Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema

OBJECTIVE: This prospective single-blinded study was performed to quantitate noninvasive pulmonary artery systolic pressure (PASP) responses to prolonged acute hypoxia and normoxic exercise. BACKGROUND: Hypoxia-induced excessive rise in pulmonary artery pressure is a key factor in high-altitude pulmonary edema (HAPE). We hypothesized that subjects susceptible to HAPE (HAPE-S) have increased pulmonary artery pressure response not only to hypoxia but also to exercise. METHODS: PASP was estimated at 45, 90 and 240 min of hypoxia (FiO2 = 12%) and during supine bicycle exercise in normoxia using Doppler-echocardiography in nine HAPE-S and in 11 control subjects. RESULTS: In the control group, mean PASP increased from 26+/-2 to 37+/-4 mm Hg (deltaPASP 10.3+/-2 mm Hg) after 90 min of hypoxia and from 27+/-4 to 36+/-3 mm Hg (deltaPASP 8+/-2 mm Hg) during exercise. In contrast, all HAPE-S subjects revealed significantly greater increases (p = 0.002 vs. controls) in mean PASP both during hypoxia (from 28+/-4 to 57+/-10 mm Hg, deltaPASP 28.7+/-6 mm Hg) and during exercise (from 28+/-4 to 55+/-11 mm Hg, deltaPASP 27+/-8 mm Hg) than did control subjects. Stress echocardiography allowed discrimination between groups without overlap using a cut off PASP value of 45 mm Hg at work rates less than 150 W. CONCLUSIONS: These data indicate that HAPE-S subjects may have abnormal pulmonary vascular responses not only to hypoxia but also to supine bicycle exercise under normoxic conditions. Thus, Doppler echocardiography during supine bicycle exercise or after 90 min of hypoxia may be useful noninvasive screening methods to identify subjects susceptible to HAPE.     

Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers

OBJECTIVES: We sought to determine the relationship between different echocardiographic indices and pulmonary capillary wedge pressures (PCWP) in normal volunteers. BACKGROUND: Indices based on tissue Doppler (TDE) and color M-mode (CMM) echocardiography have been proposed to reflect left (LV) ventricular filling pressures. These include the ratio of early diastolic transmitral velocity (E) to early myocardial velocity measured by TDE (E') and the ratio of E to the wave propagation velocity (Vp) measured from CMM images. These indices, however, have not been validated in normal individuals. METHODS: We studied seven volunteers during two phases of preload altering maneuvers, baseline, with two stages of lower body negative pressure, and repeat baseline with two stages of volume loading. The PCWP obtained from right heart catheterization was compared with diastolic indices using pulsed Doppler, TDE and CMM echocardiography. RESULTS: The PCWP ranged from 2.2 to 23.5 mm Hg. During preload alterations, significant changes in E and septal E' (both p < 0.05) but not lateral E' or Vp were observed. Furthermore, E, septal E' and E/Vp correlated with PCWP (all r > 0.80) but not combined E and TDE indices (both r < 0.15). Within individuals, a similar linear relationship was observed among E/Vp, E and septal E' (average r > 0.80). CONCLUSIONS: In subjects without heart disease, E, septal E' and E/Vp correlate with PCWP. Because the influence of ventricular relaxation is minimized, the ratio E/Vp may be the best overall index of LV filling pressures.     

Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema

RATIONALE: High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung. Objectives: We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature. METHODS: During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects. MAIN RESULTS: Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02). CONCLUSIONS: Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.     

Importance of the left ventricular filling pressure on diastolic filling in idiopathic dilated cardiomyopathy

