Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Identifies Abnormal Calf Muscle-Specific Energetics in Peripheral Artery Disease.

BACKGROUND: Peripheral artery disease (PAD) results in exercise-induced ischemia in leg muscles. 31Phosphorus (P) magnetic resonance spectroscopy demonstrates prolonged phosphocreatine recovery time constant after exercise in PAD but has low signal to noise, low spatial resolution, and requires multinuclear hardware. Chemical exchange saturation transfer (CEST) is a quantitative magnetic resonance imaging method for imaging substrate (CEST asymmetry [CESTasym]) concentration by muscle group. We hypothesized that kinetics measured by CEST could distinguish between patients with PAD and controls. METHODS: Patients with PAD and age-matched normal subjects were imaged at 3T with a transmit-receive coil around the calf. Four CEST mages were acquired over 24-second intervals. The subjects then performed plantar flexion exercise on a magnetic resonance imaging-compatible ergometer until calf exhaustion. Twenty-five CEST images were obtained at end exercise. Regions of interest were drawn around individual muscle groups, and (CESTasym) decay times were fitted by exponential curve to CEST values. In 10 patients and 11 controls, 31P spectra were obtained 20 minutes later after repeat exercise. Five patients and 5 controls returned at a mean of 1±1 days later for repeat CEST studies. RESULTS: Thirty-five patients with PAD (31 male, age 66±8 years) and 29 controls (11 male, age 63±8 years) were imaged with CEST. The CESTasym decay times for the whole calf (341±332 versus 153±72 seconds; P<0.03) as well as for the gastrocnemius and posterior tibialis were longer in patients with PAD. Agreement between CESTasym decay and phosphocreatine recovery time constant was good. CONCLUSIONS: CEST is a magnetic resonance imaging method that can distinguish energetics in patients with PAD from age-matched normal subjects on a per muscle group basis. CEST agrees reasonably well with the gold standard 31P magnetic resonance spectroscopy. Moreover, CEST has higher spatial resolution, creates an image, and does not require multinuclear hardware and thus may be more suitable for clinical studies in PAD.

Functional and Economic Impact of INOCA and Influence of Coronary Microvascular Dysfunction.

OBJECTIVES: This study sought to better characterize the quality of life and economic impact in patients with symptoms of ischemia and no obstructive coronary disease (INOCA) and to identify the influence of coronary microvascular dysfunction (CMD). BACKGROUND: Patients with INOCA have a high symptom burden and an increased incidence of major adverse cardiac events. CMD is a frequent cause of INOCA. The morbidity associated with INOCA and CMD has not been well-characterized. METHODS: Sixty-six patients with INOCA underwent stress cardiac magnetic resonance with calculation of myocardial perfusion reserve (MPR); MPR 2.0 to 2.4 was considered borderline-reduced (possible CMD) and MPR <2.0 was defined as reduced (definite CMD). Subjects completed quality of life questionnaires to assess the morbidity and economic impact of INOCA. Questionnaire results were compared between INOCA patients with and without CMD. In addition, logistic regression was used to determine the predictors of CMD within the INOCA population. RESULTS: The prevalence of definite CMD was 24%. Definite or borderline CMD was present in 59% (MPR ≤2.4). Patients with INOCA reported greater physical limitation, angina frequency, and reduced quality of life compared to referent stable coronary artery disease and acute myocardial infarction populations. In addition, Patients with INOCA reported frequent time missed from work and work limitations, suggesting a substantial economic impact. No difference was observed in reported symptoms between INOCA patients with and without CMD. Glomerular filtration rate and body-mass index were significant predictors of CMD in multivariable regression analysis. CONCLUSIONS: INOCA is associated with high morbidity similar to other high-risk cardiac populations, and work limitations reported by Patients with INOCA suggest a substantial economic impact. CMD is a common cause of INOCA but is not associated with increased morbidity. These results suggest that there is significant symptom burden in the INOCA population regardless of etiology.

Coronary Computed Tomography Angiography Demonstrates a High Burden of Coronary Artery Disease Despite Low-Risk Nuclear Studies in Pre-Liver Transplant Evaluation.

We investigated the presence and severity of coronary artery disease (CAD) in orthotopic liver transplantation (OLT) candidates using coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA) as compared with the prevalence of normal and abnormal single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). A total of 140 prospective OLT candidates without known CAD underwent coronary artery calcium (CAC) scans with (n = 77) or without CCTA and coronary computed tomography angiography-derived fractional flow reserve (FFRCT ; n = 57) using a dual-source computed tomography (CT) and were followed for 2.6 ± 1.4 years. Coronary plaque was quantified using the segment-involvement score (SIS) and segment stenosis score (SSS). The mean age was 59 ± 6 years, and 65.0% of patients were male. Mean Agatston CACS was 367 ± 653, and 15.0% of patients had CACSs of 0; 83.6% received a SPECT MPI, of which 95.7% were interpreted as normal/probably normal. By CCTA, 9.1% had obstructive CAD (≥70% stenosis), 67.5% had nonobstructive CAD, and 23.4% had no CAD. Nonobstructive CAD was diffuse with mean SIS 3.0 ± 2.9 and SSS 4.5 ± 5.4. Only 14 patients had high risk-findings (severe 3v CAD, n = 4, CACS >1000 n = 10) that prompted X-ray angiography in 3 patients who had undergone CCTA, resulting in revascularization of a high-risk obstruction in 1 patient who had a normal SPECT study. Patients with end-stage liver disease have a high prevalence of nonobstructive CAD by CCTA, which is undiagnosed by SPECT MPI, potentially underestimating cardiovascular risk. Deferring X-ray angiography unless high-risk CCTA findings are present is a potential strategy for avoiding unnecessary X-ray angiography.

Cardiovascular Imaging Techniques to Assess Microvascular Dysfunction.

The understanding of microvascular dysfunction without evidence of epicardial coronary artery disease pales in comparison with that of obstructive epicardial coronary artery disease. A primary limitation in the past had been the lack of development of noninvasive methods of detecting and quantifying microvascular dysfunction. This limitation has particularly affected the ability to study the pathophysiology, morbidity, and treatment of this disease. More recently, almost all of the noninvasive cardiac imaging modalities have been used to quantify blood flow and advance understanding of microvascular dysfunction.

CMR DENSE and the Seattle Heart Failure Model Inform Survival and Arrhythmia Risk After CRT.

OBJECTIVES: This study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators. BACKGROUND: The SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function. METHODS: CMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies. RESULTS: The cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD ≥0.60 or SHFM-D ≥0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response (r = -0.57; p < 0.0001) than CURE-SVD with feature tracking (r = -0.28; p = 0.004). CONCLUSIONS: A combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future.

Free-breathing cine imaging with motion-corrected reconstruction at 3T using SPiral Acquisition with Respiratory correction and Cardiac Self-gating (SPARCS).

PURPOSE: To develop a continuous-acquisition cardiac self-gated spiral pulse sequence and a respiratory motion-compensated reconstruction strategy for free-breathing cine imaging. METHODS: Cine data were acquired continuously on a 3T scanner for 8 seconds per slice without ECG gating or breath-holding, using a golden-angle gradient echo spiral pulse sequence. Cardiac motion information was extracted by applying principal component analysis on the gridded 8 × 8 k-space center data. Respiratory motion was corrected by rigid registration on each heartbeat. Images were reconstructed using a low-rank and sparse (L+S) technique. This strategy was evaluated in 37 healthy subjects and 8 subjects undergoing clinical cardiac MR studies. Image quality was scored (1-5 scale) in a blinded fashion by 2 experienced cardiologists. In 13 subjects with whole-heart coverage, left ventricular ejection fraction (LVEF) from SPiral Acquisition with Respiratory correction and Cardiac Self-gating (SPARCS) was compared to that from a standard ECG-gated breath-hold balanced steady-state free precession (bSSFP) cine sequence. RESULTS: The self-gated signal was successfully extracted in all cases and demonstrated close agreement with the acquired ECG signal (mean bias, -0.22 ms). The mean image score across all subjects was 4.0 for reconstruction using the L+S model. There was good agreement between the LVEF derived from SPARCS and the gold-standard bSSFP technique. CONCLUSION: SPARCS successfully images cardiac function without the need for ECG gating or breath-holding. With an 8-second data acquisition per slice, whole-heart cine images with clinically acceptable spatial and temporal resolution and image quality can be acquired in <90 seconds of free-breathing acquisition.

Role of Cardiac Magnetic Resonance Imaging in Valvular Heart Disease: Diagnosis, Assessment, and Management.

PURPOSE OF REVIEW: This article will review the current techniques in cardiac magnetic resonance imaging (CMR) for diagnosing and assessing primary valvular heart disease. RECENT FINDINGS: The recent advancements in CMR have led to an increased role of this modality for qualifying and quantifying various native valve diseases. Phase-contrast velocity encoded imaging is a well-established technique that can be used to quantify aortic and pulmonic flow. This technique, combined with the improved ability for CMR to obtain accurate left and right ventricular volumetrics, has allowed for increased accuracy and reproducibility in assessing valvular dysfunction. Advancements in CMR technology also allows for improved spatial and temporal resolution imaging of various valves and their regurgitant or stenotic jets. Therefore, CMR can be a powerful tool in evaluation of native valvular heart disease. The role of CMR in assessing valvular heart disease is growing and being recognized in recent guidelines. CMR has the ability to assess valve morphology along with qualifying and quantifying valvular disease. In addition, the ability to obtain accurate volumetric measurements may improve more precise management strategies and may lead to improvements in mortality and morbidity.

Computed Tomography Fractional Flow Reserve to Guide Coronary Angiography and Intervention.

Computed tomography angiography (CTA) has played a significant role in evaluation of coronary artery disease in the last decade and has demonstrated high sensitivity and negative predictive values. However, the positive predictive value as compared with invasive fractional flow reserve (FFR) is limited. CT-FFR has emerged as a disruptive noninvasive technology with higher specificity and diagnostic accuracy for detection of hemodynamically significant coronary lesions as compared with invasive FFR than conventional coronary CTA. CT-FFR has been shown to be cost-effective as a gate-keeper to invasive coronary angiography and has the potential to limit unnecessary invasive angiography studies.

Recent advances in magnetic resonance imaging for peripheral artery disease.

The global burden of peripheral artery disease (PAD) is significant. This has led to numerous recent advances in magnetic resonance imaging (MRI) techniques in PAD. Older techniques such as time of flight MRI or phase contrast MRI are burdened by long acquisition times and significant issues with artifacts. In addition, the most used MRI modality, contrast-enhanced MR angiography (CE-MRA) is limited by the use of gadolinium contrast and its potential toxicity. Novel MRI techniques such as arterial spin labeling (ASL), blood-oxygen-level dependent imaging (BOLD), and first-pass perfusion gadolinium enhancement are advancing the field by providing skeletal muscle perfusion/oxygenation data while maintaining excellent spatial and temporal resolution. Perfusion data can be critical to providing objective clinical data of a visualized stenosis. In addition, there are a number of new MRI sequences assessing plaque composition and lesion severity in the absence of contrast. These approaches used in combination can provide useful clinical and prognostic data and provide critical endpoints in PAD research.

Quantitative cardiovascular magnetic resonance perfusion imaging identifies reduced flow reserve in microvascular coronary artery disease.

BACKGROUND: Preliminary semi-quantitative cardiovascular magnetic resonance (CMR) perfusion studies have demonstrated reduced myocardial perfusion reserve (MPR) in patients with angina and risk factors for microvascular disease (MVD), however fully quantitative CMR has not been studied. The purpose of this study is to evaluate whether fully quantitative CMR identifies reduced MPR in this population, and to investigate the relationship between epicardial atherosclerosis, left ventricular hypertrophy (LVH), extracellular volume (ECV), and perfusion. METHODS: Forty-six patients with typical angina and risk factors for MVD (females, or males with diabetes or metabolic syndrome) who had no obstructive coronary artery disease by coronary angiography and 20 healthy control subjects underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse sequence to quantify MPR. Subjects also underwent T1 mapping to quantify ECV, and computed tomographic (CT) coronary calcium scoring to assess atherosclerosis burden. RESULTS: In patients with risk factors for MVD, both MPR (2.21 [1.95,2.69] vs. 2.93 [2.763.19], p < 0.001) and stress myocardial perfusion (2.65 ± 0.62 ml/min/g, vs. 3.17 ± 0.49 ml/min/g p < 0.002) were reduced as compared to controls. These differences remained after adjusting for age, left ventricular (LV) mass, body mass index (BMI), and gender. There were no differences in native T1 or ECV between subjects and controls. CONCLUSIONS: Stress myocardial perfusion and MPR as measured by fully quantitative CMR perfusion imaging are reduced in subjects with risk factors for MVD with no obstructive CAD as compared to healthy controls. Neither myocardial hypertrophy nor fibrosis accounts for these differences.