SCMR expert consensus statement for cardiovascular magnetic resonance of patients with a cardiac implantable electronic device.

Cardiovascular magnetic resonance (CMR) is a proven imaging modality for informing diagnosis and prognosis, guiding therapeutic decisions, and risk stratifying surgical intervention. Patients with a cardiac implantable electronic device (CIED) would be expected to derive particular benefit from CMR given high prevalence of cardiomyopathy and arrhythmia. While several guidelines have been published over the last 16 years, it is important to recognize that both the CIED and CMR technologies, as well as our knowledge in MR safety, have evolved rapidly during that period. Given increasing utilization of CIED over the past decades, there is an unmet need to establish a consensus statement that integrates latest evidence concerning MR safety and CIED and CMR technologies. While experienced centers currently perform CMR in CIED patients, broad availability of CMR in this population is lacking, partially due to limited availability of resources for programming devices and appropriate monitoring, but also related to knowledge gaps regarding the risk-benefit ratio of CMR in this growing population. To address the knowledge gaps, this SCMR Expert Consensus Statement integrates consensus guidelines, primary data, and opinions from experts across disparate fields towards the shared goal of informing evidenced-based decision-making regarding the risk-benefit ratio of CMR for patients with CIEDs.

Risk stratification in patients with structurally normal hearts: Does fibrosis type matter?

OBJECTIVES: The study sought to assess the prognostic significance of nonischemic myocardial fibrosis (MF) on cardiovascular magnetic resonance (CMR)-both macroscopic MF assessed by late gadolinium enhancement (LGE) and diffuse microscopic MF quantified by extracellular volume fraction (ECV)-in patients with structurally normal hearts. BACKGROUND: The clinical relevance of tissue abnormalities identified by CMR in patients with structurally normal hearts remains unclear. METHODS: Consecutive patients undergoing CMR were screened for inclusion to identify those with LGE imaging and structurally normal hearts. ECV was calculated in patients with available T1 mapping. The associations between myocardial fibrosis and the outcomes of all-cause mortality, new-onset heart failure [HF], and an arrhythmic outcome were evaluated. RESULTS: In total 525 patients (mean age 43.1±14.2 years; 30.5% males) were included. Over a median follow-up of 5.8 years, 13 (2.5%) patients died and 18 (3.4%) developed new-onset HF. Nonischemic midwall /subepicardial LGE was present in 278 (52.9%) patients; isolated RV insertion fibrosis was present in 80 (15.2%) patients. In 276 patients with available T1 mapping, the mean ECV was 25.5 ± 4.4%. There was no significant association between LGE and all-cause mortality (HR: 1.36, CI: 0.42-4.42, p = 0.61), or new-onset HF (HR: 0.64, CI: 0.25-1.61, p = 0.34). ECV (per 1% increase) correlated with all-cause mortality (HR: 1.19, CI: 1.04-1.36, p = 0.009), but not with new-onset HF (HR: 0.97, CI: 0.86-1.10, p = 0.66). There was no significant association between arrhythmic outcomes and LGE (p = 0.60) or ECV (p = 0.49). In a multivariable model after adjusting for covariates, ECV remained significantly associated with all-cause mortality (HR per 1% increase in ECV: 1.26, CI: 1.06-1.50, p = 0.009). CONCLUSION: Nonischemic LGE in patients with structurally normal hearts is common and does not appear to be associated with adverse outcomes, whereas elevated ECV is associated with all-cause mortality and may be an important risk stratification tool.

Preservation of Circumferential and Radial Left Ventricular Function as a Mitigating Mechanism for Impaired Longitudinal Strain in Early Cardiac Amyloidosis.

BACKGROUND: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden. METHODS: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CAHFpEF, CAHFrEF) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CAHFpEF and CAHFrEF and between ECV quartiles. RESULTS: While echocardiography-derived GLS was impaired in both CAHFpEF (-13.4% ± 3.1%, P < .003) and CAHFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CAHFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CAHFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CAHFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles. CONCLUSIONS: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective.

Parametric mapping by cardiovascular magnetic resonance imaging in sudden cardiac arrest survivors.

Etiology of sudden cardiac arrest (SCA) is identified in less than 30% of survivors without coronary artery disease. We sought to assess the diagnostic role of myocardial parametric mapping using cardiovascular magnetic resonance (CMR) in identifying SCA etiology. Consecutive SCA survivors undergoing CMR with myocardial parametric mapping were included in the study. The determination if CMR was decisive or contributory in identifying SCA etiology was made if the diagnosis was unclear prior to CMR, and the discharge diagnosis was consistent with the CMR result. Parametric mapping was considered essential for establishing probable SCA etiology by CMR if the SCA cause could not have been determined without its utilization. If the CMR diagnosis could have been potentially based on the combination of cine and LGE imaging, parametric mapping was considered contributory. Of the 35 patients (mean age 46.9 ± 14.1 years; 57% males) included, SCA diagnosis was based on CMR in 23 (66%) patients. Of those, parametric mapping was essential for the diagnosis of myocarditis and tako-tsubo cardiomyopathy (11/48%) and contributed to the diagnosis in 10 (43%) additional cases. Inclusion of quantitative T1 and T2 parametric mapping in the SCA CMR protocol has the potential to increase diagnostic yield of CMR and further specify SCA etiology, especially myocarditis.

Non-invasive diagnosis of transthyretin cardiac amyloidosis utilizing typical late gadolinium enhancement pattern on cardiac magnetic resonance and light chains.

AIMS: While cardiac magnetic resonance (CMR) is often obtained early in the evaluation of suspected cardiac amyloidosis (CA), it currently cannot be utilized to differentiate immunoglobulin (AL) and transthyretin (ATTR) CA. We aimed to determine whether a novel CMR and light-chain biomarker-based algorithm could accurately diagnose ATTR-CA. METHODS AND RESULTS: Patients with confirmed AL or ATTR-CA with typical late gadolinium enhancement (LGE) and Look-Locker pattern for CA on CMR were retrospectively identified at three academic medical centres. Comprehensive light-chain analysis including free light chains, serum, and urine electrophoresis/immunofixation was performed. The diagnostic accuracy of the typical CMR pattern for CA in combination with negative light chains for the diagnosis of ATTR-CA was determined both in the entire cohort and in the subset of patients with invasive tissue biopsy as the gold standard. A total of 147 patients (age 70 ± 11, 76% male, 51% black) were identified: 89 ATTR-CA and 58 AL-CA. Light-chain biomarkers were abnormal in 81 (55%) patients. Within the entire cohort, the sensitivity and specificity of a typical LGE and Look-Locker CMR pattern and negative light chains for ATTR-CA was 73 and 98%, respectively. Within the subset with biopsy-confirmed subtype, the CMR and light-chain algorithm were 69% sensitive and 98% specific. CONCLUSION: The combination of a typical LGE and Look-Locker pattern on CMR with negative light chains is highly specific for ATTR-CA. The successful non-invasive diagnosis of ATTR-CA using CMR has the potential to reduce diagnostic and therapeutic delays and healthcare costs for many patients.

Impairment in quantitative microvascular function in non-ischemic cardiomyopathy as demonstrated using cardiovascular magnetic resonance.

