Correlation of Right Ventricular Wall Stress With Plasma B-Type Natriuretic Peptide Levels in Patients With Pulmonary Hypertension.

BACKGROUND: This study was designed to investigate the relationship between right ventricular wall stress (RVWS) and plasma B-type natriuretic peptide (BNP) levels in patients with pulmonary hypertension (PH). Methods and Results: The 57 consecutive PH patients and 8 control subjects were enrolled. Right heart catheterization (RHC), echocardiography, and BNP measurements were performed, and RVWS and left ventricular wall stress (LVWS) were calculated with the formula based on Laplace's law. Systolic RVWS and end-diastolic RVWS were higher in PH patients compared with controls (systolic RVWS: 77±41 vs. 17±5 kdynes/cm2(P<0.0001), end-diastolic RVWS: 15±12 vs. 8±2 kdynes/cm2(P<0.0005)). Univariate analyses showed that logBNP at baseline correlated with systolic RVWS (r=0.58, P<0.0001) and end-diastolic RVWS (r=0.61, P<0.0001). We performed multivariate regression analysis and determined that end-diastolic RVWS was an independent determinant of logBNP in patients with PH. In addition, change in plasma BNP levels after treatment correlated with change in systolic RVWS (r=0.70, P<0.0001) and change in end-diastolic RVWS (r=0.68, P<0.0001). CONCLUSIONS: Both systolic and end-diastolic RVWS were elevated in patients with PH, and correlated with the symptoms of PH. End-diastolic RVWS was an independent determinant of plasma BNP levels in PH patients.

Analysis of Biphasic Right Ventricular Outflow Doppler Waveform in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH) with pulmonary vascular disease (PVD) is a progressive and debilitating disease associated with increased pulmonary vascular resistance (PVR). Biphasic right ventricular outflow tract (RVOT) Doppler flow is frequently seen in severe PH patients with PVD. In association with hemodynamics, the precise analysis of biphasic RVOT Doppler flow (RVDF) has not been fully elucidated. Therefore, the purpose of the present study is to analyze the relation between the hemodynamics and indices of biphasic RVDF in PH patients with PVD.Seventy PH patients with biphasic RVDF were analyzed. All patients underwent transthoracic echocardiography and right heart catheterization. For the analysis of biphasic RVDF, the early waveform was determined as P1 while the late waveform was determined as P2. For each P1 and P2, the duration (D, seconds) and peak flow velocity (PFV, in m/second) were measured.P1D and P2PFV were significantly correlated with PVR (P1D: r = -0.542, P < 0.0001, P2PFV: r = -0.513, P < 0.0001). Therefore, we propose a novel RVDF formula for estimation of PVR, as follows. PVR = 26 - 77 × P1D - 14 × P2PFV. The PVR could be estimated by this proposed formula (r = 0.649, P < 0.0001), which is derived from one Doppler image only unlike previously used PVR prediction formula.P1D and P2PFV were associated with PVR. Moreover, this simple RVDF formula proposed herein can estimate PVR in PH patients with PVD.

Effects of vitamin K antagonist on aortic valve degeneration in non-valvular atrial fibrillation patients: Prospective 4-year observational study.

