A novel experimental thrombotic myocardial infarction and primary angioplasty model in swine.

AIMS: We sought to develop a reproducible animal model for acute myocardial infarction (AMI) in adult atherosclerosis-prone pigs. METHODS AND RESULTS: A coil was placed in the right coronary artery or the left anterior descending artery in 26 downsized spontaneously hypercholesterolaemic pigs and left untreated until thrombotic occlusion. Then, we crossed the thrombotic occlusion with a guidewire, followed by predilatation, thrombus visualisation with optical coherence tomography (OCT) imaging and, finally, deployment of a stent and repeated OCT. After revascularisation, we calculated the index of microcirculatory resistance (IMR). After a feasibility phase (six animals), acute thrombotic occlusion was achieved in all 20 pigs. Eighteen animals were successfully revascularised and survived until sacrifice. Thrombus formation was confirmed by OCT, measurement of thrombin-antithrombin complexes and pathology examination. Myocardial necrosis was confirmed by troponin T elevation, myocardial staining and pathology examination. Distal thrombotic embolisation and microvascular obstruction were supported by increased IMR and pathology examination. CONCLUSIONS: A porcine model of thrombotic occlusion AMI in miniaturised adult spontaneously atherosclerosis-prone pigs is feasible by percutaneous intracoronary placement of a coil. The reperfusion by angioplasty completed this model which mirrors human pathological conditions with myocardial infarction, necrosis and distal embolisation.

Antithrombotic therapy in TAVI.

Transcatheter aortic valve implantation (TAVI) carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials (RCT) were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3-6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3-12 months. Four non-randomized trials were identified, comparing single vs. dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.

Antiplatelet Therapy in TAVI: Current Clinical Practice and Recommendations.

Transcatheter aortic valve implantation (TAVI) is all the more used therapeutic option for patients suffering from symptomatic severe aortic valvular stenosis declined by surgeons because of high surgical risk. Given the high bleeding and ischemic risk of this vulnerable population, their antithrombotic treatment becomes a crucial issue. There is no consensus on antithrombotic treatment after TAVI and dual antiplatelet therapy (DAPT) with aspirin (indefinitely) and clopidogrel (1-6 months) is, in general, recommended. With regards to patients with an indication for oral anticoagulation (OAC), a combination of OAC plus aspirin or clopidogrel is commonly suggested. This review underscores that it is extremely difficult to compare different antithrombotic regimens in patients undergoing TAVI because of their variable demographic characteristics. Nevertheless, available data suggest that DAPT results to more bleeding events. Still, whether it positively affects ischemic episodes is doubtful. Ongoing trials are expected to draw a clearer picture on the field.

Atrial Fibrillation During or After TAVI: Incidence, Implications and Therapeutical Considerations.

INTRODUCTION: Aortic stenosis is one of the most frequent valvulopathy of modern time necessitating interventional therapy when symptoms arise and stenosis becomes severe. First line treatment has traditionally been surgical aortic valve replacement (SAVR). However in the last decade transcatheter aortic valve implantation (TAVI) with bioprosthetic valves has proved to be a sound solution for high-risk for SAVR or inoperable patients. As expected implantation of the bioprosthetic device requires administration of antiplatelet regimen to the patients for a certain period. Atrial fibrillation (AF) may occur frequently during the peri-procedural period. In this background, the occurrence of AF after device implantation may be a challenging issue. METHODS: We performed a literature search of PubMed and Embase database. Published articles reporting the incidence, clinical implications and description of antithrombotic regimen of New-onset atrial fibrillation (NOAF) in individuals undergoing TAVI were considered eligible. Incidence, Implications and Antithrombotic Regimen: The overall occurrence of NOAF is reported to be 1%-32% after TAVI. Left atrial enlargement and transapical approach constitute independent predictors for NOAF. Additionally it has been shown that patients with AF face an increased risk of death irrespective of the type of AF. Patients, with a history of AF, present greater rate of death than individuals with NOAF. NOAF is responsible for cerebrovascular events (CVE) occurring in the subacute phase (days 1-30) after the procedure. The risk of stroke/transient ischemic attack after TAVI is increased at least two fold by the presence of atrial fibrillation. Empirically, a dual antiplatelet strategy has been used for patients undergoing TAVR, including aspirin and a thienopyridine. In cases where patients are in need of oral anticoagulation after TAVI a combination of aspirin or thienopyridine with acenocoumarol has been the preferred regimen. DISCUSSION: Despite the continuously crescent use of TAVI for patients with symptomatic severe aortic stenosis, there are still many aspects of this procedure to be clarified. A lack of data exists from the available clinical trials regarding the appropriate anticoagulation therapy for patients with greater risk for thromboembolic events. As a result, patient's treatment remains at the discretion of the physician. CONCLUSION: Limited data are available regarding the optimal therapeutic regimen in patients undergoing TAVI who need therapy for AF. Carefully designed clinical studies might further clarify the incidence and interrelation between atrial fibrillation and TAVI. The balance between the efficacy and risk of anticoagulation needs to be further clarified in patients undergoing TAVI.