BACKGROUND: Microvascular dysfunction (MVD) is present in various cardiovascular diseases and portends worse outcomes. We assessed the prevalence of MVD in patients with non-ischemic cardiomyopathy (NICM) as compared to subjects with preserved ejection fraction (EF) using stress cardiovascular magnetic resonance (CMR). METHODS: We retrospectively studied consecutive patients with NICM and 58 subjects with preserved left ventricular (LV) EF who underwent stress CMR between 2011-2016. MVD was defined visually as presence of a subendocardial perfusion defect and semiquantitatively by myocardial perfusion reserve index (MPRI<1.51). MPRI was compared between groups using univariate analysis and multivariable linear regression. RESULTS: In total, 41 patients with NICM (mean age 51 ± 14, 59% male) and 58 subjects with preserved LVEF (mean age 51 ± 13, 31% male) were identified. In the NICM group, MVD was present in 23 (56%) and 11 (27%) by semiquantitative and visual evaluation respectively. Compared to those with preserved LVEF, NICM patients had lower rest slope (3.9 vs 4.9, p = 0.05) and stress perfusion slope (8.8 vs 11.7, p<0.001), and MPRI (1.41 vs 1.74, p = 0.02). MPRI remained associated with NICM after controlling for age, gender, hypertension, ethnicity, diabetes, and late gadolinium enhancement (log MPR, ß coefficient = -0.19, p = 0.007). CONCLUSIONS: MVD-as assessed using CMR-is highly prevalent in NICM as compared to subjects with preserved LVEF even after controlling for covariates. Semiquantitative is able to detect a greater number of incidences of MVD compared to visual methods alone. Further studies are needed to determine whether treatment of MVD is beneficial in NICM.

T2 mapping in myocardial disease: a comprehensive review.

Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for myocardial tissue characterization. Elevated transverse relaxation time (T2) is specific for increased myocardial water content, increased free water, and is used as an index of myocardial edema. The strengths of quantitative T2 mapping lie in the accurate characterization of myocardial edema, and the early detection of reversible myocardial disease without the use of contrast agents or ionizing radiation. Quantitative T2 mapping overcomes the limitations of T2-weighted imaging for reliable assessment of diffuse myocardial edema and can be used to diagnose, stage, and monitor myocardial injury. Strong evidence supports the clinical use of T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy. Accumulating data support the utility of T2 mapping for the assessment of other cardiomyopathies, rheumatologic conditions with cardiac involvement, and monitoring for cancer therapy-related cardiac injury. Importantly, elevated T2 relaxation time may be the first sign of myocardial injury in many diseases and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. This comprehensive review discusses the technical considerations and clinical roles of myocardial T2 mapping with an emphasis on expanding the impact of this unique, noninvasive tissue parameter.

Validating an Idiopathic Dilated Cardiomyopathy Diagnosis Using Cardiovascular Magnetic Resonance: The Dilated Cardiomyopathy Precision Medicine Study.

BACKGROUND: Coronary angiography to identify coronary artery disease has been foundational to distinguish the cause of dilated cardiomyopathy (DCM), including the assignment of idiopathic or ischemic cardiomyopathy. Late gadolinium enhancement (LGE) with cardiovascular magnetic resonance (CMR) has emerged as an approach to identify myocardial scar and identify etiology. METHODS: The DCM Precision Medicine Study included patients with left ventricular dilation and dysfunction attributed to idiopathic DCM, after expert clinical review excluded ischemic or other cardiomyopathies. Ischemic cardiomyopathy was defined as coronary artery disease with >50% narrowing at angiography of ≥1 epicardial coronary artery. CMR was not required for study inclusion, but in a post hoc analysis of available CMR reports, patterns of LGE were classified as (1) no LGE, (2) ischemic-pattern LGE: subendocardial/transmural, (3) nonischemic LGE: midmyocardial/epicardial. RESULTS: Of 1204 idiopathic DCM patients evaluated, 396 (32.9%) had a prior CMR study; of these, 327 (82.6% of 396) had LGE imaging (mean age 46 years; 53.2% male; 55.4% White); 178 of the 327 (54.4%) exhibited LGE, and 156 of the 178 had LGE consistent with idiopathic DCM. The remaining 22 had transmural or subendocardial LGE. Of these 22, coronary angiography was normal (13), showed luminal irregularities (3), a distant thrombus (1), coronary artery disease with <50% coronary artery narrowing (1), or was not available (4). CONCLUSIONS: Of 327 probands enrolled in the DCM Precision Medicine Study cohort who had LGE-CMR data available, an ischemic-pattern of LGE was identified in 22 (6.7%), all of whom had idiopathic DCM as adjudicated by expert clinical review. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Prevalence and haemodynamic profiles of pulmonary hypertension in cardiac amyloidosis.

OBJECTIVES: While cardiac amyloidosis (CA) classically involves the left ventricle (LV), less is known about its impact on the right ventricle (RV) and pulmonary vasculature. We performed a retrospective analysis to identify the prevalence and types of pulmonary hypertension (PH) profiles in CA and to determine haemodynamic and cardiovascular magnetic resonance (CMR) predictors of major adverse cardiovascular events (MACE). METHODS: Patients with CA who underwent CMR and right heart catheterisation (RHC) within 1 year between 2010 and 2019 were included. Patients were assigned the following haemodynamic profiles based on RHC: no PH, precapillary PH, isolated postcapillary PH (IPCPH), or combined precapillary and postcapillary PH (CPCPH). The relationship between PH profile and MACE (death, heart failure hospitalisation) was assessed using survival analysis. CMR and RV parameters were correlated with MACE using Cox-regression analysis. RESULTS: A total of 52 patients were included (age 69±9 years, 85% men). RHC was performed during biopsy in 44 (85%) and for clinical indications in 8 (15%) patients. Rates of no PH, precapillary PH, IPCPH and CPCPH were 5 (10%), 3 (6%), 29 (55%) and 15 (29%), respectively. Haemodynamic PH profile did not correlate with risk of death (p=0.98) or MACE (p=0.67). Transpulmonary gradient (TPG) (HR 0.88, CI 0.80 to 0.97), RV, (HR 0.95, CI 0.92 to 0.98) and LV ejection fraction (HR 0.95, CI 0.92 to 0.98) were significantly associated with MACE. CONCLUSIONS: PH is highly prevalent in CA, even at the time of diagnosis. While IPCPH was most common, CPCPH is not infrequent. TPG and RV ejection fraction (RVEF) are prognostic markers in this population.

Atrial function and geometry differences in transthyretin versus immunoglobulin light chain amyloidosis: a cardiac magnetic resonance study.

To determine the differences in left atrial (LA) function and geometry assessed by cardiac magnetic resonance (CMR) between transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis (CA). We performed a retrospective analysis of 54 consecutive patients (68.5% male, mean age 67 ± 11 years) with confirmed CA (24 ATTR, 30 AL) who underwent comprehensive CMR examinations. LA structural and functional assessment including LA volume, LA sphericity index, and LA strain parameters were compared between both subtypes. In addition, 15 age-matched controls were compared to all groups. Patients with ATTR-CA were older (73 ± 9 vs. 62 ± 10 years, p < 0.001) and more likely to be male (83.3% vs. 56.7%, p = 0.036) when compared to AL-CA. No significant difference existed in LA maximum volume and LA sphericity index between ATTR-CA and AL-CA. LA minimum volumes were larger in ATTR-CA when compared with AL-CA. There was a significant difference in LA function with worse strain values in ATTR vs AL: left atrial reservoir [7.4 (6.3-12.8) in ATTR vs. 13.8 (6.90-24.8) in AL, p = 0.017] and booster strains [3.6 (2.6-5.5) in ATTR vs. 5.2 (3.6-12.1) in AL, p = 0.039]. After adjusting for age, LA reservoir remained significantly lower in ATTR-CA compared to AL-CA (p = 0.03), but not LA booster (p = 0.16). We demonstrate novel differences in LA function between ATTR-CA and AL-CA despite similar LA geometry. Our findings of more impaired LA function in ATTR may offer insight into higher AF burden in these patients.

Inherited Variants in SCARB1 Cause Severe Early-Onset Coronary Artery Disease.