BACKGROUND: The prevalence of atrial fibrillation (AF) is high in elder subjects. Our previous observational study suggested that vitamin K antagonist (VKA) promotes aortic valve degeneration, a principal cause of aortic stenosis in the elderly, and that angiotensin receptor blocker (ARB) attenuates its progression. This study aimed to prospectively investigate these observations in non-valvular AF patients. METHODS: Of enrolled 430 patients with calcification on no or one aortic valve leaflet, all of the planned 4-year follow-up data were obtained in 122 non-valvular AF patients treated with warfarin (warfarin group) and 101 patients with cardiovascular diseases and without AF and prescription of warfarin (non-warfarin group). RESULTS: Despite higher atherosclerotic risks in the non-warfarin group, 2 or 3 newly calcified leaflets emerged during 4years in 18.0% of patients in the warfarin group and in 6.9% in the non-warfarin group (p=0.014). Aortic valve area (AVA) did not significantly change in the non-warfarin group during the follow-up, but tended to decrease in the warfarin group (p=0.057). Non-vitamin K antagonist oral anticoagulant got available in Japan after this study started, and warfarin was discontinued in 15 patients of the warfarin group. The reduction of AVA was significant in the remaining 107 patients on the continuous warfarin treatment (p=0.002). The effects of ARB on AVA were obscure. CONCLUSION: Major bleeding associated with VKA is well recognized. This study suggests that the development of aortic valve degeneration is another risk of long-term use of VKA in non-valvular AF patients with no or mild aortic valve degeneration.

Fabry disease.

Fabry disease resulting from a deficiency of α-galactosidase A leads to the accumulation of globotriaosylceramide in various organs. Because the disease is an X-linked recessive disorder, males tend to develop more symptoms and more severe symptoms than females. There are also some variants of Fabry disease, and cardiac variant (cardiac Fabry disease) has the dysfunctions only in heart. Cardiac manifestations in Fabry disease are initially symmetrical and concentric left ventricular hypertrophy, and later progressive cardiac dysfunction with localized thinning of the basal posterior wall. In recent years, enzyme replacement therapy has been performed as a treatment for Fabry disease, and the initiation of this therapy is expected before the cardiac fibrosis develops. Therefore, early diagnosis of Fabry disease is essential, and echocardiography is an indispensable tool for clinical practice of this disease. Then, it is necessary to remember this disease as a differential diagnosis when encountering unexplained left ventricular hypertrophy.

Risk Factors for Progression of Degenerative Aortic Valve Disease in the Japanese- The Japanese Aortic Stenosis Study (JASS) Prospective Analysis.

BACKGROUND: Because of ethnic difference in the risk of degenerative aortic valve disease (DAVD), risk factors should be clarified in each race to establish prophylactic strategies for severe aortic valve stenosis (AS). METHODS AND RESULTS: This study prospectively followed 359 Japanese subjects with DAVD and age ≥50 years for 3 years. As both patients with peak aortic transvalvular flow velocity ≥2 m/s and <2 m/s were enrolled, subgroup analysis was also conducted. Most patients were under treatment for their comorbidities. The use of warfarin, but none of the traditional risk factors for atherosclerosis, was related to greater reduction in aortic valve area indexed to body surface area (iAVA). In patients with peak aortic transvalvular flow velocity <2 m/s, the use of an angiotensin-receptor blocker (ARB) was associated with less decrease in iAVA. In patients with peak velocity ≥2 m/s, changes in iAVA were not related to any baseline characteristics, but peak velocity was less increased under treatment with an angiotensin-converting enzyme inhibitor (ACEI). CONCLUSIONS: In Japanese, the use of warfarin may exacerbate DAVD, and augmented management of atherosclerotic risk factors beyond the recommendations in the current guidelines is unlikely to exert additional benefit. The prescription of ARB for DAVD patients before the development of AS or ACEI after the development of AS may be useful.

Prosthetic tricuspid valve dysfunction assessed by three-dimensional transthoracic and transesophageal echocardiography.

A 39-year-old male who had undergone tricuspid valve replacement for severe tricuspid regurgitation was admitted with palpitation and general edema. Two-dimensional (2D) echocardiography showed tricuspid prosthetic valve dysfunction. Additional three-dimensional (3D) transthoracic and transesophageal echocardiography (TEE) could clearly demonstrate the disabilities of the mechanical tricuspid valve. Particularly, 3D TEE demonstrated a mass located on the right ventricular side of the tricuspid prosthesis, which may have caused the stuck disk. This observation was confirmed by intra-operative findings.

