Dataset Information

Circulating miR-499a and miR-125b as Potential Predictors of Left Ventricular Ejection Fraction Improvement after Cardiac Resynchronization Therapy.

ABSTRACT: Cardiac resynchronization therapy represents a therapeutic option for heart failure drug-refractory patients. However, due to the lack of success in 30% of the cases, there is a demand for an in-depth analysis of individual heterogeneity. In this study, we aimed to evaluate the prognostic value of circulating miRNA differences. Responder patients were defined by a composite endpoint of the presence of left ventricular reverse remodelling (a reduction ≥15% in telesystolic volume and an increment ≥10% in left ventricular ejection fraction). Circulating miRNAs signature was analysed at the time of the procedure and at a 6-month follow-up. An expression analysis showed, both at baseline and at follow-up, differences between responders and non-responders. Responders presented lower baseline expressions of miR-499, and at follow-up, downregulation of miR-125b-5p, both associated with a significant improvement in left ventricular ejection fraction. The miRNA profile differences showed a marked sensitivity to distinguish between responders and non-responders. Our data suggest that miRNA differences might contribute to prognostic stratification of patients undergoing cardiac resynchronization therapy and suggest that preimplant cardiac context as well as remodelling response are key to therapeutic success.

SUBMITTER: Moscoso I

PROVIDER: S-EPMC8773679 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Circulating miR-499a and miR-125b as Potential Predictors of Left Ventricular Ejection Fraction Improvement after Cardiac Resynchronization Therapy.

Moscoso Isabel I Cebro-Márquez María M Martínez-Gómez Álvaro Á Abou-Jokh Charigan C Martínez-Monzonís María Amparo MA Martínez-Sande José Luis JL González-Melchor Laila L García-Seara Javier J Fernández-López Xesús Alberte XA Moraña-Fernández Sandra S González-Juanatey José R JR Rodríguez-Mañero Moisés M Lage Ricardo R

Cells 20220113 2

Cardiac resynchronization therapy represents a therapeutic option for heart failure drug-refractory patients. However, due to the lack of success in 30% of the cases, there is a demand for an in-depth analysis of individual heterogeneity. In this study, we aimed to evaluate the prognostic value of circulating miRNA differences. Responder patients were defined by a composite endpoint of the presence of left ventricular reverse remodelling (a reduction ≥15% in telesystolic volume and an increment ...[more]

PMID: 35053387

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Project description:ObjectivesTo investigate the predictive roles of pre-operative left ventricular (LV) size and ejection fraction (EF) in EF improvement and outcome following revascularization in patients with coronary artery disease (CAD) and LV dysfunction.BackgroundRevascularization may improve EF and long-term outcomes of patients with LV dysfunction. However, the determinants of EF improvement have not yet been investigated comprehensively.Materials and methodsPatients with EF measurements before and 3 months after revascularization were enrolled in a cohort study (No. ChiCTR2100044378). All patients had baseline EF ≤ 40%. EF improvement was defined as absolute increase in EF > 5%. According to LV end-systolic diameter (LVESD) (severely enlarged or not) and EF (≤35% or of 36-40%) at baseline, patients were categorized into four groups.ResultsA total of 939 patients were identified. A total of 549 (58.5%) had EF improved. Both LVESD [odds ratio (OR) per 1 mm decrease, 1.05; 95% CI, 1.04-1.07; P < 0.001] and EF (OR per 1% decrease, 1.06; 95% CI, 1.03-1.10; P < 0.001) at baseline were predictive of EF improvement after revascularization. Patients with LVESD not severely enlarged and EF ≤ 35% had higher odds of being in the EF improved group in comparison with other three groups both in unadjusted and adjusted analysis (all P < 0.001). The median follow-up time was 3.5 years. Patients with LVESD not severely enlarged and EF ≤ 35% had significantly lower risk of all-cause death in comparison with patients with LVESD severely enlarged and EF ≤ 35% [hazard ratio (HR), 2.73; 95% CI, 1.28-5.82; P = 0.009], and tended to have lower risk in comparison with patients with LVESD severely enlarged and EF of 36-40% (HR, 2.00; 95% CI, 0.93-4.27; P = 0.074).ConclusionAmong CAD patients with reduced EF (≤ 40%) who underwent revascularization, smaller pre-operative LVESD and lower EF had greatest potential to have EF improvement and better outcome. Our findings imply the indication for revascularization in patients with LV dysfunction who presented with lower EF but smaller LV size.

Project description:Aims: Evidence-based guidelines for heart failure management depend mainly on current left ventricular ejection fraction (LVEF). However, fewer studies have examined the impact of prior LVEF. Patients may enter the heart failure with midrange ejection fraction (HFmrEF) category when heart failure with preserved ejection fraction (HFpEF) deteriorates or heart failure with reduced ejection fraction (HFrEF) improves. In this study, we examined the association between change in LVEF and adverse outcomes. Methods: HFmrEF patients with at least two or more echocardiograms 3 months apart at the First Affiliated Hospital of Dalian Medical University between September 1, 2015 and November 30, 2019 were identified. According to the prior LVEF, the subjects were divided into improved group (prior LVEF < 40%), stable group (prior LVEF between 40 and 50%), and deteriorated group (prior LVEF ≥ 50%). The primary outcomes were cardiovascular death, all-cause mortality, hospitalization for worsening heart failure, and composite event of all-cause mortality or all-cause hospitalization. Results: A total of 1,168 HFmrEF patients (67.04% male, mean age 63.60 ± 12.18 years) were included. The percentages of improved, stable, and deteriorated group were 310 (26.54%), 334 (28.60%), and 524 (44.86%), respectively. After a period of follow-up, 208 patients (17.81%) died and 500 patients met the composite endpoint. The rates of all-cause mortality were 35 (11.29%), 55 (16.47%), and 118 (22.52%), and the composite outcome was 102 (32.90%), 145 (43.41%), and 253 (48.28%) for the improved, stable, and deteriorated groups, respectively. Cox regression analysis showed that the deterioration group had higher risk of cardiovascular death (HR: 1.707, 95% CI: 1.064-2.739, P = 0.027), all-cause death (HR 1.948, 95% CI 1.335-2.840, P = 0.001), and composite outcome (HR 1.379, 95% CI 1.096-1.736, P = 0.006) compared to the improvement group. The association still remained significant after fully adjusted for both all-cause mortality (HR = 1.899, 95% CI 1.247-2.893, P = 0.003) and composite outcome (HR: 1.324, 95% CI: 1.020-1.718, P = 0.035). Conclusion: HFmrEF patients are heterogeneous with three different subsets identified, each with different outcomes. Strategies for managing HFmrEF should include previously measured LVEF to allow stratification based on direction changes in LVEF to better optimize treatment.

Project description:Importance:The incidence of chemotherapy-induced cardiomyopathy is increasing and is associated with poor clinical outcomes. Objective:To assess the association of cardiac resynchronization therapy (CRT) with improvement in cardiac function, as well as clinical improvement in patients with chemotherapy-induced cardiomyopathy. Design, Setting, and Participants:The Multicenter Automatic Defibrillator Implantation Trial-Chemotherapy-Induced Cardiomyopathy was an uncontrolled, prospective, cohort study conducted between November 21, 2014, and June 21, 2018, at 12 tertiary centers with cardio-oncology programs in the United States. Thirty patients were implanted with CRT owing to reduced left ventricular ejection fraction (LVEF≤35%), New York Heart Association class II-IV heart failure symptoms, and wide QRS complex, with established chemotherapy-induced cardiomyopathy and were followed up for 6 months after CRT implantation. The date of final follow-up was February 6, 2019. Exposures:CRT implantation according to standard of care. Main Outcomes and Measures:The primary end point was change in LVEF from baseline to 6 months after initiating CRT. Secondary outcomes included all-cause mortality and change in left ventricular end-systolic volume and end-diastolic volume. Results:Among 30 patients who were enrolled (mean [SD] age, 64 [11] years; 26 women [87%]; 73% had a history of breast cancer; 20% had a history of lymphoma or leukemia), primary end point data were available for 26 patients and secondary end point data were available for 23 patients. Patients had nonischemic cardiomyopathy with left bundle branch block, median LVEF of 29%, and a mean QRS duration of 152 ms. Patients with CRT experienced a statistically significant improvement in mean LVEF at 6 months from 28% to 39% (difference, 10.6% [95% CI, 8.0%-13.3%]; P < .001). This was accompanied by a reduction in LV end-systolic volume from 122.7 to 89.0 mL (difference, 37.0 mL [95% CI, 28.2-45.8]) and reduction in LV end-diastolic volume from 171.0 to 143.2 mL (difference, 31.9 mL [95% CI, 22.1-41.6]) (both P < .001). Adverse events included a procedure-related pneumothorax (1 patient), a device pocket infection (1 patient), and heart failure requiring hospitalization during follow-up (1 patient). Conclusions and Relevance:In this preliminary study of patients with chemotherapy-induced cardiomyopathy, CRT was associated with improvement in LVEF after 6 months. The findings are limited by the small sample size, short follow-up, and absence of a control group. Trial Registration:ClinicalTrials.gov Identifier: NCT02164721.

Project description:Background Although potential therapeutic candidates for heart failure with preserved ejection fraction (HFpEF) are emerging, it is still unclear whether they will be effective in patients with left ventricular ejection fraction (LVEF) of 60% or higher. Our aim was to identify the clinical characteristics of these patients with HFpEF by comparing them to patients with LVEF below 60%. Methods and Results From a multicenter, prospective, observational cohort (PURSUIT-HFpEF [Prospective Multicenter Obsevational Study of Patients with Heart Failure with Preserved Ejection Fraction]), we investigated 812 consecutive patients (median age, 83 years; 57% women), including 316 with 50% ≤ LVEF <60% and 496 with 60% ≤ LVEF, and compared the clinical backgrounds of the 2 groups and their prognoses for cardiac mortality or HF readmission. Two hundred four adverse outcomes occurred at a median of 366 days. Multivariable Cox regression tests adjusted for age, sex, heart rate, atrial fibrillation, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and prior heart failure hospitalization revealed that systolic blood pressure (hazard ratio [HR], 0.925 [95% CI, 0.862-0.992]; P=0.028), high-density lipoprotein to C-reactive protein ratio (HR, 0.975 [95% CI, 0.944-0.995]; P=0.007), and left ventricular end-diastolic volume index (HR, 0.870 [95% CI, 0.759-0.997]; P=0.037) were uniquely associated with outcomes among patients with 50% ≤ LVEF <60%, whereas only the ratio of peak early mitral inflow velocity to velocity of mitral annulus early diastolic motion e'(HR, 1.034 [95% CI, 1.003-1.062]; P=0.034) was associated with outcomes among patients with 60% ≤ LVEF. Conclusions Prognostic factors show distinct differences between patients with HFpEF with 50% ≤ LVEF <60% and with 60% ≤ LVEF. These findings suggest that the 2 groups have different inherent pathophysiology. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414; Unique identifier: UMIN000021831 PURSUIT-HFpEF.

Dataset Information

Circulating miR-499a and miR-125b as Potential Predictors of Left Ventricular Ejection Fraction Improvement after Cardiac Resynchronization Therapy.

Publications

Circulating miR-499a and miR-125b as Potential Predictors of Left Ventricular Ejection Fraction Improvement after Cardiac Resynchronization Therapy.

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