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Background: The distal superficial femoral artery (SFA) is most commonly affected in peripheral artery disease (PAD). The effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab added to statin therapy on SFA atherosclerosis, downstream flow, and walking performance are unknown. Methods: Thirty-five patients with PAD on maximally tolerated statin therapy were recruited. Patients were randomized to alirocumab 150 mg subcutaneously (n = 18) or matching placebo (n = 17) therapy every 2 weeks for 1 year. The primary outcome was change in SFA plaque volume by black blood magnetic resonance imaging (MRI). Secondary outcomes were changes in calf muscle perfusion by cuff/occlusion hyperemia arterial spin labeling MRI, 6-minute walk distance (6MWD), low-density lipoprotein (LDL) cholesterol, and other biomarkers. Results: Age (mean ± SD) was 64 ± 8 years, 20 (57%) patients were women, 17 (49%) were Black individuals, LDL was 107 ± 36 mg/dL, and the ankle–brachial index 0.71 ± 0.20. The LDL fell more with alirocumab than placebo (mean [95% CI]) (−49.8 [−66.1 to −33.6] vs −7.7 [−19.7 to 4.3] mg/dL; p < 0.0001). Changes in SFA plaque volume and calf perfusion showed no difference between groups when adjusted for baseline (+0.25 [−0.29 to 0.79] vs −0.04 [−0.47 to 0.38] cm3; p = 0.37 and 0.22 [−8.67 to 9.11] vs 3.81 [−1.45 to 9.08] mL/min/100 g; p = 0.46, respectively), nor did 6MWD. Conclusion: In this exploratory study, the addition of alirocumab therapy to statins did not alter SFA plaque volume, calf perfusion or 6MWD despite significant LDL lowering. Larger studies with longer follow up that include plaque characterization may improve understanding of the effects of intensive LDL-lowering therapy in PAD (ClinicalTrials.gov Identifier: NCT02959047). [ABSTRACT FROM AUTHOR]

Angiotensin II type 2 receptor ([AT.sub.2]R) overexpression ([AT.sub.2]TG) attenuates left ventricular remodeling in a mouse model of anterior myocardial infarction (MI). We hypothesized that the beneficial effects of cardiac [AT.sub.2]TG are mediated via the bradykinin subtype 2 receptor ([B.sub.2]R). Fourteen transgenic mice overexpressing the [AT.sub.2]R ([AT.sub.2]TG mice), 10 mice with a [B.sub.2]R deletion ([B.sub.2]KO mice), 13 [AT.sub.2]TG mice with [B.sub.2]R deletion ([AT.sub.2]TG/[B.sub.2]KO mice), and 11 wild-type (WT) mice were studied. All mice were on a C57BL/6 background. Mice were studied by cardiac magnetic resonance imaging at baseline and days 1, 7, and 28 after MI induced by 1 h of occlusion of the left anterior descending artery followed by reperfusion. Short-axis images from apex to base were used to compare ventricular volumes and ejection fraction (EF). At baseline, end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) were lower and EF higher in [AT.sub.2]TG mice compared with the other three strains. Infarct size was similar between groups. No differences were observed in global remodeling parameters at day 28 between [AT.sub.2]TG and [AT.sub.2]TG/[B.sub.2]KO mice; however, EDVI and ESVI were lower and EF higher in both transgenic groups than in WT or [B.sub.2]KO mice. Both strains lacking [B.sub.2]R demonstrated increased collagen content and less hypertrophy in adjacent noninfarcted regions at day 28. Attenuation of postinfarct remodeling by overexpression of [AT.sub.2]R is not directly mediated via a [B.sub.2]R pathway. However, [B.sub.2]R does appear to have a role in the smaller cavity size and hyperdynamic function observed at baseline in [AT.sub.2]TG mice and in limiting collagen deposition during postinfarct remodeling. magnetic resonance imaging; remodeling

