Myocardial Characterization for Early Diagnosis, Treatment Response Monitoring, and Risk Assessment in Systemic Light-Chain Amyloidosis.

Aims: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor prognosis. Using myocardial characteristics on magnetic resonance imaging (MRI), this study aimed to detect early myocardial alterations, to analyze temporal changes with plasma cell therapy, and to predict risk of major adverse cardiac events (MACE) in AL amyloidosis. Methods and Results: Participants with recently diagnosed AL amyloidosis were prospectively enrolled. Presence of AL cardiomyopathy (AL-CMP vs. AL-non-CMP) was determined by abnormal cardiac biomarkers. MRI was performed at baseline and 6 months, with 12-month imaging in AL-CMP cohort. MACE was defined as all-cause death, heart failure hospitalization, or cardiac transplantation. Mayo AL stage was based on troponin T, NT-proBNP, and difference in free light chains. The study cohort included 80 participants (median age 62 years, 58% males). Median left ventricular extracellular volume (ECV) was significantly higher in AL-CMP (53% vs. 30%, p<0.001). ECV was abnormal (>32%) in all AL-CMP and in 47% of AL-non-CMP. ECV tended to increase at 6 months and decreased significantly from 6 to 12 months in AL-CMP (median -3%, p=0.011). ECV was strongly associated with MACE (p<0.001), and improved MACE prediction when added to Mayo AL stage (p=0.002). ECV≤32% identified a cohort without MACE, while ECV>48% identified a cohort with 74% MACE. Conclusions: In AL amyloidosis, ECV detects subclinical cardiomyopathy. ECV tends to increase from baseline to 6 months and decreases significantly from 6 and 12 months of plasma cell therapy in AL-CMP. ECV provides excellent risk stratification and offers additional prognostic performance over Mayo AL stage.

Role of Exercise Treadmill Testing in the Assessment of Coronary Microvascular Disease.

OBJECTIVES: The authors aimed to study the sensitivity and specificity of exercise treadmill testing (ETT) in the diagnosis of coronary microvascular disease (CMD), as well as the prognostic implications of ETT results in patients with CMD. BACKGROUND: ETT is validated to evaluate for flow-limiting coronary artery disease (CAD), however, little is known about its use for evaluating CMD. METHODS: We retrospectively studied 249 consecutive patients between 2006 and 2016 who underwent ETT and positron emission tomography within 12 months. Patients with obstructive CAD or left ventricular systolic dysfunction were excluded. CMD was defined as a coronary flow reserve <2. Patients were followed for the occurrence of a first major adverse event (composite of death or hospitalization for myocardial infarction or heart failure). RESULTS: The sensitivity and specificity of a positive ETT to detect CMD were 34.7% (95% CI: 25.4%-45.0%) and 64.9% (95% CI: 56.7%-72.5%), respectively. The specificity of a positive ETT to detect CMD increased to 86.8% (95% CI: 80.3%-91.7%) when only classifying studies with ischemic electrocardiogram changes that lasted at least 1 minute into recovery as positive, although at a cost of lower sensitivity (15.3%; 95% CI: 8.8%-24.0%). Over a median follow-up of 6.9 years (IQR: 5.1-8.2 years), 30 (12.1%) patients met the composite endpoint, including 13 (13.3%) with CMD (n = 98). In patients with CMD, ETT result was not associated with the composite endpoint (P = 0.076). CONCLUSIONS: Our data suggest limited sensitivity of ETT to detect CMD. However, a positive ETT with ischemic changes that persist at least 1 minute into recovery in the absence of obstructive CAD should raise suspicion for the presence of CMD given a high specificity. Further study is needed with larger patient sample sizes to assess the association between ETT results and outcomes in patients with CMD.

Natural language processing for the assessment of cardiovascular disease comorbidities: The cardio-Canary comorbidity project.

