Myocardial Tissue Reverse Remodeling after Guideline-directed Medical Therapy in Idiopathic Dilated Cardiomyopathy

Background - The prognosis of idiopathic dilated cardiomyopathy (DCM) patients has improved remarkably in recent decades with guideline-directed medical therapy (GDMT). Left ventricular reverse remodeling (LVRR) is one of the major therapeutic goals. Whether myocardial fibrosis or inflammation would reverse associated with LVRR remains unknown. Methods - A total of 157 prospectively enrolled DCM patients underwent baseline and follow-up CMR examinations with a median interval of 13.7 months (interquartile range: 12.2-18.5 months). LVRR was defined as an absolute increase in LV ejection fraction (LVEF) of >10% to the final value of ≥ 35% and a relative decrease in LV end-diastolic volume (EDV) of >10%. Statistical analyses were performed using paired t-test and student t-test, logistic regression analysis, and linear regression analysis. Results - Forty-eight (31%) patients reached LVRR. At baseline, younger age, worse NYHA class, new-onset heart failure, lower LVEF, absence of late gadolinium enhancement (LGE), lower myocardial T2, and extracellular volume (ECV) were significant predictors of LVRR. During the follow-up, patients with and without LVRR both showed a significant decrease of myocardial native T1 (LVRR: [baseline]1303.0±43.6ms; [follow-up]1244.7±51.8ms; without LVRR: [baseline]1308.5±80.5ms; [follow-up]1287.6±74.9ms, both p < 0.001), matrix and cellular volumes while no significant difference was observed in T2 or ECV values after treatment. Conclusions - In idiopathic DCM patients, the absence of LGE, lower T2, and ECV values at baseline are significant predictors of LVRR. The myocardial T1, matrix, and cell volume decrease significantly in patients with LVRR after GDMT.

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P337Natural history, reversibility and arrhythmias associated with truncating titin variants in dilated cardiomyopathy

European Heart Journal ◽

10.1093/eurheartj/ehz747.0171 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

C R Vissing ◽

T B Rasmussen ◽

M S Olesen ◽

L N Pedersen ◽

A Dybro ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Medical Therapy ◽

Ventricular Arrhythmias ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Reverse Remodeling ◽

Absolute Increase ◽

The Mean

Abstract Background Truncating genetic variants in titin (TTNtv) are identified in 15–25% of patients with primary dilated cardiomyopathy (DCM). Previous genotype/phenotype studies have reported conflicting results regarding disease severity and pathologic features associated with TTNtv. Purpose To investigate the natural history, reversibility and burden of arrhythmias associated with TTNtv in a Danish cohort with long-term follow-up. Methods Patients with DCM, recruited from two Danish tertiary centers, were included based on the presence of a TTNtv in a cardiac expressed titin exon. Data on patients' medical history including symptoms, demography, family history, comorbidities, treatment, ECG features, and echocardiograms were registered. Outcome data including all-cause mortality, need of heart transplantation (HTX) or left ventricular assist device (LVAD), and presence of ventricular and supraventricular arrhythmias were registered. Left ventricular reverse remodeling (LVRR) was defined as an absolute increase in left ventricular ejection fraction (LVEF) ≥10% points or normalization. Results A total of 104 patients (71 men, 69%; 72 probands) with definite TTNtv-DCM were included. The mean age at DCM diagnosis was (mean±SD) 45±13 years (43±13 for men; 49±14 for women, p<0.04) and median follow-up was 8.1 years. The mean LVEF was 28±13% at time of diagnosis (26±12% for men; 30±13% for women, p=0.173). During follow-up, 31 patients (30%; 24 men) died or needed HTX/LVAD. Medical therapy was associated with LVRR in 79% of patients 3.6 years after diagnosis. LVRR was maintained long-term in 64% of patients. Women had a better response to medical therapy compared to men (mean LVEF increase 19%; vs 15% in men, p<0.04). Atrial fibrillation/flutter was observed in 40% of patients and ventricular arrhythmias in 23% of patients. Men had an earlier occurrence of both supraventricular and ventricular arrhythmias (p=0.005) with half of the men having experienced an arrhythmia at the age of 54 years. Freedom from arrhythmias with age Conclusion TTNtv leads to a DCM phenotype associated with a marked gender-difference in age at DCM diagnosis and high burden of both supraventricular and ventricular arrhythmias. Importantly, the DCM-TTNtv phenotype was associated with a high degree of reversibility of systolic function following medical therapy.