Left ventricular dysfunction assessed by cardiac time interval analysis among different geometric patterns in untreated hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy is a powerful independent predictor of morbidity and mortality in hypertensive patients. Abnormal LV geometric patterns are also associated with hypertensive complications, and concentric hypertrophy is associated with the highest mortality in hypertensive patients. However, the relationship between geometric patterns and cardiac dysfunction is not fully established. We hypothesized that the Tei index, which is a measure of global cardiac function, is a feasible parameter for estimating cardiac dysfunction among the different LV geometric patterns in hypertensive patients. METHODS AND RESULTS: We enrolled 60 consecutive patients with untreated essential hypertension. Subjects were divided into 4 groups: normal geometry, concentric remodeling, eccentric hypertrophy and concentric hypertrophy. We measured ejection fraction, mitral E/A ratio, Tei index, ejection time, and isovolumic contraction and relaxation times. There were significant correlations between LV mass index and systolic blood pressure (P<0.01), ejection fraction (P<0.05), mitral E/A ratio (P<0.05) and Tei index (P<0.0001). In multiple regression analysis, only the Tei index independently correlated with LV mass index (P<0.01). Concentric hypertrophy significantly increased the Tei index compared with the other 3 groups. CONCLUSIONS: The Tei index provides a better marker for LV dysfunction by hypertensive hypertrophy than conventional parameters. LV function in concentric hypertrophy was most impaired among all the geometric patterns in untreated hypertensive patients.

Different flow patterns between left and right internal thoracic artery grafts influence the evaluation of severe graft stenosis by transthoracic Doppler echocardiography.

OBJECTIVE: An increase in the diastolic to systolic flow velocity ratio (D/S) in the proximal left internal thoracic artery (ITA) after coronary artery bypass grafting (CABG) enables noninvasive assessment of graft patency by transthoracic Doppler echocardiography (TTDE). The increase in the D/S can be less pronounced at a site distant from the anastomosis. We postulated that proximal ITA flow patterns differ between the left and right ITAs and that the increase in D/S is less pronounced in the right than in the left proximal ITA. METHODS: Proximal ITA flow was examined by TTDE in 129 consecutive patients after CABG of the left (75) or right (69) ITA to the left coronary artery. The mean D/S of the ITAs was compared with coronary angiography. RESULTS: The D/S was lower in the group with a patent right ITA than in the group with a patent left ITA (P < .05). The D/S of both the left and right ITAs negatively correlated with angiographic stenosis (r = 0.56 or 0.67, P < .001, respectively). The regression line was significantly shifted downward in the right ITA compared with the left ITA, according to analysis of covariance (P = .01). Graft stenosis was predicted by a D/S of <0.57 and <0.28 with an accuracy of 91% and 97% in the left and right ITAs, respectively. CONCLUSION: The patency of both left and right ITA grafts to the left coronary artery can be assessed using TTDE, but different cutoff values of D/S are required to diagnose severe ITA stenosis.

Left ventricular global systolic dysfunction has a significant role in the development of diastolic heart failure in patients with systemic hypertension.

Regional left ventricular (LV) systolic dysfunction has been identified in diastolic heart failure (DHF). However, the relationship between regional or global LV systolic function and heart failure symptoms in DHF has not been evaluated in detail. The present study evaluates such relationships in patients with systemic hypertension (HT) and DHF. We assessed LV systolic and diastolic function in 220 consecutive patients with systemic HT and in 30 normal individuals (Control) using Doppler echocardiography. Patients with HT were assigned to groups with DHF, asymptomatic diastolic dysfunction (ADD) and no diastolic dysfunction (Simple HT). Ejection fraction in DHF was significantly decreased (63±8%) compared with the Control, Simple HT and ADD groups (67±5, 66±7 and 68±8%, respectively). Isovolumetric contraction time in DHF (70±30 msec) was significantly increased compared with those in the ADD, Simple HT and Control groups (31±17, 31±15 and 30±19 msec, respectively). Mitral annular systolic velocities were significantly decreased in the DHF and ADD groups (6.4±1.5 and 7.2±1.3 cm sec⁻¹, respectively) compared with those in the Simple HT and Control groups (8.5±1.8 and 8.4±3.0 cm sec⁻¹, respectively), and in the DHF group compared with the ADD group. LV global systolic dysfunction has a significant role in the development of heart failure symptoms associated with DHF in patients with systemic HT.

