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Background: Challenges remain in our understanding of implications of right ventricle (RV) dysfunction in heart failure. Cardiac magnetic resonance imaging (CMR) is the reference standard for RV quantification, but has seldomly been studied for this purpose in cardiomyopathy patients. We evaluated the predictors and outcomes of reduced CMR-derived right ventricle function in non-ischemic cardiomyopathy (NICM). Methods: Adult NICM patients undergoing CMR quantifying the RV during 2002-2017 were retrospectively studied. Multivariable linear and Cox proportional hazards regression were used to identify factors associated with reduced RV ejection fraction (RVEF) and adverse outcomes. The primary endpoint was all-cause mortality, heart transplant and/or left ventricular assist device implantation. Results: Amongst 624 NICM patients, mean age was 52.7±15.9 years, 253 (40.5%) were female, and RVEF was 43±13%. Factors independently associated with RVEF (beta-coefficients, P-values) were male (-3.26, P Conclusion: Reduced RVEF was prevalent in NICM patients, and was independently associated with worse prognosis in NICM. Important clinical and CMR factors associated with lower RVEF were identified, as well as the optimal prognostic RVEF thresholds.

Background: The impact of cardiomyopathy on left atrial function is currently unclear. The aim of this study was to assess the predictors of left atrial function in patients with non-ischemic dilated cardiomyopathy (NICM) utilizing cardiovascular magnetic resonance (CMR) assessment. Methods: We evaluated 251 NICM patients who underwent CMR in our study, between 12/2008 - 1/2014. LA volumes were measured by the modified biplane method from 2- and 4-chamber long axis views at end-systole and end-diastole. Left atrial ejection fraction (LAEF) was calculated. Multivariable linear regression was performed to determine significant covariate associations with LA EF. Results: We studied 251consecutive patients (61 % male), mean age of 52.5 ± 15.5 years . The results of the multivariable linear regression are provided in Figure 1. Younger age, female sex, and less myocardial fibrosis were significantly associated with higher LAEF (p=0.008, p= 0.004, and p= 0.031, respectively). Additionally, increasing left ventricular end diastolic volume index (LVEDVi) and left ventricular ejection fraction (LVEF) was significantly associated with increasing LAEF (both with a significance of p Conclusions: In patients with NICM, age, sex, LVEDVi, LVEF, myocardial fibrosis, and LAVi were independently associated with LAEF. Keywords: Nonischemic cardiomyopathy, left atrial ejection fraction, left atrial function, cardiovascular magnetic resonance

Background: Left atrial (LA) size has been shown to be predictive of adverse outcomes in patients with various cardiac conditions. However, the significance of left atrial function (LAF) is not clearly defined in patients with advanced ischemic cardiomyopathy (ICM). We assess the effect of cardiac magnetic resonance imaging (CMR) based LA ejection fraction (LAEF), LA volume index (LAVi) and total LA strain(Las) on outcomes in patients with ICM. Methods: Patients with ICM, who underwent cardiac magnetic resonance (CMR) between January 2002 and January 2017, were included in our study. Clinical characteristics and CMR parameters were collected and analyzed. Maximum and minimum left atrial volume (LAV) and LAEF were calculated using the biplane area-length method. Multi-variable Cox proportional hazards models were then built to test whether LAEF, LAs, and LAVi predict all-cause mortality or time to transplant. The proportionality assumption test and supremum test for functional form were used to verify the model. Results: LA functional data on 656 patients were analyzed. Patients were followed for a median of 1900 days (5.2 years). There were 336 deaths and 17 transplants. LAEF and Las were significant predictors of outcome: HR=0.98, 95% CI [0.97, 0.99], p Conclusion: Left atrial function is a more powerful predictor of adverse outcome than left atrial size and ischemic mitral regurgitation. Further studies are needed to assess impact of treatment on LA function.

