Abstract Body (Do not enter title and authors here): Background. In HFpEF patients transendocardial CD34+ cell therapy was shown to improve systolic and diastolic properties of the myocardium. However, the underlying mechanisms remain poorly defined.
Aim. As coronary microvascular dysfunction is thought to represent a central pathophysiological mechanism of HFpEF, we sought to evaluate the potential correlation between CD34+ cell therapy and myocardial perfusion in HFpEF patients.
Methods. We performed a cardiac MRI (cMRI)-based subanalysis of a prospective pilot study that investigated clinical effects of transendocardial CD34+ cell therapy in HFpEF patients. All patients underwent transendocardial autologous CD34+ cell transplantation using electroanatomical mapping system targeting areas of local mechanical diastolic delay >50 ms. At baseline and 6 months we performed clinical, biochemical, echocardiographic and cMRI evaluation. A 17-segment model was used for cMRI segmental perfusion analysis, which was assessed using gadolinium contrast and a first pass perfusion approach. We analyzed segmental myocardial perfusion using cMRI segmental perfusion data normalized to baseline blood pool (BP) AUC for each patient.
Results. Of 12 patients 2 (17%) were female and the average age was 68±6 years. 6 (100%) patients had a history of hypertension, 2 (17%) had diabetes and 3 (33%) had hyperlipidemia. We found no differences between baseline and follow-up in creatinine (99±28 μmol/L vs. 100±29 μmol/L; P=0.91), bilirubin (18±10 mmol/L vs. 15±5 mmol/L; P=0.33), and NT-proBNP (1581±1079 pg/mL vs. 1437±902 pg/mL; P=0.74) serum levels. Left ventricular systolic function also remained unchanged (LVEF; 62±8% vs. 63±8%; P=0.75 and GLS;-13.3±1.9% vs. -13.5±2.4%; P=0.86). However, left ventricular diastolic function significantly improved at 6 months (E/e'; 17.6±3.6 vs. 12.5±2.0; P=0.002). When performing myocardial segmental analysis, we found significantly higher myocardial viability in injected (N=54) than in noninjected (N=45) electroanatomical segments (15.3±3.8 mV vs. 11.3±4.5 mV; P=0.00001). Moreover, at 6 months myocardial perfusion was significantly improved in 89 injected corresponding cMRI segments, but it remained unchanged in 103 noninjected segments (111±44% vs. 97±21%; P=0.004).
Conclusion. In HFpEF patients, CD34+ cell therapy may be associated with an increase in myocardial perfusion of the target myocardium, which may result in beneficial echocardiographic and clinical benefits observed in this patient cohort.