Prognostic factors for progression of early- and late-stage calcific aortic valve disease in Japanese: the Japanese Aortic Stenosis Study (JASS) Retrospective Analysis.

Calcific aortic valve disease (CAVD) is the most common etiology of acquired valvular heart disease, and hypertension is a principal underlying disease. The Japanese Aortic Stenosis Study (JASS) Retrospective Analysis is a retrospective observational study to clarify the prognostic factors for progression of CAVD in Japanese. Data from 556 subjects who met the following criteria were analyzed: (1) >or=50 years old; (2) calcification in any aortic valve leaflet or peak aortic jet velocity >or=2 m s(-1) on an echocardiographic study performed between July 2004 and June 2007; and (3) availability of earlier echocardiographic data from within the previous 2-5 years to assess the progression of CAVD. The subjects were divided into two groups according to CAVD severity on the preceding echocardiographic examination. In early-stage subjects with calcification in one or zero leaflets who were without aortic stenosis on the preceding echocardiographic study (n=157), the prognostic factors for progression were the following: (1) no use of angiotensin receptor blockers (ARB) and (2) use of warfarin. In late-stage subjects with calcification in two or three leaflets and/or aortic stenosis on the preceding echocardiographic study (n=399), progression was observed in females and in subjects with low hemoglobin and a concentric left ventricle. There was no relation between medications and changes in CAVD. Prognostic factors for the progression of CAVD were different between the early and late stages. Initiation of ARB treatment during the early stage may be effective, and we should be vigilant about progression of CAVD in patients treated with warfarin.

Left ventricular systolic function is abnormal in diastolic heart failure: re-assessment of systolic function using cardiac time interval analysis.

OBJECTIVES: The purpose of this study was to re-assess the left ventricular (LV) systolic function in diastolic heart failure (DHF) using Doppler echocardiography. BACKGROUND: Systolic function in DHF is defined as the preserved LV ejection fraction (EF). EF may not fully reflect the systolic function in DHF, especially in the presence of abnormalities during the isovolumetric contraction time (ICT). METHODS: We examined LV systolic and diastolic function in 80 consecutive patients with DHF, 30 patients with asymptomatic diastolic dysfunction (ADD), and 30 normal subjects (Control). The LV and left atrial volumes, LV EF, LV ICT, and isovolumetric relaxation time (IRT), early diastolic mitral flow velocity, systolic mitral annular velocity (S'), and early diastolic mitral annular velocity were obtained. RESULTS: LV ICT in DHF (69+/-30 ms) was significantly increased compared to those with ADD (37+/-23 ms) and Control (35+/-26 ms) (P<0.0001). ICT in ADD was equal to that in Control. The LV end-diastolic volume index in DHF (49+/-14 ml/m(2)) was significantly increased compared to those with ADD (42+/-12 ml/m(2)) and Control (43+/-8 ml/m(2)) (P<0.05). S' in DHF (5.9+/-1.4 cm/s) and ADD (6.7+/-1.1 cm/s) was significantly decreased compared to that in Control (8.7+/-2.5 cm/s). CONCLUSIONS: Our results revealed that the major differences between ADD and DHF were global and longitudinal LV systolic dysfunction and LV enlargement. This study suggests that LV systolic dysfunction plays an important role in the development of DHF.

Transient late-onset ischemic mitral regurgitation following Dor's procedure.