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Abstract 15126: Myocardial Tissue Reverse Remodeling After Guideline-directed Medical Therapy in Idiopathic Dilated Cardiomyopathy

Circulation ◽

10.1161/circ.142.suppl_3.15126 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Pengfei Yue ◽

Yuanwei Xu ◽

Yangjie Li ◽

Xiaoyue Zhou ◽

Yucheng Chen

Keyword(s):

Dilated Cardiomyopathy ◽

Medical Therapy ◽

Left Ventricular ◽

Idiopathic Dilated Cardiomyopathy ◽

Reverse Remodeling ◽

Myocardial Tissue ◽

Native T1 ◽

Tissue Characteristics ◽

Cell Volumes

Background: The prognosis of idiopathic dilated cardiomyopathy (DCM) patients has improved remarkably in the recent decades with guideline-directed medical therapy (GDMT) and some patients undergo left ventricular reverse remodeling (LVRR). Objectives: We aim to study the dynamic changes of myocardial tissue characteristics by cardiovascular magnetic resonance (CMR), and investigate the association between myocardial tissue characteristics and cardiac functional remodeling in DCM patients after treatment. Methods: A total of 133 prospectively and consecutively enrolled DCM patients underwent baseline and follow-up CMR examinations with a median interval of 13.7 months (IQR: 12.2-18.5 months). The CMR protocol included cine, late gadolinium enhancement (LGE), pre- and post-contrast T1, and T2 mapping. LVRR was defined as an absolute increase in LV ejection fraction (EF) of >10% to a final value of ≥ 35% with a relative decrease in LV end-diastolic volume (EDV) of >10%. Results: Forty-two (31.6%) patients experienced LVRR during follow-up. At baseline, new onset heart failure, lower LVEF and the absence of LGE were independent predictors of LVRR. Patients with LVRR showed significant decrease of myocardial native T1, indexed matrix and cell volumes, while patients without LVRR also showed significant albeit smaller decrease of native T1 and indexed matrix and cell volumes. The changes of myocardial tissue characteristics were significantly correlated with the improvement of LVEF and indexed LVEDV. Conclusions: In idiopathic DCM patients, significant improvements in myocardial tissue characteristics were observed and accompanied with the improvement in LVEF and reduction in indexed LVEDV after GDMT.

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Sex-Specific Prognostic Implications in Dilated Cardiomyopathy After Left Ventricular Reverse Remodeling

Journal of Clinical Medicine ◽

10.3390/jcm9082426 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2426 ◽

Cited By ~ 1

Author(s):

Antonio Cannata ◽

Paolo Manca ◽

Vincenzo Nuzzi ◽

Caterina Gregorio ◽

Jessica Artico ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Reverse Remodeling ◽

Ventricular Assist ◽

Ventricular Ejection Fraction ◽

Left Ventricular Reverse Remodeling ◽

Significant Difference

Background. Women affected by Dilated Cardiomyopathy (DCM) experience better outcomes compared to men. Whether a more pronounced Left Ventricular Reverse Remodelling (LVRR) might explain this is still unknown. Aim. We investigated the relationship between LVRR and sex and its long-term outcomes. Methods. A cohort of 605 DCM patients with available follow-up data was consecutively enrolled. LVRR was defined, at 24-month follow-up evaluation, as an increase in left ventricular ejection fraction (LVEF) ≥ 10% or a LVEF > 50% and a decrease ≥ 10% in indexed left ventricular end-diastolic diameter (LVEDDi) or an LVEDDi ≤ 33 mm/m2. Outcome measures were a composite of all-cause mortality/heart transplantation (HTx) or ventricular assist device (VAD) and a composite of Sudden Cardiac Death (SCD) or Major Ventricular Arrhythmias (MVA). Results. 181 patients (30%) experienced LVRR. The cumulative incidence of LVRR at 24-months evaluation was comparable between sexes (33% vs. 29%; p = 0.26). During a median follow-up of 149 months, women experiencing LVRR had the lowest rate of main outcome measure (global p = 0.03) with a 71% relative risk reduction compared to men with LVRR, without significant difference between women without LVRR and males. A trend towards the same results was found regarding SCD/MVA (global p = 0.06). Applying a multi-state model, male sex emerged as an independent adverse prognostic factor even after LVRR completion. Conclusions. Although the rate of LVRR was comparable between sexes, females experiencing LVRR showed the best outcomes in the long term follow up compared to males and females without LVRR. Further studies are advocated to explain this difference in outcomes between sexes.

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Abstract 14919: Myocardial T 1 Mapping for Prediction of Left Ventricular Reverse Remodeling in Patients With Recent-onset Dilated Cardiomyopathy: a Comparison With Histological Tissue Characterization

Circulation ◽

10.1161/circ.142.suppl_3.14919 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Junko Ishiura ◽

Shiro Nakamori ◽

Kyoko Imanaka-yoshida ◽

Michiaki Hiroe ◽

Kei Nakata ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Tissue Characterization ◽

Volume Fraction ◽

Left Ventricular ◽

Reverse Remodeling ◽

Post Contrast ◽

Absolute Increase ◽

Left Ventricular Reverse Remodeling ◽

C Statistic ◽

Significant Difference

Background: Accurate prediction of left ventricular reverse remodeling (LVRR) in dilated cardiomyopathy (DCM) remains challenging. The purpose of this study is to assess the potential of cardiovascular magnetic resonance (CMR) T 1 mapping to predict LVRR by histological confirmation. Methods: Twenty-one DCM patients (12 male, mean age 49 ± 13 years) underwent cine, late gadolinium enhancement (LGE) CMR, and triple-slice T 1 mapping using a modified Look-Locker inversion recovery sequence at 3T before receiving optimal medical therapy. LVRR was defined as an absolute increase in LV ejection fraction (LVEF) from ≥10% to a final value of >35%, accompanied by a decrease in LV end-diastolic volume (LVEDV) ≧10% at midterm (mean time 18 months) CMR follow-up. Extra-cellular volume (ECV) was quantified from pre and post-contrast T 1 values of the blood and myocardium with hematocrit correction. Biopsy samples were used for quantification of collagen volume fraction (CVF). Results: LVRR was observed in 11 patients (52%). The mean native T 1 , ECV, and histological CVF were 1395 ± 49 ms, 0.33 ± 0.03, 0.13 ± 0.04, respectively. Native T 1 yielded comparable ability to ECV measurements for detecting histological CVF (r=0.49, 0.52, both p <0.05). While 14 patients (67%) showed focal scar on LGE, there was no significant difference in histological CVF between patients with and without focal scarring (p=0.6). Native T 1, but not ECV and CVF, correlated well with absolute LVEF increase and relative percent decrease of LVEDV and LV end-systolic volume (r=-0.55, 0.55, 0.56, all p <0.05). Native T 1 <1400 ms provided 90% sensitivity and 82% specificity, with the C-statistic of 0.86 (95% CI 0.64-0.97), for predicting LVRR. On the other hand, the C-statistic of ECV, LGE and histological CVF were 0.72 (95% CI 0.48-0.89), 0.53 (95% CI 0.31-0.75) and 0.66 (95% CI 0.43-0.85), respectively. Conclusions: Myocardial native T 1 have the potential to predict LVRR beyond LGE and histological assessment.

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The role of inflammation in recent-onset dilated cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.2101 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Chaloupka ◽

J Krejci ◽

H Poloczkova ◽

P Hude ◽

E Ozabalova ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Left Ventricular ◽