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Indexed left ventricular mass to QRS voltage ratio is associated with heart failure hospitalizations in patients with cardiac amyloidosis.

In cardiac amyloidosis (CA), amyloid infiltration results in increased left ventricular (LV) mass disproportionate to electrocardiographic (EKG) voltage. We assessed the relationship between LV mass-voltage ratio with subsequent heart failure hospitalization (HHF) and mortality in CA. Patients with confirmed CA and comprehensive cardiovascular magnetic resonance (CMR) and EKG exams were included. CMR-derived LV mass was indexed to body surface area. EKG voltage was assessed using Sokolow, Cornell, and Limb-voltage criteria. The optimal LV mass-voltage ratio for predicting outcomes was determined using receiver operating characteristic curve analysis. The relationship between LV mass-voltage ratio and HHF was assessed using Cox proportional hazards analysis adjusting for significant covariates. A total of 85 patients (mean 69 ± 11 years, 22% female) were included, 42 with transthyretin and 43 with light chain CA. At a median of 3.4-year follow-up, 49% of patients experienced HHF and 60% had died. In unadjusted analysis, Cornell LV mass-voltage ratio was significantly associated with HHF (HR, 1.05; 95% CI 1.02-1.09, p = 0.001) and mortality (HR, 1.05; 95% CI 1.02-1.07, p = 0.001). Using ROC curve analysis, the optimal cutoff value for Cornell LV mass-voltage ratio to predict HHF was 6.7 gm/m2/mV. After adjusting for age, NYHA class, BNP, ECV, and LVEF, a Cornell LV mass-voltage ratio > 6.7 gm/m2/mV was significantly associated with HHF (HR 2.25, 95% CI 1.09-4.61; p = 0.03) but not mortality. Indexed LV mass-voltage ratio is associated with subsequent HHF and may be a useful prognostic marker in cardiac amyloidosis.

T-wave and its association with myocardial fibrosis on cardiovascular magnetic resonance examination.

BACKGROUND: Risk stratification in non-ischemic myocardial disease poses a challenge. While cardiovascular magnetic resonance (CMR) is a comprehensive tool, the electrocardiogram (ECG) provides quick impactful clinical information. Studying the relationships between CMR and ECG can provide much-needed risk stratification. We evaluated the electrocardiographic signature of myocardial fibrosis defined as presence of late gadolinium enhancement (LGE) or extracellular volume fraction (ECV) ≥29%. METHODS: We evaluated 240 consecutive patients (51% female, 47.1 ± 16.6 years) referred for a clinical CMR who underwent 12-lead ECGs within 90 days. ECG parameters studied to determine association with myocardial fibrosis included heart rate, QRS amplitude/duration, T-wave amplitude, corrected QT and QT peak, and Tpeak-Tend. Abnormal T-wave was defined as low T-wave amplitude ≤200 µV or a negative T wave, both in leads II and V5. RESULTS: Of the 147 (61.3%) patients with myocardial fibrosis, 67 (28.2%) had ECV ≥ 29%, and 132 (54.6%) had non-ischemic LGE. An abnormal T-wave was more prevalent in patients with versus without myocardial fibrosis (66% versus 42%, p < .001). Multivariable analysis demonstrated that abnormal T-wave (OR 1.95, 95% CI 1.09-3.49, p = .03) was associated with myocardial fibrosis (ECV ≥ 29% or LGE) after adjustment for clinical covariates (age, gender, history of hypertension, and heart failure). Dynamic nomogram for predicting myocardial fibrosis using clinical parameters and the T-wave was developed: https://normogram.shinyapps.io/CMR_Fibrosis/. CONCLUSION: Low T-wave amplitude ≤ 200 µV or negative T-waves are independently associated with myocardial fibrosis. Prospective evaluation of T-wave amplitude may identify patients with a high probability of myocardial fibrosis and guide further indication for CMR.