Risk Stratification In Dilated Cardiomyopathy Research Articles

Extracellular volume is an independent predictor of arrhythmic burden in dilated cardiomyopathy

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.

Magnetic resonance imaging of dilated cardiomyopathy: prognostic benefit of identifying late gadolinium enhancement in Asian patients.

Risk stratification in dilated cardiomyopathy (DCM) is imprecise, relying largely on echocardiographic left ventricular ejection fraction (LVEF) and severity of heart failure symptoms. Adverse cardiovascular events are increased by the presence of myocardial scarring. Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is the gold standard for identifying myocardial scars. We examined the association between LGE on CMR imaging and adverse clinical outcomes during long-term follow-up of Asian patients with DCM. Consecutive patients with DCM undergoing CMR imaging at a single Asian academic medical centre between 2005 and 2015 were recruited. Clinical outcomes were tracked using comprehensive electronic medical records and mortality was determined by cross-linkages with national registries. Presence and distribution of LGE on CMR imaging were determined by investigators blinded to patient outcomes. Primary endpoint was a composite of heart failure hospitalisations, appropriate implantable cardioverter-defibrillator shocks and cardiovascular mortality. Of 86 patients, 64.0% had LGE (80.2% male; mean LVEF 30.1% ± 12.7%). Mid-wall fibrosis (71.7%) was the most common pattern of LGE distribution. Over a mean follow-up period of 4.9 ± 3.2 years, 19 (34.5%) patients with LGE reached the composite endpoint compared to 4 (12.9%) patients without LGE (p = 0.01). Presence of LGE, but not echocardiographic LVEF, independently predicted the primary endpoint (hazard ratio 4.15 [95% confidence interval 1.28-13.50]; p = 0.02). LGE presence independently predicted adverse clinical events in Asian patients with DCM. Routine use of CMR imaging to characterise the myocardial substrate is recommended for enhanced risk stratification and should strongly influence clinical management.

Myocardial mechanics in dilated cardiomyopathy: prognostic value of left ventricular torsion and strain

BackgroundData on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT).MethodsCMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome.ResultsGLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p < 0.001). The primary endpoint occurred in 59 (18.7%) patients [median follow-up 4.2 (2.0–5.6) years]. In the univariate analyses all strain parameters showed a significant prognostic value (p < 0.05). In the multivariate model, LV strain parameters, particularly GLS provided an incremental prognostic value compared to established CMR parameters like LV ejection fraction and late gadolinium enhancement. A scoring model including six categorical variables of standard CMR and strain parameters differentiated further risk subgroups.ConclusionLV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.

Prognostic value of cardiovascular magnetic resonance T1 mapping techniques in non-ischemic dilated cardiomyopathy: A systematic review and meta-analysis

BackgroundCardiovascular magnetic resonance T1 mapping is a non-invasive tool for quantifying tissue alterations in the myocardium. Its prognostic value in non-ischemic dilated cardiomyopathy (DCM) remains unclear. The purpose of this study was to synthetize available data and explore the prognostic value of T1 mapping in DCM. MethodsWe searched Pubmed, Embase, Cochrane Library and Scopus for cohort studies up to 28 March 2020 that reported prognostic data for cardiovascular magnetic resonance T1 mapping in patients with DCM. Hazard ratios (HRs) were pooled using random-effects meta-analysis. Values were expressed as standard deviation (SD) of normal controls. Heterogeneity was assessed with the I2 statistic. ResultsEight studies were included in the meta-analysis, with a total of 1242 patients. Extracellular volume fraction (ECV) had high prognostic value for a composite outcome of mortality and morbidity with HR 1.38 (95% confidence interval, 1.18–1.61). Native T1 was also shown to have high prognostic value for a composite outcome of mortality and morbidity with HR 1.20 (95% confidence interval, 1.14–1.27). Heterogeneity was moderate for the ECV analysis (I2 = 64%). ConclusionsECV and native T1 could potentially be used to improve risk stratification in DCM. Future studies should investigate the prognostic value of T1 mapping by separating mortality and morbidity as primary outcomes and evaluate its incremental value in addition to standard risk stratification criteria.

Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing?

