Kensaku Kagawa

Marked expression of plasma brain natriuretic peptide is a special feature of hypertrophic obstructive cardiomyopathy

OBJECTIVES We examined whether plasma brain natriuretic peptide levels are abnormally elevated in hypertrophic obstructive cardiomyopathy compared with other cardiac diseases. BACKGROUND We previously reported that plasma brain and atrial natriuretic peptide levels were elevated in hypertrophic cardiomyopathy. METHODS We compared plasma concentrations of brain and atrial natriuretic peptide and hemodynamic and echocardiographic data in 50 patients with hypertrophic obstructive cardiomyopathy (n = 15, mean [+/-SD] intraventricular pressure gradient 37 +/- 16 mm Hg), hypertrophic nonobstructive cardiomyopathy (n = 15), aortic stenosis (n = 10, mean pressure gradient 41 +/- 18 mm Hg) and hypertensive heart disease (n = 10, mean systolic/diastolic blood pressure 203 +/- 16/108 +/- 11 mm Hg, respectively) and 10 normal subjects. RESULTS Plasma brain natriuretic peptide levels were higher in the hypertrophic obstructive cardiomyopathy group (397.1 +/- 167.8 pg/ml*) than in the hypertrophic nonobstructive cardiomyopathy (60.0 +/- 48.1 pg/ml*), hypertensive heart disease (53.9 +/- 31.4 pg/ml*), aortic stenosis (75.4 +/- 54.3 pg/ml*) and normal groups (9.8 +/- 6.4 pg/ml [*p < 0.05 vs. normal group, p < 0.05 vs. hypertrophic obstructive cardiomyopathy group]). Although plasma atrial natriuretic peptide levels were higher in the hypertrophic obstructive cardiomyopathy group than the other patient groups, the brain/atrial natriuretic peptide ratio in the hypertrophic obstructive cardiomyopathy group was higher (4.5 +/- 2.3) than those in the other three patient groups (1.1 to 1.4) and the normal group (0.7 +/- 0.5). Left ventricular end-diastolic pressure and left ventricular end-diastolic volume index were similar among the four patient groups. The interventricular septal thickness and the ratio of interventricular septal thickness to left ventricular posterior wall thickness were similar between the hypertrophic obstructive and nonobstructive cardiomyopathy groups. CONCLUSIONS Abnormal elevations of plasma brain natriuretic peptide levels are difficult to explain on the basis of hemodynamic and echocardiographic data and are a special feature of hypertrophic obstructive cardiomyopathy.

Age-related increase in systolic fraction of pulmonary vein flow velocity-time integral from transesophageal doppler echocardiography in subjects without cardiac disease

The pulmonary vein flow velocity-time profile would be equivalent to the pulmonary vein flow volume-time profile, provided that the cross-sectional area of the pulmonary vein remains unchanged during 1 cardiac cycle. The systolic fraction of the pulmonary vein flow velocity-time integral, a ratio of velocity-time integral of the S wave to the sum of velocity-time integrals of the S and D waves, represents the ratio of left atrial storage volume to left ventricular stroke volume. This systolic fraction may help early filling of the left ventricle through an appropriate storage of blood and generation of driving pressure in the left atrium. Because early filling of the left ventricle is progressively impaired with age, it was hypothesized that this systolic fraction is increased with age. Forty-four noncardiac surgical patients (age range 17 to 70 years) who underwent transesophageal Doppler echocardiography under general anesthesia were studied, and left upper pulmonary vein flow and mitral inflow velocities were recorded. The ratio of peak velocity of the E wave to that of the A wave of mitral inflow velocity-time profile (y) decreased with age (y = -0.0245 x age + 2.41; r = -0.672, p < 0.01). Systolic fraction (y) increased with age (y = 0.00373 x age + 0.514; r = 0.656, p < 0.01). The age-related increase in the systolic fraction of pulmonary vein flow velocity-time integral may account for the compensation for impaired early filling of the left ventricle in elderly patients.

