Objectives
We sought to relate imaging findings on PET to adverse cardiac events in patients referred for evaluation of known or suspected cardiac sarcoidosis (CS).
Background
Although cardiac positron emission tomography (PET) is commonly used to evaluate patients with suspected CS, the relationship between PET findings and clinical outcomes has not been reported.
Methods
We studied 118 consecutive patients with no history of CAD who were referred for PET using 18F-fluorodeoxyglucose (FDG) [to assess for inflammation] and 82Rubidium [to evaluate for perfusion defects (PD)] following a high fat / low carbohydrate diet to suppress normal myocardial glucose uptake. Blind reads of the PET data categorized cardiac findings as (a) normal; (b) positive PD or FDG; (c) positive PD and FDG. Images were also used to identify if findings for extra cardiac sarcoidosis were present. Adverse events (AE) -- death or sustained ventricular tachycardia (VT) -- were ascertained by electronic medical records, defibrillator interrogation, patient questionnaires and phone interviews.
Results
Among the 118 patients (age 52±11; males 57%, mean ejection fraction 47%±16%), 47 (40%) had normal and 71 (60%) abnormal cardiac PET findings. Over a median follow-up of 1.5 years, there were 31 (26%) adverse events (27 VT and 8 deaths). Cardiac PET findings were predictive of AE with the presence of both a PD and abnormal FDG (29% of patients) being associated with hazard ratio of 3.9 (p<0.01) and remaining significant after adjusting for left ventricular ejection fraction (LVEF) and clinical criteria. Extra-cardiac FDG uptake (26% of patients) was not associated with AE.
Conclusions
The presence of focal PD and FDG uptake on cardiac PET identifies patients at higher risk of death or VT. These findings offer prognostic value beyond Japanese clinical criteria, the presence of extra cardiac sarcoidosis and LVEF.
Hulsmans et al. show that cardiac macrophages expand in left ventricular diastolic dysfunction, a hallmark of heart failure with preserved ejection fraction (HFpEF) and cardiac aging. In HFpEF, macrophages shift toward a profibrotic subset that promotes ventricular stiffness.
In symptomatic patients without overt CAD, impaired CFR was independently associated with diastolic dysfunction and adverse events, especially HFpEF hospitalization. The presence of both coronary microvascular and diastolic dysfunctions was associated with a markedly increased risk of HFpEF events.
Background
It is suggested that the integration of maximal myocardial blood flow (MBF) and coronary flow reserve (CFR), termed coronary flow capacity, allows comprehensive evaluation of patients with known or suspected stable coronary artery disease. As 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 4,029 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 post-scan (adjusted Hazard Ratio, HR [95% Confidence-Interval, CI]: 1.79 [1.38-2.31], p<0.001 per unit decrease in CFR after adjustment for maximal MBF and clinical covariates, and 1.03 [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 four 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 disease.
In a longitudinal cohort of CS patients, a reduction in the intensity and extent of myocardial inflammation on FDG PET is associated with improvement in EF. These data suggest serial PET scanning may help guide titration of immunosuppressive therapy to improve or prevent heart failure in CS.
These findings suggest that baclofen is reasonably tolerated in an alcohol-dependent population, although the high dropout rate in the study is of concern. Baclofen may be effective for the reduction of drinking, anxiety, and craving for some alcohol-dependent individuals. A larger-scale placebo-controlled study is needed to further explore these effects and to determine the characteristics of those who respond to this medication.
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