Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

Sleep-Disordered Breathing and Nocturnal Hypoxemia in Precapillary Pulmonary Hypertension: Prevalence, Pathophysiological Determinants, and Clinical Consequences.

BACKGROUND AND OBJECTIVE: The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood. METHODS: Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (n = 34). RESULTS: Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to <15/h; 34% moderate to severe, AHI ≥15/h) versus 5% in controls (p < 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO2] <90%) was present in 48% of patients with PH, independent of the presence of OSA. There were no significant differences in mean nocturnal SpO2, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all p > 0.05). Right ventricular (RV) end-diastolic (r = -0.39; p = 0.03) and end-systolic (r = -0.36; p = 0.04) volumes were inversely correlated with mean nocturnal SpO2 but not with measures of OSA severity or daytime clinical variables. CONCLUSION: OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO2, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.

Clinical experience regarding safety and diagnostic value of cardiovascular magnetic resonance in patients with a subcutaneous implanted cardioverter/defibrillator (S-ICD) at 1.5 T.

BACKGROUND: Cardiovascular magnetic resonance (CMR) studies in patients with implanted cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. However, the clinical experience regarding the feasibility as well as clinical value of CMR studies in patients with subcutaneous ICD (S-ICD) is still limited. Besides safety issues, image quality and analysis can be impaired primarily due the presence of image artefacts associated with the generator. METHODS: Twenty-three patients with an implanted S-ICD (EMBLEM, Boston Scientific, Marlborough, Massachusetts, USA; MR-conditional) with suspected cardiomyopathy and/or myocarditis underwent multi-parametric CMR imaging. Studies were performed on a 1.5 T CMR scanner after device interrogation and comprised standard a) balanced steady state free precession cine, b) T2 weighted-edema, c) velocity-encoded cine flow, d) myocardial perfusion, e) late-gadolinium-enhancement (LGE)-imaging and f) 3D-CMR angiography of the aorta. In case of substantial artefacts, alternative CMR techniques such as spoiled gradient-echo cine-sequences and wide-band inversion-recovery LGE (wb-LGE) sequences were applied. RESULTS: Successful CMR studies could be performed in all patients without any case of unexpected early termination or relevant technical complication other than permanent loss of the S-ICD system beeper volume in 52% of our patients. Assessment of cine-CMR images was predominantly impaired in the left ventricular (LV) anterior, lateral and inferior wall segments and a switch to spoiled gradient echo-based cine-CMR allowed an accurate assessment of cine-images in N = 17 (74%) patients with only limited artefacts. Hyperintensity artefacts in conventional LGE-images were predominantly observed in the LV anterior, lateral and inferior wall segments and image optimisation by use of the wb-LGE was helpful in 15 (65%) cases. Aortic flow measurements and 3D-CMR angiography were assessable in all patients Perfusion imaging artefacts precluded a meaningful assessment in at least one half of the patients. A benefit in clinical-decision making was documented in 17 (74%) patients in the present study. CONCLUSION: Safe 1.5 T CMR imaging was possible in all patients with an S-ICD, though the majority had permanent loss of the S-ICD beeper volume. Achieving good image quality may be challenging in some patients - particularly for perfusion imaging. Using spoiled gradient echo-based cine-sequences and wb-LGE sequences may help to reduce the extent of artefacts, thereby allowing accurate cardiac assessment. Thus, 1.5 T CMR studies should not be withhold in patients with S-ICD for safety concerns and/or fear of extensive imaging artefacts precluding successful image analysis.

Impact of Simulated Hyperventilation and Periodic Breathing on Sympatho-Vagal Balance and Hemodynamics in Patients with and without Heart Failure.

BACKGROUND: The effects of hyperventilation and hyperventilation in the context of periodic breathing (PB) on sympatho-vagal balance (SVB) and hemodynamics in conditions of decreased cardiac output and feedback resetting, such as heart failure (HF) or pulmonary arterial hypertension (PAH), are not completely understood. OBJECTIVES: To investigate the effects of voluntary hyperventilation and simulated PB on hemodynamics and SVB in healthy subjects, in patients with systolic HF and reduced or mid-range ejection fraction (HFrEF and HFmrEF) and in patients with PAH. METHODS: Study participants (n = 20 per group) underwent non-invasive recording of diastolic blood pressure, heart rate variability (HRV), baroreceptor-reflex sensitivity (BRS), total peripheral resistance index (TPRI) and cardiac index (CI). All measurements were performed at baseline, during voluntary hyperventilation and during simulated PB with different length of the hyperventilation phase. RESULTS: In healthy subjects, voluntary hyperventilation led to a 50% decrease in the mean BRS slope and a 29% increase in CI compared to baseline values (p < 0.01 and p < 0.05). Simulated PB did not alter TPRI or CI and showed heterogeneous effects on BRS, but analysis of dPBV revealed decreased sympathetic drive in healthy volunteers depending on PB cycle length (p < 0.05). In HF patients, hyperventilation did not affect BRS and TPRI but increased the CI by 10% (p < 0.05). In HF patients, simulated PB left all of these parameters unaffected. In PAH patients, voluntary hyperventilation led to a 15% decrease in the high-frequency component of HRV (p < 0.05) and a 5% increase in CI (p < 0.05). Simulated PB exerted neutral effects on both SVB and hemodynamic parameters. CONCLUSIONS: Voluntary hyperventilation was associated with sympathetic predominance and CI increase in healthy volunteers, but only with minor hemodynamic and SVB effects in patients with HF and PAH. Simulated PB had positive effects on SVB in healthy volunteers but neutral effects on SVB and hemodynamics in patients with HF or PAH.

Pattern and prognostic value of cardiac involvement in patients with late-onset pompe disease: a comprehensive cardiovascular magnetic resonance approach.

BACKGROUND: Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal α-1,4-glucosidase leading to accumulation of glycogen in target tissues with progressive organ failure. While the early infantile-onset form is characterized by early severe hypertrophic cardiomyopathy with cardiac and respiratory failure, clinically relevant cardiomyopathy seems to be uncommon in patients with late-onset Pompe disease, and the prevalence and nature of myocardial abnormalities are still to be clarified. METHODS: Seventeen patients with genetically proven late-onset Pompe disease (50 ± 18 years, 11 male) and 18 age- and gender-matched healthy controls (44 ± 10 year, 12 male) underwent comprehensive cardiovascular magnetic resonance (CMR) including conventional and advanced techniques: cine and feature tracking-based strain imaging for depiction of (even subtle) systolic LV dysfunction as well as late gadolinium enhancement (LGE) and myocardial extracellular volume fraction (ECV) quantification for focal and diffuse fibrosis detection. RESULTS: All patients had normal left ventricular (LV) and right ventricular (RV) volumes and normal LV and RV ejection fraction. In comparison to healthy controls, neither conventional cine nor advanced feature-tracking based-strain imaging could depict any (subclinical) myocardial systolic dysfunction. Three (18%) of the patients had non-ischemic LGE in the basal inferolateral wall and 21% demonstrated elevated global ECV values suggestive of interstitial myocardial fibrosis. Non-specific abnormalities such as left atrial (LA) dilatation were present in two patients, while LV hypertrophy was seen only in one. Two of the three LGE-positive patients were also hypertensive and demonstrated high global ECV values (>30%) in addition to dilated LA. After a median follow-up of 25 (11-29) months, only one cardiovascular event occurred: one of the LGE-positive patients with a high cardiovascular risk profile suffered an acute coronary syndrome. CONCLUSION: In contrast to the early infantile-onset form of Pompe disease, mild and rather non-specific cardiac abnormalities can be detected by CMR only in a small proportion of patients with late-onset Pompe disease. The observed structural abnormalities seem to result from an interplay between the storage disease and other comorbidities and they did not affect short-term to mid-term prognosis in adult Pompe patients.

Identification of cardiomyopathy associated circulating miRNA biomarkers in patients with muscular dystrophy using a complementary cardiovascular magnetic resonance and plasma profiling approach.

