Case Report: Severe Peripartum Cardiac Disease in Myotonic Dystrophy Type 1.

Background: Myotonic dystrophy type 1 (DM1) is a hereditary muscular dystrophy affecting ∼2.1-14.3/100,000 adults. Cardiac manifestations of DM1 include conduction disorders and rarely cardiomyopathies. DM1 increases the risk of obstetric complications, however, little is known about the relationship between pregnancy and cardiomyopathy in DM1 due to disease rarity. Case: A 23-year-old with DM1 developed cardiomyopathy during pregnancy. Despite initial medical stabilization, she subsequently developed multiple spontaneous coronary artery dissections postpartum, worsening cardiomyopathy and multiorgan failure. She died 5 months postpartum. Conclusion: Though cardiomyopathy and arterial dissection are both known complications of pregnancy, this case suggests individuals with myotonic dystrophy type 1 may be at heightened risk for cardiac disease during the peripartum period. Physicians caring for women with suspected or proven DM1 should offer counseling and be alerted to the risk of cardiac complications with pregnancy and in the peripartum period. Pregnant and peripartum women with DM1 are likely to benefit from more frequent assessments of cardiac function including echocardiograms and early institution of heart failure management protocols when symptoms of cardiomyopathy present.

Unexpected diagnosis of metastatic breast carcinoma in an endomyocardial biopsy done for cardiac allograft rejection evaluation.

We report a case of a 75-year-old female post orthotopic heart transplantation, who presented to the emergency department with a six-week history of shortness of breath, hand tremor and ultimately delirium. She had lobular breast carcinoma more than 5 years prior to her heart transplant, treated by lumpectomy followed by anthracycline based chemotherapy. The reason for her heart transplant was heart failure that was suspected to be from anthracycline cardiomyopathy, however, her explanted heart actually showed cardiac sarcoidosis. She was placed on long-term immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. Two years after her heart transplant, she underwent bilateral mastectomies for recurrent breast cancer. Her neurological workup, including brain imaging (CT, MRI, LP and EEG) did not show any structural abnormalities, ischemia, mass or neurosarcoidosis as cause for delirium. Tacrolimus was held due to renal dysfunction and hemolytic anemia, and then she developed signs of right heart failure so an endomyocardial biopsy was carried out for suspected allograft rejection. The biopsy did not show any evidence of cellular or antibody medicated rejection; however, it demonstrated infiltration by bland appearing cells with signet ring morphology cells many of which showed intracytoplasmic mucin. The cells were strongly positive with cytokeratins AE1/3, CK7 and mammaglobin. The morphology and immunoprofile were consistent with metastatic lobular breast carcinoma and this was thought to be the cause of her clinical presentation with delirium, hemolytic anemia and renal dysfunction as a paraneoplastic syndrome.

Serial Cardiovascular Magnetic Resonance Strain Measurements to Identify Cardiotoxicity in Breast Cancer: Comparison With Echocardiography.

OBJECTIVES: This study sought to compare the prognostic value of cardiovascular magnetic resonance (CMR) and 2-dimensional echocardiography (2DE) derived left ventricular (LV) strain, volumes, and ejection fraction for cancer therapy-related cardiac dysfunction (CTRCD) in women with early stage breast cancer. BACKGROUND: There are limited comparative data on the association of CMR and 2DE derived strain, volumes, and LVEF with CTRCD. METHODS: A total of 125 prospectively recruited women with HER2+ early stage breast cancer receiving sequential anthracycline/trastuzumab underwent 5 serial CMR and 6 of 2DE studies before and during treatment. CMR LV volumes, left ventricular ejection fraction tagged-CMR, and feature-tracking (FT) derived global systolic longitudinal (GLS) and global circumferential strain (GCS) and 2DE-based LV volumes, function, GLS, and GCS were measured. CTRCD was defined by the cardiac review and evaluation committee criteria. RESULTS: Twenty-eight percent of patients developed CTRCD by CMR and 22% by 2DE. A 15% relative reduction in 2DE-GLS increased the CTRCD odds by 133% at subsequent follow-up, compared with 47%/50% by tagged-CMR GLS/GCS and 87% by FT-GCS. CMR and 2DE-LVEF and indexed left ventricular end-systolic volume (LVESVi) were also associated with subsequent CTRCD. The prognostic threshold change in CMR-left ventricular ejection fraction and FT strain for subsequent CTRCD was similar to the known minimum-detectable difference for these measures, whereas for tagged-CMR strain it was lower than the minimum-detectable difference; for 2DE, only the prognostic threshold for GLS was greater than the minimum-detectable difference. Of all strain methods, 2DE-GLS provided the highest increase in discriminatory value over baseline clinical risk factors for subsequent CTRCD. The combination of 2DE-left ventricular ejection fraction or LVESVi and strain provided greater increase in the area under the curve for subsequent CTRCD over clinical risk factors than CMR left ventricular ejection fraction or LVESVi and strain (18% to 22% vs. 9% to 14%). CONCLUSIONS: In women with HER2+ early stage breast cancer, changes in CMR and 2DE strain, left ventricular ejection fraction, and LVESVi were prognostic for subsequent CTRCD. When LVEF can be measured precisely by CMR, FT strain may function as an additional confirmatory prognostic measure, but with 2DE, GLS is the optimal prognostic measure. (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

Antioxidant Solution in Combination with Angiotensin-(1-7) Provides Myocardial Protection in Langendorff-Perfused Rat Hearts.

As progressive organ shortage in cardiac transplantation demands extension of donor criteria, effort is needed to optimize graft survival. Reactive oxygen and nitrogen species, generated during organ procurement, transplantation, and reperfusion, contribute to acute and late graft dysfunction. The combined application of diverse substances acting via different molecular pathways appears to be a reasonable approach to face the complex mechanism of ischemia reperfusion injury. Thus, an antioxidant solution containing α-ketoglutaric acid, 5-hydroxymethylfurfural, N-acetyl-L-methionine, and N-acetyl-selenium-L-methionine was combined with endogenous angiotensin-(1-7). Its capacity of myocardial protection was investigated in isolated Langendorff-perfused rat hearts subjected to warm and cold ischemia. The physiological cardiac parameters were assessed throughout the experiments. Effects were evaluated via determination of the oxidative stress parameters malondialdehyde and carbonyl proteins as well as immunohistochemical and ultrastructural tissue analyses. It was shown that a combination of 20% (v/v) antioxidant solution and 220 pM angiotensin-(1-7) led to the best results with a preservation of heart tissue against oxidative stress and morphological alteration. Additionally, immediate cardiac recovery (after warm ischemia) and normal physiological performance (after cold ischemia) were recorded. Overall, the results of this study indicate substantial cardioprotection of the novel combination with promising prospective for future clinical use.

Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity.

OBJECTIVES: To compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD). METHODS: We prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM. RESULTS: Patients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities. CONCLUSION: Temporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.

The Added Value of Cardiac Magnetic Resonance in Muscular Dystrophies.

Muscular dystrophies (MD) represent a heterogeneous group of rare genetic diseases that often lead to significant weakness due to progressive muscle degeneration. In many forms of MD, cardiac manifestations including heart failure, atrial and ventricular arrhythmias and conduction abnormalities can occur and may be a predominant feature of the disease. Cardiac magnetic resonance (CMR) can assess cardiac anatomy, global and regional ventricular function, volumes and mass as well as presence of myocardial inflammation, infiltration or fibrosis. The role for cardiac MRI has been well-established in a wide range of muscular dystrophies related cardiomyopathies. CMR is a more sensitive technique than echocardiography for early diagnosis of cardiac involvement. It has also great potential to improve the prediction of long-term outcome, particularly the development of heart failure and arrhythmic events; however it still has to be validated by longitudinal studies including large populations. This review will outline the utility of CMR in patients with muscular dystrophies for assessment of myocardial involvement, risk stratification, and in guiding therapeutic management.

Quantification of myocardial deformation by deformable registration-based analysis of cine MRI: validation with tagged CMR.

OBJECTIVES: To validate deformable registration algorithms (DRAs) for cine balanced steady-state free precession (bSSFP) assessment of global longitudinal strain (GLS) and global circumferential strain (GCS) using harmonic phase (HARP) cardiovascular magnetic resonance as standard of reference (SoR). METHODS: Seventeen patients and 17 volunteers underwent short axis stack and 2-/4-chamber cine bSSFP imaging with matching slice long-axis and mid-ventricular spatial modulation of magnetization (SPAMM) myocardial tagging. Inverse DRA was applied on bSSFP data for assessment of GLS and GCS while myocardial tagging was processed using HARP. Intra- and inter-observer variability assessment was based on repeated analysis by a single observer and analysis by a second observer, respectively. Standard semi-automated short axis stack segmentation was performed for analysis of left ventricular (LV) volumes and ejection fraction (EF). RESULTS: DRA demonstrated strong relationships to HARP for myocardial GLS (R2 = 0.75; p < 0.0001) and endocardial GLS (R2 = 0.61; p < 0.0001). GCS result comparison also demonstrated significant relationships between DRA and HARP for myocardial strain (R2 = 0.61; p < 0.0001) and endocardial strain (R2 = 0.51; p < 0.0001). Both methods demonstrated small systematic errors for intra- and inter-observer variability but DRA demonstrated consistently lower CV. Global LVEF was significantly lower (p = 0.0099) in patients (53.7%; IQR 43.9/64.0%) than in healthy volunteers (62.6%; IQR 61.1/66.2%). DRA and HARP strain data demonstrated significant relationships to LVEF. CONCLUSIONS: Non-rigid deformation method-based DRA provides a reliable measure of peak systolic GCS and GLS based on cine bSSFP with superior intra- and inter-observer reproducibility compared to HARP. KEY POINT: • Myocardial strain can be reliably analyzed using inverse deformable registration algorithms (DRAs) on cine CMR. • Inverse DRA-derived strain shows higher reproducibility than tagged CMR. • DRA and tagged CMR-based myocardial strain demonstrate strong relationships to global left ventricular function.

Quantification of global myocardial function by cine MRI deformable registration-based analysis: Comparison with MR feature tracking and speckle-tracking echocardiography.

OBJECTIVES: To evaluate deformable registration algorithms (DRA)-based quantification of cine steady-state free-precession (SSFP) for myocardial strain assessment in comparison with feature-tracking (FT) and speckle-tracking echocardiography (STE). METHODS: Data sets of 28 patients/10 volunteers, undergoing same-day 1.5T cardiac MRI and echocardiography were included. LV global longitudinal (GLS), circumferential (GCS) and radial (GRS) peak systolic strain were assessed on cine SSFP data using commercially available FT algorithms and prototype DRA-based algorithms. STE was applied as standard of reference for accuracy, precision and intra-/interobserver reproducibility testing. RESULTS: DRA showed narrower limits of agreement compared to STE for GLS (-4.0 [-0.9,-7.9]) and GCS (-5.1 [1.1,-11.2]) than FT (3.2 [11.2,-4.9]; 3.8 [13.9,-6.3], respectively). While both DRA and FT demonstrated significant differences to STE for GLS and GCS (all p<0.001), only DRA correlated significantly to STE for GLS (r=0.47; p=0.006). However, good correlation was demonstrated between MR techniques (GLS:r=0.74; GCS:r=0.80; GRS:r=0.45, all p<0.05). Comparing DRA with FT, intra-/interobserver coefficient of variance was lower (1.6 %/3.2 % vs. 6.4 %/5.7 %) and intraclass-correlation coefficient was higher. DRA GCS and GRS data presented zero variability for repeated observations. CONCLUSIONS: DRA is an automated method that allows myocardial deformation assessment with superior reproducibility compared to FT. KEY POINTS: • Inverse deformable registration algorithms (DRA) allow myocardial strain analysis on cine MRI. • Inverse DRA demonstrated superior reproducibility compared to feature-tracking (FT) methods. • Cine MR DRA and FT analysis demonstrate differences to speckle-tracking echocardiography • DRA demonstrated better correlation with STE than FT for MR-derived global strain data.

Effects of slice orientation on reproducibility of sequential assessment of right ventricular volumes and ejection fraction: short-axis vs transverse SSFP cine cardiovascular magnetic resonance.

BACKGROUND: Test-retest reproducibility is of utmost importance in follow-up of right ventricular (RV) volumes and function; optimal slice orientation though is not yet known. We compared test-retest reproducibility and intra-/inter-observer variability of right ventricular (RV) volumes and function assessed with short-axis and transverse cardiovascular magnetic resonance (CMR). METHODS: Eighteen volunteers underwent cine CMR for RV assessment obtaining ventricular coverage in short-axis and transverse slice orientation. Additional 2D phase contrast flow imaging of the main pulmonary artery (MPA) was performed. After complete repositioning repeat acquisitions were performed. Data sets were contoured by two blinded observers. Statistical analysis included Student's t-test, Bland-Altman plots, intra-class correlation coefficient (ICC) and 2-way ANOVA, SEM and minimal detectable difference calculations. RESULTS: Heart rates (65.0 ± 7.4 vs. 67.6 ± 9.9 bpm; P = 0.1) and MPA flow (89.8 ± 16.6 vs. 87.2 ± 14.9 mL; P = 0.1) did not differ between imaging sessions. EDV and ESV demonstrated an inter-study bias of 0.4 %[-9.5 %,10.3 %] and 2.1 %[-12.3 %,16.4 %] for short-axis and 1.1 %[-7.3 %,9.4 %] and 0.8 %[-16.0 %,17.6 %] for transverse orientation, respectively. There was no significant interaction between imaging orientation and interstudy reproducibility (p = 0.395-0.824), intra-observer variability (p = 0.726-0.862) or inter-observer variability (p = 0.447-0.706) by 2-way ANOVA. Inter-observer agreement by ICC was greater for short axis versus transverse orientation for all parameters (0.769-0.986 vs. 0.625-0.983, respectively). Minimal detectable differences for short axis and transverse orientations were 10.1 mL/11.5 mL for EDV, 8.3 mL/8.4 mL for ESV and 4.1 % vs. 4.7 % for EF, respectively. CONCLUSION: Short-axis and transverse orientation both provide reliable and reproducible measures for follow-up of RV volumes and global function. Therefore, additional transverse SSFP cine CMR may not necessarily be required if performed for the sole purpose of quantitative volumetric RV assessment.