Trial of an Intervention to Improve Acute Heart Failure Outcomes.

BACKGROUND: Patients with acute heart failure are frequently or systematically hospitalized, often because the risk of adverse events is uncertain and the options for rapid follow-up are inadequate. Whether the use of a strategy to support clinicians in making decisions about discharging or admitting patients, coupled with rapid follow-up in an outpatient clinic, would affect outcomes remains uncertain. METHODS: In a stepped-wedge, cluster-randomized trial conducted in Ontario, Canada, we randomly assigned 10 hospitals to staggered start dates for one-way crossover from the control phase (usual care) to the intervention phase, which involved the use of a point-of-care algorithm to stratify patients with acute heart failure according to the risk of death. During the intervention phase, low-risk patients were discharged early (in ≤3 days) and received standardized outpatient care, and high-risk patients were admitted to the hospital. The coprimary outcomes were a composite of death from any cause or hospitalization for cardiovascular causes within 30 days after presentation and the composite outcome within 20 months. RESULTS: A total of 5452 patients were enrolled in the trial (2972 during the control phase and 2480 during the intervention phase). Within 30 days, death from any cause or hospitalization for cardiovascular causes occurred in 301 patients (12.1%) who were enrolled during the intervention phase and in 430 patients (14.5%) who were enrolled during the control phase (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.78 to 0.99; P = 0.04). Within 20 months, the cumulative incidence of primary-outcome events was 54.4% (95% CI, 48.6 to 59.9) among patients who were enrolled during the intervention phase and 56.2% (95% CI, 54.2 to 58.1) among patients who were enrolled during the control phase (adjusted hazard ratio, 0.95; 95% CI, 0.92 to 0.99). Fewer than six deaths or hospitalizations for any cause occurred in low- or intermediate-risk patients before the first outpatient visit within 30 days after discharge. CONCLUSIONS: Among patients with acute heart failure who were seeking emergency care, the use of a hospital-based strategy to support clinical decision making and rapid follow-up led to a lower risk of the composite of death from any cause or hospitalization for cardiovascular causes within 30 days than usual care. (Funded by the Ontario SPOR Support Unit and others; COACH ClinicalTrials.gov number, NCT02674438.).

Increased Spread of Native T1 Values Assessed With MRI as a Marker of Cardiac Involvement in Fabry Disease.

OBJECTIVE. Cardiac involvement is the leading cause of mortality in Fabry disease. Noninvasive markers of cardiac involvement are needed to identify patients at high risk. The purpose of this study was to evaluate the diagnostic potential of segmental native T1 spread as an imaging biomarker in Fabry disease. SUBJECTS AND METHODS. In this prospective study, 43 patients with confirmed Fabry disease (mean ± SD age, 46±14 years; 70% women) and 17 healthy control subjects (mean ± SD age, 44 ±13 years; 53% women) underwent 3-T cardiac MRI including modified Look-Locker inversion recovery T1 mapping. Segmental native T1 spread was calculated as the difference between maximum and minimum segmental native T1 values, expressed as an absolute value and as a relative percentage of global native T1. RESULTS. Absolute and relative segmental native T1 spreads were significantly higher in patients with Fabry disease than in healthy control subjects (absolute median, 115 vs 98 ms [p = 0.004]; relative median, 9.9% vs 8.0% [p < 0.001]) and correlated positively with quantitative late gadolinium enhancement (absolute, r = 0.434, p < 0.001; relative, r = 0.436, p < 0.001), indexed left ventricular mass (absolute, r = 0.316, p = 0.01; relative, r = 0.347, p = 0.007), and global longitudinal strain (absolute, r = 0.289, p = 0.03; relative, r = 0.277, p = 0.03). Relative segmental native T1 spread differentiated patients with Fabry disease from healthy control subjects (odds ratio, 1.44 [95% CI, 1.10-1.89]; p = 0.009). Interob-server agreement was excellent for both absolute (intraclass correlation coefficient, 0.932) and relative (intraclass correlation coefficient, 0.926) segmental native T1 spread. CONCLUSION. Increased native T1 spread is a reproducible imaging biomarker of cardiac involvement in Fabry disease and may be particularly useful in the evaluation of patients who cannot undergo late gadolinium enhancement imaging.

Left Ventricular Hypertrophy and Late Gadolinium Enhancement at Cardiac MRI Are Associated with Adverse Cardiac Events in Fabry Disease.

Background Cardiac involvement is the leading cause of mortality in patients with Fabry disease. Identification of imaging findings that predict adverse cardiac events is needed to enable identification of high-risk patients. Purpose To establish the prognostic value of cardiac MRI findings in men and women with Fabry disease. Materials and Methods Consecutive women and men with gene-positive Fabry disease who had undergone cardiac MRI at a single large tertiary referral hospital between March 2008 and January 2019 were included in this retrospective cohort study. Evaluators of cardiac MRI studies were blinded to all clinical information. Adverse cardiac events were assessed as a composite end point, defined as ventricular tachycardia, bradycardia requiring device implantation, severe heart failure, and cardiac death. Statistical analysis included Cox proportional hazard models adjusted for age and Mainz Severity Score Index (a measure of the severity of Fabry disease). Results Ninety patients (mean age, 44 years ± 15 [standard deviation]; 59 women) were evaluated. After a median follow-up period of 3.6 years, the composite end point was reached in 21 patients (incidence rate, 7.6% per year). Left ventricular hypertrophy (LVH) and late gadolinium enhancement (LGE) were independent predictors of the composite end point in adjusted analysis (LVH hazard ratio [HR], 3.0; 95% confidence interval [CI]: 1.1, 8.1; P = .03; and LGE HR, 7.2; 95% CI: 1.5, 34; P = .01). Patients with extensive LGE (≥15% of left ventricular mass) were at highest risk (HR, 12; 95% CI: 2.0, 67; P = .006). Sex did not modify the relationship between the composite end point and any of the cardiac MRI parameters, including LVH (P = .15 for interaction term) and LGE (P = .38 for interaction term). Conclusion Cardiac MRI findings of left ventricular hypertrophy and late gadolinium enhancement can be used to identify patients with Fabry disease who are at high risk of adverse cardiac events. © RSNA, 2019 See also the editorial by Zimmerman in this issue.

Loss of base-to-apex circumferential strain gradient assessed by cardiovascular magnetic resonance in Fabry disease: relationship to T1 mapping, late gadolinium enhancement and hypertrophy.

BACKGROUND: Cardiac involvement is common and is the leading cause of mortality in Fabry disease (FD). We explored the association between cardiovascular magnetic resonance (CMR) myocardial strain, T1 mapping, late gadolinium enhancement (LGE) and left ventricular hypertrophy (LVH) in patients with FD. METHODS: In this prospective study, 38 FD patients (45.0 ± 14.5 years, 37% male) and 8 healthy controls (40.1 ± 13.7 years, 63% male) underwent 3 T CMR including cine balanced steady-state free precession (bSSFP), LGE and modified Look-Locker Inversion recovery (MOLLI) T1 mapping. Global longitudinal (GLS) and circumferential (GCS) strain and base-to-apex longitudinal strain (LS) and circumferential strain (CS) gradients were derived from cine bSSFP images using feature tracking analysis. RESULTS: Among FD patients, 8 had LVH (FD LVH+, 21%) and 17 had LGE (FD LGE+, 45%). Nineteen FD patients (50%) had neither LVH nor LGE (FD LVH- LGE-). None of the healthy controls had LVH or LGE. FD patients and healthy controls did not differ significantly with respect to GLS (- 15.3 ± 3.5% vs. - 16.3 ± 1.5%, p = 0.45), GCS (- 19.4 ± 3.0% vs. -19.5 ± 2.9%, p = 0.84) or base-to-apex LS gradient (7.5 ± 3.8% vs. 9.3 ± 3.5%, p = 0.24). FD patients had significantly lower base-to-apex CS gradient (2.1 ± 3.7% vs. 6.5 ± 2.2%, p = 0.002) and native T1 (1170.2 ± 37.5 ms vs. 1239.0 ± 18.0 ms, p < 0.001). Base-to-apex CS gradient differentiated FD LVH- LGE- patients from healthy controls (OR 0.42, 95% CI: 0.20 to 0.86, p = 0.019), even after controlling for native T1 (OR 0.24, 95% CI: 0.06 to 0.99, p = 0.049). In a nested logistic regression model with native T1, model fit was significantly improved by the addition of base-to-apex CS gradient (χ2(df = 1) = 11.04, p < 0.001). Intra- and inter-observer agreement were moderate to good for myocardial strain parameters: GLS (ICC 0.849 and 0.774, respectively), GCS (ICC 0.831 and 0.833, respectively), and base-to-apex CS gradient (ICC 0.737 and 0.613, respectively). CONCLUSIONS: CMR reproducibly identifies myocardial strain abnormalities in FD. Loss of base-to-apex CS gradient may be an early marker of cardiac involvement in FD, with independent and incremental value beyond native T1.

Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy.

Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.0 years ± 14.1) and 30 patients with HCM (57% male; mean age, 49.3 years ± 13.5) were prospectively recruited between June 2016 and September 2017 to undergo cardiac MR imaging T1 mapping with a modified Look-Locker inversion recovery (MOLLI) acquisition scheme at 3.0 T (repetition time msec/echo time msec, 280/1.12; section thickness, 8 mm). LV and RV T1 values were evaluated. Statistical analysis included independent samples t test, receiver operating characteristic curve analysis, multivariable logistic regression, and likelihood ratio test. Results Septal LV, global LV, and RV native T1 values were significantly lower in AFD compared with those in HCM (1161 msec ± 47 vs 1296 msec ± 55, respectively [P < .001]; 1192 msec ± 52 vs 1268 msec ± 55 [P < .001]; and 1221 msec ± 54 vs 1271 msec ± 37 [P = .001], respectively). A septal LV native T1 cutoff point of 1220 msec or lower distinguished AFD from HCM with sensitivity of 97%, specificity of 93%, and accuracy of 95%. Septal LV native T1 values differentiated AFD from HCM after adjustment for age, sex, and conventional imaging features (odds ratio, 0.94; 95% confidence interval: 0.91, 0.98; P = < .001). In a nested logistic regression model with age, sex, and conventional imaging features, model fit was significantly improved by the addition of septal LV native T1 values (χ2 [df = 1] = 33.4; P < .001). Conclusion Cardiac MR imaging native T1 values at 3.0 T are significantly lower in patients with AFD compared with those with HCM and provide independent and incremental diagnostic value beyond age, sex, and conventional imaging features. © RSNA, 2018.

Diagnostic and prognostic significance of transient ischemic dilation (TID) in myocardial perfusion imaging: A systematic review and meta-analysis.

BACKGROUND: Transient ischemic dilatation (TID) of the left ventricle is a potential marker of high risk obstructive coronary artery disease on stress myocardial perfusion imaging (MPI). There is, however, interstudy variation in the diagnostic performance of TID for identification of severe and extensive coronary disease anatomy, and varied prognostic implications in the published literature. METHODS: We searched MEDLINE, EMBASE, and COCHRANE databases for studies where TID was compared with invasive or CT coronary angiography for evaluation of coronary artery stenosis. Two reviewers independently evaluated and abstracted data from each study. A bivariate random effects model was used to derive pooled sensitivities and specificities, in order to account for correlation between TID in MPI and anatomic disease severity. RESULTS: A total of 525 articles were reviewed, of which 51 met inclusion criteria. Thirty-one studies contributed to the analysis, representing a total of 2037 patients in the diagnostic meta-analysis and 9003 patients in the review of prognosis. The ratio above which TID was deemed present ranged from 1.13 to 1.38. Pooled sensitivity was 44% (95% CI 30%-60%) and specificity was 88% (95% CI 83%-92%) for the detection of extensive or severe anatomic coronary artery disease. Analysis of outcome data demonstrated increased cardiac event rates in patients with TID and an abnormal MPI. In otherwise normal perfusion, TID is an indicator of poor prognosis in patients with diabetes and/or a history of coronary disease. CONCLUSIONS: Among patients undergoing MPI, the presence of TID is specific for the detection of extensive or severe coronary artery disease.

Prognostic impact of SPECT-MPI after renal transplantation.

