Comprehensive Phenotypic Characterization of Late Gadolinium Enhancement Predicts Sudden Cardiac Death in Coronary Artery Disease.

BACKGROUND: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD). OBJECTIVES: The authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD). METHODS: Patients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD. RESULTS: Of 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell's C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell's C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models. CONCLUSIONS: Comprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in implantable cardioverter-defibrillator (ICD) insertion guidelines. These results signify the potential for a more personalized approach to determining ICD candidacy in CAD.

Myocardial strain analysis by cardiac magnetic resonance 3D feature-tracking identifies subclinical abnormalities in patients with neuromuscular disease and no overt cardiac involvement.

AIMS: Cardiovascular magnetic resonance (CMR) is valuable for the detection of cardiac involvement in neuromuscular diseases (NMDs). We explored the value of 2D- and 3D-left ventricular (LV) myocardial strain analysis using feature-tracking (FT)-CMR to detect subclinical cardiac involvement in NMD. METHODS AND RESULTS: The study included retrospective analysis of 111 patients with NMD; mitochondrial cytopathies (n = 14), Friedreich's ataxia (FA, n = 27), myotonic dystrophy (n = 27), Becker/Duchenne's muscular dystrophy (BMD/DMD, n = 15), Duchenne's carriers (n = 6), or other (n = 22) and 57 age- and sex-matched healthy volunteers. Biventricular volumes, myocardial late gadolinium enhancement (LGE), and LV myocardial deformation were assessed by FT-CMR, including 2D and 3D global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and torsion. Compared with the healthy volunteers, patients with NMD had impaired 2D-GCS (P < 0.001) and 2D-GRS (in the short-axis, P < 0.001), but no significant differences in 2D-GRS long-axis (P = 0.101), 2D-GLS (P = 0.069), or torsion (P = 0.122). 3D-GRS, 3D-GCS, and 3D-GLS values were all significantly different to the control group (P < 0.0001 for all). Especially, even NMD patients without overt cardiac involvement (i.e. LV dilation/hypertrophy, reduced LVEF, or LGE presence) had significantly impaired 3D-GRS, GCS, and GLS vs. the control group (P < 0.0001). 3D-GRS and GCS values were significantly associated with the LGE presence and pattern, being most impaired in patients with transmural LGE. CONCLUSIONS: 3D-FT CMR detects subclinical cardiac muscle disease in patients with NMD even before the development of replacement fibrosis or ventricular remodelling which may be a useful imaging biomarker for early detection of cardiac involvement.

The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of etiology in dilated cardiomyopathy.

Background: Guidelines recommend genetic testing and cardiovascular magnetic resonance (CMR) for the investigation of dilated cardiomyopathy (DCM). However, the incremental value is unclear. We assessed the impact of these investigations in determining etiology. Methods: Sixty consecutive patients referred with DCM and recruited to our hospital biobank were selected. Six independent experts determined the etiology of each phenotype in a step-wise manner based on (1) routine clinical data, (2) clinical and genetic data and (3) clinical, genetic and CMR data. They indicated their confidence (1-3) in the classification and any changes to management at each step. Results: Six physicians adjudicated 60 cases. The addition of genetics and CMR resulted in 57 (15.8%) and 26 (7.2%) changes in the classification of etiology, including an increased number of genetic diagnoses and a reduction in idiopathic diagnoses. Diagnostic confidence improved at each step (p < 0.0005). The number of diagnoses made with low confidence reduced from 105 (29.2%) with routine clinical data to 71 (19.7%) following the addition of genetics and 37 (10.3%) with the addition of CMR. The addition of genetics and CMR led to 101 (28.1%) and 112 (31.1%) proposed changes to management, respectively. Interobserver variability showed moderate agreement with clinical data (κ = 0.44) which improved following the addition of genetics (κ = 0.65) and CMR (κ = 0.68). Conclusion: We demonstrate that genetics and CMR, frequently changed the classification of etiology in DCM, improved confidence and interobserver variability in determining the diagnosis and had an impact on proposed management.

Reliability of pediatric ventricular function analysis by short-axis "single-cycle-stack-advance" single-shot compressed-sensing cines in minimal breath-hold time.

OBJECTIVES: Cardiovascular magnetic resonance (CMR) cine imaging by compressed sensing (CS) is promising for patients unable to tolerate long breath-holding. However, the need for a steady-state free-precession (SSFP) preparation cardiac cycle for each slice extends the breath-hold duration (e.g. for 10 slices, 20 cardiac cycles) to an impractical length. We investigated a method reducing breath-hold duration by half and assessed its reliability for biventricular volume analysis in a pediatric population. METHODS: Fifty-five consecutive pediatric patients (median age 12 years, range 7-17) referred for assessment of congenital heart disease or cardiomyopathy were included. Conventional multiple breath-hold SSFP short-axis (SAX) stack cines served as the reference. Real-time CS SSFP cines were applied without the steady-state preparation cycle preceding each SAX cine slice, accepting the limitation of omitting late diastole. The total acquisition time was 1 RR interval/slice. Volumetric analysis was performed for conventional and "single-cycle-stack-advance" (SCSA) cine stacks. RESULTS: Bland-Altman analyses [bias (limits of agreement)] showed good agreement in left ventricular (LV) end-diastolic volume (EDV) [3.6 mL (- 5.8, 12.9)], LV end-systolic volume (ESV) [1.3 mL (- 6.0, 8.6)], LV ejection fraction (EF) [0.1% (- 4.9, 5.1)], right ventricular (RV) EDV [3.5 mL (- 3.34, 10.0)], RV ESV [- 0.23 mL (- 7.4, 6.9)], and RV EF [1.70%, (- 3.7, 7.1)] with a trend toward underestimating LV and RV EDVs with the SCSA method. Image quality was comparable for both methods (p = 0.37). CONCLUSIONS: LV and RV volumetric parameters agreed well between the SCSA and the conventional sequences. The SCSA method halves the breath-hold duration of the commercially available CS sequence and is a reliable alternative for volumetric analysis in a pediatric population. KEY POINTS: • Compressed sensing is a promising accelerated cardiovascular magnetic resonance imaging technique. • We omitted the steady-state preparation cardiac cycle preceding each cine slice in compressed sensing and achieved an acquisition speed of 1 RR interval/slice. • This modification called "single-cycle-stack-advance" enabled the acquisition of an entire short-axis cine stack in a single short breath hold. • When tested in a pediatric patient group, the left and right ventricular volumetric parameters agreed well between the "single-cycle-stack-advance" and the conventional sequences.

Diagnostic and Prognostic Value of Cardiovascular Magnetic Resonance in Neuromuscular Cardiomyopathies.

Neuromuscular diseases (NMD) encompass a broad spectrum of diseases with variable type of cardiac involvement and there is lack of clinical data on Cardiovascular Magnetic Resonance (CMR) phenotypes or even prognostic value of CMR in NMD. We explored the diagnostic and prognostic value of CMR in NMD-related cardiomyopathies. The study included retrospective analysis of a cohort of 111 patients with various forms of NMD; mitochondrial: n = 14, Friedreich's ataxia (FA): n = 27, myotonic dystrophy: n = 27, Becker/Duchenne's muscular dystrophy (BMD/DMD): n = 15, Duchenne's carriers: n = 6, other: n = 22. Biventricular volumes and function and myocardial late gadolinium enhancement (LGE) pattern and extent were assessed by CMR. Patients were followed-up for the composite clinical endpoint of death, heart failure development or need for permanent pacemaker/intracardiac defibrillator. The major NMD subtypes, i.e. FA, mitochondrial, BMD/DMD, and myotonic dystrophy had significant differences in the incidence of LGE (56%, 21%, 62% & 30% respectively, chi2 = 9.86, p = 0.042) and type of cardiomyopathy phenotype (chi2 = 13.8, p = 0.008), extent/pattern (p = 0.006) and progression rate of LGE (p = 0.006). In survival analysis the composite clinical endpoint differed significantly between NMD subtypes (p = 0.031), while the subgroup with LGE + and LVEF < 50% had the worst prognosis (Log-rank p = 0.0034). We present data from a unique cohort of NMD patients and provide evidence on the incidence, patterns, and the prognostic value of LGE in NMD-related cardiomyopathy. LGE is variably present in NMD subtypes and correlates with LV remodelling, dysfunction, and clinical outcomes in patients with NMD.

Clinical Significance of Partial Anomalous Pulmonary Venous Connections (Isolated and Atrial Septal Defect Associated) Determined by Cardiovascular Magnetic Resonance.

