Juhana Karha

Early and long-term clinical outcomes associated with reinfarction following fibrinolytic administration in the Thrombolysis in myocardial infarction trials

OBJECTIVES We hypothesized that early recurrent myocardial infarction (MI) following fibrinolytic administration would be assessed with higher mortality at both 30 days and 2 years. BACKGROUND Although early recurrent MI after fibrinolytic therapy has been associated with increased early mortality in the acute MI setting, its relation to long-term mortality has not been fully explored. METHODS Mortality data were ascertained in 20,101 patients enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 4, 9, and 10B and Intravenous NPA for the Treatment of Infarcting Myocardium Early (InTIME-II) acute MI trials. RESULTS The frequency of symptomatic recurrent MI during the index hospitalization was 4.2% (836/20,101). Recurrent MI during the index hospital period was associated with increased 30-day mortality (16.4% [137/836] vs. 6.2% [1,188/19,260], p < 0.001). Likewise, recurrent MI was associated with a sustained increase in mortality up to two years, even after adjustments were made for covariates known to be associated with mortality and recurrent MI (hazard ratio 2.11, p < 0.001). However, this higher mortality at 2 years was due to an early divergence in mortality by 30 days and was not due to a significant increase in late mortality between 30 days and 2 years (4.38% [31/707] vs. 3.76% [685/18,206], p = NS). Percutaneous coronary intervention during the index hospitalization was associated with a lower rate of in-hospital recurrent MI (1.6% vs. 4.5%, p < 0.001) and lower two-year mortality (5.6% vs. 11.6%, p < 0.001). Performance of coronary artery bypass graft surgery was also associated with a lower recurrent rate of MI (0.7% vs. 4.3%, p < 0.001) and lower two-year mortality rate (7.95% vs. 10.6%, p = 0.0008). CONCLUSIONS Early recurrent MI is associated with increased mortality up to two years. However, most deaths occur early, and the risk of additional deaths between the index hospital period and two years was not significantly increased among patients with recurrent MI. Percutaneous coronary intervention during the index hospitalization was associated with a lower risk of recurrent MI and a lower risk of two-year mortality.

Evaluation of the association of proximal coronary culprit artery lesion location with clinical outcomes in acute myocardial infarction

Impaired coronary artery blood flow and left anterior descending (LAD) artery culprit location are angiographic variables that have been associated with poorer outcomes after fibrinolytic administration in patients with acute myocardial infarction (AMI). We hypothesized that culprit lesion location in the proximal portion of the culprit artery would also be associated with poorer clinical outcomes compared with a mid or distal location. Lesion location and clinical outcomes were evaluated in 2,488 patients from the Thrombolysis In Myocardial Infarction (TIMI) 4, 10A, 10B, and 14 trials. Proximal lesions were located before or at the first major branch of the parent artery, mid lesions were between the first and the second major branches, and all other lesions were classified as distal. Proximal lesions were associated with a higher incidence of in-hospital death or recurrent AMI compared with mid or distal lesions (10.5% [n = 478] vs 6.1% [n = 1,498] vs 3.7% [n = 511], p <0.001), and they were associated with a higher rate of in-hospital death (6.7% [n = 478] vs 3.2% [n = 1,498] vs 2.5% [n = 511], p = 0.001). In a multiple logistic regression model adjusting for TIMI flow grade, age, gender, and pulse, the planimetered distance from the ostium to the LAD culprit lesion was associated with 30-day death or recurrent AMI (odds ratio 0.79 per centimeter increase in distance down the artery, p = 0.01). Proximal culprit lesion location is associated with an increased risk of adverse outcomes after fibrinolytic administration, which is likely due to a larger area of subtended myocardium. In patients with a LAD culprit lesion, proximal lesion location is a multivariate correlate of adverse outcomes even after adjustment for coronary blood flow and other covariates.

Development of Coronary Aneurysm after Drug-Eluting Stent Implantation

Background: The problem of drug-eluting stents increasing the risk for late thrombosis, especially when antiplatelet therapy becomes interupted, is a growing concern (1). Recently, a new association with these devices was observed at our institution (Cleveland Clinic, Cleveland, Ohio). Objective: To report cases of coronary aneurysm after drug-eluting stent implantation and to describe the different strategies used to treat the problem. Case Report: An aneurysm (8 mm in diameter by intravascular ultrasonography) was discovered in a 49-year-old woman 19 months after implantation of a sirolimus-eluting stent (CYPHER, Cordis Corp., Miami Lakes, Florida) (Figure 1). The patient underwent excision of the aneurysm with a bypass graft to the distal artery. Pathologic examination of the aneurysm revealed eosinophilic infiltration. Figure 1. Coronary aneurysm after stent implantation. A 44-year-old man had a coronary aneurysm (14 mm in diameter by intravascular ultrasonography) that was discovered 21 months after implantation of 2 paclitaxel-eluting stents (TAXUS, Boston Scientific, Natick, Massachusetts) (Figure 2). The patient underwent successful coiling of the aneurysm. Figure 2. Coronary aneurysm after stent implantation ( A ) and coronary aneurysm coiling ( B ). A 45-year-old man had an aneurysm that was discovered 6 months after implantation of a paclitaxel-eluting stent. After 12 months of clinical surveillance, repeated angiography revealed nearly complete resolution of the aneurysm (Figure 3). Figure 3. Stent implantation ( A ), coronary aneurysm after stent implantation ( B ), and nearly complete aneurysm resolution after stent implantation ( C ). A 49-year-old woman had a coronary aneurysm that was discovered 10 months after implantation of a sirolimus-eluting stent. Intravascular ultrasonography of the left main artery revealed an aneurysm without evidence of dissection or thrombus (Figure 4). The plan is for continued clinical surveillance. Figure 4. Left main artery aneurysm ( white arrow ) and dilatation of the left anterior descending sirolimus-eluting stent ( black arrow ). Discussion: The incidence of coronary aneurysm after the use of drug-eluting stents is currently unknown. In the Treatment of De Novo Coronary Disease Using a Single Paclitaxel Eluting Stent V (TAXUS-V) trial (2), the incidence was 1.4% with paclitaxel-eluting stents, compared with a 0.2% prevalence with bare metal stents (P= 0.07). Moreover, in 2 of our patients, no angiographic abnormalities with coexisting bare-metal stents were found. Late stent thrombosis and coronary aneurysm formation may share the same pathogenesis of localized hypersensitivity to drug-eluting stents (3). Similar inflammatory reactions have not been seen with bare-metal stents (4). Aneurysm formation was also not explained by obvious technical factors, such as the use of excessive pressure during stent deployment or the use of oversized stents. In all patients, stent size appeared to be well-matched to reference vessel diameter. Conclusion: Coronary aneurysm formation can occur in all coronary distributions after the use of drug-eluting stents. Currently, the natural history and best treatment for the problem is unknown; however, some aneurysms resolve. Because they may be serious problems, some aneurysms should be considered for surgical excision, percutaneous coiling, or placement of a covered stent.

Distance from the Coronary Ostium to the Culprit Lesion in Acute ST-Elevation Myocardial Infarction and its Implications Regarding the Potential Prevention of Proximal Plaque Rupture

AbstractBackground: Shorter distances from the coronary ostia to culprit lesions have been associated with a higher incidence of adverse outcomes in ST elevation acute myocardial infarction (STEMI). As drug-eluting stents are associated with low rates of restenosis and formation of a stable intima, we sought to develop a mathematical model to estimate how far down the coronary artery a drug-eluting stent would have to be placed to theoretically mitigate the risk of proximal plaque rupture. Objectives and Methods: Distances from the ostia to the end of the culprit lesions were planimetered in 1,914 patients from the TIMI 14, INTEGRITI, FASTER and ENTIRE/TIMI 23 trials. Results: The first 60 mm of the coronary artery contained 75% of STEMI culprit lesions. The median distance from the vessel ostium to the end of the culprit lesion was 43 mm (mean 50 ± 34) and the relative distance from the vessel ostium to the end of the lesion was 29% (mean 33 ± 17%) of the total culprit artery length. Diabetes was the only baseline clinical characteristic associated with a longer absolute distance to the end of the culprit lesion (46 mm vs. 43 mm, p = 0.03) as well as relative to total artery length (31% vs. 29%, p = 0.04). Median distances from the artery ostium to the end of the culprit lesion were shortest among the left anterior descending culprits (40 mm), followed by circumflex lesions (43 mm) and then right coronary artery lesions (47 mm, 3-way p < 0.0001). Conclusion: The majority of culprit lesions in STEMI are contained within the proximal 30% of the major epicardial coronary arteries, but the distance varies depending upon which epicardial artery is involved. Cumulative distribution functions are presented to allow estimation of the percent of culprit lesions lying proximal to any given distance from the ostium to model the feasibility of prophylactic drug-eluting stenting to minimize the risk of subsequent proximal plaque rupture.

Association of the Fibonacci Cascade with the distribution of coronary artery lesions responsible for ST-segment elevation myocardial infarction

This is the first study to demonstrate the appearance of the Fibonacci Cascade within the distribution of coronary artery lesions in the human heart. The propensity for this ratio to appear in nature may also be because this ratio optimizes the efficiency of packing structures in a limited space in such a way that wasted space is minimized and the supply of energy or nutrients is optimized.

Safety and efficacy of tenecteplase in acute myocardial infarction

The use of intravenous thrombolytic agents has revolutionised the treatment of acute myocardial infarction. However, the improved mortality achieved with these drugs is tempered by the risk of serious bleeding complications, especially intracranial haemorrhage (ICH). Tenecteplase (TNKase™, Genetech Inc.) is an engineered variant of alteplase (Activase®, Genentech Inc.) designed to have increased fibrin specificity, greater efficacy and a longer half-life. The longer half-life of tenecteplase compared to alteplase allows for convenient single bolus administration of the drug. In addition, tenecteplase dosing is based on actual or estimated patient weight, which enhances both the safety and efficacy outcomes. Large clinical trials have demonstrated equivalence in mortality and ICH between tenecteplase and alteplase. Compared to alteplase, tenecteplase use leads to lower rates of bleeding complications and a decreased risk of ICH among low weight, elderly women.

Percutaneous Coronary Intervention in Diabetics

Diabetes mellitus (DM) is a common illness with significant cardiovascular importance. The prevalence and incidence of diabetes are increasing due to an aging population on the one hand and increasing obesity and physical inactivity on the other [1–9]. Diabetics are at an increased risk of developing coronary artery disease as well as its complications, including death [10,11]. An estimated 65% of diabetics ultimately die from cardiovascular causes [10– 15]. In fact, a history of diabetes yields an added incremental risk similar to a history of a prior myocardial infarction [16]. Diabetics also have a worse prognosis in the setting of acute coronary syndromes (ACS) whether the presentation is unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), or acute ST elevation myocardial infarction (STEMI) [17–26]. Percutaneous coronary intervention (PCI) is an effective therapy for stable angina [27–30] as well as for unstable angina [31] and myocardial infarction [32,33]. Diabetics increasingly undergo PCI [34,35]. This article will review the complications, benefits, and special considerations related to PCI in a diabetic patient.

Patient Selection for Carotid Stenting

The goal in treating carotid artery atherosclerotic disease is to reduce the risk of stroke. Three therapeutic options for management of carotid disease exist: medical therapy, carotid artery stenting, and carotid endarterectomy. Clinical and anatomic characteristics of the individual patient dictate which of these options should be chosen. This chapter will review the indications and contraindications to carotid artery stenting.

Percutaneous coronary intervention during the index hospitalization is associated with reduced recurrent myocardial infarction and improved survival following thrombolytic administration

Background: Recurrent myocardial infarction (reMI). remains a limitation of fibrinolytic therapy. We hypothesized that following fibrinolytic administration, performance of percutaneous coronary intervention (PCI) during the index hospitalization is associated with lower rates of recurrent MI and death compared to conservative management. Methods: Performance of PCI thru hospital discharge and mortality up to 2 years were ascertained in the TIMI 4, 9A, 98, 106 and 17 acute Ml trials (n=20,043). Patients whose PCI followed a recurrent Ml (n=266) were included in the medical therapy arm. Results: PCI was performed in 21.4% of patients at a median of 4 days (IQ range l-6). In-hospital recurrent Ml occurred less frequently in patients treated with PCI vs. patients without PCI (1.6% vs. 4.5%, p<O.OOl). Mortality was also lower in patients treated with PCI (pc0.0001; Figure). Similar results were seen across the low, intermediate, and high TIMI risk scores (Figure). Both PCI and recurrent MI remained associated with 2 year mortality in a model adjusting for age, anterior MI. pulse on admission, and gender (PCI hazard ratio=0.51, p<O.OOl; recurrent Ml hazard ratio=l.95, p<O.OOl). Conclusion: Following thrombolytic administration, PCI during the index hospitalization was associated with a lower rate of in-hospital recurrent MI and improved 2 year survival.