Hirohiko Motoki

Prognostic Significance of Exercise Induced Right Ventricular Dysfunction in Asymptomatic Degenerative Mitral Regurgitation

Background— The role of exercise-induced pulmonary hypertension in decision making regarding surgical timing for asymptomatic chronic mitral regurgitation is controversial. We reasoned that the exercise-induced pulmonary hypertension response could not be interpreted without knowledge of right ventricular (RV) function. The aim of this study was to assess the role of RV measures at rest and during exercise as predictors of prognosis in asymptomatic mitral regurgitation. Methods and Results— Comprehensive resting and exercise echocardiography was performed in 196 consecutive patients (56±13 years; 64% male) with isolated moderate to severe mitral regurgitation (effective regurgitant orifice area, 38±18 mm2) and preserved left ventricular function in whom initial management was expectant. Left ventricular and RV longitudinal strain were analyzed at rest using velocity vector imaging. Tricuspid annular plane systolic excursion and systolic pulmonary arterial pressure were measured at rest and during exercise. Valve surgery was performed in 88 patients (45%) over 27±15 months. After adjustment for age and sex in a Cox proportional-hazards model, exercise tricuspid annular plane systolic excursion (hazard ratio, 0.26; P<0.001), was associated with valve surgery-free survival, independent of resting left ventricular strain (hazard ratio, 1.09; P=0.027), exercise systolic pulmonary arterial pressure (hazard ratio, 1.03; P<0.001), and resting RV strain (hazard ratio, 1.10; P=0.004). In sequential Cox models, a model based on clinical data and left ventricular strain (&khgr;2, 15.9) was improved by RV strain and RV chamber size (&khgr;2, 28.8; P=0.003) and exercise systolic pulmonary arterial pressure (&khgr;2, 40.1; P=0.002) and further increased by exercise tricuspid annular plane systolic excursion (&khgr;2, 52.2; P=0.002). Conclusions— Exercise-induced RV dysfunction provides important incremental prognostic value in the management of asymptomatic mitral regurgitation.

Biventricular Mechanics in Constrictive Pericarditis Comparison With Restrictive Cardiomyopathy and Impact of Pericardiectomy

Background— The aim of our study was to compare myocardial mechanics of constrictive pericarditis (CP) with restrictive cardiomyopathy (RCM), or healthy controls; to assess the impact of pericardial thickening detected by cardiac magnetic resonance on regional myocardial mechanics in CP; and to quantitate the effect of pericardiectomy on myocardial mechanics in CP. Methods and Results— Myocardial mechanics were evaluated by 2-dimensional speckle tracking in 52 consecutive patients with CP who underwent cardiac magnetic resonance examination before pericardiectomy, 35 patients with RCM, and 26 control subjects. CP patients had selectively depressed left ventricular (LV) anterolateral wall strain (LWS) and right ventricular (RV) free wall longitudinal systolic strain (FWS) but preserved LV septal wall systolic strain (SWS). In a comparison of RCM and normals, CP patients had significantly lower regional longitudinal systolic strain ratios (CP versus RCM and normal; LVLWS/LVSWS: 0.8±0.2 versus 1.1±0.2 and 1.0±0.2; P<0.001, RVFWS/LVSWS: 0.8±0.4 vs. 1.4±0.5 and 1.2±0.2; P<0.001). LVLWS/LVSWS was more robust than the LV lateral wall to LV septal wall ratio of early diastolic velocities at the LV base (LE′/SE′) in differentiating CP from RCM (area under the curve=0.91 versus 0.76; P=0.011). There was a significant inverse correlation between pericardial thickness and respective ventricular strains (P=0.001). Pericardiectomy resulted in the improvement of the depressed LVLWS/LVSWS (0.83±0.18–0.95±0.12; P<0.001). Conclusions— Regional longitudinal systolic strain ratios are robust novel diagnostic tools for CP. Regional myocardial mechanics inversely correlates with adjacent pericardial segment thickness detected by cardiac magnetic resonance, and pericardiectomy leads to systolic strain improvement, which is more pronounced in right ventricular and LV free walls.