Both mitral regurgitation and elevated left ventricular (LV) filling pressures may normalize or enhance rapid filling in patients with idiopathic dilated cardiomyopathy. To assess the individual effects of the LV filling pressure and mitral regurgitation, 33 normal subjects, 14 patients with cardiomyopathy and normal LV filling pressures (measured as mean pulmonary capillary pressure) and 26 patients with elevated LV filling pressures (greater than 15 mm Hg) were studied with transmitral spectral tracings derived from pulsed Doppler echocardiography. Both cardiomyopathy groups demonstrated similarly dilated left ventricles with reduced systolic dysfunction. Patients with cardiomyopathy and normal LV filling pressures had prolonged isovolumic relaxation periods and a reduced ratio of the rapid filling to atrial filling integrals. Patients with cardiomyopathy and elevated LV pressures demonstrated an increased peak rapid filling velocity (97 +/- 21 cm/s) and rapid filling fraction (74.8 +/- 16.2%) compared with normal subjects (80 +/- 16 cm/s, p less than 0.01; 62.4 +/- 12.5%, p less than 0.05) and patients with cardiomyopathy and normal LV filling pressures (81 +/- 27 cm/s, p less than 0.05; 59.3 +/- 8.8%, p less than 0.05). Conversely, the atrial filling fraction was decreased in the cardiomyopathy group with elevated LV filling pressures compared with normal subjects and patients with cardiomyopathy and normal LV filling pressures. Mitral regurgitation increased the peak rapid filling velocity in both cardiomyopathy groups without altering the distribution of diastolic filling. In conclusion, elevated LV filling pressures appear to affect the distribution of diastolic filling, whereas mitral regurgitation affects the peak rate of rapid filling.     

Influence of alterations in loading on mitral annular velocity by tissue Doppler echocardiography and its associated ability to predict filling pressures

STUDY OBJECTIVES: Early diastolic mitral annular velocity (E') by tissue Doppler echocardiography (TD) has been reported to be a load-independent index of left ventricular (LV) diastolic function, allowing the early diastolic mitral inflow velocity (E)/E' ratio to be used clinically to predict LV filling pressures. However, preload independence of E' has remained controversial, and E/E' may not consistently be predictive of LV filling pressures. Our objectives were to test the hypotheses that E' is affected by preload, and that alterations of preload, afterload, and contractility also affect E/E'. DESIGN, INTERVENTIONS, AND MEASUREMENTS: An open-chest dog model was used (n = 8). High-fidelity pressure and conductance catheters were used for pressure-volume relations, and E' was obtained by pulsed TD from the apical four-chamber view. Changes in preload and afterload were induced by vena caval and partial aortic occlusions, respectively. Data were collected during control phase and during infusions of dobutamine and esmolol to alter contractility. RESULTS: E' was consistently and significantly associated with acute decreases in LV end-diastolic pressure in each dog (n = 200 beats; r = 0.93 +/- 0.06 [mean +/- SD]). Similar results occurred with dobutamine and esmolol infusions. This preload sensitivity was reflected in E/E', which was inversely (rather than directly) correlated with LV diastolic pressure (r = - 0.67). E/E' was less affected by preload when diastolic dysfunction was induced by sustained partial aortic occlusion (time constant of relaxation increased from 46 +/- 19 to 53 +/- 21 ms, p < 0.001). CONCLUSIONS: E' was significantly influenced by preload with preserved LV function and low filling pressures (< 12 mm Hg); accordingly, E/E' was less predictive of LV filling pressures in this scenario. E/E' was more predictive of LV filling pressures in the presence of diastolic dysfunction.     

Comparative value of tissue Doppler imaging and m-mode color Doppler mitral flow propagation velocity for the evaluation of left ventricular filling pressure

BACKGROUND: Recently, two new indexes based on the ratio of transmitral early diastolic velocity (E) to tissue Doppler imaging (TDI), and early diastolic velocity of mitral annulus (E') and E to propagation velocity (Vp) have been proposed to predict left ventricular (LV) filling pressures. However, little is known about the comparative value of these two indexes. METHODS: We studied 71 consecutive patients referred for coronary angiography (mean age +/- SD, 65 + 11 years; 21 patients with LV ejection fraction [EF] < 50%). Complete Doppler echocardiographic examination including TDI and Vp measurements and direct measurement of LV end-diastolic pressure (LVEDP) were performed simultaneously in the catheterization laboratory. LV filling pressures were considered elevated when LVEDP was > or = 15 mm Hg. RESULTS: The correlation coefficients between E/E' and E/Vp and LVEDP were 0.68 (p = 0.01) and 0.54 (p = 0.01), respectively, in the overall population. The correlations were better in patients with low LV EF (< 50%) [0.8 (p = 0.01) and 0.77(p = 0.01)] and poor in patients with normal LV EF (0.57 [p = 0.05] and 0.41 [not significant]), respectively. Moreover, Vp measurements had higher interobserver variability compared to E' (14% vs 7%). The cutoff values for both indexes giving the best sensitivity and specificity in identifying LVEDP > or = 15 mm Hg were 9 for (E/E') and 2 for (E/Vp). CONCLUSION: Both E/E' and E/Vp can be used for the evaluation of LV filling pressures. However, the sensitivity of these indexes, especially E/Vp, is hampered by EF. E/E' has a lower variability than Vp and should be preferred for estimation of filling pressures especially in patients with EF > 50%.     

Impact of left ventricular diastolic function on exercise capacity in patients with chronic mitral regurgitation: an exercise echocardiography study

BACKGROUND: Mitral regurgitation (MR) is known as one of the most frequent causes of heart failure and sudden death. In spite of increasing prevalence of MR, there have been no available data on cardiac determinants of exercise capacity in patients with chronic MR. HYPOTHESIS: This study aimed to investigate cardiac determinants of exercise capacity in patients with chronic MR. METHODS: We consecutively enrolled 32 patients (11 men, mean age: 44 +/- 14 years) who had greater than moderate MR with normal left ventricular (LV) systolic function (LV ejection fraction >50%). Conventional echocardiographic indices and parameters measured by Doppler tissue imaging at septal side of mitral annulus were obtained before exercise. Mitral regurgitation fraction, forward stroke volume, pulmonary venous flow velocities, and systolic pulmonary artery pressure (sPAP) were also obtained with standard methods. RESULTS: Left ventricular ejection fraction was 61 +/- 6% and MR fraction was 48 +/- 13%. All patients finished a symptom-limited treadmill exercise test with a peak heart rate of >85% of predicted maximum heart rate. Mean exercise time was 9.95 +/- 2.17 min, corresponding to 11 +/- 2 metabolic equivalents. Among pre-exercise echocardiographic variables, only early diastolic mitral annulus velocity (E') and pulmonary venous reversal flow velocity (PVa) showed a significant correlation with exercise time (r = 0.44, p = 0.011, and r = -0.40, p = 0.040, respectively), which persisted after multivariate analysis (p = 0.011 and 0.038, respectively). Other parameters such as systolic mitral annulus velocity, resting and postexercise sPAP, forward stroke volume, LV size, LV ejection fraction, left atrial size, and regurgitant fraction showed no significant correlation. CONCLUSIONS: Left ventricular diastolic function is an important determinant of exercise capacity in patients with chronic MR. Both E' and PVa, accepted surrogate estimates for LV diastolic function, may be useful for identifying patients with chronic MR and with poor exercise capacity.     

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.     

Sustained improvement in left ventricular diastolic function after alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

AIMS: Impaired diastolic function is responsible for many of the clinical features of hypertrophic cardiomyopathy. In patients with hypertrophic obstructive cardiomyopathy (HOCM) whose symptoms are refractory to medical therapy, alcohol septal ablation (ASA) reduces left ventricular (LV) outflow tract gradient, with short-term improvement in LV diastolic function. Little is known about the longer term impact of ASA on diastolic function. METHODS AND RESULTS: We evaluated LV diastolic function at baseline and 1- and 2-year follow-up after successful ASA. In 30 patients (58+/-15 years, 22 men) who underwent successful ASA, New York Heart Association class was lower at 1-year follow-up compared with baseline (3.0+/-0.5 to 1.5+/-0.7; P<0.0001). LV outflow tract gradient (76+/-37 to 19+/-12; P<0.0001), interventricular septal thickness (19+/-2 to 14+/-2; P<0.0001), and left atrial volume (26+/-5 to 20+/-4; P<0.0001) were decreased. Significant improvement in E-wave deceleration time, isovolumic relaxation time, early diastolic mitral lateral annular velocity (E'), mitral inflow propagation velocity (V(p)), ratio of transmitral early LV filling velocity (E) to early diastolic Doppler tissue imaging of the mitral annulus (E/E'), and E/V(p) were observed at 1 year following successful ASA. These changes persisted in the subset cohort (n=21) for whom 2-year data were available. CONCLUSION: Successful ASA for HOCM leads to significant and sustained improvement in echocardiographic measures of diastolic function, which may contribute to improved functional status after successful ASA.     

Impact of left ventricular diastolic dysfunction on maximal treadmill performance in normotensive subjects with well-controlled type 2 diabetes mellitus

Patients with type 2 diabetes often have impaired exercise capacity compared with nondiabetic subjects. Left ventricular (LV) diastolic dysfunction has been shown to limit exercise performance in nondiabetic subjects. Men with well-controlled type 2 diabetes were divided into 2 groups: normal LV diastolic function (group 1, n = 9) or LV diastolic dysfunction (group 2, n = 10) based on standard echocardiographic criteria using pulmonary veins and transmitral flow recordings. They were matched for age and had no evidence of systemic hypertension, macroalbuminuria, coronary artery disease, congestive heart failure, clinical diabetic complications, and thyroid disease. Good metabolic control was demonstrated by glycated hemoglobin levels of 6.7+/-1.6% and 6.6+/-2.5% (means +/- SD) in patients with LV diastolic dysfunction and in controls, respectively. Each subject performed a symptom-limited modified Bruce protocol treadmill exercise test. Maximal treadmill performance was higher in subjects with normal diastolic function compared with subjects with LV diastolic dysfunction when expressed in time (803+/-29 vs. 662+/-44 seconds, respectively, p<0.02) or in METs (11.4+/-1.2 vs. 9.5+/-1.9 METs, respectively, p<0.02). Moreover, there was a correlation between E/A ratio and exercise duration (r = 0.64, p = 0.004) or E/A ratio and METs (r = 0.658, p = 0.003). There were no significant differences in maximal heart rate, maximal systolic and diastolic blood pressure, or maximal rate-pressure product attained during the exercise test. In conclusion, this study demonstrated that LV diastolic dysfunction influences maximal treadmill performance and could explain lower maximal performance observed in patients with type 2 diabetes.     

Pattern of left ventricular diastolic filling associated with right ventricular enlargement

Right ventricular (RV) dilatation associated with pressure overload may alter left ventricular (LV) geometry resulting in abnormal diastolic function as demonstrated by a smaller LV diastolic volume for a given LV diastolic pressure. To determine whether abnormalities in LV geometry due to RV dilatation result in abnormalities in the LV diastolic filling pattern, we obtained pulsed Doppler transmitral recordings from 23 patients with RV dilatation with RV systolic pressure estimated to be less than 40 mm Hg (group 1), 18 patients with RV dilatation and RV systolic pressures greater than or equal to 40 mm Hg (group 2) and 33 normal patients. RV systolic pressures were estimated from continuous wave Doppler peak tricuspid regurgitation velocities using the modified Bernoulli equation. Diastolic filling parameters in group 1 patients were similar to normals. In group 2 patient, increased peak atrial filling velocity (76 +/- 14 vs 57 +/- 12 cm/s, p less than 0.001), decreased peak rapid filling velocity/peak atrial filling velocity (1.1 +/- 0.4 vs 1.5 +/- 0.4, p less than 0.01), increased atrial filling fraction (41 +/- 14 vs 30 +/- 10%, p less than 0.01) and prolongation of the atrial filling period (171 +/- 47 vs 152 +/- 39 ms, p less than 0.05) were noted compared with the normal group. RV end-diastolic size and LV end-systolic shape were significantly correlated with the atrial filling fraction in group 2 patients. In patients with RV dilatation and RV systolic pressures greater than or equal to 40 mm Hg, there is increased reliance on atrial systolic contribution to the LV filling volume.     

Effects of preload reduction on mitral flow velocity pattern in normal subjects

In the last few years, alterations in transmitral diastolic flow pattern have been used to assess changes in left ventricular diastolic properties. However, since diastolic flow primarily reflects the atrioventricular pressure gradient, loading conditions, as well as intrinsic left ventricular properties, should be able to affect this pattern. This study was selectively designed to decrease preload (a major determinant of the atrioventricular pressure gradient) in normal subjects to observe the effects on the Doppler transmitral flow pattern without pharmacologic interventions that may also affect left ventricular diastolic properties. In 12 normal subjects, preload was reduced by inflation of blood pressure cuffs placed at the level of the root of the 4 limbs. The peak velocity of early mitral flow (E wave) decreased from 62 +/- 8 to 51 +/- 7 cm/s (p less than 0.001), while no changes were found in the maximal velocity after atrial contraction; this caused a significant decrease in the ratio of these 2 velocities (the E to A ratio) from 1.5 +/- 0.3 to 1.1 +/- 0.1 (p less than 0.001). The time-velocity integral of early diastolic inflow decreased from 7.8 +/- 1.3 to 6.1 +/- 1.3 cm (p less than 0.001) with no significant changes of the time-velocity integral of inflow after atrial contraction. Therefore, preload reduction in normal subjects significantly reduces transmitral flow in early diastole with preserved late ventricular filling, producing a pattern that can mimic the changes previously described in left ventricular diastolic dysfunction.     

