less than 0.001). LV mass correlated closely with mean exercise blood pressure during an 8-hour exercise test in 14 triathletes (r = 0.88). Systolic function at rest was similar in both groups, with no differences in fractional shortening or end-systolic stress. Diastolic LV function measured by digitized M-mode echo was similar in normal subjects and triathletes, with no differences in peak rates of cavity enlargement and wall thinning by echocardiogram. In contrast, the Doppler-derived ratio of early-to-late LV inflow velocities was slightly increased in triathletes (p less than 0.05). It is concluded that ultraendurance training produces a physiologic pattern of moderate pressure overload LV hypertrophy, in proportion to the hemodynamic load imposed during prolonged exercise. Unlike the abnormal hypertrophy of systemic hypertension, early diastolic function remains normal in the triathlete heart.     

Relation of left ventricular chamber stiffness at rest to exercise capacity in hypertrophic cardiomyopathy

The degree of exercise capacity is poorly predicted by conventional markers of disease severity in patients with hypertrophic cardiomyopathy (HC). The principal mechanism of exercise intolerance in patients with HC is the failure of stroke volume augmentation due to left ventricular (LV) diastolic dysfunction. The role of LV chamber stiffness, assessed noninvasively, as a determinant of exercise tolerance is unknown. Sixty-four patients with HC were studied with Doppler echocardiography, exercise testing, and gadolinium cardiac magnetic resonance. The LV chamber stiffness index was determined as the ratio of pulmonary capillary wedge pressure (derived from the E/Ea ratio) to LV end-diastolic volume (assessed by cardiac magnetic resonance). Maximal exercise tolerance was defined as achieved METs. There were inverse correlations between METs achieved and age (r = -0.38, p = 0.003), heart rate deficit (r = -0.39, p = 0.002), LV outflow tract gradient (r = -0.33, p = 0.009), the E/Ea ratio (r = -0.4, p = 0.001), mean LV wall thickness (r = -0.26, p = 0.04), and LV stiffness (r = -0.56, p <0.001) and a positive correlation between METs achieved and LV end-diastolic volume (r = 0.33, p = 0.01). On multivariate analysis, only LV chamber stiffness was associated with exercise capacity. A LV stiffness level of 0.18 mm Hg/ml had 100% sensitivity and 75% specificity (area under the curve 0.84) for predicting < or =7 METs achieved. In conclusion, LV diastolic dysfunction at rest, as manifested by increased LV chamber stiffness, is a major determinant of maximal exercise capacity in patients with HC.     

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.     

Doppler-derived left ventricular end-diastolic pressure prediction model using the combined analysis of mitral and pulmonary A waves in patients with coronary artery disease and preserved left ventricular systolic function

The aim of this study was to analyze the components of mitral and pulmonary A waves and to construct a Doppler-derived left ventricular (LV) end-diastolic pressure (EDP) prediction model based on the combined analysis of transmitral and pulmonary venous flow velocity curves. Combined analysis of transmitral and pulmonary venous flow velocity curves at atrial contraction is a reliable predictor of increased LV filling pressure. The duration of pulmonary and mitral A waves is determined by the sum of respective acceleration and deceleration time. Mitral flow and left upper pulmonary vein flow velocity curves were recorded simultaneously with LVEDP in 40 consecutive patients (aged 59 +/- 8 years) with coronary artery disease and preserved LV systolic function. Differences in all parameters represent values of pulmonary minus those of mitral A wave curve. The difference in deceleration time was the strongest candidate, being included in all models. After redundancy evaluation, we reached the following model: LVEDP = 20.61 + 0.229 x difference in deceleration time (r(2) = 0.80, p <0.001). In the entire study group, the difference in duration and in deceleration time of the A wave was highly correlated with LVEDP (r = 0.79, p <0.001, and r = 0.88, p <0.001, respectively). The entire study group was further divided according to whether LVEDP was above (group I, 20 patients) or below (group II, 20 patients) the median value (15.5 mm Hg). In group I, the difference in duration and in deceleration time correlated well (r = 0.62, p = 0.01, and r = 0.75, p = 0.001, respectively) with LVEDP, whereas in group II only the difference in deceleration time correlated well (r = 0.68, p = 0.005). In patients with coronary artery disease and preserved LV systolic function, the combined analysis of mitral and pulmonary A waves can predict LVEDP. The difference in deceleration time between pulmonary and mitral A waves can reliably evaluate high and normal LVEDP.     

Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler

OBJECTIVES: Our goal was to identify the hemodynamic determinants of the mitral annulus (MA) diastolic velocities by tissue Doppler. BACKGROUND: The MA diastolic velocities are promising indexes of left ventricular (LV) diastolic function. However, their hemodynamic determinants have not yet been evaluated. METHODS: Ten adult mongrel dogs underwent left atrial (LA) and LV pressure measurements by Millar catheters while tissue Doppler was applied to record the MA diastolic velocities at the septal and lateral comers. Conventional transmitral flow was also obtained. Left atrial and LV pressures were modified utilizing fluid administration and caval occlusion, whereas dobutamine and esmolol were used to change LV and LA relaxation. Left ventricular filling pressures were altered during different lusitropic states to evaluate for the possible interaction of preload and LV relaxation on the early diastolic velocity (Ea). RESULTS: In the majority of dogs, a positive significant relation was observed between Ea and the transmitral pressure gradient (r = 0.57, p = 0.04). The Ea had strong correlations with tau (r = -0.83, p < 0.001), LV -dP/dt (r = 0.8, p < 0.001) and minimal LV pressure (r = -0.76, p < 0.01). However, there was no relation between Ea and the transmitral pressure gradient in experimental stages where tau >50 ms. Furthermore, the late diastolic velocity at both corners of the MA had significant positive relations with LA dP/dt (r = 0.67, p < 0.01) and LA relaxation (r = 0.73, p < 0.01) but an inverse correlation with LV end-diastolic pressure (r = -0.53, p = 0.01). CONCLUSIONS: Left ventricular relaxation, minimal pressure and preload determine Ea while late diastolic velocity determinants include LA dP/dt, LA relaxation and LV end-diastolic pressure.     

Usefulness of mitral annular velocity in predicting exercise tolerance in patients with impaired left ventricular systolic function

Left ventricular (LV) diastolic function is 1 of the determinants of exercise tolerance. However, the relation between early diastolic velocity of the mitral annulus (Ea) obtained by tissue Doppler imaging and exercise tolerance is unknown in patients with impaired LV systolic function. To investigate the feasibility of evaluating exercise tolerance using tissue Doppler imaging, we studied 53 consecutive patients (mean age 58 +/- 14 years) with a LV ejection fraction of <50% (mean 37 +/- 9%). We measured the peak early diastolic velocity of transmitral flow (E) and Ea at the lateral border of the mitral annulus and then calculated the E/Ea ratio. After echocardiography, we measured the peak oxygen consumption and anaerobic threshold (AT) by cardiopulmonary exercise testing. Of all the echocardiographic parameters, the best correlation for AT was the E/Ea ratio (r = -0.74, p <0.001). Peak oxygen consumption correlated well with Ea and the E/Ea ratio (r = 0.64 and r = -0.68, respectively, p <0.001). The AT and peak oxygen consumption did not correlate with conventional Doppler indexes. Using an AT of 8 ml/min/kg as the cutoff to separate severe exercise intolerance from normal, mild, or moderate exercise intolerance, a receiver-operating characteristic curve showed that an E/Ea ratio of >11.3 had the best combination of sensitivity (88%) and specificity (86%). Exercise tolerance correlated with the E/Ea ratio in patients with impaired LV systolic function. In conclusion, the evaluation of LV diastolic function using tissue Doppler imaging is useful for predicting exercise tolerance in patients with heart failure.     

Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics

Left ventricular systolic function does not correlate well with functional class in patients with dilated cardiomyopathy. To determine whether the correlation is better with Doppler indexes of left ventricular diastolic function, 34 patients with dilated cardiomyopathy (M-mode echocardiographic end-diastolic dimension greater than 60 mm, fractional shortening less than 25%, increased E point-septal separation) were studied. Patients were classified into two groups according to functional class. Group 1 consisted of 16 patients in New York Heart Association functional class I or II; group 2 included 18 patients in functional class III or IV. Left ventricular dimensions, fractional shortening, left ventricular mass, meridional end-systolic wall stress, peak early and late transmitral filling velocities and their ratio, isovolumetric relaxation period and time to peak filling rate were computed from pulsed wave Doppler and M-mode echocardiograms and calibrated carotid pulse tracings. Right heart catheterization was performed in 20 of 34 patients. No differences were observed between groups with regard to age, gender distribution, heart rate, blood pressure and M-mode echocardiographic-derived indexes of systolic function. Peak early filling velocity (72 +/- 13 versus 40 +/- 10 cm/s, p less than 0.001) was higher and atrial filling fraction (27 +/- 4% versus 46 +/- 8%, p less than 0.001) was lower in group 2 than in group 1. The ratio of early to late transmitral filling velocities was higher in group 2 patients (2.3 +/- 0.5 versus 0.7 +/- 0.2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of exercise capacity in hypertrophic cardiomyopathy

Exercise capacity in hypertrophic cardiomyopathy is thought to relate to elevated left atrial pressure as a consequence of impaired diastolic function, but this assumption has not previously been evaluated. Twenty-three patients with hypertrophic cardiomyopathy underwent hemodynamic assessment during symptom-limited maximal exercise with objective measurement of exercise capacity by respiratory gas analysis. Maximal oxygen consumption and anaerobic threshold were 28.1 +/- 7.5 and 21.5 +/- 6.1 ml/kg per min, respectively (the lower limit of reference range in our laboratory is 39 and 27 ml/kg per min, respectively). Maximal oxygen consumption was reduced in 11 of 13 patients who were in New York Heart Association functional class I and who denied limitation of exercise capacity and in all 10 patients who were in functional class II or III. Maximal oxygen consumption and anaerobic threshold were related to peak cardiac index (r = 0.650, p less than 0.001 and r = 0.459, p = 0.03, respectively) and to the increase in cardiac index on exercise (r = 0.677, p less than 0.001 and r = 0.509, p = 0.016, respectively), but not to cardiac index at rest, peak and rest pulmonary capillary wedge pressure, pulmonary capillary wedge pressure at an oxygen consumption of 15 ml/kg per min or the rise in pulmonary capillary wedge pressure on exercise. These findings are not consistent with the hypothesis that elevated left atrial pressure is the major determinant of exercise capacity in patients with hypertrophic cardiomyopathy and they suggest that, as in patients with chronic cardiac failure, other mechanisms should be considered.     

Left ventricular hypertrophy differences in male professional runners and in young patients suffering from mild hypertension

AIMS: This study was executed to evaluate left ventricular (LV) geometry, diastolic and systolic function assessed by B- and M-mode and pulsed Doppler echocardiography in a group of professional sprinter runners (group I), in young patients suffering from mild hypertension (group II) and in control young adults (group III). Twenty-one male sprinter runners were checked during a period of training and compared with 19 young patients suffering from mild hypertension and 15 healthy controls matched for gender and body size. FINDINGS: LV septum thickness, LV posterior wall thickness, LV ejection fraction, LV shortening fraction, midwall fractional shortening and stroke volume were significantly higher in runners compared to hypertensive patients and controls (p < 0.001). A significant increase of diastolic function parameters of the early peak flow velocity, E, and the early/late diastolic wave ratio, E/A, and in the isovolumic relaxation time or in the E velocity deceleration time wave was observed in hypertensive patients when compared to runners and controls (p < 0.05). The study of the pulmonary venous flow revealed a significant increase in the early systolic flow velocity, S, in hypertensive patients compared to runners (p < 0.05); the late diastolic flow velocity, D, appeared to be similar in all groups, while atrial backward flow velocity, Ar, was higher in group I and II respect to control (p < 0.001). CONCLUSIONS: Our data indicate that LV concentric hypertrophy in sportsmen is associated with improvement of systolic and diastolic performance, whereas diastolic dysfunction can occurs even in the early stages of hypertension in young patients, in whom an alteration in the LV filling appears even in absence of systolic dysfunction and evident concentric myocardial hypertrophy.     