Torsion analysis in the early detection of anthracycline-mediated cardiomyopathy

AIMS Anthracyclines have profound consequences on the structure and function of the heart, which over time cause a cardiomyopathy that leads to congestive heart failure. Early detection of subclinical left ventricular (LV) dysfunction following a low dose of anthracyclines may be a preventive strategy. The aim of this study was to determine torsion analysis using two-dimensional speckle-tracking imaging (STI), useful for detecting early anthracycline-mediated cardiotoxicity. METHODS AND RESULTS Conventional and Doppler echocardiography images were obtained from 25 patients (mean age 58 ± 11 years) before chemotherapy and 1 and 3 months after treatment. The cumulative anthracycline doses were 98 ± 59 and 170 ± 87 g/m(2) at 1 and 3 months, respectively. After standard echocardiography, LV torsion and twisting velocity profiles from apical and basal short-axis images were analysed using STI. LV dimensions and ejection fraction did not change throughout follow-up. Although isovolumic relaxation time showed prolongation 3 months after chemotherapy, other Doppler indices did not show significant changes. However, significant deteriorations in torsion (P < 0.0001 by ANOVA), twisting rate (P < 0.0001 by ANOVA), and untwisting rate (P < 0.001 by ANOVA) were found 1 month after chemotherapy. A significant negative correlation was observed between cumulative anthracycline doses and torsion (r = -0.524, P < 0.0001). CONCLUSION LV torsion analysis could be a useful non-invasive approach for early detection of subclinical anthracycline cardiotoxicity.

Comparison of three-dimensional Echocardiographic findings to those of Magnetic Resonance Imaging for determination of left ventricular mass in patients With Ischemic and Non-Ischemic Cardiomyopathy

The standard echocardiographic evaluation of left ventricular (LV) mass, particularly in ischemic cardiomyopathy (IC) is challenging because it is based on geometric assumptions. The aim of this study was to assess the accuracy of LV mass calculation using echocardiographic modalities compared with cardiac magnetic resonance (CMR) in IC and in nonischemic cardiomyopathy (non-IC). Echocardiography was performed in 104 patients (mean age 55 ± 15 years) referred for CMR: 63 with IC and 41 with non-IC. CMR, M-mode echocardiography, 2-dimensional echocardiography, and 3-dimensional echocardiography (3DE) were analyzed using standard commercial tools to obtain LV mass. LV mass on 3DE showed a higher correlation with CMR than 2-dimensional echocardiography (r = 0.87 vs r = 0.70, p <0.001). M-mode echocardiography overestimated LV mass (bias +30%) and 2-dimensional echocardiography underestimated LV mass (bias -11%), whereas measurements on 3DE showed only minimal bias (-2%). LV mass on 3DE in non-IC showed a significantly higher correlation with CMR than in IC (r = 0.92 vs r = 0.84, z = 2.3, p <0.05). In non-IC, the mean difference was -2 g (-1% of the mean), with 95% limits of agreement of ±33 g (±19% of the mean). In IC, the mean difference was -7 g (-4% of the mean), with limits of agreement of ±56 g (±31% of the mean). There was a correlation between the absolute LV mass differences (3DE derived and CMR derived) and scar percentage (infarcted mass/total LV mass) using delayed-hyperenhancement images (r = 0.40, p <0.05). The net reclassification index with 3DE was +16% for concentric LV hypertrophy. In conclusion, the most accurate and reliable echocardiographic measurement of LV mass is 3DE, but underestimation and variability remain challenges in IC.

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

Inflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). Kaplan- Meier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 - 1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ(2) = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF15 provided an incremental prognostic value over clinical features.