Pcr Analysis ◽

Myocardial Inflammation ◽

Gene Variants ◽

Absolute Increase ◽

Recent Onset ◽

Cardiotropic Viruses

Abstract Background The aetiology of recent-onset dilated cardiomyopathy (RODCM) includes inflammatory, genetic, toxic and metabolic causes. Delineating the role of inflammation on the genetic background could improve risk stratification. Purpose We aimed to ascertain the role of inflammation evaluated by serum CRP immunohistochemical and PCR analysis of endomyocardial biopsy (EMB) in conjunction with genetic testing in left ventricular reverse remodelling (LVRR) in 12-month follow-up. Methods 83 RODCM patients enrolled in this prospective observational study underwent 12-month echocardiographic follow up whole-exome sequencing, and EMB. Presence of cardiotropic viruses was determined by PCR analysis of the EMB samples. Inflammation was defined according to TIMIC immunohistochemical criteria as the presence of >7 CD3+ lymphocytes/mm2 and/or >14 infiltrating leukocytes (LCA+ cells/mm2). LVRR was defined as an absolute increase in LV ejection fraction > +10% and a relative decrease of LV end-diastolic diameter >−10% at 12 months. Results LVRR occurred in 28 (34%) of all cases. PCR analysis uncovered cardiotropic viruses in 55 (66%) patients, with highest prevalence of parvovirus B19 (47%). (Figure 1) EMB analysis detected inflammation in 28 (34%) cases and inflammation significantly positively predicted LVRR (P=0.019). Sequencing identified disease-related gene variants (ACMG class 3–5) in 45 (54%) patients. Carriers of non-titin gene variants showed a lowest probability of 12-month LVRR (19%) P=0.041. Combination of genetic findings and inflammation did not improve the prediction of LVRR in 12 months. (Table 1) Conclusion Both myocardial inflammation and disease-causing variants can be identified in a large proportion of RODCM cases. Prognostic value of CRP and virus detection is low. Non-titin disease-related variants carriers of are less likely to reach LVRR. In contrast, myocardial inflammation detected by EMB predicts favourable remodelling in 12 months. Figure 1 Funding Acknowledgement Type of funding source: None

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Myocardial work analysis in screening of familial dilated cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.0092 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Triantafyllou ◽

R Monteiro ◽

A Protonotarios ◽

T Gossios ◽

P Elliott ◽

...

Keyword(s):

Blood Pressure ◽

Dilated Cardiomyopathy ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Systemic Hypertension ◽

Work Efficiency ◽

Work Analysis ◽

Significant Difference ◽

Global Work

Abstract Introduction Early detection of affected family relatives of patients with dilated cardiomyopathy (DCM) is essential in order to guide follow up, outcomes and initiate early treatment. Myocardial work analysis is a novel method which integrated strain imaging and blood pressure and has the potential to identify patients with subclinical disease. Purpose We analysed myocardial work in family relatives of DCM patients with positive genotype but negative phenotype in order to identify whether myocardial work can identify early changes. Methods Seventy-four family relatives of DCM patients attending for screening were examined. All individuals were asymptomatic with either positive (45/74, G+) or negative (29/74, G-) genotype and no echocardiographic evidence of left ventricular dilatation or systolic impairment. Non-invasive myocardial work analysis using two-dimensional (2D) speckle tracking echocardiography was analysed. Global longitudinal strain (GLS) was measured by the same vendor specific software used for myocardial work analysis. Left ventricular (LV) ejection fraction (EF) was measured with the Simpson's biplane method. The peak systolic arm cuff blood pressure (BP) measurement at the time of echocardiography was used for the myocardial work study. Results In total we included 74 individuals (37±15 years old, 50.7% women) with mean systolic and diastolic BP of 121.3±14 and 73.2±10 mmHg respectively, mean EF was 58±5% and mean GLS at 18.4±2.5%. G+ individuals had pathogenic and very likely pathogenic mutations in 8 different genes (TTN, BAG3, DSP, FLNC, LMNA, DMD, RBM20, TPM1). There was no difference in age, systemic hypertension, diabetes or medical treatment between the 2 groups. No significant difference was found among G+ and G- individuals in mean systolic and diastolic BP (121.2±14.7 vs 121.2±15.2 mmHg), mean EF (57.3±5 vs 59.1±4%), GLS (−18.2±1.5 vs −18.6±2.9%), mean global work index (1818±403 vs 1928±295 mmHg%) and global constructive work (2192±464 vs 2260±318 mmHg%). However, we found significant reduction of the global work efficiency (GWE) with a GWE of 94.4±2.7% in the G+ versus 95.9±1.6% in the G- individuals (p 0.02). Moreover, the global wasted work (GWW) was increased in the G+ with a GWW of 111±58 mmHg% versus 82±41 mmHg% in the G- individuals (p 0.03). Conclusion DCM gene carriers show, early on, decreased myocardial work efficiency and increased wasted work compared to unaffected family members, which appears to be earlier than other parameters such as EF and GLS. Myocardial work analysis could potentially recognize individuals showing early cardiac involvement and guide closer follow up and early initiation of treatment. Funding Acknowledgement Type of funding source: None

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