The current stratification of arrhythmic risk in dilated cardiomyopathy (DCM) is sub-optimal. Cardiac fibrosis is involved in the pathology of arrhythmias; however, the relationship between cardiovascular magnetic resonance (CMR) derived extracellular volume (ECV) and arrhythmic burden (AB) in DCM is unknown. This study sought to evaluate the presence and extent of replacement and interstitial fibrosis in DCM and to compare the degree of fibrosis between DCM patients with and without AB. This is a prospective, single-center, observational study. Between May 2019 and September 2020, 102 DCM patients underwent CMR T1 mapping. 99 DCM patients (88 male, mean age 45.2 ± 11.8 years, mean EF 29.7 ± 10%) composed study population. AB was defined as the presence of VT or a high burden of PVCs. There were 41 (41.4%) patients with AB and 58 (58.6%) without AB. Replacement fibrosis was assessed with late gadolinium enhancement (LGE), whereas interstitial fibrosis with ECV. Overall, LGE was identified in 41% of patients. There was a similar distribution of LGE (without AB 50% vs. with AB 53.7%; p = 0.8) and LGE extent (without AB 4.36 ± 5.77% vs. with AB 4.68 ± 3.98%; p = 0.27) in both groups. ECV at nearly all myocardial segments and a global ECV were higher in patients with AB (global ECV: 27.9 ± 4.9 vs. 30.3 ± 4.2; p < 0.02). Only indexed left ventricular end-diastolic diameter (HR 1.1, 95%CI 1.0–1.2; p < 0.02) and global ECV (HR 1.12, 95%CI 1.0–1.25; p < 0.02) were independently associated with AB. The global ECV cut-off value of 31.05% differentiated both groups (AUC 0.713; 95%CI 0.598–0.827; p < 0.001). Neither qualitative nor quantitative LGE-based assessment of replacement fibrosis allowed for the stratification of DCM patients into low or high AB. Interstitial fibrosis, expressed as ECV, was an independent predictor of AB in DCM. Incorporation of CMR parametric indices into decision-making processes may improve arrhythmic risk stratification in DCM.
Chronic ischemic mitral regurgitation (IMR) is associated with a markedly worse prognosis after myocardial infarction (MI).The study aimed to evaluate the relationship between anterior and posterior mitral leaflet angle (MLA) values, left ventricle remodeling and severity of ischaemic mitral regurgitation (IMR). Methods: Forty-two patients (age 63.5 ± 9.7 years, 36 men) with chronic IMR (regurgitant volume, RV > 20 ml; >6 months after MI) underwent transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) imaging. Anterior and posterior MLA, determined by echocardiography, were correlated with indices of LV remodeling, mitral apparatus deformation and IMR severity by CMR. The anterior and posterior MLA was 25.41 ± 4.28 and 38.37 ± 8.89° (mean ± SD). In 5 patients (11.9%) the posterior MLA was ≥45°. There was a significant correlation between anterior MLA and RV (r = 0.74, P = 0.01). For patients with RV > 30 ml this correlation was stronger (r = 0.97, P = 0.005) and, in addition, there was a correlation between the RV and posterior MLA (r = 0.90, P = 0.037), between tenting area and posterior MLA (r = 0.90, P = 0.04), and between tenting area and anterior MLA (r = 0.82, P = 0.08). With regard to LV remodeling parameters, there was weaker but significant correlation between posterior MLA and LV end-diastolic volume index (r = 0.35, P = 0.031), LV end-systolic volume index (r = 0.37, P = 0.021), stroke volume (r = 0.35, P = 0.03), sphericity index (r = 0.33, P = 0.041). Anterior MLA correlated with wall motion score index (r = 0.41, P = 0.019). Besides, there was a correlation between posterior MLA and left atrial volume (r = 0.41, P = 0.012). Measurement of anterior and posterior MLA may play an important role in evaluating patients with IMR.
Exercise intolerance in adults with repaired ToF is markedly depressed. The decreased exercise capacity is correlated with impaired RV function and may be associated also with LV dysfunction, which suggests right-to-left ventricular interaction.
Aims. A major clinical concern is the continuous increase in the number of patients diagnosed with advanced coronary artery disease, ischemic heart failure, and refractory angina, and one of the most promising treatment options for these conditions is stem cell-based therapy. The aim of this study was to assess the functional improvement following intramyocardial injection of adipose-derived stromal cells, using cardiac magnetic resonance. Methods and Results. Thirteen patients with ischemic heart failure, reduced left ventricular ejection fraction, refractory angina, and who have been disqualified from any form of direct revascularization were enrolled in the study with transthoracic autologous adipose-derived stromal cell implantation. All patients underwent cardiac magnetic resonance prior to the procedure and after 12 months of follow-up. A significant increase in stroke volume ( 83.1 ± 8.5 mL vs 93.8 ± 13.8 mL , p = 0.025 ) and stroke volume index ( 43.3 ± 7.6 mL / m 2 vs 48.7 ± 9.1 mL / m 2 , p = 0.019 ), a statistical trend toward an increase in left ventricle ejection fraction ( 36.7 ± 13.2 vs 39.7 ± 14.9 , p = 0.052 ), and cardiac output improvement ( 5.0 ± 0.7 vs 5.5 ± 0.9 , p = 0.073 ) was observed in the patient postprocedure. Enhanced relative regional thickening was noted in the segments with adipose-derived stromal cell implantation. Conclusions. Intramyocardial adipose-derived stromal cell implantation is a promising therapeutic option for selected, symptomatic patients with ischemic heart failure, who have preserved myocardial viability despite being unsuitable for direct revascularization.
Background Chronic ischaemic heart failure (CIHF) remains an important health problem on the patient/family- and society level. In animal models, Wharton's jelly (umbilical cord matrix) multipotent stem cells (WJMSCs) effectively promote angiogenesis, can differentiate to cardiomyocytes, and drive functional myocardial regeneration. Effective uptake of regenerative cells in ischaemic-impaired tissue is fundamental for any therapeutic effect. Purpose To evaluate safety and myocardial uptake of WJMSCs transcoronary transfer in CIHF applied as a novel myocardial regeneration strategy employing allogenic yet hypo-immunogenic, off-the-shelf “unlimited” source of therapeutic cells (NCT03418233 pilot cohort). Material and methods In ten consecutive patients (age 62.6±2.5), with stable CIHF and no current need for revascularization (LVEF 29.3±3% by echo and 26.3±6% by SPECT; NT-proBNP 1746±329pg/mL; myocardial scar tissue 39.9±3.9% by SPECT) and patency of at least two major native coronary arteries or by-pass graft(s), the CardioCell Investigational Medical Product, based on 30x106 WJMSCs, was administered to viable yet hypokinetic segments using a novel algorithm including a dedicated catheter for transcoronary delivery of cellular therapies. The cells were labeled with 99mTc-extametazime to routinely evaluate their myocardial uptake magnitude. Results No symptoms or signs of novel myocardial ischaemia occurred with cell delivery and no patient showed any adverse periprocedural events. One hour after administration, myocardial WJMSCs uptake (SPECT) was 40.3±6%; see Fig for a typical raw data image. By 6 months there were no adverse events in the study cohort. Figure 1 Conclusions This work indicates safety and unprecedented high-grade myocardial uptake of WJMSCs in CIHF patients. Together with animal data, this provides basis for continued assessment of this strategy in an endpoint-powered randomized controlled clinical trial employing CardioCell as an “unlimited” off-the-shelf cellular therapy strategy. Acknowledgement/Funding K/ZDS/005644 and 265761 (National Centre for Research and Development STRATEGMED)
Background It is commonly accepted that myocardial fibrosis (MF) is implicated in the pathology of dilated cardiomyopathy (DCM). However, MF is not a “fixed” abnormality but evolves over time. It is unknown what the natural history of MF is in optimally treated DCM patients. Methods This is a prospective, single-center, observational study. Between May 2019 and September 2020, 90 DCM (81 male, mean age 47.2±9.8 years, mean EF 34.5±12.2%) patients underwent cardiac magnetic resonance (CMR). All patients were optimally treated with heart failure approved medications (beta-blockers in 100%, ACE-I/ARNI/ARB – 98%, MRA – 95%). Both, replacement via late gadolinium enhancement (LGE) and interstitial via T1 mapping MF were assessed. Replacement MF was expressed as LGE mass and LGE extent, whereas interstitial MF as extracellular volume (ECV). Left ventricular (LV) matrix and cell volumes were calculated based on LV mass and ECV as: LV matrix volume = (LV mass/1.05 g/mL) × ECV and LV cell volume = (LV mass/1.05 g/mL) × (1 − ECV). After 12 months CMR studies with MF assessment were repeated. Results Overall, index LV end-diastolic and end-systolic volumes (LVEDvol, LVESvol) and LV mass significantly decreased, whereas EF increased during follow-up (Table 1). Both, LGE mass (8.7±8.1 vs. 8.6±7.7 g; p=0.6) and LGE extent (4.6±4.2 vs. 4.97±4.6%; p=0.14) were similar between two measurements. There was a trend towards ECV decrease between baseline and follow-up studies but it did not reach statistical significance (28.5±4.9 vs. 27.7±4.1%; p=0.09). LV matrix volume significantly decreased during follow-up (49.1±17.8 vs. 46.1±15.7 ml; p<0.05); however LV cell volume remained unchanged (123.1±35.6 vs. 119.7±39.6 ml; p=0.2). Conclusions Beneficial regression of LV volumes and improvement of systolic function is common in DCM over mid-term period (one year). Replacement fibrosis seems to be a “fixed” pathology without much room for improvement. On the other hand, interstitial fibrosis seems to be a subject for substantial change. Left ventricular cells compartment does not change over time. Two types of MF – replacement and interstitial behaved differently during follow-up. Interstitial MF is amenable for treatment, whereas replacement MF does not respond to currently available therapy. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was founded through the National Science Centre, Poland (grant number 2018/29/B/NZ5/02588) and the Department of Scientific Research and Structural Funds of Medical College, Jagiellonian University (grant number K/ZDS/007192)
Non-sustained ventricular tachycardia (nsVT) creates the electrical basis for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). We aimed to evaluate the relationship between interstitial fibrosis on cardiac magnetic resonance (CMR) and nsVT in HCM. A total of 50 HCM patients underwent CMR with a 3 T scanner to determine the presence of replacement fibrosis expressed by late gadolinium enhancement (LGE), and interstitial fibrosis expressed by native T₁, post-contrast T₁, and extracellular volume (ECV). The incidence of nsVT was assessed by Holter monitoring. We detected nsVT in 14 (28%) out of 50 HCM patients. Replacement fibrosis expressed by LGE was present in 37 (74%) patients and only showed a trend towards a differentiation between the groups with and without nsVT (p = 0.07). However, the extent of LGE was clearly higher in the nsVT group (3.8 ± 4.9% vs. 7.94 ± 4.5%, p = 0.002) and was an independent predictor of nsVT in a multivariable regression analysis (OR 1.2; 95%CI 1.02–1.4; p = 0.02). No relationship was observed between interstitial fibrosis and nsVT. To conclude, it was found that it is not the mere presence but the actual extent of LGE that determines the occurrence of nsVT in HCM patients; the role of interstitial fibrosis remains unclear.
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