A real-time three-dimensional echocardiographic quantitative analysis of left atrial function in left ventricular diastolic dysfunction

The evaluation of left ventricular diastolic function provides important information about hemodynamics and has prognostic implications for various cardiac diseases. In particular, left atrial (LA) volume is an increasingly significant prognostic biomarker for diastolic dysfunction. The aim of this study was to assess left ventricular diastolic function by measuring changes in LA volume using real-time 3-dimensional echocardiography. The 106 subjects were divided into 4 groups (normal, impaired relaxation, pseudonormal, and restrictive) on the basis of diastolic function, as assessed by transmitral flow patterns. LA volume was measured during a heart cycle using real-time 3-dimensional echocardiography. LA stroke volume (maximum LA volume - minimum LA volume) and the LA ejection fraction (LA stroke volume/maximum LA volume x 100) were calculated using Doppler imaging to assess their correlation with other parameters used to evaluate left ventricular diastolic function, including transmitral flow pattern and early diastolic mitral annular velocity (E'). LA volume indexed to body surface area was dilated in subjects with left ventricular diastolic dysfunction, whereas the LA ejection fraction was lower. The maximum LA volume, minimum LA volume, and LA ejection fraction were significantly different between each group, and each was significantly correlated with the ratio of early diastolic transmitral flow velocity (E) to E' (E/E'). The LA ejection fraction correlated best with E/E' (r = -0.68, p <0.0001). In conclusion, cyclic changes in LA volume could be measured using real-time 3-dimensional echocardiography, and measuring LA function with this method may be a viable alternative for the accurate assessment of left ventricular diastolic function.     

Patients with a hypertensive response to exercise have impaired left ventricular diastolic function

An exaggerated increase in systolic blood pressure prolongs myocardial relaxation and increases left ventricular (LV) chamber stiffness, resulting in an increase in LV filling pressure. We hypothesize that patients with a marked hypertensive response to exercise (HRE) have LV diastolic dysfunction leading to exercise intolerance, even in the absence of resting hypertension. We recruited 129 subjects (age 63+/-9 years, 64% male) with a preserved ejection fraction and a negative stress test. HRE was evaluated at the end of a 6-min exercise test using the modified Bruce protocol. Patients were categorized into three groups: a group without HRE and without resting hypertension (control group; n=30), a group with HRE but without resting hypertension (HRE group; n=25), and a group with both HRE and resting hypertension (HTN group; n=74). Conventional Doppler and tissue Doppler imaging were performed at rest. After 6-min exercise tests, systolic blood pressure increased in the HRE and HTN groups, compared with the control group (226+/-17 mmHg, 226+/-17 mmHg, and 180+/-15 mmHg, respectively, p<0.001). There were no significant differences in LV ejection fraction, LV end-diastolic diameter, and early mitral inflow velocity among the three groups. However, early diastolic mitral annular velocity (E') was significantly lower and the ratio of early diastolic mitral inflow velocity (E) to E' (E/E') was significantly higher in patients of the HRE and HTN groups compared to controls (E': 5.9+/-1.6 cm/s, 5.9+/-1.7 cm/s, 8.0+/-1.9 cm/s, respectively, p<0.05). In conclusion, irrespective of the presence of resting hypertension, patients with hypertensive response to exercise had impaired LV longitudinal diastolic function and exercise intolerance.     

Effect of intravenous administration of cibenzoline on left ventricular diastolic pressures in patients with hypertrophic cardiomyopathy: its relationship to transmitral Doppler flow profiles.

