Kaoru Dohi

Novel Speckle-Tracking Radial Strain From Routine Black-and-White Echocardiographic Images to Quantify Dyssynchrony and Predict Response to Cardiac Resynchronization Therapy

Background— Mechanical dyssynchrony is a potential means to predict response to cardiac resynchronization therapy (CRT). We hypothesized that novel echocardiographic image speckle tracking can quantify dyssynchrony and predict response to CRT. Methods and Results— Seventy-four subjects were studied: 64 heart failure patients undergoing CRT (aged 64±12 years, ejection fraction 26±6%, QRS duration 157±28 ms) and 10 normal controls. Speckle tracking applied to routine midventricular short-axis images calculated radial strain from multiple circumferential points averaged to 6 standard segments. Dyssynchrony from timing of speckle-tracking peak radial strain was correlated with tissue Doppler measures in 47 subjects (r=0.94, P<0.001; 95% CI 0.90 to 0.96). The ability of baseline speckle-tracking radial dyssynchrony (time difference in peak septal wall–to–posterior wall strain ≥130 ms) to predict response to CRT was then tested. It predicted an immediate increase in stroke volume in 48 patients studied the day after CRT with 91% sensitivity and 75% specificity. In 50 patients with long-term follow-up 8±5 months after CRT, baseline speckle-tracking radial dyssynchrony predicted a significant increase in ejection fraction with 89% sensitivity and 83% specificity. Patients in whom left ventricular lead position was concordant with the site of latest mechanical activation by speckle-tracking radial strain had an increase in ejection fraction from baseline to a greater degree (10±5%) than patients with discordant lead position (6±5%; P<0.05). Conclusions— Speckle-tracking radial strain can quantify dyssynchrony and predict immediate and long-term response to CRT and has potential for clinical application.

Right ventricular dyssynchrony in patients with pulmonary hypertension is associated with disease severity and functional class

BackgroundAbnormalities in right ventricular function are known to occur in patients with pulmonary arterial hypertension.ObjectiveTest the hypothesis that chronic elevation in pulmonary artery systolic pressure delays mechanical activation of the right ventricle, termed dyssynchrony, and is associated with both symptoms and right ventricular dysfunction.MethodsFifty-two patients (mean age 46 ± 15 years, 24 patients with chronic pulmonary hypertension) were prospectively evaluated using several echocardiographic parameters to assess right ventricular size and function. In addition, tissue Doppler imaging was also obtained to assess longitudinal strain of the right ventricular wall, interventricular septum, and lateral wall of the left ventricle and examined with regards to right ventricular size and function as well as clinical variables.ResultsIn this study, patients with chronic pulmonary hypertension had statistically different right ventricular fractional area change (35 ± 13 percent), right ventricular end-systolic area (21 ± 10 cm2), right ventricular Myocardial Performance Index (0.72 ± 0.34), and Eccentricity Index (1.34 ± 0.37) than individuals without pulmonary hypertension (51 ± 5 percent, 9 ± 2 cm2, 0.27 ± 0.09, and 0.97 ± 0.06, p < 0.005, respectively). Furthermore, peak longitudinal right ventricular wall strain in chronic pulmonary hypertension was also different -20.8 ± 9.0 percent versus -28.0 ± 4.1 percent, p < 0.01). Right ventricular dyssynchrony correlated very well with right ventricular end-systolic area (r = 0.79, p < 0.001) and Eccentricity Index (r = 0.83, p < 0.001). Furthermore, right ventricular dyssynchrony correlates with pulmonary hypertension severity index (p < 0.0001), World Health Organization class (p < 0.0001), and number of hospitalizations (p < 0.0001).ConclusionLower peak longitudinal right ventricular wall strain and significantly delayed time-to-peak strain values, consistent with right ventricular dyssynchrony, were found in a small heterogeneous group of patients with chronic pulmonary hypertension when compared to individuals without pulmonary hypertension. Furthermore, right ventricular dyssynchrony was associated with disease severity and compromised functional class.

The Negative Inotropic Effect of β3-Adrenoceptor Stimulation in the Beating Guinea Pig Heart

Although beta3-adrenoceptors (ARs) have been extensively characterized in brown and white adipocytes, their actions in the beating heart are unclear. We examined the effects of a beta3-AR agonist, BRL37344, on cardiac function and calcium transients in Langendorff-perfused guinea pig hearts by simultaneously measuring left ventricular (LV) pressure and Ca2+-dependent indo-1 fluorescence. BRL37344 induced a dose-dependent negative inotropic effect at concentrations from 10(-11) to 10(-8) M. Maximally, LV developed pressure decreased to 80+/-2%, +dP/dt to 81+/-2%. and -dP/dt to 81+/-3% of their respective control values (p < 0.01). The amplitude of the Ca2+ transient also decreased (to 92+/-3% of the control level; p < 0.01). The BRL37344 dose-response curve was not altered by nadolol (10(-5) M), a potent beta1- and beta2-AR antagonist, but completely suppressed by bupranolol (10(-6) M), a potent beta1-, beta2- and beta3-AR antagonist. To assess the potential role of a nitric oxide synthase (NOS) pathway, we determined whether the NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), modified the contractile response to BRL37344. L-NAME (10(-7) and 10(-4) M) attenuated the negative inotropic effects on LV developed pressure by 35 and 50%, suggesting that beta3-AR stimulation induces a negative inotropic effect on guinea pig hearts partly through a decrease in the Ca2+ transient and partly by the NOS pathway.

