Yasuhiko Takemoto

Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women

OBJECTIVE To evaluate the contribution of left atrial (LA) volume in predicting atrial fibrillation (AF). PATIENTS AND METHODS In this retrospective cohort study, a random sample of 2200 adults was identified from all Olmsted County, Minnesota, residents who had undergone transthoracic echocardiographic assessment between 1990 and 1998 and were 65 years of age or older at the time of examination, were in sinus rhythm, and had no history of AF or other atrial arrhythmias, stroke, pacemaker, congenital heart disease, or valve surgery. The LA volume was measured off-line by using a biplane area-length method. Clinical characteristics and the outcome event of incident AF were determined by retrospective review of medical records. Echocardiographic data were retrieved from the laboratory database. From this cohort, 1655 patients in whom LA size data were available were followed from baseline echocardiogram until development of AF or death. The clinical and echocardiographic associations of AF, especially with respect to the role of LA volume in predicting AF, were determined. RESULTS A total of 666 men and 989 women, mean +/- SD age of 75.2 +/- 7.3 years (range, 65-105 years), were followed for a mean +/- SD of 3.97 +/- 2.75 years (range, < 1.00-10.78 years); 189 (11.4%) developed AF. Cox model 5-year cumulative risks of AF by quartiles of LA volume were 3%, 12%, 15%, and 26%, respectively. With Cox proportional hazards multivariate models, logarithmic LA volume was an independent predictor of AF, incremental to clinical risk factors. After adjusting for age, sex, valvular heart disease, and hypertension, a 30% larger LA volume was associated with a 43% greater risk of AF, incremental to history of congestive heart failure (hazard ratio [HR], 1.887; 95% confidence interval [CI], 1.230-2.895; P = .004), myocardial infarction (HR, 1.751; 95% CI, 1.189-2.577; P = .004), and diabetes (HR, 1.734; 95% CI, 1.066-2.819; P = .03). Left atrial volume remained incremental to combined clinical risk factors and M-mode LA dimension for prediction of AF (P < .001). CONCLUSION This study showed that a larger LA volume was associated with a higher risk of AF in older patients. The predictive value of LA volume was incremental to that of clinical risk profile and conventional M-mode LA dimension.

Early detection of cardiac involvement in patients with sarcoidosis by a non-invasive method with ultrasonic tissue characterisation

Objectives: To clarify the value of cycle dependent variation of myocardial integrated backscatter (CV-IB) analysis, which non-invasively measures acoustic properties of the myocardium, for early detection of cardiac involvement in patients with sarcoidosis. Methods: The study population consisted of 22 consecutive patients with biopsy proven sarcoidosis who did not have any abnormal findings on conventional two dimensional echocardiogram. Cardiac sarcoidosis was diagnosed by radionuclide testing including thallium-201 scintigraphy, gallium-67 scintigraphy, and cardiac fluorine-18-deoxyglucose positron emission tomography. The magnitude and delay of the CV-IB were analysed in the basal mid septum and the basal mid posterior wall of the left ventricle of all patients. Results: The patients were divided into two groups: 8 patients with cardiac involvement and 14 patients without cardiac involvement. In the basal septum, a major reduction in the magnitude (mean (SD) 1.8 (4.4) v 6.6 (1.3), p  =  0.012) and an increase in the time delay (1.3 (0.5) v 1.0 (0.1), p  =  0.038) of CV-IB were observed in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. The sensitivity for detecting cardiac involvement was such that the magnitude of CV-IB in the basal septum discriminated 75% of patients with cardiac sarcoidosis from those with non-cardiac sarcoidosis, whereas two dimensional echocardiographic parameters did not discriminate between these two groups. Conclusions: The CV-IB is decreased in the basal septum in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. Analysis of CV-IB may be a useful method to detect early myocardial involvement in patients with sarcoidosis.

Long acting calcium antagonist amlodipine prevents left ventricular remodeling after myocardial infarction in rats

OBJECTIVE The purpose of this study was to examine the effect of amlodipine, a long-acting calcium antagonist, on the left ventricular remodeling, including systolic and diastolic dysfunction, the change of cardiac gene expression in the myocardial infarcted rats (MI). METHODS On the first day after myocardial infarction, the animals were randomly assigned to amlodipine treatment (n = 8) or untreated groups (MI; n = 9). We then performed Doppler-echocardiographic examinations and measured the hemodynamics at four weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. RESULTS Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 22 +/- 1 mmHg and 5 +/- 1 mmHg. Amlodipine reduced LVEDP and CVP to 15 +/- 1 mmHg (P < 0.01) and 3 +/- 0 mmHg (P < 0.01). The weight of right ventricle in MI was significantly larger than in the control rats (Control; 0.48 +/- 0.01 g/kg, MI; 0.79 +/- 0.04 g/kg, P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3 mm (P < 0.01) (Control; 6.2 +/- 0.3 mm). Amlodipine prevented an increase of the weight of right ventricle (0.62 +/- 0.03 g/kg, P < 0.01) and LVDd (7.9 +/- 0.2 mm, P < 0.01 to MI). The rats in MI showed systolic dysfunction shown by the decreased fractional shortening (Control; 31 +/- 2% versus MI; 15 +/- 1%, P < 0.01), and diastolic dysfunction shown by E wave deceleration rate (Control; 18.1 +/- 2.0 m/s2, MI; 32.6 +/- 2.1 m/s2, P < 0.01). Amlodipine significantly prevented systolic and diastolic dysfunction. The increases in beta-MHC, alpha-skeletal actin, and ANP mRNAs in the non-infarcted left ventricle and right ventricle at four weeks after the myocardial infarction were all significantly suppressed by the treatment with amlodipine. On the other hand, depressed alpha-MHC was restored to normal levels by amlodipine in both regions. CONCLUSIONS Amlodipine prevents the left ventricular remodeling process accompanied by systolic and diastolic dysfunction, and inhibits abnormal cardiac gene expression after myocardial infarction.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals

Background: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. Objective: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). Methods: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. Results: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months’ supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). Conclusion: Three months’ supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

Effect of Cilazapril on Ventricular Remodeling Assessed by Doppler-Echocardiographic Assessment and Cardiac Gene Expression

The purpose of this study is to determine whether the administration of the ACE inhibitor cilazapril can lessen the adverse effects of ventricular remodeling, including systolic and diastolic dysfunction, modulation of fetal gene expression, increase of collagen genes, and depression of the sarcoplasmic reticulum (SR) Ca2+ ATPase gene in a myocardial infarcted (MI) rat model. At 1 day after MI, the animals were randomly assigned to cilazapril treatment or no treatment. We performed Doppler-echocardiographic examinations and measured cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The weights of the right (RV) and left ventricles (LV) in 1- and 3-month MI rats were significantly larger than those of the control rats. Cilazapril significantly prevented the increase. The MI rats showed systolic dysfunction, as evidenced by decreased fractional shortening (control, 34 ± 3% vs. MI, 17 ± 3%; P <0.01) and ejection fraction measured by the modified Simpson’s method (control, 61 ± 2% vs. MI, 36 ± 3%; P < 0.01) in rats at 1 month after operation. MI rats showed diastolic dysfunction, defined as increased peak early filling velocity, increased deceleration rate of the early filling wave, decreased late filling velocity, and an increase in the ratio of early filling to late filling velocity. Cilazapril significantly prevented systolic and diastolic dysfunction in rats after MI. The increases in β-MHC, α-skeletal actin, ANP, and collagen I and III mRNAs in the nonischemic LV and RV were significantly suppressed by treatment with cilazapril. Depressed SR Ca2+-ATPase mRNA (nonischemic LV, 0.7-fold, P < 0.05 vs. control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after MI was significantly restored to normal levels by cilazapril. Cilazapril improved the adverse remodeling process by attenuating the progression of systolic and diastolic dysfunction, and prevented abnormal cardiac gene expression following MI.

Polymorphisms of norepinephrine transporter and adrenergic receptor alpha1D are associated with the response to beta-blockers in dilated cardiomyopathy

Recent clinical trials have clearly demonstrated that the administration with β-blockers decreases the mortality in the patients with chronic heart failure (CHF). However, significant heterogeneity exists in the effectiveness of β-blockers among individual cases. We focused on 39 polymorphisms in 16 genes related to adrenergic system and investigated their association with the response to β-blockers among 80 patients with CHF owing to idiopathic dilated cardiomyopathy. The polymorphisms of NET T-182C (P=0.019), ADRA1D T1848A (P=0.023) and ADRA1D A1905G (P=0.029) were associated with the improvement of left ventricular fractional shortening (LVFS) by β-blockers. Furthermore, combined genotype analysis of NET T-182C and ADRA1D T1848A revealed a significant difference in LVFS improvement among genotype groups (P=0.011). These results suggest that NET (T-182C) and ADRA1D (T1848A and A1905G) polymorphisms are predictive markers of the response to β-blockers. Genotyping of these polymorphisms may provide clinical insights into an individual difference in the response to the β-blocker therapy in CHF.

Reliability of measurement of endothelial function across multiple institutions and establishment of reference values in Japanese.

AIMS For the standardization of flow-mediated vasodilatation (FMD) assessment as a clinical tool, validation of its reliability across multiple institutions and the establishment of normal/reference values based on reliable data from multiple institutions are needed. METHODS AND RESULTS In Study 1, assessment of FMD (scan recording and analysis) using an ultrasonographic semi-automatic measuring system (sFMD) was conducted at 18 participating institutions (sFMD-INST) (n = 981). All of the brachial arterial scans were also analyzed at a core laboratory (sFMD-COLB). After 111 subjects with inadequate sFMD recordings were excluded (n = 880), the correlation between the sFMD-INST and sFMD-COLB improved from R = 0.725 to R = 0.838 (p < 0.001). In Study 2, based on good-quality sFMD data obtained from 6660 subjects without cardiovascular disease (CVD) and 729 subjects with CVD from 27 institutions, reference values of sFMD are proposed by the Framingham risk score (FRS)-based risk categories and according to gender and age. The receiver-operating characteristic curve analysis revealed a significant power of sFMD values in reference ranges to discriminate between subjects with and without CVD (e.g., area under curve = 0.64 in the FRS-low risk group). CONCLUSIONS When the analysis was limited to cases with clear sFMD recordings, the reliability of the sFMD assessment (scan and its analysis) conducted in individual institutions appeared to be acceptable. Reference sFMD values (lower cuff occlusion) for the Japanese population are proposed based on reliable data derived from multiple institutions, and the reference values may identify patients without advanced vascular damage.

Acute improvement of atrial mechanical stunning after electrical cardioversion of persistent atrial fibrillation: comparison between biatrial and single atrial pacing

Objective: To evaluate the acute effects of atrial pacing at different pacing sites on mechanical stunning after cardioversion of atrial fibrillation (AF). Setting: Tertiary referral centre. Patients: 20 patients with persistent AF were studied. Interventions: Spontaneous echo contrast (SEC), left atrial appendage emptying velocity (LAAEV), and left atrial appendage emptying fraction (LAAEF) were assessed by transoesophageal echocardiography (TOE) during AF, after conversion to sinus rhythm, and during atrial pacing from the right atrial appendage, left lateral atrium, and both atria simultaneously. Transmitral inflow velocity of the atrial wave (TMIF-A) by TOE and the maximum P wave duration in 12 lead ECG were also measured during sinus rhythm and atrial pacing. Main outcome measures: Comparison of atrial mechanical function and P wave duration in 12 lead ECG during atrial pacing from different sites after cardioversion of AF. Results: Compared with sinus rhythm, atrial pacing at 80 beats/min increased LAAEV from mean (SD) 14.6 (10.1) to 33.4 (19.8) cm/s (p  =  0.001), LAAEF from 13.8 (8.5) to 32.1 (11.2)% (p < 0.001), and TMIF-A from 24.6 (11.9) to 45.6 (21.0) cm/s (p < 0.001) and reduced SEC grade from 2.6 (1.0) to 1.6 (0.9) (p < 0.001). These effects had a positive force–frequency relation. Biatrial pacing produced the shortest P wave duration and resulted in the most significant improvement in atrial function (LAAEV, 33.2 (19.3) v 53.7 (23.9) cm/s, p  =  0.0001; LAAEF, 31.9 (11.1) v 46.2 (12.6)%, p < 0.0001; TMIF-A, 37.7 (18.3) v 54.1 (21.2) cm/s, p < 0.001; SEC grade, 1.4 (1.1) v 0.8 (0.9), p  =  0.001, right atrial appendage versus biatrial pacing). Conclusions: Atrial pacing at increased rates can improve atrial mechanical function after cardioversion of persistent AF. Biatrial pacing may be the most effective technique to reverse atrial mechanical stunning.

Impaired Coronary Circulation in Patients with Apical Hypertrophic Cardiomyopathy: Noninvasive Analysis by Transthoracic Doppler Echocardiography

Objectives: We designed this study to examine the characteristics of coronary circulation in patients with apical hypertrophic cardiomyopathy (ApHCM) using noninvasive transthoracic Doppler echocardiography (TTDE). Background: Recent advances in TTDE have allowed noninvasive assessment of coronary circulation by the measurement of coronary flow velocity (CFV) patterns and coronary flow velocity reserve (CFVR). However, there have been no previous studies evaluating coronary circulation in ApHCM. Methods: We analyzed CFV and CFVR in the left anterior descending coronary artery (LAD), and apical wall thickness in the left ventricle, in 10 ApHCM subjects and 10 control subjects. Mean diastolic velocity (MDV) and time from the beginning of diastole to peak velocity (TPV), and CFVR, defined as a ratio of drug‐induced hyperemic to basal MDV, were measured. Results: At baseline, MDV was higher, and TPV was longer, in ApHCM subjects than in control subjects (29 ± 5.7 versus 19 ± 6.5 cm/sec; p < 0.01 and 5.2 ± 1.0 versus 3.5 ± 0.6 msec; p < 0.005, respectively). CFVR in ApHCM subjects was significantly lower than in control subjects (1.9 ± 0.4 versus 3.1 ± 0.8; p < 0.005). CFVR and basal MDV in ApHCM subjects showed significant correlations with apical/posterior wall thickness ratio [CFVR; r =–0.84, p < 0.01 and MDV; r = 0.74, p < 0.05, respectively].Conclusion: Noninvasive coronary flow assessment by TTDE revealed an impaired coronary circulation with reduced CFVR, high MDV at baseline and prolonged TPV. These results suggest that these characteristics of coronary circulation may provide an additional index for the assessment of ApHCM.

Single-plane and biplane echocardiography: use of targeted scan planes improves the estimates of left ventricular volume and shape for analysis of postinfarction remodeling ☆

OBJECTIVE Acute myocardial infarction and subsequent left ventricular (LV) remodeling induce complex geometric changes quantifiable by 3-dimensional (3D) echocardiography. Our objective was to determine accurate 2-dimensional echocardiographic techniques for analysis of diastolic and systolic LV volume and shape in remodeled hearts. METHODS We obtained 3D apical scans from 16 patients at the acute stage, and at 1 and 6 months after acute myocardial infarction. LV volumes were calculated by 7 methods: (1) Teichholz; (2) Teichholz including the infarcted area; (3) single-plane area-length (AL) using a 2-chamber (2CH) view; (4) single-plane AL using a 4-chamber (4CH) view; (5) single-plane AL using a view including the infarcted area; (6) biplane AL using 2CH and 4CH views; and (7) biplane AL using a view including the infarction region and corresponding orthogonal view (method ALBMIO). LV shape was assessed by 5 methods: (1) a 2CH view; (2) a 4CH view; (3) a single-plane view including the infarcted area; (4) biplane (2CH and 4CH) views; and (5) biplane views including the infarction region and corresponding orthogonal view (method BMIO). RESULTS For end-diastolic and end-systolic LV volume assessments, all 7 methods correlated with the 3D reference, but method ALBMIO performed best (end-diastolic: r = 0.931, bias = 17.4 mL; end-systolic: r = 0.946, bias = 11.2 mL). For LV shape assessments, method BMIO showed the smallest difference from the 3D reference. CONCLUSIONS With 2-dimensional echocardiographic techniques, quantitative analysis of LV volume and shape is most accurate when a component scan plane is targeted through the infarcted myocardial region.