Dr. Cristian Romeo Revnic,*Dr. Mihai Mereuta*, Dr. Gabriel Ioan Prada*, Dr. Speranta Prada**, Dr. Catalina Pena**, Dr. Flory Revnic**, Dr. Bogdan Paltineanu**
*UMF”Carol Davila”,**NIGG ”Ana Aslan”, Bucharest
REZUMAT:
Introducere: Intrucat disfunctia endoteliala poate fi responsabila de ischemia miocardica chiar si in absenta unor leziuni coronariene semnificative, ne-am propus sa evaluam corelatia dintre functia vasomotoare dependenta de enoteliu si ischemia indusa tarziu dupa o angioplastie coronariana efectuata cu succes.
Metoda: S-a lucrat pe un lot de 30 de pacienti fara restenoze angiografice, ori cu boala coronariana in progres, la care s-a determinat functia endoteliala coronariana prin infuzie de acetilcolina, la 3 luni dupa stentarea unui vas unic coronarian de la nivelul arterei coronare stangi. Schimbarile in diametrul vascular induse de acetilcolina au fost evaluate in segmentul distal si proximal, atat pentru vasele stentate cat si pentru contralaterale, prin intermediul angiografiei coronariene cantitative. S-a utilizat un test ergometric maximal inainte de testarea functiei endoteliale.
Rezultate: Acetilcolina a indus raspunsuri vasoconstrictive semnificative in segmentele distale, nu si in cele proximale, atat in cazul vaselor stentate (-11±7%
vs. baseline; p<0.01) cat si in cazul vaselor contralaterale (-11±6%; p<0.01), care au fost corelate din punct de vedere al semnificatiei statistice (R=0.48;p<0.05) si au fost complet reversate de catre nitroglicerina. Ischemia indusa a fost doar un factor predictiv pentru vasoconstrictia distala in vasele stentate (p<0.01) dar nu si in vasele contralaterale (p=0.06). Pacientii cu semne minore de ischemie la testul de efort ergometric au manifestat o vasoconstrictie mai accentuata, comparativ cu cei cu test normal la efort. (-16±7% vs. -7±6%; p<0.01).
Concluzii: Ischemia indusa de exercitiul fizic la pacientii care au fost supusi interventiei de angioplastie percutanata, efectuata cu succes este legata de disfunctia endoteliala coronariana.
ABSTRACT:
Introduction: As endothelial dysfunction can be responsible for myocardial ischemia even in the absence of significant coronary lesions, we aimed to assess the correlation between endothelium-dependent vasomotor function and inducible ischemia late after successful coronary angioplasty.
Methods: In 30 patients without angiographic restenosis or coronary disease progression, coronary endothelial function was determined by acetylcholine infusion, 3 months after elective single-vessel stenting of the left coronary artery. Acetylcholine-induced diameter changes were assessed in the proximal and distal segments, both of the stented and the
contra-lateral vessel, by means of quantitative coronary angiography. A maximal workload ergometric test was also performed prior to endothelial function testing.
Results: Acetylcholine induced significant vasoconstrictive responses in the distal, but not in the proximal segments, both of the stented (-11±7% vs. baseline; p<0.01) and the contra-lateral vessel (-11±6%; p<0.01), which were significantly correlated R=0.48;p<0.05) and were completely reverted by nitro-glycerine. Inducible ischemia was the only predictive factor for distal vasoconstriction in the stented (p<0.01) but not in the contra-lateral vessel (p=0.06). Patients with minor signs of ischemia at the ergometric
test showed a greater vasoconstriction than those with a completely normal tests (-16±7% vs. -7±6%; p<0.01).
Conclusion: Exercise-induced ischemia late after successful PCI is related to distal coronary endothelial dysfunction.
INTRODUCTION
Inducible myocardial ischemia can be frequently detected also in the absence of significant coronary stenosis (1) and after successful revascularisation procedures (2). Endothelial dysfunction has been held responsible for impaired coronary vasomotor function, cardiac adverse events and myocardial ischemia, also in the presence of mild coronary artery disease (3). Percutaneous coronary interventions (PCI) have proven to be an effective treatment for occlusive coronary disease, and,among all the available techniques, coronary stenting is by far the best in obtaining long-term clinical and angiographic results (4;). However, evidences of persistent endothelial dysfunction in reperfused coronary vessels have been provided both after successful balloon angioplasty (5)and stenting (6). The aim of this experimental study was to assess the impact of endothelial dysfunction on inducible ischemia in a stented and contralateral coronary vessel in the absence of angiographically detectable coronary artery disease late after successful stenting.
METHODS
Patients’ selection. The selection has been made from consecutive patients submitted to elective percutaneous coronary intervention with stent placement for the presence of a flow-limiting stenosis (lumen reduction in percentage >80%) in a single vessel disease involving a major branch of the left coronary artery were asked permission for re-catheterisation and a provocative test with acetylcholine for endothelial function assessment at one month follow-up.
Exclusion criteria were severe systemic hypertension, previous myocardial infarction, primary stenting or small vessels (≤2.5 mm), or left bundle block at basal ECG.
The study protocol was approved by our written informed consent was obtained from all patients.
Standard exercise stress testing was performed by upright bicycle ergometry, beginning at a workload of 50W and increasing in 10 W increments every 30 seconds.
Coronary angiography. The angiographic study was performed by femoral approach with 6F common diagnostic catheters. Patients with in-stent restenosis, or newly developed stenosis on any branch of the left or in the right coronary artery were excluded from further endothelial function testing.
Acetylcholine-mediated endothelial function testing.
Acetylcholine was then injected in three increasing dosages (10 8, 10-7, 10-6 Molar; 3 minutes each), under continuous ECG and blood pressure monitoring. Angiograms were acquired within 1 minute after each infusion. Finally, a bolus (500 g) of nitro-glycerine (NTG) was administered and the angiogram was repeated. Images were digitally stored for post-processing analysis.
RESULTS
Acetylcholine provocative test.
Acetylcholine test was successfully completed in all but 4 patients. In these 4 patients acetylcholine infusion was interrupted because of severe chest pain with or without ECG changes(14) after 10-8 and 10-7 Molar (2 and 4 patients respectively). In that case final angiograms were promptly acquired and nitro-glycerine was administered with rapid restoration of the basal conditions. The proximal coronary segments, both in the stented and in the contra-lateral vessel, did not show any significant change, after acetylcholine and after nitro-glycerine
Inducible ischemia (p=0.06) and smoking (p=0.38) showed a tendency
toward statistical significance. While patients with signs of ischemia at pre-catheterisation ergometric testshowed a significantly higher vasoconstrictive response to acetylcholine than controls in the distal segments of the stented coronary artery (-16 ± 7% vs. –7 ± 6 %; p<0.01), they showed only a tendency toward increasedvasoconstriction in the distal segments of the contra-lateral vessel (-14 ±7% vs. –9 ± 6%; p=0.06)
DISCUSSION
The main findings of this study are: a) a distal vasoconstrictive response toacetylcholine in non-stenotic stented and contra-lateral vessels,3 months after successful coronary stenting; and b) a correlation between inducible ischemia and distal impaired endothelium-dependent vasomotor function in stented but not in contra-lateral non-treated vessels.
Paradoxical vasoconstriction to acetylcholine in the distal epicardial coronary segments of our study cohort can be reasonably explained by the pre-existence of diffuse atherosclerosis. In fact, as already demonstrated by other authors (7;8),
Our study demonstrated a blunted endothelium-dependent vasomotor function homogeneously distributed both in contra-lateral non-stenotic, and in reperfused non-stenotic coronary vessels, 3 months after the angioplasty procedure, thus suggesting that aberrant vasomotion is an independent event from the presence of coronary stent implantation.
Though stents have proved to be superior to only-balloon angioplasty in terms of acute and long term success (1;2), nevertheless they exert a strong mechanical injury, and require a long period before complete reendothelisation (9). Stents are also indicated to trigger a diffuse
inflammatory process in the coronary artery (10). Our data are in accordance wth literature findings (6), who showed a sustained impairment of endothelium-dependent vasomotor function in distal coronary segments after coronary stenting. They also proved that coronary stenting induces inflammation of endothelium. Our study demonstrates that exercise-induced ischemia after successful PCI is related to distal coronary endothelial dysfunction in absence of a significantangiographic stenosis.
CONCLUSIONS
Endothelium-dependent vasomotor function both in reperfused and nonstenotic contra-lateral vessels appears impaired, 3 months after successful coronary stenting. Marked endothelial dysfunction in the epicardial vessels submitted to coronary stenting, and possibly in the tributary microcirculation, can be the cause for mild inducible ischemia at late follow-up. impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms.
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