Outcome In Dilated Cardiomyopathy Research Articles

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

CORONARY FLOW AT REST AND CLINICAL OUTCOMES IN DILATED CARDIOMYOPATHY

CORONARY FLOW AT REST AND CLINICAL OUTCOMES IN DILATED CARDIOMYOPATHY

Temporal progression of replacement and interstitial fibrosis in optimally managed dilated cardiomyopathy patients: A prospective study

Background: To prospectively examine the dynamic evolution of fibrotic processes within a one-year in patients with dilated cardiomyopathy (DCM). Methods: Between May 2019 and September 2020, 102 DCM patients (mean age 45.2 ± 11.8 years, EF 29.9 ± 11.6%) underwent cardiac magnetic resonance (CMR-1). After 13.9 ± 2.9 months, 92 of these patients underwent a follow-up CMR (CMR-2). Replacement fibrosis was assessed via late gadolinium enhancement (LGE), quantified in terms of LGE mass and extent. Interstitial fibrosis was evaluated via T1-mapping and expressed as extracellular volume fraction (ECV). This data, along with left ventricular (LV) mass, facilitated the calculation of LV matrix and cellular volumes. Results: At CMR-1, LGE was present in 45 patients (48.9%), whereas at CMR-2 LGE was detected in 46 (50%) (p = 0.88). Although LGE mass remained stable, LGE extent increased from 2.18 ± 4.1% to 2.7 ± 4.6% (p < 0.01). Conversely, ECV remained unchanged [27.7% (25.5–31.3) vs. 26.7% (24.5–29.9); p = 0.19]; however, LV matrix and cell volumes exhibited a noteworthy regression. During a subsequent follow-up of 19.2 ± 9 months (spanning from CMR-2 to April 30th, 2023), the composite primary outcome (all-cause mortality, HTX, LVAD or heart failure worsening) was evident in 18 patients. Only the LV matrix volume index at follow-up was an independent predictor of outcome (OR 1.094; 95%CI 1.004–1.192; p < 0.05). Conclusions: In optimally managed DCM patients, both replacement and interstitial fibrosis remained stable over the course of one year. In contrast, LV matrix and cell volumes displayed significant regression. LV matrix volume index at 12-month follow-up was found to be an independent predictor of outcome in DCM.

Clinical characteristics, treatment, trajectories and outcome of patients with dilated cardiomyopathy in a national heart failure registry

BackgroundAvailable data on the clinical characteristics and prognosis of patients with heart failure (HF) due to dilated cardiomyopathy (DCM) derive mainly from tertiary care centres for cardiomyopathies or from drug trial sub-studies, which may entail a referral bias. MethodsFrom 2008 to 2021, we enrolled in a nationwide HF Registry 1886 DCM patients and 3899 with ischemic heart disease (IHD). ResultsPatients with DCM were younger, more often female, had more commonly recent onset HF, left bundle branch block, and showed higher LV end-diastolic volume and lower LVEF than IHD. With respect to IHD, DCM patients received more often mineralocorticoid receptor antagonists, renin angiotensin system inhibitors and betablockers, the latter more commonly at doses ≥50% of target, and triple guideline-directed medical therapy (GDMT) (adjusted OR 1.411, 95% CI 1.247-1.595, p < .0001). During one-year follow-up, 819 patients (14.2%) died or were hospitalized for HF [187 (9.9%) DCM, 632 (16.2%) IHD]; DCM was associated with lower risk of the combined end-point (adjusted HR 0.745, 95% CI 0.625- 0.888, p = .0011). Among the 1954 patients with 1-year echocardiograms available, 1483 had LVEF≤40% at baseline; of these,166 (30.6%) DCM and 165 (17.5%) IHD improved their LVEF to >40% (p < .0001). DCM aetiology was associated with higher likelihood of LVEF improvement (adjusted OR 1.722, 95% CI 1.328 -2.233, p < .0001). ConclusionsDCM patients have a different clinical profile, greater uptake of GDMT and better outcomes than IHD subjects. A comprehensive management approach is needed to further address the risk of unfavorable outcomes in DCM.

Diverse distribution patterns of segmental longitudinal strain are associated with different clinical features and outcomes in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) presents with diverse clinical courses, hardly predictable solely by the left ventricular (LV) ejection fraction (EF). Longitudinal strain (LS) offers distinct information from LVEF and exhibits various distribution patterns. This study aimed to evaluate the clinical significance of LS distribution patterns in DCM. We studied 139 patients with DCM (LVEF ≤ 35%) who were admitted for heart failure (HF). LS distribution was assessed using a bull's eye map and the relative apical LS index (RapLSI), calculated by dividing apical LS by the sum of basal and mid-LS values. We evaluated the associations of LS distribution with cardiac events (cardiac death, LV assist device implantation, or HF hospitalization) and LV reverse remodeling (LVRR), as indicated by subsequent LVEF changes. Twenty six (19%) and 29 (21%) patients exhibited a pattern of relatively apical impaired or preserved LS (defined by RapLSI < 0.25 or > 0.75, signifying a 50% decrease or increase in apical LS compared to other segments), and the remaining patients exhibited a scattered/homogeneously impaired LS pattern. The proportion of new-onset heart failure and LVEF differed between the three groups. During the median 595-day follow-up, patients with relatively-impaired apical LS had a higher rate of cardiac events (both log-rank p < 0.05) and a lower incidence of LVRR (both p < 0.01) compared to patients with other patterns. RapLSI was significantly associated with cardiac event rates after adjusting for age, sex, and new-onset HF or global LS. DCM patients with reduced EF and distinct distribution patterns of impaired LS experienced different outcomes.

The Prognostic Value of Serum Calcium Levels in Elderly Dilated Cardiomyopathy Patients.

It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan-Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Serum calcium level could be served as a simple and affordable tool to evaluate patients' prognosis in DCM.

Association between late gadolinium enhancement and outcome in dilated cardiomyopathy: A meta-analysis.

The prognostic value of late gadolinium enhancement (LGE) derived from cardiovascular magnetic resonance (CMR) is well studied, and several new metrics of LGE have emerged. However, some controversies remain; therefore, further discussion is needed, and more precise risk stratification should be explored. To investigate the associations between the positivity, extent, location, and pattern of LGE and multiple outcomes in dilated cardiomyopathy (DCM). PubMed, Ovid MEDLINE, and Cochrane Library were searched for studies that investigated the prognostic value of LGE in patients with DCM. Pooled hazard ratios (HRs) and 95% confidence intervals were calculated to assess the role of LGE in the risk stratification of DCM. Nineteen studies involving 7330 patients with DCM were included in this meta-analysis and covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 21% and 50%. The meta-analysis revealed that the presence of LGE was associated with an increased risk of multiple adverse outcomes (all-cause mortality, HR: 2.14; arrhythmic events, HR: 5.12; and composite endpoints, HR: 2.38; all P < 0.001). Furthermore, every 1% increment in the extent of LGE was associated with an increased risk of all-cause mortality. Analysis of a subgroup revealed that the prognostic value varied based on different location and pattern of LGE. Additionally, we found that LGE was a stronger predictor of arrhythmic events in patients with greater left ventricular ejection fraction. LGE by CMR in patients with DCM exhibited a substantial value in predicting adverse outcomes, and the extent, location, and pattern of LGE could provide additional information for risk stratification.

Genotype influences end-stage heart failure occurrence in dilated cardiomyopathy

Abstract Introduction A monogenic cause of a dilated cardiomyopathy (DCM) phenotype is found in upto 37% of patients [1]. Purpose Evaluate the influence of genotype on end-stage heart failure (ESHF) outcomes in DCM. Methods Consecutive patients carrying variants from the 3 most prevalent DCM genotypes in a database from a cardiomyopathy unit (TTN, DSP and LMNA) and with features of DCM at baseline were retrospectively recruited. Consecutive DCM patients returning a negative result from a next generation DCM panel were recruited for comparison. ESHF was defined as left ventricular assist device implantation, heart transplantation or heart-failure related death. The incidence of ESHF was compared between genotypes during follow-up. Results 493 patients from 445 families (311 (63.1%) males, presenting at a median [IQR] age of 50.8 years [37.3 – 59.8]) with a median follow-up of 46.5 [28.1 – 88.2] months were recruited (Table 1). 26/493 (5.3%) of patients had ESHF by last evaluation. The highest incidence of ESHF was seen in LMNA variant-carriers and the lowest in genotype-negative patients (Figure 1). In a multivariable Cox model including age at presentation, sex and proband status, LMNA variant-carriage was associated with an increased risk of ESHF (HR 9.7 [4.6 – 20.6], p &amp;lt; 0.001) and genotype-negative status was associated with a reduced risk of ESHF (HR 0.08 [0.02 – 0.41], p = 0.002) Conclusions Genotype impacts the incidence of ESHF in patients with DCM. Close monitoring with early initiation of heart failure therapies is essential to mitigate this risk, particularly in LMNA variant-carriers.Table 1Figure 1