Prognostic Significance of Neuroadrenergic Dysfunction for Cardiovascular Events in Patients With Acute Myocardial Infarction

BACKGROUND The dysregulation of systemic blood pressure (BP) variation or cardiac neuroadrenergic dysfunction is associated with adverse cardiovascular events. We aimed to clarify the prognostic significance of neuroadrenergic dysfunction for cardiovascular events in patients with acute myocardial infarction (AMI). METHODSANDRESULTS We enrolled 63 AMI patients (mean age, 67±12 years) underwent ambulatory BP monitoring (ABPM) and cardiac iodine-(123)metaiodobenzylguanidine (MIBG) imaging within 4 weeks after AMI onset. We analyzed the circadian BP pattern and heart-to-mediastinum (H/M) MIBG uptake ratio. All the patients were followed for 2 years. The study endpoint was a composite of major adverse cardiovascular events, including all-cause death, MI, coronary revascularization except for the MI culprit lesion, and stroke. Patients with a non-dipper pattern (n=29) or an H/M ratio <1.96 (n=28) had a worse prognosis than those with either a dipper pattern (n=34) or an H/M ratio ≥1.96 (n=35; log-rank, P=0.013 and 0.010, respectively). Patients with both a non-dipper pattern and an H/M ratio <1.96 (n=12) had a significantly worse prognosis than did the other patients (P=0.0020). CONCLUSIONS Dysregulation of BP variation and cardiac MIBG uptake were associated with cardiovascular events following AMI. Examining ABPM with MIBG imaging may potentially improve risk stratification in these patients.

Pericardiectomy is Associated with Improvement in Longitudinal Displacement of Left Ventricular Free Wall Due to Increased Counterclockwise Septal-to-Lateral Rotational Displacement.

BACKGROUND Pericardiectomy is an effective intervention for constrictive pericarditis. Speckle-tracking echocardiography can provide quantitative information not only about longitudinal strain (LS) but about longitudinal displacement (LD) and septal-to-lateral rotational displacement (SLRD). The aim of this study was to investigate whether pericardiectomy improves myocardial mechanics using speckle-tracking analysis. METHODS Eighty-three patients with constrictive pericarditis who underwent echocardiography were retrospectively assessed (mean age, 58 ± 12 years; 72 men; 50 idiopathic, 20 postoperative, four viral, three radiation, and six others) and compared with 20 healthy volunteers. LD and SLRD were measured from the apical four-chamber view and global LS from three apical views. RESULTS LD was less in the constrictive pericarditis group compared with control subjects (P < .001). Only lateral LS was significantly less than that of control subjects (P < .001), but septal LS was similar (P = .48). In pre- and post-pericardial surgery comparisons (n = 27), values of septal and lateral LD were almost identical (mean, 13.6 ± 4.7 vs 13.3 ± 5.4 mm; P = .70) before pericardiectomy, but septal LD decreased (mean, 9.3 ± 3.5 mm; P < .001) and lateral LD increased (mean, 16.8 ± 4.7 mm; P = .0106) after the surgery, even though the difference in LS between the septal and lateral walls decreased (from 5.6 ± 5.3% to 2.5 ± 4.2%, P = .008). Systolic whole-heart swinging motion significantly increased to a counterclockwise direction after surgery (mean SLRD, -0.8 ± 3.3° vs 2.1 ± 3.0°; P = .001). Although the change in SLRD after pericardiectomy was not different between patients with decreases and increases in New York Heart Association class, SLRD change was significantly greater in patients who received fewer diuretics after surgery (mean, 4.00 ± 0.91 vs 0.27 ± 1.47; P = .027). CONCLUSIONS After surgical removal of the pericardium, LD of the septal and lateral walls became significantly different, and counterclockwise SLRD increased, reflecting loss of pericardial support.

