ΔΙΑΤΑΡΑΧΕΣ ΣΤΕΦΑΝΙΑΙΑΣ ΜΙΚΡΟΚΥΚΛΟΦΟΡΙΑΣ αντιμετώπιση Ανδρουλάκης Αριστείδης, F.E.S.C. Κρατική Καρδιολογική Κλινική Ιπποκράτειο Νοσοκομείο Αθηνών
Τι βλέπαμε Myocardial blush: Angiographic term referring to the adequacy of perfusion and blood flow through an area served by a coronary artery; the longer the blush persists, the poorer the blood flow Τι δεν βλέπουμε
Το στεφανιαίο δίκτυο έχει υψηλή οργάνωση και υπάρχουν πάρα πολλοί ρυθμιστές της ροής ώστε να ικανοποιηθούν σε ΤΟΠΙΚΟ ΕΠΙΠΕΔΟ οι μεταβολικές ανάγκες του μυοκαρδίου small artery small vein systole diastole systole diastole Σε αντίθεση με άλλα όργανα, στο μυοκάρδιο η αρτηριακή ροή είναι σχεδόν αποκλειστικά διαστολική ενώ η φλεβική απορροή συστολική Σε ταχυκαρδία, η υπενδοκαρδιακή αιμάτωση μειώνεται στο 50% της υπεπικάρδιας αιμάτωσης
Coronary Vascular tone Metabolic Myogenic Endothelial Neural the influence of these control mechanisms varies depending upon location within the coronary vasculature Intramural subendocardial arterioles and venules decrease their diameter by 10 20% due to cardiac contraction, whereas the subepicardial arteriolar diameter changed little during cardiac cycle. Τhe subendocardial perfusion is the most under the influence of cardiac contraction (Συνθήκες φόρτισης της αρ. Κοιλίας: ισχαιμία, υπέρταση, διαστολική δυσλειτουργία )
physical inactivity obesity metabolic syndrome Type 2 diabetes mellitus Tachy-myo pathies - Reduced coronary flow reserve - Impaired exercise-induced coronary vasodilation - Increased vasoconstrictor mechanisms ((AT II and a-adrenoreceptor signaling) - Reduced coronary vasodilator mechanisms (such as smooth muscle K+ channel activity) 1. Dysfunction of the endothelium is causally involved in atherosclerosis, heart failure, ischemia-reperfusion injury, and diabetes 2. Abnormalities of coronary vasomotor function occur during the development of obesity and Type 2 diabetes 3. Attenuation of endothelium-dependent NO production 4. Oxidized LDL inhibits endothelium-dependent vasodilation 5. Leptin in the range found in obesity produce acute impairment of acetylcholine-induced coronary vasodilation 6. Endothelium-dependent relaxation responses to acetylcholine, ADP, and the calcium ionophore, A23187, were significantly reduced in isolated coronary arterioles following ischemia and reperfusion but were unaltered in large epicardial arteries 7. Vasoconstrictor responses to pharmacological stimuli are augmented in coronary arteries from atherosclerotic animals
Ιmpairment of coronary flow reserve is associated with increased cardiac mortality among both diabetic and nondiabetic patients in the absence of known large artery disease V. L. Murthy, et al., Association between coronary vascular dysfunction and cardiacmortality in patients with and without diabetes mellitus, Circulation 2012 (126); 1858 68 Ιnability to augment myocardial blood flow in response to stress identified subjects with significantly higher cardiac mortality Murthy VL, et alimproved Cardiac Risk Assessment With Noninvasive Measures of Coronary Flow Reserve. Circulation. 2011;124(20):2215 2224.
There is a significant coupling between ventricular function and microvascular function in the progression of diabetic cardiac dysfunction Does the coronary microcirculation constitute a therapeutic target for treatment of myocardial disease and dysfunction? in prediabetic and diabetic patients and in patients with hypertension without atherosclerotic disease and evidence of diastolic dysfunction? Patients with dilated cardiomyopathy showed evidence of microvascular dysfunction by PET. It remains to be determined whether microvascular disease contributes to progression of fibrosis and myocyte dysfunction, or whether myocardial dysfunction and pathologic hypertrophy lead to aberrant microvascular signaling and function. Angina after successful revascularization procedures: persisting microvascular dysfunction?
