Assessment of coronary vascular function with cardiac PET in relation to serum uric acid

Background: Elevated serum uric acid (SUA) levels have been independently associated with cardiovascular disease. Stress myocardial perfusion positron emission tomography (PET) allows for measurement of absolute myocardial blood flow (MBF) and quantification of global left ventricular coronary flow reserve (CFR). A CFR <2.0 is considered impaired coronary vascular function, and it is associated with increased cardiovascular risk. We evaluated the relationship between SUA and PET-measured markers of coronary vascular function. Methods: We studied adults undergoing a stress myocardial perfusion PET on clinical grounds (1/2006-3/2014) who also had ≥1 SUA measurement within 180 days from the PET date. Multivariable linear regression estimated the association between SUA and PET-derived MBF and CFR. We also stratified analyses by diabetes status. Results: We included 382 patients with mean (SD) age of 68.4 (12.4) years and mean (SD) SUA level of 7.2 (2.6) mg/dl. 36% were female and 29% had gout. Median [IQR] CFR was reduced at 1.6 [1.2, 2.0] and median [IQR] stress MBF was 1.5 [1.1, 2.1] ml/min/g. In the adjusted analysis, SUA was inversely associated with stress MBF (β = -0.14, p = 0.01) but not with CFR. Among patients without diabetes (n = 215), SUA had a negative association with CFR (β = -0.15, p = 0.02) and stress MBF (β = -0.19, p = 0.01) adjusting for age, sex, extent of myocardial scar and ischemia, serum creatinine and gout. In diabetic patients (n = 167), SUA was not associated with either CFR or MBF. Conclusions: In this cross-sectional study, higher SUA is modestly associated with worse CFR and stress MBF among patients without diabetes

Characteristics of patients with diabetes.

<p>Characteristics of patients with diabetes.</p

Association between serum uric acid level and coronary vascular function^*.

<p>Association between serum uric acid level and coronary vascular function^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192788#t002fn002" target="_blank">*</a>}.</p

Association between serum uric acid level and coronary vascular function for patients stratified by diabetes^*.

<p>Association between serum uric acid level and coronary vascular function for patients stratified by diabetes^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192788#t005fn002" target="_blank">*</a>}.</p

Study cohort characteristics.

<p>Study cohort characteristics.</p

Asymptomatic hyperuricemia and coronary flow reserve in patients with metabolic syndrome

Abstract Background Patients with metabolic syndrome (MetS) are at increased risk of asymptomatic hyperuricemia (i.e., elevated serum uric acid (SUA) level without gout) and cardiovascular disease. We conducted a cross-sectional study to examine associations between SUA levels and coronary flow reserve and urate deposits in carotid arteries in patients with asymptomatic hyperuricemia and MetS. Methods Adults aged ≥40 years with MetS and SUA levels ≥6.5 mg/dl, but no gout, were eligible. Using a stress myocardial perfusion positron emission tomography (PET), we assessed myocardial blood flow (MBF) at rest and stress and calculated coronary flow reserve (CFR). CFR < 2.0 is considered abnormal and associated with increased cardiovascular risk. We also measured insulin resistance by homeostatic model assessment (HOMA-IR) method and urate deposits using dual-energy CT (DECT) of the neck for the carotid arteries. Results Forty-four patients with the median age of 63.5 years underwent a blood test, cardiac PET and neck DECT scans. Median (IQR) SUA was 7.8 (7.1–8.4) mg/dL. The median (IQR) CFR was abnormally low at 1.9 (1.7–2.4) and the median (IQR) stress MBF was 1.7 (1.3–2.2) ml/min/g. None had urate deposits in the carotid arteries detected by DECT. In multivariable linear regression analyses, SUA had no association with CFR (β = − 0.12, p = 0.78) or stress MBF (β = − 0.52, p = 0.28). Among non-diabetic patients (n = 25), SUA was not associated with HOMA-IR (β = 2.08, p = 0.10). Conclusions Among MetS patients with asymptomatic hyperuricemia, we found no relationship between SUA and CFR, stress MBF, and insulin resistance. No patients had any DECT detectable subclinical urate deposition in the carotid arteries

Prior SARS‐CoV‐2 Infection Is Associated With Coronary Vasomotor Dysfunction as Assessed by Coronary Flow Reserve From Cardiac Positron Emission Tomography

Background Cardiovascular complications from COVID‐19 contribute to its high morbidity and mortality. The effect of COVID‐19 infection on the coronary vasculature is not known. The objective of this study was to investigate the prevalence of coronary vasomotor dysfunction identified by coronary flow reserve from cardiac positron emission tomography in patients with previous COVID‐19 infection. Methods and Results All patients who had polymerase chain reaction–confirmed SARS‐CoV‐2 infection referred for myocardial stress perfusion positron emission tomography imaging at Brigham and Women's Hospital from April 2020 to July 2021 were compared with a matched control group without prior SARS‐CoV‐2 infection imaged in the same period. The main outcome was the prevalence of coronary vasomotor dysfunction. Myocardial perfusion and myocardial blood flow reserve were quantified using N13‐ammonia positron emission tomography imaging. Thirty‐four patients with prior COVID‐19 were identified and compared with 103 matched controls. The median time from polymerase chain reaction–confirmed SARS‐CoV‐2 to cardiac positron emission tomography was 4.6 months (interquartile range,1.2–5.6 months). There were 16 out of 34 (47%) patients previously hospitalized for COVID‐19 infection. Baseline cardiac risk factors were common, and 18 (53%) patients in the COVID‐19 group had abnormal myocardial perfusion. Myocardial blood flow reserve was abnormal (<2) in 44.0% of the patients with COVID‐19 compared with 11.7% of matched controls (P<0.001). The mean myocardial blood flow reserve was 19.4% lower in patients with COVID‐19 compared with control patients (2.00±0.45 versus 2.48±0.47, P<0.001). Conclusions Myocardial blood flow reserve was impaired in patients with prior COVID‐19 infection compared with cardiovascular risk factor–matched controls, suggesting a relationship between SARS‐CoV‐2 infection and coronary vascular health. These data highlight the need to assess long‐term consequences of COVID‐19 on vascular health in future prospective studies

Integrated Noninvasive Physiological Assessment of Coronary Circulatory Function and Impact on Cardiovascular Mortality in Patients With Stable Coronary Artery Disease

BACKGROUND: It is suggested that the integration of maximal myocardial blood flow (MBF) and coronary flow reserve (CFR), termed coronary flow capacity, allows for comprehensive evaluation of patients with known or suspected stable coronary artery disease. Because management decisions are predicated on clinical risk, we sought to determine the independent and integrated value of maximal MBF and CFR for predicting cardiovascular death. METHODS: MBF and CFR were quantified in 4029 consecutive patients (median age 66 years, 50.5% women) referred for rest/stress myocardial perfusion positron emission tomography scans from January 2006 to December 2013. The primary outcome was cardiovascular mortality. Maximal MBF <1.8 mL.g(-1).min(-1) and CFR <2 were considered impaired. Four patient groups were identified based on the concordant or discordant impairment of maximal MBF or CFR. Association of maximal MBF and CFR with cardiovascular death was assessed using Cox and Poisson regression analyses. RESULTS: A total of 392 (9.7%) cardiovascular deaths occurred over a median follow-up of 5.6 years. CFR was a stronger predictor of cardiovascular mortality than maximal MBF beyond traditional cardiovascular risk factors, left ventricular ejection fraction, myocardial scar and ischemia, rate-pressure product, type of radiotracer or stress agent used, and revascularization after scan (adjusted hazard ratio, 1.79; 95% confidence interval [CI], 1.38-2.31; P <0.001 per unit decrease in CFR after adjustment for maximal MBF and clinical covariates; and adjusted hazard ratio, 1.03; 95% CI, 0.84-1.27; P=0.8 per unit decrease in maximal MBF after adjustment for CFR and clinical covariates). In univariable analyses, patients with concordant impairment of CFR and maximal MBF had high cardiovascular mortality of 3.3% (95% CI, 2.9-3.7) per year. Patients with impaired CFR but preserved maximal MBF had an intermediate cardiovascular mortality of 1.7% (95% CI, 1.3-2.1) per year. These patients were predominantly women (70%). Patients with preserved CFR but impaired maximal MBF had low cardiovascular mortality of 0.9% (95% CI, 0.6-1.6) per year. Patients with concordantly preserved CFR and maximal MBF had the lowest cardiovascular mortality of 0.4% (95 CI, 0.3-0.6) per year. In multivariable analysis, the cardiovascular mortality risk gradient across the 4 concordant or discordant categories was independently driven by impaired CFR irrespective of impairment in maximal MBF. CONCLUSIONS: CFR is a stronger predictor of cardiovascular mortality than maximal MBF. Concordant and discordant categories based on integrating CFR and maximal MBF identify unique prognostic phenotypes of patients with known or suspected coronary artery diseas

Accuracy and Reproducibility of Myocardial Blood Flow Quantification by Single Photon Emission Computed Tomography Imaging in Patients With Known or Suspected Coronary Artery Disease

BackgroundSingle photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique.MethodsAccuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio.ResultsSPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P&lt;0.001) and MFR estimates (r=0.74, P&lt;0.001). Correlations were substantially weaker for standard reconstruction without splines (r=0.61, P&lt;0.001 and r=0.34, P=0.07, for MBF and MFR, respectively). Reproducibility of global MBF estimates with splines in paired SPECT scans was good (r=0.77, P&lt;0.001), while ordered subset expectation maximization without splines led to decreased MBF (r=0.68, P&lt;0.001) and MFR correlations (r=0.33, P=0.3). There were no significant differences in MBF or MFR between the 2 reproducibility scans independently of the reconstruction algorithm (P&gt;0.05 for all).ConclusionsMBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation