Hongkun Wang

Multifactorial Determinants of Functional Capacity in Peripheral Arterial Disease: Uncoupling of Calf Muscle Perfusion and Metabolism

OBJECTIVES We aimed to investigate the pathophysiology of peripheral arterial disease (PAD) by examining magnetic resonance imaging (MRI) and spectroscopic (MRS) correlates of functional capacity. BACKGROUND Despite the high prevalence, morbidity, and cost of PAD, its pathophysiology is incompletely understood. METHODS Eighty-five patients (age 68 +/- 10 years) with mild-to-moderate PAD (ankle-brachial index 0.69 +/- 0.14) had their most symptomatic leg studied by MRI/MRS. Percent wall volume in the superficial femoral artery was measured with black blood MRI. First-pass contrast-enhanced MRI calf muscle perfusion and (31)P MRS phosphocreatine recovery time constant (PCr) were measured at peak exercise in calf muscle. All patients underwent magnetic resonance angiography (MRA), treadmill testing with maximal oxygen consumption measurement, and a 6-min walk test. RESULTS Mean MRA index of number and severity of stenoses was 0.84 +/- 0.68 (normal 0), % wall volume 74 +/- 11% (normal 46 +/- 7%), tissue perfusion 0.039 +/- 0.015 s(-1) (normal 0.065 +/- 0.013 s(-1)), and PCr 87 +/- 54 s (normal 34 +/- 16 s). MRA index, % wall volume, and ankle-brachial index correlated with most functional measures. PCr was the best correlate of treadmill exercise time, whereas calf muscle perfusion was the best correlate of 6-min walk distance. No correlation was noted between PCr and tissue perfusion. CONCLUSIONS Functional limitations in PAD are multifactorial. As measured by MRI and spectroscopy, atherosclerotic plaque burden, stenosis severity, tissue perfusion, and energetics all play a role. However, cellular metabolism is uncoupled from tissue perfusion. These findings suggest a potential role for therapies that regress plaque, increase tissue perfusion, and/or improve cellular metabolism. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).

Reproducibility and Reliability of Atherosclerotic Plaque Volume Measurements in Peripheral Arterial Disease with Cardiovascular Magnetic Resonance

A high resolution, noninvasive approach to quantify atherosclerotic plaque in the peripheral vasculature could have significant clinical and research utility. Seventeen patients with peripheral arterial disease (PAD) were studied in a 1.5T CMR scanner. Atherosclerotic plaque volume in the superficial femoral artery was measured and interobserver, intraobserver, and test-retest variability determined. Nineteen vessels were studied with mean acquisition time of 13.1 minutes per vessel. Mean plaque volume was 7.27 +/- 3.73 cm3. Intra-observer intraclass correlation was R = 0.997, inter-observer was R = 0.987, and test-retest reproducibility was R = 0.996. Thus, high resolution measurement of plaque volume in PAD is reliable and reproducible.

The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline

BACKGROUND Both statins and ezetimibe lower LDL-C, but ezetimibes effect on atherosclerosis is controversial. We hypothesized that lowering LDL-C cholesterol by adding ezetimibe to statin therapy would regress atherosclerosis measured by magnetic resonance imaging (MRI) in the superficial femoral artery (SFA) in peripheral arterial disease (PAD). METHODS Atherosclerotic plaque volume was measured in the proximal 15-20 cm of the SFA in 67 PAD patients (age 63 ± 10, ABI 0.69 ± 0.14) at baseline and annually × 2. Statin-naïve patients (n=34) were randomized to simvastatin 40 mg (S, n=16) or simvastatin 40 mg+ezetimibe 10mg (S+E, n=18). Patients already on statins but with LDL-C >80 mg/dl had open-label ezetimibe 10mg added (E, n=33). Repeated measures models estimated changes in plaque parameters over time and between-group differences. RESULTS LDL-C was lower at year 1 in S+E (67 ± 7 mg/dl) than S (91 ± 8 mg/dl, p<0.05), but similar at year 2 (68 ± 10 mg/dl vs. 83 ± 11 mg/dl, respectively). Plaque volume did not change from baseline to year 2 in either S+E (11.5 ± 1.4-10.5 ± 1.3 cm(3), p=NS) or S (11.0 ± 1.5-10.5 ± 1.4 cm(3), p=NS). In E, plaque progressed from baseline to year 2 (10.0 ± 0.8-10.8 ± 0.9, p<0.01) despite a 22% decrease in LDL-C. CONCLUSIONS Statin initiation with or without ezetimibe in statin-naïve patients halts progression of peripheral atherosclerosis. When ezetimibe is added to patients previously on statins, peripheral atherosclerosis progressed. Thus, ezetimibes effect on peripheral atherosclerosis may depend upon relative timing of statin therapy.

Low-Density Lipoprotein Lowering Does Not Improve Calf Muscle Perfusion, Energetics, or Exercise Performance in Peripheral Arterial Disease

OBJECTIVES We hypothesized that low-density lipoprotein (LDL) reduction regardless of mechanism would improve calf muscle perfusion, energetics, or walking performance in peripheral arterial disease (PAD) as measured by magnetic resonance imaging and magnetic resonance spectroscopy. BACKGROUND Statins improve cardiovascular outcome in PAD, and some studies suggest improved walking performance. METHODS Sixty-eight patients with mild to moderate symptomatic PAD (age 65 ± 11 years; ankle-brachial index [ABI] 0.69 ± 0.14) were studied at baseline and annually for 2 years after beginning simvastatin 40 mg (n = 20) or simvastatin 40 mg/ezetimibe 10 mg (n = 18) if statin naïve, or ezetimibe 10 mg (n = 30) if taking a statin. Phosphocreatine recovery time was measured by (31)P magnetic resonance spectroscopy immediately after symptom-limited calf exercise on a 1.5-T scanner. Calf perfusion was measured using first-pass contrast-enhanced magnetic resonance imaging with 0.1 mM/kg gadolinium at peak exercise. Gadolinium-enhanced magnetic resonance angiography was graded. A 6-min walk and a standardized graded Skinner-Gardner exercise treadmill test with peak Vo(2) were performed. A repeated-measures model compared changes over time. RESULTS LDL reduction from baseline to year 2 was greater in the simvastatin 40 mg/ezetimibe 10 mg group (116 ± 42 mg/dl to 56 ± 21 mg/dl) than in the simvastatin 40 mg group (129 ± 40 mg/dl to 90 ± 30 mg/dl, p < 0.01). LDL also decreased in the ezetimibe 10 mg group (102 ± 28 mg/dl to 79 ± 27 mg/dl, p < 0.01). Despite this, there was no difference in perfusion, metabolism, or exercise parameters between groups or over time. Resting ABI did improve over time in the ezetimibe 10 mg group and the entire study group of patients. CONCLUSIONS Despite effective LDL reduction in PAD, neither tissue perfusion, metabolism, nor exercise parameters improved, although rest ABI did. Thus, LDL lowering does not improve calf muscle physiology or functional capacity in PAD. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).

Patterns of Late Gadolinium Enhancement in Chronic Hemodialysis Patients

OBJECTIVES The aim of this work was to characterize patterns of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance imaging in a hemodialysis population at high risk for cardiovascular events. BACKGROUND The prevalence and distribution of LGE and its relationship to left ventricular mass (LVM) and function in this population is unknown. METHODS Chronic hemodialysis patients at high risk for cardiovascular events-age >50 years, diabetes, or known cardiovascular disease-were enrolled prior to concerns regarding nephrogenic systemic fibrosis. Cardiovascular magnetic resonance imaging was performed in 24 patients (age, 59 +/- 11 years; dialysis, 45 +/- 38 months) and included steady-state free precession cine imaging and late gadolinium-enhanced, phase-sensitive, inversion-recovery gradient echo images. Left ventricular mass, volumes, and function were calculated and indexed to body surface area. A 16-segment analysis was performed to calculate percentage of LGE, LV wall thickness, and percentage of wall thickening. RESULTS Left ventricular ejection fraction was 48 +/- 15%, and the LV mass index was 100 +/- 52 g/m(2). Late gadolinium enhancement was observed in 79% (19 of 24) of patients in 3 distinct patterns: infarct-related (32%, 6 of 19), diffuse (37%, 7 of 19), and focal noninfarct (37%, 7 of 19). Late gadolinium enhancement constituted 15 +/- 18% of the LVM and correlated with LVM (r = 0.44, p = 0.03). A significant, inverse relationship existed between segmental LGE and the percentage of wall thickening (p > 0.0001). Excluding infarct-related segments, as end-diastolic wall thickness increased, so did LGE (p < 0.0001), and as LGE increased, the percentage of wall thickening decreased (p = 0.0012). After 23 +/- 3 months of follow-up, 1 patient had developed nephrogenic systemic fibrosis. Seven of the patients (29%) had developed a hard cardiovascular event, 5 of 19 (26%) with LGE and 2 of 5 (40%) without. CONCLUSIONS Late gadolinium enhancement is prevalent in the hemodialysis population and its extent is related to LVM. Most cases of LGE are not infarct-related and are associated with hypertrophied, dysfunctional LV segments. Non-infarct-related LGE may signify fibrosis from LV hypertrophy and/or an infiltrative process. Further studies in this patient population will not be possible due to the risk of nephrogenic systemic fibrosis.

The prevalence of extracardiac findings by multidetector computed tomography before atrial fibrillation ablation

BACKGROUND AND OBJECTIVES The study was designed to determine the prevalence of extracardiac findings discovered during multidetector computed tomography (CT) (MDCT) examinations before atrial fibrillation ablation. Multidetector CT has become a valuable tool in detailing left atrial anatomy before catheter ablation. The incidence of extracardiac findings has been reported for electron beam CT calcium scoring and coronary MDCT, but no data exist for the prevalence of extracardiac findings discovered before atrial fibrillation ablation with MDCT. METHODS AND RESULTS Clinical reports from MDCT examinations before atrial fibrillation ablation and interpretations by 2 radiologists blinded to the clinical reports were reviewed for significant additional extracardiac findings and recommendations for follow-up. In 149 patients who underwent MDCT, the mean age was 55.9 +/- 11.0 years, 75% were men, and 47% had a history of smoking. Extracardiac findings were identified in 69% of patients with clinical, 90% of reader 1, and 97% of reader 2 interpretations (kappa = 0.086). Follow-up was recommended in 30% of clinical, 50% of reader 1, and 38% of reader 2 interpretations (kappa = 0.408). Pulmonary nodules were the most common additional finding and reason for suggested follow-up for all interpreters. CONCLUSIONS The prevalence of extracardiac abnormalities detected by MDCT is considerable. Significant variability in their identification exists between interpreters, but there is good agreement about the need for further follow-up. It is important that those who interpret these examinations are adequately trained in the identification and interpretation of both cardiac and extracardiac findings.