Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina.
BACKGROUND
Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA).


METHODS
From May 2005 to October 2006, 14 patients, age 68 +/- 20 years old, with CRA and ischemic stress-induced myocardial segments assessed by SPECT received a median 8.19*10(8) ± 4.3*10(8) mononuclear and 1.65*10(7) ± 1.42*10(7) CD34(+) cells by PRCSP.


RESULTS
ABMMC delivery was successful in all patients with no arrhythmias, elevated cardiac enzymes or complications related to the delivery. All but one patient improved by at least one Canadian Cardiovascular Society class at 2 year follow-up compared to baseline (p < 0.001). The median baseline area of ischemic myocardium by SPECT of 38.2% was reduced to 26.5% at one year and 23.5% at two years (p = 0.001). The median rest left ventricular ejection fraction by SPECT at baseline was 31.2% and improved to 35.5% at 2 year follow up (p = 0.019).


CONCLUSIONS
PRCSP should be considered as an alternative method of delivery for cell therapy with the ability to safely deliver large number of cells regardless of coronary anatomy, valvular disease or myocardial dysfunction. The clinical improvement in angina, myocardial perfusion and function in this phase 1 study is encouraging and needs to be confirmed in randomized placebo controlled trials.
Division of Interventional Cardiology and Regenerative Medicine, Clínica Maisón de Santé, Lima, Peru.
Jorge
J
Tuma
Roberto
R
Fernández-Viña
Antonio
A
Carrasco
Jorge
J
Castillo
Carlos
C
Cruz
Alvaro
A
Carrillo
Jose
J
Ercilla
Carlos
C
Yarleque
Jaime
J
Cunza
Timothy D
TD
Henry
Amit N
AN
Patel
D000368:Aged; D000787:Angina Pectoris / Q000503:physiopathology / Q000628:therapy*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002908:Chronic Disease; D054326:Coronary Sinus / Q000473:pathology* / Q000503:physiopathology; D003710:Demography; D015444:Exercise; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D055414:Myocardial Perfusion Imaging; D010477:Perfusion / Q000379:methods*; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology