A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction

ObjectivesThis study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure.BackgroundA cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI).MethodsThe Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score.ResultsThere were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score.ConclusionsThis noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850)     

Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease: A Large Retrospective Registry

ObjectivesThis study explored the association of ischemic burden, as measured by vasodilator stress cardiovascular magnetic resonance (CMR), with all-cause mortality and the effect of revascularization on all-cause mortality in patients with stable ischemic heart disease (SIHD).BackgroundIn patients with SIHD, the association of ischemic burden, derived from vasodilator stress CMR, with all-cause mortality and its role for decision-making is unclear.MethodsThe registry consisted of 6,389 consecutive patients (mean age: 65 ± 12 years; 38% women) who underwent vasodilator stress CMR for known or suspected SIHD. The ischemic burden (at stress first-pass perfusion imaging) was computed (17-segment model). The effect of CMR-related revascularization (within the following 3 months) on all-cause mortality was retrospectively explored using the electronic regional health system registry.ResultsDuring a 5.75-year median follow-up, 717 (11%) deaths were documented. In multivariable analyses, more extensive ischemic burden (per 1-segment increase) was independently related to all-cause mortality (hazard ratio: 1.04; 95% confidence interval: 1.02 to 1.07; p < 0.001). In 1,032 1:1 matched patients using a limited number of variables (516 revascularized, 516 non-revascularized), revascularization within the following 3 months was associated with less all-cause mortality only in patients with extensive CMR-related ischemia (>5 segments, n = 432; 10% vs. 24%; p = 0.01).ConclusionsIn a large retrospective registry of unselected patients with known or suspected SIHD who underwent vasodilator stress CMR, extensive ischemic burden was related to a higher risk of long-term, all-cause mortality. Revascularization was associated with a protective effect only in the restricted subset of patients with extensive CMR-related ischemia. Further research will be needed to confirm this hypothesis-generating finding.     

Machine Learning Identifies Clinical Parameters to Predict Mortality in Patients Undergoing Transcatheter Mitral Valve Repair

ObjectivesThe aim of this study was to develop a machine learning (ML)–based risk stratification tool for 1-year mortality in transcatheter mitral valve repair (TMVR) patients incorporating metabolic and hemodynamic parameters.BackgroundThe lack of appropriate, well-validated, and specific means to risk-stratify patients with mitral regurgitation complicates the evaluation of prognostic benefits of TMVR in clinical trials and practice.MethodsA total of 1,009 TMVR patients from 3 university hospitals within the Heart Failure Network Rhineland were included; 1 hospital (n = 317) served as external validation. The primary endpoint was all-cause 1-year mortality. Model performance was assessed using receiver-operating characteristic curve analysis. In the derivation cohort, different ML algorithms were tested using 5-fold cross-validation. The final model, called MITRALITY (transcatheter mitral valve repair mortality prediction system) was tested in the validation cohort with respect to existing clinical scores.ResultsExtreme gradient boosting was selected for the MITRALITY score, using only 6 baseline clinical features for prediction (in order of predictive importance): urea, hemoglobin, N-terminal pro–brain natriuretic peptide, mean arterial pressure, body mass index, and creatinine. In the external validation cohort, the MITRALITY score’s area under the curve was 0.783 (95% CI: 0.716-0.849), while existing scores yielded areas under the curve of 0.721 (95% CI: 0.63-0.811) and 0.657 (95% CI: 0.536-0.778) at best.ConclusionsThe MITRALITY score is a novel, internally and externally validated ML-based tool for risk stratification of patients prior to TMVR, potentially serving future clinical trials and daily clinical practice.     

An Explainable Machine Learning Approach Reveals Prognostic Significance of Right Ventricular Dysfunction in Nonischemic Cardiomyopathy

ObjectivesThe authors implemented an explainable machine learning (ML) model to gain insight into the association between cardiac magnetic resonance markers and adverse outcomes of cardiovascular hospitalization and all-cause death (composite endpoint) in patients with nonischemic dilated cardiomyopathy (NICM).BackgroundRisk stratification of patients with NICM remains challenging. An explainable ML model has the potential to provide insight into the contributions of different risk markers in the prediction model.MethodsAn explainable ML model based on extreme gradient boosting (XGBoost) machines was developed using cardiac magnetic resonance and clinical parameters. The study cohorts consist of patients with NICM from 2 academic medical centers: Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women’s Hospital (BWH), with 328 and 214 patients, respectively. XGBoost was trained on 70% of patients from the BIDMC cohort and evaluated based on the other 30% as internal validation. The model was externally validated using the BWH cohort. To investigate the contribution of different features in our risk prediction model, we used Shapley additive explanations (SHAP) analysis.ResultsDuring a mean follow-up duration of 40 months, 34 patients from BIDMC and 33 patients from BWH experienced the composite endpoint. The area under the curve for predicting the composite endpoint was 0.71 for the internal BIDMC validation and 0.69 for the BWH cohort. SHAP analysis identified parameters associated with right ventricular (RV) dysfunction and remodeling as primary markers of adverse outcomes. High risk thresholds were identified by SHAP analysis and thus provided thresholds for top predictive continuous clinical variables.ConclusionsAn explainable ML-based risk prediction model has the potential to identify patients with NICM at risk for cardiovascular hospitalization and all-cause death. RV ejection fraction, end-systolic and end-diastolic volumes (as indicators of RV dysfunction and remodeling) were determined to be major risk markers.     

Prognostic Value of Magnetic Resonance Phenotype in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

BackgroundCardiac magnetic resonance (CMR) is widely used to assess tissue and functional abnormalities in arrhythmogenic right ventricular cardiomyopathy (ARVC). Recently, a ARVC risk score was proposed to predict the 5-year risk of malignant ventricular arrhythmias in patients with ARVC. However, CMR features such as fibrosis, fat infiltration, and left ventricular (LV) involvement were not considered.ObjectivesThe authors sought to evaluate the prognostic role of CMR phenotype in patients with definite ARVC and to evaluate the effectiveness of the novel 5-year ARVC risk score to predict cardiac events in different CMR presentations.MethodsA total of 140 patients with definite ARVC were enrolled (mean age 42 ± 17 years, 97 males) in this multicenter prospective registry. As per study design, CMR was performed in all the patients at enrollment. The novel 5-year ARVC risk score was retrospectively calculated using the patient’s characteristics at the time of enrollment. During a median follow-up of 5 years (2 to 8 years), the combined endpoint of sudden cardiac death, appropriate implantable cardioverter-defibrillator intervention, and aborted cardiac arrest was considered.ResultsCMR was completely negative in 14 patients (10%), isolated right ventricular (RV) involvement was found in 58 (41%), biventricular in 52 (37%), and LV dominant in 16 (12%). During the follow-up, 48 patients (34%) had major events, but none occurred in patients with negative CMR. At Kaplan-Meier analysis, patients with LV involvement (LV dominant and biventricular) had a worse prognosis than those with lone RV (p < 0.0001). At multivariate analysis, the LV involvement, a LV-dominant phenotype, and the 5-year ARVC risk score were independent predictors of major events. The estimated 5-year risk was able to predict the observed risk in patients with lone RV but underestimated the risk in those with LV involvement.ConclusionsDifferent CMR presentations of ARVC are associated with different prognoses. The 5-year ARVC risk score is valid for the estimation of risk in patients with lone-RV presentation but underestimated the risk when LV is involved.     

Magnetic Resonance Imaging in Pediatric Myocarditis: Trends and Associations With Cost and Outcome

BackgroundCardiac magnetic resonance (CMR) provides tissue characterization and structural and functional data. CMR has high sensitivity and specificity for myocarditis in adults and children. The relationship between pediatric CMR use, cost, and clinical outcome has not been studied.ObjectivesThis work aims to describe temporal trends in CMR imaging for pediatric myocarditis and examine associations between CMR use, hospital cost, and outcomes.MethodsA retrospective cohort study of all inpatients <21 years of age with a diagnosis of myocarditis reported to the Pediatric Health Information System (2004-2019) was performed. Trends in CMR use were examined. A propensity-matched subcohort using center and patient level variables was used to assess whether outcomes differed by CMR use.ResultsA total of 4,195 children with myocarditis from 47 hospitals were identified. The median age was 11.5 years (IQR: 1.5-16.0 years) and 2,617 (62%) were male. CMR was used in 23% and mortality occurred in 6%. CMR use during hospitalization increased from 2% in 2004 to 37% in 2019 (odds ratio [OR]: 1.19 [95% CI: 1.17-1.21]). After propensity score matching, CMR use was associated with higher median cost (+$5,340 [95% CI: +$1,739 to +$9,936]) and similar median length of stay (0 days [95% CI: ?1 to +1 days]). Using quantile regression, CMR was associated with lower 90th percentile cost (?$77,200 [95% CI: ?$127,373 to ?$31,339]). More children receiving CMR were discharged alive in the first 30 days after admission (OR: 1.89 days [95% CI: 1.28-2.29]). Within the propensity matched cohort, <10 of 790 CMR recipients died compared to 42 of 790 in the non-CMR group.ConclusionsCMR use in children with myocarditis has increased over the past 15 years. CMR use is associated with higher cost of hospitalization and similar length of stay for most children but lower cost among the sickest children. CMR use in specific patients may improve clinical outcomes at a lower cost.     