OBJECTIVE: Accurate ascertainment of comorbidities is paramount in clinical research. While manual adjudication is labor-intensive and expensive, the adoption of electronic health records enables computational analysis of free-text documentation using natural language processing (NLP) tools. HYPOTHESIS: We sought to develop highly accurate NLP modules to assess for the presence of five key cardiovascular comorbidities in a large electronic health record system. METHODS: One-thousand clinical notes were randomly selected from a cardiovascular registry at Mass General Brigham. Trained physicians manually adjudicated these notes for the following five diagnostic comorbidities: hypertension, dyslipidemia, diabetes, coronary artery disease, and stroke/transient ischemic attack. Using the open-source Canary NLP system, five separate NLP modules were designed based on 800 "training-set" notes and validated on 200 "test-set" notes. RESULTS: Across the five NLP modules, the sentence-level and note-level sensitivity, specificity, and positive predictive value was always greater than 85% and was most often greater than 90%. Accuracy tended to be highest for conditions with greater diagnostic clarity (e.g. diabetes and hypertension) and slightly lower for conditions whose greater diagnostic challenges (e.g. myocardial infarction and embolic stroke) may lead to less definitive documentation. CONCLUSION: We designed five open-source and highly accurate NLP modules that can be used to assess for the presence of important cardiovascular comorbidities in free-text health records. These modules have been placed in the public domain and can be used for clinical research, trial recruitment and population management at any institution as well as serve as the basis for further development of cardiovascular NLP tools.

Association of Socioeconomic Disadvantage With Long-term Mortality After Myocardial Infarction: The Mass General Brigham YOUNG-MI Registry.

Importance: Socioeconomic disadvantage is associated with poor health outcomes. However, whether socioeconomic factors are associated with post-myocardial infarction (MI) outcomes in younger patient populations is unknown. Objective: To evaluate the association of neighborhood-level socioeconomic disadvantage with long-term outcomes among patients who experienced an MI at a young age. Design, Setting, and Participants: This cohort study analyzed patients in the Mass General Brigham YOUNG-MI Registry (at Brigham and Women's Hospital and Massachusetts General Hospital in Boston, Massachusetts) who experienced an MI at or before 50 years of age between January 1, 2000, and April 30, 2016. Each patient's home address was mapped to the Area Deprivation Index (ADI) to capture higher rates of socioeconomic disadvantage. The median follow-up duration was 11.3 years. The dates of analysis were May 1, 2020, to June 30, 2020. Exposures: Patients were assigned an ADI ranking according to their home address and then stratified into 3 groups (least disadvantaged group, middle group, and most disadvantaged group). Main Outcomes and Measures: The outcomes of interest were all-cause and cardiovascular mortality. Cause of death was adjudicated from national registries and electronic medical records. Cox proportional hazards regression modeling was used to evaluate the association of ADI with all-cause and cardiovascular mortality. Results: The cohort consisted of 2097 patients, of whom 2002 (95.5%) with an ADI ranking were included (median [interquartile range] age, 45 [42-48] years; 1607 male individuals [80.3%]). Patients in the most disadvantaged neighborhoods were more likely to be Black or Hispanic, have public insurance or no insurance, and have higher rates of traditional cardiovascular risk factors such as hypertension and diabetes. Among the 1964 patients who survived to hospital discharge, 74 (13.6%) in the most disadvantaged group compared with 88 (12.6%) in the middle group and 41 (5.7%) in the least disadvantaged group died. Even after adjusting for a comprehensive set of clinical covariates, higher neighborhood disadvantage was associated with a 32% higher all-cause mortality (hazard ratio, 1.32; 95% CI, 1.10-1.60; P = .004) and a 57% higher cardiovascular mortality (hazard ratio, 1.57; 95% CI, 1.17-2.10; P = .003). Conclusions and Relevance: This study found that, among patients who experienced an MI at or before age 50 years, socioeconomic disadvantage was associated with higher all-cause and cardiovascular mortality even after adjusting for clinical comorbidities. These findings suggest that neighborhood and socioeconomic factors have an important role in long-term post-MI survival.

Reproducibility and Repeatability of Assessment of Myocardial Light Chain Amyloidosis Burden Using 18F-Florbetapir PET/CT.

