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      Role of sCD40L in the prediction of super-response to cardiac resynchronization therapy Translated title: Rol de sCD40L en la predicción de súper-respuesta a la terapia de resincronización cardiaca

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          Abstract

          Background

          The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor α, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before.

          Methods

          Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV ≥ 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed.

          Results

          50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p = 0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p < 0.0001) and lateral (0 vs. 18%, p = 0.03), inferior (4 vs. 33%, p = 0.01) and posterior infarction (0 vs. 22%, p = 0.01); absence of mitral regurgitation (47% vs. 22%, p = 0.04), wider QRS width (157.7 ± 22.9 vs. 140.8 ± 19.2ms, p = 0.01), higher concentrations of sCD40L (6.9 ± 5.1 vs. 4.4 ± 3.3 ng/mL, p = 0.02), and left ventricular lead more frequent in lateral medial position (69 vs. 26%, p = 0.002). QRS width, lateral medial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showed a moderate direct correlation with SR (r = 0.39, p = 0.02) and with the reduction of LVESV (r = 0.44, p = 0.02).

          Conclusion

          sCD40L correlates significantly with SR to CRT. QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SR in this cohort.

          Resumen

          Fundamento

          Analizar los biomarcadores Interleuquina 6, factor de necrosis tumoral α, sCD40L, troponina T hipersensible, proteína C-reactiva hipersensible y galectina-3 en la predicción de súper-respuesta (SR) a la terapia de resincronización cardiaca (TRC), ya que no han sido valorados con anterioridad.

          Material y métodos

          Se recopilaron datos clínicos, electrocardiográficos y ecocardiográficos preimplante y al año. Se definió SR como disminución del VTSVI ≥ 30% al año de seguimiento. Las muestras sanguíneas fueron extraídas preimplante. Se realizó regresión logística multivariante y curvas ROC.

          Resultados

          Se incluyeron 50 pacientes, 23 (46%) fueron SR.Las características relacionadas con la SR fueron: ser mujer (35 vs. 11%, p = 0,04), sufrir menos cardiopatía isquémica (13 vs. 63%, p < 0,0001) e infarto lateral (0 vs. 18%, p = 0,03), inferior (4 vs. 33%, p = 0,01) y posterior (0 vs. 22%, p = 0,01); ausencia de insuficiencia mitral (47% vs. 22%, p = 0,04), mayor anchura del QRS (157,7 ± 22,9 vs. 140,8 ± 19,2 ms, p = 0,01), mayor concentración de sCD40L (6,9 ± 5,1 vs. 4,4 ± 3,3 ng/mL, p = 0,02), y electrodo ventricular izquierdo más frecuentemente en posición lateral media (69 vs. 26%, p = 0,002). El QRS, la posición lateral media del electrodo y la ausencia de insuficiencia mitral fueron predictores independientes de SR. sCD40L mostró una correlación moderada directa con SR (r = 0,39, p = 0,02) y con la disminución del VTSVI (r = 0,44, p = 0,02).

          Conclusiones

          sCD40L se correlaciona significativamente con SR a la TRC. El QRS, la ausencia de insuficiencia mitral y la posición lateral media del electrodo son predictores independientes de SR en esta cohorte.

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          Most cited references28

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          Cardiac-resynchronization therapy for the prevention of heart-failure events.

          Arthur Moss, W Hall, David S Cannom … (2009)
          This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heart-failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P=0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT00180271.) 2009 Massachusetts Medical Society
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            Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms.

            Cecilia Linde, William T. Abraham, Michael Gold … (2008)
            We sought to determine the effects of cardiac resynchronization therapy (CRT) in New York Heart Association (NYHA) functional class II heart failure (HF) and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. Cardiac resynchronization therapy improves left ventricular (LV) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS. Six hundred ten patients with NYHA functional class I or II heart failure with a QRS > or =120 ms and a LV ejection fraction < or =40% received a CRT device (+/-defibrillator) and were randomly assigned to active CRT (CRT-ON; n = 419) or control (CRT-OFF; n = 191) for 12 months. The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The prospectively powered secondary end point was LV end-systolic volume index. Hospitalization for worsening HF was evaluated in a prospective secondary analysis of health care use. The HF clinical composite response end point, which compared only the percent worsened, indicated 16% worsened in CRT-ON compared with 21% in CRT-OFF (p = 0.10). Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index (-18.4 +/- 29.5 ml/m2 vs. -1.3 +/- 23.4 ml/m2, p < 0.0001) and other measures of LV remodeling. Time-to-first HF hospitalization was significantly delayed in CRT-ON (hazard ratio: 0.47, p = 0.03). The REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial demonstrates that CRT, in combination with optimal medical therapy (+/-defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154).
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              Results of the Predictors of Response to CRT (PROSPECT) trial.

              Jing Sun, Luigi Tavazzi, Cheuk-Man Yu … (2008)
              Data from single-center studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronization therapy (CRT). In a prospective, multicenter setting, the Predictors of Response to CRT (PROSPECT) study tested the performance of these parameters to predict CRT response. Fifty-three centers in Europe, Hong Kong, and the United States enrolled 498 patients with standard CRT indications (New York Heart Association class III or IV heart failure, left ventricular ejection fraction or = 130 ms, stable medical regimen). Twelve echocardiographic parameters of dyssynchrony, based on both conventional and tissue Doppler-based methods, were evaluated after site training in acquisition methods and blinded core laboratory analysis. Indicators of positive CRT response were improved clinical composite score and > or = 15% reduction in left ventricular end-systolic volume at 6 months. Clinical composite score was improved in 69% of 426 patients, whereas left ventricular end-systolic volume decreased > or = 15% in 56% of 286 patients with paired data. The ability of the 12 echocardiographic parameters to predict clinical composite score response varied widely, with sensitivity ranging from 6% to 74% and specificity ranging from 35% to 91%; for predicting left ventricular end-systolic volume response, sensitivity ranged from 9% to 77% and specificity from 31% to 93%. For all the parameters, the area under the receiver-operating characteristics curve for positive clinical or volume response to CRT was < or = 0.62. There was large variability in the analysis of the dyssynchrony parameters. Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis, no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines. Efforts aimed at reducing variability arising from technical and interpretative factors may improve the predictive power of these echocardiographic parameters in a broad clinical setting.
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                Author and article information

                Journal
                Journal ID (nlm-ta): An Sist Sanit Navar
                Journal ID (iso-abbrev): An Sist Sanit Navar
                Journal ID (publisher-id): assn
                Title: Anales del Sistema Sanitario de Navarra
                Publisher: Gobierno de Navarra. Departamento de Salud
                ISSN (Print): 1137-6627
                ISSN (Electronic): 2340-3527
                Publication date (Electronic, pub): 15 June 2021
                Publication date (Electronic, collection): May-Aug 2021
                Volume: 44
                Issue: 2
                Pages: 205-214
                Affiliations
                [1 ] originalDepartment of Congenital Heart Diseases. German Heart Center of Munich. Germany. orgdiv1Department of Congenital Heart Diseases orgnameGerman Heart Center of Munich Germany
                [2 ] originalDepartment of Clinical Biochemistry. Clínica Universidad de Navarra. Pamplona. Spain. orgdiv1Department of Clinical Biochemistry orgnameClínica Universidad de Navarra Pamplona, Spain
                [3 ] originalDepartment of Cardiology. Hospital Clínico Universitario de Santiago. Santiago de Compostela. Spain. orgdiv1Department of Cardiology orgnameHospital Clínico Universitario de Santiago Santiago de Compostela, Spain
                [4 ] originalDepartment of Cardiology. Clínica Universidad de Navarra. Pamplona. Spain. orgdiv1Department of Cardiology orgnameClínica Universidad de Navarra Pamplona, Spain
                [5 ] originalDepartment of Cardiology. Hospital General Nuestra Señora del Prado. Talavera de la Reina. Spain. orgdiv1Department of Cardiology orgnameHospital General Nuestra Señora del Prado Talavera de la Reina, Spain
                Author notes
                [Correspondence: ] José Ignacio García Bolao. Department of Cardiology, Clínica Universidad de Navarra Avda. Pío XII 36, 31008 Pamplona, Spain. E-mail: igarciab@ 123456unav.es
                Article
                DOI: 10.23938/ASSN.0947
                PMC ID: 10019534
                PubMed ID: 34132247
                SO-VID: a1dacfcf-dbe7-47a7-8a21-5da8e72bbc12
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                Date received : 03 September 2020
                Date revision received : 09 October 2020
                Date accepted : 09 December 2020
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 27, Pages: 10
                Categories
                Subject: Artículos Originales

                Keywords: super-response,scd40l,lateral medial position,qrs width,absence of mitral regurgitation,súper-respuesta,posición lateral media,tamaño qrs,ausencia insuficiencia mitral
                Data availability:
                Keywords: super-response, scd40l, lateral medial position, qrs width, absence of mitral regurgitation, súper-respuesta, posición lateral media, tamaño qrs, ausencia insuficiencia mitral

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