Yuchi Han

Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance

William A. Zoghbi, MD, FASE (Chair), David Adams, RCS, RDCS, FASE, Robert O. Bonow, MD, Maurice Enriquez-Sarano, MD, Elyse Foster, MD, FASE, Paul A. Grayburn, MD, FASE, Rebecca T. Hahn, MD, FASE, Yuchi Han, MD, MMSc,* Judy Hung, MD, FASE, Roberto M. Lang, MD, FASE, Stephen H. Little, MD, FASE, Dipan J. Shah, MD, MMSc,* Stanton Shernan, MD, FASE, Paaladinesh Thavendiranathan, MD, MSc, FASE,* James D. Thomas, MD, FASE, and Neil J. Weissman, MD, FASE, Houston and Dallas, Texas; Durham, North Carolina; Chicago, Illinois; Rochester, Minnesota; San Francisco, California; New York, New York; Philadelphia, Pennsylvania; Boston, Massachusetts; Toronto, Ontario, Canada; and Washington, DC

Recurrence of Atrial Fibrillation Correlates With the Extent of Post-Procedural Late Gadolinium Enhancement : A Pilot Study

OBJECTIVES We sought to evaluate radiofrequency (RF) ablation lesions in atrial fibrillation (AF) patients using cardiac magnetic resonance (CMR), and to correlate the ablation patterns with treatment success. BACKGROUND RF ablation procedures for treatment of AF result in localized scar that is detected by late gadolinium enhancement (LGE) CMR. We hypothesized that the extent of scar in the left atrium and pulmonary veins (PV) would correlate with moderate-term procedural success. METHODS Thirty-five patients with AF, undergoing their first RF ablation procedure, were studied. The RF ablation procedure was performed to achieve bidirectional conduction block around each PV ostium. AF recurrence was documented using a 7-day event monitor at multiple intervals during the first year. High spatial resolution 3-dimensional LGE CMR was performed 46 +/- 28 days after RF ablation. The extent of scarring around the ostia of each PV was quantitatively (volume of scar) and qualitatively (1: minimal, 3: extensive and circumferential) assessed. RESULTS Thirteen (37%) patients had recurrent AF during the 6.7 +/- 3.6-month observation period. Paroxysmal AF was a strong predictor of nonrecurrent AF (15% with recurrence vs. 68% without, p = 0.002). Qualitatively, patients without recurrence had more completely circumferentially scarred veins (55% vs. 35% of veins, p = NS). Patients without recurrence more frequently had scar in the inferior portion of the right inferior pulmonary vein (RIPV) (82% vs. 31%, p = 0.025, Bonferroni corrected). The volume of scar in the RIPV was quantitatively greater in patients without AF recurrence (p < or = 0.05) and was a univariate predictor of recurrence using Cox regression (p = 0.049, Bonferroni corrected). CONCLUSIONS Among patients undergoing PV isolation, AF recurrence during the first year is associated with a lesser degree of PV and left atrial scarring on 3-dimensional LGE CMR. This finding was significant for RIPV scar and may have implications for the procedural technique used in PV isolation.

Overexpression of HAX-1 Protects Cardiac Myocytes From Apoptosis Through Caspase-9 Inhibition

Caspase-9 is a critical regulator of mitochondria-mediated apoptosis. We found that adult cardiac myocytes, but not nonmyocytes, have high caspase-9 expression, and exhibit relative resistance to caspase-9–induced cell death. Thus, we hypothesized that cardiac myocytes possess factors that resist apoptosis. Through a yeast two-hybrid screening of adult human heart cDNA library, we identified HS-1 associated protein-1 (HAX-1), a 35-kD BH-domain containing protein localized to the mitochondria as one of the molecules that interacts with caspase-9. Recombinant HAX-1 protein inhibited caspase-9 processing in a dose-dependent manner in a cell-free caspase activation assay. Overexpression of HAX-1 in adult cardiac myocytes conferred 30% protection from apoptosis as compared with the control. Suppression of HAX-1 expression using siRNA-HAX-1 resulted in significant cell death in adult cardiac myocytes, suggesting the importance of HAX-1 in cardiac myocyte resistance to apoptotic stimulation. On apoptotic stimulation, some caspase-9 translocated to the mitochondria and co-localized with HAX-1, confirming the spatial proximity of caspase-9 and HAX-1. In summary, HAX-1 is a newly identified anti-apoptotic factor and its mechanism of action is through caspase-9 inhibition.

Cardiovascular magnetic resonance characterization of mitral valve prolapse.