BACKGROUND: Cibenzoline is able to improve left ventricular (LV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM), but the exact mechanism remains to be determined. METHODS AND RESULTS: The present study was designed to elucidate the effect of intravenous administration of 1.4 mg/kg of cibenzoline on aortic and LV pressures, and transmitral Doppler flow pattern in 7 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 9 patients with hypertrophic nonobstructive cardiomyopathy (HNCM). Before and at the end of the administration, aortic and LV pressures, LV pressure gradient (LVPG) and transmitral Doppler velocity profiles were examined. After the administration of cibenzoline, LV minimal and end-diastolic pressures decreased from 9+/-4 mmHg to 1+/-5 mmHg (p=0.0049) and from 22+/-7 mmHg to 14+/-5 mmHg (p=0.0106) in patients with HOCM, and from 9+/-5 mmHg to 5+/-3 mmHg (p=0.0036) and from 20+/-6 mmHg to 14+/-3 mmHg (p=0.0033) in patients with HNCM. LVPG decreased in all patients with HOCM. E-wave velocity increased, A-wave velocity decreased, and thus the E/A ratio increased from 0.77+/-0.29 to 1.20+/-0.48 (p=0.0004). CONCLUSIONS: Reduction of LV diastolic pressures by intravenous administration of cibenzoline may be related to an improvement in the E/A ratio in patients with HCM.     

Doppler assessment of pulmonary hypertension induced by hypoxic breathing in subjects susceptible to high altitude pulmonary edema

To verify the abnormal pulmonary vascular response implicated in the pathogenesis of high altitude pulmonary edema (HAPE), we examined the hemodynamic responses to hypoxia in HAPE-susceptible subjects (HAPE-S) by means of both right heart catheterization and pulsed Doppler echocardiography. The HAPE-S were seven men and one woman with a history of HAPE. Six healthy volunteers who had repeated experiences of mountain climbing without any history of altitude-related problems served as control subjects. The HAPE-S showed much greater increase in pulmonary vascular resistance (PVR) than did the control subjects, resulting in a much higher level of pulmonary arterial pressure (Ppa) under acute hypoxia both of 15% O2 and 10% O2. We then evaluated the usefulness of pulsed Doppler echocardiography in the prediction of pulmonary hypertension. Acceleration time (AcT) and right ventricular ejection time (RVET) were measured from the flow velocity pattern in the right ventricular outflow tract. The ratio of AcT to RVET was correlated to invasively determined mean Ppa (Ppa) and PVR. The results were as follows: (1) AcT/RVET = 0.52 to 0.0047 (Ppa), r = -0.93, SEE = 0.017, p less than 0.001 (HAPE-S); (2) AcT/RVET = 0.55 to 0.0055 (Ppa), r = -0.70, SEE = 0.030, p less than 0.001 (HAPE-S); (4) AcT/RVET = 0.52 to 0.00077 (PVR), r = -0.91, SEE = 0.016, p less than 0.001 (control subjects). We conclude that HAPE-S have a constitutional abnormality in the pulmonary vascular response to hypoxia, which is a possible causative factor of HAPE, and that pulsed Doppler echocardiography may be supportive to assess the pulmonary vascular pressor response in the HAPE-S.     

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.     

Cardiac structure and function before and after acute and chronic verapamil administration in hypertensive patients.

The aim of this study has been to analyze the acute and chronic effects of oral verapamil on diastolic function indices, derived from Doppler echocardiography, and left-ventricular (LV) dimensions and mass, assessed by M-mode echocardiography, in hypertensive patients without LV hypertrophy. 12 patients with essential hypertension were studied in basal conditions and (1) after a single oral administration of verapamil 160 mg and placebo in a double-blind protocol and (2) over chronic treatment (12 months) with verapamil 240 mg/day. At baseline, the ratio between early and atrial-induced transmitral velocities (E/A ratio) was lower in patients than in 12 age-matched normal subjects (1.08 +/- 0.2 vs. 1.51 +/- 0.3, p less than 0.01). Acute verapamil administration significantly decreased arterial blood pressure (162 +/- 26/101 +/- 8 to 142 +/- 12/88 +/- 7 mm Hg, p less than 0.01 after 2 h) and increased the E/A ratio to 1.26 +/- 0.3 (p less than 0.05) after 3 h. No change in ventricular dimensions and heart rate was observed. After chronic therapy, we found a further increase in the E/A ratio in 10 responder patients (1.49 +/- 0.3, p less than 0.01). The LV mass index, that was higher than in normal subjects before the treatment (118 +/- 16 vs. 91 +/- 11 g/m2, p less than 0.01), was significantly reduced (100 +/- 17 g/m2, p less than 0.05 vs. basal, nonsignificant vs. normal subjects). Our results demonstrate that acute administration of verapamil only partially improves the abnormal indices of diastolic function in hypertensive patients, whereas chronic treatment, by reducing LV mass indices and blood pressure to normal values, can completely normalize the indices of LV diastolic filling.     