Nonspecific intraventricular conduction delay predicts the prognosis of dilated cardiomyopathy

PurposeLeft bundle branch block (LBBB) has been confirmed to be independently associated with adverse outcomes in dilated cardiomyopathy (DCM). However, prognostic data on nonspecific intraventricular conduction delay (NSIVCD) are still limited and conflicting. We aimed to evaluate the prognosis of DCM with NSIVCD.MethodsA total of 548 DCM patients who underwent cardiovascular magnetic resonance imaging (CMR) from January 2016 to December 2017 were consecutively enrolled. The cohort was divided into four groups: 87 with LBBB, 27 with RBBB, 61 with NSIVCD, and 373 without intraventricular conduction delay (IVCD). After a median follow-up of 58 months (interquartile range: 47–65), 123 patients reached the composite endpoints, which included cardiovascular death, heart transplantation, and malignant arrhythmias. The associations between different patterns of IVCD and the outcomes of DCM were analysed by Kaplan‒Meier analysis and Cox proportional hazards regression analysis.ResultsOf 548 DCM patients, there were 398 males (72.6%), and the average age was 46 ± 15 years, ranging from 18 to 76 years. In Kaplan‒Meier analysis, patients with NSIVCD and LBBB showed higher event rates than patients without IVCD, while RBBB patients did not. By multivariate Cox regression analysis, LBBB, NSIVCD, NYHA class, left ventricular ejection fraction (LVEF), indexed left ventricular end-diastolic diameter (LVEDDI), percentage of late gadolinium enhancement mass (LGE%), and global longitudinal strain (GLS) were found to be independently associated with the outcomes of DCM.ConclusionsIn addition to LBBB, NSIVCD was an unfavourable prognostic marker in patients with DCM, independent of LVEDDI, NYHA class, LVEF, LGE%, and GLS.

Circulating biomarker- and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) has a high mortality rate and is the most common indication for heart transplantation. Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation (ACM/HTx) risk in DCM patients. The present study is a retrospective cohort study. The demographic, clinical, blood test, and cardiac magnetic resonance imaging (CMRI) data of DCM patients in the tertiary center (Fuwai Hospital) were collected. The primary endpoint was ACM/HTx. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for variable selection. Multivariable Cox regression was used to develop a nomogram. The concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. A total of 218 patients were included in the present study. They were randomly divided into a training cohort and a validation cohort. The nomogram was established based on eight variables, including mid-wall late gadolinium enhancement, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume index, free triiodothyronine, and N-terminal pro-B type natriuretic peptide. The AUCs regarding 1-year, 3-year, and 5-year ACM/HTx events were 0.859, 0.831, and 0.840 in the training cohort and 0.770, 0.789, and 0.819 in the validation cohort, respectively. The calibration curve and DCA showed good accuracy and clinical utility of the nomogram. We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.

Left atrial strain at CMR is a strong independent prognostic predictor in DCM, superior to LV-GLS, LVEF and LAVI, and incremental to LGE