Background: Assessment of calf muscle perfusion requires a physiological challenge. Exercise and cuff-occlusion hyperemia are commonly used methods, but it has been unclear if one is superior to the other. We hypothesized that post-occlusion calf muscle perfusion (Cuff) with pulsed arterial spin labeling (PASL) cardiovascular magnetic resonance (CMR) at 3 Tesla (T) would yield greater perfusion and improved reproducibility compared to exercise hyperemia in studies of peripheral arterial disease (PAD). Methods: Exercise and Cuff cohorts were independently recruited. PAD patients had an ankle brachial index (ABI) between 0.4-0.9. Controls (NL) had no risk factors and ABI 0.9-1.4. Subjects exercised until exhaustion (15 NL-Ex, 15 PAD-Ex) or had a thigh cuff inflated for 5 minutes (12 NL-Cuff, 11 PAD-Cuff). Peak exercise and average cuff (Cuff mean ) perfusion were compared. Six participants underwent both cuff and exercise testing. Reproducibility was tested in 8 Cuff subjects (5 NL, 3 PAD). Results: Controls had greater perfusion than PAD independent of stressor (NL-Ex 74 ± 21 vs. PAD-Ex 43 ± 10, p = 0.01; NL-Cuff mean 109 ± 39 vs. PAD-Cuff mean 34 ± 17 ml/min-100 g, p < 0.001). However, there was no difference between exercise and Cuff mean perfusion within groups (p > 0.6). Results were similar when the same subjects had the 2 stressors performed. Cuff mean had superior reproducibility (Cuff mean ICC 0.98 vs. Exercise ICC 0.87) and area under the receiver operating characteristic curve (Cuff mean 0.992 vs. Exercise 0.905). Conclusions: Cuff hyperemia differentiates PAD patients from controls, as does exercise stress. Cuff mean and exercise calf perfusion values are similar. Cuff occlusion hyperemia has superior reproducibility and thus may be the preferred stressor. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Angiotensin II type 2 receptor (AT 2 -R) overexpression in the mouse heart preserves left ventricular (LV) size and global LV function during post-MI remodeling. We hypothesized that CMR tagging would localize regional improvements in myocardial function during post-MI remodeling in AT 2 -R cardiac overexpressed transgenic mice (TG), which could explain the preservation of global LV function post-MI. Six male wild-type (WT) C57BL/6 mice and 10 TG mice were studied by CMR at baseline (day 0) and days 1, 7, and 28 post-MI. MI was induced by 1 hour occlusion of the LAD followed by reperfusion. On day 1 post-MI, gadolinium-DTPA was injected to assess infarct size. LV size and function was assessed by cine CMR. Mean % circumferential shortening (%CS) was calculated within infarcted, adjacent, and remote regions at each time point in WT and TG mice. Quantitative interstitial collagen and mean myocyte cross-sectional area was measured postmortem at day 28 post-MI. LV end-systolic volume was lower and ejection fraction higher at baseline in the TG group and these differences were maintained post-MI. Within infarcted and remote zones, although %CS was higher in TG mice at day 0, there was no difference by day 28 between groups. Within adjacent regions, while there was no difference at day 0 or 1 in TG vs. WT, %CS was significantly higher in TG mice by day 7, and these changes persisted out to day 28 post-MI. Regional interstitial collagen and myocyte size were similar between groups. Thus, myocardial tagging can detect regional differences in contractile function post-MI in TG mice, and AT 2 -R overexpression is associated with improved contractile function in adjacent noninfarcted myocardium. [ABSTRACT FROM AUTHOR]

Delayed contrast-enhanced cardiac magnetic resonance imaging (ceCMR) delineates infarct size. The presence of hypoenhancement consistent with microvascular obstruction (MO) signifies larger infarcts with a worse prognosis. We hypothesized that the size of the contrast defect (CD) on ceCMR in acutely infarcted myocardium may change during infarct healing and depend upon the presence of MO. Twenty-five patients underwent CMR on weeks 1 and 8 after reperfused myocardial infarction. After short-axis cine CMR was performed, gadolinium was infused and ceCMR images and matched tagged cine MR images were obtained in the three most dysfunctional short-axis slices on cine CMR. The area and transmural extent of hyperenhancement (HE) with or without MO representing total CD size were planimetered. Between week I and week 8, the CD area fell from 1729 ± 970 mm2 at week 1 to 1270±706 mm2 (p<0.001), as did the transmural extent of infarction (7 1±22% to 63±24%, p<0.001). The decline in CD trended to be higher in patients with MO (840± 807 mm2) than in HE (3 12±485 mm2, p<0.07). In the patient group as a whole, ejection fraction (Eli improved (56±9% to 60± 10%, p=0.002) between weeks I and 8, but patients with MO showed no increase in EF. Segments with some HE demonstrated partial functional improvement whereas no improvement was seen in HE+MO segments. In patients 8 weeks after reperfused myocardial infarction (MI), the size of infarction by ceCMR decreases compared to week 1 post-MI, especially in those with microvascular obstruction in whom there is little improvement in regional or global function. [ABSTRACT FROM AUTHOR]

An abstract of the paper "Does Measurement of Exercise/ Rest Calf Muscle Perfusion Reserve With First-pass Contrast-enhanced MRI in Peripheral Arterial Disease Perform Better Than Exercise-only Perfusion?," by Amy M. West and his colleagues, from the 2011 SCMR/Euro CMR Joint Scientific Sessions, held in Nice, France, from February 3-6, 2011, is presented.

An abstract of the paper "Changes in atherosclerotic plaque composition assessed by MRI in the superficial femoral artery with two years of lipid lowering therapy," by Amy M. West, and colleagues from the 2011 SCMR/Euro CMR Joint Scientific Sessions in Nice, France from February 3-6, 2011 is presented.

An abstract of the paper "Arterial Spin Labeling MRI to Measure Peak-exercise Calf Muscle Perfusion Reproducibly Discriminates Peripheral Arterial Disease from Normal," by Amy M. West and colleagues from the 2011 SCMR/Euro CMR Joint Scientific Sessions in Nice, France from February 3-6, 2011 is presented.

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 31P 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) [Copyright &y& Elsevier]

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 31P 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) [Copyright &y& Elsevier]

Background: Obesity is a known risk factor for heart failure with preserved ejection fraction (HFpEF) and is considered a distinct phenotype with more concentric remodeling. Epicardial adipose tissue (EAT) is also increased in obesity-related HFpEF and is associated with adverse events., Objective: The Cardiac Magnetic Resonance (CMR) Substudy of the SUMMIT trial was aimed to examine the effects of tirzepatide on cardiac structure and function with the underlying hypothesis that it would reduce left ventricular (LV) mass and EAT in obesity-related HFpEF., Methods: One hundred seventy-five patients with obesity-related HFpEF from the parent study of tirzepatide (2.5mg SQ weekly, increasing to a maximum of 15mg weekly) or matching placebo underwent CMR at baseline, which consisted of multiplanar cine imaging. One hundred six patients completed the CMR and had adequate image quality for analysis of LV and LA structure and function and paracardiac (epicardial plus pericardial) adipose tissue at both baseline and 52 weeks. The prespecified primary endpoint of this substudy was between-group changes in LV mass., Results: LV mass decreased by 11 g (95% C.I. -19 to -4) in the treated group (n = 50) when corrected for placebo (n =56) (p=0.004). Paracardiac adipose tissue decreased in the treated group by 45 ml (95% C.I. -69 to -22) when corrected for placebo (p<0.001). The change in LV mass in the treated group correlated with changes in body weight (p<0.02) and, tended to correlate with changes in waist circumference and blood pressure (p=0.06 for both). The LV mass change also correlated with changes in LV end diastolic volume and LA end diastolic and end systolic volumes (p<0.03 for all)., Conclusion: The CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared to placebo and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The Investigational Review Board approved the protocol, and all patients provided signed informed consent. The protocol was compliant with HIPAA. The purpose of the study was to prospectively test the hypothesis that addition of low-dose dobutamine and quantification of inotropic reserve in segments with 1%-50% infarct transmurality (IT) would improve the predictive value for functional recovery after revascularization in chronic infarction. Fifteen patients with multivessel coronary artery disease and left ventricular systolic dysfunction were enrolled prior to coronary artery bypass grafting (CABG). Late gadolinium-enhanced cardiac magnetic resonance (MR) imaging was used to assess IT. The percentage of wall thickening was measured with cine cardiac MR imaging at rest and during infusion of 10 (microg . kg(-1))/min dobutamine. Repeat cardiac MR imaging was performed 20 weeks +/- 4 (standard error) later. Functional parameters according to segment were compared before and after CABG by using F tests with repeated-measures models. In segments with 1%-50% IT, similar functional recovery was noted in those with 1%-25% or 26%-50% IT. However, in the same segments, those that improved with dobutamine to normal range demonstrated greater improvement in the percentage of wall thickening (22% +/- 4) after revascularization than those that did not (9% +/- 4) (P < .04). In 1%-50% IT, a normal dobutamine response helps differentiate segments with greater functional recovery after CABG., ((c) RSNA, 2006.)