Background Sudden cardiac death (SCD) risk stratification in dilated cardiomyopathy (DCM) has been based on left ventricular ejection fraction (LVEF), even though SCD may occur with LVEF > 35%. Family history of unexplained SCD, especially in the young, raises concern about potential inheritable risk factors. It remains largely unknown how genetic tests can be integrated into clinical practice, particularly in the selection of implantable cardioverter defibrillator (ICD) candidates. We aimed to assess the diagnostic yield of genetic testing in DCM patients with a class I recommendation for ICD implantation, based on current guidelines. Methods We included ambulatory stable adult patients with idiopathic or familial DCM with previously implanted ICD. Molecular analysis included 15 genes (LMNA, MYH7, MYBPC3, TNNT2, ACTC1, TPM1, CSRP3, TCAP, SGCD, PLN, MYL2, MYL3, TNNI3, TAZ, and LDB3) using next-generation sequencing. Results We evaluated 21 patients, 12 (57%) males and 9 (43%) with familial DCM, including 3 (14%) with a family history of premature unexplained SCD. Mean age at DCM diagnosis was 40 ± 2 years, and mean age at ICD implantation was 50 ± 12 years. LVEF was 27 ± 9%, and LV end-diastolic diameter was 65 ± 7 mm. Genetic variants were found in six (29%) patients, occurring in 5 genes: TPM1, TNNT2, MYH7, PLN, and MYBPC3. The majority were classified as variants of uncertain significance. Family history of SCD was present in both patients with PLN variants. Conclusion In patients with DCM and ICD, genetic variants could be identified in a significant proportion of patients in several genes, highlighting the potential role of genetics in DCM SCD risk stratification.

005 Multimodality assessment of risk in dilated cardiomyopathy- the importance of CMR

Background Dilated cardiomyopathy (DCM) has a 20% 5 year mortality. Cardiac MR (CMR) is an established outcome predictor. We evaluate the additive role of novel genetic and circulating biomarkers.Purpose Perform an integrated assessment to evaluate the prognostic importance of CMR parameters in DCM in the context of clinical, genetic and biomarker data.Methods Prospectively recruited DCM patients underwent comprehensive clinical evaluation, CMR with late-gadolinium enhancement (LGE), sequencing for rare variants in major DCM genes (titin-TTNtv, myosin heavy chain-MYH7, troponin T2-TNNT2, lamin-LMNA), biomarker assessment of BNP, troponin I (hsTnI), Galectin 3 and ST2, and follow up for clinical events. Cox proportional hazard modelling evaluated the primary composite endpoint of cardiovascular death, major arrhythmic events (aborted sudden cardiac death, appropriate ICD activation, sustained ventricular tachycardia, ventricular fibrillation) and major heart failure events (heart transplant, left ventricular assist device, unplanned heart failure hospitalisation).Results In total, 423 patients with DCM (mean age 53.6±14.1 years, 67% male) were followed up for a median of 4.0 years (IQR 2.1–5.8). Mean left ventricular ejection fraction (LVEF) was 40%±12.5%. One third of patients had mid-wall fibrosis (MWF-LGE) (n=137, 32%). Mean indexed left atrial volume (LAVi) was 61±27.6 mls.On genetic analysis, 53 patients (12.5%) had TTNtv, 14 patients (3.3%) had non-truncating variants in MYH7, 5 patients (1.2%) had non-truncating variants in TNNT2 and 5 patients (1.2%) had LMNA variants.In total, 44 patients (10.4%) met the primary endpoint. On multivariable analysis, an optimal model predicting the primary endpoint was built without genetic or biomarker data (Table 1). This consisted of LVEF, LAVi, and MWF-LGE (Table 2).On univariable analysis, BNP, Galectin 3 and hsTnI were associated with the primary endpoint (Table 2). When the novel variables were added to the optimised model, Galectin 3 and LMNA variants were predictive of the primary endpoint (Table 3). In the final adjusted model, CMR parameters remained predictive of the primary endpoint. Of these, MWF-LGE was the strongest predictor (adjusted HR 2.12 (1.06–4.02), p=0.02).View this table:Abstract 005 Table 1 Variables evaluated in building baseline Cox proportional hazard model predicting primary endpointView this table:Abstract 005 Table 2 Results of baseline Cox proportional hazard modelling predicting primary endpointView this table:Abstract 005 Table 3 Results of evaluation of biomarkers and genetic variants using Cox proportional hazard modelling predicting primary endpointView this table:Abstract 005 Table 4 Results of final adjusted Cox proportional hazard model predicting primary endpointConclusion On integrated multi-modality risk stratification in DCM, while circulating and genetic biomarkers improve risk stratification, CMR parameters remain strong independent predictors of outcome.Acknowledgements UT is supported by a Medical Research Council (UK) Clinical Research Training Fellowship. The study has also been supported by the Rosetrees Foundation, the Alexander Jansons Foundation, the Wellcome Trust and the NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.%U http://heart.bmj.com/content/heartjnl/103/Suppl_1/A4.2.full.pdf

