Cellular Communication Network Factor 1 (CCN1) PredictsAll-Cause Mortality in Patients with Dilated Cardiomyopathy – a Derivation and Validation Study

Roland Klingenberg (Bad Nauheim)1, S. Groß (Greifswald)2, K. Lehnert (Greifswald)2, K. Grote (Marburg)3, A. Benkner (Greifswald)2, D. Wegner (Greifswald)2, C. W. Hamm (Gießen)4, S. B. Felix (Greifswald)2, T. Keller (Bad Nauheim)5, S. Pankuweit (Marburg)6, M. Dörr (Greifswald)2

1Kerckhoff Klinik GmbH Abteilung für Kardiologie Bad Nauheim, Deutschland; 2Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B Greifswald, Deutschland; 3Universitätsklinikum Gießen und Marburg GmbH Kardiologie Marburg, Deutschland; 4Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland; 5Justus-Liebig-Universität Giessen Franz-Groedel-Institut (FGI) Bad Nauheim, Deutschland; 6Universitätsklinikum Giessen und Marburg GmbH Klinik für Innere Medizin - Schwerpunkt Kardiologie Marburg, Deutschland


Aim     Circulating cellular communication network factor 1 (CCN1) improves risk stratification in patients with acute coronary syndromes. We here investigated the prognostic value of CCN1 for all-cause mortality in patients with dilated cardiomyopathy (DCM).

Methods and Results       Patients with a primary diagnosis of DCM, defined as LVEF <45% and increased LVEDD (LVEDD >117%) were included in a derivation and a validation cohort. Exclusion criteria comprised primary valvular diseases, acute myocarditis, active infectious diseases, pulmonary diseases, cancer, chronic alcoholism, and heart failure of other origins. CCN1 levels were determined in serum from study inclusion using an enzyme-linked immunosorbent assay. In the (derivation) and [validation] cohort, respectively, a total of 283 [236] predominantly male (78% [75%]) DCM patients with a median age of 56 [51] years with a severely reduced LVEF (31% [30%]), enlarged LVEDD (67 [67] mm) and normal eGFR (90.9 [83.6] ml/min) were analyzed. During a median follow-up of 10.6 [14.9] years, a total of 107 (37%) [100 (42%)] patients died. Patients in the highest CCN1 tertile had a significantly higher mortality risk than those in the lower tertile (p=0.007) [p=0.004]. In the derivation cohort CCN1 remained predictive for all-cause mortality (HR 1.82; 95% CI 1.06, 3.14; P=0.030) in adjusted multivariable Cox regression models. Adding CCN1 to the MAGGIC risk score improved c-statistics for prognostic accuracy of all-cause mortality (0.624 to 0.645, p=0.012), unlike NT-proBNP (0.624 to 0.630, p=0.123).

Conclusion  CCN1 predicts all-cause mortality in DCM patients, warranting further research into the underlying pathophysiology.


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