Plasma N-terminal pro-brain natriuretic peptide: a marker of left ventricular hypertrophy in hypertrophic cardiomyopathy.

BACKGROUND: B-type natriuretic peptide is secreted mainly in the left ventricle in response to elevated wall tension. Plasma levels of the peptide correlate positively with cardiac filling pressures, making it an excellent marker for the presence of left ventricular dysfunction. In hypertrophic cardiomyopathy, enhanced production of B-type natriuretic peptide is observed. However, the relationship of the various structural and functional features present in the disease with the high plasma levels described is not yet fully clarified. In the present study, we prospectively assessed in hypertrophic cardiomyopathy the relationship of plasma NT-proBNP levels with the extent of left ventricular hypertrophy, presence of left ventricular outflow obstruction and echocardiographic parameters of left ventricular diastolic function. METHODS: The study population included 190 individuals: 53 patients with hypertrophic cardiomyopathy and well-preserved left ventricular systolic function (group A), 92 healthy relatives with no disease expression (group B), and an additional group of 46 healthy volunteers (group C) as controls for NT-proBNP levels. Groups A and B were characterized clinically and by echocardiography and compared with each other. Plasma NT-proBNP levels were measured (ECLIA-Elecsys proBNP) and compared in the 3 groups of individuals included in the study. In hypertrophic cardiomyopathy patients, correlation was sought between NT-proBNP levels, NYHA functional class and echocardiographic data. RESULTS: Groups A and B differed (p < 0.001) in septal thickness, maximal wall thickness, left ventricular hypertrophy score, left atrial size, left atrial fractional shortening, derived transmitral filling indices and plasma NT-proBNP levels (group A: 909.9 +/- 1554.2 pg/ml; group B: 40.7 +/- 45.1 pg/ml). Left ventricular diastolic size and pulmonary venous flow velocity-derived indices were similar in the 2 groups. NT-proBNP levels in group B and C (39.4 +/- 34.5 pg/ml) were similar (p = NS). In hypertrophic cardiomyopathy patients, NT-proBNP levels correlate directly with NYHA functional class (r = 0.56, p < 0.001), septal thickness (r = 0.53, p < 0.001), maximal wall thickness (r = 0.59, p < 0.001), left ventricular hypertrophy score (r = 0.63, p < 0.001), left atrial size (r = 0.32, p = 0.023) and mitral deceleration time (r = 0.46, p = 0.001) and inversely with left atrial fractional shortening (r = -0.41, p = 0.005). Functional class also correlates directly with left ventricular hypertrophy score (r = 0.39, p = 0.006), with the most symptomatic patients having the highest scores. CONCLUSIONS: In hypertrophic cardiomyopathy, plasma NT-proBNP levels depend mainly on the severity of left ventricular hypertrophy rather than on the presence of obstruction. Measurement of the peptide may help in the clinical characterization and follow-up of patients with this disease.     

Usefulness of N-terminal pro-B-type natriuretic peptide levels to predict exercise capacity in hypertrophic cardiomyopathy

Most patients with hypertrophic cardiomyopathy (HC) have reduced maximal oxygen consumption (VO2max) during exercise. The degree of impairment is poorly predicted by the magnitude of hypertrophy, left ventricular (LV) outflow tract obstruction, and other conventional markers of disease severity. The aim of this study was to determine the usefulness of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) as a marker of exercise performance in HC. Plasma NT-pro-BNP was measured in 171 consecutive patients (mean age 46 +/- 18 years) who underwent echocardiography and cardiopulmonary exercise testing. The mean log NT-pro-BNP was 2.79 +/- 0.5; log NT-pro-BNP levels were higher in women patients (p = 0.001) and patients with chest pain (p = 0.010), in New York Heart Association class > or = II (p = 0.009), with atrial fibrillation (p < 0.001), with systolic impairment (p = 0.025), and with LV outflow tract obstructions (p < 0.0001). NT-pro-BNP levels were also correlated with maximal wall thickness (r = 0.335, p < 0.0001), left atrial size (r = 0.206, p = 0.007), and the mitral Doppler E/A ratio (r = 0.197, p = 0.012). The mean percent VO2max achieved was 73.8 +/- 22.6%; percent VO2max was smaller in patients with systolic impairment (p = 0.044) and LV outflow tract obstructions (p = 0.025). There were inverse correlations between percent VO2max and NT-pro-BNP (r = -0.352, p = 0.001), LV end-systolic cavity size (r = -0.182, p = 0.031), and left atrial size (r = -0.251, p = 0.003). On multivariate analysis, only NT-pro-BNP was correlated with percent VO2max. A NT-pro-BNP level of 316 ng/L had 78% sensitivity and 44% specificity (area under the curve 0.616) for predicting percent VO2max < 80%. In conclusion, NT-pro-BNP levels correlate with peak oxygen consumption in HC and are more predictive of functional impairment than other conventional markers of disease severity.     

Relationship of Doppler indexes of left ventricular filling and exertion tolerance]

The aim of this study was to evaluate if Doppler indexes of left ventricular filling are related to exercise capacity. Since a correlation between left ventricular filling pattern and causal blood pressure has been recently reported along a wide range of pressure values, a group of subjects with blood pressure ranging from normal to severely elevated values was studied. Twenty-four subjects (11 normotensives, 13 mild to severe hypertensive patients) underwent an echo-Doppler study and a maximal multistage cycloergometric exercise test. Since the cycloergometric test was limited by fatigue or dyspnea in all subjects, exercise duration was used as an effort tolerance index. Echocardiographic indexes of systolic function resulted normal in all subjects. Significant relationships with exercise duration were found for several indexes of left ventricular filling (A peak: r = -.743, p < .0001; A/E ratio: r = -.606, p < .005; early filling fraction: r = .639, p < .001). Exercise time was also significantly related to casual blood pressure, both systolic and diastolic. The relationships between transmitral blood flow and exercise capacity seem to indicate that an impairment of ventricular relaxation (as indicated by the progressive increase of atrial contribution) is associated with a decreased exercise tolerance, possibly because a progressively lower activation of Frank-Starling mechanism. Diastolic function thus seems to be able to affect exercise tolerance even in subjects with normal systolic function and blood pressure ranging from normal to severely elevated values.     

Acute changes in pulmonary artery pressures due to exercise and exposure to high altitude do not cause left ventricular diastolic dysfunction

BACKGROUND: Altitude-induced pulmonary hypertension has been suggested to cause left ventricular (LV) diastolic dysfunction due to ventricular interaction. In this study, we evaluate the effects of exercise- and altitude-induced increase in pulmonary artery pressures on LV diastolic function in an interventional setting investigating high-altitude pulmonary edema (HAPE) prophylaxis. METHODS: Among 39 subjects, 29 were HAPE susceptible (HAPE-S) and 10 served as control subjects. HAPE-S subjects were randomly assigned to prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo bid, starting 1 day before ascent. Doppler echocardiography at rest and during submaximal exercise was performed at low altitude (490 m) and high altitude (4,559 m). The ratio of early transmitral inflow peak velocity (E) to atrial transmitral inflow peak velocity (A), pulmonary venous flow parameters, and tissue velocity within the septal mitral annulus during early diastole (E') were used to assess LV diastolic properties. LV filling pressures were estimated by E/E'. Systolic right ventricular to atrial pressure gradients (RVPGs) were measured in order to estimate pulmonary artery pressures. RESULTS: At 490 m, E/A decreased similarly with exercise in HAPE-S and control subjects (HAPE-S, 1.5 +/- 0.3 to 1.3 +/- 0.3; control, 1.7 +/- 0.4 to 1.3 +/- 0.3; p = 0.12 between groups) [mean +/- SD], whereas RVPG increased significantly more in HAPE-S subjects (20 +/- 5 to 43 +/- 9 mm Hg vs 18 +/- 3 to 28 +/- 3 mm Hg, p < 0.001). Changes in RVPG levels during exercise did not correlate with changes in E/A (p > 0.1). From 490 to 4,559 m, no correlations between changes in RVPG and changes in E/A or atrial reversal (both p > 0.1) were observed. Neither of the groups showed an increase in E/E' from 490 to 4,559 m. CONCLUSION: Increased pulmonary artery pressure associated with exercise and acute exposure to 4,559 m appears not to cause LV diastolic dysfunction in healthy subjects. Therefore, ventricular interaction seems not to be of hemodynamic relevance in this setting.     

