Satoru Kawano

Mechanical Dyssynchrony Assessed by Speckle Tracking Imaging as a Reliable Predictor of Acute and Chronic Response to Cardiac Resynchronization Therapy

Speckle tracking echocardiography (STE) has the potential to detect the heterogeneous initiation of active myocardial contraction, which is the primary cause of left ventricular (LV) systolic dysfunction in patients with mechanical dyssynchrony. This study was designed to assess the ability to predict response to cardiac resynchronization therapy (CRT) of STE-derived dyssynchrony parameters in comparison with invasive hemodynamic assessments. Thirty patients referred for CRT were studied. The time difference of first peak (Td-(first peak)) and the maximum peak (Td-(max peak)) on the radial strain-time curves of the earliest and the latest segments were measured as the dyssynchrony parameter. Peak positive dP/dt (dP/dt(max)) was measured as the indicator of global LV systolic performance. CRT responders were defined as patients with LV end-systolic volume reduction greater than 15% at 3 months after CRT. CRT increased the dP/dt(max) compared with the baseline study (P < .001). Percent changes in the dP/dt(max) (dP/dt(max)) were significantly correlated with Td-(first peak) (R = 0.743, P < .001), but weakly correlated with Td-(max peak) (R = 0.390, P = .03). Twenty patients (66%) were identified as chronic CRT responders. Receiver operating characteristics analysis revealed that Td-(first peak) shared a similar ability with dP/dt(max) to detect chronic responders (Td-(first peak) >167.0 ms, area under the curve [AUC] 0.945; dP/dt(max) >16.2%, AUC 0.934) compared with Td-(max peak) (>194.5 ms, AUC 0.820). STE-derived Td-(first peak) showed a reliable ability to predict the acute and chronic response to CRT as well as dP/dt(max).

The wake of a large vortex is associated with intraventricular filling delay in impaired left ventricles with a pseudonormalized transmitral flow pattern.

Although an intraventricular filling delay has been observed in patients with a psuedonormalized transmitral flow pattern, little is known about the underlying hydrodynamic nature of this phenomenon. Methods: To examine those hydrodynamics, we studied every echocardiographic frame showing ventricular inflow (80 Hz) in the apical long‐axis view and M‐mode image using contrast echocardiography in 29 patients with a psuedonormalized pattern and in 26 normal controls. The velocity of the filling flow front (Vp), the ratio of Vp to E, and the mean radius of the vortices associated with the filling flow were measured. Results: In both groups, vortices were observed at the ridge of the mitral valve during acceleration of the E‐wave. The mean radius of the vortices was greater in the pseudonormalized filling group than that in the control group (8 ± 2 vs 3 ± 1 mm, P < 0.0001). Vp was smaller in the pseudonormalized group than in the control group (36 ± 6 vs 47 ± 6 cm/sec, P = 0.0008). Vp/E was <1 and smaller in the pseudonormalized group than that in the control group (0.46 ± 0.13 vs 0.59 ± 0.07, P = 0.014) and negatively correlated with the mean radius of the vortices (r = 0.54, P < 0.0001). Conclusions: Contrast echocardiography identified uniform flow characteristics with blood in the filling flow front moving in well‐developed vortices and resulting in a left ventricular filling delay in the impaired left ventricle in spite of an increased early transmitral flow velocity.

Response to isoproterenol as a prognostic indicator of evolution from hypertrophic cardiomyopathy to a phase resembling dilated cardiomyopathy

OBJECTIVES We sought to assess whether isoproterenol stress echocardiography could detect in advance in which patients hypertrophic cardiomyopathy would progress to a phase resembling dilated cardiomyopathy. BACKGROUND In a few patients, hypertrophic cardiomyopathy has been reported to progress to a phase characterized by systolic dysfunction and left ventricular dilation, resembling dilated cardiomyopathy. METHODS Echocardiograms were recorded before and immediately after intravenous infusion of isoproterenol (0.02 microgram/kg body weight per min) for 5 min in 18 patients with typical hypertrophic cardiomyopathy (i.e., hypertrophied, hyperdynamic and nondilated) to determine the difference in fractional shortening. The patients were categorized into those with a good response (difference in fractional shortening > 7%, 14 patients) and those with a poor response (difference < or = 7%, 4 patients). Changes in left ventricular end-diastolic diameter and fractional shortening were evaluated by using serial echocardiography over an average follow-up period of 5.4 years. RESULTS In the good response group, neither end-diastolic diameter nor fractional shortening changed significantly during the follow-up period. In the poor response group, end-diastolic diameter significantly increased from a mean +/- SD of 41 +/- 5 to 53 +/- 5 mm (p < 0.05), and fractional shortening significantly decreased from 40 +/- 12% to 29 +/- 10% (p < 0.05). All patients in the poor response group showed a substantial decrease (> or = 5%) in fractional shortening and an increase (> or = 5 mm) in end-diastolic diameter. One patient developed congestive heart failure due to systolic dysfunction during the observation period. CONCLUSIONS The present study confirmed that impaired responses to isoproterenol infusion are related to future deterioration of left ventricular performance in patients with typical hypertrophic cardiomyopathy.

