Vorapaxar in acute coronary syndrome patients undergoing coronary artery bypass graft surgery: subgroup analysis from the TRACER trial (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome).

OBJECTIVES: This study evaluated effects of protease-activated receptor-1 antagonist vorapaxar (Merck, Whitehouse Station, New Jersey) versus placebo among the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass grafting (CABG). BACKGROUND: Platelet activation may play a key role in graft occlusion, and antiplatelet therapies may reduce ischemic events, but perioperative bleeding risk remains a major concern. Although the TRACER study did not meet the primary quintuple composite outcome in the overall population with increased bleeding, an efficacy signal with vorapaxar was noted on major ischemic outcomes, and preliminary data suggest an acceptable surgical bleeding profile. We aimed to assess efficacy and safety of vorapaxar among CABG patients. METHODS: Associations between treatment and ischemic and bleeding outcomes were assessed using time-to-event analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox hazards model. Event rates were estimated using the Kaplan-Meier method. RESULTS: Among 12,944 patients, 1,312 (10.1%) underwent CABG during index hospitalization, with 78% on the study drug at the time of surgery. Compared with placebo CABG patients, vorapaxar-treated patients had a 45% lower rate of the primary endpoint (i.e., a composite of death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization during index hospitalization) (HR: 0.55; 95% CI: 0.36 to 0.83; p = 0.005), with a significant interaction (p = 0.012). The CABG-related Thrombolysis In Myocardial Infarction major bleeding was numerically higher with vorapaxar, but not significantly different between vorapaxar and placebo (9.7% vs. 7.3%; HR: 1.36; 95% CI: 0.92 to 2.02; p = 0.12), with no excess in fatal bleeding (0% vs. 0.3%) or need for reoperation (4.7% vs. 4.6%). CONCLUSIONS: In non-ST-segment elevation acute coronary syndrome patients undergoing CABG, vorapaxar was associated with a significant reduction in ischemic events and no significant increase in major CABG-related bleeding. These data show promise for protease-activated receptor 1 antagonism in patients undergoing CABG and warrant confirmatory evidence in randomized trials. (Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome [TRA·CER] [Study P04736AM3]; NCT00527943).

Thrombolysis followed by coronary angiography versus primary percutaneous coronary intervention in non-anterior ST-elevation myocardial infarction.

BACKGROUND: Previous studies demonstrated the superiority of primary percutaneous coronary intervention (PCI) over thrombolysis for treatment of ST-elevation myocardial infarction (STEMI); however, this advantage is less evident in low-risk populations. The aim of this study was to assess whether a strategy of thrombolysis followed by routine coronary angiography in patients with non-anterior STEMI is non-inferior to primary PCI. METHODS: Consecutive patients with non-anterior STEMI presenting within 6 hours of symptom onset who received reperfusion treatment were included. Mortality, infarct size, and in-hospital and long-term major adverse events were compared between patients treated with primary PCI to those who received thrombolysis followed by coronary angiography and intervention as needed. RESULTS: A total of 300 patients were included: 180 who received thrombolysis and 120 treated with primary PCI. No significant differences were found in mortality, infarct size, or long-term adverse events between groups. Higher rates of in-hospital recurrent ischemic events and longer hospitalization were noted in the thrombolysis group. CONCLUSIONS: The strategy of thrombolysis followed by routine coronary angiography in non-anterior STEMI patients results in major outcomes similar to primary PCI. Thrombolysis serves as a viable approach for patients presenting with non-anterior STEMI to hospitals without catheterization facilities. The optimal time between thrombolysis and coronary angiography should be within 2 days to avoid recurrent ischemia.

Cardiac structure and function in persons 85 years of age.

Individuals aged >85 years constitute the world's most rapidly growing age group. Despite the rapid growth of this population and its high incidence of cardiovascular morbidity, normative data concerning cardiac structure and function are limited. The objective of this study was to define cardiac structure and function in an age-homogenous, community-dwelling population of subjects born in 1920 and 1921. Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed using a portable echocardiograph at the subject's place of residence. Standard echocardiographic assessment of cardiac structure and function was performed. Four hundred fifty subjects (219 men, 231 women) were enrolled in the study. The cohort exhibited large left atrial volumes (64.6 ± 26 ml) and high left ventricular (LV) mass indexes (122 ± 36 g/m(2)) with normal LV volumes. Ejection fractions were preserved (55.3 ± 10.2%), but tissue Doppler s-wave velocities (lateral 7.8 ± 2.1 cm/s, septal 6.7 ± 1.9 cm/s) were reduced. Reduced tissue Doppler e waves (lateral 7.3 ± 2.2 cm/s, septal 6.2 ± 2 cm/s) and elevated E/e' ratios (12.2 ± 4.9) indicated significantly impaired diastolic function. In conclusion, the findings of this study demonstrate a high prevalence of left atrial enlargement, elevated LV mass, evidence of LV systolic dysfunction with preserved ejection fractions, and significant LV diastolic dysfunction in a community-dwelling cohort of 85-year-olds. The finding of elevated E/e' ratios in a subset free of known cardiovascular disease should be considered when clinical assessment of LV diastolic dysfunction in this age group is performed.