Early coronary revascularization improves 24h survival and neurological function after ischemic cardiac arrest. A randomized animal study.

BACKGROUND: Survival after out-of-hospital cardiac arrest (OHCA) remains poor. Acute coronary obstruction is a major cause of OHCA. We hypothesize that early coronary reperfusion will improve 24h-survival and neurological outcomes. METHODS: Total occlusion of the mid LAD was induced by balloon inflation in 27 pigs. After 5min, VF was induced and left untreated for 8min. If return of spontaneous circulation (ROSC) was achieved within 15min (21/27 animals) of cardiopulmonary resuscitation (CPR), animals were randomized to a total of either 45min (group A) or 4h (group B) of LAD occlusion. Animals without ROSC after 15min of CPR were classified as refractory VF (group C). In those pigs, CPR was continued up to 45min of total LAD occlusion at which point reperfusion was achieved. CPR was continued until ROSC or another 10min of CPR had been performed. Primary endpoints for groups A and B were 24-h survival and cerebral performance category (CPC). Primary endpoint for group C was ROSC before or after reperfusion. RESULTS: Early compared to late reperfusion improved survival (10/11 versus 4/10, p=0.02), mean CPC (1.4±0.7 versus 2.5±0.6, p=0.017), LVEF (43±13 versus 32±9%, p=0.01), troponin I (37±28 versus 99±12, p=0.005) and CK-MB (11±4 versus 20.1±5, p=0.031) at 24-h after ROSC. ROSC was achieved in 4/6 animals only after reperfusion in group C. CONCLUSIONS: Early reperfusion after ischemic cardiac arrest improved 24h survival rate and neurological function. In animals with refractory VF, reperfusion was necessary to achieve ROSC.

Monitoring persistent platelet reactivity in patients with unprotected left main stenting.

OBJECTIVE: This study sought to determine the rate and potential clinical impact of persistent platelet reactivity (PPR) in unprotected left main (ULMD) stenting. BACKGROUND: PPR under aspirin or thienopyridines is associated with acute events after angioplasty. METHODS: We prospectively included 125 patients referred for ULMD stenting. For the first 64 patients (ALMA-1), angioplasty was performed under aspirin and clopidogrel without platelet reactivity assessment. For the last 61 patients (ALMA-2), platelet reactivity was assessed before angioplasty: in patients with aspirin-related PPR, aspirin twice daily was given and in those with clopidogrel-related PPR, clopidogrel double dose or prasugrel was used. RESULTS: Overall, patients' mean age was 69 ± 13 years, 37% were diabetic, and 37% had non-ST segment elevation myocardial infarction (NSTEMI). Patients' characteristics were similar in both studies with isolated left main in 14% and associated with 1-, 2-, or 3-vessel disease in 23%, 36%, and 27%, respectively. Mean SYNTAX score was 23 ± 9. Procedural characteristics were similar using provisional T stenting in 69%, T stenting in 27%, and other techniques in 4%. In ALMA-2, 28% patients had PPR for aspirin, 29% for clopidogrel, and 8% for both. Aspirin twice daily was given in 28% of patients, clopidogrel double dose in 26%, and prasugrel in 31%. The rate of 1-year major adverse cardiovascular and cerebrovascular events (MACCE) was lower in ALMA-2 versus ALMA-1 (8.2% vs. 20.8%; P = 0.04) as a composite end-point of cardiovascular death or stent thrombosis (0.0% vs. 8.3%; P = 0.02). CONCLUSION: PPR under aspirin and thienopyridines is frequent in ULMD stenting and could be related to subsequent major events.