Incidence and prognosis implications of long term left ventricular reverse remodeling in patients with dilated cardiomyopathy

Background: Tenascin-C (TN-C) is an extracellular matrix protein, and may regulate matrix organization during tissue remodeling. Although serum TN-C is reported as a prognostic biomarker in patients with dilated cardiomyopathy (DCM), the clinical significance of myocardial expression of TN-C remains undetermined. The objective of this study is to clarify the significance of myocardial TN-C expression on left ventricular (LV) remodeling and long-term prognosis in patients with DCM. Methods: Eighty consecutive patients in 2005 and 2006, who were diagnosed with DCM by excluding ischemic cardiomyopathy and secondary cardiomyopathy by coronary angiography and right ventricular endomyocardial biopsy, were analyzed. Those patients were followed up to 73±34 months, and their clinical data were obtained. Immunohistochemistry for TN-C was performed on stored biopsy specimens to examine the association of TN-C deposition with the occurrence of LV reverse remodeling as well as long-term mortality. Immunostained area of myocardial TN-C was measured densitometrically and calculated in percent by the fraction of TN-C stained area to the whole myocardium (TN-C area). LV reverse remodeling was defined as LV end-diastolic dimension ≤55 mm and fractional shortening ≥25% by 60 months after diagnosis. Results: TN-C area was 1.2±1.6% on average. Twenty-two patients (28%) underwent LV reverse remodeling. Patients with LV reverse remodeling showed less TN-C area at diagnosis than those without (TN-C area; 0.6±0.5 vs. 1.5±1.8%, p=0.021). Patients were divided into two groups according to the extent of TN-C area; high TN-C group (TN-C area≥1.5%, n=19) and low TN-C group (TN-C area<1.5%, n=61). LV reverse remodeling occurred less frequently in high TN-C group compared with low TN-C group (5% vs 33%, p=0.01). Eleven patients (14%) died during the observation period. Kaplan-Meier analysis revealed high TN-C group had worse prognosis than low TN-C group (p=0.009). Conclusions: Patients with higher immunohistological expression of myocardial TN-C in DCM were characterized with lower occurrence of later LV reverse remodeling and poorer long-term prognosis. Myocardial TN-C may have some crucial role in LV remodeling process in patients with DCM.

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Left Ventricular Reverse Remodeling in Long-Term (>12 Years) Survivors With Idiopathic Dilated Cardiomyopathy

The American Journal of Cardiology ◽

10.1016/j.amjcard.2012.08.056 ◽

2013 ◽

Vol 111 (1) ◽

pp. 106-110 ◽

Cited By ~ 24

Author(s):

Yoshihisa Matsumura ◽

Eri Hoshikawa-Nagai ◽

Toru Kubo ◽

Naohito Yamasaki ◽

Takashi Furuno ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Left Ventricular ◽

Idiopathic Dilated Cardiomyopathy ◽

Reverse Remodeling ◽

Left Ventricular Reverse Remodeling

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Left Ventricular Reverse Remodeling After Beta-blocker Therapy in Dilated Cardiomyopathy: Is it Maintained at Long-term Follow-up?

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2009.07.011 ◽

2009 ◽

Vol 15 (7) ◽

pp. S153

Author(s):

Yuichi Baba ◽

Yoshihisa Matsumura ◽

Toru Kubo ◽

Eri Hoshikawa ◽

Makoto Okawa ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Beta Blocker ◽

Left Ventricular ◽

Reverse Remodeling ◽

Blocker Therapy ◽

Beta Blocker Therapy ◽

Left Ventricular Reverse Remodeling ◽

Long Term Follow Up

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Prevalence, Predictors and Prognostic Value of Left Ventricular Reverse Remodeling and Relapse in Patients Hospitalized with Dilated Cardiomyopathy with Long-term Echocardiographic Follow-up

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2020.09.276 ◽

2020 ◽

Vol 26 (10) ◽

pp. S94

Author(s):

Chang Hong Zou ◽

Jian Zhang

Keyword(s):

Dilated Cardiomyopathy ◽

Prognostic Value ◽

Left Ventricular ◽

Reverse Remodeling ◽

Left Ventricular Reverse Remodeling

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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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Combination of left ventricular reverse remodeling and brain natriuretic peptide level at one year after cardiac resynchronization therapy predicts long-term clinical outcome

PLoS ONE ◽

10.1371/journal.pone.0219966 ◽

2019 ◽

Vol 14 (7) ◽

pp. e0219966

Author(s):

Tomas Roubicek ◽

Jan Stros ◽

Pavel Kucera ◽

Pavel Nedbal ◽

Jan Cerny ◽

...

Keyword(s):

Clinical Outcome ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Reverse Remodeling ◽

Resynchronization Therapy ◽

Left Ventricular Reverse Remodeling ◽

Natriuretic Peptide Level ◽

Peptide Level ◽

One Year

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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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