Hideaki Kanzaki

Noninvasive Estimation of Pulmonary Vascular Resistance by Doppler Echocardiography in Patients With Pulmonary Arterial Hypertension

Pulmonary vascular resistance (PVR) is an important hemodynamic variable in the management of patients with pulmonary hypertension. To establish a method of estimating PVR in patients with pulmonary arterial hypertension (PAH), Doppler echocardiography was performed within 24 hours of right heart catheterization in 43 patients with PAH (idiopathic PAH, n = 20; chronic thromboembolic pulmonary hypertension, n = 9; congenital heart disease, n = 9; and others). Correlations between invasive PVR and Doppler variables of pulmonary artery flow and tricuspid regurgitation were examined. Mean invasive PVR was 1,294 +/- 680 dyne s cm(-5). Linear regression analysis revealed significant correlations with invasive PVR for the time-velocity integral (TVI; r = -0.63, p = 0.009) of right ventricular outflow and peak tricuspid regurgitant pressure gradient (TRPG; r = 0.77, p <0.001). The TRPG/TVI ratio, which approximated the ratio of pulmonary artery pressure to pulmonary blood flow, showed an improved correlation coefficient of 0.82 (PVR = 187 + TRPG/TVI x 118, p <0.001). After excluding 5 patients with an intracardiac shunt, 26 of the remaining 38 patients (68%) met the hemodynamic criteria in international guidelines for the selection of lung transplantation candidates and were defined as the poor-prognosis group. A TRPG/TVI >7.6 showed 85% sensitivity and 92% specificity for identifying patients in the poor-prognosis group. In conclusion, TRPG/TVI provides a reliable estimation of PVR over a wide range in patients with PAH with various underlying causes.

Extensive late gadolinium enhancement on cardiovascular magnetic resonance predicts adverse outcomes and lack of improvement in LV function after steroid therapy in cardiac sarcoidosis

Background Gadolinium-enhanced cardiovascular magnetic resonance is an emerging tool for the diagnosis of cardiac sarcoidosis (CS); however, the correlations between extent of late gadolinium enhancement (LGE) and efficacy of steroid therapy and adverse outcomes in patients with CS remain unclear. Objective We aimed to clarify the prognostic impact of extent of LGE in patients with CS. Methods Before the start of steroid therapy, 43 consecutive LGE-positive patients with CS were divided into two groups based on the extent of LGE by a median value: small-extent LGE (LGE mass <20% of LV mass; n=21) and large-extent LGE (LGE mass ≥20% of LV mass; n=22). We examined the correlations between extent of LGE and outcomes after steroid therapy. Results Among the 6 patients who died from heart disorders, 11 patients who were hospitalised because of heart failure and 6 patients who suffered life-threatening arrhythmia during the follow-up period, large-extent LGE predicted higher incidences of cardiac mortality and hospitalisation for heart failure. Multivariate Cox regression analysis showed that large-extent LGE was independently associated with combined adverse outcomes including cardiac death, hospitalisation for heart failure, and life-threatening arrhythmias. In the small-extent LGE group, LV end-diastolic volume index significantly decreased and LVEF significantly increased after steroid therapy, whereas in the large-extent LGE group, neither LV volume nor LVEF changed substantially. Conclusions Large-extent LGE correlates with absence of LV functional improvement and high incidence of adverse outcomes in patients with CS after steroid therapy.

Left Atrial Volume Combined With Atrial Pump Function Identifies Hypertensive Patients With a History of Paroxysmal Atrial Fibrillation

Identifying patients at high risk for the occurrence of atrial fibrillation is one means by which subsequent thromboembolic complications may be prevented. Left atrial enlargement is associated with progression of atrial remodeling, which is a substrate for atrial fibrillation, but impaired atrial pump function is also another aspect of the remodeling. Our objective was to differentiate patients with a history of paroxysmal atrial fibrillation using echocardiography. We studied 280 hypertensive patients (age: 66±7 years; left ventricular ejection fraction: 65±8%), including 140 consecutive patients with paroxysmal atrial fibrillation and 140 age- and sex-matched control subjects. Left atrial volume was measured using the modified Simpson method at both left ventricular end systole and preatrial contraction and was indexed to body surface area. Peak late-diastolic mitral annular velocity was measured during atrial contraction using pulsed tissue Doppler imaging as an atrial pump function. Left atrial volume index measured at left ventricular end systole had a 74% diagnostic accuracy and a 71% positive predictive value for identifying patients with paroxysmal atrial fibrillation; these values for the ratio of left atrial volume index at left ventricular end systole to the peak late-diastolic mitral annular velocity were 82% and 81%, respectively, and those for the ratio of left atrial volume index at preatrial contraction to the peak late-diastolic mitral annular velocity were 86% and 90%, respectively. In conclusion, left atrial size combined with atrial pump function enabled a more accurate diagnosis of a history of paroxysmal atrial fibrillation than conventional parameters.

