Amy M. West

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).

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.

Cardiovascular Magnetic Resonance Imaging of Myocardial Infarction, Viability, and Cardiomyopathies

Cardiovascular magnetic resonance provides the opportunity for a truly comprehensive evaluation of patients with a history of myocardial infarction, with regard to characterizing the extent of disease, effect on left ventricular function, and degree of viable myocardium. The use of contrast-enhanced cardiac magnetic resonance (CMR) imaging for first-pass perfusion and late gadolinium enhancement is a powerful technique for delineating areas of myocardial ischemia and infarction. Using a combination of T2-weighted and contrast-enhanced CMR images, information about the acuity of an infarct can be obtained. There is extensive published data using contrast-enhanced CMR to predict myocardial functional recovery with revascularization in patients with ischemic cardiomyopathies. In addition, CMR imaging in patients with cardiomyopathies can distinguish between ischemic and nonischemic etiologies, with the ability to further characterize the underlying pathology of nonischemic cardiomyopathies.

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).

Percutaneous intervention in peripheral artery disease improves calf muscle phosphocreatine recovery kinetics: A pilot study

We hypothesized that percutaneous intervention in the affected lower extremity artery would improve calf muscle perfusion and cellular metabolism in patients with claudication and peripheral artery disease (PAD) as measured by magnetic resonance imaging (MRI) and spectroscopy (MRS). Ten patients with symptomatic PAD (mean ± SD: age 57 ± 9 years; ankle–brachial index (ABI) 0.62 ± 0.17; seven males) were studied 2 months before and 10 months after lower extremity percutaneous intervention. Calf muscle phosphocreatine recovery time constant (PCr) in the revascularized leg was measured by 31P MRS immediately after symptom-limited exercise on a 1.5-T scanner. Calf muscle perfusion was measured using first-pass gadolinium-enhanced MRI at peak exercise. A 6-minute walk and treadmill test were performed. The PCr recovery time constant improved significantly following intervention (91 ± 33 s to 52 ± 34 s, p < 0.003). Rest ABI also improved (0.62 ± 0.17 to 0.93 ± 0.25, p < 0.003). There was no difference in MRI-measured tissue perfusion or exercise parameters, although the study was underpowered for these endpoints. In conclusion, in this pilot study, successful large vessel percutaneous intervention in patients with symptomatic claudication, results in improved ABI and calf muscle phosphocreatine recovery kinetics.

256- and 320-row coronary CTA: is more better?

This editorial refers to ‘The diagnostic accuracy of 256-row computed tomographic angiography compared with invasive coronary angiography in patients with suspected coronary artery disease’, by S.-P. Chao et al. doi:10.1093/eurheartj/ehq072 and ‘Diagnostic accuracy of 320-row multidetector computed tomography coronary angiography in the non-invasive evaluation of significant coronary artery disease’, by F.R. de Graaf et al. doi:10.1093/eurheartj/ehp571 The gold standard for evaluating coronary anatomy is invasive coronary angiography because of excellent spatial resolution. Significant advances in coronary CT angiography (CCTA) using multiple-row detectors (MDCT) have made it possible to evaluate the heart and coronary arteries non-invasively. The development of MDCT, beginning with four detector rows and improving to the current clinical standard of 64 rows, allows imaging of the heart in a sufficiently short breath hold as to minimize motion artefacts. However, research with much higher numbers of detector rows, such as the 256- and 320-row MDCT now makes it possible to image the entire heart in one or two heart beats. With 64-row and higher MDCT, image quality is influenced by the cardiac volume imaged per gantry rotation, the high number of thin images obtained, as well as spatial and temporal resolution. Furthermore, to image a beating heart, high temporal resolution is needed which is determined by the gantry rotation, use of prospective or retrospective electrocardiographic (ECG) gating, and whether the image reconstruction requires significant data overlap during scanning. A further challenge of MDCT is obtaining diagnostic quality images with low radiation doses. Many factors influence radiation dose with MDCT, including type of ECG gating, ECG dose modulation where the tube current voltage is low outside of diastole, table pitch, scan time, and adjustments in tube current for patient size and tube voltage (kV). Two studies of CCTA have been published recently; Chao et al. 1 use a 256-row and …

Arterial spin labeling MRI reproducibly measures peak-exercise calf muscle perfusion in healthy volunteers and patients with peripheral arterial disease

OBJECTIVES This study hypothesized that arterial spin labeling (ASL) magnetic resonance (MR) imaging at 3-T would be a reliable noncontrast technique for measuring peak exercise calf muscle blood flow in both healthy volunteers and patients with peripheral arterial disease (PAD) and will discriminate between these groups. BACKGROUND Prior work demonstrated the utility of first-pass gadolinium-enhanced calf muscle perfusion MR imaging in patients with PAD. However, patients with PAD often have advanced renal disease and cannot receive gadolinium. METHODS PAD patients had claudication and an ankle brachial index of 0.4 to 0.9. Age-matched normal subjects (NL) had no PAD risk factors and were symptom-free with exercise. All performed supine plantar flexion exercise in a 3-T MR imaging scanner using a pedal ergometer until exhaustion or limiting symptoms and were imaged at peak exercise with 15 averaged ASL images. Peak perfusion was measured from ASL blood flow images by placing a region of interest in the calf muscle region with the greatest signal intensity. Perfusion was compared between PAD patients and NL and repeat testing was performed in 12 subjects (5 NL, 7 PAD) for assessment of reproducibility. RESULTS Peak exercise calf perfusion of 15 NL (age: 54 ± 9 years) was higher than in 15 PAD patients (age: 64 ± 5 years, ankle brachial index: 0.70 ± 0.14) (80 ± 23 ml/min - 100 g vs. 49 ± 16 ml/min/100 g, p < 0.001). Five NL performed exercise matched to PAD patients and again demonstrated higher perfusion (84 ± 25 ml/min - 100 g, p < 0.002). As a measure of reproducibility, intraclass correlation coefficient between repeated studies was 0.87 (95% confidence interval [CI]: 0.61 to 0.96). Interobserver reproducibility was 0.96 (95% CI: 0.84 to 0.99). CONCLUSIONS ASL is a reproducible noncontrast technique for quantifying peak exercise blood flow in calf muscle. Independent of exercise time, ASL discriminates between NL and PAD patients. This technique may prove useful for clinical trials of therapies for improving muscle perfusion, especially in patients unable to receive gadolinium.

Noninvasive Imaging of the Heart and Coronary Arteries

There are multiple imaging modalities currently available to noninvasively evaluate the heart and coronary arteries. Choosing the most appropriate modality depends on the pertinent clinical question and the underlying patient characteristics. This article provides an overview of the fields of echocardiography, myocardial perfusion imaging, cardiac computed tomography, and cardiac magnetic resonance imaging, with particular attention to specific clinical applications for cardiac surgery patients.