Background: Cardiac magnetic resonance imaging (CMR) is central to the evaluation of cardiac amyloidosis (CA). Native T1 mapping and extracellular volume (ECV) are novel CMR techniques with evolving utility in cardiovascular diseases including CA. This study aims to meta-analyze the diagnostic and prognostic data of native T1 mapping and extracellular volume (ECV) techniques for assessing CA. Methods: Pubmed, Cochrane and Embase were searched until 31 March 2020 for studies reporting the accuracy of native T1 mapping and ECV for diagnosing CA or predicting all-cause mortality. Area under the receiver-operative characteristics curves (AUC) and hazards ratios (HR) with 95% confidence intervals (95% CI) respectively were pooled using random-effects models and Open-Meta(Analyst) software. Results: Amongst 459 records obtained from the literature search, 41 full-text articles were assessed and 10 studies were eligible totalling 2364 subjects and 1528 patients with confirmed CA. Pooled AUCs (95% CI) for diagnosing CA were 0.924 (0.889-0.959) for native T1 mapping and 0.963 (0.925-1.000) for ECV (Figure panel A/B). Both techniques had similarly high detection rates for AL- and ATTR CA (pooled AUCs of 0.935 and 0.916 for native T1 mapping and 0.980 and 0.952 for ECV). Pooled HRs (95% CI) for predicting all-cause mortality were 1.15 (1.08-1.22) for native T1 mapping as a continuous parameter, 1.19 (1.01-1.40) for ECV as a continuous parameter (Figure panel C/D), and 4.93 (2.64-9.20) for ECV as a binary threshold. Conclusion: Both native T1 mapping and ECV had high diagnostic performance for CA and predicted all-cause mortality after CA. These CMR techniques can play important roles in the multi-modality imaging assessment of CA, including when contrast administration is contraindicated.

Background: Functional mitral regurgitation (MR) grading by echocardiography is often challenging, and cardiac magnetic resonance (CMR) may provide more accurate and reproducible assessment, however optimal CMR thresholds have not been established. We aimed to determine clinically significant thresholds of MR-volume and MR-fraction by CMR in patients with non-ischemic cardiomyopathy (NICM). Methods: All patients having CMR with confirmed NICM between 2001/4/1-2019/3/31 were retrospectively studied. Time to death, heart transplant and/or left ventricular assist device is the primary endpoint, and receiver-operative (ROC) characteristics analyses were used to identify significant cut-points for MR-volume and MR-fraction. Results: Mean MR-volume was 11±12% and MR-fraction 14±13% in 840 NICM patients. C-statistics for the primary endpoint (141 events) were MR-volume 0.629 (95%CI: 0.577-0.691) and MR-fraction 0.594 (95%CI 0.542-0.647). Thresholds of MR-volume≥10mL and MR-fraction≥15% had the highest products of sensitivities and specificities (57.4%, 56.8%; and 54.6%, 63.4% respectively) reflecting elevated risk. MR-volume≥35mL and MR-fraction≥40% were associated the best combination of positive and negative predictive values (40.1%, 84.2%; and 38.4%, 84.6% respectively) representing severe risk. The figure illustrates Kaplan-Meier curves of the primary endpoint, categorized into three subgroups based on aforementioned MR-volume and MR-fraction thresholds. Conclusion: Adverse prognosis are observed when MR-volume≥10mL or MR-fraction≥15%, with increasing risk of adverse outcomes as functional MR severity increased in NICM. The proposed MR thresholds from this study for elevated and severe risk are lower than current valvular regurgitation guidelines, suggesting the need for separate classification schema for functional MR.

Background: Functional mitral regurgitation (MR) is associated with poor outcomes and the prognostic role of cardiac magnetic resonance imaging (CMR) quantification of secondary MR has rarely been studied. We evaluated the associations between CMR-derived MR-fraction and adverse outcomes in non-ischemic cardiomyopathy (NICM) patients. Methods: We retrospectively studied 840 consecutive NICM patients undergoing CMR during 2001/4/1-2019/3/31. Multivariable Cox proportional hazards regression was performed for MR-fraction and two composite endpoints: primary (time to death, heart transplant and/or left ventricular assist device) and secondary (primary endpoint plus heart failure hospitalizations). Results: The cohort had mean age of 53.0±15.9 years, 319 (38.0) were female, and mean MR-fraction of 14±13% by CMR. There were 141 (16.8%) primary and 223 (26.5%) secondary endpoints over a mean follow-up of 3.6±3.0 years. Multivariable analyses results are shown in the Table. MR-fraction was independently associated with the primary and secondary endpoints with hazards ratios of 1.13 (95%CI 1.07-1.20) and 1.13 (95%CI 1.07-1.19) respectively per 5% increase in MR-fraction. MR-fraction provided stronger prognostic power compared to late gadolinium enhancement (LGE) in both models. Older age and diabetes were independently associated with both composite endpoints, while lower LVEF was independently associated with the secondary endpoint only. Conclusion: CMR quantification of functional MR is a powerful predictor of adverse outcomes and demonstrated stronger associations with poor prognosis compared to LGE and left ventricular remodeling in a large cohort of patients with NICM.