Reversible Right Ventricular Regional Non-Uniformity Quantified by Speckle-Tracking Strain Imaging in Patients With Acute Pulmonary Thromboembolism

BACKGROUND The aim of this study was to evaluate the effects of acute right ventricular (RV) pressure overload (RVPO) on RV systolic function and its regional uniformity using speckle-tracking strain analysis in patients with acute pulmonary thromboembolism (APTE). METHODS Twenty-three patients with APTE (mean age, 59 +/- 16 years) and 23 age-matched and gender-matched normal subjects (the control group) were examined using echocardiography. Global and segmental longitudinal RV peak systolic strain (PSS) was analyzed using speckle-tracking strain echocardiography. The heterogeneity of RV regional function was assessed by calculating the standard deviation from 6-segmental PSS divided by the absolute value of global PSS. The standard deviation of the heart rate-corrected intervals from QRS onset to PSS for the 6 segments was used to quantify RV dyssynchrony. RESULTS Patients with APTE had reduced regional PSS, resulting in reduced global PSS and augmented regional heterogeneity, and had delayed myocardial contraction in the basal and mid RV lateral walls, resulting in large dyssynchrony (global PSS, -14 +/- vs -25 +/- 3%; heterogeneity, 0.54 +/- 0.26 vs 0.24 +/- 0.09; dyssynchrony, 91 +/- 38 vs 25 +/- 10 ms; P < .05 vs controls for all comparisons). After the amelioration of acute RVPO by primary treatment, both RV heterogeneity and dyssynchrony returned to normal values. CONCLUSION Speckle-tracking strain echocardiography can effectively quantify reversible RV regional nonuniformity caused by acute RVPO and can characterize the pattern of RV regional impairment in patients with APTE.

Circadian rhythm of blood pressure is transformed from a dipper to a non-dipper pattern in shift workers with hypertension

Shift workers make great use of health care services because they are associated with increased cardiovascular morbidity and mortality. Whether the circadian rhythm of blood pressure rapidly adapts to shift work is controversial. It is unknown if shift work has adverse effects on blood pressure in patients with hypertension. To evaluate the effects of shift work, we examined 12 male shift workers with untreated hypertension aged 53.6 ± 2.5 years. Twenty-four hour ambulatory blood pressure monitoring was performed three times as follows: the last day of a 4-day period of day shifts (09.00 to 21.00), the first day of a 4-day period of night shifts (21.00 to 09.00), and the fourth day of night shifts (21.00 to 09.00). Blood pressure at night-time dropped significantly in the day-shift workers, showing a dipper pattern. Average differences in blood pressure in the sleep-wake cycle were decreased by 8.5% at the beginning of night shift work showing a non-dipper pattern. After 4 days the pattern was completely reversed to a dipper pattern. The results indicate that the circadian blood pressure pattern is changed from a dipper to a non-dipper pattern on the first day of the night shift and reverses to a dipper pattern within a few days. We suggest that night shift work may have unfavourable effects on blood pressure in patients with hypertension.

Role of Radial Strain and Displacement Imaging to Quantify Wall Motion Dyssynchrony in Patients With Left Ventricular Mechanical Dyssynchrony and Chronic Right Ventricular Pressure Overload

Left ventricular (LV) deformation with ventricular septal shift is one of the most distinctive echocardiographic observations in patients with chronic right ventricular (RV) pressure overload (PO). However, little is known about the effects of RVPO on LV performance and regional synchrony. Accordingly, our objective was to test the hypothesis that chronic RVPO affects regional wall motion, synchronicity, and global LV function using a novel speckle-tracking approach to quantify and characterize regional LV wall motion dyssynchrony. Displacement and strain imaging echocardiographic studies were performed in 20 patients with RVPO from pulmonary arterial hypertension or pulmonic stenosis (mean age 53 +/- 16 years, New York Heart Association class 2.6 +/- 0.7, and peak RV systolic pressure 73 +/- 28 mm Hg) and 20 age-matched normal subjects (mean age 47 +/- 16 years). Segmental signals from 6 segments around the mid-LV short axis were defined as dyssynchronous if their changes were opposite to that of the global LV signal at each time frame, and overall LV dyssynchrony was calculated as the percentage of dyssynchrony in all 6 segments within the specified time interval from onset of QRS to the end of isovolumic relaxation. RVPO was associated with a large degree of regional dyssynchrony with paradoxical ventricular septal motion observed by displacement imaging (21 +/- 6%, p <0.05 vs control group), which was closely associated with LV eccentricity index (r = 0.79, p <0.05) and LV myocardial performance index with linear regression (r = 0.76, p <0.05). In contrast, strain imaging showed uniform segmental radial thickening in the RVPO group, which was similar to the control group, and suggests that there was no intrinsic LV contractile dyssynchrony. In conclusion, LV wall motion dyssynchrony assessed by displacement imaging, not intrinsic contractile dyssynchrony by strain imaging, coexists with LV chamber deformation with ventricular septal shift and is closely associated with impairment of LV performance.