Abstract Background The left atrium (LA) is an early sensor of left ventricular (LV) dysfunction. LA size and new-onset atrial fibrillation (AF) are associated with an increased risk of mortality and heart failure (HF) progression in patients with dilated cardiomyopathy (DCM). Whether abnormal LA strain measured at cardiac magnetic resonance (CMR) – a new technology to study atrial function – may predict overall outcome in DCM – either or not leading to new onset AF – remains completely unknown. Purpose To determine the prognostic value of CMR derived LA strain in DCM patients. Methods A total of 488 DCM patients (age 54 [46–62] years, 61% male) undergoing CMR were prospectively enrolled in the Maastricht Cardiomyopathy Registry between 2004 and 2018. Outcome consisted of the combination of sudden or cardiac death, HF hospitalization or life-threatening arrhythmias. LA reservoir (passive LA filling), conduit (passive LV filling), and booster strain (active LV filling) were measured using feature tracking strain analysis of the 2- and 4-chamber long-axis cines (Figure 1). Given the non-linearity of continuous variables, cubic spline analysis was performed to dichotomize. Results Seventy out of 488 DCM patients (14%) reached the endpoint (follow-up 6 [4–9] years). Age, NYHA class ≥3, late gadolinium enhancement (LGE) presence, LV ejection fraction (EF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with worse outcome (all p-values &amp;lt;0.02). LA conduit strain was superior to reservoir strain to predict outcome. LA conduit strain, NYHA class ≥3 and LGE remained associated in the multivariable model (Figure 2A), while age, NTproBNP, LVEF, LA ejection fraction, LAVI and LV-GLS did not. Adding LA conduit strain to NYHA class and LGE significantly improved the calibration, accuracy, and reclassification of the prediction model (p&amp;lt;0.05). In patients without known AF and sinus rhythm (n=425) during CMR, 10% developed new-onset AF (paroxysmal or persistent) at long-term. Higher age, male sex, NYHA class ≥3, higher LAVI and impaired booster strain were all univariably associated with new-onset AF. Age and impaired booster strain remained as independent predictors of new-onset AF in the multivariable analysis (Figure 2B). Conclusions LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV-GLS, LVEF and LAVI, and incremental to LGE. In addition, LA booster strain is an independent predictor of new-onset AF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation

Pregnancy in women with dilated cardiomyopathy.

Only a few studies describe the pathophysiology and outcomes of dilated cardiomyopathy (DCM) in pregnancy, which the authors aim to review here. DCM causes enlargement of the ventricles and reduced systolic function. Fluid overload and raised cardiac output in pregnancy may contribute to cardiac complications that lead to cardiac remodeling and heart failure, a common cause of maternal mortality. The risk of cardiac complications is higher in women with New York Heart Association class III and IV. Fetal and neonatal complications are common with coexisting obstetric risk factors. Hence, prepregnancy counseling and a multi-disciplinary approach are essential. Renin-angiotensin-aldosterone system blockers prevent cardiac remodeling but are teratogenic. Drugs, such as β-blockers to control cardiac remodeling, thiazide diuretics to reduce preload, hydralazine and nitrates to reduce afterload and digoxin to increase inotropy, are safe and should be used to manage DCM in pregnancy.

Abstract 9320: Biological Sex as a Modifier of the Natural History of Dilated Cardiomyopathy

Introduction: Dilated cardiomyopathy (DCM) has a ~20% 5-year mortality rate. Understanding the impact of biological sex offers scope to improve outcomes. Objective: Investigate potential sex specific differences in the outcome of DCM. Methods: Prospective longitudinal observational cohort study of 604 patients (n=206 women, 398 men) with DCM confirmed by cardiac MRI. The median follow up for cardiovascular death, major heart failure and arrhythmic events was 3.9 years. Results: At baseline women had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less myocardial fibrosis and lower serum troponin concentrations (all p&lt;0.05, Table 1), with no difference in age at study enrolment or medication. Despite this favourable profile, within 2 years women had more primary outcome events than men (Figure) with Kaplan Meier estimates of 10.7% vs 5.1%; adjusted* hazard ratio 3.47, 95% CI 1.81 to 6.65, [*age, LVEF, troponin, LMNA , left atrial volume and myocardial fibrosis]. Between 2-5 years, men and women had similar outcomes (adjusted* HR 0.55; 0.17,1.78). An LVEF &lt;35% in men (HR 3.21, 1.67 to 6.18, C-statistic 0.647) but &lt;40% in women (HR 2.37, 1.05 to 5.36, C statistic 0.602) had the greatest discrimination for predicting outcome. Conclusions: Female sex is an adverse modifier of the early natural history of DCM. There is evidence for sex specific risk stratification thresholds. Sex should be considered a determining variable in DCM care.

Left Atrial Function Predicts Outcome in Dilated Cardiomyopathy: Fast Long-Axis Strain Analysis Derived from MRI.

Background There is increasing recognition that left atrial (LA) function is prognostically important in cardiovascular disease. LA strain is a sensitive parameter to describe complex LA phasic function. However, the prognostic value of LA strain in participants with idiopathic dilated cardiomyopathy (DCM) remains unclear. Purpose To evaluate the prognostic value of LA strain derived from cardiac MRI in study participants with idiopathic DCM. Materials and Methods Participants with idiopathic DCM who underwent cardiac MRI between June 2012 and November 2018 were prospectively enrolled. The fast long-axis strain MRI method was performed to assess LA strain. The primary end point was all-cause mortality and heart transplant, and the secondary end point was a combination of primary end point, heart failure readmission, and aborted sudden cardiac death. Cox regression analyses and Kaplan-Meier survival analysis were performed to identify the association between variables and outcomes. Results There were 497 participants (mean age, 47 years ± 14 [standard deviation]; 357 men) evaluated. During a median follow-up of 36 months (interquartile range, 26-54 months), 113 participants reached primary end points and 203 participants reached secondary end points. LA reservoir, conduit and booster strain, and strain rate were lower in participants with primary end points (P < .001). In multivariable Cox regression analysis, LA reservoir strain and conduit strain were independent predictors for primary end point (hazard ratio [HR] per 1% increase, 0.95 [95% CI: 0.91, 0.99; P = .008] and 0.92 [95% CI: 0.87, 0.98; P = .010], respectively) and secondary end points (HR per 1% increase, 0.95 [95% CI: 0.93, 0.97; P < .001] and 0.93 [95% CI: 0.89, 0.97; P < .001], respectively). In addition, LA reservoir strain and conduit strain added incremental prognostic value to clinical risk factors and late gadolinium enhancement presence (all, P < .05). Conclusion Left atrial reservoir and conduit strain, derived from cardiac MRI by using the fast long-axis method, were independent predictors of adverse clinical outcomes in idiopathic dilated cardiomyopathy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh in this issue.

Temporal trends in outcome and patient characteristics in dilated cardiomyopathy, data from the Swedish Heart Failure Registry 2003\u20132015

BackgroundTemporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003–2015.MethodsDCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003–2007 (Period 1, n = 2029), 2008–2011 (Period 2, n = 3363), 2012–2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry.ResultsOver the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043).ConclusionsFrom 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.

Relationships between circulating galectin-3, extracellular matrix fibrosis and outcomes in dilated cardiomyopathy.

Galectin-3 is an emerging biomarker in cardiovascular disease. Myocardial galectin-3 is involved in the pathology of cardiac fibrosis; however, the role of circulating galectin-3 is not yet established. To assess the relationships between circulating galectin-3, fibrosis and outcomes in dilated cardiomyopathy (DCM). We included 70 patients (age: 48 ±12.1 years, ejection fraction (EF) 24.4 ±7.4%) with new-onset DCM (n = 35, ≤6 months). Galectin-3 and procollagen type I and III (PICP, PINP, PIIICP, and PIIINP), transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), osteopontin (OPN), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitor (TIMP-1) were determined in serum at baseline and after 3 and 12 months. Patients underwent endomyocardial biopsy. The endpoint was a combination of death and urgent hospitalization at 12 months. Galectin-3 did not correlate with biopsy-determined fibrosis. Baseline galectin-3 correlated with OPN,, TIMP-1, PIIICP, and MMP-2. In new-onset DCM, galectin-3 levels at baseline were higher than at 3 and 12 months, whereas in chronic DCM there was no difference. Galectin-3 was a predictor of the endpoint (hazard ratio (HR) = 1.115; 95% confidence interval (95% CI) = 1.009-1.231; p < 0.05). The best cut-off value was 14.54 ng/mL (area under the curve (AUC) = 0.67). Patients with galectin-3 ≥14.54 ng/mL had an increased risk of events (HR = 2.569; 95% CI = 1.098-6.009; p < 0.05). Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.

86 Amniotic fluid microRNA profiles in twin-twin transfusion syndrome with and without severe cardiomyopathy

Twin-twin transfusion syndrome (TTTS) presents many challenges for clinicians, and the optimal means of identifying which pregnancies will benefit most from intervention is controversial. There is currently no clinically significant biomarker to detect or risk-stratify TTTS. microRNAs (miRs) are small RNAs that regulate gene expression and are biomarkers in various disease processes, including adult and pediatric heart failure. To date no studies have investigated amniotic fluid (AF) miR as a biomarker for severe TTTS. This study aims to assess whether AF miRs could be useful as biomarkers to identify pregnancies at greatest risk of severe cardiomyopathy due to TTTS. AF was collected at the time of amniocentesis or selective fetoscopic laser photocoagulation from monochorionic diamniotic twin pregnancies with TTTS at any stage and stored at -80° C. Fetal echocardiography was available for all subjects, and right ventricular Tei index of the recipient fetus ≥ 0.64 was used to define severe cardiomyopathy. RNA was extracted from the AF samples using the miRNeasy Mini Kit (Qiagen) and miR arrays were performed using the TaqMan Open Array miR panel (ThermoFisher). Student’s t-test was performed between groups and a stringent q-value of <0.005 was used to determine differentially expressed miRs. Hierarchical cluster analysis (HCA) was used to determine if these miRs properly separated the two groups. A total of 11 AF samples from pregnancies with severe cardiomyopathy were compared to 12 control TTTS samples without severe cardiomyopathy. 40 miRs were differentially expressed. HCA (Fig 1) based on these 40 miRs show a strong ability to differentiate the two groups. All differentially expressed miRs were downregulated in the severe cardiomyopathy group with the exception of upregulation of miR-208 (Fig 2), which has previously been shown to be associated with adverse outcomes in dilated cardiomyopathy. AF miRs demonstrate differential expression in TTTS with and without severe cardiomyopathy, and can be an important biomarker of disease severity in this population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Trends in outcome and patient composition in dilated cardiomyopathy in Sweden over time

Abstract Background We studied prognosis and patient composition over time in dilated cardiomyopathy (DCM): a well-defined category of heart failure (HF), often affecting younger individuals. We expected improved prognosis over time, due to emerging diagnostic and therapeutic options. Methods All patients from the Swedish Heart Failure Registry (SwedeHF) fulfilling criteria for DCM (exclusion of ischemic, valvular, or alcoholic etiology and affirmed by clinical judgment in the protocol) (n=3739), were analyzed with respect to three time periods of inclusion in the registry, 2003–2007 (n=814), 2008–2011 (n=1448), 2012–2016 (n=1477), regarding mortality, transplantations, and hospital admissions during one year after inclusion. Results Over the three time periods, registered cohorts were older with time (mean 59.3 years/ 60 years/ 61.0 years, p=0.0035), and the proportion of females incresased (24.1% / 27.2% / 30.7%, p=0.0006). For clinical variables, the distribution of left ventricular ejection fraction (LVEF) with time showed significantly higher LVEF (p=0.0024), and functional classification (NYHA) showed lower class (p=0.0011). Hypertension as a comorbidity (i.e. not judged to be responsible for HF) was more frequently occurring with time: (34.0%/ 40.6%/ 44.1%, p&amp;lt;0.0001). As for HF treatment: use of device increased (p&amp;lt;0.0001 for categorical combinations), mineralocorticoid receptor antagonists (MRA) increased (41.9%/ 37.3%/ 46.7%, p=0.0023), and diuretics dropped (76.1%/ 71.1%/ 67.0%, p≤0.0001) in the different cohorts with time. Mortality (6.9%, 5.1%, 5.5%), transplantation (0.5%, 0.8%, 0.6%) and hospital admissions for HF (28.4%, 26.3%, 24.6%) were stable over time (ns for all), whereas cardiovascular (CV) (33.8%, 33.8%, 29.7%, p=0.043) and all cause admissions (39.1%, 38.8%, 33.7%, p=0.0099) decreased. After adjustment for age, sex, LVEF, NYHA, hypertension and device treatment only all cause admissions remained significantly decreased. Conclusion In this nationwide study between 2003–2016, one-year outcome in DCM in Sweden remained stationary over time, despite advances in HF therapy. During the time period, we observed a continuous change in the clinical profile in the DCM population. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Region Västra Götaland agreement concerning research and education of physicians.