Progenitor cells and implementation of therapies (mesenchymal stem cells immediately after myocardial infarction) that increase the activation and homing of these cells may represent novel therapeutic mechanisms for the restoration of coronary arteries and arterioles, thereby reducing injury of the myocardium following ischemic events Statins, ACE-I, Spironolactone Chronic treatment with carvedilol improved coronary vasodilatory reserve in patients with idiopathic dilated cardiomyopathy D. Neglia, et al., Effects of longterm treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy, Heart 2007 (93); 7: 808 13 studies of stem cell therapy also indicate that the greatest improvements in functional recovery following injection of cells occurs when cells differentiate into cardiac, endothelial, and smooth muscle cells C. Bearzi, et al., Human cardiac stemcells, Proceedings of the National Academy of Sciences of the USA 2007; vol. 104, no. 35, pp. 14068 73 progenitor and pluripotent stem cells may constitute important therapeutic means of improving coronary perfusion in diseased or injured myocardium A.Abdel-Latif,et al., Adult bonemarrowderived cells for cardiac repair: a systematic review and metaanalysis, Archives of Internal Medicine 2007; 167 (10): 989 97
- The majority of coronary vascular resistance resides in the coronary microvasculature - Large conduit arteries and resistance vessels often display disparate responses to similar vasoactive stimuli - Even within the microcirculation, responses to the same vasoactive stimulus may differ between large and small arterioles - Metabolic vasodilation has been shown to be an important factor in local control of coronary blood flow - Endothelium-dependent release of NO may modulate myogenic and α-adrenergic responses Clearly, no single control mechanism exerts a predominant effect and these control mechanisms are not uniformly distributed throughout the coronary microcirculation
TIMI 3 flow after primary PCI is being achieved in 93-96 % (PAMI, CADILLAC trials of more than 5400 patients) Suboptimal reperfusion after primary PCI may be caused by one or more of several factors, including: Persistent stenosis or thrombosis Coronary dissection Intramural hematoma Side branch occlusion Coronary spasm Distal macroembolism Acute stent thrombosis Reperfusion injury No-reflow phenomenon
ΠΡΩΤΟΓΕΝΗΣ ΑΓΓΕΙΟΠΛΑΣΤΙΚΗ ΕΠΙ ΟΞΕΟΣ ΕΝΦΡΑΓΜΑΤΟΣ ΜΥΟΚΑΡΔΙΟΥ
NO-REFLOW PHENOMENON Α profound reduction in antegrade coronary blood flow TIMI flow grade 2 despite vessel patency and the absence of: - Dissection - Spasm - Distal macroembolus (distal filling defect with an abrupt "cutoff" in a branch distal to the site of PCI
NO-REFLOW PHENOMENON - AITIA Distal embolization of plaque and/or thrombus Microvascular ischemic damage Myocardial necrosis and stunning Reperfusion injury resulting from oxygen free radical production Release of active tissue factor from the dissected plaque Vasoconstriction secondary to alpha adrenergic tone, thromboxane A2, or serotonin released from platelets Myocardial capillary damage with loss of pinocytotic vesicles in the endothelial cells Endothelial blisters or blebs Endothelial gaps with neutrophil infiltration Intraluminal capillary plugging by neutrophils and/or microthrombi Myocardial cell swelling
Oedema develops within minutes of myocardial ischaemia and reperfusion, induces microvascular coronary compression and thus aggravates myocardial ischaemia Intracellular cardiomyocyte and also endothelial oedema are a result of ionic overload secondary to failure of active ion transport systems interstitial oedema is a consequence of increased microvascular permeability Reactive oxygen species and degradation of the endothelial glycocalyx are causally responsible for interstitial oedema development, and again as in endothelial dysfunction TNFa is important for the degradation of the glycocalyx.
- TIMI frame count - TIMI myocardial perfusion (TMP) grade (or myocardial blush grade) - Doppler flow (both systolic retrograde flow and rapid deceleration of diastolic flow - Myocardial contrast echocardiography (MCE) - Contrast-enhanced cardiovascular magnetic resonance (CEMR) ) Pts with no-reflow have: - more congestive heart failure and arrhythmias early after MI - progressive LV dilatation in the convalescent stage of the MI - significantly higher rates of in-hospital mortality (15 vs. 2 %) - significantly higher rates of MACE (20 vs. 6 %) risk factors for a final Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 after primary PCI Age 70 years Diabetes Longer time to reperfusion Initial TIMI flow grade 1 Left ventricular ejection fraction <50 percent A correlate of suboptimal reperfusion is incomplete ST segment elevation resolution
A 2013 systematic review and meta-analysis of nine small randomized trials of adenosine and one of verapamil found no evidence that either agent reduced short-term, all-cause mortality or non-fatal myocardial infarction. Aung Naing K, Li L, Su Q, Wu T. Adenosine and verapamil for no-reflow during primary percutaneous coronary intervention in people with acute myocardial infarction. Cochrane Database Syst Rev 2013; 6:CD009503. 534 patients randomly assigned to either an ic or an iv bolus of abciximab after primary PCI with thrombus aspiration. There was no significant difference in the incidence of complete ST-segment resolution (64 vs. 62 %). Myocardial blush grade and enzymatic infarct size were better in the intracoronary infusion group. Gu YL, et al. Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial. Circulation 2010; 122:2709.
Intracoronary infusion of adenosine, verapamil, streptokinase, or abciximab has been evaluated in small studies for its ability to improve myocardial reperfusion, prevent reperfusion injury, and salvage ischemic myocardium at the time of primary PCI. None of these agents is associated with a convincing improvement in outcomes (either myocardial flow or clinical) However, we use these agents from time to time despite convincing evidence of benefit. It is possible that the absence of benefit noted in studies is due to small size or suboptimal design. Better outcomes are seen in patients with improvement in coronary flow and there is general agreement within the interventional community that coronary flow often improves after the infusion of vasodilators such as verapamil and adenosine.
ΘΕΡΑΠΕΥΤΙΚΑ ΜΕΤΡΑ ΕΠΙ NO-REFLOW 1. Ελεγχος ACT (250 300 s) 2. Ενδοστεφανιαία νιτρώδη (1 mg) για αποκλεισμό επικαρδιακού σπασμού 3. Σκέψη για χρήση μικροκαθετήρα (child-in-mother) για εγχύσεις, μέτρηση πίεσης, ενδοστεφανιαία χορήγηση φαρμάκων 4. Abciximab: 0 25mg/kg bolus (IV ή IC), και 10 mcg/min IV για 12 h (όχι σε νόσο SVG) 5. Αναρρόφηση αίματος και γρήγορη, έντονη επανέγχυσή του πίσω 6. Ενδοστεφανιαία verapamil (0 25 mg to 2 5 mg) papaverine (10 20 mg) nicorandil (2 mg) nitroprusside (50 200 g) adenosine έντονα bolusses 300-600 γ (έως 50 g) και μετά IV 70-140 mcg/kg/min για 3 ώρες Αδρεναλίνη (50-200γ) bolus Σιμβαστατίνη (zocor) 7. Σε αιμοδυναμική αστάθεια Ινότροπα, Ενδαορτική αντλία υποβοήθησης ή Impella Και τέλος, ΠΑΝΤΟΤΕ
ΘΕΡΑΠΕΥΤΙΚΑ ΜΕΤΡΑ ΕΠΙ NO-REFLOW Η αξιόπιστη αντιμετώπιση του φαινομένου μη επαναρροής (no-reflow) μετά την αποκατάσταση της εγγύς βατότητας της στεφ. αρτηρίας παραμένει ΑΓΝΩΣΤΗ Ευχαριστώ!