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This study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States.Despite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing.From the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined.Out of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively.In a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

INTRODUCTION Multiple risk models are used to predict the presence of obstructive coronary artery disease (CAD) in patients with chest pain. We aimed to compare the performance of these models to an experienced cardiologist's assessment utilizing coronary angiography (CA) as a reference. MATERIALS AND METHODS We prospectively enrolled patients without known CAD referred for elective CA. We assessed pretest probability of CAD using the following risk models: Diamond-Forrester (original and updated), Duke Clinical score, ACC/AHA, CAD consortium (basic and clinical) and PROMISE minimal risk tool. All patients completed self-administrative Rose angina questionnaire. Independently, an experienced cardiologist assessed the patients to provide a binary prediction of obstructive CAD prior to CA. Obstructive CAD was defined as >80% stenosis in epicardial coronary arteries by visual assessment, or fractional flow reserve

Objectives This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR) feature-tracking–derived right ventricular (RV) free wall longitudinal strain (RVFWLS) in a large multicenter population of patients with severe functional tricuspid regurgitation. Background Tricuspid regurgitation imposes a volume overload on the RV that can lead to progressive RV dilation and dysfunction. Overt RV dysfunction is associated with poor prognosis and increased operative risk. Abnormalities of myocardial strain may provide the earliest evidence of ventricular dysfunction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of RV strain measured using CMR feature tracking have prognostic value in patients with tricuspid regurgitation is unknown. Methods Consecutive patients with severe functional tricuspid regurgitation undergoing CMR at 4 U.S. medical centers were included in this study. Feature-tracking RVFWLS was calculated from 4-chamber cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between RVFWLS and death. The incremental prognostic value of RVFWLS was assessed in nested models. Results Of the 544 patients in this study, 128 died during a median follow-up of 6 years. By Kaplan-Meier analysis, patients with RVFWLS ≥median (−16%) had significantly reduced event-free survival compared with those with RVFWLS Conclusions CMR feature-tracking–derived RVFWLS is an independent predictor of mortality in patients with severe functional tricuspid regurgitation, incremental to common clinical and imaging risk factors.

Background: Nonischemic cardiomyopathy is a leading cause of reduced left ventricular ejection fraction (LVEF) and is associated with high mortality risk from progressive heart failure and arrhythmias. Myocardial scar on cardiovascular magnetic resonance imaging is increasingly recognized as a risk marker for adverse outcomes; however, left ventricular dysfunction remains the basis for determining a patient’s eligibility for primary prophylaxis with implantable cardioverter-defibrillator. We investigated the relationship of LVEF and scar with long-term mortality and mode of death in a large cohort of patients with nonischemic cardiomyopathy. Methods: This study is a prospective, longitudinal outcomes registry of 1020 consecutive patients with nonischemic cardiomyopathy who underwent clinical cardiovascular magnetic resonance imaging for the assessment of LVEF and scar at 3 centers. Results: During a median follow-up of 5.2 (interquartile range, 3.8, 6.6) years, 277 (27%) patients died. On survival analysis, LVEF ≤35% and scar were strongly associated with all-cause (log-rank test P =0.002 and P P =0.001 and P P =0.001), there was no significant association between LVEF ≤35% and SCD risk ( P =0.57). On multivariable analysis including established clinical factors, LVEF and scar are independent risk markers of all-cause and cardiac death. The addition of LVEF provided incremental prognostic value but insignificant discrimination improvement by C-statistic for all-cause and cardiac death, but no incremental prognostic value for SCD. Conversely, scar extent demonstrated significant incremental prognostic value and discrimination improvement for all 3 end points. On net reclassification analysis, the addition of LVEF resulted in no significant improvement for all-cause death (11.0%; 95% CI, −6.2% to 25.9%), cardiac death (9.8%; 95% CI, −5.7% to 29.3%), or SCD (7.5%; 95% CI, −41.2% to 42.9%). Conversely, the addition of scar extent resulted in significant reclassification improvement of 25.5% (95% CI, 11.7% to 41.0%) for all-cause death, 27.0% (95% CI, 11.6% to 45.2%) for cardiac death, and 40.6% (95% CI, 10.5% to 71.8%) for SCD. Conclusions: Myocardial scar and LVEF are both risk markers for all-cause and cardiac death in patients with nonischemic cardiomyopathy. However, whereas myocardial scar has strong and incremental prognostic value for SCD risk stratification, LVEF has no incremental prognostic value over clinical measures. Scar assessment should be incorporated into patient selection criteria for primary prevention implantable cardioverter-defibrillator placement.

The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Objectives This study analyzed changes in depressive symptoms in patients with heart failure and preserved ejection fraction (HFpEF) who were enrolled in the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Background There are limited longitudinal data for depressive symptoms in patients with HFpEF. Methods In patients enrolled in the United States and Canada (n = 1,431), depressive symptoms were measured using Patient Health Questionnaire-9 (PHQ-9). Clinically meaningful changes in PHQ-9 scores were defined as worse (≥3-point increase) or better (≥3-point decrease). Multivariate models were used to identify predictors of change in depressive symptoms. Cox proportional hazard models were used to determine the impact of symptom changes from baseline on subsequent incident cardiovascular events. Results At 12 months, 19% of patients experienced clinically worsening depressive symptoms, 31% better, and 49% unchanged. Independent predictors of clinically meaningful improvement in depressive symptoms included higher baseline PHQ-9 scores, male sex, lack of chronic obstructive pulmonary disease, and randomization to spironolactone. After data were adjusted for cardiovascular comorbidities, higher baseline PHQ-9 was associated with all-cause mortality (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.02 to 1.16; p = 0.011), whereas worsening depressive symptoms at 12 months were associated with cardiovascular death (HR: 2.47; 95% CI: 1.32 to 4.63; p = 0.005) and all-cause mortality (HR: 1.82; 95% CI: 1.13 to 2.93; p = 0.014). Randomization to spironolactone was associated with modest but statistically significant reduction in depressive symptoms over the course of the trial (p = 0.014). Conclusions Higher baseline depressive symptoms and worsening depressive symptoms were associated with all-cause mortality. Randomization to spironolactone was associated with modest reduction in depressive symptoms. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)

Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia.This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia.In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE).UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p 0.001), statin (p 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE.In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891).

Objectives The aim of this study was to compare, using results from the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, the incremental cost-effectiveness of a stress cardiovascular magnetic resonance (CMR)–first strategy against 4 other clinical strategies for patients with stable symptoms suspicious for myocardial ischemia: 1) immediate x-ray coronary angiography (XCA) with selective fractional flow reserve for all patients; 2) single-photon emission computed tomography; 3) coronary computed tomographic angiography with selective computed tomographic fractional flow reserve; and 4) no imaging. Background Stress CMR perfusion imaging has established excellent diagnostic utility and prognostic value in coronary artery disease (CAD), but its cost-effectiveness in current clinical practice has not been well studied in the United States. Methods A decision analytic model was developed to project health care costs and lifetime quality-adjusted life years (QALYs) for symptomatic patients at presentation with a 32.4% prevalence of obstructive CAD. Rates of clinical events, costs, and quality-of-life values were estimated from SPINS and other published research. The analysis was conducted from a U.S. health care system perspective, with health and cost outcomes discounted annually at 3%. Results Using hard cardiovascular events (cardiovascular death or acute myocardial infarction) as the endpoint, total costs per person were lowest for the no-imaging strategy ($16,936) and highest for the immediate XCA strategy ($20,929). Lifetime QALYs were lowest for the no-imaging strategy (12.72050) and highest for the immediate XCA strategy (12.76535). The incremental cost-effectiveness ratio for the CMR-based strategy compared with the no-imaging strategy was $52,000/QALY, whereas the incremental cost-effectiveness ratio for the immediate XCA strategy was $12 million/QALY compared with CMR. Results were sensitive to variations in model inputs for prevalence of disease, hazard rate ratio for treatment of CAD, and annual discount rate. Conclusions Prior to invasive XCA, stress CMR can be a cost-effective gatekeeping tool in patients at risk for obstructive CAD in the United States. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891

Background Ivabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. Methods PRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated β-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, β-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). Results Overall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean −10.0 beats/min, 95% CI −15.7 to −4.3 vs 0.7 beats/min, 95% CI −5.4 to 6.7, P = .011). Patient-reported outcomes, β-blocker use/dose, and safety events were similar (all P > .05). Conclusions Ivabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing β-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed.

Objectives The goal of this study was to evaluate the prognostic value of global longitudinal strain (GLS) derived from cardiac magnetic resonance (CMR) feature-tracking in a large multicenter population of patients with preserved ejection fraction. Background Ejection fraction is the principal parameter used clinically to assess cardiac mechanics and provides prognostic information. However, significant abnormalities of myocardial deformation can be present despite preserved ejection fraction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of strain measured by using CMR feature-tracking have prognostic value in patients with preserved ejection fraction is unknown. Methods Consecutive patients with preserved ejection fraction (≥50%) and a clinical indication for CMR at 4 U.S. medical centers were included in this retrospective study. Feature-tracking GLS was calculated from 3 long-axis cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between GLS and death. The incremental prognostic value of GLS was assessed in nested models. Results Of the 1,274 patients in this study, 115 died during a median follow-up of 6.2 years. By Kaplan-Meier analysis, patients with GLS ≥ median (–20%) had significantly reduced event-free survival compared with those with GLS Conclusions GLS derived from CMR feature-tracking is a powerful independent predictor of mortality in patients with preserved ejection fraction, incremental to common clinical and imaging risk factors.

Mobile health (mHealth) platforms can affect health behaviors but have not been rigorously tested in randomized trials.We sought to evaluate the effectiveness of a pragmatic mHealth intervention in patients with heart failure (HF) and diabetes (DM).We conducted a multicenter randomized trial in 187 patients with both HF and DM to assess an mHealth intervention to improve physical activity and medication adherence compared to usual care. The primary endpoint was change in mean daily step count from baseline through 3 months. Other outcomes included medication adherence, health-related quality of life and metabolomic profiling.The mHealth group had an increase in daily step count of 151 steps/day at 3 months, whereas the usual-care group had a decline of 162 steps/day (least squares mean between-group difference = 313 steps/day; 95% CI: 8 619; P = 0.044). Medication adherence, measured using the Voils Adherence Questionnaire, did not change from baseline to 3 months (LS-mean change -0.08 in mHealth vs -0.15 in usual care; P = 0.47). The mHealth group had an improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score compared to the usual-care group (LS-mean difference = 5.5 points, 95% CI: 1.4, 9.6; P = 0.009). Thirteen metabolites, primarily medium- and long-chain acylcarnitines, changed differently between treatment groups from baseline to 3 months (P0.05).In patients with HF and DM, a 3-month mHealth intervention significantly improved daily physical activity, health-related quality of life and metabolomic markers of cardiovascular health but not medication adherence.Heart failure (HF) and diabetes (DM) have overlapping biological and behavioral risk factors. We conducted a multicenter randomized, clinical trial in 187 patients with both HF (regardless of ejection fraction) and DM to assess whether an mHealth intervention could improve physical activity and medication adherence. The mHealth group had an increase in mean daily step count and quality of life but not in medication adherence. Medium- and long-chain acylcarnitines changed differently in treatment groups from baseline to 3 months (P0.05). These data have important implications for designing effective lifestyle interventions in HF and DM.

Michael R Sood,1,2 Sahar S Abdelmoneim,1 Nripen Dontineni,1 Alexander Ivanov,1 Ernest Lee,1 Michael Rubin,1 Michael Vittoria,1 Marcella Meykler,1 Vidhya Ramachandran,1 Terrence Sacchi,1 Sorin Brener,1 Igor Klem,3 John F Heitner1,4 1Division of Cardiology, New York-Presbyterian Hospital, Brooklyn, NY, USA; 2Division of Cardiology, Mount Sinai South Nassau, Oceanside, NY, USA; 3Duke University, Raleigh Durham, NC, USA; 4Division of Cardiology, New York University-Langone Health, Brooklyn, NY, USACorrespondence: Michael R Sood, Division of Cardiology, Mount Sinai South Nassau, Oceanside, NY, USA, Email mike.sood@gmail.comBackground: Aortic distensibility (AD) is an important determinant of cardiovascular (CV) morbidity and mortality. There is scant data on the association between AD measured within the descending thoracic aorta and CV outcomes.Objective: We evaluated the association of AD at the descending thoracic aorta (AD desc) with the primary outcome of all-cause mortality, myocardial infarction (MI), stroke or coronary revascularization in patients referred for a cardiovascular magnetic resonance (CMR) study.Methods: 928 consecutive patients [(mean age 60 ± 17; 33% with prior cardiovascular disease (CVD))] were evaluated. AD desc was measured at the cross-section of the descending thoracic aorta in the 4-chamber view (via steady-state free precession [SSFP] cine sequences) and was grouped into quintiles (with the 1st quintile corresponding to the least AD, i.e., the stiffest aorta). Cox proportional-hazards regression analysis were performed for the primary outcome.Results: A total of 315 patients (34%) experienced the primary outcome during a median (25% IQR, 75% IQR) follow-up of 5.0 (0.56, 9.3) years. A decreased AD was significantly associated with hypertension, diabetes, renal disease, and dyslipidemia (p < 0.0001). A primary outcome occurred in 43% of patients with AD desc ≤ median compared to 25% with AD desc > median, p < 0.0001, and in 44% of patients with AD desc in the 1st quintile compared to 31% with AD desc in the other quintiles (p = 0.0004). Event free survival was incrementally reduced amongst quintiles (p < 0.0001). However, AD desc ≤ median was not an independent predictor of the primary endpoint after multivariable adjustment in the overall population [adjusted HR 1.09 (95% CI:0.82– 1.45), p = 0.518] or in the subgroup analysis of patients with or without prior CVD.Conclusion: In this real-world cohort of 928 patients referred for CMR, AD desc is not an independent predictor of CV outcomes.Keywords: cardiovascular magnetic resonance, aortic distensibility, descending aorta, AD, CMR

Introduction: LV ischemia has been linked to functional mitral regurgitation (FMR) but ischemia is present many pts without FMR. CMR concomitantly assesses MR, ischemia and LV function but has not been used to test factors modifying impact of ischemia on FMR. Methods: Vasodilator stress CMR was performed in CAD pts in a multicenter registry, in whom advanced (≥moderate) FMR was confirmed by core lab. LV ischemia was categorized by subpapillary involvement (subtending mitral apparatus). To test mechanism by which ischemia impacts FMR, LV strain was measured in pts with ischemia and Results: 2639 pts were studied; 7% had advanced FMR. While FMR pts had more ischemia in subpapillary (21.8 ± 28.3 vs 13.4 ± 21.9%) and nonpapillary (19.2 ± 25.5 vs 13.0 ± 22.2%) regions (pFigure ). Adverse mitral remodeling associated with impaired strain; mitral tenting area (OR -0.01 per % [-0.02, -0.004] p Conclusions: Ischemia mediated LV dysfunction on multiparametric CMR modulates likelihood of FMR and adverse prognosis.

Objective: To describe from a noninterventional registry (Utilization of Ticagrelor in the Upstream Setting for Non-ST-Segment Elevation Acute Coronary Syndrome), the short-term ischemic and hemorrhagic outcomes in patients with non-ST elevation myocardial infarction (MI) are managed with a loading dose (LD) of a P2Y12 inhibitor (P2Y12i) given at least 4 hours before diagnostic angiography and delineation of coronary anatomy. Prior data on the effects of such “upstream loading” have been inconsistent. Methods: In 53 US hospitals, we evaluated the in-hospital care and outcomes of patients with confirmed non-ST elevation MI managed with an interventional strategy and loaded upstream (at least 4 h before diagnostic angiography) with oral P2Y12i therapy. Patients entered into the database were grouped into 1 of 4 cohorts for analysis: (1) overall cohort, (2) thienopyridine (clopidogrel or prasugrel) load, (3) ticagrelor load, and (4) ticagrelor-consistent. The fourth cohort is a subset of cohort 3 that received ticagrelor throughout the index hospital stay and at discharge. We evaluated in-hospital clinical course and ischemic and bleeding outcomes in all patients and also 30-day outcomes in the ticagrelor-consistent cohort. Results: A total of 3355 patients were enrolled, of whom 1087 had 30-day follow-up. The mean (±SD) age was 63.3 ± 12.5 years, and 62.6% were male. Thrombolysis in MI and Global Registry of Acute Coronary Events scores placed these patients in the intermediate risk range, and CRUSADE scores were in the moderate risk range. The LD in Utilization of Ticagrelor in the Upstream Setting for Non-ST-Segment Elevation Acute Coronary Syndrome was clopidogrel in 45.6%, ticagrelor in 53.6%, and prasugrel in 0.8%. The median upstream interval (LD to angiography) was 17:27 hours and did not change appreciably over the course of the data collection period (2/15–10/19). Access was radial in 48.6% and femoral in 51.4%. Postangiography management was medical only in 32.3%, percutaneous coronary intervention in 59.4%, and coronary artery bypass grafting in 8.3%. Median length of stay was 2.7 days, and median time from angiography to coronary artery bypass grafting was 3.6 days. In-hospital mortality was 0.51%, and major bleeding (thrombolysis in MI) was 0.24%; the in-hospital major adverse cardiovascular events rate was 0.7%, and stent thrombosis occurred in 0.18%. No significant differences were seen between the ticagrelor and clopidogrel cohorts in hospital, but 16% received more than 1 P2Y12i in-hospital. On follow-up (93.2% response), 86.7% of patients reported taking ticagrelor as directed. Conclusions: Upstream loading of P2Y12i was associated with very low rates of bleeding and short length of stay in a large cohort of non-ST elevation MI (NSTEMI) patients managed invasively.

The objective of this meta-analysis was to assess the predictive value of late gadolinium enhancement (LGE) and global systolic impairment for future major adverse cardiovascular events in left ventricular noncompaction (LVNC). The prognosis of patients with LVNC, with and without left ventricular dysfunction and LGE, is still unclear. A systematic review of published research and a meta-analysis reporting a combined endpoint of hard (cardiac death, sudden cardiac death, appropriate defibrillator firing, resuscitated cardiac arrest, cardiac transplantation, assist device implantation) and minor (heart failure hospitalization and thromboembolic events) events was performed. Four studies with 574 patients with LVNC and 677 with no LVNC and an average follow-up duration of 5.2 years were analyzed. In patients with LVNC, LGE was associated with the combined endpoint (pooled odds ratio: 4.9; 95% confidence interval: 1.63 to 14.6; p = 0.005) and cardiac death (pooled odds ratio: 9.8; 95% confidence interval: 2.44 to 39.5; p < 0.001). Preserved left ventricular systolic function was found in 183 patients with LVNC: 25 with positive LGE and 158 with negative LGE. In LVNC with preserved ejection fraction, positive LGE was associated with hard cardiac events (odds ratio: 6.1; 95% confidence interval: 2.1 to 17.5; p < 0.001). No hard cardiac events were recorded in patients with LVNC, preserved ejection fraction, and negative LGE. Patients with LVNC but without LGE have a better prognosis than those with LGE. When LGE is negative and global systolic function is preserved, no hard cardiac events are to be expected. Currently available criteria allow diagnosis of LVNC, but to further define the presence and prognostic significance of the disease, LGE and/or global systolic impairment must be considered for better risk stratification.

Background: Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies. Objectives: This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States. Methods: In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates. Results: In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers. Conclusions: In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891).

Objectives This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived mitral annular plane systolic excursion (MAPSE) in a large multicenter population of patients with hypertension. Background In patients with hypertension, cardiac abnormalities are powerful predictors of adverse outcomes. Long-axis mitral annular movement plays a fundamental role in cardiac mechanics and is an early marker for a number of pathological processes. Given the adverse consequences of cardiac involvement in hypertension, the authors hypothesized that lateral MAPSE may provide incremental prognostic information in these patients. Methods Consecutive patients with hypertension and a clinical indication for CMR at 4 U.S. medical centers were included in this study (n = 1,735). Lateral MAPSE was measured in the 4-chamber cine view. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the association between lateral MAPSE and death. The incremental prognostic value of lateral MAPSE was assessed in nested models. Results Over a median follow-up period of 5.1 years, 235 patients died. By Kaplan-Meier analysis, risk of death was significantly higher in patients with a lateral MAPSE Conclusions CMR-derived lateral MAPSE is a powerful, independent predictor of mortality in patients with hypertension and a clinical indication for CMR, incremental to common clinical and CMR risk factors. These findings may suggest a role for CMR-derived lateral MAPSE in identifying hypertensive patients at highest risk of death.

OBJECTIVE To determine the prevalence and prognostic significance of unrecognized myocardial infarction (MI) by delayed-enhancement MRI (DE-MRI) in asymptomatic patients with diabetes. RESEARCH DESIGN AND METHODS In this prospective, two-center study of asymptomatic patients without known cardiac disease (n = 120), two prespecified cohorts underwent a research MRI: 1) a high-risk group with type 1 diabetes and chronic renal insufficiency (n = 50) and 2) an average-risk group with type 2 diabetes (n = 70). The primary end point was a composite of all-cause mortality and clinical MI. RESULTS Overall, the prevalence of unrecognized MI was 19% by DE-MRI (28% high-risk group and 13% average-risk group) and 5% by electrocardiography. During up to 5 years of follow-up with a total of 460 patient-years of follow-up, the rate of death/MI was markedly higher in patients with diabetes with (vs. without) unrecognized MI (all 44% vs. 7%, high-risk group 43% vs. 6%, and average-risk group 44% vs. 8%; all P < 0.01). After adjustment for Framingham risk score, left ventricular ejection fraction, and diabetes type, the presence of unrecognized MI by DE-MRI conferred an eightfold increase in risk of death/MI (95% CI 3.0–21.1, P < 0.0001). Addition of unrecognized MI to clinical indices significantly improved model discrimination for adverse events (integrated discrimination improvement = 0.156, P = 0.001). CONCLUSIONS Unrecognized MI is prevalent in asymptomatic patients with diabetes without a history of cardiac disease and confers a markedly increased risk of death and clinical MI.

The purpose of this study was to assess whether the presence and extent of fibrosis changes over time in patients with nonischemic, dilated cardiomyopathy (DCM) receiving optimal medical therapy and the implications of any such changes on left ventricular ejection fraction (LVEF) and clinical outcomes.Myocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM.In total, 85 patients (age 56 ± 15 years, 45% women) with DCM underwent serial CMR (median interval 1.5 years) for assessment of LVEF and fibrosis. The primary outcome was all-cause mortality; the secondary outcome was a composite of heart failure hospitalization, aborted sudden cardiac death, left ventricular (LV) assist device implantation, or heart transplant.On CMR-1, fibrosis (median 0.0 [interquartile range: 0% to 2.6%]) of LV mass was noted in 34 (40%) patients. On CMR-2, regression of fibrosis was not seen in any patient. Fibrosis findings were stable in 70 (82%) patients. Fibrosis progression (increase1.8% of LV mass or new fibrosis) was seen in 15 patients (18%); 46% of these patients had no fibrosis on CMR-1. Although fibrosis progression was on aggregate associated with adverse LV remodeling and decreasing LVEF (40 ± 7% to 34 ± 10%; p 0.01), in 60% of these cases the change in LVEF was minimal (5%). Fibrosis progression was associated with increased hazards for all-cause mortality (hazard ratio: 3.4 [95% confidence interval: 1.5 to 7.9]; p 0.01) and heart failure-related complications (hazard ratio: 3.5 [95% confidence interval: 1.5 to 8.1]; p 0.01) after adjustment for clinical covariates including LVEF.Once myocardial replacement fibrosis in DCM is present on CMR, it does not regress in size or resolve over time. Progressive fibrosis is often associated with minimal change in LVEF and identifies a high-risk cohort.

Prosthetic valve endocarditis (PVE) represents 20% of all cases of endocarditis. Herein, we present a rare cause of PVE by Staphylococcus auricularis (S. auricularis) exhibiting features of subacute endocarditis causing severe aortic stenosis and acute myocardial infarction.

Introduction: New onset postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery that is associated with an increased risk for stroke and all-cause mortality. Long term data on POAF recurrence and anticoagulation remains sparse. We aimed to characterize the natural progression and recurrence of new onset POAF during a long-term follow up post cardiac surgery utilizing continuous event monitoring. Methods: This is a single-center, prospective observational study evaluating 42 patients undergoing cardiac surgery and diagnosed during indexed admission with new onset, transient POAF who were discharged in sinus rhythm between May 2015 and December 2019. Prior to discharge, all patients received implantable loop recorders (ILR) for continuous monitoring. Study outcomes were the presence and timing of AF recurrence (first and repeated AF recurrence), all-cause mortality and cerebrovascular accidents (CVA). Results: Forty-two patients [mean age 67.6± 9.6 years, 74% male, mean CHADS 2- VASc 3.5±1.5] were evaluated during a mean follow-up of 1.7 ± 1.2 years. AF recurrence after discharge occurred in 30 patients (71%). Twenty-four of these 30 patients (80%) had their first AF recurrence within the first month, 3 (10%) patients during months 1-12, and 3 (10%) patients beyond 1 year. Repeated AF recurrence occurred in 13 (43%) patients between 1 and 12-months. Beyond one year of follow-up, 5 (17%) patients had either their first AF recurrence (3) or repeated AF recurrence (2). During follow-up, there was one death ((-) AF recurrence) and two CVAs ((+) AF recurrence). Conclusions: In this study of continuous monitoring with ILR , the recurrence of AF in patients who develop transient POAF is common. Seventy percent of patients had either their first AF recurrence 6 (20%) or repeated episodes of recurrent AF 15 (50%) after 1-month post-operative follow-up.

Introduction: Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. While previous studies have shown outpatient intravenous (IV) diuretic therapy to be safe and cost-effective, there have been no randomized controlled trials to evaluate the utilization of continued outpatient IV furosemide diuretic maintenance treatment in patients with HF following hospitalization for ADHF. Hypothesis: We hypothesized that 30-day hospital readmission from ADHF would be lower with routine, standardized outpatient IV diuretic treatment along with a comprehensive HF care approach vs standard treatment. Methods: In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3 hours, biweekly for a one-month period following hospitalization for ADHF. Patients in Groups 2 and 3 also received a comprehensive HF care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment, laboratory, weight, and blood pressure-monitoring, and education during infusion visits. Echocardiography, Kansas City Cardiomyopathy Questionnaire (KCCQ) and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. Results: Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American, 70% HF reduced ejection fraction). There were a total of 14 (15%) readmissions for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p=0.11; p=0.037 comparing Group 2 and Group 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. Conclusions: The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR) feature-tracking-derived right ventricular (RV) free wall longitudinal strain (RVFWLS) in a large multicenter population of patients with severe functional tricuspid regurgitation.Tricuspid regurgitation imposes a volume overload on the RV that can lead to progressive RV dilation and dysfunction. Overt RV dysfunction is associated with poor prognosis and increased operative risk. Abnormalities of myocardial strain may provide the earliest evidence of ventricular dysfunction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of RV strain measured using CMR feature tracking have prognostic value in patients with tricuspid regurgitation is unknown.Consecutive patients with severe functional tricuspid regurgitation undergoing CMR at 4 U.S. medical centers were included in this study. Feature-tracking RVFWLS was calculated from 4-chamber cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between RVFWLS and death. The incremental prognostic value of RVFWLS was assessed in nested models.Of the 544 patients in this study, 128 died during a median follow-up of 6 years. By Kaplan-Meier analysis, patients with RVFWLS ≥median (-16%) had significantly reduced event-free survival compared with those with RVFWLS median (log-rank p 0.001). By Cox multivariable regression modeling, RVFWLS was associated with increased risk-of-death after adjustment for clinical and imaging risk factors, including RV size and ejection fraction (hazard ratio: 1.14 per %; p 0.001). Addition of RVFWLS in this model resulted in significant improvement in the global chi-square (31 to 78; p 0.001).CMR feature-tracking-derived RVFWLS is an independent predictor of mortality in patients with severe functional tricuspid regurgitation, incremental to common clinical and imaging risk factors.

Introduction Tricuspid regurgitation imposes a volume overload on the right ventricle (RV) that can lead to progressive RV dilation and dysfunction. Overt RV dysfunction is associated with poor prognosis and increased operative risk. Abnormalities of myocardial strain may provide the earliest evidence of ventricular dysfunction. CMR feature-tracking techniques now allow assessment of strain from routine cine-images, without specialized pulse sequences. Whether abnormalities of RV strain measured using CMR feature-tracking have prognostic value in patients with tricuspid regurgitation is unknown Purpose To evaluate the prognostic value of CMR feature-tracking derived RV free wall longitudinal strain (RVFWLS) in a large multicenter population of patients with severe tricuspid regurgitation. Methods Consecutive patients with severe tricuspid regurgitation undergoing CMR at four US medical centers were included in this study. Feature-tracking RVFWLS was calculated from 4 chamber cine-views (Figure-left panel). The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between RVFWLS and death. The incremental prognostic value of RVFWLS was assessed in nested models. Results Of the 406 patients in this study,115 died during a median follow-up of 8.8 years. By Kaplan-Meier-analysis, patients with RVFWLS ≥median (−16%) had significantly reduced event free survival compared to those with RVFWLS < median (log-rank p Conclusions CMR feature-tracking derived RVFWLS is an independent predictor of mortality in patients with severe tricuspid regurgitation, incremental to common clinical and imaging risk factors. Funding Acknowledgement Type of funding source: None

This study aimed to characterize the natural progression and recurrence of new-onset postoperative atrial fibrillation (POAF) during an intermediate-term follow-up post cardiac surgery by using continuous event monitoring.New-onset POAF is a common complication after cardiac surgery and is associated with an increased risk for stroke and all-cause mortality. Long-term data on new POAF recurrence and anticoagulation remain sparse.This is a single-center, prospective observational study evaluating 42 patients undergoing cardiac surgery and diagnosed during indexed admission with new-onset, transient, POAF between May 2015 and December 2019. Before discharge, all patients received implantable loop recorders for continuous monitoring. Study outcomes were the presence and timing of atrial fibrillation (AF) recurrence (first, second, and more than 2 AF recurrences), all-cause mortality, and cerebrovascular accidents. A "per-month interval" analysis of proportion of patients with any AF recurrence was assessed and reported per period of follow-up time. Kaplan-Meier analysis was used to calculate the time to first AF recurrence and report the first AF recurrence rates.Forty-two patients (mean age 67.6 ± 9.6 years, 74% male, mean CHADSIn this study of continuous monitoring with implantable loop recorders, the recurrence of AF in patients who develop transient POAF is common in the first month postoperatively. Of the patients who developed postoperative AF, 76% had any recurrence in months 1 to 12, and 30% had any recurrence beyond 1-year follow-up. Current guidelines recommend anticoagulation for POAF for 30 days. The results of this study warrant further investigation into continued monitoring and longer-term anticoagulation in this population within the context of our findings that AF duration was30 minutes beyond 1 month.

Over the past 2 decades, cardiac magnetic resonance (CMR) has become an essential component of cardiovascular clinical care and contributed to imaging-guided diagnosis and management of coronary artery disease, cardiomyopathy, congenital heart disease, cardio-oncology, valvular, and vascular disease, amongst others. The widespread availability, safety, and capability of CMR to provide corresponding anatomical, physiological, and functional data in 1 imaging session can improve the design and conduct of clinical trials through both a reduction of sample size and provision of important mechanistic data that may augment clinical trial findings. Moreover, prospective imaging-guided strategies using CMR can enhance safety, efficacy, and cost-effectiveness of cardiovascular pathways in clinical practice around the world. As the future of large-scale clinical trial design evolves to integrate personalized medicine, cost-effectiveness, and mechanistic insights of novel therapies, the integration of CMR will continue to play a critical role. In this document, the attributes, limitations, and challenges of CMR's integration into the future design and conduct of clinical trials will also be covered, and recommendations for trialists will be explored. Several prominent examples of clinical trials that test the efficacy of CMR-imaging guided pathways will also be discussed.

Aims Non-invasive assessment and risk stratification of coronary artery disease in patients with large body habitus is challenging. We aim to examine whether body mass index (BMI) modifies the prognostic value and diagnostic utility of stress cardiac magnetic resonance imaging (CMR) in a multicentre registry. Methods and results The SPINS Registry enrolled consecutive intermediate-risk patients who presented with a clinical indication for stress CMR in the USA between 2008 and 2013. Baseline demographic data including BMI, CMR indices, and ratings of study quality were collected. Primary outcome was defined by a composite of cardiovascular death and non-fatal myocardial infarction. Of the 2345 patients with available BMI included in the SPINS cohort, 1177 (50%) met criteria for obesity (BMI ≥ 30) with 531 (23%) at or above Class 2 obesity (BMI ≥ 35). In all BMI categories, >95% of studies were of diagnostic quality for cine, perfusion, and late gadolinium enhancement (LGE) sequences. At a median follow-up of 5.4 years, those without ischaemia and LGE experienced a low annual rate of hard events ( Conclusion In this large multicentre registry, elevated BMI did not negatively impact the diagnostic quality and the effectiveness of risk stratification of patients referred for stress CMR.

Background: Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing. Methods: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months. Results: Both the prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomly assigned to CTA in comparison with 4602 patients randomly assigned to functional testing (33.4% versus 78.0%, and 0.9% versus 2.1%, respectively; both P P P =0.87], 2.65 [ P =0.001], 3.88 [ P P =0.04). If 2714 patients with at least an intermediate Framingham Risk Score (>10%) who had a normal functional test were reclassified as being mildly abnormal, the discriminatory capacity improved to 0.69 (95% CI, 0.64–0.74). Conclusions: Coronary CTA, by identifying patients at risk because of nonobstructive CAD, provides better prognostic information than functional testing in contemporary patients who have stable chest pain with a low burden of obstructive CAD, myocardial ischemia, and events. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01174550.

Introduction Ejection fraction is the principal measure used clinically to assess cardiac mechanics and provides significant prognostic information. However, echocardiographic strain imaging has shown significant abnormalities of myocardial deformation can be present despite preserved ejection fraction, which maybe associated with adverse prognosis. Cardiac-Magnetic-Resonance (CMR) feature-tracking techniques now allow assessment of strain from routine cine-images, without specialized pulse sequences. Whether abnormalities of strain measured using CMR feature-tracking have prognostic value in patients with preserved ejection fraction is unknown. Purpose To evaluate the prognostic value of CMR feature-tracking derived global longitudinal strain (GLS) in a large multicenter population of patients with preserved ejection fraction. Methods Consecutive patients with preserved ejection fraction (EF ≥50%) and a clinical indication for CMR at four US medical centers were included in this study. Feature-tracking GLS was calculated from 3 long-axis-cine-views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between GLS and death. The incremental prognostic value of GLS was assessed in nested models. Results Of the 1274 patients in this study, 115 died during a median follow-up of 6.2 years. By Kaplan-Meier analysis, patients with GLS ≥ median (−20%) had significantly reduced event free survival compared to those with GLS < median (log-rank p Conclusions CMR feature-tracking derived GLS is a powerful independent predictor of mortality in patients with preserved ejection fraction, incremental to common clinical and imaging risk factors.

To determine the prevalence and prognostic significance of unrecognized myocardial infarction (MI) by delayed-enhancement MRI (DE-MRI) in asymptomatic patients with diabetes.In this prospective, two-center study of asymptomatic patients without known cardiac disease (Overall, the prevalence of unrecognized MI was 19% by DE-MRI (28% high-risk group and 13% average-risk group) and 5% by electrocardiography. During up to 5 years of follow-up with a total of 460 patient-years of follow-up, the rate of death/MI was markedly higher in patients with diabetes with (vs. without) unrecognized MI (all 44% vs. 7%, high-risk group 43% vs. 6%, and average-risk group 44% vs. 8%; allUnrecognized MI is prevalent in asymptomatic patients with diabetes without a history of cardiac disease and confers a markedly increased risk of death and clinical MI.

Determining the infarct-related artery (IRA) in non-ST-segment-elevation myocardial infarction (MI) can be challenging. Delayed-enhancement cardiac magnetic resonance (DE-CMR) can accurately identify small MIs. The purpose of this study was to determine whether DE-CMR improves the ability to identify the IRA in patients with non-ST-segment-elevation MI.In this 3-center, prospective study, we enrolled 114 patients presenting with their first MI. Patients underwent DE-CMR followed by coronary angiography. The interventional cardiologist was blinded to the DE-CMR results. Later, coronary angiography and DE-CMR images were reviewed independently and blindly for identification of the IRA. The pattern of DE-CMR hyperenhancement was also used to determine whether there was a nonischemic pathogenesis for myocardial necrosis. The IRA was not identifiable by coronary angiography in 37% of patients (n=42). In these, the IRA or a new noncoronary artery disease diagnosis was identified by DE-CMR in 60% and 19% of patients, respectively. Even in patients with an IRA determined by coronary angiography, a different IRA or a noncoronary artery disease diagnosis was identified by DE-CMR in 14% and 13%, respectively. Overall, DE-CMR led to a new IRA diagnosis in 31%, a diagnosis of nonischemic pathogenesis in 15%, or either in 46% (95% CI, 37%-55%) of patients. Of 55 patients undergoing revascularization, 27% had revascularization solely to nonculprit coronary artery territories as determined by DE-CMR.Identification of the IRA by coronary angiography can be challenging in patients with non-ST-segment-elevation MI. In nearly half, DE-CMR may lead to a new IRA diagnosis or elucidate a nonischemic pathogenesis. Revascularization solely of coronary arteries that are believed to be nonculprit arteries by DE-CMR is not uncommon.

Background: Prior studies suggest that the hospital setting provides an important opportunity to initiate guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF). Ivabradine is a specific inhibitor of the I f current in the sinoatrial node that is FDA-approved for use in chronic HFrEF. A randomized trial conducted outside the US demonstrated that heart rate reduction with ivabradine improved clinical outcomes for ambulatory patients with chronic, symptomatic HFrEF. The initiation of ivabradine specifically in patients following stabilization for acute HF has not been evaluated and there are limited trial data on the use of ivabradine in US patients. Methods: The PredischaRge Initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) trial was a randomized, open-label study of pre-discharge initiation of twice-daily ivabradine versus usual care (i.e., post-discharge initiation of ivabradine at discretion of routine physician) for 180 days. Eligible patients were those hospitalized for acute HF but stabilized and preparing for discharge, with left ventricular ejection fraction ≤35%, in sinus rhythm with resting heart rate ≥70 bpm and on optimal GDMT including maximally-tolerated doses of beta-blockers. Given an aim to understand real-world use and barriers to medication acquisition, study drug was not provided. The primary endpoint was the proportion of patients using ivabradine at 180 days. Additional endpoints included heart rate change, patient-reported outcomes, beta-blocker use, barriers to ivabradine acquisition and clinical outcomes. Results: A total of 104 patients were randomized at 23 US hospitals. The primary results of the PRIME-HF study and important secondary endpoints will be presented. Conclusion: PRIME-HF is a trial evaluating implementation of evidence in the hospital following stabilization from acute HF in patients with HFrEF receiving optimal GDMT. This study also provides important data on the use of ivabradine in patients from the US.

Right ventricular (RV) failure has proven to be independently associated with adverse outcomes. Electrocardiographic parameters assessing RV function are largely unknown, making echocardiography the first line for RV function assessment. It is however, limited by geometrical assumptions and is inferior to cardiac magnetic resonance imaging (CMRI) which is widely regarded as the most accurate tool for assessing RV function.We seek to determine the correlation of ECG parameters of right bundle branch block (RBBB) with RV ejection fraction (EF) and RV dimensions using the CMRI. QRS duration, R amplitude and R' duration were obtained from precordial lead V1; S duration and amplitude were obtained from lead I and AVL. RV systolic dysfunction was defined as RV EF40%. RV systolic dysfunction group (mean EF of 24±10%) were compared with normal RV systolic function group which acted as control (mean EF of 48±8%). CMRI and ECG parameters were compared between the two groups. Rank correlations and scatter diagrams between individual CMRI parameters and ECG parameters were done using medcalc for windows, version 12.5. Sensitivity, specificity and area under the curve (AUC) were calculated.RV systolic dysfunction group was found to have larger RV end systolic volumes (90±42Larger RV end systolic volumes seen with RV dysfunction can affect the latter part of right bundle branch leading to prolonged R' duration. We here found prolonged R' duration in lead V1 to have a highly specific inverse correlation to RV systolic function. ECG can be used as an inexpensive tool for RV function assessment and should be used alongside echocardiography to evaluate RV dysfunction when CMRI is not available.

IMPORTANCE: The role of stress cardiac magnetic resonance (CMR) imaging in clinical decision-making by reclassification of risk across American College of Cardiology/American Heart Association guideline–recommended categories has not been established. OBJECTIVE: To examine the utility of stress CMR imaging for risk reclassification in patients without a history of coronary artery disease (CAD) who presented with suspected myocardial ischemia. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter cohort study with median follow-up of 5.4 years (interquartile range, 4.6-6.9) was conducted at 13 centers across 11 US states. Participants included 1698 consecutive patients aged 35 to 85 years with 2 or more coronary risk factors but no history of CAD who presented with suspected myocardial ischemia to undergo stress CMR imaging. The study was conducted from February 18, 2019, to March 1, 2020. MAIN OUTCOMES AND MEASURES: Cardiovascular (CV) death and nonfatal myocardial infarction (MI). Major adverse CV events (MACE) including CV death, nonfatal MI, hospitalization for heart failure or unstable angina, and late, unplanned coronary artery bypass graft surgery. RESULTS: Of the 1698 patients, 873 were men (51.4%); mean (SD) age was 62 (11) years, accounting for 67 CV death/nonfatal MIs and 190 MACE. Clinical models of pretest risk were constructed and patients were categorized using guideline-based categories of low (3% year) risk. Stress CMR imaging provided risk reclassification across all baseline models. For CV death/nonfatal MI, adding stress CMR-assessed left ventricular ejection fraction, presence of ischemia, and late gadolinium enhancement to a model incorporating the validated CAD Consortium score, hypertension, smoking, and diabetes provided significant net reclassification improvement of 0.266 (95% CI, 0.091-0.441) and C statistic improvement of 0.086 (95% CI, 0.022-0.149). Stress CMR imaging reclassified 60.3% of patients in the intermediate pretest risk category (52.4% reclassified as low risk and 7.9% as high risk) with corresponding changes in the observed event rates of 0.6% per year for low posttest risk and 4.9% per year for high posttest risk. For MACE, stress CMR imaging further provided significant net reclassification improvement (0.361; 95% CI, 0.255-0.468) and C statistic improvement (0.092; 95% CI, 0.054-0.131), and reclassified 59.9% of patients in the intermediate pretest risk group (48.7% reclassified as low risk and 11.2% as high risk). CONCLUSIONS AND RELEVANCE: In this multicenter cohort of patients with no history of CAD presenting with suspected myocardial ischemia, stress CMR imaging reclassified patient risk across guideline-based risk categories, beyond clinical risk factors. The findings of this study support the value of stress CMR imaging for clinical decision-making, especially in patients at intermediate risk for CV death and nonfatal MI.

Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown.To determine whether stress CMR is associated with patient mortality.Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index.All-cause patient mortality.Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (HR, 1.883; 95% CI, 1.680-2.112; P .001), patients with (HR, 1.955; 95% CI, 1.712-2.233; P .001) and without (HR, 1.578; 95% CI, 1.235-2.2018; P .001) a history of CAD, and patients with normal (HR, 1.385; 95% CI, 1.194-1.606; P .001) and abnormal left ventricular ejection fraction (HR, 1.836; 95% CI, 1.299-2.594; P .001).Clinical vasodilator stress CMR is associated with patient mortality in a large, diverse population of patients with known or suspected CAD as well as in multiple subpopulations defined by history of CAD and left ventricular ejection fraction. These findings provide a foundational motivation to study the comparative effectiveness of stress CMR against other modalities.

This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived mitral annular plane systolic excursion (MAPSE) in a large multicenter population of patients with hypertension.In patients with hypertension, cardiac abnormalities are powerful predictors of adverse outcomes. Long-axis mitral annular movement plays a fundamental role in cardiac mechanics and is an early marker for a number of pathological processes. Given the adverse consequences of cardiac involvement in hypertension, the authors hypothesized that lateral MAPSE may provide incremental prognostic information in these patients.Consecutive patients with hypertension and a clinical indication for CMR at 4 U.S. medical centers were included in this study (n = 1,735). Lateral MAPSE was measured in the 4-chamber cine view. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the association between lateral MAPSE and death. The incremental prognostic value of lateral MAPSE was assessed in nested models.Over a median follow-up period of 5.1 years, 235 patients died. By Kaplan-Meier analysis, risk of death was significantly higher in patients with a lateral MAPSEmedian (10 mm) (log-rank; p 0.0001). Lateral MAPSE was associated with risk of death after adjustment for clinical and imaging risk factors (hazard ratio [HR]: 1.402-per-millimeter decrease; p 0.001). Addition of lateral MAPSE in this model resulted in significant improvement in the C-statistic (0.735 to 0.815; p 0.0001). Continuous net reclassification improvement was 0.739 (95% confidence interval: 0.601 to 0.902). Lateral MAPSE remained significantly associated with death even after adjustment for feature tracking global longitudinal strain (HR: 1.192-per-millimeter decrease; p 0.001). Lateral MAPSE was independently associated with death among the subgroups of patients with preserved ejection fraction (HR = 1.339; p 0.001) and in those without history of myocardial infarction (HR: 1.390; p 0.001).CMR-derived lateral MAPSE is a powerful, independent predictor of mortality in patients with hypertension and a clinical indication for CMR, incremental to common clinical and CMR risk factors. These findings may suggest a role for CMR-derived lateral MAPSE in identifying hypertensive patients at highest risk of death.