BACKGROUND: While renal transplantation is increasingly performed for end-stage renal disease, there is a paucity of data on cardiac screening and prognostication post-transplant. We determined the prognostic value of SPECT-MPI in a cohort who underwent renal transplantation. METHODS: Among 4933 renal transplant recipients identified from the Canadian Organ Replacement Register, we examined outcomes of patients who underwent SPECT-MPI in Ontario, Canada. We determined morbidity and mortality using hospitalization and vital statistics registries, according to SPECT-MPI findings. RESULTS: We studied 282 renal transplant recipients (median age 46 years [25th, 75th percentile 37, 58]) with detailed SPECT-MPI results available, followed for a median of 5.7 (3.3, 7.7) years. Among those undergoing SPECT-MPI (66% pharmacologic stress), 41% had an abnormal summed stress score (SSS > 0) and 31% demonstrated abnormal summed difference score (SDS > 0). Rates of cardiovascular death were 0.4 per 100 person-years among those with normal stress perfusion (SSS = 0) and 0.4 per 100 person-years with SDS = 0. After adjusting for age, sex, prior myocardial infarction (MI), and cardiac risk factors, an SSS ≥ 4 conferred increased risk of cardiovascular death or cardiovascular hospitalization with adjusted hazard ratios of 2.52 (95% CI 1.41, 4.52, P = .002) for SSS 4-6 and 2.61 (95% CI 1.52, 4.49, P < .001) for SSS ≥ 7. SDS was a significant predictor of cardiovascular death or hospitalization, with adjusted hazard ratios of 2.96 (95% CI 1.72, 5.09, P < .001) for SDS 4-6 and 3.26 (95% CI 1.64, 6.50, P < .001) for SDS ≥ 7. CONCLUSION: Among renal transplant recipients, SPECT-MPI predicted risk of cardiovascular death and cardiovascular hospitalization events.

Cardiovascular outcomes after pharmacologic stress myocardial perfusion imaging.

BACKGROUND: While pharmacologic stress single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is used for noninvasive evaluation of patients who are unable to perform treadmill exercise, its impact on net reclassification improvement (NRI) of prognosis is unknown. METHODS: We evaluated the prognostic value of pharmacologic stress MPI for prediction of cardiovascular death or non-fatal myocardial infarction (MI) within 1 year at a single-center, university-based laboratory. We examined continuous and categorical NRI of pharmacologic SPECT-MPI for prediction of outcomes beyond clinical factors alone. RESULTS: Six thousand two hundred forty patients (median age 66 years [IQR 56-74], 3466 men) were studied and followed for 5963 person-years. SPECT-MPI variables associated with increased risk of cardiovascular death or non-fatal MI included summed stress score, stress ST-shift, and post-stress resting left ventricular ejection fraction ≤50%. Compared to a clinical model which included age, sex, cardiovascular disease, risk factors, and medications, model χ(2) (210.5 vs. 281.9, P < .001) and c-statistic (0.74 vs. 0.78, P < .001) were significantly increased by addition of SPECT-MPI predictors (summed stress score, stress ST-shift and stress resting left ventricular ejection fraction). SPECT-MPI predictors increased continuous NRI by 49.4% (P < .001), reclassifying 66.5% of patients as lower risk and 32.8% as higher risk of cardiovascular death or non-fatal MI. Addition of MPI predictors to clinical factors using risk categories, defined as <1%, 1% to 3%, and >3% annualized risk of cardiovascular death or non-fatal MI, yielded a 15.0% improvement in NRI (95% CI 7.6%-27.6%, P < .001). CONCLUSIONS: Pharmacologic stress MPI substantially improved net reclassification of cardiovascular death or MI risk beyond that afforded by clinical factors.

Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease.

BACKGROUND: Although it is known that Anderson-Fabry Disease (AFD) can mimic the morphologic manifestations of hypertrophic cardiomyopathy (HCM) on echocardiography, there is a lack of cardiovascular magnetic resonance (CMR) literature on this. There is limited information in the published literature on the distribution of myocardial fibrosis in patients with AFD, with scar reported principally in the basal inferolateral midwall. METHODS: All patients with confirmed AFD undergoing CMR at our center were included. Left ventricular (LV) volumes, wall thicknesses and scar were analyzed offline. Patients were categorized into 4 groups: (1) no wall thickening; (2) concentric hypertrophy; (3) asymmetric septal hypertrophy (ASH); and (4) apical hypertrophy. Charts were reviewed for clinical information. RESULTS: Thirty-nine patients were included (20 males [51%], median age 45.2 years [range 22.3-64.4]). Almost half (17/39) had concentric wall thickening. Almost half (17/39) had pathologic LV scar; three quarters of these (13/17) had typical inferolateral midwall scar. A quarter (9/39) had both concentric wall thickening and typical inferolateral scar. A subgroup with ASH and apical hypertrophy (n = 5) had greater maximum wall thickness, total LV scar, apical scar and mid-ventricular scar than those with concentric hypertrophy (n = 17, p < 0.05). Patients with elevated LVMI had more overall arrhythmia (p = 0.007) more ventricular arrhythmia (p = 0.007) and sustained ventricular tachycardia (p = 0.008). CONCLUSIONS: Concentric thickening and inferolateral mid-myocardial scar are the most common manifestations of AFD, but the spectrum includes cases morphologically identical to apical and ASH subtypes of HCM and these have more apical and mid-ventricular LV scar. Significant LVH is associated with ventricular arrhythmia.

Evaluation of a comprehensive cardiovascular magnetic resonance protocol in young adults late after the arterial switch operation for d-transposition of the great arteries.

BACKGROUND: In adults with prior arterial switch operation (ASO) for d-transposition of the great arteries, the need for routine coronary artery assessment and evaluation for silent myocardial ischemia is not well defined. In this observational study we aimed to determine the value of a comprehensive cardiovascular magnetic resonance (CMR) protocol for the detection of coronary problems in adults with prior ASO for d-transposition of the great arteries. METHODS: Adult ASO patients (≥18 years of age) were recruited consecutively. Patients underwent a comprehensive stress perfusion CMR protocol that included measurement of biventricular systolic function, myocardial scar burden, coronary ostial assessment and myocardial perfusion during vasodilator stress by perfusion CMR. Single photon emission computed tomography (SPECT) was performed on the same day as a confirmatory second imaging modality. Stress studies were visually assessed for perfusion defects (qualitative analysis). Additionally, myocardial blood flow was quantitatively analysed from mid-ventricular perfusion CMR images. In unclear cases, CT coronary angiography or conventional angiography was done. RESULTS: Twenty-seven adult ASO patients (mean age 23 years, 85% male, 67% with a usual coronary pattern; none with a prior coronary artery complication) were included in the study. CMR stress perfusion was normal in all 27 patients with no evidence of inducible perfusion defects. In 24 cases the coronary ostia could conclusively be demonstrated to be normal. There was disagreement between CMR and SPECT for visually-assessed perfusion defects in 54% of patients with most disagreement due to false positive SPECT. CONCLUSIONS: Adult ASO survivors in this study had no CMR evidence of myocardial ischemia, scar or coronary ostial abnormality. Compared to SPECT, CMR provides additional valuable information about the coronary artery anatomy. The data shows that the asymptomatic and clinically stable adult ASO patient has a low pre-test probability for inducible ischemia. In this situation it is likely that routine evaluation with stress CMR is unnecessary.

Combined FDG PET/MRI versus Standard-of-Care Imaging in the Evaluation of Cardiac Sarcoidosis.

Purpose: To compare combined cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI with standard-of-care evaluation using cardiac MRI, 18F-FDG PET/CT, and SPECT perfusion imaging in suspected cardiac sarcoidosis (CS) with respect to radiation dose, imaging duration, and diagnostic test performance. Materials and Methods: Consecutive patients with suspected CS undergoing clinical evaluation with cardiac 18F-FDG PET/CT and gated rest technetium 99m sestamibi SPECT perfusion imaging were prospectively recruited between November 2017 and May 2021 for parallel assessment with combined cardiac 18F-FDG PET/MRI on the same day (ClinicalTrials.gov identifier, NCT03356756). Total effective radiation dose and imaging duration were compared between approaches (combined cardiac PET/MRI vs separate cardiac MRI, PET/CT, and SPECT). MRI findings were initially interpreted without PET data, and then PET and late gadolinium enhancement images were fused and interpreted together. Final diagnosis of CS was established using Japanese Ministry of Health and Welfare guidelines. Results: Forty participants (mean age, 54 years ± 14 [SD]; 26 [65%] male participants) were included, 14 (35%) with a final diagnosis of CS. Compared with separate cardiac MRI, PET/CT, and SPECT perfusion imaging, combined cardiac PET/MRI had 52% lower total radiation dose (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001) and 43% lower total imaging duration (122 minutes ± 15 vs 214 minutes ± 26, P < .001). Combined PET/MRI had the highest area under the curve for diagnosis of CS (0.84) with 96% specificity and 71% sensitivity for colocalized FDG uptake and late gadolinium enhancement in a pattern typical for CS. Conclusion: In the evaluation of suspected CS, combined cardiac 18F-FDG PET/MRI had a lower radiation dose, shorter imaging duration, and higher diagnostic performance compared with standard-of-care imaging.Clinical trial registration no. NCT03356756Keywords: Cardiac Sarcoidosis, 18F-FDG PET/MRI, 18F-FDG PET/CT, SPECT Perfusion Imaging, Cardiac MRI, Standard-of-Care Imaging Supplemental material is available for this article. © RSNA, 2023.

Myocardial Inflammation on FDG PET/MRI and Clinical Outcomes in Symptomatic and Asymptomatic Participants after COVID-19 Vaccination.

Purpose: To evaluate potential cardiac sequelae of COVID-19 vaccination at 2-month follow-up and relate cardiac symptoms to myocardial tissue changes on fluorodeoxyglucose (FDG) PET/MRI, blood biomarkers, health-related quality of life, and adverse outcomes. Materials and Methods: In this prospective study (ClinicalTrials.gov: NCT04967807), a convenience sample of individuals aged ≥17 years were enrolled after COVID-19 vaccination and were categorized as symptomatic myocarditis (new cardiac symptoms within 14 days of vaccination and met diagnostic criteria for acute myocarditis), symptomatic no myocarditis (new cardiac symptoms but did not meet criteria for myocarditis), and asymptomatic (no new cardiac symptoms). Standardized evaluation was performed 2 months after vaccination, including cardiac fluorine 18 FDG PET/MRI, blood biomarkers, and health-related quality of life. Statistical analysis included Kruskal-Wallis and Fisher exact tests. Results: Fifty-four participants were evaluated a median of 72 days (IQR: 42, 91) after COVID-19 vaccination, 17 symptomatic with myocarditis (36±[SD]15 years, 13 males), 17 symptomatic without myocarditis (42±12 years, 7 males), and 20 asymptomatic (45±14 years, 9 males). No participants in the symptomatic without myocarditis or asymptomatic groups had focal FDG-uptake, myocardial edema or impaired ventricular function. Two participants with symptomatic myocarditis had focal FDG-uptake, and three had high T2 on MRI. Health-related quality of life was lower in the symptomatic myocarditis group than the asymptomatic group. There were no adverse cardiac events beyond myocarditis in any participant. Conclusions: At two-month follow-up, FDG PET/MRI showed evidence of myocardial inflammation in 2/17 participants diagnosed with acute myocarditis early after COVID-19 vaccination, but not in symptomatic and asymptomatic participants without acute myocarditis.Keywords: Myocarditis, Vaccination, COVID-19, PET/MRI, Cardiac MRI, FDG-PET.

Systolic myocardial mechanics in patients with Anderson-Fabry disease with and without left ventricular hypertrophy and in comparison to nonobstructive hypertrophic cardiomyopathy.

OBJECTIVES: Anderson-Fabry disease (AFD) is a lysosomal storage disease, which can involve the heart, mimicking hypertrophic cardiomyopathy (HCM). The underlying mechanism of disease in AFD is an infiltrative, diffuse process, whereas HCM is a primary heart muscle condition with patchy distribution, which may prompt differences in myocardial mechanics. The aim of this study was to assess myocardial mechanics in AFD according to the presence of left ventricular hypertrophy (LVH) compared to nonobstructive HCM (NHCM) and healthy controls. METHODS AND RESULTS: We carried out a single-center, retrospective study in a small, genetically confirmed AFD cohort, which was divided into a subgroup with LVH (LVH+, n = 19), and without LVH (LVH-, n = 21). Comparison groups were healthy controls (n = 40) and NHCM patients (n = 19). Vector Velocity Imaging was applied to two-dimensional echocardiography studies for assessment of longitudinal strain (LS), circumferential strain (CS), and base-to-apex CS gradients. AFD LVH+ patients had lower global LS than AFD LVH- patients (-14 ± 4% vs -17 ± 3%, P < 0.05), but similarly lowered global CS (-24 ± 5% vs -22 ± 5%, P = ns). AFD LVH+ and NHCM had similarly lowered global LS compared to normals, but significantly lower global CS was observed in AFD LVH+ (-24 ± 5% vs -28 ± 4%, P < 0.05), whereas it was significantly increased in NHCM (-31 ± 2% vs -28 ± 4%, P < 0.05). Unlike NHCM, in both AFD subgroups, patients lost their normal base-to-apex CS gradient. CONCLUSIONS: AFD patients without LVH already show abnormal systolic myocardial mechanics. Relevant differences in myocardial mechanics between AFD patients with LVH compared to NHCM reflect the different underlying mechanisms of disease.

Combined Cardiac Fluorodeoxyglucose-Positron Emission Tomography/Magnetic Resonance Imaging Assessment of Myocardial Injury in Patients Who Recently Recovered From COVID-19.

