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      Towards cardiac MRI based risk stratification in idiopathic dilated cardiomyopathy

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      Heart
      BMJ

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          Abstract

          Sudden cardiac death (SCD) secondary to arrhythmia remains a risk in those with dilated cardiomyopathy (DCM), an implantable cardiac defibrillator (ICD) is an effective strategy to prevent SCD. Current guidelines recommend selection for ICD based on ejection fraction (EF) less than 35%, however, most SCD occurs in those with EF>35%. Although meta-analysis has demonstrated a survival benefit for primary prevention ICD in DCM, no randomised trial has shown a significant reduction in overall mortality including the most recent ‘Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heat Failure on Mortality’ study. Clearly, a more sophisticated selection strategy is required. Cardiac MRI (CMR) is an ideal non-invasive imaging technique which allows calculation of EF as well as tissue characterisation with gadolinium contrast, parametric mapping and feature tracking. Late gadolinium enhancement detects mid-wall fibrosis in approximately 30% of those with DCM, three meta-analyses have demonstrated an association between fibrosis in DCM and SCD, and those without fibrosis are at low risk of SCD. T1 mapping and extracellular volume (ECV) calculation are methods of demonstrating diffuse fibrosis in the myocardium. Raised ECV and native T1 have been associated with worse outcomes but the relationship to SCD has not been well studied. Undoubtedly, more research is required but CMR has several tools which offer incremental value above EF to improve risk stratification and consequent outcomes and resource utilisation in those with DCM.

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          Most cited references25

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          Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy.

          Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P = .001 and 0.29 [95% CI, 0.11-0.48]; P = .002, respectively). Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.
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            Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy.

            We studied the prognostic implications of midwall fibrosis in dilated cardiomyopathy (DCM) in a prospective longitudinal study. Risk stratification of patients with nonischemic DCM in the era of device implantation is problematic. Approximately 30% of patients with DCM have midwall fibrosis as detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR), which may increase susceptibility to arrhythmia and progression of heart failure. Consecutive DCM patients (n = 101) with the presence or absence of midwall fibrosis were followed up prospectively for 658 +/- 355 days for events. Midwall fibrosis was present in 35% of patients and was associated with a higher rate of the predefined primary combined end point of all-cause death and hospitalization for a cardiovascular event (hazard ratio 3.4, p = 0.01). Multivariate analysis showed midwall fibrosis as the sole significant predictor of death or hospitalization. However, there was no significant difference in all-cause mortality between the 2 groups. Midwall fibrosis also predicted secondary outcome measures of sudden cardiac death (SCD) or ventricular tachycardia (VT) (hazard ratio 5.2, p = 0.03). Midwall fibrosis remained predictive of SCD/VT after correction for baseline differences in left ventricular ejection fraction between the 2 groups. In DCM, midwall fibrosis determined by CMR is a predictor of the combined end point of all-cause mortality and cardiovascular hospitalization, which is independent of ventricular remodeling. In addition, midwall fibrosis by CMR predicts SCD/VT. This suggests a potential role for CMR in the risk stratification of patients with DCM, which may have value in determining the need for device therapy.
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              Population-based analysis of sudden cardiac death with and without left ventricular systolic dysfunction: two-year findings from the Oregon Sudden Unexpected Death Study.

              We sought to evaluate the contribution of left ventricular (LV) dysfunction toward occurrence of sudden cardiac death (SCD) in the general population, and to identify distinguishing characteristics of SCD in the absence of LV dysfunction. Patients who manifest warning symptoms and signs are more likely to undergo evaluation before SCD. Although prevalence of LV dysfunction in this subgroup may overestimate the prevalence in overall SCD, this is the only means of assessment in the general population. All cases of SCD in Multnomah County, Oregon (population 660,486; 2002 to 2004) were prospectively ascertained in the ongoing Oregon Sudden Unexpected Death Study. We retrospectively assessed LV ejection fraction (LVEF) among subjects who underwent evaluation of LV function before SCD (normal: > or =55%; mildly to moderately reduced: 36% to 54%; and severely reduced: < or =35%). Of a total of 714 SCD cases (annual incidence 54 per 100,000), LV function was assessed in 121 (17%). The LVEF was severely reduced in 36 patients (30%), mildly to moderately reduced in 27 (22%), and normal in 58 (48%). Patients with normal LVEF were distinguishable by younger age (66 +/- 15 years vs. 74 +/- 10 years; p = 0.001), higher proportion of females (47% vs. 27%; p = 0.025), higher prevalence of seizure disorder (14% vs. 0%; p = 0.002), and lower prevalence of established coronary artery disease (50% vs. 81%; p < 0.001). In this community-wide study, only one-third of the evaluated SCD cases had severe LV dysfunction meeting current criteria for prophylactic cardioverter-defibrillator implantation. The SCD cases with normal LV function had several distinguishing clinical characteristics. These findings support the aggressive development of alternative screening methods to enhance identification of patients at risk.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Heart
                Heart
                BMJ
                1355-6037
                1468-201X
                January 29 2019
                February 2019
                February 2019
                October 30 2018
                : 105
                : 4
                : 270-275
                Article
                10.1136/heartjnl-2018-313767
                30377260
                518e284c-f8ce-4858-9942-49e039399107
                © 2018
                History

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