Background: Decreased right ventricular (RV) ejection fraction (RVEF) portends poor prognosis in patients with ischemic cardiomyopathy, and previous studies have suggested an association between mitral regurgitation (MR) and RVEF. We sought to evaluate this association and whether mitral valve repair or replacement affects the relationship between RV function and mortality. Methods: We included 588 patients (mean age, 63±11 years; 75% male) with ischemic cardiomyopathy who underwent cardiac magnetic resonance imaging between 2002 and 2008. Baseline characteristics, left ventricular ejection fraction, MR severity, treatment modality, scar burden, and RVEF were assessed. Multivariable linear regression and Cox proportional hazards models were used to assess the association between MR and RVEF and between RVEF and mortality, respectively. Results: After adjustment for age, sex, left ventricular ejection fraction, right bundle-branch block, and RV scar, MR severity was found to be associated independently with RVEF. There were a total of 240 deaths during a median follow-up time of 5.7 years. After multivariable adjustment, every 10% decrease in RVEF was associated with a 17% increased risk of death ( P =0.008). Although decreasing RVEF was associated with a poor prognosis in the nonrepair group (hazard ratio, 1.28; 95% confidence interval, 1.12–1.47; P P for interaction=0.046). ConclusionS: MR severity was found to be an independent predictor of RVEF, as were right bundle-branch block, left ventricular ejection fraction, and the presence of RV scar. Decreasing RVEF is associated with increased mortality in patients with ischemic cardiomyopathy; however, this association may be mitigated in patients who undergo mitral valve repair or replacement.

Introduction: Reversible constrictive pericarditis (CP) has been described with resolution of constriction after treatment with anti-inflammatory medications. In our study, we assessed the improvement of biventricular myocardial strain in CP patients treated medically compared to CP patients who underwent pericardiectomy. Methods and Results: We compared myocardial mechanics by 2-dimensional speckle tracking in 16 CP patients (age: 56±13; 75% males) who received anti-inflammatory medications to an age and sex matched CP group (age: 57±12; 75% males) who underwent pericardiectomy. At baseline, both treatment groups had depressed left ventricular (LV) anterolateral wall strain (LWS) and right ventricular (RV) free wall longitudinal systolic strain (FWS) but preserved LV septal wall systolic strain (SWS). In a median follow-up of 150 days the medically treated patients showed improvement of the depressed LVLWS/LVSWS (Pre: 0.61±0.17, Post: 0.89±0.21;P Conclusions: Biventricular myocardial strain imaging is a robust technique for assessment of response to anti-inflammatory therapy in CP patients. Medical treatment of CP leads to systolic strain improvement that is more pronounced in the LV and RV free walls, hence having similar impact on the biventricular myocardial mechanics as pericardiectomy.

Introduction: Ischemic mitral regurgitation (IMR) is associated with poor outcomes. Determining risk for the presence and progression of IMR may be critical for risk stratification. Hypothesis: We hypothesize that a multi-modality approach can evaluate the progression of IMR in patients with advanced ischemic cardiomyopathy (ICM) and create a risk model for the prediction of IMR progression. Methods: Consecutive ICM patients who underwent cardiac magnetic resonance (CMR) and echocardiograms at baseline with echocardiographic follow-up were included. CMR was used to assess global and regional left ventricular (LV) remodeling, myocardial scarring, and mitral valve geometry. The effective regurgitant orifice area (EROA) was calculated from the proximal isovelocity surface area by echocardiography. We identified the best performing model for prediction of worsening IMR based on the c-index. Results: We evaluated 693 patients (age 62±11). The following factors were independently predictive of an increased EROA at baseline (n=693): higher total scar% (p=0.002) and higher ESVi (p Conclusions: The variables which predict IMR at baseline and progression of IMR over time slightly differ. Higher total scar% and higher ESVi are independently associated with increasing IMR at baseline. However, higher EROA at baseline, lower tenting area, higher ESVi and total scar% * treatment type were associated with progression of IMR over time. The risk model of IMR progression was moderately predictive in this cohort.