Diastolic compliance of the left atrium in man: A determinant of preload of the left ventricle

SummaryDuring the ventricular slow-filling period, both the left atrium and left ventricle fill passively, and their respective internal pressures equalize, becoming evenly elevated. If the diastolic chamber compliance of the left atrium is smaller than that of the left ventricle, we expect the inflowing blood to be distributed more to the left ventricle than to the left atrium during this period. We examined the magnitude of the diastolic compliance of the left atrium and the left ventricle at the end of the slow-filling period.We studied 10 patients, mostly with a mild degree of coronary artery disease, in whom hemodynamic variables were almost within normal limits. To estimate the compliance of the left atrium, we recorded the left atrial pressure directly (by the Brockenbrough technique) and determined the left atrial volume by biplane cineatriography. We determined the diastolic compliance of the left atrium from the pressure-volume relations between the nadir of the x trough and the peak of the v wave by fitting them to an exponential equation, P=b · eaV (P = pressure, V = volume, a, b = constants). The diastolic compliance of the left ventricle was determined from the pressure-volume relations during the ventricular slow-filling period.The compliances of the left atrium and the left ventricle at the pressure at the end of the ventricular slow-filling period were 1.60±0.41 (mean ± SD) ml · mmHg−1 · m−2 and 4.22±1.12, respectively. The ratio of compliance of the left ventricle to that of the left atrium was 2.60±0.71.Since the diastolic compliance of the left ventricle is 2–3 times larger than that of the left atrium, we suggest that during the slow-filling period, the interaction between the left atrial and left ventricular diastolic compliances provides preferential delivery of blood to the left ventricle and acts as a determinant of volume at the end of the slow-filling period of the left ventricle.

Transesophageal Doppler echocardiographic assessment of pulmonary venous flow pattern in subjects without cardiovascular disease

This study was designed to assess pulmonary venous flow dynamics using transesophageal Doppler echocardiography. Under general anesthesia, we studied 54 surgical patients with no history or physical evidence of cardiac disorders. In all patients pulmonary venous flow was easily identified by transesophageal color flow mapping. Pulmonary venous flow pattern, which was obtained clearly in 85% (4654) of patients by transesophageal pulsed Doppler echocardiography, was tri- or quadriphasic. The first wave, which was often biphasic in elderly patients, occurred during ventricular systole (S wave). The second wave occurred in diastole during the early ventricular filling phase of mitral flow (D wave). The third wave was reverse flow toward the pulmonary vein during atrial contraction (A wave). The following variables were measured: the peak flow velocities of each wave (PFVs, PFVd, PFVa), and the ratio of PFVs to PFVd (PFV(S/D)). The PFVd correlated with age (r=−0.56, P<0.001), indicating age-related decrease. The PFV(S/D) correlated with age (r=0.61, p<0.001), indicating age-related increase. These results would indicate that the contribution of pulmonary venous flow during diastole to total pulmonary venous flow decreases with age.Our data suggest that age-related diastolic dysfunction of the left ventricle would affect pulmonary venous flow dynamics and that left atrial storage volume during ventricular systole would increase with age.

Time-course of recovery of atrial contraction after cardioversion of chronic atrial fibrillation

SummaryWe aimed to study the time-course of recovery of atrial contraction after cardioversion of chronic atrial fibrillation (duration of more than 3 months) to sinus rhythm. Using M-mode, two-dimensional and pulsed Doppler echocardiography, we determined left atrial (LA) and ventricular (LV) dimensions, peak velocities, and velocity-time integrals of early and atrial filling velocity-time profiles in both LV and right ventricular (RV) inflows (peak E and peak A, Ea and Aa). Results of the LA and LV functions in seven elderly patients (an initial study group) were as follows. The extent of the LA dimensional reduction resulting from atrial contraction was significantly increased up to 5–8 weeks compared with values 0–1 day after cardioversion [from 1.3 ± 0.8(mean ± SD) mm to 3.9 ± 1.1,P < 0.01]. In conjunction with the progressive increase in peak A, the ratio of peak E to peak A (peak E/A) was significantly decreased and reached a plateau at 5–8 weeks (from 1.93 ± 0.59 to 0.67 ± 0.11,P < 0.01). LV fractional shortening was increased significantly 5–8 weeks after cardioversion (from 0.20 ± 0.06 to 0.29 ± 0.05,P < 0.01). Since a large part of the improvement in LA contraction was expected to occur in an early stage after cardioversion, we studied eight additional patients more frequently in the early stage (an additional study group). Furthermore, we studied the time course of LA and right atrial (RA) contractions. The peak A in LV inflow velocity was significantly and progressively increased up to 1–3 weeks compared with values within 24 h after cardioversion (from 23.1 ± 7.6 cm/s to 40.6 ± 9.9,P < 0.01). The peak A in RV inflow velocity was similarly increased (from 17.6 ± 7.2 cm/s to 28.1 ± 5.4,P < 0.01). Peak E/A in LV inflow velocity was significantly and progressively decreased at 1–3 weeks, and this was also the case with peak E/A in RV inflow velocity. We conclude that it takes several weeks for each of the left and right atria to restore full strength after cardioversion of chronic atrial fibrillation.

Atrial reservoir and active transport function after cardioversion of chronic atrial fibrillation

SummaryAtrial reservoir function has not been studied after successful cardioversion of chronic atrial fibrillation. Using transthoracic and transesophageal Doppler echocardiography, we measured flow velocitytime integrals of the systolic forward (Sa), diastolic forward (Da), and diastolic reversed (rAa) waves of flow velocity waveforms in the pulmonary vein and the superior vena cava, and those of the early diastolic (Ea) and late diastolic (Aa) waves of the transmitral and transtricuspid flow velocity waveforms. The left and right atrial storage fractions (LASF, RASF), indexes of atrial reservoir function, were determined as the ratios of the atrial storage volume to the ventricular stroke volume; (Sa − rAa)/(Sa − rAa + Da). The left and right atrial active contraction fractions (LAACF, RAACF), indexes of atrial active transport function, were also determined as the ratios of the atrial active contraction volume to the left ventricular stroke volume; Aa/(Ea + Aa). These indices were evaluated periodically in 12 patients with non-valvular chronic atrial fibrillation before and 1–4 days after direct current cardioversion of atrial fibrillation; in 8 of the patients, the indices were also evaluated 1–3 months after the cardioversion. An additional 10 patients in sinus rhythm served as controls. Both the LASF and RASF were low during atrial fibrillation; the values increased significantly 1–4 days after successful cardioversion (P < 0.01,P < 0.01), and continued to increase at 1–3 months. The LASF and RASF values 1–3 months after cardioversion were comparable to those in control subjects. Both the LAACF and RAACF also increased significantly from 1–4 days to 1–3 months after cardioversion (P < 0.05,P < 0.01), becoming comparable to those in control subjects. During the 3 months after successful cardioversion of non-valvular chronic atrial fibrillation, left and right atrial reservoir function and left and right atrial active transport function increased progressively, becoming comparable to values in the control subjects.

Usefulness of the Pulmonary Vein Flow Velocity-Time Profile as an Estimate of Left Atrial Storage Fraction

During ventricular systole, the left atrium (LA) stores a certain amount of ventricular stroke volume; this is defined as an LA storage volume. From cineangiocardiograms, an LA storage fraction is obtained as the ratio of the LA storage volume to left ventric ular stroke volume. From the pulmonary vein (PV) flow velocity-time profile, the LA storage fraction may be estimated as a ratio of the PV flow velocity-time integral during systole (Sa) to a sum of that during systole and diastole (Sa+Da), namely, Sa/(Sa+Da), provided that the PV cross-sectional area remains relatively unchanged during one cardiac cycle and that the PV flow velocity-time profile is similar in any of the PVs draining to the LA. To evaluate usefulness of Doppler echocardiographic method of estimating the LA storage fraction, the authors measured the LA storage fraction from the left upper PV flow velocity-time profile by transesophageal Doppler echocardiography and compared it with the LA storage fraction from conventional cineangiocardiographic volumes. (continued on next page) Subjects were 23 patients with a variety of cardiac diseases in normal sinus rhythm, ranging from eighteen to seventy-four years of age. The LA storage fraction was 0.58 ±0.12 (mean ±SD) from cineangiocardiography and 0.64 ±0.08 from Doppler echocar diography. Although the LA storage fraction from Doppler echocardiography was signif icantly larger than that from cineangiocardiography (P < 0.01), the correlation was good (r=0.643). The authors conclude that the left upper PV flow velocity-time profile appears to provide a better correlation with that by cineangiography and may be used as a reliable quantitative estimate of the LA storage fraction.

Estimation of left ventricular contractile performance in atrial fibrillation: Experimental and clinical studies

SummaryThere are few studies regarding the assessment of left ventricular contractile function in patients with atrial fibrillation (AF). The aim of this study was to assess the left ventricular (LV) contractile function, i.e., the end-systolic pressure-volume relation (Ees) and a recently developed LV systolic myocardial stiffness constant (Ksm), without load manipulation in AF. In an experimental study of acute AF in dogs (n = 5), we were able to assess these indexes of the LV contractile function during acute AF, and found that the values were similar to those obtained during occlusion of the inferior vena cava (IVC) at the baseline state. During rapid ventricular pacing (140 or 160 bpm), the indices of LV contractile function increased due to the forcefrequency relation (4.56 ± 1.85, Ees baseline; 6.42 ± 2.54*+, Ees pacing; 5.15 ± 2.01 mmHg/ml, Ees AF;*P < 0.05 vs baseline,+P < 0.05 vs. AF) (4.73 ± 0.48, Ksm baseline; 6.24 ± 1.12*+, Ksm pacing; 3.99 ± 1.14, Ksm AF;*P < 0.05 vs baseline,+P < 0.05 vs AF). In a study of chronic clinical AF in patients without heart disease (lone AF,n = 7), the indexes of LV contractile function were preserved compared with those of control patients (CTL,n = 10) obtained during IVC occlusion; the values were decreased in patients with both AF and dilated cardiomyopathy (AFDCM,n = 5) (2.5 ± 1.1, Ees CTL; 2.4 ± 0.4, Ees lone AF; 1.1 ± 0.3 mmHg/ml*+, Ees AFDCM;*P < 0.05 vs CTL,+P < 0.05 vs lone AF) (5.3 ± 1.8, Ksm CTL; 4.9 ± 1.6, Ksm lone AF; 2.7 ± 0.2*+, Ksm AFDCM;*P < 0.05 vs CTL,+P < 0.05 vs lone AF). Thus, during acute AF in dogs and in chronic AF patients, LV contractile function was assessed without load manipulation. In both the acute AF dogs and the chronic lone AF patients, LV contractile function was preserved, and in the AFDCM patients it was depressed.

Pulmonary Vein Flow Velocity-Time Profile for Semiquantitative Estimates of Left Atrial Storage Fraction

To evaluate the usefulness of a method of estimating the ratio of left atrial (LA) storage volume to left ventricular (LV) stroke volume (i.e., the LA storage fraction) by Doppler echocardiography, we compared the LA storage fraction from the pulmonary vein (PV) flow velocity—time profile by Doppler echocardiography with the estimate obtained by conventional cineangiocardiography in 19 patients. From cineangiocardiograms, we calculated the LA storage fraction as the ratio of the LA storage volume to LV stroke volume. From the flow velocity—time profile of the left upper PV recorded by transesophageal Doppler echocardiography, we measured the flow velocity—time integrals during systole and diastole (Sa, Da). Provided that the cross-sectional area remains relatively unchanged during one cardiac cycle, the flow velocity—time integral is equivalent to the volumetric flow rate—time integral. The LA storage fraction was calculated as Sa/(Sa+Da). The LA storage fraction from cineangiocardiography was 0.57 ± 0.10 (mean ± SD), and 0.64 ± 0.08 from Doppler echocardiography, and the difference was not significant. Although estimates of the LA storage fraction from Doppler echocardiography tended to be slightly higher than those from cineangiocardiography, the PV flow velocity—time profile obtained by Doppler echocardiography appears to be clinically useful.