Giant precordial T wave inversion in a patient with gastroenteritis.

Giant precordial T wave inversion (GPTI) on ECG may be the result of several pathologies, including myocardial ischemia, pulmonary edema, pulmonary embolism, subarachnoid hemorrhage, apical hypertrophy, and postpacing. We describe a case of a 75-year-old woman who developed GPTI after an episode of gastroenteritis. To our knowledge, this is the first report of this ECG pattern associated with gastroenteritis.

Combination of the Killip and TIMI classifications for early risk stratification of patients with acute ST elevation myocardial infarction.

OBJECTIVE: The Killip classification and the Thrombolysis in Myocardial Infarction (TIMI) score have been proven to be useful tools for the early risk stratification of patients with acute myocardial infarction (MI). The Killip classification is simpler and less time consuming compared to the TIMI score. We sought to evaluate the added value of applying the TIMI score to patients prestratified with the Killip classification. METHODS: A total of 1,773 consecutive acute MI patients were hospitalized in 25 coronary care units operating in Israel, and were followed up to 1 year. RESULTS: Higher Killip class was associated with increased 1-year mortality: 6, 24, 42 and 60% in Killip 1-4, respectively. Applying the TIMI score to Killip 1 patients resulted in further stratifying the patients to low-, medium- and high-risk patient groups with 1, 8 and 19% 1-year mortality rates. CONCLUSIONS: The Killip classification is a useful tool for early risk stratification of acute MI patients. Applying the TIMI score to patients classified as Killip 1 further stratified them into low-, medium- and high-risk subgroups significantly improving stratification by the Killip classification alone.

Effect of gradual computerized angioplasty on outcomes of patients undergoing coronary stenting.

Mechanical trauma caused by percutaneous coronary intervention is a major factor contributing to subsequent cardiac events, restenosis, and the need for target lesion revascularization (TLR). To minimize this trauma, we developed a Computerized Angioplasty Pressure Sensor and Inflator Device (CAPSID) for gradual inflation. The objective of the present prospective randomized study was to examine whether the use of this novel device reduced TLR, as well as cardiac events, in patients undergoing stenting. Patients undergoing coronary stenting were eligible and randomized to receive CAPSID or standard manual percutaneous coronary intervention. In the CAPSID group, slow, gradual balloon inflation was performed using a personal computer. Patients with acute ST-elevation myocardial infarction or the need for percutaneous coronary intervention for total occlusions, left main disease, and vein grafts were excluded. Clinical follow-up for major adverse cardiac events, including death, acute myocardial infarction, and TLR, was performed at 12 months. A total of 310 patients were enrolled in the study. No significant differences were found in the clinical characteristics between the CAPSID and control groups. At 1 year of follow-up, the CAPSID group had had a significantly lower rate of major adverse cardiac events (8% vs 18%, p <0.01) driven by significantly lower rates of acute myocardial infarction (1% vs 7%, p <0.01) and TLR (5% vs 12%, p <0.05). In conclusion, gradual computerized balloon inflation using CAPSID as a platform for angioplasty and stenting significantly reduced TLR and major adverse cardiac events at 1 year in patients undergoing coronary stenting. The use of this novel device may improve outcomes in patients undergoing coronary stenting.

Acute hyperglycemia and spontaneous reperfusion in acute myocardial infarction.

BACKGROUND: Spontaneous reperfusion (SR) may occur in patients with ST elevation myocardial infarction (STEMI) prior to reperfusion therapy. Hyperglycemia is common on admission in patients with STEMI and is associated with a worse prognosis. Mechanisms remain unclear but may include impairment of coronary flow. The objective of this study was to examine whether acute hyperglycemia influenced the occurrence of SR in patients with STEMI. METHODS: All patients presenting to our institution with acute STEMI with measurement of glucose levels on presentation were eligible. SR was defined as a combination of significant relief of chest pain associated with an at least 70% resolution of ST segment elevation on follow-up ECG. RESULTS: 465 patients were studied of whom 77 patients met criteria for SR. Average glucose levels were not significantly different between the SR and non-SR groups (10.0+/-5.6 mmol/l versus 10.1+/-5.3; P=NS). When patients were divided into normoglycemic and hyperglycemic groups, there was no significant difference in the percentages of such patients in the SR and non-SR groups. (52% versus 54%; P=NS). CONCLUSIONS: Acute hyperglycemia on admission does not predict the occurrence of SR in a general population of patients with acute MI.

Effect of severe aortic stenosis on the outcome in elderly patients undergoing repair of hip fracture.

BACKGROUND: The perioperative assessment and management of elderly patients with hip fracture and significant aortic stenosis (AS) is an increasingly common clinical problem with little data available to guide perioperative management. OBJECTIVES: It was the aim of this study to examine the incidence of perioperative events in an elderly population of patients with severe AS undergoing repair of hip fracture as compared with controls without severe AS. METHODS: Patients over the age of 70 with an echocardiographic diagnosis of severe AS defined as an aortic valve area

Computerized gradual balloon inflation: a novel strategy of coronary angioplasty superior to a standard manual approach.

BACKGROUND: Mechanical trauma caused by PCI is a primary reason for restenosis and subsequent target lesion revascularization (TLR). To minimize this trauma, we developed a computerized angioplasty pressure sensor and inflator device (CAPSID) for gradual inflation. The objective of this prospective randomized study was to examine whether use of CAPSID reduces early and late cardiac events in patients undergoing PCI. METHODS: Patients undergoing PCI were eligible and randomized to CAPSID or standard balloon inflation (plain old balloon angioplasty). In the CAPSID group, a slow, gradual balloon inflation was performed by a personal computer. Stenting was used in both groups only for suboptimal results. Patients with total occlusions and vein grafts were excluded. Clinical follow-up for major adverse cardiac events (MACE) was performed at 6 and 12 months, with repeat coronary angiography performed for clinical symptoms or positive stress testing. RESULTS: A total of 234 patients completed the study. At 1-year follow-up, the CAPSID group had a significantly lower rate of MACE (21% vs. 37%, P<.005). In patients who underwent angiography, there was a significantly lower rate of restenosis in the CAPSID group (20.2% vs. 35.5%). The reduction in TLR was even more pronounced in the subgroup undergoing stenting (8% vs. 24%; P<.001). CONCLUSIONS: We conclude that gradual computerized balloon inflation is more effective than standard manual balloon inflation in reducing adverse coronary events. The combination of CAPSID and subsequent stent deployment was especially effective in reducing TLR.

Coronary artery stenting in patients treated by clopidogrel without aspirin.

BACKGROUND: Combined therapy with aspirin and clopidogrel is currently the standard treatment for patients undergoing coronary artery stenting. Some stented patients do not tolerate aspirin and are treated by clopidogrel only, the risk of major adverse clinical events (MACE) in such patients is unclear. OBJECTIVE: To assess the risk of MACE in stented patients treated by clopidogrel only. METHODS: We reviewed records of consecutive patients who underwent bare metal coronary stenting between 1999 and 2004, looking for patients that were treated by clopidogrel without aspirin. Our search revealed 43 such patients with adequate clinical follow-up for at least 1 year following the procedure. We collected information regarding stent thrombosis, acute MI, death or repeat PCI. RESULTS: Two patients (4.7%) were admitted due to acute MI within 30 days of stenting. Stent thrombosis was documented by coronary angiography and target vessel revascularization was performed. CONCLUSIONS: Clopidogrel as a sole anti-platelet treatment after coronary stenting resulted in a relatively high percentage of subacute stent thrombosis. Even higher percentages may be expected when using drug eluting stents. More aggressive anti-platelet therapy may be needed in patients who cannot tolerate aspirin. PTCA alone may be preferable to stenting in such patients.

ST deviation pattern in acute myocardial infarction is not related to lesion location.

BACKGROUND: In ST-elevation MI (STEMI) the culprit artery is usually occluded, whereas non-STEMI (NSTEMI) it is usually patent. The location of the ruptured plaque may influence MI type. We examine whether the distance from the coronary ostium to the culprit lesion is different in STEMI as compared to NSTEMI. METHODS: We selected patients who presented with an acute MI and underwent coronary angiography during hospitalization. The analysis included 754 patients of whom 514 had STEMI and 240 had NSTEMI. The distance from the coronary ostium to the site of thrombosis was measured. RESULTS: For both STEMI and NSTEMI patients the first 60 mm of the coronary artery contained 75% of the culprit lesions. There were no significant differences in median distances from the vessel ostium to the site of thrombosis as well. CONCLUSIONS: The distance from coronary ostium to culprit lesion is similar in STEMI and NSTEMI. Culprit lesion location does not appear to influence the development of STEMI as opposed to NSTEMI.

Relation of spontaneous reperfusion in ST-elevation myocardial infarction to more distal coronary culprit narrowings.

Spontaneous reperfusion (SR) of the infarct-related artery may occur in patients with ST-segment-elevation myocardial infarctions (STEMIs). Limited data are available on the angiographic characteristics of these patients. The objective of this study was to determine if there are differences in the distance of the culprit lesion from the coronary ostium in patients with STEMIs with and without SR. Patients who presented with acute STEMIs<12 hours after pain onset and who underwent coronary angiography were entered into the study. Measurement of the distance from the coronary ostium to the culprit lesion was performed. A total of 469 patients with STEMIs were included in the study, of whom 77 met criteria for SR (significant relief of chest pain associated with >or=50% resolution of ST-segment elevation on follow-up electrocardiography) and 392 did not. A highly significant difference was seen in ostial to culprit lesion distance, with the culprit lesions in the SR group being more distal than those in the non-SR group (45+/-22 vs 39+/-20 mm, p<0.009). In conclusion, the findings of this study demonstrate that the location of the culprit lesion in patients with STEMIs who undergo SR is more distal in the involved artery than in patients with STEMIs who do not undergo SR.

Removal of contrast medium from the coronary sinus during coronary angiography: feasibility of a simple and available technique for the prevention of nephropathy.

BACKGROUND: Contrast-induced nephropathy (CIN) is a major complication of percutaneous coronary interventions with currently limited preventive measures. OBJECTIVES: To prevent CIN, we assessed the safety and feasibility of contrast removal from the coronary sinus (CS) during coronary angiography. METHODS: We attempted contrast removal on seven patients undergoing coronary angiography with preexisting renal insufficiency (mean serum creatinine=262+/-56 mg%). RESULTS: In four patients, a balloon catheter could not be successfully deployed in the CS. In three patients, a balloon catheter with distal side holes was positioned in the CS orifice. The balloon was inflated to occlude the CS concurrent with coronary injections, and 12-16 ml of blood was aspirated after each injection. The procedure appeared to be safe, without adverse events and elevations of serum creatinine levels. Contrast media were effectively withdrawn (44%+/-8%) as assessed by fluoroscopy and dilution of blood. The increased venous pressure at the time of injection reduced coronary flow, allowing for small volumes of administered contrast. CONCLUSIONS: Occlusion of the CS during coronary angiography with aspiration of contrast media is safe and effective in reducing contrast load during coronary interventions. This procedure may reduce the risk for CIN in prone patients.

Smoking cessation does not alter ST deviation pattern of recurrent myocardial infarctions.

BACKGROUND: Myocardial infarction (MI) may be classified as ST elevation MI (STEMI) or non ST elevation MI (NSTEMI). We used the term recurrent MI (RMI's) to denote repeated MI episodes, in a particular patient, in which a different coronary site is responsible for each episode. Recently we reported that most patients with recurrent MI episodes will have either STEMI's or NSTEMI's but not both. A history of smoking was associated with recurrent STEMI's. OBJECTIVE: To determine whether smoking cessation will alter the type of RMI in patients with an index MI of STE type. METHODS: The analysis included 128 patients who underwent at least 2 MI episodes. We attempted to include only MI's of native vessels, without the presence of extra cardiac conditions that intensify myocardial ischemia. All 128 patients were active smokers who presented with an index MI of the STE type. Of these patients 94 had recurrent STEMI and 34 had recurrent NSTEMI (STE/NSTE group). RESULTS: We identified all patients who were no longer active smokers at the time of the recurrent MI: there were 31 (33%) such patients in the STEMI group and 13 (38%) in the STE/NSTE group (p=NS). CONCLUSION: Smoking cessation did not influence the type of recurrent MI in these patients.

Brain natriuretic peptide levels predict perioperative events in cardiac patients undergoing noncardiac surgery: a prospective study.

OBJECTIVES: Brain natriuretic peptide (BNP) levels correlate with prognosis in patients with cardiac disease and may be useful in the risk stratification of cardiac patients undergoing noncardiac surgery (NCS). The objective of this study was to examine whether BNP levels predict perioperative events in cardiac patients undergoing NCS. METHODS: Patients undergoing NCS with at least 1 of the following criteria were included: a clinical history of congestive heart failure (CHF), ejection fraction <40%, or severe aortic stenosis. All patients underwent echocardiography and measurement of BNP performed using the ADVIA-Centaur BNP assay (Bayer HealthCare). Clinical endpoints were death, myocardial infarction or pulmonary congestion requiring intravenous diuretics at 30 days of follow-up. RESULTS: Forty-four patients were entered into the study; 15 patients (34%) developed cardiac postoperative complications. The mean BNP level was 1,366 +/- 1,420 pg/ml in patients with events and 167 +/- 194 pg/ml in patients without events, indicating a highly significant difference (p < 0.001). The ROC area under the curve was 0.91 (95% CI 0.83-0.99) with an optimal cutoff of >165 pg/ml (100% sensitivity, 70% specificity). CONCLUSIONS: BNP levels may predict perioperative complications in cardiac patients undergoing NCS, and the measurement of BNP should be considered to assess the preoperative cardiac risk.

Measurement of wall thickness alone does not accurately assess the presence of left ventricular hypertrophy.

Clinical echocardiographic assessment of left ventricular hypertrophy (LVH) is generally performed by measuring wall thickness alone (WT). The objective of this study was to compare the assessment of LVH using the measurement of WT to that using indexed LV mass. Hypertensive patients underwent echocardiography with the measurement of LV WT and LV mass. For each patient, the presence of LVH was assessed by both methods with WT compared to the gold standard of LV mass index. In all, 92 patients (51M/41F) were entered, and in only 55 patients (60%) were the two methods concordant. There was a tendency for WT to underestimate LVH in females (sensitivity 37%, specificity 79%) and overestimate LVH in males (sensitivity 88%, specificity 56%). The measurement of WT alone overestimates LVH in males and underestimates LVH in females and should not be used as a surrogate marker for increased LV mass.

ST-deviation patterns in recurrent myocardial infarctions.

Myocardial infarction (MI) may be classified as ST-elevation MI (STEMI) or non-STEMI (NSTEMI). We used the term "recurrent MI" (RMI) to denote repeat MI episodes in a particular patient in which a different coronary site is responsible for each episode. We investigated whether the type of RMI is more likely to be of the same type as the index MI or whether patients may have the 2 types of MI at random. The analysis included 305 patients who had >or=2 MI episodes. Acute MIs were classified as STEMI or NSTEMI. We attempted to include only MIs of native vessels, without the presence of extracardiac conditions that intensify myocardial ischemia. Most patients (76%) had repeat episodes of the same MI type, i.e., STEMI or NSTEMI. Recurrent STEMI occurred in 44% of patients, recurrent NSTEMI in 32%, and STEMI and NSTEMI in 24%. Thus, most patients with RMI episodes will have STEMIs or NSTEMIs but not the 2 types, suggesting a predilection of some patients to repeat episodes of occlusive thrombi and others to repeat episodes of nonocclusive thrombi.

Comparison of cardiovascular risk of noncardiac surgery following coronary angioplasty with versus without stenting.

Previous studies have shown a high incidence of cardiovascular complications when noncardiac surgery (NCS) is performed after coronary stenting. No study has compared the outcomes of NCS after stenting compared with percutaneous transluminal coronary angioplasty (PTCA) alone. The records of all patients who underwent NCS within 3 months of percutaneous coronary intervention at our institution were reviewed for adverse clinical events with the end points of acute myocardial infarction, major bleeding, and death < or = 6 months after NCS. A total of 216 consecutive patients were included in the study. Of these, 122 (56%) underwent PTCA and 94 (44%) underwent stenting. A total of 26 patients (12%) died, 13 in the stent group (14%) and 13 in the PTCA group (11%), a nonsignificant difference. The incidence of acute myocardial infarction and major bleeding was 7% and 16% in the stent group and 6% and 13% in the PTCA group (p = NS), respectively. Significantly more events occurred in the 2 groups when NCS was performed within 2 weeks of percutaneous coronary intervention. In conclusion, our study has demonstrated high rates of perioperative morbidity and mortality after NCS in patients undergoing PTCA alone, as well as stenting. These findings support the current guidelines regarding the risk of NCS after stenting but suggest they be extended to PTCA as well.