Screening for gestational diabetes mellitus and its prevalence in Bangladesh

BACKGROUND The prevalence of gestational diabetes mellitus (GDM) has important health complications for both mother and child and is increasing all over the world. Although prevalence estimates for GDM are not new in developed and many developing countries, data are lacking for many low-income countries like Bangladesh. OBJECTIVE To evaluate the prevalence of GDM in Bangladesh. RESEARCH DESIGN AND METHODS This cross-sectional study included 3447 women who consecutively visited the antenatal clinics with an average gestation age of 26 weeks. GDM was defined according to WHO criteria (fasting plasma glucose [FPG] ≥7.0 mmol/L or 2-h ≥7.8 mmol/L) and the new ADA criteria (FPG ≥5.3 mmol/L or 2-h ≥8.6 mmol/L OGTT). We also calculated overt diabetes as FPG ≥7.0 mmol/L. RESULTS Prevalence of GDM was 9.7% according to the WHO criteria and 12.9% according to the ADA criteria in this study population. Prevalence of overt diabetes was 1.8%. Women with GDM were older, higher educated, had higher household income, higher parity, parental history of diabetes, and more hypertensive, compared with non-GDM women. CONCLUSION This study demonstrates a high prevalence of GDM in Bangladesh. These estimates for GDM may help to formulate new policies to prevent and manage diabetes.

Combined approach with Doppler echocardiography and B-type natriuretic peptide to stratify prognosis of patients with decompensated systolic heart failure

BACKGROUND Based on the importance of left ventricular (LV) diastolic function in stratification of the cardiac prognosis in patients with systolic heart failure (SHF), we attempted to identify the prognostic impact of Doppler echocardiographic examinations and plasma B-type natriuretic peptide (BNP) concentration. METHODS Of 73 patients admitted with decompensated SHF (ejection fraction <45%), 58 were included. Among these, 21 patients had ischemic heart disease and 27 non-ischemic dilated cardiomyopathy. In all patients, Doppler echocardiographic examinations and measurements of the plasma B-type natriuretic peptide concentration were simultaneously performed before discharge. Patients were followed up for 36 months after discharge. Primary end point for the follow-up was readmission for acute decompensated heart failure or cardiac death. RESULTS During the mean follow-up period of 28±12 months, 16 patients (27.6%) were readmitted with decompensated heart failure. Based on the stepwise multivariate Cox regression analysis, mitral E/A ratio (chi-square=6.5, relative risk=1.7, p=0.01) and BNP (chi-square=3.9, relative risk=1.7, p=0.04) were identified as independent predictors of primary endpoints. Based on ROC analysis, the optimal cutoff point of E/A was 1.05 (AUC=0.836, p=0.002) and that of plasma BNP concentration was ≥254.5 pg/ml (AUC=0.768, p=0.002). In high-risk patients with E/A ≥1, event-free survival rates were significantly lower in patients with BNP <254.5 pg/ml (p<0.001). CONCLUSIONS The complementary assessment of Doppler transmitral flow and plasma BNP concentration may be reliable in identifying the prognosis of patients with SHF.

Enhanced washout of 99mTc-tetrofosmin in hypertrophic cardiomyopathy: quantitative comparisons with regional 123I-BMIPP uptake and wall thickness determined by MRI

The diagnostic value of technetium-99m tetrofosmin (TF) washout in hypertrophic cardiomyopathy (HCM) was examined by investigating its relation to the metabolic abnormality depicted by iodine-123 β-methyl-p-iodophenylpentadecanoic acid (BMIPP) uptake and the left ventricular (LV) myocardial wall thickness as measured by magnetic resonance imaging (MRI). TF washout was evaluated in 31 patients with HCM and 23 normal control subjects using 30-min (early) and 3-h (delayed) TF single-photon emission tomography images. The LV myocardial wall was divided into 19 segments and the percentage TF washout, regional BMIPP uptake and LV wall thickness were measured in each segment. Mean TF washout in the patients with HCM was significantly faster than that in normal control subjects (23.7±5.7 vs 13.4±4.1, P<0.0001). In the patients with HCM, TF washout showed an excellent correlation with MRI wall thickness (r=0.82, P<0.0001) and a good inverse correlation with regional BMIPP uptake (r=−0.72, P<0.0001). In addition, a good linear correlation was observed between TF uptake and MRI wall thickness in the 19 regional segments. In conclusion, the degree of TF washout corresponds well with the severity of myocardial wall thickness and the degree of metabolic abnormality in patients with HCM. These results suggest that enhanced TF washout might provide additional clinical information regarding metabolic alterations in HCM.

Higher circulatory level of endothelin-1 in hypertensive subjects screened through a cross-sectional study of rural Bangladeshi women

Endothelin-1 (ET-1) is a potential marker of the endothelial dysfunction, which has been shown to be elevated in hypertensive subjects. No previous study has investigated the circulatory level of ET-1 and hypertension in a South Asian country. The present study assessed the circulating levels of ET-1 in subjects with or without hypertension and further examined the association of ET-1 with clinical and metabolic parameters. A total of 2543 rural Bangladeshi women with a mean age of 44.5 years were studied using a cross-sectional survey. Multiple regressions were used to examine the association between the circulatory ET-1 levels and hypertension. The prevalence of hypertension was 29.3%. The ET-1 levels were significantly higher in the hypertensive (mean 3.08 pg ml–1, s.e. (0.19)) than in the non-hypertensive subjects (mean 2.01 pg ml–1, s.e. (0.03)) (P=0.001). After adjusting for age, the ET-1 level had significant positive associations with the diastolic blood pressure (P=0.002), systolic blood pressure (P=0.001), mean arterial pressure (P=0.002) and fasting blood glucose (P=0.002). In a tertile analysis, we found that hypertension in the subjects was significantly increased as the levels of ET-1 increased (P for the trend=0.001). In a stepwise multiple regression analysis, after adjusting for age and all other potential variables, we found that the mean arterial pressure and the fasting plasma levels have significant associations with the ET-1 level. The present study demonstrates that there is a higher concentration of ET-1 among the hypertensive subjects in an apparently healthy population of Bangladeshi rural women. The relationship between ET-1 and hypertension requires further investigation to define the clinical utility and predictive value of serum ET-1 levels for hypertension for a South Asian population.

Significant reversal of cardiac upregulated endothelin-1 system in a rat model of sepsis by landiolol hydrochloride.

AIMS Landiolol hydrochloride, an ultra-short-acting highly cardio-selective β-1 blocker, has become useful for various medical problems. Recent studies have demonstrated that co-treatment with landiolol protects against acute lung injury and cardiac dysfunction in rats of lipopolysaccharide (LPS)-induced systemic inflammation, and was also associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage. Endothelin (ET)-1, a potent vasoconstrictor, has been implicated in pathogenesis of sepsis and sepsis-induced multiple organ dysfunction syndrome. Here, we investigated whether landiolol hydrochloride can play important roles in ameliorating LPS-induced alterations in cardiac ET system of septic rats. MAIN METHODS Eight-week-old male Wistar rats were administered LPS only for 3 h and the rest were treated with LPS as well as with landiolol non-stop for 3 h. KEY FINDINGS At 3 h after LPS (only) administration, circulatory tumor necrosis factor (TNF)-α level, blood lactate concentration and percentage of fractional shortening of heart were significantly increased. In addition, LPS induced a significant expression of various components of cardiac ET-1 system compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized LPS-induced blood lactate levels and cardiac functional compensatory events, without altering levels of plasma TNF-α and ET-1. Most strikingly, landiolol treatment significantly normalized various components of cardiac ET-1 signaling system in septic rat. SIGNIFICANCE Taken together, these data led us to conclude that landiolol may be cardio-protective in septic rats by normalizing the expression of cardiac vasoactive peptide such as ET, without altering the circulatory levels of inflammatory cytokines.

Potential amelioration of upregulated renal HIF-1alpha–endothelin-1 system by landiolol hydrochloride in a rat model of endotoxemia

AIMS Endothelin (ET)-1 is the best known potent vasoconstrictor and has been implicated in pathogenesis of sepsis-associated acute kidney injury (AKI) in human or lipopolysaccharide (LPS)-induced AKI in animal models. We have previously shown that ET-1 is highly up-regulated in renal tissues and in plasma after LPS administration. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting beta-blocker, can play an important role in ameliorating levels of LPS-induced up-regulation of renal HIF-1α-ET-1 system and inflammatory cytokines in a rat model of endotoxemia. MAIN METHODS Male Wistar rats at 8 weeks of age were either administered with: a) lipopolysaccharide (LPS) only for three hours (3 h) or b) LPS, followed by continuous administration of landiolol for 3 h; c) third group was only treated with vehicle. KEY FINDINGS At 3 h after LPS administration there was: a) minimal injury in kidney tissues; b) circulatory levels of creatinine, blood urea nitrogen and NGAL increased and c) expression of inflammatory cytokines, such as TNF-α, IL-6 and iNOS increased at the level of both circulatory and renal tissues. In addition, LPS significantly induced renal expression of ET-1 and HIF-1α compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized elevated serum markers of renal injury and up-regulated levels of renal HIF-1α-ET-1 system with normalization of TNF-α. SIGNIFICANCE Taken together, these data led us to conclude that landiolol ameliorates the up-regulation of HIF-1α-ET-1 system in minimally morphologically-injured kidney and normalizes biomarkers of renal injury in early hours of endotoxemia of a rat model.

Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode

AIMS Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. MAIN METHODS Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. KEY FINDINGS An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. SIGNIFICANCE The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide.