Kihei Yoneyama

Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis

AIMS Left ventricular (LV) circumferential strain (Ecc) is a sensitive index of regional myocardial function. Currently, no studies have assessed its prognostic value in general population. We sought to investigate whether Ecc has a prognostic value for predicting incident heart failure (HF) and other major cardiovascular events in asymptomatic individuals without a history of previous cardiovascular diseases. METHODS AND RESULTS We, prospectively, assessed incident HF and atherosclerotic events during a 5.5 ± 1.3-year period in 1768 asymptomatic individuals aged 45-84 (mean age 65 years; 47% female) who underwent tagged magnetic resonance imaging for strain determination. During the follow-up period, 39 (2.2%) participants experienced incident HF and 108 (6.1%) participants had atherosclerotic cardiovascular events. Average of peak Ecc of 12-LV segments (Ecc-global) and mid-slice (Ecc-mid) was -17.0 ± 2.4 and -17.5 ± 2.7%, respectively. Participants with average absolute Ecc-mid lower than -16.9% had a higher cumulative hazard of incident HF (log-rank test, P = 0.001). In cox regression analysis, Ecc-mid predicted incident HF independent of age, diabetes status, hypertension, interim myocardial infarction, LV mass index, and LV ejection fraction (hazard ratio 1.15 per 1%, 95% CI: 1.01-1.31, P = 0.03). This relationship remained significant after adjustment for LV-end-systolic wall stress into covariates. In addition, by adding Ecc-mid to risk factors, LV ejection fraction, and the LV mass index, both the global χ(2) value (76.6 vs. 82.4, P = 0.04) and category-less net-reclassification index (P = 0.01, SE = 0.18, z = 2.53) were augmented for predicting HF. Circumferential strain was also significantly related to the composite atherosclerotic cardiovascular events, but its relationship was attenuated after introducing the LV mass index. CONCLUSION Circumferential shortening provides robust, independent, and incremental predictive value for incident HF in asymptomatic subjects without any history of previous clinical cardiovascular disease. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Age, Sex, and Hypertension-Related Remodeling Influences Left Ventricular Torsion Assessed by Tagged Cardiac Magnetic Resonance in Asymptomatic Individuals The Multi-Ethnic Study of Atherosclerosis

Background—The aim of the present study was to evaluate how torsion is influenced by left ventricular (LV) remodeling associated with age, sex, and hypertension in a large community-based population. Methods and Results—Myocardial shortening and torsion were assessed by tagged cardiac magnetic resonance in 1478 participants without clinically apparent cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Torsion was defined as the difference between apical and basal rotation divided by slice distance. In multivariable linear regression models, older age was associated with lower stroke volume (−3.6 mL per decade; P<0.001) and higher LV mass-to-volume ratio (0.03 g/mL per decade; P<0.001), along with lower circumferential shortening (−0.17% per decade; P<0.05). Torsion, however, was greater at older ages (0.14° per decade; P<0.001) and in women (0.37°/cm versus men; P<0.001). Hypertensive participants had higher LV mass and LV mass-to-volume ratio (15.5 g and 0.07 g/mL, respectively; P<0.001 for both). Circumferential shortening was lower in hypertensive (−0.42%; P<0.01), whereas torsion was higher after adjustment for age and sex (0.17°/cm; P<0.05). Conclusions—Older age is associated with lower LV volumes and greater relative wall thickness and is accompanied by lower circumferential myocardial shortening, whereas torsion is greater with older age. Hypertensive individuals have greater LV volumes and relative wall thickness and lower circumferential shortening. Torsion, however, is greater in hypertension independently of age and sex. Torsion may therefore represent a compensatory mechanism to maintain an adequate stroke volume and cardiac output in the face of the progressively reduced LV volumes and myocardial shortening associated with hypertension and aging.

N-terminal Pro-B-Type Natriuretic Peptide, Left Ventricular Mass, and Incident Heart Failure: Multi-Ethnic Study of Atherosclerosis

Background—Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population. Methods and Results—A total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54–2.46, P<0.001). This relationship held among different ethnic groups, non-Hispanic whites, African-Americans, and Hispanics. Most importantly, NT-proBNP provided additive prognostic value beyond both traditional risk factors and LV mass index for predicting incident HF (integrated discrimination index=0.046, P<0.001; net reclassification index; 6-year risk probability categorized by <3%, 3–10%, >10% =0.175, P=0.019; category-less net reclassification index=0.561, P<0.001). Conclusions—Plasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Interstitial fibrosis, left ventricular remodeling, and myocardial mechanical behavior in a population-based multiethnic cohort: the Multi-Ethnic Study of Atherosclerosis (MESA) study.

Background—Tagged cardiac magnetic resonance provides detailed information on regional myocardial function and mechanical behavior. T1 mapping by cardiac magnetic resonance allows noninvasive quantification of myocardial extracellular expansion (ECE), which has been related to interstitial fibrosis in previous clinical and subclinical studies. We assessed sex-associated differences in the relation of ECE to left ventricular (LV) remodeling and myocardial systolic and diastolic deformation in a large community-based multiethnic population. Methods and Results—Midventricular midwall peak circumferential shortening and early diastolic strain rate and LV torsion and torsional recoil rate were determined using cardiac magnetic resonance tagging. Midventricular short-axis T1 maps were acquired in the same examination pre- and postcontrast injection using Modified Look-Locker Inversion-Recovery sequence. Multivariable linear regression (estimated regression coefficient, B) was used to adjust for risk factors and subclinical disease measures. Of 1230 participants, 114 had a visible myocardial scar by late gadolinium enhancement. Participants without a visible myocardial scar (n=1116) had no history of previous clinical events. In the latter group, multivariable linear regression demonstrated that lower postcontrast T1 times, reflecting greater ECE, were associated with lower circumferential shortening (B=−0.1; P=0.0001), lower LV end-diastolic volume index (B=0.6; P=0.0001), and lower LV end-diastolic mass index (B=0.4; P=0.0001). In addition, lower postcontrast T1 times were associated with lower early diastolic strain rate (B=0.01; P=0.03) in women only and lower LV torsion (B=0.005; P=0.03) and lower LV ejection fraction (B=0.2, P=0.01) in men only. Conclusions—Greater ECE is associated with reduced LV end-diastolic volume index and LV end-diastolic mass index in a large multiethnic population without history of previous cardiovascular events. In addition, greater ECE is associated with reduced circumferential shortening, lower early diastolic strain rate, and a preserved ejection fraction in women, whereas in men, greater ECE is associated with greater LV dysfunction manifested as reduced circumferential shortening, reduced LV torsion, and reduced ejection fraction.

Aligning Coronary Anatomy and Myocardial Perfusion Territories: An Algorithm for the CORE320 Multicenter Study

Background—Appropriate clinical decisions concerning diagnosis and treatment of coronary artery disease rely on correct integration of data on coronary anatomy and myocardial perfusion. The purpose of this article is to introduce a new left ventricular segmentation model for improved alignment of coronary arterial segments and myocardial perfusion territories, designed for the CORE320 study. Methods and Results—CORE320 is a prospective, multicenter study with a primary objective to evaluate the diagnostic accuracy of 320-row detector computed tomography (CT) to detect coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected coronary artery disease compared with the gold standard of conventional coronary angiography and single-photon emission CT myocardial perfusion imaging. We describe a 19-coronary segment and 13-myocardial territory alignment model, its application in both standard and CT image data sets, and the adjudication process of the initial cohort of patients recruited for the CORE320 study. Adjudication committees reviewed the images of the first 101 gold standard and 107 CT data sets. On the basis of the presented model and rules, all cases for adjudication were correctly identified. During image review, 6 (5.9%) gold standard and 9 (8.4%) CT data sets needed further realignment not triggered by the algorithm. Conclusions—We present a vascular territory distribution model developed for the CORE320 multicenter study, which accounts for variability in coronary anatomy and potential myocardial perfusion territory overlap. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037.Background— Appropriate clinical decisions concerning diagnosis and treatment of coronary artery disease rely on correct integration of data on coronary anatomy and myocardial perfusion. The purpose of this article is to introduce a new left ventricular segmentation model for improved alignment of coronary arterial segments and myocardial perfusion territories, designed for the CORE320 study. Methods and Results— CORE320 is a prospective, multicenter study with a primary objective to evaluate the diagnostic accuracy of 320-row detector computed tomography (CT) to detect coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected coronary artery disease compared with the gold standard of conventional coronary angiography and single-photon emission CT myocardial perfusion imaging. We describe a 19-coronary segment and 13-myocardial territory alignment model, its application in both standard and CT image data sets, and the adjudication process of the initial cohort of patients recruited for the CORE320 study. Adjudication committees reviewed the images of the first 101 gold standard and 107 CT data sets. On the basis of the presented model and rules, all cases for adjudication were correctly identified. During image review, 6 (5.9%) gold standard and 9 (8.4%) CT data sets needed further realignment not triggered by the algorithm. Conclusions— We present a vascular territory distribution model developed for the CORE320 multicenter study, which accounts for variability in coronary anatomy and potential myocardial perfusion territory overlap. Clinical Trial Registration— URL: . Unique identifier: [NCT00934037][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00934037&atom=%2Fcirccvim%2F5%2F5%2F587.atom

Diastolic function assessed from tagged MRI predicts heart failure and atrial fibrillation over an 8-year follow-up period: the multi-ethnic study of atherosclerosis

OBJECTIVES The strain relaxation index (SRI), a novel diastolic functional parameter derived from tagged magnetic resonance imaging (MRI), is used to assess myocardial deformation during left ventricular relaxation. We investigated whether diastolic function indexed by SRI predicts heart failure (HF) and atrial fibrillation (AF) over an 8-year follow-up. METHODS As a part of the multi-ethnic study of atherosclerosis, 1544 participants free of known cardiovascular disease (CVD) underwent tagged MRI in 2000-02. Harmonic phase analysis was used to compute circumferential strain. Standard parameters, early diastolic strain rate (EDSR) and the peak torsion recoil rate were calculated. An SRI was calculated as difference between post-systolic and systolic times of the strain peaks, divided by the EDSR peak. It was normalized by the total interval of relaxation. Over an 8-year follow-up period, we defined AF (n = 57) or HF (n = 36) as combined (n = 80) end-points. Cox regression assessed the ability of SRI to predict events adjusted for risk factors and markers of subclinical disease. Integrated discrimination index (IDI) and net reclassification index (NRI) of SRI, compared with conventional indices, were also assessed. RESULTS The hazard ratio for SRI remained significant for the combined HF and AF end-points as well as for HF alone after adjustment. For the combined end-point, IDI was 1.5% (P < 0.05) and NRI was 11.4% (P < 0.05) for SRI. Finally, SRI was more robust than all other existing cardiovascular magnetic resonance diastolic functional parameters. CONCLUSION SRI predicts HF and AF over an 8-year follow-up period in a large population free of known CVD, independent of established risk factors and markers of subclinical CVD.

Association of Aortic Stiffness With Left Ventricular Remodeling and Reduced Left Ventricular Function Measured by Magnetic Resonance Imaging The Multi-Ethnic Study of Atherosclerosis

Background—This study sought to assess cross-sectional associations of aortic stiffness assessed by magnetic resonance imaging with left ventricular (LV) remodeling and myocardial deformation in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results—Aortic arch pulse wave velocity (PWV) was measured with phase contrast cine magnetic resonance imaging. LV circumferential strain (Ecc), torsion, and early diastolic strain rate were determined by tagged magnetic resonance imaging. Multivariable linear regression models were used to adjust for demographics and cardiovascular risk factors. Of 2093 participants, multivariable linear regression models demonstrated that higher arch PWV was associated with higher LV mass index (B=0.53 per 1 SD increase for log-transformed PWV, P<0.05) and LV mass to volume ratio (B=0.015, P<0.01), impaired LV ejection fraction (LVEF; B=−0.84; P<0.001), Ecc (B=0.55; P<0.001), torsion (B=−0.11; P<0.001), and early diastolic strain rate (B=−0.003; P<0.05). In sex stratified analysis, higher arch PWV was associated with higher MVR (B=0.02; P<0.05), impaired Ecc (B=0.60; P<0.001), and LVEF (B=−0.45; P<0.05), but with maintained torsion in women. Higher PWV was associated with impaired Ecc (B=0.49; P<0.001) and LVEF (B=−1.21; P<0.001), with lower torsion (B=−0.17; P<0.001) in men. Conclusions—Higher arch PWV is associated with LV remodeling, and reduced LV systolic and diastolic function in a large multiethnic population. Greater aortic arch stiffness is associated with concentric LV remodeling and relatively preserved LVEF with maintained torsion in women, whereas greater aortic arch stiffness is associated with greater LV dysfunction demonstrated as impaired Ecc, torsion, and LVEF, with less concentric LV remodeling in men.

Simple exercise echocardiography using a Master's two-step test for early detection of pulmonary arterial hypertension

BACKGROUND Early detection of pulmonary arterial hypertension (PAH) is indispensable, although, echocardiography at rest alone does not provide sufficient evidence for it. Here, this study aimed to investigate the usefulness of simple exercise echocardiography using a Masters two-step test for detecting early PAH. METHODS This study included 52 connective tissue disease patients who had mild symptoms in World Health Organization functional classification 2, suspected as having early PAH, and underwent exercise echocardiography and right heart catheterization. Echocardiography was performed before and after the Masters two-step exercise test; the study patients were classified into the non-PAH (mean pulmonary arterial pressure <25 mmHg, n=37) or PAH (mean pulmonary arterial pressure ≥25 mmHg, n=15) groups. RESULTS Rest systolic pulmonary artery pressure estimated using echocardiography did not significantly differ between the two groups; however, a significant difference in post-exercise systolic pulmonary artery pressure was found (non-PAH, 58.8±10.8 mmHg; PAH, 80.2±14.3 mmHg, p<0.0001). The multiple logistic regression analysis indicated post-exercise systolic pulmonary artery pressure as an independent predictor of PAH (p=0.013). The area under the curve by post-exercise systolic pulmonary artery pressure was 0.91 for PAH. Post-exercise systolic pulmonary artery pressure ≥69.6 mmHg predicted PAH with the sensitivity of 93% and the specificity of 90%. CONCLUSIONS Simple exercise echocardiography using the Masters two-step test could detect PAH in mildly symptomatic connective tissue disease patients. The usefulness of this method should be verified for the early detection of PAH.

Relationship between sleep apnea syndrome and sleep blood pressure in patients without hypertension.

BACKGROUND AND PURPOSE Ambulatory blood pressure monitoring (ABPM) provides an accurate assessment of blood pressure (BP) and shows non-dipper BP pattern in many sleep apnea syndrome (SAS) patients with hypertension (HTN); however, little information is available on the relationship between the severity of SAS and circadian BP changes in SAS patients without HTN. This study investigated whether SAS patients without HTN would have different BP courses in the severity of SAS. METHODS AND SUBJECTS Seventy-four consecutive outpatients without HTN [systolic BP (BPs) at clinic <140mmHg and/or diastolic BP (BPd) at clinic <90mmHg], who received no antihypertensives, underwent overnight polysomnography (PSG) and ABPM. The apnea-hypopnea index (AHI) was calculated from the PSG results; patients were stratified into the following 4 groups based on their AHI: non-SAS, mild-, moderate-, or severe-SAS. RESULTS The diurnal BPs and BPd showed no differences in the severity of SAS; however, the sleep BPs, lowest BPs, and pre-awake BPs were significantly higher in the severe-SAS group than the non-SAS group (p=0.02, p=0.04, and p=0.006, respectively). The sleep BPd and pre-awake BPd were significantly higher in the severe-SAS than the non-SAS (p=0.01 and p=0.0003, respectively) and mild-SAS (p=0.01 and p=0.008, respectively) groups. CONCLUSIONS The results of this study suggested that SAS affected nocturnal BP elevation even in SAS patients without HTN. The diurnal BP showed no difference in the severity of SAS; however, the severe-SAS group revealed significant nocturnal BP elevation.

Peak time of acute coronary syndrome in patients with sleep disordered breathing.

BACKGROUND Recently, sleep disordered breathing (SDB) has gained attention in the field of cardiology. Until now, no study describing the relationship between acute coronary syndrome (ACS) and SDB has been carried out in Japan. METHODS Among ACS patients admitted to our hospital, 44 patients (mean age 60.6+/-13.5 years) who received a portable polysomnography to measure apnea hypopnea index (AHI) were selected for this study. The circadian pattern of ACS onset was studied in 6-h intervals. In addition, all subjects were divided into three groups according to AHI severity (AHI < 5, 5 < or = AHI < 15, and 15 < or = AHI). Then, a comparative study between peak time of ACS and AHI severity was conducted for each group. RESULTS In the AHI < 5 group, 66.0% patients suffered from ACS between 12:00 h and 18:00 h and 17.0% between 18:00 h and 24:00 h, and a total of 83.0% patients had ACS between 12:00 h and 24:00 h. In the 5 < or = AHI < 15 group, 49.9% patients had ACS between 24:00 h and 06:00 h, 16.7% patients between 06:00 h and 12:00 h. 12:00-18:00 h and 18:00-24:00 h showed no significant difference. All 22 patients in the 15 < or = AHI group suffered from ACS between 24:00 h and 12:00 h. CONCLUSION The results of this study suggest a possible relationship between SDB and the onset of ACS between midnight to morning.