IMPORTANCE: Although myocardial injury can occur with acute COVID-19, there is limited understanding of changes with myocardial metabolism in recovered patients. OBJECTIVE: To examine myocardial metabolic changes early after recovery from COVID-19 using fluorodeoxyglucose-positron emission tomography (PET) and associate these changes to abnormalities in cardiac magnetic resonance imaging (MRI)-based function and tissue characterization measures and inflammatory blood markers. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study took place at a single-center tertiary referral hospital system. A volunteer sample of adult patients within 3 months of a diagnosis of COVID-19 who responded to a mail invitation were recruited for cardiac PET/MRI and blood biomarker evaluation between November 2020 and June 2021. EXPOSURES: Myocardial inflammation as determined by focal fluorodeoxyglucose (FDG) uptake on PET. MAIN OUTCOMES AND MEASURES: Demographic characteristics, cardiac and inflammatory blood markers, and fasting combined cardiac 18F-FDG PET/MRI imaging were obtained. All patients with focal FDG uptake at baseline returned for repeated PET/MRI and blood marker assessment 2 months later. RESULTS: Of 47 included patients, 24 (51%) were female, and the mean (SD) age was 43 (13) years. The mean (SD) interval between COVID-19 diagnosis and PET/MRI was 67 (16) days. Most patients recovered at home during the acute infection (40 [85%]). Eight patients (17%) had focal FDG uptake on PET consistent with myocardial inflammation. Compared with those without FDG uptake, patients with focal FDG uptake had higher regional T2, T1, and extracellular volume (colocalizing with focal FDG uptake), higher prevalence of late gadolinium enhancement (6 of 8 [75%] vs 9 of 39 [23%], P = .009), lower left ventricular ejection fraction (mean [SD], 55% [4%] vs 62% [5%], P < .001), worse global longitudinal and circumferential strain (mean [SD], -16% [2%] vs -17% [2%], P = .02 and -18% [2%] vs -20% [2%], P = .047, respectively), and higher systemic inflammatory blood markers including interleukin 6, interleukin 8, and high-sensitivity C-reactive protein. Among patients with focal FDG uptake, PET/MRI, and inflammatory blood markers resolved or improved at follow-up performed a mean (SD) of 52 (17) days after baseline PET/MRI. CONCLUSIONS AND RELEVANCE: In this study of patients recently recovered from COVID-19, myocardial inflammation was identified on PET in a small proportion of patients, was associated with cardiac MRI abnormalities and elevated inflammatory blood markers at baseline, and improved at follow-up.

Cardiovascular outcomes are predicted by exercise-stress myocardial perfusion imaging: Impact on death, myocardial infarction, and coronary revascularization procedures.

BACKGROUND: The aim of this study was to determine the impact of myocardial perfusion imaging (MPI) on the outcomes of death, myocardial infarction (MI), and late coronary revascularization procedures. METHODS: In patients undergoing exercise-stress MPI (January 1, 2003-March 31, 2007), we determined the impact of summed stress score (SSS) and percent left ventricular (LV) ischemia on (a) death or MI and (b) composite of death, MI, or late coronary revascularization occurring more than 90 days post-MPI. RESULTS: During 35,007 person-years of follow-up among 9,605 patients (mean ± SD age 54.4 ± 13.2 years, 60.3% men), there were 290 deaths, 175 MIs, and 525 coronary revascularization procedures. Of those who attained ≥10 metabolic equivalents (METS) workload, major stress perfusion defects (SSS ≥7) were present in 4.2% overall and in 3.7% without ST-segment shifts, whereas large ischemic defects (≥10% LV ischemia) were present in 1% overall and 0.7% without ST-segment shifts. For those with 1% to 4%, 5% to 9%, and ≥10% LV ischemia, adjusted hazard ratios were 1.40 (95% CI 1.13-1.73, P = .002), 2.07 (95% CI 1.56-2.74, P < .001), and 3.03 (95% CI 2.21-4.16, P < .001) for the outcome of late revascularization, MI, or death versus no ischemia. Summed stress scores ≥7 were associated with increased risk of death or MI, with an adjusted hazard ratio of 1.57 (95% CI 1.16-2.13, P = .004) compared with those with no stress perfusion defects. CONCLUSION: Although workload ≥10 METS conferred lower frequency of major ischemia (≥10%), %LV ischemia predicted the occurrence of cardiovascular events and death (eg, MI, late coronary revascularization, or death). Presence of a large stress perfusion defect (SSS ≥7) predicted increased risk of MI or death.

Clinical Significance of Papillary Muscles on Left Ventricular Mass Quantification Using Cardiac Magnetic Resonance Imaging: Reproducibility and Prognostic Value in Fabry Disease.

PURPOSE: Accurate and reproducible assessment of left ventricular mass (LVM) is important in Fabry disease. However, it is unclear whether papillary muscles should be included in LVM assessed by cardiac magnetic resonance imaging (MRI). The purpose of this study was to evaluate the reproducibility and predictive value of LVM in patients with Fabry disease using different analysis approaches. MATERIALS AND METHODS: A total of 92 patients (44±15 y, 61 women) with confirmed Fabry disease who had undergone cardiac MRI at a single tertiary referral hospital were included in this retrospective study. LVM was assessed at end-diastole using 2 analysis approaches, including and excluding papillary muscles. Adverse cardiac events were assessed as a composite end point, defined as ventricular tachycardia, bradycardia requiring device implantation, severe heart failure, and cardiac death. Statistical analysis included Cox proportional hazard models, Akaike information criterion, intraclass correlation coefficients, and Bland-Altman analysis. RESULTS: Left ventricular end-diastolic volume, end-systolic volume, ejection fraction, and LVM all differed significantly between analysis approaches. LVM was significantly higher when papillary muscles were included versus excluded (157±71 vs. 141±62 g, P<0.001). Mean papillary mass was 16±11 g, accounting for 10%±3% of total LVM. LVM with pap illary muscles excluded had slightly better predictive value for the composite end point compared with LVM with papillary muscles included based on the model goodness-of-fit (Akaike information criterion 140 vs. 142). Interobserver agreement was slightly better for LVM with papillary muscles excluded compared with included (intraclass correlation coefficient 0.993 [95% confidence interval: 0.985, 0.996] vs. 0.989 [95% confidence interval: 0.975, 0.995]) with less bias and narrower limits of agreement. CONCLUSIONS: Inclusion or exclusion of papillary muscles has a significant effect on LVM quantified by cardiac MRI, and therefore, a standardized analysis approach should be used for follow-up. Exclusion of papillary muscles from LVM is a reasonable approach in patients with Fabry disease given slightly better predictive value and reproducibility.

Combined simultaneous FDG-PET/MRI with T1 and T2 mapping as an imaging biomarker for the diagnosis and prognosis of suspected cardiac sarcoidosis.

PURPOSE: To evaluate the diagnostic and prognostic significance of combined cardiac 18F-fluorodeoxyglucose (FDG) PET/MRI with T1/T2 mapping in the evaluation of suspected cardiac sarcoidosis. METHODS: Patients with suspected cardiac sarcoidosis were prospectively enrolled for cardiac 18F-FDG PET/MRI, including late gadolinium enhancement (LGE) and T1/T2 mapping with calculation of extracellular volume (ECV). The final diagnosis of cardiac sarcoidosis was established using modified JMHW guidelines. Major adverse cardiac events (MACE) were assessed as a composite of cardiovascular death, ventricular tachyarrhythmia, bradyarrhythmia, cardiac transplantation or heart failure. Statistical analysis included Cox proportional hazard models. RESULTS: Forty-two patients (53 ± 13 years, 67% male) were evaluated, 13 (31%) with a final diagnosis of cardiac sarcoidosis. Among patients with cardiac sarcoidosis, 100% of patients had at least one abnormality on PET/MRI: FDG uptake in 69%, LGE in 100%, elevated T1 and ECV in 100%, and elevated T2 in 46%. FDG uptake co-localized with LGE in 69% of patients with cardiac sarcoidosis compared to 24% of those without, p = 0.014. Diagnostic specificity for cardiac sarcoidosis was highest for FDG uptake (69%), elevated T2 (79%), and FDG uptake co-localizing with LGE (76%). Diagnostic sensitivity was highest for LGE, elevated T1 and ECV (100%). After median follow-up duration of 634 days, 13 patients experienced MACE. All patients who experienced MACE had LGE, elevated T1 and elevated ECV. FDG uptake (HR 14.7, p = 0.002), elevated T2 (HR 9.0, p = 0.002) and native T1 (HR 1.1 per 10 ms increase, p = 0.044) were significant predictors of MACE even after adjusting for left ventricular ejection fraction and immune suppression treatment. The presence of FDG uptake co-localizing with LGE had the highest diagnostic performance overall (AUC 0.73) and was the best predictor of MACE based on model goodness of fit (HR 14.9, p = 0.001). CONCLUSIONS: Combined cardiac FDG-PET/MRI with T1/T2 mapping provides complementary diagnostic information and predicts MACE in patients with suspected cardiac sarcoidosis.