Clinical and CMR characteristics associated with cardiac events in patients with Fabry disease

BACKGROUND The assessment of late gadolinium enhancement (LGE) and left ventricular hypertrophy (LVH) by cardiac magnetic resonance (CMR) as diagnostic and prognostic maker in Fabry disease is advancing. We aimed to investigate the impact of clinical characteristics and CMR findings on cardiac outcome in patients with FD. METHODS In this study 55 patients with genetically confirmed FD and available CMR imaging were included. The primary endpoint was defined as a composite of cardiac events including cardiac death, new occurrence of atrial fibrillation, heart failure, ventricular tachycardia and bradycardia requiring device insertion. RESULTS During a median follow-up of 4.9 years (IQR 3.7-5.9), 9 patients (16.3%) reached the primary cardiac end point. The global amount of LGE was associated with an increased risk for primary endpoint in the univariate analysis (HR 1.4 per 10% increase in LGE, p = 0.002). However maximal wall thickness (MWT) was the sole independent predictor of the primary endpoint in a stepwise logistic regression model (HR 9.8 per mm increase in MWT, p < 0.0001). Kaplan-Meier analysis revealed significant difference in event free survival rate between patients with and without LVH (Long-rank p = 0.006) and in patients with and without LGE (Long-rank p < 0.001). Patients without LVH and LGE were free of adverse cardiac events. CONCLUSION LVH and LGE detected by CMR were associated with adverse cardiac events in FD. In particular maximal wall thickness can be useful in cardiac risk stratification of FD patients

Right ventricular involvement in left ventricular non-compaction cardiomyopathy

Background: Left ventricular non-compaction cardiomyopathy (LVNC) features extensive trabeculations. Involvement of the right ventricle (RV) has been reported; however, distinction from normal RV trabeculation is difficult. This study aimed at assessing RV morphology and function in LVNC by cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE).Methods: Dimensional and functional parameters were assessed according to guidelines. Novel CMR parameters were RV end-diastolic (ED) trabeculated area, RV ED trabeculated volume, and RV ED non-compacted to compacted (NC/N) ratio in short axis (SAX) as well as in four-chamber view (4CH).Results: Twenty patients with LVNC and 20 controls were included. RV size and function were comparable in LVNC and controls and exhibited a good correlation between TTE and CMR. Although RV trabeculated area, RV trabeculated volume, and RV ED NC/C ratio in SAX as well as in 4CH were larger in LVNC, there was a major overlap with values in controls. RV ED NC/C ratio in SAX correlated with LV ED NC/C ratio (not in 4CH). Quantitative assessment of RV non-compaction was not feasible in TTE.Conclusions: Right ventricle size and function in LVNC can be measured by CMR and TTE, while RV trabeculation can only be quantified by CMR. RV myocardium displays more trabeculations in LVNC; however, overlap with normal individuals is extensive, not allowing separation of patients with LVNC from controls

Myocardial Fibrosis Quantification Methods by Cardiovascular Magnetic Resonance Imaging in Patients with Fabry Disease

Background/Objectives: The presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) in patients with Fabry disease (FD) is a predictor of adverse cardiac events. The aim of this study was to establish the most reliable and reproducible technique for quantifying LGE in patients with FD. Methods: Twenty FD patients with LGE who underwent CMR on the same scanner and LGE sequence were included. LGE quantifications were done using gray-scale thresholds of 2, 3, 4, 5 and 6 standard deviations (SD) above the mean signal intensity of the remote myocardium, the full width at half maximum method (FWHM), visual assessment with threshold (VAT) and the fully manual method (MM). Results: The mean amount of fibrosis varied between quantification techniques from 36 ± 19 at 2SD to 2 ± 2 g using the FWHM (p < 0.0001). Intraobserver reliability was excellent for most methods, except for the FWHM which was good (ICC 0.84; all p < 0.05). Interobserver reliability was excellent for VAT (ICC 0.94) and good for other techniques (all p < 0.05). Intraobserver reproducibility showed the lowest coefficient of variation (CV, 6%) at 5SD and at 2SD and VAT (35% and 38%) for interobserver reproducibility. The FWHM revealed the highest CV (63% and 94%) for both intra- and interobserver reproducibility. Conclusions: The available methods for LGE quantification demonstrate good to excellent intra- and interobserver reproducibility in patients with FD. The most reliable and reproducible techniques were VAT and 5SD, whereas the FWHM was the least reliable in the setting of our study. The total amount of LGE varies strongly with the quantification technique used

Assessment of treatment response in cardiac sarcoidosis based on myocardial 18^{18}F-FDG uptake

OBJECTIVE Immunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by $^{18}$F-fluorodeoxyglucose positron emission tomography/computed tomography ($^{18}$F-FDG PET/CT) of the heart. METHODS We conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020. RESULTS We identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial $^{18}$F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed. CONCLUSION TNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF

Changes in serum biomarker profiles after percutaneous mitral valve repair with the MitraClip system

Background: Mitral regurgitation (MR) is one of the most common valvular diseases. Percu­taneous mitral valve repair with the MitraClipTM system is a novel percutaneous mitral valve repair (PMVR) technique for high-surgical-risk patients. However, the effect of PMVR on cir­culating cardiac or inflammatory biomarkers and their association with individual functional, echocardiographic and clinical outcomes is poorly investigated. Methods: A group of 144 patients with functional or degenerative MR (age, 75 ± 11 years; 41% females) underwent PMVR with the MitraClip system at the University Heart Center Zu­rich. Serum biomarkers as N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and creatinine were obtained from venous sampling at baseline and follow-up of 3–6 months. Results: Median NT-proBNP decreased insignificantly from 2,942 (IQR 1,596–5,722) to 2,739 (IQR 1,440–4,296) ng/L, p = 0.21. NT-proBNP changes did not correlate with baseline left ventricular (LV) ejection fraction or LV dimensions, with New York Heart Association class on follow-up, or with clinical events on follow-up. CRP levels reached a peak on the third postoperative day at 34.0 mg/L with a subsequent slow decrease over the ensuing days. Conclusions: Despite successful PMVR, NT-proBNP remain fairly unchanged on follow-up and changes in NT-proBNP levels are poor predictors of functional improvement or clinical outcome after MitraClip treatment

Changes in serum biomarker profiles after percutaneous mitral valve repair with the MitraClip system

BACKGROUND Mitral regurgitation (MR) is one of the most common valvular diseases. Percu-taneous mitral valve repair with the MitraClipTM system is a novel percutaneous mitral valve repair (PMVR) technique for high-surgical-risk patients. However, the effect of PMVR on cir-culating cardiac or inflammatory biomarkers and their association with individual functional, echocardiographic and clinical outcomes is poorly investigated. METHODS A group of 144 patients with functional or degenerative MR (age, 75 ± 11 years; 41% females) underwent PMVR with the MitraClip system at the University Heart Center Zu-rich. Serum biomarkers as N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and creatinine were obtained from venous sampling at baseline and follow-up of 3-6 months. RESULTS Median NT-proBNP decreased insignificantly from 2,942 (IQR 1,596-5,722) to 2,739 (IQR 1,440-4,296) ng/L, p = 0.21. NT-proBNP changes did not correlate with baseline left ventricular (LV) ejection fraction or LV dimensions, with New York Heart Association class on follow-up, or with clinical events on follow-up. CRP levels reached a peak on the third postoperative day at 34.0 mg/L with a subsequent slow decrease over the ensuing days. CONCLUSIONS Despite successful PMVR, NT-proBNP remain fairly unchanged on follow-up and changes in NT-proBNP levels are poor predictors of functional improvement or clinical outcome after MitraClip treatment

Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy

Aims Cardiovascular magnetic resonance (CMR) has improved diagnostic and management strategies in hypertrophic cardiomyopathy (HCM) by expanding our appreciation for the diverse phenotypic expression. We sought to characterize the prevalence and clinical significance of a recently identified accessory left ventricular (LV) muscle bundle extending from the apex to the basal septum or anterior wall (i.e. apical-basal). Methods and results CMR was performed in 230 genotyped HCM patients (48 ± 15 years, 69% male), 30 genotype-positive/phenotype-negative (G+/P−) family members (32 ± 15 years, 30% male), and 126 controls. Left ventricular apical-basal muscle bundle was identified in 145 of 230 (63%) HCM patients, 18 of 30 (60%) G+/P− family members, and 12 of 126 (10%) controls (G+/P− vs. controls; P < 0.01). In HCM patients, the prevalence of an apical-basal muscle bundle was similar among those with disease-causing sarcomere mutations compared with patients without mutation (64 vs. 62%; P = 0.88). The presence of an LV apical-basal muscle bundle was not associated with LV outflow tract obstruction (P = 0.61). In follow-up, 33 patients underwent surgical myectomy of whom 22 (67%) were identified to have an accessory LV apical-basal muscle bundle, which was resected in all patients. Conclusion Apical-basal muscle bundles are a unique myocardial structure commonly present in HCM patients as well as in G+/P− family members and may represent an additional morphologic marker for HCM diagnosis in genotype-positive statu

Assessment of treatment response in cardiac sarcoidosis based on myocardial 18F-FDG uptake

ObjectiveImmunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of the heart.MethodsWe conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020.ResultsWe identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial 18F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed.ConclusionTNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF