Is it possible to predict CRT response by analyzing damaged-DNA in blood taken from coronary sinus?

Introduction: Heart failure (HF) patient selection for Cardiac Resynchronization Therapy (CRT) continues to be a real issue nowadays and still needs improve-ment. Up to 30% of CRT patients are currently non-res-ponders to therapy. New bio – markers could be helpful in identifying CRT responders, before procedure.

Objectives: T he aim of our prospective study was to evaluate both damaged- DNA and total antioxidant ca-pacity (TAC) –both being part of the oxidative stress panel – in HF patients. Measurements were done prior to cardiac resynchronization therapy and after implant, in order to assess the magnitude of oxygen related stress and its evolution before and after therapy (both in responders and non-responders).

Methods: We enrolled 28 patients with conventional guideline indication for CRT: NYHA Class (II-III), EF <35%, LBBB, QRS >130 ms. Blood samples were taken during CRT intervention (both peripheral and directly from the coronary sinus). We followed-up with them every 3 months and a third sample of peripheral blood was taken 6 to 12 months after intervention. Dama-ged DNA and TAC were then assessed using ELISA method. Although taking blood from the coronary sinus may seem an invasive approach, almost all pati-ents undergoing CRT implant are referred a priori for coronary angiogram; at this point coronary angiogram could be completed with the catheterization of the co-ronary sinus.

Results: Out of 28 patients, 15 were responders to CRT– using clinical and echocardiography data. The assess-ment of damaged DNA from peripheral blood prior and after intervention showed no specific pattern and no obvious evolution, both in responders and non-res-ponders. By contrast, the level of damaged DNA taken from the coronary sinus identified a clear and distinct population – all the responders to therapy seemed to have greater levels of Damaged DNA in contrast with the non-responder population. As expected, TAC was lower in the responders group vs. non-responders. Our theory is that greater levels of damaged DNA should be present in heart failures with high percent of re-maining viable myocardium. On the contrary, hearts with extensive fibrosis/scar with no or very little viable myocardium are unable to produce high quantities of damaged DNA due to the lack of active cardiac fibers. These patients are less likely to reverse-remodel and consequently are candidates for non-response to CRT. There was no correlation between oxidative stress ob-served in peripheral and central cardiac blood. Interes-ting correlations also occurred between QRS duration and the levels of oxidized DNA.

Conclusion: Damaged- DNA and TAC measured from coronary sinus pre-procedural blood sample could be a new biomarker to identify responders to CRT, but it needs further research. Peripheral oxidative stress mar-kers seem to be of no use.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)