Prognostic Improvement by Multidisciplinary Therapy in Patients With Critical Limb Ischemia

Although limb salvage rate has improved in critical limb ischemia (CLI), an improvement in CLI prognosis has been scarcely reported. Multidisciplinary therapy (MT) including revascularization, wound bed preparation, treatment of comorbidity, and education of patients with CLI may improve prognosis. The aim of this study was to investigate the effectiveness of MT in prognostic improvement. We retrospectively analyzed 72 patients with CLI and assessed whether MT improved prognosis. The incidence of amputation-free survival (freedom from major amputation [MA] and death) was significantly different between the MT and conventional groups at 2 years (0% vs 33%; P = .024). After multivariate analysis, transfusion (hazard ratio [HR] 5.778; 95% confidence interval [CI], 2.372-14.073; P < .001), multivessel coronary disease (HR 3.353; 95% CI, 1.309-8.590; P = .012), and C-reactive protein >5 mg/dL (HR 3.958; 95% CI, 1.359-11.531; P = .012) were independent predictors for MA or death. We concluded that MT was effective in improved mortality and limb salvage rate.

Importance of fatty acid compositions in patients with peripheral arterial disease.

Objective Importance of fatty acid components and imbalances has emerged in coronary heart disease. In this study, we analyzed fatty acids and ankle-brachial index (ABI) in a Japanese cohort. Methods Peripheral arterial disease (PAD) was diagnosed in 101 patients by ABI ≤0.90 and/or by angiography. Traditional cardiovascular risk factors and components of serum fatty acids were examined in all patients (mean age 73.2±0.9 years; 81 males), and compared with those in 373 age- and sex-matched control subjects with no evidence of PAD. Results The presence of PAD (mean ABI: 0.71±0.02) was independently associated with low levels of gamma-linolenic acid (GLA) (OR: 0.90; 95% CI: 0.85–0.96; P = 0.002), eicosapentaenoic acid∶arachidonic acid (EPA∶AA) ratio (OR: 0.38; 95% CI: 0.17–0.86; P = 0.021), and estimated glomerular filtration rate (OR: 0.97; 95% CI: 0.96–0.98; P<0.0001), and with a high hemoglobin A1c level (OR: 1.34; 95% CI: 1.06–1.69; P = 0.013). Individuals with lower levels of GLA (≤7.95 µg/mL) and a lower EPA∶AA ratio (≤0.55) had the lowest ABI (0.96±0.02, N = 90), while the highest ABI (1.12±0.01, N = 78) was observed in individuals with higher values of both GLA and EPA∶AA ratio (P<0.0001). Conclusion A low level of GLA and a low EPA∶AA ratio are independently associated with the presence of PAD. Specific fatty acid abnormalities and imbalances could lead to new strategies for risk stratification and prevention in PAD patients.

Diagnostic Value of Peripheral Fractional Flow Reserve in Isolated Iliac Artery Stenosis: A Comparison With the Post- Exercise Ankle-Brachial Index

Purpose To examine in claudicant patients with aortoiliac lesions the relationship between the post-exercise ankle-brachial index (ABI) and the peripheral fractional flow reserve (p-FFR), a physiological test that has heretofore been used to assess coronary and renal artery stenosis. Methods Sixteen male patients (mean age 68.1±7.5 years) with isolated iliac artery lesions detected by ultrasound in 17 limbs were enrolled in this study. Resting ABI was measured and a treadmill test was administered to measure the post-exercise ABI. During angiography, the p-FFR was measured using a pressure guidewire after administration of papaverine to induce hyperemia. Changes in the ABI during exercise and p-FFR at hyperemia were calculated. Results The mean resting ABI and post-exercise ABI were 0.87±0.12 and 0.65±0.24, respectively. There was no complication during the measurement of p-FFR. The mean p-FFR at hyperemia was 0.71±0.14. A significant linear correlation was observed between post-exercise ABI and p-FFR at hyperemia (r=0.857, p<0.001), which was stronger than the correlation between post-exercise ABI and peak-to-peak pressure gradient at hyperemia (r = −0.626, p=0.013). Conclusions Measuring p-FFR appears to be a feasible and safe procedure, and there is a significant linear correlation between post-exercise ABI and p-FFR in aortoiliac lesions. The p-FFR was more accurate than a peak-to-peak pressure gradient in assessing the physiological significance of a stenosis. Though larger studies are required, p-FFR might be used to physiologically assess stenosis in PAD patients with isolated aortoiliac lesions.