Clinical utility and prognostic value of left atrial volume assessment by cardiovascular magnetic resonance in non‐ischaemic dilated cardiomyopathy

Echocardiographic studies have shown that left atrial volume (LAV) predicts adverse outcome in small heart failure (HF) cohorts of mixed aetiology. However, the prognostic value of LAV in non-ischaemic dilated cardiomyopathy (DCM) is unknown. Cardiovascular magnetic resonance (CMR) allows accurate and reproducible measurement of LAV. We sought to determine the long-term prognostic significance of LAV assessed by CMR in DCM. We measured LAV indexed to body surface area (LAVi) in 483 consecutive DCM patients referred for CMR. Patients were prospectively followed up for a primary endpoint of all-cause mortality or cardiac transplantation. During a median follow-up of 5.3 years, 75 patients died and 9 underwent cardiac transplantation. After adjustment for established risk factors, LAVi was an independent predictor of the primary endpoint [hazard ratio (HR) per 10 mL/m(2) 1.08; 95% confidence interval (CI) 1.01-1.15; P = 0.022]. LAVi was also independently associated with the secondary composite endpoints of cardiovascular mortality or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.19; P = 0.003), and HF death, HF hospitalization, or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.18; P = 0.001). The optimal LAVi cut-off value for predicting the primary endpoint was 72 mL/m(2). Patients with LAVi >72 mL/m(2) had a three-fold elevated risk of death or transplantation (HR 3.00; 95% CI 1.92-4.70; P < 0.001). LAVi provided incremental prognostic value for the prediction of transplant-free survival (net reclassification improvement 0.17; 95% CI 0.05-0.29; P = 0.002). LAVi is a powerful independent predictor of transplant-free survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.

Abstract 9638: Left Atrial Volume Provides Independent and Incremental Prognostic Information in Non-Ischemic Dilated Cardiomyopathy

Introduction: Echo data have shown that left atrial (LA) diameter and area predict adverse outcome in heart failure (HF) cohorts of mixed etiology. Since LA dilatation is asymmetric, LA volume (LAV) is a better measure of LA size. CMR allows more accurate measurement of LAV due to its superior spatial resolution and endocardial border definition. We hypothesized that CMR assessment of LAV provides independent and incremental prognostic information in non-ischemic dilated cardiomyopathy (DCM). Methods: Consecutive patients with DCM referred for CMR between 2000-08 were prospectively enrolled. Patients with IHD, primary valvar disease and infiltrative CM were excluded. LAV was measured at LV end-systole by a single blinded specialist using the biplane area-length method and indexed to body surface area (LAVi). The primary endpoint was cardiovascular (CV) death or cardiac transplantation (CTx). The secondary endpoint was a composite of HF death, HF hospitalization or CTx. Results: In total 483 patients (327 male, mean age 51 yrs, mean LVEF 37%) were followed up for a median duration of 64 months. There were 75 deaths (60 CV deaths) and 9 patients underwent CTx. ROC analysis identified that the optimal LAVi cut-off value for predicting the primary endpoint was 77 ml/m 2 . Kaplan-Meier analysis demonstrated that patients with a LAVi&gt;77 ml/m 2 had a significantly higher rate of CV death or CTx (p&lt;0.001, Fig.1). After stepwise Cox regression multivariate analysis, LAVi remained a significant independent predictor of CV death or CTx (HR per 10 ml/m 2 , 1.11, 95% CI 1.04 to 1.19; p=0.003) and the secondary HF composite (HR per 10 ml/m 2 , 1.11, 95% CI 1.04 to 1.18; p=0.001), alongside conventional prognosticators such as LVEF and NYHA class. Conclusions: LAV has independent and incremental prognostic value for the prediction of transplant-free CV survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.

Lagged segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy

The objectives of this study were to introduce a new type of heart-rate variability analysis improving risk stratification in patients with idiopathic dilated cardiomyopathy (DCM) and to provide additional information about impaired heart beat generation in these patients. Beat-to-beat intervals (BBI) of 30-min ECGs recorded from 91 DCM patients and 21 healthy subjects were analyzed applying the lagged segmented Poincaré plot analysis (LSPPA) method. LSPPA includes the Poincaré plot reconstruction with lags of 1-100, rotating the cloud of points, its normalized segmentation adapted to their standard deviations, and finally, a frequency-dependent clustering. The lags were combined into eight different clusters representing specific frequency bands within 0.012-1.153 Hz. Statistical differences between low- and high-risk DCM could be found within the clusters II-VIII (e.g., cluster IV: 0.033-0.038 Hz; p = 0.0002; sensitivity = 85.7 %; specificity = 71.4 %). The multivariate statistics led to a sensitivity of 92.9 %, specificity of 85.7 % and an area under the curve of 92.1 % discriminating these patient groups. We introduced the LSPPA method to investigate time correlations in BBI time series. We found that LSPPA contributes considerably to risk stratification in DCM and yields the highest discriminant power in the low and very low-frequency bands.

Can cardiac MRI be the index metric for risk stratification in dilated cardiomyopathy; the impact of an LV mid-myocardial stripe on subsequent risk of LVAD, transplantation and death

Summary The mid-wall intramyocardial ‘stripe’ is now shown to be robust in its prediction of subsequent need for LVAD and/or transplantion and death out to 12 months following index CMR exam. Background Patients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of CMR via LGE (late gadolinium enhancement) in this cohort of high-risk patients. Hypothesis Utilizing cardiovascular MRI (CMR), we assessed the prognostic value of LGE in primary dilated DCM patients referred for possible transplantation/ LVAD consideration. Methods

Can cardiac MRI be the 'crystal ball' for risk stratification in dilated cardiomyopathy? The impact of an LV mid-myocardial stripe on LVAD and transplantation risk

Patients with newly diagnosed dilated cardiomyopathy and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of CMR via LGE in this cohort of patients.

Troponin in Non-ischaemic Dilated Cardiomyopathy

Non-ischaemic dilated cardiomyopathy (DCM) is a disease characterised by progressive left ventricular remodelling and dysfunction. DCM represents a major cause of morbidity and mortality. Cardiac troponins are sensitive biohumoral markers of myocyte injury that are used for diagnostic purposes in acute coronary syndromes but that are also detected in DCM. Several pathophysiological factors (wall stress, neurohormonal activation, inflammation, metabolic dysfunction, microvascular ischaemia) have been advocated to explain subtle ongoing necrosis in DCM. In particular, new ultrasensitive assays expand the detection range toward physiological cardiac troponin levels, allowing accurate biohumoral characterisation of myocardial remodelling from the early stages of DCM. Moreover, several clinical studies have demonstrated that increased cardiac troponin plasma levels are associated with worse prognosis and that further increases in cardiac troponin over time contribute to additional risk. Serial plasma cardiac troponin evaluation represents an accurate marker of disease evolution and risk stratification in DCM, identifying high-risk patients who need strict follow-up and enhanced therapeutic effort.

Relationship between cardiac autonomic function and sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillators

Low left ventricular ejection fraction (LVEF) is the main indication of implantable cardioverter defibrillators (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death, but ICD therapy at follow-up occurs in a minority of patients. We investigated whether heart rate variability (HRV) may improve risk stratification in DCM patients. We studied 42 patients (age 67.3 ± 3.5; 37 males) who had undergone ICD implant for either idiopathic or ischaemic DCM (LVEF <40%) 34.6 ± 19.7 months prior to the study (range 6-84). Patients underwent 24 h electrocardiographic Holter monitoring, and HRV was assessed over 2 hours in the afternoon showing stable sinus rhythm. Left ventricular ejection fraction was measured by two-dimensional echocardiography. The serum levels of C-reactive protein and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also obtained. The primary endpoint was the occurrence of appropriate ICD shocks in the 6 months preceding the study. The occurrence of appropriate ICD discharge from ICD implant was considered as a secondary endpoint. In the last 6 months, appropriate ICD shocks had occurred in seven patients (17%). There were no differences between patients with and without ICD shocks in clinical variables, as well as in LVEF and in C-reactive protein and NT-proBNP serum levels. In contrast, most HRV parameters were significantly depressed in patients with, compared with those without, ICD shocks; the most significant difference was shown for the average of the standard deviations of RR intervals in all consecutive 5 min segments (n ¼ 12) within the 2 h (26.7 ± 9 vs. 39.7 ± 14 ms; P = 0.02) in the time domain and for LF amplitude (8.4 ± 3 vs. 14.8 ± 7 ms; P = 0.02) in the frequency domain. Implantable cardioverter defibrillator discharge had occurred in 11 patients (26%) since ICD implant (average 35 months). No clinical or laboratory variable showed significant differences between patients with or without ICD discharge, except very low-frequency (VLF) amplitude (23.8 ± 7 vs. 30.8 ± 10.6 ms, respectively; P = 0.049). In ICD patients with reduced LVEF, several depressed HRV indices were significantly associated with appropriate ICD shocks in the previous 6 months, and VLF amplitude was the only variable significantly associated with ICD shocks recorded since ICD implant. These data suggest that full HRV analysis might be helpful for improving risk stratification for life-threatening ventricular arrhythmias and ICD indication in patients with DCM.

Segmented Poincaré Plot Analysis for Risk Stratification in Patients with Dilated Cardiomyopathy

The prognostic value of heart rate variability in patients with dilated cardiomyopathy (DCM) is limited and does not contribute to risk stratification although the dynamics of ventricular repolarization differs considerably between DCM patients and healthy subjects. Neither linear nor nonlinear methods of heart rate variability analysis could discriminate between patients at high and low risk for sudden cardiac death. The aim of this study was to analyze the suitability of the new developed segmented Poincaré plot analysis (SPPA) to enhance risk stratification in DCM. In contrast to the usual applied Poincaré plot analysis the SPPA retains nonlinear features from investigated beat-to-beat interval time series. Main features of SPPA are the rotation of cloud of points and their succeeded variability depended segmentation. Significant row and column probabilities were calculated from the segments and led to discrimination (up to p<0.005) between low and high risk in DCM patients. For the first time an index from Poincaré plot analysis of heart rate variability was able to contribute to risk stratification in patients suffering from DCM.

Heart rate turbulence and other autonomic risk markers for arrhythmia risk stratification in dilated cardiomyopathy

Background Noninvasive arrhythmia risk stratification in patients with nonischemic dilated cardiomyopathy (DCM) using autonomic markers have yielded disappointing results. Heart rate turbulence is a new method to assess cardiac autonomic function. Aim The aim of the study was to compare the predictive value of heart rate turbulence with those of conventional autonomic risk markers for ventricular tachyarrhythmic events in patients with DCM. Methods The predictive value of heart rate turbulence, baroreflex sensitivity (phenylephrine method), and heart rate variability was assessed in patients with symptomatic congestive heart failure due to DCM who were in sinus rhythm and had a 24-hour Holter recording. Patients were followed for a combined end point of ventricular tachyarrhythmic events. Results A total of 114 patients (mean left ventricular ejection fraction, 28 ± 11%), included in the Frankfurt DCM database between 1996 and 2000, fulfilled the criteria for inclusion in this study. Determinate test results were obtained for heart rate variability in 98%, for baroreflex sensitivity in 90%, and for heart rate turbulence in 75% of patients ( P = .008). Correlation between the different autonomic markers were only modest ( r values, 0.36-0.43). During a follow-up of 22 ± 17 months, an end point event occurred in 15 patients. On univariate analysis, left ventricular ejection fraction and baroreflex sensitivity were significant predictors of arrhythmic events. On multivariate analysis, only baroreflex sensitivity remained an independent predictor ( χ 2 = 3.17; P = .07). Conclusion Reliable analysis of heart rate turbulence is possible in approximately 75% of eligible patients with DCM. Whereas blunted baroreflex sensitivity is a predictor of arrhythmic events, heart rate variability and turbulence do not yield predictive power in these patients.