BACKGROUND: Duchenne and Becker muscular dystrophy (DMD and BMD) are X-chromosomal recessive neuromuscular disorders that are caused by mutations in the dystrophin gene and characterized by cardiac involvement. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers for various cardiovascular diseases. However, circulating miRNAs reflecting the presence and/or disease severity of cardiac involvement in DMD/BMD patients have not been described so far. METHODS: Sixty-three male patients with known MD and 26 age-matched healthy male controls were prospectively enrolled. All MD patients and controls underwent comprehensive cardiovascular magnetic resonance (CMR) studies as well as venous blood sampling on the same day. RESULTS: An impaired left ventricular (LV) systolic function (defined as LV-EF <55 %) was detected in 29 (46 %) and presence of late gadolinium enhancement (LGE) indicative of myocardial fibrosis in 48 (76 %) MD patients with an exclusively non-ischemic pattern. Whereas no significant differences were observed for the 27 selected circulating miRNAs in MD patients with abnormal CMR findings (comprising structural and/or functional impairments) compared to those with completely normal CMR studies, a significant up-regulation of three miRNAs was observed in LGE-positive MD patients compared to LGE-negative ones: miR-222 (1.8-fold, p = 0.035), miR-26a (2.1-fold, p = 0.03) and miR-378a-5p (2.4-fold, p = 0.026). A signature of these three miRNAs (miR-26a, miR-222 and miR-378a-5p) resulted in an area under the curve (AUC) value of 0.74 for the diagnosis of LGE-positive MD patients. In a multivariable model, three independent predictors for LGE presence were identified comprising not only clinical and laboratory markers (LV-EF: OR 0.47, 95 % CI 0.24-0.89, p = 0.021 and elevated hs-Trop: OR 2559, 95 % CI 2.97-22.04*10(5), p = 0.023) but also the circulating miR-222 (OR 938, 95 % CI 938.46, 3.56-24.73*10(4), p = 0.016). CONCLUSIONS: Up-regulation of circulating miRNAs miR-222, miR-26a and miR-378a-5p indicates the presence of myocardial scars in MD patients. Plasma miR-222 appears to be a promising novel biomarker reflecting structural - but not functional - cardiac alterations in MD patients.

The diagnostic value of iron oxide nanoparticles for imaging of myocardial inflammation--quo vadis?

Cardiovascular magnetic resonance (CMR) is an integral part in the diagnostic work-up of cardiac inflammatory diseases. In this context, superparamagnetic iron oxide-based contrast agents can provide additional diagnostic information regarding the assessment of myocardial infarction and myocarditis. After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies. Furthermore, first clinical studies with a new iron oxide-complex that was clinically approved for the treatment of iron deficiency anaemia recently demonstrated a superior diagnostic value of iron oxide nanoparticles compared to gadolinium-based compounds for imaging of myocardial inflammation in patients with acute myocardial infarction. In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis. Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.

Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy.

BACKGROUND: Mitochondrial myopathies (MM) are a heterogeneous group of inherited conditions resulting from a primary defect in the mitochondrial respiratory chain with consecutively impaired cellular energy metabolism. Small sized studies using mainly electrocardiography (ECG) and echocardiography have revealed cardiac abnormalities ranging from conduction abnormalities and arrhythmias to hypertrophic or dilated cardiomyopathy in these patients. Recently, characteristic patterns of cardiac involvement were documented by cardiovascular magnetic resonance (CMR) in patients with chronic progressive external ophthalmoplegia (CPEO)/Kearns-Sayre syndrome (KSS) and with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). The present study aimed to characterize the prevalence and pattern of cardiac abnormalities and to test the additional diagnostic value of CMR in this patient population. The hypothesis that different neuromuscular MM syndromes present with different cardiac disease phenotypes was evaluated. METHODS: Sixty-four MM patients (50 ± 15 years, 44% male) and 25 matched controls (52 ± 14 years, 36% male) prospectively underwent cardiac evaluations including CMR (comprising cine- and late-gadolinium-enhancement (LGE) imaging). Based on the neuromuscular phenotype and genotype, the patients were grouped: (a) CPEO/KSS (N = 33); (b) MELAS/-like (N = 11); c) myoclonic epilepsy with ragged-red fibers (MERRF) (N = 3) and d) other non-specific MM forms (N = 17). RESULTS: Among the 64 MM patients, 34 (53%) had at least one abnormal CMR finding: 18 (28%) demonstrated an impaired left ventricular ejection-fraction (LV-EF <60%), 14 (22%) had unexplained LV hypertrophy and 21 (33%) were LGE-positive. Compared to controls, MM patients showed significantly higher maximal wall thickness (10 ± 3 vs. 8 ± 2 mm, p = 0.005) and concentricity (LV mass to end-diastolic volume: 0.84 ± 0.27 vs. 0.67 ± 0.11, p < 0.0001) with frequent presence of non-ischemic LGE (30% vs. 0%, p = 0.001). CPEO/KSS showed a predominantly intramural pattern of LGE mostly confined to the basal LV inferolateral wall (8/10; 80%) in addition to a tendency toward concentric remodelling. MELAS/-like patients showed the highest frequency of cardiac disease (in 10/11 (91%)), a mostly concentric LV hypertrophy (6/9; 67%) with or without LV systolic dysfunction and a predominantly focal, patchy LGE equally distributed among LV segments (8/11; 73%). Patients with MERRF and non-specific MM had no particular findings. Pathological CMR findings indicating cardiac involvement were detected significantly more often than pathological ECG results or elevated cardiac serum biomarkers (34 (53%) vs. 18 (28%) vs. 21 (33%); p = 0.008). CONCLUSION: Cardiac involvement is a frequent finding in MM patients - and particularly present in KSS/CPEO as well as MELAS/-like patients. Despite a high variability in clinical presentation, CPEO/KSS patients typically show an intramural pattern of LGE in the basal inferolateral wall whereas MELAS patients are characterized by overt concentric hypertrophy and a rather unique, focally accentuated and diffusely distributed LGE.

Left ventricular systolic function and the pattern of late-gadolinium-enhancement independently and additively predict adverse cardiac events in muscular dystrophy patients.

BACKGROUND: Cardiac involvement is a frequent finding in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies. With this study, we aimed at elucidating the relationship between the phenotypic expression of cardiac involvement and the occurrence of adverse cardiac events in DMD/BMD patients. METHODS: Eighty-eight male DMD/BMD patients (age 29 ± 14 yrs) were prospectively enrolled. All patients underwent cardiovascular magnetic resonance (CMR) comprising cine- and late-gadolinium-enhancement (LGE)-CMR at study entry and were subsequently followed-up for adverse cardiac events. The primary endpoint was defined as all-cause/cardiac death or cardiac transplantation. Secondary endpoints were (1) hospitalization for heart failure and/or (2) occurrence of non-/sustained ventricular tachycardia (VT). RESULTS: During a mean follow-up time of 47 ± 18 months, the primary endpoint was observed in three (3%) and the secondary endpoint in 21 (24%) patients. On multivariable analysis, LV-EF (HR, 95% CI: 0.94, 0.89-0.97, p = 0.001) and the presence of "transmural" LGE (HR, 95% CI: 2.89, 1.09-7.68, p = 0.033) were the only independent predictors for secondary endpoints. A cut-off for LV-EF of 45% was associated with the highest hazard ratio (HR, 95% CI: 11.50, 4.49-29.43, p < 0.0001) in a Cox regression survival analysis. In the group of patients with a LV-EF (>45%), those patients already showing "transmural" LGE had a significantly lower event-free-survival (HR, 95% CI: 13.48, 1.89-96.12, p = 0.009) compared to those without. CONCLUSIONS: An impaired LV systolic function (LV-EF ≤45%) and a "transmural" pattern of myocardial fibrosis independently predict the occurrence of adverse cardiac events in DMD/BMD patients. Even in DMD/BMD patients with relatively preserved LV-EF (>45%), the simple and visually assessable parameter "transmural LGE" is of additive prognostic value.

Arrhythmic Mitral Valve Prolapse Phenotype: An Unsupervised Machine Learning Analysis Using a Multicenter Cardiac MRI Registry.