Significance of left atrial volume in patients < 20 years of age with hypertrophic cardiomyopathy

Left atrial (LA) enlargement is an indicator of chronic elevation in left ventricular (LV) end-diastolic pressure as well as diastolic dysfunction. There is a lack of data on the significance of LA volume in the pediatric population. The objective of this study was to elucidate the relation between LA volume and diastolic dysfunction, clinical symptoms, and exercise capacity in young patients with hypertrophic cardiomyopathy. All patients aged <20 years with obstructive hypertrophic cardiomyopathy who underwent evaluation at the Mayo Clinic from 2002 to 2006 were retrospectively identified. Reviews of the LA volume index and other traditional diastolic Doppler echocardiographic parameters, as well as clinical data, were performed. A total of 88 patients (66 male) were studied. The median age at evaluation was 14 years. The mean LA volume index was 39 +/- 19 ml/m(2). Additional echocardiographic parameters included a mean LV outflow gradient of 55 +/- 51 mm Hg, a mean E/E' ratio of 14.0 +/- 7.6, and a mean maximal septal wall thickness of 23 +/- 9 mm. On univariate linear regression analysis, LA volume index had an excellent correlation with diastolic dysfunction grade (p <0.001, r(2) = 0.6), LV outflow tract gradient, mitral E/E', and the degree of mitral regurgitation. LA volume index was also positively associated with symptom score (p = 0.005) and maximal oxygen consumption on exercise test (n = 22; p = 0.01). On multivariate analysis, LA volume index was related to diastolic dysfunction grade (p <0.001) and mean mitral regurgitation grade (p = 0.05). In conclusion, this study demonstrates the potential clinical importance of LA volume index in pediatric hypertrophic cardiomyopathy as a marker of the severity of underlying diastolic dysfunction, symptom score, and decreased exercise capacity. LA volume index has significant diagnostic and prognostic value in these patients.     

Effect of mitral regurgitation on diastolic filling with left ventricular hypertrophy

Earlier studies have suggested that mitral regurgitation (MR) augments early left ventricular (LV) diastolic filling. To determine whether MR affects early diastolic filling in patients with abnormal diastolic filling, transmitral pulsed-wave Doppler recordings were used to study 32 normal subjects, 21 patients with LV hypertrophy, 23 with LV hypertrophy and MR and 15 patients with MR. Patients with MR had increased peak early filling velocities (MR 108 +/- 27 cm/s, normal 80 +/- 16 cm/s, p less than 0.01), peak atrial filling velocities (MR 72 +/- 18 cm/s, normal 55 +/- 12 cm/s, p less than 0.05) and increased deceleration rates (MR 5.0 +/- 1.9 m/s2, normal 3.5 +/- 1.2 m/s2, p less than 0.05). Patients with LV hypertrophy had reduced peak early filling velocities (69 +/- 14 cm/s, p less than 0.05) and increased peak atrial filling velocities (83 +/- 16 cm/s, p less than 0.001). There was also an increase in the atrial filling fraction and reduction in the rapid filling fraction as compared with normal patients. Patients with LV hypertrophy and MR had increased peak early filling velocities (98 +/- 26 cm/s, p less than 0.01 vs normal, p less than 0.001 vs LV hypertrophy patients), increased atrial filling velocities (84 +/- 27 cm/s, p less than 0.001 vs normal), increased deceleration rates (4.4 +/- 2.4 m/s2, p less than 0.05 vs normal) and a normal distribution of diastolic filling. Within the LV hypertrophy and MR group, diastolic filling parameters were similar when patients were subgrouped on the basis of auscultability of MR. MR augments early diastolic filling and may tend to normalize diastolic filling patterns in LV hypertrophy patients.(ABSTRACT TRUNCATED AT 250 WORDS)