A 60-year-old man developed anteroseptal acute myocardial infarction with subsequent left hemiplegia. Echocardiography detected apical aneurysm with thrombus. Coronary artery bypass grafting with Dor's procedure were performed. Chronic heart failure (CHF) developed three months after the surgery. CHF with mitral regurgitation (MR) continued for more than two months and then disappeared. When surgical intervention is considered for late MR after Dor's procedure, it is important to consider that late-onset MR after Dor's procedure can be transient with full medication, which may require four or more months to achieve its full effects.

No reflow-like pattern in intramyocardial coronary artery suggests myocardial ischemia in patients with hypertrophic cardiomyopathy.

BACKGROUND AND PURPOSE: To evaluate intramyocardial coronary flow velocity pattern by transthoracic Doppler echocardiography and its clinical significance in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: In 48 patients with HCM who had angiographically normal coronary artery, coronary flow velocity in the left anterior descending coronary artery (LAD) and intramyocardial coronary artery (IMCA) derived from LAD were evaluated using transthoracic Doppler echocardiography. Two clearly different flow patterns in the IMCA were observed in patients with HCM. Twenty-seven HCM patients (group A) had slow deceleration slope in the IMCA flow (average diastolic deceleration time, 989+/-338; range, 585-1680) and the remaining 21 patients (group B) had steep deceleration slope with diastolic deceleration time <300 ms, resulting in a no reflow-like pattern in the IMCA flow (average diastolic deceleration time, 166+/-67; range, 55-280). There were no significant differences in the clinical characteristics and LAD flow velocity profiles between the two groups. The incidence of cardiovascular symptoms (chest pain or syncope) was significantly higher in group B than in group A (67% vs. 26%, p<0.01). Additionally, exercise-induced ischemia as detected by thallium-201 scintigraphy was significantly more frequent in group B than in group A (6 of 9 (67%) vs. 0 of 9 (0%), p<0.01). CONCLUSIONS: Two different intramyocardial coronary flow velocity patterns are observed in patients with HCM using transthoracic Doppler echocardiography. No reflow-like pattern in the IMCA is strongly related to myocardial ischemia in the absence of epicardial coronary artery stenosis, suggesting that coronary microvascular dysfunction may be a causative mechanism.

Thermal therapy improves left ventricular diastolic function in patients with congestive heart failure: a tissue doppler echocardiographic study.

OBJECTIVES: We previously reported that systemic thermal therapy using 60 degrees C dry sauna improves left ventricular systolic function and clinical symptoms in patients with chronic heart failure. The aim of this study was to investigate the effects of thermal therapy on left ventricular diastolic function. METHODS: We examined transmitral inflow and mitral annular velocity before and after sauna in 10 patients with congestive heart failure using pulsed and tissue Doppler echocardiography. RESULTS: Left ventricular and left atrial dimensions and left ventricular percentage fractional shortening did not change after sauna. Early diastolic mitral inflow velocity (E) increased and the deceleration time of the E wave decreased significantly after sauna compared to before sauna. Early diastolic mitral annular velocity (E') significantly increased after sauna. The deceleration time of E' significantly decreased after sauna compared to before sauna. The E/E' significantly decreased 30 min after sauna. CONCLUSIONS: Thermal therapy improves acute left ventricular diastolic function in patients with congestive heart failure.

Usefulness of a novel ultrasound transducer for continuous monitoring treadmill exercise echocardiography to assess coronary artery disease.

BACKGROUND: The feasibility of a novel ultrasound probe, which can be attached to the left ventricular (LV) apex chest wall and allows free rotation around its long axis direction for the continuous monitoring of LV wall motion, was tested. METHODS AND RESULTS: There were 36 subjects who had coronary artery disease (CAD). By attaching a novel ultrasound probe to the chest wall, the LV apical views were recorded during treadmill exercise stress echocardiography (Echo). The continuous monitoring of LV wall motion was satisfactorily feasible in 30 of 36 patients. The visualization rate of the overall LV segments was higher at rest (90%) compared to that during peak exercise (77%). The segments were better visualized in apical portions (90-100%) than in mid (77-96%) or basal portions (68-87%). The sensitivity, specificity, and accuracy for detecting CAD were 61, 100 and 77%, respectively. The wall motion score index 3 and 6 min after exercise decreased significantly compared to those at peak exercise. The number of segments with dyssynergy was highest at the peak exercise. Ischemic ST-T depression on electrocardiography was observed only at peak stress periods. CONCLUSIONS: Continuous monitoring treadmill exercise Echo using a novel ultrasound probe seems feasible for the non-invasive and physiological assessment of CAD.

Mechanism of recurrent/persistent ischemic/functional mitral regurgitation in the chronic phase after surgical annuloplasty: importance of augmented posterior leaflet tethering.

BACKGROUND: Surgical annuloplasty can potentially hoist the posterior annulus anteriorly, exaggerate posterior leaflet (PML) tethering, and lead to recurrent ischemic/functional mitral regurgitation (MR). Characteristics of leaflet configurations in late postoperative MR were investigated. METHODS AND RESULTS: In 30 patients with surgical annuloplasty for ischemic MR and 20 controls, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, posterior and apical displacement of the coaptation and the MR grade were measured by echocardiography before, early after, and late after surgery. Early after surgery, grade of MR and AML tethering generally decreased (P<0.01), whereas PML tethering significantly worsened (P<0.01). Nine of the 30 patients showed recurrent/persistent MR late after surgery. Compared with patients without late MR, those with the MR showed similar reduction in the annular area, significant re-increase in posterior displacement of the coaptation, and progressive worsening in PML tethering (P<0.05) late after surgery in comparison to the early phase. Both preoperative MR and late postoperative MR were significantly correlated with all tethering variables in univariate analysis. Although apical displacement of the coaptation was the primary determinant of preoperative MR (r2=0.60, P<0.0001), increased PML tethering was the primary determinant of late MR (r2=0.75, P<0.0001). CONCLUSIONS: Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/persistent ischemic/functional MR late after surgical annuloplasty.

Increased Tei index suggests absence of adequate coronary reperfusion in patients with first anteroseptal acute myocardial infarction.

BACKGROUND: The estimation of coronary reperfusion in acute myocardial infarction (AMI) is important. The left ventricular (LV) Tei index is a noninvasive and sensitive parameter expressing overall LV function. We hypothesized that patients without good coronary reperfusion have worse LV function with a higher or worse Tei index compared to those with good reperfusion. METHODS AND RESULTS: In 85 patients with first anteroseptal AMI, without other cardiac lesions such as prior myocardial infarction, LV hypertrophy or valvular disease, the Tei index was measured using Doppler echocardiography immediately after patients' arrival to the hospital, and the Thrombolysis in Myocardial Infarction (TIMI) grade was evaluated through subsequent coronary angiography. The Tei index was significantly greater in patients who did not have TIMI score of 3 compared to those with a TIMI of 3 (0.60+/-0.13 vs 0.46+/-0.06, p<0.0001). A Tei index >0.50 as the criteria for the absence of TIMI 3 had the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 75, 86, 94, 54 and 78%, respectively. CONCLUSION: An increased Tei index suggests the absence of adequate coronary reperfusion in patients with first anterior AMI without other lesion.

Mechanism of persistent ischemic mitral regurgitation after annuloplasty: importance of augmented posterior mitral leaflet tethering.

BACKGROUND: We hypothesized that surgical annuloplasty for ischemic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischemic MR after the annuloplasty were investigated. METHODS AND RESULTS: In 31 patients with surgical annuloplasty for ischemic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (P<0.01), no improvement in AML tethering, greater worsening in PML tethering (P<0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r2=0.46, P<0.0001), increased PML tethering was the primary determinant afterward (r2=0.60, P<0.0001). CONCLUSIONS: Although tethering of both leaflets is the major determinant of ischemic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the annnuloplasty.