Purpose To use unsupervised machine learning to identify phenotypic clusters with increased risk of arrhythmic mitral valve prolapse (MVP). Materials and Methods This retrospective study included patients with MVP without hemodynamically significant mitral regurgitation or left ventricular (LV) dysfunction undergoing late gadolinium enhancement (LGE) cardiac MRI between October 2007 and June 2020 in 15 European tertiary centers. The study end point was a composite of sustained ventricular tachycardia, (aborted) sudden cardiac death, or unexplained syncope. Unsupervised data-driven hierarchical k-mean algorithm was utilized to identify phenotypic clusters. The association between clusters and the study end point was assessed by Cox proportional hazards model. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 female, 230 male) with two phenotypic clusters were identified. Patients in cluster 2 (199 of 474, 42%) had more severe mitral valve degeneration (ie, bileaflet MVP and leaflet displacement), left and right heart chamber remodeling, and myocardial fibrosis as assessed with LGE cardiac MRI than those in cluster 1. Demographic and clinical features (ie, symptoms, arrhythmias at Holter monitoring) had negligible contribution in differentiating the two clusters. Compared with cluster 1, the risk of developing the study end point over a median follow-up of 39 months was significantly higher in cluster 2 patients (hazard ratio: 3.79 [95% CI: 1.19, 12.12], P = .02) after adjustment for LGE extent. Conclusion Among patients with MVP without significant mitral regurgitation or LV dysfunction, unsupervised machine learning enabled the identification of two phenotypic clusters with distinct arrhythmic outcomes based primarily on cardiac MRI features. These results encourage the use of in-depth imaging-based phenotyping for implementing arrhythmic risk prediction in MVP. Keywords: MR Imaging, Cardiac, Cardiac MRI, Mitral Valve Prolapse, Cluster Analysis, Ventricular Arrhythmia, Sudden Cardiac Death, Unsupervised Machine Learning Supplemental material is available for this article. © RSNA, 2024.

Magnetic resonance of the heart in a muscular dystrophy patient with an MR conditional ICD: assessment of safety, diagnostic value and technical limitations.

Cardiovascular magnetic resonance (CMR) studies in patients with pacemakers or implantable cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. Therefore, in the last years the manufacturers developed not only MR-conditional pacemakers, but also MR-conditional ICDs. However, the clinical experience regarding the feasibility and limitations of MR studies of the heart in patients with ICDs is still limited. In particular, there are hardly any CMR studies in the same patients performed prior to and post ICD implantation allowing a one-to-one comparison of the obtained CMR images. This is the first presentation of a CMR study in a patient with the world's first and so far only MR-conditional ICD. In our case, a major problem related to the presence of the MR conditional ICD was an image artifact caused by the device's generator which hampered the visualization of the midventricular and apical anterior and antero-lateral segments in all sequences performed. Considering previous studies, right chest implantation of the ICD could probably have helped in this setting and may be preferred in future ICD implantations. Our case report nicely illustrates the real clinical need for specially designed implantable devices that ensure safe and high-quality imaging in patients in whom serial CMR is required.

Does two-dimensional image reconstruction from three-dimensional full volume echocardiography improve the assessment of left ventricular morphology and function?

AIMS: (i) To investigate geometric differences between apical views of the left ventricle (LV) derived from standard 2D echocardiography (std2D) and triplane (TP) views, as well as the "ideally" reconstructed 2D (rec2D) views derived from 3D full volume (3DFV) acquisitions, and their influence on the assessment of LV morphology and function. (ii) To determine the feasibility and accuracy of the automatic reconstruction of 2D apical views from 3DFV datasets. METHODS AND RESULTS: In 59 patients with structurally normal, dilated, and hypertrophic hearts, rec2D was reconstructed manually and automatically and compared to std2D, TP, and 3DFV regarding the image plane orientation (true vs. ideal probe position, plane intersection angles), LV dimensions, volumes, and EF. The ideal probe position deviated from the true one by 6.9 ± 4.1 mm and 9.5 ± 4.5 mm, for manually and automatically rec2D, respectively, regardless of LV geometry. The mean difference ± SD between manual and automatic reconstruction was -2.5 ± 4.4 mm. LV long axis was measured minimally, but significantly longer in rec2D than std2D and TP. LV volumes and EF did not differ between methods. The intersection angle of the two-chamber view and the three-chamber view with the four-chamber view for manual and automatic reconstruction was 53° ± 7° and 129° ± 7° and 60° and 130°, respectively. CONCLUSION: Ideal reconstruction of nonforeshortened 2D images from 3DFV does not lead to a relevant improvement in image geometry or the assessment of LV morphology and function. The automatic reconstruction algorithm deviates only slightly from manual results.

