Assessment of Left Ventricular Myocardial Fibrosis in Adult Patients With Ebstein Anomaly: A Retrospective Cohort Study Based on Cardiac Magnetic Resonance and Histopathological Samples.

BACKGROUND: The association between Ebstein anomaly and myocardial fibrosis, particularly in the left ventricle, has been controversial. We aimed to assess the prevalence of replacement fibrosis with a focus on the left ventricle (LV) using cardiac magnetic resonance (CMR), make a histopathological association between LV fibrosis and CMR findings, and explore whether LV fibrosis is an independent risk factor for cardiovascular disease mortality using a derived risk score. METHODS: We performed a 12-year (2009-2021) retrospective cohort of adult patients with Ebstein anomaly who underwent CMR. The CMR evaluation included a comprehensive assessment of myocardial fibrosis by late gadolinium enhancement (LGE). Four postmortem samples were obtained from our cohort and stained using Masson trichrome to characterize LV fibrosis. We used Cox-regression analysis to identify and derive a prediction score that associated LV fibrosis with cardiovascular disease mortality. RESULTS: We included 57 adults with Ebstein anomaly (52% men; median age, 29.52 [interquartile range, 21.24-39.17] years), of whom 12 died during follow-up. LGE prevalence by CMR was observed in 52.6% in any chamber; LV-LGE in 29.8%. Histopathological findings revealed a mid-wall pattern with predominantly interstitial fibrosis and minimal replacement fibrosis. LV-LGE was associated with increased risk of cardiovascular disease mortality (hazard ratio, 6.02 [95% CI, 1.22-19.91]) attributable to lateral and mid-wall LV segment involvement. Our mortality score achieved an overall good prediction capacity (R2, 0.435; C statistic, 0.93; Dxy, 0.86). CONCLUSIONS: There is a high prevalence of LV fibrosis replacement in adults with Ebstein anomaly, characterized by specific CMR and histological patterns. Furthermore, LV-LGE fibrosis is an independent predictor of cardiovascular disease mortality, which could be integrated into risk assessment in clinical management.

Aortic regurgitation: multimodal assessment of quantification and impact.

BACKGROUND: The assessment of severity of aortic regurgitation (AR) by transthoracic echocardiography (TTE) remains challenging in routine practice. Contemporary guidelines recommend cardiovascular magnetic resonance imaging (CMR) in patients with significant disease and suboptimal TTE images. The objective of this study was to assess the role of CMR in the evaluation of severity of AR and to compare both modalities in the quantification of regurgitation and left ventricular volumes. METHODS: Fifty consecutive patients who had isolated chronic AR and who underwent TTE and CMR within an interval of less than three months between May 2009 and June 2020 were included. The main indication for CMR was difficulties in quantifying AR, either because of lack of multiparametric analysis (only one method possible) or because of discrepancies in the different methods by TTE. RESULTS: In 25 patients, precise grading of AR was not possible by echocardiography. Among them, CMR finally detected seven patients with mild AR, 11 with moderate AR and seven with severe AR. For the 25 patients who had AR quantification by TTE, there was concordance between TTE and CMR in only seven patients (28%), and the AR was re-graded by CMR in 18 patients, including eight patients with severe AR by TTE and moderate AR by CMR. The concordance between TTE and CMR was weakly significant (intraclass correlation coefficient = 0.39, 95% confidence interval: 0.003-0.67, p = 0.02). There was a moderate correlation between left ventricular volumes measured by TTE and by CMR (left ventricular end-diastolic volume: r = 0.57; p = 0.01; left ventricular end-systolic volume: r = 0.47, p = 0.01) but regurgitant volumes were not correlated (r = 0.04; p = 0.8). No TTE parameter of quantification was correlated with regurgitant volume measured by CMR. CONCLUSIONS: The concordance of AR quantification by CMR and TTE was weak. CMR re-graded some patients with severe AR by TTE into moderate AR. This should motivate practitioners to systematically assess all significant AR by CMR in order to improve quantification and optimise clinical management.

Safety and feasibility of dobutamine stress cardiac magnetic resonance for cardiovascular assessment prior to renal transplantation.

AIMS: Current guidelines recommend cardiovascular risk assessment prior to renal transplantation. There is currently no evidence for the role of cardiovascular magnetic resonance (CMR) in this population, despite an established evidence base in the non-chronic kidney disease (CKD) population. Our aim is to determine the feasibility and safety of dobutamine stress CMR (DSCMR) imaging in the risk stratification of CKD patients awaiting renal transplantation. METHODS: CKD patients who were deemed at high risk for coronary artery disease (CAD) and awaiting renal transplantation underwent DSCMR. RESULTS: Forty-one patients whose median age was 56 years (range 28­73 years) underwent DSCMR. Nineteen were undergoing haemodialysis, 10 peritoneal dialysis and 12 pre-dialysis. The aetiology of the renal failure was diabetes mellitus in 29%, glomerulonephritis in 24%, hypertension in 22% and autosomal dominant polycystic kidney disease in 10%. Thirty-eight patients (93%) achieved the end point, either positive for ischaemia or negative, achieving at least 85% of age-predicted heart rate. Two of them did not achieve target heart rate and one was discontinued because of severe headache. Of the 38 patients who achieved the end point, 35 (92%) were negative for inducible wall motion abnormalities and four (10%) were positive. There were no serious adverse effects. CONCLUSION: DSCMR is a well tolerated and viable investigation for the cardiovascular risk stratification of high-risk CKD patients prior to renal transplantation. DSCMR already has an established evidence base in the non-CKD population with superiority over other noninvasive techniques. Larger studies with outcome data are now required to define its true utility in the CKD population.

Dobutamine stress MRI for the assessment of coronary artery disease: initial clinical experience in Israel.

BACKGROUND: Over the past few years dobutamine stress magnetic resonance (DSMR) has proven its efficacy as an integral part of the diagnosis of coronary artery disease (CAD). OBJECTIVES: To present the feasibility and safety of DSMR in Israel. METHODS: Thirty patients with suspected or known CAD were studied. DSMR images were acquired during short breath-holds in three short axis views and four-, two-, and three-chamber views. Patients were examined at rest and during a standard dobutamine-atropine protocol. Regional wall motion was assessed in a 16-segment model and the image quality was evaluated using a four-point scale for the visibility of the endocardial border. RESULTS: In 28 patients (93.4%) DSMR was successfully performed and completed within an average of 55 +/- 6 minutes. One patient could not be examined because of claustrophobia and another patient, who was on beta-blockers, did not reach the target heart rate. Image quality was excellent and there was no difference between the rest and stress images in short axis (3.91 +/- 0.29 vs. 3.88 +/- 0.34, P = 0.13, respectively) and long axis (3.83 +/- 0.38 vs. 3.70 +/- 0.49, P = 0.09, respectively) views. Segmental intra-observer agreement for wall motion contractility at rest and stress cine images was almost perfect (K = 0.88, 95% confidence interval = 0.93-0.84, and K = 0.82, 95% CI = 0.88-0.76) respectively. No serious side effects were observed during DSMR. CONCLUSION: The present study confirms the feasibility, safety and excellent image quality of DSMR for the diagnosis of coronary artery diseases.

Preliminary assessment of cardiac short term safety and efficacy of manganese chloride for cardiovascular magnetic resonance in humans.

BACKGROUND: Manganese based agents are intracellular and accumulate inside myocytes allowing for different imaging strategies compared to gadolinium contrasts. While previous agents release manganese very slowly in the circulation, MnCl2 allows for rapid Mn2+ uptake in myocytes, creating a memory effect that can be potentially explored. Data on animal models are very encouraging but the safety and efficacy of this approach in humans has not yet been investigated. Therefore, our objectives were to study the safety and efficacy of a rapid infusion of manganese chloride (MnCl2) for cardiovascular magnetic resonance (CMR) in humans. METHODS: Fifteen healthy volunteers underwent a CMR scan on a 1.5 T scanner. Before the infusion, cardiac function was calculated and images of a short axis mid-ventricular slice were obtained using a 2D and 3D gradient-echo inversion recovery (GRE-IR) sequence, a phase-sensitive IR sequence and a single breath-hold segmented IR prepared steady-state precession acquisition for T1 calculations. MnCl2 was infused over three minutes at a total dose of 5 µMol/kg. Immediately after the infusion, and at 15 and 30 minutes later, new images were obtained and cardiac function re-evaluated. RESULTS: There was a significant decrease in T1 values compared to baseline, sustained up to 30 minutes after the MnCl2 infusion (pre,839 ± 281 ms; 0 min, 684 ± 99; 15 min, 714 ± 168; 30 min, 706 ± 172, P = 0.003). The 2D and 3D GRE-IR sequence showed the greatest increase in signal-to-noise ratio compared to the other sequences (baseline 6.6 ± 4.2 and 9.7 ± 5.3; 0 min, 11.3 ± 4.1 and 15.0 ± 8.7; 15 min, 10.8 ± 4.0 and 16.9 ± 10.2; 30 min, 10.6 ± 5.2 and 16.5 ± 8.3, P < 0.001 for both). There was a slight increase in systolic pressure and heart rate after three and four minutes of the infusion with normalization of these parameters thereafter. Patients showed good tolerance to MnCl2 with no major adverse events, despite all reporting transient facial flush. CONCLUSIONS: In the short term, MnCl2 appears safe for human use. It effectively decreases myocardium T1, maintaining this effect for a relatively long period of time and allowing for the development of new imaging strategies in CMR, especially in ischemia research.