The usefulness of tissue doppler imaging in the determination of left ventricular diastolic filling pressure. Comparison with other techniques

The further examination of left ventricular diastolic function (LVDF) is important in terms of early diagnosis, therapy and follow-up of heart failure. Although cardiac catheterization is considered as the most accurate method in the evaluation of diastolic function, since it is invasive, noninvasive methods are preferred. This study was undertaken to examine whether mitral annular velocities assessed by pulsed tissue Doppler imaging (PTDI) were associated with invasive measures of diastolic LV pressure and whether additional information was gained over traditional transmitral and pulmonary venous flow velocity parameters. Doppler examination was performed in 102 patients referred to our clinic for cardiac catheterization. Doppler signals from the mitral inflow, pulmonary venous inflow, and PTDI of the mitral annulus were obtained. Mean left ventricular diastolic pressure (M-LVDP) was measured.The relationship between echocardiographic parameters and M-LVDP was investigated.A significant correlation was observed between M-LVDP and E/septal Em (r = 0.52, p < 0.000), E/lateral Em (r = 0.45, p < 0.0001), E/posterior Em (r = 0.46, p < 0.0001) E/anterior Em (r = 0.49, p < 0.0001), E/mean Em (r = 0.49, p < 0.0001), PVadur - MVadur (r = 0.51, p < 0.0001). The best echocardiographic parameters correlating with M-LVDP were E/septal Em and PVa-dur - MVa-dur. In conclusion, PTDI could be used in the assessment of LVDP. However, the combination of transmitral flow and pulmonary venous flow velocities with annular velocity can be proposed as the best method for assessing LV filling pressure that combines the influence of transmitral driving pressure and myocardial relaxation.     

Postnatal left ventricular diastolic function after fetal aortic valvuloplasty

Fetal aortic balloon valvuloplasty (FAV) has shown promise in altering in utero progression of aortic stenosis to hypoplastic left heart syndrome. In patients who achieve a biventricular circulation after FAV, left ventricular (LV) compliance may be impaired. Echocardiographic indexes of diastolic function were compared between patients with biventricular circulation after FAV, congenital aortic stenosis (AS), and age-matched controls. In the neonatal period, patients with FAV had similar LV, aortic, and mitral valve dimensions but more evidence of endocardial fibroelastosis than patients with AS. Patients with FAV underwent more postnatal cardiac interventions than patients with AS (p = 0.007). Mitral annular early diastolic tissue velocity (E') was lower in patients with FAV and those with AS and controls in the neonatal period and over follow-up (p <0.001). Septal E' was similar among all 3 groups in the neonatal period. In follow-up patients, with FAV had lower septal E' than patients with AS or controls (p <0.001). Early mitral inflow velocity/E' was higher in patients with FAV as neonates and at follow-up (p <0.001). Mitral inflow pulse-wave Doppler-derived indexes of diastolic function were similar between groups. In conclusion, echocardiographic evidence of LV diastolic dysfunction is common in patients with biventricular circulation after FAV and persists in short-term follow-up. LV diastolic dysfunction in this unique population may have important implications on long-term risk of left atrial and subsequent pulmonary hypertension.     

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.