Hybrid CMR- and FDG-PET-Imaging Gives New Insights Into the Relationship of Myocardial Metabolic Activity and Fibrosis in Patients With Becker Muscular Dystrophy.

BACKGROUND: Cardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course. PURPOSE: Since the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach. METHODS: Hybrid CMR- and FDG-PET-imaging was performed in N = 14 patients with BMD on a whole-body Biograph mMR system (Siemens, Erlangen, Germany). The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 min starting with tracer injection. Uptake values from 60 to 65 min p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake. RESULTS: A characteristic pattern of LGE in the LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. There was one patient without any LGE. Segmental FDG uptake was 88 ± 6% in the LV lateral wall vs. 77 ± 10% in the septal wall (p < 0.001). There was an inverse relationship between segmental FDG activity compared to segmental LGE extent (r = -0.33, p = 0.089). There were N = 6 LGE-positive patients with a segmental difference in FDG uptake of >15% in the LV lateral wall compared to the septal wall = ΔFDG-high group (lateral FDG = 91±3% vs. septal FDG = 69±8%; p < 0.001) while the remaining N = 7 LGE-positive patients showed a segmental difference in FDG uptake of ≤ 15% = ΔFDG-low group (lateral FDG = 85±7% vs. septal FDG = 83 ± 5%; p = 0.37). Patients in the ΔFDG-high group showed only a minor difference in the LGE extent between the LV lateral wall vs. septal wall (p = 0.09) whereas large differences were observed in the ΔFDG-low group (p < 0.004). CONCLUSIONS: Segmental FDG uptake-reflecting myocardial metabolic activity-is higher in the LV free wall of BMD patients-possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging.

Cardiac Outcomes in Adults With Mitochondrial Diseases.

BACKGROUND: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE). OBJECTIVES: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population. METHODS: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases. RESULTS: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively. CONCLUSIONS: We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.

Genome silencer therapy leading to 'regression' of cardiac amyloid load on cardiovascular magnetic resonance: a case report.

BACKGROUND: Hereditary or variant transthyretin amyloidosis (ATTRv) is a progressive disease manifesting with neuropathy and/or cardiomyopathy. An early and accurate diagnosis of cardiac amyloidosis is a pre-requisite for timely and appropriate patient management, including anti-amyloid therapies, as it is associated with heart failure, conduction disease, and arrhythmias, leading to reduced quality of life and early death. CASE SUMMARY: We present the case of an ATTRv male patient presenting with a mixed amyloidosis phenotype (neuropathy and cardiomyopathy). Cardiac disease manifestation comprised tachyarrhythmias (atrial fibrillation) and conduction abnormalities (atrio-ventricular block) in addition to segmental left ventricular (LV) hypertrophy (septal wall) due to regionally pronounced amyloid deposits in the basal LV myocardium. Interestingly, by means of serial cardiovascular magnetic resonance (CMR) studies, we were able to demonstrate an impressive and unexpected improvement of cardiomyopathy findings within a relatively short period-of-time after the implementation of genome-silencer therapies. DISCUSSION: This is our second case report that showed ATTRv cardiomyopathy reversal under anti-amyloid therapy-documented by multi-parametric CMR. Our findings support the hypothesis that amyloid infiltration leading to cardiomyopathy is not an irreversible pathological process-but rather a dynamic one, that cannot only be stopped but even reversed (to a certain degree) by currently emerging anti-amyloid therapies. Moreover, the role of serial multi-parametric CMR imaging for surveillance of cardiomyopathy dynamics under these therapies is nicely illustrated.

Diagnostic value of the novel CMR parameter "myocardial transit-time" (MyoTT) for the assessment of microvascular changes in cardiac amyloidosis and hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is present in various non-ischemic cardiomyopathies and in particular in those with left-ventricular hypertrophy. This study evaluated the diagnostic value of the novel cardiovascular magnetic resonance (CMR) parameter "myocardial transit-time" (MyoTT) in distinguishing cardiac amyloidosis from other hypertrophic cardiomyopathies. METHODS: N = 20 patients with biopsy-proven cardiac amyloidosis (CA), N = 20 patients with known hypertrophic cardiomyopathy (HCM), and N = 20 control patients without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as first-pass perfusion acquisitions at rest for MyoTT measurement. MyoTT was defined as the blood circulation time from the orifice of the coronary arteries to the pooling in the coronary sinus (CS) reflecting the transit-time of gadolinium in the myocardial microvasculature. RESULTS: MyoTT was significantly prolonged in patients with CA compared to both groups: 14.8 ± 4.1 s in CA vs. 12.2 ± 2.5 s in HCM (p = 0.043) vs. 7.2 ± 2.6 s in controls (p < 0.001). Native T1 and extracellular volume (ECV) were significantly higher in CA compared to HCM and controls (p < 0.001). Both parameters were associated with a higher diagnostic accuracy in predicting the presence of CA compared to MyoTT: area under the curve (AUC) for native T1 = 0.93 (95% confidence interval (CI) = 0.83-1.00; p < 0.001) and AUC for ECV = 0.95 (95% CI = 0.88-1.00; p < 0.001)-compared to the AUC for MyoTT = 0.76 (95% CI = 0.60-0.92; p = 0.008). In contrast, MyoTT performed better than all other CMR parameters in differentiating HCM from controls (AUC for MyoTT = 0.93; 95% CI = 0.81-1.00; p = 0.003 vs. AUC for native T1 = 0.69; 95% CI = 0.44-0.93; p = 0.20 vs. AUC for ECV = 0.85; 95% CI = 0.66-1.00; p = 0.017). CONCLUSION: The relative severity of CMD (measured by MyoTT) in relationship to extracellular changes (measured by native T1 and/or ECV) is more pronounced in HCM compared to CA-in spite of a higher absolute MyoTT value in CA patients. Hence, MyoTT may improve our understanding of the interplay between extracellular/intracellular and intravasal changes that occur in the myocardium during the disease course of different cardiomyopathies.

Prevalence and clinical outcomes of dystrophin-associated dilated cardiomyopathy without severe skeletal myopathy.

AIMS: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. METHODS AND RESULTS: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5-311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. CONCLUSIONS: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.

Surprising diagnosis in a patient with acute coronary syndrome: a case report of acute streptococcal pharyngitis-associated perimyocarditis.

BACKGROUND: Streptococcal pharyngitis is a common infection, with both suppurative and non-suppurative complications. Most importantly, a streptococcal infection can cause heart disease in different pathophysiological pathways. Acute non-rheumatic perimyocarditis appears to be a more frequent pathological entity associated with streptococcal pharyngitis as once thought, which is poorly understood and explored. CASE SUMMARY: We present the case of a middle-aged man with acute chest pain, electrocardiogram (ECG) abnormalities, and elevated cardiac enzymes following a recent episode of pharyngitis in which streptococcal-associated perimyocarditis was diagnosed. Cardiovascular magnetic resonance (CMR) imaging established the diagnosis and allowed cardiac disease monitoring after successful antibiotic therapy resulting in complete clinical recovery. DISCUSSION: Patients presenting with acute chest pain, ECG abnormalities, and cardiac enzyme elevations do not always suffer from an ischaemic heart attack. A thorough investigation comprising a detailed past medical history and non-invasive imaging such as CMR are the cornerstones for unravelling a correct diagnosis and implementing a proper treatment-as was shown in the present clinical case.