Beta-Blocker Use Is Associated With Prevention of Left Ventricular Remodeling in Recovered Dilated Cardiomyopathy.
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SUBMITTER: Enzan N
PROVIDER: S-EPMC8477863 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMineralocorticoid receptor antagonist (MRA) treatment produces beneficial left ventricular (LV) remodeling in nonischemic dilated cardiomyopathy (NIDCM). This study addressed the timing of maximal beneficial LV remodeling in NIDCM when adding MRA.Materials and methodsWe studied 12 patients with NIDCM on stable β-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy who underwent cardiac magnetic resonance imaging before and after 6-31 months of continuous MRA therapy.ResultsAt baseline, the LV ejection fraction (LVEF) was 24% (19-27); median [interquartile range]. The LV end-systolic volume index (LVESVI) was 63 ml (57-76) and the LV stroke volume index (LVSVI) was 19 ml (14-21), all depressed. After adding MRA to the HF regimen, the LVEF increased to 47% (42-52), with a decrease in LVESVI to 36 ml (33-45) and increase in LVSVI to 36 ml (28-39) (for each, P < 0 .0001). Using generalized least squares analysis, the maximal beneficial remodeling (defined by maximal increase in LVEF, the maximal decrease in LVESVI and maximal increase in LVSVI) was achieved after approximately 12-16 months of MRA treatment.ConclusionsAdding MRA to a standard medical regimen for NIDCM resulted in beneficial LV remodeling. The maximal beneficial remodeling was achieved with 12-16 months of MRA therapy. These results have implications for the timing of other advanced therapies, such as placing internal cardioverter-defibrillators.
| S-EPMC7388723 | biostudies-literature
Project description: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.
| S-EPMC7464387 | biostudies-literature
Project description:BackgroundWhen β-blockers produce reverse-remodeling in idiopathic dilated cardiomyopathy, they partially reverse changes in fetal-adult/contractile protein, natriuretic peptide, SR-Ca(2+)-ATPase gene program constituents. The objective of the current study was to further test the hypothesis that reverse-remodeling is associated with favorable changes in myocardial gene expression by measuring additional contractile, signaling, and metabolic genes that exhibit a fetal/adult expression predominance, are thyroid hormone-responsive, and are regulated by β1-adrenergic receptor signaling. A secondary objective was to identify which of these putative regulatory networks is most closely associated with observed changes.Methods and resultsForty-seven patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction, 0.24±0.09) were randomized to the adrenergic-receptor blockers metoprolol (β1-selective), metoprolol+doxazosin (β1/α1), or carvedilol (β1/β2/α1). Serial radionuclide ventriculography and endomyocardial biopsies were performed at baseline, 3, and 12 months. Expression of 50 mRNA gene products was measured by quantitative polymerase chain reaction. Thirty-one patients achieved left ventricular ejection fraction reverse-remodeling response defined as improvement by ≥0.08 at 12 months or by ≥0.05 at 3 months (Δ left ventricular ejection fraction, 0.21±0.10). Changes in gene expression in responders versus nonresponders were decreases in NPPA and NPPB and increases in MYH6, ATP2A2, PLN, RYR2, ADRA1A, ADRB1, MYL3, PDFKM, PDHX, and CPT1B. All except PDHX involved increase in adult or decrease in fetal cardiac genes, but 100% were concordant with changes predicted by inhibition of β1-adrenergic signaling.ConclusionsIn addition to known gene expression changes, additional calcium-handling, sarcomeric, adrenergic signaling, and metabolic genes were associated with reverse-remodeling. The pattern suggests a fetal-adult paradigm but may be because of reversal of gene expression controlled by a β1-adrenergic receptor gene network.Clinical trial registrationURL: www.clinicaltrials.gov. Unique Identifier: NCT01798992.
| S-EPMC7205443 | biostudies-literature
Project description:Background: The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Methods: Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. Results: There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Conclusions: Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.
| S-EPMC8415784 | biostudies-literature
Project description:BackgroundPediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end-diastolic dimension (LVEDD), LV end-diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes.Methods and resultsWe studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end-diastolic posterior wall thickness, and the LV end-diastolic posterior wall thickness:LVEDD ratio between baseline and follow-up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1-year follow-up had died, received a heart transplant, or were alive and transplant-free. Within 1 year after diagnosis, 40 (5.0%) of the 794 eligible children had died, 117 (14.7%) had undergone cardiac transplantation, and 585 (73.7%) had survived without transplantation. At diagnosis, survivors had higher median LVFS and lower median LVEDD Z scores. Median LVFS and LVEDD Z scores improved among survivors (Z score changes of +2.6 and -1.1, respectively) but remained stable or worsened in the other 2 groups. The LV end-diastolic posterior wall thickness:LVEDD ratio increased in survivors only, suggesting beneficial reverse LV remodeling. The risk for death or cardiac transplantation up to 7 years later was lower when LVFS was improved at 1 year (hazard ratio [HR], 0.83; P=0.004) but was higher in those with progressive LV dilation (HR, 1.45; P<0.001).ConclusionsProgressive deterioration in LV contractile function and increasing LV dilation are associated with both early and continuing mortality in children with dilated cardiomyopathy. Serial echocardiographic monitoring of these children is therefore indicated.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00005391.
| S-EPMC10926795 | biostudies-literature
Project description:AimsRemodelling of the left ventricular (LV) shape is one of the hallmarks of non-ischaemic dilated cardiomyopathy (DCM) and may contribute to ventricular arrhythmias and sudden cardiac death. We sought to investigate a novel three dimensional (3D) shape analysis approach to quantify LV remodelling for arrhythmia prediction in DCM.Methods and resultsWe created 3D LV shape models from end-diastolic cardiac magnetic resonance images of 156 patients with DCM and late gadolinium enhancement (LGE). Using the shape models, principle component analysis, and Cox-Lasso regression, we derived a prognostic LV arrhythmic shape (LVAS) score which identified patients who reached a composite arrhythmic endpoint of sudden cardiac death, aborted sudden cardiac death, and sustained ventricular tachycardia. We also extracted geometrical metrics to look for potential prognostic markers. During a follow-up period of up to 16 years (median 7.7, interquartile range: 3.9), 25 patients met the arrhythmic endpoint. The optimally prognostic LV shape for predicting the time-to arrhythmic event was a paraboloidal longitudinal profile, with a relatively wide base. The corresponding LVAS was associated with arrhythmic events in univariate Cox regression (hazard ratio = 2.0 per quartile; 95% confidence interval: 1.3-2.9), in univariate Cox regression with propensity score adjustment, and in three multivariate models; with LV ejection fraction, New York Heart Association Class III/IV (Model 1), implantable cardioverter-defibrillator receipt (Model 2), and cardiac resynchronization therapy (Model 3).ConclusionBiomarkers of LV shape remodelling in DCM can help to identify the patients at greatest risk of lethal ventricular arrhythmias.
| S-EPMC9301973 | biostudies-literature
Project description:We employed ABI high-density oligonucleotide microarrays containing 31,700 sixty-mer probes (representing 27,868 annotated human genes) to determine differential gene expression in idiopathic dilated cardiomyopathy (DCM). We identified 626 up-regulated and 636 down-regulated genes in DCM compared to controls. Most significant changes occurred in the tricarboxylic acid cycle, angiogenesis, and apoptotic signaling pathways, among which 32 apoptosis- and 13 MAPK activity-related genes were altered. Inorganic cation transporter, catalytic activities, energy metabolism and electron transport-related processes were among the most critically influenced pathways. Among the up-regulated genes were HTRA1 (6.9-fold), PDCD8(AIFM1) (5.2) and PRDX2 (4.4) and the down-regulated genes were NR4A2 (4.8), MX1 (4.3), LGALS9 (4), IFNA13 (4), UNC5D (3.6) and HDAC2 (3) (p<0.05), all of which have no clearly defined cardiac-related function yet. Gene ontology and enrichment analysis also revealed significant alterations in mitochondrial oxidative phosphorylation, metabolism and Alzheimer's disease pathways. Concordance was also confirmed for a significant number of genes and pathways in an independent validation microarray dataset. Furthermore, verification by real-time RT-PCR showed a high degree of consistency with the microarray results. Our data demonstrate an association of DCM with alterations in various cellular events and multiple yet undeciphered genes that may contribute to heart muscle disease pathways.
| S-EPMC4152850 | biostudies-literature
Project description:Left ventricular (LV) systolic dysfunction is the most frequent initial presentation of patient with LV noncompaction (NC). Our objectives were to evaluate myocardial contraction properties in patients with LVNC and the relationship of non-compacted segments with the degree of global and regional systolic deformation.We included 50 LVNC with an echocardiography and speckle imaging calculation of peak longitudinal strain (PLS). Each of the 16 LV myocardial segments was defined as NC (ratio NC/compacted layer > 2), borderline (NC/C 0-2) and compacted (NC/C = 0). Basal, median and apical strain values were calculated as the average of segmental strain values. For comparison a group of 50 patients with dilated cardiomyopathy (DCM) underwent the same measurements.There was no statistical difference between the 2 groups for any conventional LV systolic parameters. A characteristic deformation pattern was observed in LVNC with higher strain values in the LV apical segments (- 12.8 ± 5.9 vs - 10.7 ± 5.7) and an apical-basal ratio (1.52 ± 0.73 vs 1.12 ± 0.42; p < 0.001). There was no correlation between LV function and the degree of NC. Among 726 segments, compacta thickness was thinner in NC vs C segments (6.4 ± 1.4 vs 7.7 ± 1.8 mm; p < 0.05). There was no difference in WMS but regional strain values were significantly higher in NC compared to C segments (- 13.1 ± 6.1 vs - 10.2 ± 6.3; p < 0.05).Compared to DCM, LVNC presented with relatively preserved apical deformation as compared to basal segments. Lower regional deformation values in compacted segments confirm the concept that LVNC is a phenotypic marker of an underlying diffuse cardiomyopathy involving both C and NC myocardium.
| S-EPMC5497160 | biostudies-other
Project description:BackgroundDilated cardiomyopathy is characterized by left ventricular dilatation and dysfunction. Inflammation and adverse remodeling of the extracellular matrix may be involved in the pathogenesis. Statins reduce levels of low density lipoprotein cholesterol, but may also attenuate inflammation and affect matrix remodeling. We hypothesized that treatment with rosuvastatin would reduce or even reverse left ventricular remodeling in dilated cardiomyopathy.Materials and methodsIn this multicenter, randomized, double blind, placebo-controlled study, 71 patients were randomized to 10 mg of rosuvastatin or matching placebo. Physical examination, blood sampling, echocardiography and cardiac magnetic resonance imaging were performed at baseline and at six months' follow-up. The pre-specified primary end point was the change in left ventricular ejection fraction from baseline to six months.ResultsOver all, left ventricular ejection fraction improved 5 percentage points over the duration of the study, but there was no difference in the change in left ventricular ejection fraction between patients allocated to rosuvastatin and those allocated to placebo. Whereas serum low density lipoprotein cholesterol concentration fell significantly in the treatment arm, rosuvastatin did not affect plasma or serum levels of a wide range of inflammatory variables, including C-reactive protein. The effect on markers of extracellular matrix remodeling was modest.ConclusionTreatment with rosuvastatin does not improve left ventricular ejection fraction in patients with dilated cardiomyopathy.Trial registrationClinicalTrials.gov NCT00505154.
| S-EPMC3934914 | biostudies-literature
Project description: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.
| S-EPMC6920763 | biostudies-literature