Progression of Myocardial Fibrosis in Nonischemic DCM and Association With Mortality and Heart Failure Outcomes

ObjectivesThe 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.BackgroundMyocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM.MethodsIn 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.ResultsOn 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 (increase >1.8% 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.ConclusionsOnce 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.     

Prognostic Role of CMR and Conventional Risk Factors in Myocardial Infarction With Nonobstructed Coronary Arteries

ObjectivesThis study sought to assess the prognostic impact of cardiac magnetic resonance (CMR) and conventional risk factors in patients with myocardial infarction with nonobstructed coronaries (MINOCA).BackgroundMyocardial infarction with nonobstructed coronary arteries (MINOCA) represents a diagnostic dilemma, and the prognostic markers have not been clarified.MethodsA total of 388 consecutive patients with MINOCA undergoing CMR assessment were identified retrospectively from a registry database and prospectively followed for a primary clinical endpoint of all-cause mortality. A 1.5-T CMR was performed using a comprehensive protocol (cines, T2-weighted, and late gadolinium enhancement sequences). Patients were grouped into 4 categories based on their CMR findings: myocardial infarction (MI) (embolic/spontaneous recanalization), myocarditis, cardiomyopathy, and normal CMR.ResultsCMR (performed at a median of 37 days from presentation) was able to identify the cause for the troponin rise in 74% of the patients (25% myocarditis, 25% MI, and 25% cardiomyopathy), whereas a normal CMR was identified in 26%. Over a median follow-up of 1,262 days (3.5 years), 5.7% patients died. The cardiomyopathy group had the worst prognosis (mortality 15%; log-rank test: 19.9; p < 0.001), MI had 4% mortality, and 2% in both myocarditis and normal CMR. In a multivariable Cox regression model (including clinical and CMR parameters), CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation electrocardiogram (ECG) remained the only 2 significant predictors of mortality. Using presentation with ECG ST-segment elevation and CMR diagnosis of cardiomyopathy as risk markers, the mortality risk rates were 2%, 11%, and 21% for presence of 0, 1, and 2 factors, respectively (p < 0.0001).ConclusionsIn a large cohort of patients with MINOCA, CMR (median 37 days from presentation) identified a final diagnosis in 74% of patients. Cardiomyopathy had the highest mortality, followed by MI. The strongest predictors of mortality were a CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation ECG.     

Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry

BackgroundCardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations.ObjectivesIn this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD.MethodsSex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) Registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting.ResultsSPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality.ConclusionsStress CMR demonstrated excellent prognostic performance with lower rates of invasive coronary angiography referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891)     

Extracellular Volume in Primary Mitral Regurgitation

ObjectivesThis study used cardiovascular magnetic resonance (CMR) to evaluate whether elevated extracellular volume (ECV) was associated with mitral valve prolapse (MVP) or if elevated ECV was a consequence of remodeling independent of primary mitral regurgitation (MR) etiology.BackgroundReplacement fibrosis in primary MR is more prevalent in MVP; however, data on ECV as a surrogate for diffuse interstitial fibrosis in primary MR are limited.MethodsPatients with chronic primary MR underwent comprehensive CMR phenotyping and were stratified into an MVP cohort (>2 mm leaflet displacement on a 3-chamber cine CMR) and a non-MVP cohort. Factors associated with ECV and replacement fibrosis were assessed. The association of ECV and symptoms related to MR and clinical events (mitral surgery and cardiovascular death) was ascertained.ResultsA total of 424 patients with primary MR (229 with MVP and 195 non-MVP) were enrolled. Replacement fibrosis was more prevalent in the MVP cohort (34.1% vs. 6.7%; p < 0.001), with bi-leaflet MVP having the strongest association with replacement fibrosis (odds ratio: 10.5; p < 0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events.ConclusionsAlthough replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823)     

Feature Tracking Myocardial Strain Incrementally Improves Prognostication in Myocarditis Beyond Traditional CMR Imaging Features

ObjectivesThis study investigated the association of cardiovascular cardiac magnetic resonance (CMR) feature tracking (FT) with outcome in a patient cohort with myocarditis and evaluated the possible incremental prognostic benefit beyond clinical features and traditional CMR features.BackgroundCMR is used to diagnose and risk stratify patients with myocarditis. CMR-FT allows quantitative strain analysis of myocardial function; however, its prognostic benefit in myocarditis is unknown.MethodsConsecutive patients with clinically suspected myocarditis and presence of midmyocardial or epicardial late gadolinium enhancement (LGE) and/or myocardial edema in CMR were included. Clinical and CMR features were analyzed with regard to major adverse cardiovascular events (MACE) (i.e., hospitalization for heart failure, sustained ventricular tachycardia, and all-cause mortality).ResultsOf 740 patients with clinically suspected myocarditis, 455 (61%) met our final diagnostic criteria based on CMR tissue characterization. At a median follow-up of 3.9 years, MACE occurred in 74 (16%) patients. In the univariable analysis, CMR-FT global longitudinal peak strain (GLS) was significantly associated with MACE. In a multivariable model adjusting for clinical variables (age, sex, body mass index, and acuteness of symptoms) and traditional CMR features (left ventricular ejection fraction [LVEF] and LGE extent), GLS remained independently associated with outcome (GLS hazard ratio: 1.21; 95% confidence interval: 1.08 to 1.36; p = 0.001) and incrementally improved prognostication (chi-square increases from 42.6 to 79.8 to 88.5; p < 0.001).ConclusionsMyocardial strain using CMR-FT provides independent and incremental prognostic value over clinical features, LVEF, and LGE in patients with myocarditis. CMR-FT may serve as a novel marker to improve risk stratification in myocarditis. (CMR Features in Patients With Suspected Myocarditis [CMRMyo]; NCT03470571)     

Prognostic Value of Late Gadolinium Enhancement Detected on Cardiac Magnetic Resonance in Cardiac Sarcoidosis

BackgroundSarcoidosis is a complex multisystem inflammatory disorder, with approximately 5% of patients having overt cardiac involvement. Patients with cardiac sarcoidosis are at an increased risk of both ventricular arrhythmias and sudden cardiac death. Previous studies have shown that the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with an increased risk of mortality and ventricular arrhythmias and may be useful in predicting prognosis.ObjectivesThis systematic review and meta-analysis assessed the value of LGE on CMR imaging in predicting prognosis for patients with known or suspected cardiac sarcoidosis.MethodsThe authors searched the Embase and MEDLINE databases from inception to March 2022 for studies reporting individuals with known or suspected cardiac sarcoidosis referred for CMR with LGE. Outcomes were defined as all-cause mortality, ventricular arrhythmia, or a composite outcome of either death or ventricular arrhythmias. The primary analysis evaluated these outcomes according to the presence of LGE. A secondary analysis evaluated outcomes specifically according to the presence of biventricular LGE.ResultsThirteen studies were included (1,318 participants) in the analysis, with an average participant age of 52.0 years and LGE prevalence of 13% to 70% over a follow-up of 3.1 years. Patients with LGE on CMR vs those without had higher odds of ventricular arrhythmias (odds ratio [OR]: 20.3; 95% CI: 8.1-51.0), all-cause mortality (OR: 3.45; 95% CI: 1.6-7.3), and the composite of both (OR: 9.2; 95% CI: 5.1-16.7). Right ventricular LGE is invariably accompanied by left ventricular LGE. Biventricular LGE is also associated with markedly increased odds of ventricular arrhythmias (OR: 43.6; 95% CI: 16.2-117.2).ConclusionsPatients with known or suspected cardiac sarcoidosis with LGE on CMR have significantly increased odds of both ventricular arrhythmias and all-cause mortality. The presence of biventricular LGE may confer additional prognostic information regarding arrhythmogenic risk.     

CMR DENSE and the Seattle Heart Failure Model Inform Survival and Arrhythmia Risk After CRT

ObjectivesThis study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators.BackgroundThe SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function.MethodsCMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies.ResultsThe cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD ≥0.60 or SHFM-D ≥0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response (r = −0.57; p < 0.0001) than CURE-SVD with feature tracking (r = −0.28; p = 0.004).ConclusionsA combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future.     

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance

ObjectivesThis study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD).BackgroundPatients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown.MethodsChest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke.ResultsA total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001).ConclusionsStress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.     

Machine Learning Adds to Clinical and CAC Assessments in Predicting 10-Year CHD and CVD Deaths

ObjectivesThe aim of this study was to evaluate whether machine learning (ML) of noncontrast computed tomographic (CT) and clinical variables improves the prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) deaths compared with coronary artery calcium (CAC) Agatston scoring and clinical data.BackgroundThe CAC score provides a measure of the global burden of coronary atherosclerosis, and its long-term prognostic utility has been consistently shown to have incremental value over clinical risk assessment. However, current approaches fail to integrate all available CT and clinical variables for comprehensive risk assessment.MethodsThe study included data from 66,636 asymptomatic subjects (mean age 54 ± 11 years, 67% men) without established ASCVD undergoing CAC scanning and followed for cardiovascular disease (CVD) and CHD deaths at 10 years. Clinical risk assessment incorporated the ASCVD risk score. For ML, an ensemble boosting approach was used to fit a predictive classifier for outcomes, followed by automated feature selection using information gain ratio. The model-building process incorporated all available clinical and CT data, including the CAC score; the number, volume, and density of CAC plaques; and extracoronary scores; comprising a total of 77 variables. The overall proposed model (ML all) was evaluated using a 10-fold cross-validation framework on the population data and area under the curve (AUC) as metrics. The prediction performance was also compared with 2 traditional scores (ASCVD risk and CAC score) and 2 additional models that were trained using all the clinical data (ML clinical) and CT variables (ML CT).ResultsThe AUC by ML all (0.845) for predicting CVD death was superior compared with those obtained by ASCVD risk alone (0.821), CAC score alone (0.781), and ML CT alone (0.804) (p < 0.001 for all). Similarly, for predicting CHD death, AUC by ML all (0.860) was superior to the other analyses (0.835 for ASCVD risk, 0.816 for CAC, and 0.827 for ML CT; p < 0.001).ConclusionsThe comprehensive ML model was superior to ASCVD risk, CAC score, and an ML model fitted using CT variables alone in the prediction of both CVD and CHD death.     

Adolescent cardiometabolic risk scores: A scoping review

AimsClustering of cardiometabolic risk factors (CMRFs) indicates cardiometabolic risk (CMR), a key driver of cardiovascular disease. Early detection and treatment of CMR are important to decrease this risk. To facilitate the identification of individuals at risk, CMRFs are commonly combined into a CMR Score. This scoping review aims to identify CMRFs and methods used to calculate adolescent CMR Scores.Data synthesisSystematic searches were executed in Child Development and Adolescent Studies, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, EBSCO CINAHL, Scopus Elsevier, Cochrane CENTRAL, and Nursing and Allied Health. No limits were placed on publication date or geographic location. Studies were included if participants were 10–19 years and the study reported CMRFs in a composite score. Key extracted information included participant characteristics, CMRFs comprising the scores, and methods of score calculation. CMRFs were categorized and data were reported as frequencies. This study identified 170 studies representing 189 CMR Scores. The most common CMRF categories were related to lipids, blood pressure, and adiposity. The most frequent CMRFs were triglyceride z-score, systolic blood pressure z-score, and inverse high-density lipoproteins z-score. Scores were mostly calculated by summing CMRF z-scores without weighting.ConclusionsThe range of CMRFs and Scores identified in adolescent CMR literature limits their use and interpretation. Published CMR Scores commonly contain two main limitations: (a) use of an internal cohort as the z-score reference population, and (b) Scores relying on adiposity measures. We highlight the need for a standard set of CMRFs and a consensus for a CMR Score for adolescents.     

A Machine-Learning Framework to Identify Distinct Phenotypes of Aortic Stenosis Severity

ObjectivesThe authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity.BackgroundIn AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty.MethodsUsing echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts.ResultsIn 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS.ConclusionsMachine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.     

Mechanisms Underlying the Association of Chronic Obstructive Pulmonary Disease With Heart Failure

ObjectivesThe purposes of this study were to determine why chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF). Specific objectives included whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalization for HF and death in COPD, and whether COPD and smoking are associated with myocardial inflammation.BackgroundCOPD is associated with HF independent of shared risk factors. The underlying pathophysiological mechanism is unknown.MethodsA prospective, multicenter, longitudinal cohort study of 572 patients undergoing cardiac magnetic resonance (CMR), including 450 patients with COPD and 122 age- and sex-matched patients with a median: 726 days (interquartile range: 492 to 1,160 days) follow-up. Multivariate analysis was used to examine the relationship between COPD and myocardial fibrosis, measured using cardiac magnetic resonance (CMR). Cox regression analysis was used to examine the relationship between myocardial fibrosis and outcomes; the primary endpoint was composite of hospitalizations for HF or all-cause mortality; secondary endpoints included hospitalizations for HF and all-cause mortality. Fifteen patients with COPD, 15 current smokers, and 15 healthy volunteers underwent evaluation for myocardial inflammation, including ultrasmall superparamagnetic particles of iron oxide CMR.ResultsCOPD was independently associated with myocardial fibrosis (p < 0.001). Myocardial fibrosis was independently associated with the primary outcome (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.08 to 1.20; p < 0.001), hospitalization for HF (HR: 1.25 [95% CI: 1.14 to 1.36]); p < 0.001), and all-cause mortality. Myocardial fibrosis was associated with outcome measurements more strongly than any other variable. Acute and stable COPD were associated with myocardial inflammation.ConclusionsThe associations between COPD, myocardial inflammation and myocardial fibrosis, and the independent prognostic value of myocardial fibrosis elucidate a potential pathophysiological link between COPD and HF.     

Extracellular Myocardial Volume in Patients With Aortic Stenosis

BackgroundMyocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.ObjectivesThis study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.MethodsPatients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.ResultsFour-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).ConclusionsIn patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.     

Cardiac Magnetic Resonance Feature Tracking Global Longitudinal Strain and Prognosis After Heart Transplantation

ObjectivesThis study determined the long-term prognostic significance of GLS assessed using CMR-FT in a large cohort of heart transplant recipients.BackgroundIn heart transplant recipients, global longitudinal strain (GLS) assessed using echocardiography has shown promise in the prediction of clinical outcomes. We hypothesized that CMR feature tracking (CMR-FT) GLS is independently associated with long-term outcomes in heart transplant recipients.MethodsIn a cohort of consecutive heart transplant recipients who underwent routine CMR for clinical surveillance, CMR-FT GLS was calculated from 3 long-axis cine CMR images. Associations between GLS and a composite endpoint of death or major adverse cardiac events (MACE), including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization, were investigated.ResultsA total of 152 heart transplant recipients (age 54 ± 15 years; 29% women; 5.0 ± 5.4 years after heart transplantation) were included. The median GLS was −11.6% (interquartile range: −13.6% to −9.2%). Over a median follow-up of 2.6 years, 59 recipients reached the composite endpoint. On Kaplan-Meier analyses, recipients with GLS worse than the median had a higher estimated cumulative incidence of the composite endpoint compared with recipients with GLS better than the median (log rank p = 0.004). On multivariate Cox proportional hazards regression, GLS was independently associated with the composite endpoint after adjustment for cardiac allograft vasculopathy, history of rejection, left ventricular ejection fraction (LVEF), right ventricular EF, and presence of myocardial fibrosis, with a hazard ratio of 1.15 for every 1% worsening in GLS (95% confidence interval: 1.06 to 1.24; p < 0.001). Similar results were seen in subgroups of recipients with LVEF >50% and with no myocardial fibrosis. GLS provided incremental prognostic value over other variables in the multivariate model as determined by the log-likelihood chi-squared test.ConclusionsIn a large cohort of heart transplant recipients, CMR-FT GLS was independently associated with the long-term risk of death or MACE.