BACKGROUND: 18F-florbetapir PET is emerging as an excellent quantitative tool to quantify cardiac light chain (AL) amyloidosis burden. The primary aim of this study was to determine interobserver reproducibility and intraobserver repeatability, defined per the recommendations of the Quantitative Imaging Biomarker Alliance technical performance group, of PET 18F-florbetapir retention index (RI) in patients with cardiac AL amyloidosis. METHODS: The study cohort comprised 37 subjects with systemic AL amyloidosis enrolled in the prospective study: Molecular Imaging of Primary Amyloid Cardiomyopathy (clinical trials.gov NCT: 02641145). Using 10 mCi of 18F-florbetapir, a 60-minute dynamic cardiac scan was acquired. Global and segmental left ventricular estimates of retention index (RI) of 18F-florbetapir were calculated (Carimas 2.9 software, Turku, Finland). RI was analyzed twice, at least 24 hours apart, by two independent observers. Intraobserver repeatability and interobserver reproducibility were evaluated using Bland-Altman plots and scatter plots with fitted linear regression curves. RESULTS: All reproducibility (interobserver, r = 0.98) and repeatability (intraobserver, R=0.99 for each observer) measures of 18F-florbetapir RI are excellent. On the Bland-Altman plots, the agreement limits for global 18F-florbetapir RI were high and ranged for reproducibility (interobserver) from - 9.3 to + 9.4% (Fig. 1), and for repeatability (observer 1 from - 10.8 to + 10.7% and from - 9.2 to + 11.4%, for observer 2). CONCLUSIONS: The present study showed excellent interobserver reproducibility and intraobserver repeatability of 18F-florbetapir PET retention index in patients with cardiac AL amyloidosis.

Association of Smoking Cessation and Survival Among Young Adults With Myocardial Infarction in the Partners YOUNG-MI Registry.

Importance: Despite significant progress in primary prevention, the rate of myocardial infarction (MI) continues to increase in young adults. Objectives: To identify the prevalence of tobacco use and to examine the association of both smoking and smoking cessation with survival in a cohort of adults who experienced an initial MI at a young age. Design, Setting, and Participants: The Partners YOUNG-MI registry is a retrospective cohort study from 2 large academic centers in Boston, Massachusetts, that includes patients who experienced an initial MI at 50 years or younger. Smoking status at the time of presentation and at 1 year after MI was determined from electronic medical records. Participants were 2072 individuals who experienced an MI at 50 years or younger between January 2000 and April 2016. The dates of analysis were October to December 2019. Main Outcomes and Measures: Deaths were ascertained from the Social Security Administration Death Master File, the Massachusetts Department of Vital Statistics, and the National Death Index. Cause of death was adjudicated independently by 2 cardiologists. Propensity score-adjusted Cox proportional hazards modeling was used to evaluate the association between smoking cessation and both all-cause and cardiovascular mortality. Results: Among the 2072 individuals (median age, 45 years [interquartile range, 42-48 years]; 1669 [80.6%] men), 1088 (52.5%) were smokers at the time of their index hospitalization. Of these, 910 patients were further classified into either the cessation group (343 [37.7%]) or the persistent smoking group (567 [62.3%]) at 1 year after MI. Over a median follow-up of 11.2 years (interquartile range, 7.3-14.2 years), individuals who quit smoking had a statistically significantly lower rate of all-cause mortality (hazard ratio [HR], 0.35; 95% CI, 0.19-0.63; P < .001) and cardiovascular mortality (HR, 0.29; 95% CI, 0.11-0.79; P = .02). These values remained statistically significant after propensity score adjustment (HR, 0.30 [95% CI, 0.16-0.56; P < .001] for all-cause mortality and 0.19 [95% CI, 0.06-0.56; P = .003] for cardiovascular mortality). Conclusions and Relevance: In this cohort study, approximately half of individuals who experienced an MI at 50 years or younger were active smokers. Among them, smoking cessation within 1 year after MI was associated with more than 50% lower all-cause and cardiovascular mortality.

Comparative effectiveness of coronary artery stenosis and atherosclerotic plaque burden assessment for predicting 30-day revascularization and 2-year major adverse cardiac events.