Short-term effects of low-dose tolvaptan on hemodynamic parameters in patients with chronic heart failure

BACKGROUND We evaluated the short-term effects of low-dose tolvaptan treatment on hemodynamic parameters in patients with chronic heart failure (HF). METHODS We studied 22 patients (69 ± 10 years) with chronic HF and excess fluid retention despite receiving appropriate medical therapy, including loop and/or thiazide diuretics. The therapeutic effects of low-dose (7.5mg) once-daily tolvaptan on hemodynamics associated with changes in fluid balance and neurohumoral activations were investigated after a seven day treatment period. RESULTS After the treatment period, body weight decreased (-2.7 ± 2.3 kg) associated with increases in daily urine output. Whereas plasma arginine-vasopressin levels, serum aldosterone concentration, and plasma renin activity mildly increased, plasma levels of B-type natriuretic peptide and atrial natriuretic peptide significantly decreased after tolvaptan treatment. Serum electrolytes were not adversely affected by tolvaptan treatment. Although cardiac index and systemic vascular resistance index remained unchanged, mean pulmonary artery wedge pressure (22 ± 7 mmHg vs. 17 ± 7 mmHg, p<0.05), mean right atrial pressure (12 ± 5 mmHg vs. 9 ± 5 mmHg, p<0.05), mean pulmonary artery pressure (32 ± 9 mmHg vs. 25 ± 7 mmHg, p<0.05), and pulmonary vascular resistance index (332 ± 207 dynes/cm(-5)/m(2) vs. 245 ± 110 dynes/cm(-5)/m(2), p<0.05) significantly decreased after tolvaptan treatment. The extent of the reduction in pulmonary vascular resistance index after tolvaptan treatment strongly correlated with baseline values. CONCLUSIONS Short-term treatment with low-dose tolvaptan improved hemodynamic parameters and correlated with significant fluid removal in patients with chronic HF.

An Abnormal Right Ventricular Apical Angle is Indicative of Global Right Ventricular Impairment

The presence of right ventricular (RV) dysfunction is an adverse prognostic indicator but current echocardiographic methods have some limitations. RV apical angles in systole and diastole were correlated with known parameters of RV function in patients without pulmonary hypertension (Group 1) and in patients with pulmonary hypertension (Group 2). RV apical angles were significantly smaller in both systole (22 ± 7°) and diastole (33 ± 6°) in Group 1 patients when compared to Group 2 (54 ± 18°, p < 0.0001 and 59 ± 17°, p < 0.0001, respectively). RV apical angles, both in systole and diastole, were strongly correlated with RV end‐systolic area (R = 0.89, p < 0.0001) and end‐diastolic area (R = 0.81, p < 0.0001), respectively. Similarly, the apical systolic and diastolic angle correlated well with decreased tricuspid annular plane systolic excursion (TAPSE, R =−0.76 and R =−0.73, p < 0.001) as well as with decreased RV fractional area change (R =−0.81 and R =−0.77, p < 0.001). Therefore, we conclude that this new measurement of RV apical angle is simple and useful to quantify RV apical structural and functional abnormalities that are well correlated with global RV impairment in patients with chronic pulmonary hypertension.

Abnormal Right Ventricular Myocardial Strain Generation in Mild Pulmonary Hypertension

Background: Although right ventricular (RV) dyssynchrony has been identified in patients with severe pulmonary hypertension due to significant RV enlargement and compromise in systolic function, a more clinically relevant question pertains to RV mechanical properties in patients with mild elevation in pulmonary artery systolic pressures (PASP). Methods: Several echocardiographic parameters and peak longitudinal strain were measured in 40 patients and divided into two groups of 20 patients based on their PASP. Results: Group I included 20 individuals (mean age 48 ± 16 years with a mean PASP of 27 ± 5 mmHg) and Group II included 20 patients (mean age 63 ± 14 years with a mean PASP of 49 ± 7 mmHg.) All time intervals were adjusted for heart rate. RV fractional area change and tricuspid annular plane systolic excursion for Group I (62 ± 12% and 2.74 ± 0.56 cm) and Group II (49 ± 14%; P < 0.02 and 2.09 ± 0.40; P < 0.002) were both normal. However, Group II had lower peak longitudinal RV free wall (RVF) strain (−27.3 ± 7.1 % vs. −31.9 ± 8.7%, P < 0.04), longer time to peak RVF strain (448 ± 57 ms vs. 411 ± 43 ms; P < 0.03) and evidence of significant RV dyssynchrony (−83 ± 55 ms vs. 1 ± 17 ms, P < 0.00001) in contrast to Group I. Conclusion: In conclusion, mild elevations in PASP affect the mechanical properties of the RV and result in RV dyssynchrony despite absence of gross abnormalities in RV size or 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.