OBJECTIVES This study sought to develop cardiovascular magnetic resonance (CMR) diagnostic criteria for mitral valve prolapse (MVP) using echocardiography as the gold standard and to characterize MVP using cine CMR and late gadolinium enhancement (LGE)-CMR. BACKGROUND Mitral valve prolapse is a common valvular heart disease with significant complications. Cardiovascular magnetic resonance is a valuable imaging tool for assessing ventricular function, quantifying regurgitant lesions, and identifying fibrosis, but its potential role in evaluating MVP has not been defined. METHODS To develop CMR diagnostic criteria for MVP, characterize mitral valve morphology, we analyzed transthoracic echocardiography and cine CMR images from 25 MVP patients and 25 control subjects. Leaflet thickness, length, mitral annular diameters, and prolapsed distance were measured. Two- and three-dimensional LGE-CMR images were obtained in 16 MVP and 10 control patients to identify myocardial regions of fibrosis in MVP. RESULTS We found that a 2-mm threshold for leaflet excursion into the left atrium in the left ventricular outflow tract long-axis view yielded 100% sensitivity and 100% specificity for CMR using transthoracic echocardiography as the clinical gold standard. Compared with control subjects, CMR identified MVP patients as having thicker (3.2 +/- 0.1 mm vs. 2.3 +/- 0.1 mm) and longer (10.5 +/- 0.5 mm/m(2) vs. 7.1 +/- 0.3 mm/m(2)) indexed posterior leaflets and larger indexed mitral annular diameters (27.8 +/- 0.7 mm/m(2) vs. 21.5 +/- 0.5 mm/m(2) for long axis and 22.9 +/-0.7 mm/m(2) vs. 17.8 +/- 0.6 mm/m(2) for short axis). In addition, we identified focal regions of LGE in the papillary muscles suggestive of fibrosis in 10 (63%) of 16 MVP patients and in 0 of 10 control subjects. Papillary muscle LGE was associated with the presence of complex ventricular arrhythmias in MVP patients. CONCLUSIONS Cardiovascular magnetic resonance image can identify MVP by the same echocardiographic criteria and can identify myocardial fibrosis involving the papillary muscle in MVP patients. Hyperenhancement of papillary muscles on LGE is often present in a subgroup of patients with complex ventricular arrhythmias.

Coronary magnetic resonance vein imaging: Imaging contrast, sequence, and timing

Recently, there has been increased interest in imaging the coronary vein anatomy to guide interventional cardiovascular procedures such as cardiac resynchronization therapy (CRT), a device therapy for congestive heart failure (CHF). With CRT the lateral wall of the left ventricle is electrically paced using a transvenous coronary sinus lead or surgically placed epicardial lead. Proper transvenous lead placement is facilitated by the knowledge of the coronary vein anatomy. Cardiovascular MR (CMR) has the potential to image the coronary veins. In this study we propose and test CMR techniques and protocols for imaging the coronary venous anatomy. Three aspects of design of imaging sequence were studied: magnetization preparation schemes (T2 preparation and magnetization transfer), imaging sequences (gradient‐echo (GRE) and steady‐state free precession (SSFP)), and imaging time during the cardiac cycle. Numerical and in vivo studies both in healthy and CHF subjects were performed to optimize and demonstrate the utility of CMR for coronary vein imaging. Magnetization transfer was superior to T2 preparation for contrast enhancement. Both GRE and SSFP were viable imaging sequences, although GRE provided more robust results with better contrast. Imaging during the end‐systolic quiescent period was preferable as it coincided with the maximum size of the coronary veins. Magn Reson Med, 2007.

Predictors of recovery of left ventricular dysfunction after ablation of frequent ventricular premature depolarizations.

BACKGROUND Frequent ventricular premature depolarizations (VPDs) can cause reversible left ventricular (LV) dysfunction. However, not all patients normalize their LV function after VPD elimination. OBJECTIVE To evaluate predictors of recovery of LV function following the elimination of frequent VPDs. METHODS We identified patients with ≥10% VPDs/24 h and an LV ejection fraction of <50% who underwent successful ablation between 2007 and 2011. Subjects were classified as having reversible (≥10% increase to a final LV ejection fraction of ≥50%) or irreversible (≤10% increase or final LV ejection fraction <50%) LV dysfunction on the basis of echocardiographic follow-up. A reference group with ≥10% VPDs but normal LV function was identified. RESULTS One hundred fourteen patients with ≥10% VPDs were identified; 66 had preserved and 48 had impaired LV function. Over a median follow-up of 10.6 months, 24 of 48 were classified as reversible and 13 of 48 as irreversible and 11 of 44 were excluded. There was a gradient of VPD QRS duration between the control, reversible, and irreversible groups (mean VPD QRS 135, 158, and 173 ms, respectively; P < .001). This gradient persisted even for the same site of origin. In multivariate analysis, the only independent predictor of irreversible LV function was VPD QRS duration (odds ratio 5.07 [95% confidence interval 1.22-21.01] per 10-ms increase). CONCLUSION In patients with LV dysfunction and frequent VPDs, we identified VPD QRS duration as the only independent predictor for the recovery of LV function after ablation. This suggests that VPD QRS duration may be a marker for the severity of underlying substrate abnormality.