BACKGROUND: Partial anomalous venous connections (PAPVC) are associated with left to right shunting and right heart dilatation. Identification of PAPVC has increased with widespread use of cross-sectional imaging modalities. However, management strategies are mostly based on expert opinion given the scarcity of data from large series. We aimed to define types and significance of isolated and atrial septal defect (ASD) associated PAPVC detected by cardiovascular magnetic resonance. METHODS: We retrospectively reviewed our cardiovascular magnetic resonance database from 2002 to 2018 to identify isolated or ASD-associated PAPVC cases. RESULTS: A total of 215 patients (median age 46 years; range, 6-83) with isolated or ASD-associated PAPVC were identified among 102 135 clinical cardiovascular magnetic resonance studies. Of these, 104 were isolated and 111 were associated with an ASD. Anomalous connection of right upper pulmonary vein was the most common single venous anomaly (99/215), but in the isolated PAPVC group there were more anomalous left than right upper pulmonary veins (39 versus 34). The Qp/Qs was significantly higher for isolated anomalous single right upper pulmonary vein than left upper pulmonary vein (1.6 versus 1.4 respectively; P=0.01) as were right ventricular end-diastolic volumes (113.7±30.9 versus 90 [57-157] mL/m2, P=0.004). In the PAPVC with an ASD group, sinus venosus ASDs (82%) were associated with right-sided PAPVCs while both right and left-sided venous anomalies were seen in secundum ASDs (18%). In a substantial number of patients (30 out of 91) with sinus venosus ASDs, PAPVCs were more complex and involved more than a single anomalous right upper pulmonary vein; and in 5 patients with ASD, PAPVC was identified only after the ASD closure. CONCLUSIONS: This large series provides descriptive and hemodynamic features for isolated and ASD-associated PAPVCs. Anomalous isolated right upper pulmonary vein may cause a significant shunt (Qp/Qs >1.5). PAPVC associated with sinus venosus and secundum ASDs might be more complex than a single anomalous pulmonary vein and missed before ASD correction.

Prognostic Significance of Nonischemic Myocardial Fibrosis in Patients With Normal LV Volumes and Ejection-Fraction.

OBJECTIVES: This study aims to investigate the prognostic significance of late gadolinium enhancement (LGE) in patients without coronary artery disease and with normal range left ventricular (LV) volumes and ejection fraction. BACKGROUND: Nonischemic patterns of LGE with normal LV volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance, but their prognostic significance, and consequently management, is uncertain. METHODS: Patients with midwall/subepicardial LGE and normal LV volumes, wall thickness, and ejection fraction on cardiovascular magnetic resonance were enrolled and compared to a control group without LGE. The primary outcome was actual or aborted sudden cardiac death (SCD). RESULTS: Of 748 patients enrolled, 401 had LGE and 347 did not. The median age was 50 years (interquartile range: 38-61 years), LV ejection fraction 66% (interquartile range: 62%-70%), and 287 (38%) were women. Scan indications included chest pain (40%), palpitation (33%) and breathlessness (13%). No patient experienced SCD and only 1 LGE+ patient (0.13%) had an aborted SCD in the 11th follow-up year. Over a median of 4.3 years, 30 patients (4.0%) died. All-cause mortality was similar for LGE+/- patients (3.7% vs 4.3%; P = 0.71) and was associated with age (HR: 2.04 per 10 years; 95% CI: 1.46-2.79; P < 0.001). Twenty-one LGE+ and 4 LGE- patients had an unplanned cardiovascular hospital admission (HR: 7.22; 95% CI: 4.26-21.17; P < 0.0001). CONCLUSIONS: There was a low SCD risk during long-term follow-up in patients with LGE but otherwise normal LV volumes and ejection fraction. Mortality was driven by age and not LGE presence, location, or extent, although the latter was associated with greater cardiovascular hospitalization for suspected myocarditis and symptomatic ventricular tachycardia.

A case report of a primary cardiac lymphoma causing superior vena cava obstruction: the value of multimodality imaging in the clinical workup.

BACKGROUND: This is a case report of a primary cardiac lymphoma with an unusual clinical presentation. We hereby illustrate the characteristic features of cardiac lymphomas by multimodality imaging and particularly cardiac magnetic resonance (CMR) that can help reach a timely diagnosis non-invasively and guide treatment decisions. CASE SUMMARY: A 58-year-old woman, without significant past medical history, presented with a 3-week history of shortness of breath associated with facial and neck swelling. Transthoracic echocardiogram confirmed the presence of a cardiac mass in the right atrium. Cardiac magnetic resonance helped to characterize the mass, assess its haemodynamic significance and relation to cardiac structures, and reach a non-invasive diagnosis that was crucial for guiding treatment decisions and interventions. DISCUSSION: Cardiac masses have distinct imaging features that can help differentiate malignant from benign cardiac tumours. More specifically, primary cardiac lymphomas can be relatively easy diagnosed by CMR in most cases thanks to their characteristic imaging appearance.