PURPOSE: To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD). METHODS: We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction. RESULTS: Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67-0.78) but improved after excluding patients with known CAD (AUC range 0.73-0.86, p < 0.05 for all). Similarly, prediction of MACE improved after excluding patients with known CAD (AUC range 0.58-0.73 vs. 0.63-0.77). CT metrics of atherosclerosis burden performed overall similarly but stenosis assessment was superior for predicting 30-day revascularization. CONCLUSIONS: Angiographic and coronary atherosclerotic plaque metrics perform only modestly well for predicting 30-day revascularization and 2-year MACE in high risk patients but improve after excluding patients with known CAD. Atherosclerotic plaque metrics did not yield incremental value over stenosis assessment for predicting events that predominantly consisted of revascularization procedures. CLINICAL TRIAL REGISTRATION: NCT00934037.

PET Perfusion and Flow Assessment: Tomorrows' Technology Today.

Quantitative myocardial perfusion PET/CT imaging is one of the most accurate tests for diagnosis and risk stratification of patients with suspected or known CAD. The test provides a comprehensive evaluation of patients with ischemic heart disease including quantitative assessments of regional myocardial perfusion, LV volumes and ejection fraction, calcified atherosclerotic burden, and myocardial blood flow and flow reserve (MFR). A normal stress myocardial blood flow and MFR (>2.0) has a very high negative predictive value and reliably excludes high-risk obstructive CAD. A global normal MFR (>2.0) identifies patients at consistently lower clinical risk. Conversely, a severely reduced MFR (<1.5) identifies patients at high clinical risk for adverse events regardless of whether this is due to obstructive CAD, microvascular dysfunction, or a combination of the 2. On the other hand, the delineation of atherosclerotic burden with either a formal quantitative coronary calcium score or by a semiquantitative assessment of the CT transmission scan is very helpful to guide the need for intensive preventive therapies. Recent evidence suggests that patients with angiographically obstructive CAD and a severe reduction in flow reserve (<1.6) may have a prognostic advantage from revascularization. This finding awaits confirmation by randomized clinical trials.

Epidemiology of Cardiac Amyloidosis-Associated Heart Failure Hospitalizations Among Fee-for-Service Medicare Beneficiaries in the United States.

Background Cardiac amyloidosis is a substantially underdiagnosed disease, and contemporary estimates of the epidemiology of amyloidosis are lacking. This study aims to determine the incidence and prevalence of cardiac amyloidosis among Medicare beneficiaries from 2000 to 2012. Methods and Results Medicare beneficiaries were counted in the prevalence cohort in each year they had (1) ≥1 principal or secondary International Classification of Diseases, Ninth Revision code for amyloidosis and (2) ≥1 principal or secondary International Classification of Diseases, Ninth Revision code for heart failure or cardiomyopathy within 2 years after the systemic amyloidosis code. A beneficiary was counted in the incidence cohort only during the first year in which they met criteria. Primary outcomes included the prevalence and incidence of hospitalizations for cardiac amyloidosis. There were 4746 incident cases of cardiac amyloidosis in 2012 and 15 737 prevalent cases in 2012. There was also a significant increase in the prevalence rate (8 to 17 per 100 000 person-years) and incidence rate (18 to 55 per 100 000 person-years) from 2000 to 2012, most notable after 2006. Incidence and prevalence increased substantially more among men, the elderly, and in blacks. Conclusions The incidence and prevalence rates of cardiac amyloidosis are higher than previously thought. The incidence and prevalence rates of cardiac amyloidosis among hospitalized patients have increased since 2000, particularly among specific patient subgroups and after 2006, suggesting improved amyloidosis awareness and higher diagnostic rates with noninvasive imaging. In light of these trends, cardiac amyloidosis should be considered during the initial work up of patients ≥65 years old hospitalized with heart failure.

Assessment of Cardiac Masses by Cardiac Magnetic Resonance Imaging: Histological Correlation and Clinical Outcomes.