Left ventricular Infarct Size, Peri-Infarct Zone and Papillary Scar Measurements: A Comparison of High Resolution 3D and Conventional 2D Late Gadolinium Enhancement Cardiac MR

To compare higher spatial resolution 3D late gadolinium enhancement (LGE) cardiovascular magnetic resonance (Cardiac MR) with 2D LGE in patients with prior myocardial infarction.

Resveratrol modifies risk factors for coronary artery disease in swine with metabolic syndrome and myocardial ischemia

Resveratrol has been purported to modify risk factors for obesity and cardiovascular disease. We sought to examine the effects of resveratrol in a porcine model of metabolic syndrome and chronic myocardial ischemia. Yorkshire swine were fed either a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with supplemental resveratrol (HCD-R; 100mg/kg/day) for 11 weeks. After 4 weeks of diet modification a baseline cardiovascular MRI was performed and an ameroid constrictor was placed on the left circumflex coronary artery of each animal to induce chronic myocardial ischemia. At 7 weeks, a second cardiovascular MRI was performed and swine were sacrificed and myocardial tissue harvested. Resveratrol supplementation resulted in lower body mass indices, serum cholesterol, and C-reactive protein levels, improved glucose tolerance and endothelial function, and favorably augmented signaling pathways associated with myocardial metabolism. Interestingly, serum tumor necrosis factor-α levels were not influenced by resveratrol treatment. Immunoblotting for markers of metabolism demonstrated that insulin receptor substrate-1, glucose transporters 1 and 4, and phospho-AMPK were increased in the HCD-R group. Peroxisome proliferator-activated receptor γ and retinol binding protein 4 were downregulated in the HCD-R group as compared to the HCD group. Myocardial perfusion and function at rest as assessed with magnetic resonance imaging were not different between groups. By favorably influencing risk factors, resveratrol may decrease the burden of chronic metabolic disease and improve cardiovascular health.

Anti-angiogenic effect of high-dose resveratrol in a swine model of metabolic syndrome

BACKGROUND Resveratrol has been reported to induce angiogenesis in ischemic tissue. We hypothesized that high-dose resveratrol would improve native angiogenesis in a swine model of metabolic syndrome and chronic myocardial ischemia. METHODS Yorkshire swine were fed a normal diet (Control, n = 7), hypercholesterolemic diet (HCD, n = 7), or hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCD-R; n = 7) beginning 1 month prior to surgery. Chronic ischemia was created by placing an ameroid constrictor on the left circumflex coronary artery. After 7 weeks, swine underwent functional MRI, coronary angiography, and serum and heart tissue harvest for analysis. RESULTS HCD-R animals had lower body mass index (P < .001), total cholesterol (P < .001), low-density lipoprotein (LDL; P < .001), blood glucose levels (P < .001), and systolic blood pressure (P = .03) than HCD animals. There was no difference in regional myocardial function at 7 weeks (P = .25). Coronary angiograms revealed no difference in Rentrop collateral scores (P = .68). Staining for platelet endothelial cell adhesion molecule-1 demonstrated higher capillary density in the Control group (versus HCD and HCD-R; P = .02). Immunoblotting demonstrated decreased expression of the pro-angiogenic protein vascular endothelial (VE)-cadherin (P = .002) and an increase in anti-angiogenic proteins angiostatin (P = .001) and thrombospondin (P = .02) in the HCD and HCD-R groups. Matrix metalloprotease 2 (MMP 2; P = .47) and MMP 9 (P = .12) were not different among groups. CONCLUSION Supplemental resveratrol positively modified cardiovascular risk factors including body mass index, cholesterol, glucose tolerance, and systolic blood pressure. However, it did not increase native collateral formation in the ischemic myocardium. This may be a result of increased angiostatin and thrombospondin leading to decreased expression of VE-cadherin and other pro-angiogenic factors.

Impact of age, sex, and indexation method on MR left ventricular reference values in the framingham heart study offspring cohort

To determine normative values for left ventricular (LV) volumes, mass, concentricity, and ejection fraction (EF) and investigate associations between sex, age, and body size with LV parameters in community‐dwelling adults.