Utility of left ventricular systolic torsion derived from 2-dimensional speckle-tracking echocardiography in monitoring acute cellular rejection in heart transplant recipients

BACKGROUND Reduced left ventricular torsion (LV-tor) has been reported to be associated with acute rejection in heart transplant (HTx) recipients. We investigated the utility of LV-tor analysis derived from 2-dimensional speckle-tracking echocardiography (2D-STE) for detecting allograft rejection. METHODS A total of 301 endomyocardial biopsies (EMBs), right heart catheterizations and echocardiograms were performed in 32 HTx recipients. Echocardiography was done within 3 hours from EMB or simultaneously with the procedures. The LV-tor was defined as the difference between apical and basal end-systolic rotations. The LV-tor values with and without cellular rejection were compared. In addition, we investigated whether the change in LV-tor values predicts the change in rejection grade in each patient. The baseline LV-tor value in each patient was defined as a mean value of the first 3 LV-tor measurements obtained when the patient was free from rejection. RESULTS According to the conventional International Society for Heart and Lung Transplantation criteria, 274 biopsies showed a rejection Grade of 0, 1a or 1b (Group AR(-)), whereas 27 biopsies were Grade 2 or higher (Group AR(+)). LV-tor decreased more in Group AR(+) than in Group AR(-) (9.3 ± 0.7 vs 12.2 ± 0.2 degrees, p < 0.0001). In the LV-tor measurement for each patient, the 25% reduction in LV-tor value from baseline predicted Grade 2 or higher rejection with a predictive accuracy of 92.9%. CONCLUSION LV-tor derived from 2D-STE could be of clinical value for non-invasive monitoring of acute rejection in HTx recipients.

A new screening method to diagnose coronary artery disease using multichannel magnetocardiogram and simple exercise.

Abstract.Background: Magnetocardiography (MCG) is a non-contact mapping technique to record cardiac action currents. The Masters two-step electrocardiogram (ECG) test is a simple exercise method for screening coronary artery disease (CAD), but it is inadequate concerning the sensitivity. Our aim was to develop a new screening method using multichannel MCG instead of ECG. Methods: Thirty subjects (aged 54 ± 16 years, 27 males), 17 of whom had CAD confirmed by coronary angiography, underwent the Masters exercise ECG test. After the exercise, MCG signals were acquired every minute during recovery with a 64-channel MCG system (MC-6400, Hitachi Ltd). We integrated tangential components of the MCG signals within QRS (during 20, 40, 80, and 120 ms centering on R-wave peak) immediately after exercise (Iex) and 5 minutes after exercise (Irec). The exercise-induced change of currents [(Iex-Irec)/Irec] was determined and normalized for each channel, and the maximal change among 64 channels, maximal QRS integral change, was used as a diagnostic index for myocardial ischemia. Results: The maximal QRS integral change during 40 ms was significantly higher in the CAD group than in the control group (0.81 ± 0.51 vs. 0.36 ± 0.19, p < 0.01). A sensitivity and specificity for predicting CAD by the change > 0.44 were 82 % and 85 %, respectively, yielding a diagnostic accuracy of 83 %. The conventional Masters ECG test identified the CAD patients with a diagnostic accuracy of 63 % (sensitivity 47 %, specificity 85 %). Conclusion: The Masters two-step exercise test with a 64-channel MCG system showed the high diagnostic accuracy, despite of non-contact recording and simple exercise. The magnetic field in the depolarization process has the potential to detect the subtle myocardial ischemia induced by exercise.

A simple method to predict impaired right ventricular performance and disease severity in chronic pulmonary hypertension using strain rate imaging.

BACKGROUND The evaluation of right ventricular (RV) function is clinically important in pulmonary hypertension (PH) because of prognostic implications. Conventional echocardiography has been used to predict adverse outcomes in chronic PH, but there were certain limitations arising from the complexity of RV anatomy. We used strain rate imaging (SRI) to evaluate RV function in PH patients. METHODS Study population consisted of 50 patients (mean age 46 ± 13 years; 39 females) with chronic PH who underwent echocardiography including SRI within 24h of right heart catheterization. Mean value of peak systolic longitudinal strain obtained from basal and mid RV free wall were calculated. Reduced RV systolic contraction (fractional area change <32%) and cardiac index (CI) <2.0 L/min/m(2) were defined as impaired RV performance. RESULTS Pulmonary vascular resistance (PVR) averaged 1195 ± 522 dyn · s · cm(-5). RV strain correlated closely with pulmonary artery systolic pressure (r = 0.53; p < 0.001) and PVR (r = 0.68; p < 0.001). RV strain best correlated with CI (r = -0.70; p < 0.001) among the invasive variables. After adjusting for various parameters that could influence the CI, this correlation remained robust (r = -0.63, p < 0.001). In a multivariate model, RV strain (odds ratio 1.65; 95% confidential interval 1.06-2.57; p = 0.028) was independently associated with impairment of RV performance. A cutoff value of -15.5% discriminated cases of impaired RV performance from those of preserved RV performance with a sensitivity of 100%, specificity of 84% and accuracy of 92%. CONCLUSIONS RV strain correlates well with hemodynamic variables indicative of disease severity and help identify the cases of impaired RV performance in PH patients.