Background Cardiac magnetic resonance imaging ( CMR ) provides useful information for characterizing cardiac masses, but there are limited data on whether CMR can accurately distinguish benign from malignant lesions. We aimed to describe the distribution and imaging characteristics of cardiac masses identified by CMR and to determine the diagnostic accuracy of CMR for distinguishing benign from malignant tumors. Methods and Results We examined consecutive patients referred for CMR between May 2008 and August 2013 to identify those with a cardiac mass. In patients for whom there was histological correlation, 2 investigators blinded to all data analyzed the CMR images to categorize the mass as benign or malignant. For benign masses, readers were also asked to specify the most likely diagnosis. Benign masses were defined as benign neoplastic or non-neoplastic. Malignant masses were defined as primary cardiac or metastatic. Of 8069 patients (mean age: 58±16 years; 55% female) undergoing CMR , 145 (1.8%) had a cardiac mass. In most cases (142, 98%), there was a known cardiac mass before the CMR study. Among 145 patients with a cardiac mass, 93 (64%) had a known history of malignancy. Among 53 cases that had histological correlation, 25 (47%) were benign, 26 (49%) were metastatic, and 2 (4%) were malignant primary cardiac masses. Blinded readers correctly diagnosed 89% to 94% of the cases as benign versus malignant, with a 95% agreement rate (κ=0.83). Conclusions Although C MR can be highly effective in distinguishing benign from malignant lesions, pathology remains the gold standard in accurately determining the type of mass.

Myocardial Scar But Not Ischemia Is Associated With Defibrillator Shocks and Sudden Cardiac Death in Stable Patients With Reduced Left Ventricular Ejection Fraction.

OBJECTIVES: This study sought to investigate the association of myocardial scar and ischemia with major arrhythmic events (MAEs) in patients with left ventricular ejection fraction (LVEF) ≤35%. BACKGROUND: Although myocardial scar is a known substrate for ventricular arrhythmias, the association of myocardial ischemia with ventricular arrhythmias in stable patients with left ventricular dysfunction is less clear. METHODS: A total of 439 consecutive patients (median age, 70 years; 78% male; 55% with implantable cardioverter defibrillator [ICD]) referred for stress/rest positron emission tomography (PET) and resting LVEF ≤35% were included. Primary outcome was time-to-first MAE defined as sudden cardiac death, resuscitated sudden cardiac death, or appropriate ICD shocks for ventricular tachyarrhythmias ascertained by blinded adjudication of hospital records, Social Security Administration's Death Masterfile, National Death Index, and ICD vendor databases. RESULTS: Ninety-one MAEs including 20 sudden cardiac deaths occurred in 75 (17%) patients during a median follow-up of 3.2 years. Transmural myocardial scar was strongly associated with MAEs beyond age, sex, cardiovascular risk factors, beta-blocker therapy, and resting LVEF (adjusted hazard ratio per 10% increase in scar, 1.48 [95% confidence interval: 1.22 to 1.80]; p < 0.001). However, non transmural scar/hibernation or markers of myocardial ischemia on PET including global or peri-infarct ischemia, coronary flow reserve, and resting or hyperemic myocardial blood flows were not associated with MAEs in univariable or multivariable analysis. These findings remained robust in subgroup analyses of patients with ICD (n = 223), with ischemic cardiomyopathy (n = 287), and in patients without revascularization after the PET scan (n = 365). CONCLUSIONS: Myocardial scar but not ischemia was associated with appropriate ICD shocks and sudden cardiac death in patients with LVEF ≤35%. These findings have implications for risk-stratification of patients with left ventricular dysfunction who may benefit from ICD therapy.

Geographic Disparities in Reported US Amyloidosis Mortality From 1979 to 2015: Potential Underdetection of Cardiac Amyloidosis.

Importance: Cardiac amyloidosis is an underdiagnosed disease and is highly fatal when untreated. Early diagnosis and treatment with the emerging novel therapies significantly improve survival. A comprehensive analysis of amyloidosis-related mortality is critical to appreciate the nature and distribution of underdiagnosis and improve disease detection. Objective: To evaluate the temporal and regional trends in age-adjusted amyloidosis-related mortality among men and women of various races/ethnicities in the United States. Design, Setting, and Participants: In this observational cohort study, death certificate information from the Centers for Disease Control and Prevention's Wide-ranging ONline Data for Epidemiologic Research database and the National Vital Statistics System from 1979 to 2015 was analyzed. A total of 30 764 individuals in the United States with amyloidosis listed as the underlying cause of death and 26 591 individuals with amyloidosis listed as a contributing cause of death were analyzed. Exposures: Region of residence. Main Outcomes and Measures: Age-adjusted mortality rate from amyloidosis per 1 000 000 population stratified by year, sex, race/ethnicity, and state and county of residence. Results: Of the 30 764 individuals with amyloidosis listed as the underlying cause of death, 17 421 (56.6%) were men and 27 312 (88.8%) were 55 years or older. From 1979 to 2015, the reported overall mean age-adjusted mortality rate from amyloidosis as the underlying cause of death doubled from 1.77 to 3.96 per 1 000 000 population (2.32 to 5.43 in men and 1.35 to 2.80 in women). Black men had the highest mortality rate (12.36 per 1 000 000), followed by black women (6.48 per 1 000 000). Amyloidosis contributed to age-adjusted mortality rates as high as 31.73 per 1 000 000 in certain counties. Most southern states reported the lowest US mortality rates despite having the highest proportions of black individuals. Conclusions and Relevance: The increased reported mortality over time and in proximity to amyloidosis centers more likely reflects an overall increase in disease diagnosis rather than increased lethality. The reported amyloidosis mortality is highly variable in different US regions. The lack of higher reported mortality rates in states with a greater proportion of black residents suggests underdiagnosis of amyloidosis, including cardiac forms of the disease, in many areas of the United States. Better understanding of the determinants of geographic and racial disparity in the reporting of amyloidosis deaths are warranted.

Cocaine and Marijuana Use Among Young Adults With Myocardial Infarction.

BACKGROUND: Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited. OBJECTIVES: The objectives of this study were to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and to determine its association with long-term outcomes. METHODS: The study retrospectively analyzed records of patients presenting with a type 1 MI at ≤50 years at 2 academic hospitals from 2000 to 2016. Substance abuse was determined by review of records for either patient-reported substance abuse during the week before MI or substance detection on toxicology screen. Vital status was identified by the Social Security Administration's Death Master File. Cause of death was adjudicated using electronic health records and death certificates. Cox modeling was performed for survival free from all-cause and cardiovascular death. RESULTS: A total of 2,097 patients had type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), with median follow-up of 11.2 years (interquartile range: 7.3 to 14.2 years). Use of cocaine and/or marijuana was present in 224 (10.7%) patients; cocaine in 99 (4.7%) patients, and marijuana in 125 (6.0%). Individuals with substance use had significantly lower rates of diabetes (14.7% vs. 20.4%; p = 0.05) and hyperlipidemia (45.7% vs. 60.8%; p < 0.001), but they were significantly more likely to use tobacco (70.3% vs. 49.1%; p < 0.001). The use of cocaine and/or marijuana was associated with significantly higher cardiovascular mortality (hazard ratio: 2.22; 95% confidence interval: 1.27 to 3.70; p = 0.005) and all-cause mortality (hazard ratio: 1.99; 95% confidence interval: 1.35 to 2.97; p = 0.001) after adjusting for baseline covariates. CONCLUSIONS: Cocaine and/or marijuana use is present in 10% of patients with an MI at age ≤50 years and is associated with worse all-cause and cardiovascular mortality. These findings reinforce current recommendations for substance use screening among young adults with an MI, and they highlight the need for counseling to prevent future adverse events.

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 (ß = -0.14, p = 0.01) but not with CFR. Among patients without diabetes (n = 215), SUA had a negative association with CFR (ß = -0.15, p = 0.02) and stress MBF (ß = -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.

Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis.

BACKGROUND: Although cardiac magnetic resonance (CMR) and positron emission tomography (PET) detect different pathological attributes of cardiac sarcoidosis (CS), the complementary value of these tests has not been evaluated. Our objective was to determine the value of combining CMR and PET in assessing the likelihood of CS and guiding patient management. METHODS AND RESULTS: In this retrospective study, we included 107 consecutive patients referred for evaluation of CS by both CMR and PET. Two experienced readers blinded to all clinical data reviewed CMR and PET images and categorized the likelihood of CS as no (<10%), possible (10%-50%), probable (50%-90%), or highly probable(>90%) based on predefined criteria. Patient management after imaging was assessed for all patients and across categories of increasing CS likelihood. A final clinical diagnosis for each patient was assigned based on a subsequent review of all available imaging, clinical, and pathological data. Among 107 patients (age, 55±11 years; left ventricular ejection fraction, 43±16%), 91 (85%) had late gadolinium enhancement, whereas 82 (76%) had abnormal F18-fluorodeoxyglucose uptake on PET, suggesting active inflammation. Among the 91 patients with positive late gadolinium enhancement, 60 (66%) had abnormal F18-fluorodeoxyglucose uptake. When PET data were added to CMR, 48 (45%) patients were reclassified as having a higher or lower likelihood of CS, most of them (80%) being correctly reclassified when compared with the final diagnosis. Changes in immunosuppressive therapies were significantly more likely among patients with highly probable CS. CONCLUSIONS: Among patients with suspected CS, combining CMR and PET provides complementary value for estimating the likelihood of CS and guiding patient management.

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 disease.

Clinical significance of noninvasive coronary flow reserve assessment in patients with ischemic heart disease.

PURPOSE OF REVIEW: The importance of physiologic assessments in ischemic heart disease is well recognized. Coronary flow reserve (CFR) is a novel physiologic imaging biomarker that complements both anatomic and semiquantitative perfusion assessments of coronary artery disease (CAD) severity. RECENT FINDINGS: Beyond this, assessment of CFR may provide clinical insights useful for refining diagnosis, prognosis, and eventually, management of patients along the full range of ischemic heart disease phenotypes, from multivessel obstructive CAD to diffuse coronary microvascular dysfunction. SUMMARY: We begin by defining the concept of noninvasive CFR, specifically focusing on quantification of blood flow using PET, for which robust observational data exist. Next, we describe the continuum of cardiovascular risk by CFR values in patients across the anatomic spectrum of CAD, including those with diabetes, chronic kidney disease, and nonobstructive CAD and coronary microvascular dysfunction. Finally, we summarize the impact of CFR on prognosis, with a focus on future directions for management strategies and potential novel therapies, particularly in patients with very low CFR and less obstructive CAD. This latter phenotype may provide a critical link to understanding hidden biological risk of ischemic heart disease in vulnerable populations, including women and patients with heart failure with preserved ejection fraction, metabolic syndrome, cardio-oncologic complications, and inflammatory-related disease.

Total coronary atherosclerotic plaque burden assessment by CT angiography for detecting obstructive coronary artery disease associated with myocardial perfusion abnormalities.

BACKGROUND: Total atherosclerotic plaque burden assessment by CT angiography (CTA) is a promising tool for diagnosis and prognosis of coronary artery disease (CAD) but its validation is restricted to small clinical studies. We tested the feasibility of semi-automatically derived coronary atheroma burden assessment for identifying patients with hemodynamically significant CAD in a large cohort of patients with heterogenous characteristics. METHODS: This study focused on the CTA component of the CORE320 study population. A semi-automated contour detection algorithm quantified total coronary atheroma volume defined as the difference between vessel and lumen volume. Percent atheroma volume (PAV = [total atheroma volume/total vessel volume] × 100) was the primary metric for assessment (n = 374). The area under the receiver operating characteristic curve (AUC) determined the diagnostic accuracy for identifying patients with hemodynamically significant CAD defined as ≥50% stenosis by quantitative coronary angiography and associated myocardial perfusion abnormality by SPECT. RESULTS: Of 374 patients, 139 (37%) had hemodynamically significant CAD. The AUC for PAV was 0.78 (95% confidence interval [CI] 0.73-0.83) compared with 0.84 [0.79-0.88] by standard expert CTA interpretation (p = 0.02). Accuracy for both CTA (0.91 [0.87, 0.96]) and PAV (0.86 [0.81-0.91]) increased after excluding patients with history of CAD (p < 0.01 for both). Bland-Altman analysis revealed good agreement between two observers (bias of 280.2 mm(3) [161.8, 398.7]). CONCLUSIONS: A semi-automatically derived index of total coronary atheroma volume yields good accuracy for identifying patients with hemodynamically significant CAD, though marginally inferior to CTA expert reading. These results convey promise for rapid, reliable evaluation of clinically relevant CAD.