Genetic variant burden and adverse outcomes in pediatric cardiomyopathy.

Previous genetic research in pediatric cardiomyopathy (CM) has focused on pathogenic variants for diagnostic purposes, with limited data evaluating genotype-outcome correlations. We explored whether greater genetic variant burden (pathogenic or variants of unknown significance, VUS) correlates with worse outcomes. Children with dilated CM (DCM) and hypertrophic CM (HCM) who underwent multigene testing between 2010 and 2018 were included. Composite endpoint was freedom from major adverse cardiac event (MACE). Three hundred and thirty-eight subjects were included [49% DCM, median age 5.7 (interquartile range (IQR) 0.2-13.4) years, 51% HCM, median age 3.0 (IQR 0.1-12.5) years]. Pathogenic variants alone were not associated with MACE in either cohort (DCM p = 0.44; HCM p = 0.46). In DCM, VUS alone [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.9-8.3] and in addition to pathogenic variants (OR 5.2, 95% CI 1.7-15.9) was associated with MACE. The presence of VUS alone or in addition to pathogenic variants were not associated with MACE in HCM (p = 0.22 and p = 0.33, respectively). Increased genetic variant burden (pathogenic variants and VUS) is associated with worse clinical outcomes in DCM but not HCM. Genomic variants that influence DCM onset may be distinct from those driving disease progression, highlighting the potential value of universal genetic testing to improve risk stratification. In pediatric CM, inconsistent findings historically have been shown between genotype and phenotype severity when only pathogenic variants have been considered. Increased genetic variant burden (including both pathogenic variants and VUS) is associated with worse clinical outcomes in DCM but not HCM. Genomic variants that influence CM onset may be distinct from those variants that drive disease progression and influence outcomes in phenotype-positive individuals. Incorporation of both pathogenic variants and VUS may improve risk stratification models in pediatric CM.

Relations between circulating and myocardial fibrosis-linked microRNAs with left ventricular reverse remodeling in dilated cardiomyopathy.

Left ventricular reverse remodeling (LVRR) determines clinical status and outcomes in dilated cardiomyopathy (DCM). The extent of myocardial fibrosis is connected to the systolic function of the heart. The recent discovery of the contribution of microRNAs (miRs) to the regulation of cardiac remodeling, LVRR and fibrosis warrants exploration. The aim of the study was to examine the predictive value of circulating and myocardial miR expression for LVRR in DCM. Seventy consecutive DCM patients (age 48 ±12.1 years, 90% male, ejection fraction (EF) 24.4% ±7.4%) were included in the study. At baseline, all patients underwent clinical assessment, echocardiography, venous blood sampling, and right ventricular endomyocardial biopsy. Circulating and myocardial miRs (miR-21, -26, -29, -30, -133a, and -423) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). LVRR was defined as an increase in EF ≥ 10%, accompanied by a decrease in left ventricle end-diastolic diameter (LVEDd) ≥10% or LVEDd ≤ 33 mm/m2 between baseline and 3-month follow-up. At the 3-month follow-up, 4 patients had died and 3 patients had incomplete data. The remaining patients were divided according to the presence of LVRR into LVRR-present (n = 32, 51%) and LVRR-absent (n = 31, 49%) groups. Out of all the circulating and tissue miRs under study, only myocardial expression of miR-133a significantly differed between the LVRR-present and LVRR-absent group (1.22 (0.47-1.90) vs 0.61 (0.25-0.99) ΔCq, respectively, p < 0.01). miR-133a was found to be a significant LVRR predictor in unadjusted (odds ratio (OR) = 2.81 (1.23-6.40), p < 0.05) and adjusted for duration of disease, left ventricle end-diastolic (LVED) volume (LVEDvol), hs-troponin-T, and NT-proBNP (OR = 5.20 (1.13-24.050, p < 0.05) models. From all of the circulating and tissue miRs, only myocardial miR-133a showed increased expression in LVRR-present patients and was found an independent LVRR predictor. This indicates a link between miR-133 and cardiac remodeling in DCM.