Regional correlation by color-coded tissue Doppler to quantify improvements in mechanical left ventricular synchrony after biventricular pacing therapy

Cardiac resynchronization therapy (CRT) can improve cardiac function in patients with heart failure and left bundle branch block. To test a new synchrony index derived from mitral annular velocity by color tissue Doppler, 19 subjects were studied: 9 patients with heart failure and left bundle branch block at baseline and at 1, 3 and 6 months after CRT and 10 normal controls. The synchrony index in patients with heart failure was less than that in controls at baseline (r = 0.60 +/- 0.13 vs 0.94 +/- 0.02; p <0.01), but improved at 6 months after CRT (r = 0.77 +/- 0.09; p <0.05 vs baseline).

Direct comparison of the diagnostic capability of cardiac magnetic resonance and endomyocardial biopsy in patients with heart failure

The diagnostic performance of cardiac magnetic resonance (CMR) has not been compared with that of other imaging modalities. Therefore, this study investigated the diagnostic capabilities of CMR and endomyocardial biopsy (EMB) in patients with heart failure (HF).

Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease

Although the important role of fibroblast growth factor (FGF)23 on cardiac remodeling has been suggested in advanced chronic kidney disease (CKD), little is known about serum (s)FGF23 levels in patients with heart failure (HF) due to nonischemic cardiac disease (NICD) and early CKD. The present study aimed to investigate sFGF23 levels in NICD patients and identify the responsible factors for the elevation of sFGF23 levels. We prospectively measured sFGF23 levels in consecutive hospitalized NICD patients with early CKD (estimated glomerular filtration rate ≥ 40 ml·min(-1)·1.73 m(-2)) and analyzed the data of both echocardiography and right heart catheterization. Of the 156 NICD patients (estimated glomerular filtration rate range: 41-128 ml·min(-1)·1.73 m(-2)), the most severe HF symptom (New York Heart Association class III-IV, 53% vs. 33%, P = 0.015) was found in the above median sFGF23 (39.1 pg/ml) group compared with the below median sFGF23 group. sFGF23 levels were higher in patients with HF hospitalization history compared with those without HF [median: 46.8 (interquartile range: 38.8-62.7) vs. 34.7 (interquartile range: 29.6-42.4) pg/ml, P < 0.0001]. In the multivariate analysis, HF hospitalization was independently related to elevated sFGF23 levels (P = 0.022). Both systolic dysfunction and high plasma aldosterone concentration were identified as predictors of high sFGF23 levels (P < 0.05). Among the neurohormonal parameters, elevated sFGF23 levels were the only factor to predict a declining left ventricular ejection fraction (P = 0.001). These findings suggest that the progression of HF per se contributes to the elevation of sFGF23 levels even in the early stages of CKD, which leads to further myocardial dysfunction, potentially creating a vicious cycle.

Plasma adiponectin is associated with plasma brain natriuretic peptide and cardiac function in healthy subjects.

The aim of this study was to evaluate the relationship between the plasma adiponectin level, plasma brain natriuretic peptide (BNP) level, and cardiac function in healthy subjects. We obtained clinical data and performed blood tests, including measurement of the plasma adiponectin and BNP levels, in 1,538 healthy persons from Arita-cho, a rural area of Japan. Six hundred and eight subjects also underwent echocardiography. There was a significant positive correlation between their plasma BNP and adiponectin levels in simple regression analysis (standardized regression coefficient [β]=0.34). Multivariate regression analysis revealed that the plasma adiponectin level was independently associated with the plasma BNP level (β=0.12), as well as with the age (β=0.22), male gender (β=−0.26), waist circumference (β=−0.16), and the plasma levels of high-density lipoprotein cholesterol (β=0.13), triglycerides (β=−0.16), aspartate aminotransferase (β=0.08), γ-glutamyl transpeptidase (β=−0.10), uric acid (β=−0.07), and creatinine (β=0.08). We also found a link between plasma adiponectin and the left atrial diameter index (β=0.08) or left ventricular diameter index (β=0.11), even after adjustment for age, sex, and body mass index. The plasma adiponectin level increased along with an increase of plasma BNP in healthy subjects independently of other confounding factors, demonstrating that adiponectin reflects cardiac function.