Background— The value of assessment of viability as a predictor of surgical revascularization benefit in ischemic cardiomyopathy has recently been questioned in a large trial. We sought to determine whether the contribution of viability as myocardial scar burden (SB) to predict revascularization outcomes could be modulated by end-systolic volume index (ESVi). Methods and Results— Delayed hyperenhancement–MRI was obtained in 450 patients with ≥70% stenosis in ≥1 epicardial coronary artery (75% men; median age, 62.8±10.7 years; mean left ventricular ejection fraction, 23±9%; mean ESVi, 115±50 mL) from 2002 to 2006. SB was quantified as scar percentage (infarcted mass/total left ventricular mass). Subsequent surgical revascularization was performed in 245 (54%) patients and subsequent percutaneous coronary interventions were performed in 28 (6%) patients. A propensity score was developed for revascularization. Cox proportional hazards models of all-cause mortality were used for risk adjustment. Over a mean follow-up of 5.8±2.7 years, 186 (41%) deaths occurred. After adjusting for prior revascularization, sex, diabetes, age, use of cardiac resynchronization therapy, implantable cardioverter defibrillator, mitral regurgitation, and mitral valve procedures; an interaction between scar percentage and ESVi ( P =0.016) and an interaction between post-MRI revascularization and ESVi ( P =0.0017) were independently associated with mortality. ESVi demonstrated a significant interaction with revascularization and female sex, such that enhanced survival was associated with ESVi. ESVi also showed an interaction with SB; better survival was associated with lower volumes and less scar. Conclusions— ESVi and SB provide independent, incremental prognostic value in patients with severe ischemic cardiomyopathy. The risk associated with SB should not be assessed in isolation.

Background: Both renal dysfunction and severe left ventricular (LV) systolic dysfunction lead to reduced survival. Delayed hyperenhancement magnetic resonance imaging (DHE-MRI) accurately detects myocardial fibrosis (scar), seen commonly in patients with severe left ventricular (LV) dysfunction. We sought to determine the association of myocardial scar and renal dysfunction on survival in patients with severe LV dysfunction. Methods: We studied 176 consecutive patients (61 ± 13 years, 73 % men) with severe LV systolic dysfunction (mean ejection fraction (24 ± 8 %) who underwent DHE-MRI (Siemens 1.5 T scanner, Erlangen, Germany) from 2005–6. Myocardial scar was determined visually on DHE-MR images, using custom software (Siemens Research), and defined as intensity >2 standard deviation above viable myocardium. Clinical and laboratory information, along with all-cause mortality, were recorded. Glomerular filtration rate (GFR, ml/min/1.73 m 2 ) was calculated using the following formula: 186 × (serum creatinine −1.154 ) × (age −0.203 ) × 1.212 (if black) × 0.742 (if female). We divided patients into 4 groups: GFR > 60, no scar (n = 28) GFR > 60 with scar (n = 85) GFR ≤ 60, no scar (n = 9) and GFR ≤ 60 with scar (n = 53). Results: There were 24 deaths in the group and 14 patients (65 %) had myocardial scar. Mean GFR was 70 ± 29 and 62 (35 %) patients had at-least moderate renal dysfunction (GFR < 60). Frequency of myocardial scar was higher in patients with GFR ≤ 60 vs. those with GFR > 60 (92 % vs. 79 %, p = 0.02). On multiple regression (including GFR, myocardial scar, coronary artery disease, hypertension, diabetes and coronary bypass), GFR and myocardial scar were associated with mortality (both p value < 0.05, overall model p value < 0.001). There were no deaths in group 1, 7 in group 2, 3 in group 3 and 14 in group 4 (p < 0.001). One year survival was significantly worse for groups 2, 3 and 4, compared to group 1 (log rank p value < 0.001). Conclusion: Renal dysfunction is associated with a higher frequency of myocardial fibrosis in patients with severe LV dysfunction. Presence of renal dysfunction, myocardial fibrosis or both is associated with worse survival in such patients. The mechanistic association between renal dysfunction and myocardial fibrosis needs to be further defined.

Background: There is a high prevalence of myocardial fibrosis in hypertrophic cardiomyopathy (HCM) patients, despite preserved left ventricular ejection fraction (LVEF). Association of myocardial fibrosis and longitudinal strain (LS) in such patients is not well understood. Methods: We studied 46 consecutive HCM patients (mean age 43±14 years, 30 men) who had transthoracic echocardiography (TTE, GE Medical, USA) and delayed hyper-enhancement magnetic resonance imaging (DHE-MRI, Siemens 1.5 T scanner, Germany), 20 minutes after injection of 0.2 mmol/kg of Gadolinium. Speckle tracking TTE was used to assess LS in LV (segmental and global) (EchoPac, GE Medical, USA). Fibrosis was determined semi-automatically on DHE-MR images, in a 12-segment short-axis model (apex, mid and base) of LV using custom software (Siemens Research) & defined as intensity >2 standard deviation above viable myocardium. Results: Global end-systolic LS correlated with number of fibrotic segments (r = 0.50, p = 0.0004; Figure ) and total myocardial fibrosis % (r = 0.43, p = 0.001). Association of fibrosis and regional LS is shown in Table . In a multivariate analysis, predictors of lower segmental LS were presence of fibrosis and basal segment location (both p < 0.001). Conclusion: Myocardial fibrosis is associated with depressed global and regional LS in HCM patients, despite preserved global LVEF. Table