Prognostic Value of Vasodilator Stress Perfusion Cardiovascular Magnetic Resonance in Patients With Prior Myocardial Infarction

ObjectivesThis study sought to assess the incremental prognostic value of vasodilator stress cardiovascular magnetic resonance (CMR) in patients with prior myocardial infarction (MI).BackgroundRecurrent MI is a major cause of mortality and morbidity among MI survivors.MethodsBetween 2008 and 2019, consecutive patients with prior MI referred for stress CMR were followed up for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular mortality or recurrent nonfatal MI. Uni- and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia and the extent of myocardial scar.ResultsAmong 1,594 patients with prior MI and myocardial scar on CMR, 1,401 (92%) (68.2 ± 11.0 years; 61.4% men) completed the follow-up (median: 6.2 years), and 205 had MACE (14.6%). Patients without inducible ischemia experienced a lower annual rate of MACE (3.1%) than those with 1–2 (4.9%), 3–5 (21.5%), or ≥6 segments of ischemia (45.7%) (all p < 0.01). Using Kaplan-Meier analysis, the presence of inducible ischemia and the extent of scar were associated with MACE (hazard ratio [HR]:3.52; 95% confidence interval [CI]: 2.67 to 4.65 and HR: 1.66; 95% CI: 1.53 to 2.18, respectively; both p < 0.001). In multivariable stepwise Cox regression, the presence of ischemia and the extent of scar were independent predictors of MACE (HR: 2.84; 95% CI: 2.14 to 3.78 and HR: 1.57; 95% CI: 1.44 to 1.72, respectively; both p < 0.001). These findings were significant in both symptomatic and asymptomatic patients. The addition of CMR parameters to the model including traditional risk factors resulted in a better discrimination for MACE (C-statistic: 0.76 vs. 0.62).ConclusionsIn patients with prior MI, vasodilator stress CMR has independent and incremental prognostic value over traditional risk factors.     

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping

ObjectivesThe authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD).BackgroundVA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD.MethodsOne hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps.ResultsIn patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%).ConclusionsVA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.     

Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation: Multicenter Data Using Stress Perfusion Cardiovascular Magnetic Resonance

BackgroundLeft ventricular (LV) ischemia has been variably associated with functional mitral regurgitation (FMR). Determinants of FMR in patients with ischemia are poorly understood.ObjectivesThis study sought to test whether contractile mechanics in ischemic myocardium underlying the mitral valve have an impact on likelihood of FMR.MethodsVasodilator stress perfusion cardiac magnetic resonance was performed in patients with coronary artery disease (CAD) at multiple centers. FMR severity was confirmed quantitatively via core lab analysis. To test relationship of contractile mechanics with ischemic FMR, regional wall motion and strain were assessed in patients with inducible ischemia and minimal (≤5% LV myocardium, nontransmural) infarction.ResultsA total of 2,647 patients with CAD were studied; 34% had FMR (7% moderate or greater). FMR severity increased with presence (P < 0.001) and extent (P = 0.01) of subpapillary ischemia: patients with moderate or greater FMR had more subpapillary ischemia (odds ratio [OR]: 1.13 per 10% LV; 95% CI: 1.05-1.21; P = 0.001) independent of ischemia in remote regions (P = NS); moderate or greater FMR prevalence increased stepwise with extent of ischemia and infarction in subpapillary myocardium (P < 0.001); stronger associations between FMR and infarction paralleled greater wall motion scores in infarct-affected territories. Among patients with inducible ischemia and minimal infarction (n = 532), wall motion and radial strain analysis showed impaired subpapillary contractile mechanics to associate with moderate or greater FMR (P < 0.05) independent of remote regions (P = NS). Conversely, subpapillary ischemia without contractile dysfunction did not augment FMR likelihood. Mitral and interpapillary dimensions increased with subpapillary radial strain impairment; each remodeling parameter associated with impaired subpapillary strain (P < 0.05) independent of remote strain (P = NS). Subpapillary radial strain (OR: 1.13 per 5% [95% CI: 1.02-1.25]; P = 0.02) and mitral tenting area (OR: 1.05 per 10 mm² [95% CI: 1.00-1.10]; P = 0.04) were associated with moderate or greater FMR controlling for global remodeling represented by LV end-systolic volume (P = NS): when substituting sphericity for LV volume, moderate or greater FMR remained independently associated with subpapillary radial strain impairment (OR: 1.22 per 5% [95% CI: 1.02-1.47]; P = 0.03).ConclusionsAmong patients with CAD and ischemia, FMR severity and adverse mitral apparatus remodeling increase in proportion to contractile dysfunction underlying the mitral valve.     

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.     

Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

ObjectivesThis study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.MethodsA total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.ResultsAt the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p < 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p < 0.0001), greater LV maximal wall thickness (p < 0.0001), apical aneurysm at CMR-1 (p < 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent >8% of LV mass, indexed LV mass >100 g/m², maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p < 0.0001), and admission for heart failure (p = 0.0006).ConclusionsMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.     

High-Resolution Cardiac Magnetic Resonance Imaging Techniques for the Identification of Coronary Microvascular Dysfunction

ObjectivesThis study assessed the ability to identify coronary microvascular dysfunction (CMD) in patients with angina and nonobstructive coronary artery disease (NOCAD) using high-resolution cardiac magnetic resonance (CMR) and hypothesized that quantitative perfusion techniques would have greater accuracy than visual analysis.BackgroundHalf of all patients with angina are found to have NOCAD, while the presence of CMD portends greater morbidity and mortality, it now represents a modifiable therapeutic target. Diagnosis currently requires invasive assessment of coronary blood flow during angiography. With greater reliance on computed tomography coronary angiography as a first-line tool to investigate angina, noninvasive tests for diagnosing CMD warrant validation.MethodsConsecutive patients with angina and NOCAD were enrolled. Intracoronary pressure and flow measurements were acquired during rest and vasodilator-mediated hyperemia. CMR (3-T) was performed and analyzed by visual and quantitative techniques, including calculation of myocardial blood flow (MBF) during hyperemia (stress MBF), transmural myocardial perfusion reserve (MPR: MBF_HYPEREMIA / MBF_REST), and subendocardial MPR (MPR_ENDO). CMD was defined dichotomously as an invasive coronary flow reserve <2.5, with CMR readers blinded to this classification.ResultsA total of 75 patients were enrolled (57 ± 10 years of age, 81% women). Among the quantitative perfusion indices, MPR_ENDO and MPR had the highest accuracy (area under the curve [AUC]: 0.90 and 0.88) with high sensitivity and specificity, respectively, both superior to visual assessment (both p < 0.001). Visual assessment identified CMD with 58% accuracy (41% sensitivity and 83% specificity). Quantitative stress MBF performed similarly to visual analysis (AUC: 0.64 vs. 0.60; p = 0.69).ConclusionsHigh-resolution CMR has good accuracy at detecting CMD but only when analyzed quantitatively. Although omission of rest imaging and stress-only protocols make for quicker scans, this is at the cost of accuracy compared with integrating rest and stress perfusion. Quantitative perfusion CMR has an increasingly important role in the management of patients frequently encountered with angina and NOCAD.     

Cardiovascular Imaging Techniques to Assess Microvascular Dysfunction

The understanding of microvascular dysfunction without evidence of epicardial coronary artery disease pales in comparison with that of obstructive epicardial coronary artery disease. A primary limitation in the past had been the lack of development of noninvasive methods of detecting and quantifying microvascular dysfunction. This limitation has particularly affected the ability to study the pathophysiology, morbidity, and treatment of this disease. More recently, almost all of the noninvasive cardiac imaging modalities have been used to quantify blood flow and advance understanding of microvascular dysfunction.     

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)     

Myocardial Perfusion PET for the Detection and Reporting of Coronary Microvascular Dysfunction: A JACC: Cardiovascular Imaging Expert Panel Statement

Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their symptoms. Positron emission tomography (PET) determined absolute quantitative myocardial blood flow (MBF) at rest and during hyperemic vasodilation with subsequent derivation of myocardial flow reserve (MFR) affords the noninvasive detection and delineation of CMD. Individualized or intensified medical therapies with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1-receptor blockers, beta-blockers, ivabradine, or ranolazine may improve symptoms, quality of life, and outcome in these patients. Standardized diagnosis and reporting criteria for ischemic symptoms caused by CMD are critical for optimized and individualized treatment decisions in such patients. In this respect, it was proposed by the cardiovascular council leadership of the Society of Nuclear Medicine and Molecular Imaging to convene thoughtful leaders from around the world to serve as an independent expert panel to develop standardized diagnosis, nomenclature and nosology, and cardiac PET reporting criteria for CMD. This consensus document aims to provide an overview of the pathophysiology and clinical evidence of CMD, its invasive and noninvasive assessment, standardization of PET-determined MBFs and MFR into “classical” (predominantly related to hyperemic MBFs) and “endogen” (predominantly related to resting MBF) normal coronary microvascular function or CMD that may be critical for diagnosis of microvascular angina, subsequent patient care, and outcome of clinical CMD trials.     

Comprehensive Cardiovascular Magnetic Resonance Diastolic Dysfunction Grading Shows Very Good Agreement Compared With Echocardiography

ObjectivesThe aims of this study were to develop a comprehensive cardiovascular magnetic resonance (CMR) approach to diastolic dysfunction (DD) grading and to evaluate the accuracy of CMR in the diagnosis of DD compared with echocardiography.BackgroundLeft ventricular DD is routinely assessed using echocardiography.MethodsConsecutive clinically referred patients (n = 46; median age 59 years; interquartile range: 46 to 68 years; 33% women) underwent both conventional echocardiography and CMR. CMR diastolic transmitral velocities (E and A) and myocardial tissue velocity (e′) were measured during breath-hold using a validated high–temporal resolution radial sector-wise golden-angle velocity-encoded sequence. CMR pulmonary artery pressure was estimated from 4-dimensional flow analysis of blood flow vortex duration in the pulmonary artery. CMR left atrial volume was measured using the biplane long-axis area-length method. Both CMR and echocardiographic data were used to perform blinded grading of DD according to the 2016 joint American and European recommendations.ResultsGrading of DD by CMR agreed with that by echocardiography in 43 of 46 cases (93%), of which 9% were normal, 2% indeterminate, 63% grade 1 DD, 4% grade 2 DD, and 15% grade 3 DD. There was a very good categorical agreement, with a weighted Cohen kappa coefficient of 0.857 (95% confidence interval: 0.73 to 1.00; p < 0.001).ConclusionsA comprehensive CMR protocol for grading DD encompassing diastolic blood and myocardial velocities, estimated pulmonary artery pressure, and left atrial volume showed very good agreement with echocardiography.     

Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology

ObjectivesThis study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two.BackgroundDifferentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow.MethodsFifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography.ResultsTwenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001).ConclusionsThis novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.     

Emerging Techniques for Risk Stratification in Nonischemic Dilated Cardiomyopathy: JACC Review Topic of the Week

Dilated cardiomyopathy (DCM) is a common condition, which carries significant mortality from sudden cardiac death and pump failure. Left ventricular ejection fraction has conventionally been used as a risk marker for sudden cardiac death, but has performed poorly in trials. There have been significant advances in the areas of cardiac magnetic resonance imaging and genetics, which are able to provide useful rick prediction in DCM. Biomarkers and cardiopulmonary exercise testing are well validated in the prediction of risk in heart failure; however, they have been tested less specifically in the DCM setting. This review will discuss these methods with a view toward multiparametric risk assessment in DCM with the hope of creating parametric risk models to predict sudden cardiac death and pump failure in the DCM population.     

Diffusion Tensor Cardiovascular Magnetic Resonance Imaging: A Clinical Perspective

Imaging the heart is central to cardiac phenotyping, but in clinical practice, this has been restricted to macroscopic interrogation. Diffusion tensor cardiovascular magnetic resonance (DT-CMR) is a novel, noninvasive technique that is beginning to unlock details of this microstructure in humans in vivo. DT-CMR demonstrates the helical cardiomyocyte arrangement that drives rotation and torsion. Sheetlets (functional units of cardiomyocytes, separated by shear layers) have been shown to reorientate between diastole and systole, revealing how microstructural function facilitates cardiac thickening. Measures of tissue diffusion can also be made: fractional anisotropy (a measure of myocyte organization) and mean diffusivity (a measure of myocyte packing). Abnormal myocyte orientation and sheetlet function has been demonstrated in congenital heart disease, cardiomyopathy, and after myocardial infarction. It is too early to predict the clinical importance of DT-CMR, but such unique in vivo information will likely prove valuable in early diagnosis and risk prediction of cardiac dysfunction and arrhythmias.     

Cost-Effectiveness Analysis of Stress Cardiovascular Magnetic Resonance Imaging for Stable Chest Pain Syndromes

ObjectivesThe 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.BackgroundStress 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.MethodsA 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%.ResultsUsing 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.ConclusionsPrior 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     

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.     

Left Atrial Strain Has Superior Prognostic Value to Ventricular Function and Delayed-Enhancement in Dilated Cardiomyopathy

BackgroundThe left atrium is an early sensor of left ventricular (LV) dysfunction. Still, the prognostic value of left atrial (LA) function (strain) on cardiac magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown.ObjectivesThe goal of this study was to evaluate the prognostic value of CMR-derived LA strain in DCM.MethodsPatients with DCM from the Maastricht Cardiomyopathy Registry with available CMR imaging were included. The primary endpoint was the combination of sudden or cardiac death, heart failure (HF) hospitalization, or life-threatening arrhythmias. Given the nonlinearity of continuous variables, cubic spline analysis was performed to dichotomize.ResultsA total of 488 patients with DCM were included (median age: 54 [IQR: 46-62] years; 61% male). Seventy patients (14%) reached the primary endpoint (median follow-up: 6 [IQR: 4-9] years). Age, New York Heart Association (NYHA) functional class >II, presence of late gadolinium enhancement (LGE), LV ejection fraction (LVEF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.02). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, NYHA functional class >II, and LGE remained associated in the multivariable model (LA conduit strain HR: 3.65 [95% CI: 2.01-6.64; P < 0.001]; NYHA functional class >II HR: 1.81 [95% CI: 1.05-3.12; P = 0.033]; and LGE HR: 2.33 [95% CI: 1.42-3.85; P < 0.001]), whereas age, N-terminal pro–B-type natriuretic peptide, LVEF, left atrial ejection fraction, LAVI, and LV GLS were not. Adding LA conduit strain to other independent predictors (NYHA functional class and LGE) significantly improved the calibration, accuracy, and reclassification of the prediction model (P < 0.05).ConclusionsLA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV GLS, LVEF, and LAVI and incremental to LGE. Including LA conduit strain in DCM patient management should be considered to improve risk stratification.     

Prevalence and Prognostic Significance of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction

BackgroundThe pathophysiological and clinical significance of microvascular dysfunction (MVD) in patients with heart failure with preserved ejection fraction (HFpEF) remains uncertain.ObjectivesThe aim of this study was to use cardiovascular magnetic resonance to: 1) quantify coronary microvascular function; 2) examine the relationship between perfusion and fibrosis; and 3) evaluate the impact of MVD and fibrosis on long-term clinical outcomes.MethodsIn a prospective, observational study, patients with HFpEF and control subjects underwent multiparametric cardiovascular magnetic resonance (comprising assessment of left ventricular volumetry, perfusion, and fibrosis [focal by late gadolinium enhancement and diffuse by extracellular volume]). The primary endpoint was the composite of death or hospitalization with heart failure.ResultsOne hundred and one patients with HFpEF (mean age 73 ± 9 years, mean ejection fraction 56% ± 5%) and 43 control subjects (mean age 73 ± 5 years, mean ejection fraction 58% ± 5%) were studied. Myocardial perfusion reserve (MPR) was lower in patients with HFpEF versus control subjects (1.74 ± 0.76 vs 2.22 ± 0.76; P = 0.001). MVD (defined as MPR <2.0) was present in 70% of patients with HFpEF (vs 48% of control subjects; P = 0.014). There was no significant linear correlation between MPR and diffuse fibrosis (r = ?0.10; P = 0.473) and no difference in MPR between those with and without focal fibrosis (mean difference ?0.03; 95% CI: ?0.37 to 0.30). In the HFpEF group, during median follow-up of 3.1 years, there were 45 composite events. MPR was independently predictive of clinical outcome following adjustment for clinical, blood, and imaging parameters (1 SD increase: HR: 0.673 [95% CI: 0.463 to 0.978; P = 0.038]; HR: 0.694 [95% CI: 0.491 to 0.982; P = 0.039]; and HR: 0.690 [95% CI: 0.489 to 0.973; P = 0.034], respectively).ConclusionsMVD is highly prevalent among patients with HFpEF and is an independent predictor of prognosis. The lack of correlation between MVD and fibrosis may challenge the assertion of a direct causal link between these entities. (Developing Imaging and Plasma Biomarkers in Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593)     

Cardiovascular Magnetic Resonance for Patients With COVID-19

COVID-19 is associated with myocardial injury caused by ischemia, inflammation, or myocarditis. Cardiovascular magnetic resonance (CMR) is the noninvasive reference standard for cardiac function, structure, and tissue composition. CMR is a potentially valuable diagnostic tool in patients with COVID-19 presenting with myocardial injury and evidence of cardiac dysfunction. Although COVID-19–related myocarditis is likely infrequent, COVID-19–related cardiovascular histopathology findings have been reported in up to 48% of patients, raising the concern for long-term myocardial injury. Studies to date report CMR abnormalities in 26% to 60% of hospitalized patients who have recovered from COVID-19, including functional impairment, myocardial tissue abnormalities, late gadolinium enhancement, or pericardial abnormalities. In athletes post–COVID-19, CMR has detected myocarditis-like abnormalities. In children, multisystem inflammatory syndrome may occur 2 to 6 weeks after infection; associated myocarditis and coronary artery aneurysms are evaluable by CMR. At this time, our understanding of COVID-19–related cardiovascular involvement is incomplete, and multiple studies are planned to evaluate patients with COVID-19 using CMR. In this review, we summarize existing studies of CMR for patients with COVID-19 and present ongoing research. We also provide recommendations for clinical use of CMR for patients with acute symptoms or who are recovering from COVID-19.     

Multiparametric Cardiovascular Magnetic Resonance Approach in Diagnosing,Monitoring, and Prognostication of Myocarditis

Myocarditis represents the entity of an inflamed myocardium and is a diagnostic challenge caused by its heterogeneous presentation. Contemporary noninvasive evaluation of patients with clinically suspected myocarditis using cardiac magnetic resonance (CMR) includes dimensions and function of the heart chambers, conventional T2-weighted imaging, late gadolinium enhancement, novel T1 and T2 mapping, and extracellular volume fraction calculation. CMR feature-tracking, texture analysis, and artificial intelligence emerge as potential modern techniques to further improve diagnosis and prognostication in this clinical setting. This review describes the evidence surrounding different CMR methods and image postprocessing methods and highlights their values for clinical decision making, monitoring, and risk stratification across stages of this condition.     

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance

ObjectivesThis study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.BackgroundExperimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.MethodsThe study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.ResultsMedian plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m² vs. 82 ± 15 ml/m²; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.ConclusionsOnly primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).