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

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.

Download Full-text

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.

Download Full-text

Use of Cardiac Biomarkers for Monitoring Improvement of Left Ventricular Function by Immunoadsorption Treatment in Dilated Cardiomyopathy

Biomolecules ◽

10.3390/biom9110654 ◽

2019 ◽

Vol 9 (11) ◽

pp. 654

Author(s):

Weinmann ◽

Werner ◽

Koenig ◽

Rottbauer ◽

Walcher ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Troponin I ◽

Troponin T ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

Lv Function ◽

Long Term Follow Up ◽

Acute Changes

Immunoadsorption and subsequent administration of intravenous immunoglobulin (IVIG) have shown beneficial effects on cardiac function and symptoms in patients with dilated cardiomyopathy. Biomarkers play an emerging role in disease monitoring and outcome prediction of heart failure (HF) patients. We aimed to analyze cardiac biomarkers as predictor for improvement of left ventricular (LV) function after immunoadsorption treatment in dilated cardiomyopathy (DCM). Thirty-one patients with dilated cardiomyopathy on optimized HF pharmacotherapy received a single cycle of immunoadsorption for five days followed by IVIG administration. Left ventricular ejection fraction (LVEF) and heart failure biomarkers (hs troponin T, hs troponin I, NT-proBNP and sST2) were evaluated before treatment, after the last cycle of immunoadsorption and during a median follow-up of 30.5 months. We correlated HF biomarkers before immunoadsorption and acute changes of HF biomarkers by immunoadsorption with LV improvement during the long-term follow-up. LV function improved significantly after immunoadsorption from 28.0 to 42.0% during the long-term follow-up (p < 0.0001). Evaluation of biomarker levels showed a significant decrease for hs troponin I (from 9.2 to 5.5 ng/L, p < 0.05) and NT-proBNP (from 789.6 to 281.2 pg/mL, p < 0.005). Correlation of biomarker levels before immunoadsorption and LVEF at the long-term follow-up show good results for hs troponin T (r = −0.40, r2 = 0.16, p < 0.05), hs troponin I (r = −0.41, r2 = 0.17, p < 0.05) and sST2 (r = −0.46, r2 = 0.19, p < 0.05). Correlation of biomarker levels before immunoadsorption and the individual increase in LV function was significant for hs troponin T (r = −0.52, r2 = 0.27, p < 0.005) and hs troponin I (r = −0.53, r2 = 0.29, p < 0.005). To imply a tool for monitoring outcome immediately after immunoadsorption treatment, we investigated the correlation of acute changes of biomarker levels by immunoadsorption treatment and individual increase in LV function. A drop in hs troponin T (r = −0.41, r2 = 0.17, p < 0.05) and hs troponin I (r = −0.53, r2 = 0.28, p < 0.005) levels demonstrate a good correlation to improvement in LVEF during the long-term follow-up. Conclusion: Hs troponin T and I levels correlate with LV function improvement during long-term follow-up. Acute decrease of troponins by immunoadsorption treatment is paralleled by individual improvement of LVEF at the long-term follow-up. Thus, troponins could serve as a monitoring tool for the improvement of LV function after immunoadsorption treatment in dilated cardiomyopathy.

Download Full-text

Abstract 17315: Low Occurrence of Left Ventricular Reverse Remodeling and Poor Long-term Prognosis in Dilated Cardiomyopathy with Higher Immunohistological Expression of Myocardial Tenascin-C

Circulation ◽

10.1161/circ.130.suppl_2.17315 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Tetsuro Yokokawa ◽

Yasuo Sugano ◽

Takafumi Nakayama ◽

Masao Takigami ◽

Toshiyuki Nagai ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Matrix Protein ◽

Left Ventricular ◽

Extracellular Matrix Protein ◽

Reverse Remodeling ◽

Tenascin C ◽

Left Ventricular Reverse Remodeling ◽

Lv Remodeling ◽

Long Term Prognosis

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.

Download Full-text

Which subgroup of patients with dilated cardiomyopathy would benefit from long-term beta-blocker therapy? A histologic viewpoint

Journal of the American College of Cardiology ◽

10.1016/0735-1097(93)90094-h ◽

1993 ◽

Vol 21 (3) ◽

pp. 628-633 ◽

Cited By ~ 58

Author(s):

Takahisa Yamada ◽

Masatake Fukunami ◽

Masaharu Ohmori ◽

Katsuomi Iwakura ◽

Kazuaki Kumagai ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Beta Blocker ◽

Blocker Therapy ◽

Beta Blocker Therapy

Download Full-text

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

International Journal of Cardiology ◽

10.1016/j.ijcard.2015.11.099 ◽

2016 ◽

Vol 203 ◽

pp. 1114-1121 ◽

Cited By ~ 6

Author(s):

Isabel Ruiz-Zamora ◽

Jorge Rodriguez-Capitan ◽

Alicia Guerrero-Molina ◽

Luis Morcillo-Hidalgo ◽

Isabel Rodriguez-Bailon ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Left Ventricular ◽

Reverse Remodeling ◽

Left Ventricular Reverse Remodeling

Download Full-text

Digoxin vs. beta-blocker therapy in atrial fibrillation: analysis from the ESC-EHRA EORP Atrial Fibrillation General Long-Term (AFGen LT) Registry

European Heart Journal ◽

10.1093/eurheartj/ehab724.0494 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

W.Y Ding ◽

M Proietti ◽

G Boriani ◽

F Marin ◽

C Blomstrom-Lundqvist ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Beta Blocker ◽

Blocker Therapy ◽

Cox Regression Analysis ◽

Beta Blocker Therapy ◽

All Cause Mortality ◽

Related Hospitalisation

Abstract Background There is a long-standing and unresolved controversy over the effects of digoxin on mortality. Furthermore, there is scarce evidence comparing the use of digoxin to beta-blocker in the general population with atrial fibrillation (AF). In this study, we aimed to evaluate the effects of digoxin over beta-blocker therapy among patients with AF. Methods Patients from the EORP-AF General Long-Term Registry with AF who were treated with either digoxin or beta-blocker were included. All patients were over 18 years old and had documented evidence of AF within 12 months prior to enrolment. The outcomes of interest were all-cause mortality, cardiovascular (CV) mortality, non-CV mortality and number of patients with unplanned hospitalisation (total and AF-related). These were recorded until the last known follow-up available. Results Of 6377 patients, 549 (8.6%) and 5828 (91.4%) were treated with digoxin and beta-blockers, respectively. Patients in the digoxin group were older (73 vs. 71 years, p<0.001) with reduced renal function (eGFR 65.4 vs. 68.7 mL/min/1.73m2, p=0.002), and had (in general) greater burden of comorbidities in terms of chronic kidney disease, chronic obstructive pulmonary disease, heart failure, hypertension and peripheral artery disease. Nonetheless, the use of anticoagulation therapy was comparable between both groups (p=0.112). Over 24 months follow-up, there were 550 (8.6%) all-cause mortality and 1304 (23.6%) patients with unplanned emergency hospitalisation. Digoxin use was associated with increased all-cause mortality (hazard ratio [HR] 1.90 [95% CI, 1.48–2.44]), both from CV and non-CV causes (CV: HR 2.21 [95% CI, 1.49–3.26]); non-CV: HR 1.70 [95% CI, 1.04–2.79]). There was no statistical difference in terms of unplanned emergency hospitalisation (HR 0.99 [95% CI, 0.80–1.21]) and AF-related hospitalisation (HR 0.78 [95% CI, 0.58–1.06]) between both groups. Using multivariable cox regression analysis, digoxin compared to beta-blocker therapy was independently linked to increased all-cause mortality (HR 1.52 [95% CI, 1.11–2.09]) and CV mortality (HR 1.82 [95% CI, 1.11–2.97]), but was not related to non-CV mortality (HR 1.31 [95% CI, 0.71–2.41]), emergency hospitalisation (HR 0.91 [95% CI, 0.71–1.16]) or AF-related hospitalisation (HR 0.88 [95% CI, 0.62–1.24]), after adjustment for known risk factors. Conclusion We demonstrated that the use of digoxin was independently associated with excess all-cause mortality, driven by CV death, but was non-inferior to beta-blocker in terms of preventing unplanned emergency or AF-related hospitalisation, after accounting for important risk factors. FUNDunding Acknowledgement Type of funding sources: None.

Download Full-text