Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study.

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Endovascular stent implantation in a coronary artery to pulmonary artery fistula in a patient with pulmonary atresia with ventricular septal defect and severe cyanosis.

A 31-year-old male with pulmonary atresia, ventricular septal defect presented with exercise intolerance and severe cyanosis. A restrictive coronary-pulmonary artery fistula was identified as the main source of pulmonary blood flow. We report transcatheter stent implantation in the fistula to augment pulmonary flow as a palliative management option in the adult patient with complex congenital heart disease.

Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience).

Earlier studies documented an increased risk of percutaneous coronary intervention (PCI) in patients with angiographic evidence of thrombus. With newer antiplatelet agents and stents, it is not known whether thrombus is a risk factor after PCI. This study examines whether outcome of PCI in patients with thrombus has improved, and whether thrombus is associated with adverse outcome after PCI in the current era. This single-institution retrospective analysis of PCI in 7,184 patients was divided into 2 periods: group I, 1990 to 1995 (n = 3,640), and group II, 1996 to 1999 (n = 3,544). The groups were subdivided according to the presence or absence of angiographic thrombus before PCI. We compared the outcome of PCI for patients with and without thrombus in group II. A comparison was made in the 2 groups in patients with angiographic thrombus. Procedural success improved in group II compared with group I patients with thrombus (93% vs 88%, p <0.001). There was significant reduction in abrupt closure in the recent era in patients with thrombus (4% vs 7%, p = 0.01). In group II, procedural success remained lower in patients with (93% vs 96%) than without thrombus (p <0.001). After adjusting for the significant univariate characteristics of group II patients, thrombus remained an independent predictor of Q-wave infarction (odds ratio 3.78; 95% confidence interval [CI], 1.8 to 8.0; p <0.0013) and the composite end point of death, Q-wave infarction, and emergency bypass surgery (odds ratio 2.37; 95% CI 1.4 to 4.1; p = 0.002). There was a trend toward increased in-hospital death among patients with thrombus (odds ratio 2.06; 95% CI 0.9 to 4.8; p = 0.09). The 1-year outcome after successful PCI was similar for those with and without thrombus. Despite improvement in the outcome of patients with thrombus undergoing PCI in recent years, thrombus is still an independent predictor of adverse in-hospital outcomes after PCI.

Incremental doses of intracoronary adenosine for the assessment of coronary velocity reserve for clinical decision making.

Achievement of maximal vasodilatation of the coronary microcirculation is a prerequisite for the measurement of coronary flow reserve (CFR). The present study was designed to address the hypothesis that intracoronary adenosine yields more complete vasodilation of the coronary microcirculation when incremental doses are used, resulting in higher and more accurate coronary flow reserve measurements. Four hundred and fifty-seven patients were divided in two groups; group I (319 patients) comprised patients without angiographic evidence of significant coronary artery disease, while group II (138 patients) comprised patients with intermediate coronary stenoses (between 40% and 70% diameter stenosis). Coronary velocity reserve (CVR, a surrogate measurement for CFR) was measured during cardiac catheterization using a Doppler-tipped guidewire. Incremental doses of intracoronary adenosine (12 to 54 microg for the left coronary artery and 6 to 42 microg for the right coronary artery) were administered. There was a significant difference between the initial dose of adenosine and the subsequent incremental doses. Of a total of 479 observations, only 192 (40%) had the maximal CVR value at the first dose. Thirty-nine percent of the patients in group I and 27% in group II with an initial CVR value < 2.5 increased CVR to > or = 2.5 with incremental doses of adenosine. This study suggests that incremental doses of adenosine should be used to achieve maximal CVR for the assessment of the functional significance of coronary lesions. Cathet Cardiovasc Intervent 2001;54:34-40.

Calcium embolism of the coronary arteries after percutaneous mitral balloon valvuloplasty.

Two cases of rare, catastrophic calcium emboli to the coronary arteries immediately after percutaneous mitral balloon valvuloplasty are presented. Preoperative echocardiographic findings may identify patients at risk for this complication. These cases should increase the awareness of calcium emboli and lead to consideration of urgent coronary angiography for patients with signs or symptoms of acute coronary occlusion after valvuloplasty.

Improving outcome over time of percutaneous coronary interventions in unstable angina.

OBJECTIVE: This study was performed to evaluate the recent changes in the outcome of coronary interventions in patients with unstable angina (UA). BACKGROUND: An early invasive strategy has not been shown to be superior to conservative treatment in patients with UA. Earlier studies had utilized older technology. Interventional approaches have changed in the recent past, but to our knowledge, no large studies have addressed the impact of these changes on the outcome of coronary interventions. METHODS: We analyzed the in-hospital and intermediate-term outcome in 7,632 patients with UA who underwent coronary interventions in the last two decades. The study population was divided into three groups: group 1, n = 2,209 who had coronary intervention from 1979 to 1989; group 2, n = 2,212 with interventions from 1990 to 1993; and group 3, n = 3,211 treated from 1994 to 1998. RESULTS: Group 2 and 3 patients were older and sicker compared with group 1 patients. The clinical success improved significantly in group 3 (94.1%) compared with group 2 (87%) and group 1 (76.5%) (p < 0.001). There was a significant reduction in in-hospital mortality, Q-wave myocardial infarction and need for emergency bypass surgery in group 3 compared with the earlier groups. One-year event-free survival was also significantly higher in the recent group compared with the earlier groups: 77% in group 3, 70% in group 2 and 74% in group 1 (p < 0.001). With the use of multivariate models to adjust for clinical and angiographic variables, treatment during the most recent era was found to be independently associated with improved in-hospital and intermediate-term outcomes. CONCLUSIONS: There has been significant improvement in the in-hospital and intermediate-term outcome of coronary interventions in patients with UA in recent years; newer trials comparing conservative and invasive strategies are therefore needed.

Application of the New York State PTCA mortality model in patients undergoing stent implantation.

BACKGROUND: This study applied the New York State conventional coronary angioplasty (PTCA) model of clinical outcomes to evaluate whether it has relevance in the current era of stent implantation. The model was developed in 62 670 patients treated with conventional PTCA from 1991 to 1994 to risk adjust mortality and bypass surgery after PTCA. Since then, stents have become the dominant form of intervention. Whether that model remains relevant is uncertain. METHODS AND RESULTS: All patients undergoing stenting at the Mayo Clinic from 1995 to 1998 were analyzed for in-hospital mortality, bypass surgery performed after attempted stenting, and longer-term mortality. No patients were excluded. The New York model was used to risk adjust and predict in-hospital and follow-up mortality. There were 3761 patients with 4063 procedural admissions for stenting; 6,472 target vessel segments were attempted, and 96.1% of procedures were successful. With the New York multivariable risk factor equation, 79 in-hospital deaths were expected (1.95%); 66 deaths (1.62%) were observed. The New York model risk score in a logistic regression model was the most significant factor associated with in-hospital mortality (OR, 1.86; P<0.001). During a mean follow-up of 1.2+/-1.0 years, there were 154 deaths. Multivariable analysis documented 6 factors associated with subsequent mortality; New York risk score was the most significant (chi(2)=16.64, P=0.0001). CONCLUSIONS: Although the New York mortality model was developed in an era of conventional angioplasty, it remains relevant in patients undergoing stenting. The risk score derived from that model is the variable most significantly associated with not only in-hospital but also longer-term outcome.

Clopidogrel versus ticlopidine after intracoronary stent placement.

OBJECTIVES: The study compared the safety and efficacy of ticlopidine with clopidogrel in patients receiving coronary stents. BACKGROUND: Stent thrombosis is reduced when ticlopidine is administered with aspirin. Clopidogrel is similar to ticlopidine in chemical structure and function but has fewer side effects; few data are available about its use in stent patients. METHODS: We compared 30-day event rates in 500 consecutive coronary stent patients treated with aspirin and clopidogrel (300 mg loading dose immediately prior to stent placement, and 75 mg/day for 14 days) to 827 consecutive stent patients treated with aspirin and ticlopidine (500 mg loading dose and 250 mg twice daily for 14 days). RESULTS: Patients treated with clopidogrel had more adverse clinical characteristics including older age, more severe angina, and more frequent infarction within the prior 24 h. Nonetheless, mortality was 0.4% in clopidogrel patients versus 1.1% in ticlopidine patients; nonfatal myocardial infarction occurred in 0% versus 0.5%, stent thrombosis in 0.2% versus 0.7%, bypass surgery or repeat angioplasty in 0.4% versus 0.5%, and any event occurred in 0.8% versus 1.6% of patients, respectively (p = NS). Based on the observed 30-day event rate of 1.6% with ticlopidine, the statistical power of the study was 43% to detect an even rate of 0.5% with clopidogrel, and 75% to detect an event rate with of 4% with clopidogrel, with a p value of 0.05. CONCLUSIONS: These data indicate that clopidogrel can be safely substituted for ticlopidine in patients receiving coronary stents.

Measuring maximal percent area stenosis poststent placement with intracoronary Doppler and the continuity equation and correlation with intracoronary ultrasound and angiography.

Quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) are methods for anatomic assessment of stent deployment. Intracoronary Doppler is primarily a method for the physiologic assessment of coronary stenoses. It correlates well with traditional noninvasive measurements of lesion significance. Intracoronary Doppler was used for the anatomic assessment of de novo coronary artery stenosis with variable success; however, its use for anatomic assessment of adequate stent deployment is unavailable. A rapid, automated software program was developed based on a modified continuity equation to calculate the maximal in-stent percent area stenosis by comparing the maximal in-stent velocity to an average reference velocity (proximal and distal). This study was designed to compare the Doppler method of an anatomic assessment with QCA and ICUS in 15 patients. Physiologic success of stent deployment was determined by the distal coronary flow reserve to 24 to 36 microg of intracoronary adenosine. Following successful stent deployment, distal coronary flow reserve increased significantly from a baseline of 1.6 +/- 0.5 to 2.9 +/- 1.1. There was a significant correlation between the maximal in-stent percent area stenosis as measured by Doppler and both QCA (r = 0.78, p <0.01) and ICUS (r = 0.84, p <0.01). This study demonstrates that maximal in-stent percent area stenosis can be measured by intracoronary Doppler and a novel software program. The intracoronary Doppler guidewire method can assess the adequacy of stent deployment using both anatomic and physiologic principles and may supplement other quantitative methodologies.

Comparison of long-term results of percutaneous mitral balloon valvotomy with closed transventricular mitral commissurotomy at a single North American Institution.

Long-term (>3 years) follow-up data were obtained from 102 consecutive patients undergoing percutaneous mitral balloon valvotomy (PMBV). Data were collected prospectively by review of the medical record, mailed questionnaire, and/or telephone. Data on patients with closed mitral commissurotomy (CMC) at our institution have been previously reported and serve as the comparison group. Follow-up data was 98% complete at a mean of 57 months for PMBV patients. Compared with patients undergoing CMC, these patients were older (54+/-14 vs 43.6+/-10 years, p <0.001) and more likely to have undergone previous mitral valve surgery (17% vs 4%, p <0.001). The observed 5-year survival in the PMBV group was no different from that observed in the CMC group (83% vs 90%, p = NS) or from that predicted by the model developed from the CMC patients. Commissural calcium was associated with death and death or repeat mitral valve procedure in the multivariate analysis. Long-term survival free from repeat procedures was equivalent when patients with commissural calcium were excluded. Thus, PMBV offers long-term survival and freedom from subsequent mitral valve procedures similar to CMC.

Prognostic importance of lower extremity arterial disease in patients undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI).

OBJECTIVES: The purpose of this study was to evaluate the prevalence and prognostic importance of lower extremity arterial disease (LEAD) in patients with multivessel coronary artery disease. BACKGROUND: The presence of clinically evident LEAD increases the risk of death in patients with known coronary artery disease. Because studies have lacked noninvasive measures of subclinical LEAD, the true prognostic importance of lower extremity atherosclerosis in this population has probably been underestimated. METHODS: Ankle blood pressures were measured in 405 consecutive patients with angiographically documented multivessel coronary disease from seven Bypass Angioplasty Revascularization Investigation (BARI) sites and a parallel study site within 3 years of enrollment. Lower extremity arterial disease was defined as an ankle/arm systolic blood pressure ratio of 0.90 or less. RESULTS: Among patients studied, 69 (17%) had LEAD. These patients were more likely to be current smokers, treated for diabetes, older and present with unstable angina compared with patients without LEAD. Among patients who underwent coronary arterial bypass grafting, major complications occurred in 2.8% of those without LEAD compared with 20.7% of those with LEAD (p = 0.002). Five-year mortality rates were similar for symptomatic LEAD (14%) and asymptomatic LEAD (14%). Patients without LEAD had a 3% mortality. After adjusting for baseline differences, the relative risk of death was 4.9 times greater for patients with LEAD compared with those without (95% confidence interval [CI]: 1.8, 13.4, p < 0.01). CONCLUSIONS: Patients with LEAD have a significantly higher risk of death than patients without LEAD, regardless of the presence of symptoms. An abnormal ankle/arm index is a strong predictor of mortality and can be used to further stratify risk among patients with multivessel coronary artery disease.

Increased incidence of periprocedural complications among patients with peripheral vascular disease undergoing myocardial revascularization in the bypass angioplasty revascularization investigation.

BACKGROUND: Risks of coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) may be different in the presence of peripheral vascular disease (PVD). METHODS AND RESULTS: We analyzed outcomes of 550 patients with PVD enrolled in the Bypass Angioplasty Revascularization Investigation randomized trial and registry. Compared with 1770 patients without PVD, those with PVD were older and had a greater prevalence of medical comorbid conditions. No significant differences in coronary anatomy or PTCA success rates were found. The risk of any major complication (death, myocardial infarction, stroke, coma, or emergency revascularization) after PTCA was significantly higher among patients with PVD (11.7% versus 7.8%, P=0.027). In multivariate analysis, this represented a 50% increase in the odds of having any major complication (multivariate odds ratio, 1.5; P=0. 032). Among patients undergoing CABG, the risk of major complications was found to be markedly higher for patients with PVD (12%) than those without (6.1%, P=0.003) even after controlling for baseline differences (multivariate odds ratio, 1.8; P=0.018). Major differences between the PTCA and CABG groups were related primarily to a higher risk of neurological complications in PVD patients who had CABG (multivariate odds ratio, 2.8; P<0.001). CONCLUSIONS: We conclude that patients with PVD are at high risk for periprocedural complications after myocardial revascularization, in particular neurological events.

Smoking status and outcome after primary coronary angioplasty for acute myocardial infarction.

BACKGROUND: Because of the increased propensity of intracoronary thrombi to form in cigarette smokers, percutaneous transluminal angioplasty (PTCA) for acute myocardial infarction (AMI) may be less effective in smokers. We sought to determine the impact of smoking status on outcome after PTCA for AMI. METHODS: Patients enrolled in the GUSTO IIb Angioplasty Substudy were randomly assigned to receive PTCA or tissue-plasminogen activator (tPA) for AMI. The interaction of smoking status (nonsmokers = 344, former smokers = 294, current smokers = 490) and treatment strategy with the occurrence of death, nonfatal reinfarction, or nonfatal, disabling stroke at 30 days was analyzed. Procedural success (residual stenosis <50% and Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) was also analyzed for patients who underwent PTCA (n = 444). RESULTS: Among patients who underwent PTCA, nonsmokers had worse percent stenosis of the culprit lesion before reperfusion (P =.03) and more often had TIMI flow grade 0 (P <.05). Procedural success was more common in smokers (65.6%) than in former smokers (53.3%) and nonsmokers (52. 4%; P =.02), reflecting a higher rate of postprocedure TIMI 3 flow. PTCA was associated with a better 30-day outcome than tPA for current smokers (odds ratio [95% confidence interval] = 0.41 [0.19 to 0.88]), with a similar trend for former smokers (0.73 [0.34 to 1. 58]) and nonsmokers (0.77 [0.42 to 1.40]). At 6 months, smokers randomly assigned to PTCA also had fewer deaths and reinfarction (0. 58 [0.31 to 1.07]). CONCLUSIONS: Although smoking status affects angiographic variables before and after PTCA for AMI, PTCA is associated with a better 30-day outcome than tPA regardless of smoking status and should be considered when readily available.

Medical therapy after successful percutaneous coronary revascularization.

BACKGROUND: Percutaneous coronary revascularization frequently relieves angina in patients with ischemic heart disease and may obviate the need for antianginal medications. OBJECTIVE: To examine the use of antianginal medications after successful percutaneous coronary revascularization. DESIGN: Retrospective cohort study of the Mayo Clinic PTCA [percutaneous transluminal coronary angioplasty] Registry. SETTING: Tertiary care center. PATIENTS: 3831 patients who underwent successful percutaneous coronary revascularization from September 1979 through August 1997 and had not had myocardial infarction within the year before the intervention. MEASUREMENTS: Use of antianginal medications (beta-adrenergic blockers, nitrates, and calcium-channel blockers) before the intervention, at hospital discharge, and 6 months after the intervention. RESULTS: 99% of patients reported improvement in their symptoms at hospital discharge. At 6 months, 87% of patients were free of myocardial infarction, coronary bypass surgery, or additional percutaneous intervention. Compared with 66% of patients before the index intervention, only 12% of patients had severe angina at 6 months and 69% were completely free of angina. Nonetheless, at 6 months, 39% of patients were receiving beta-adrenergic blockers (preprocedure proportion, 43%; P < 0.001), 36% were receiving nitrates (preprocedure proportion, 41%; P < 0.001), and 57% were receiving calcium-channel blockers (preprocedure proportion, 50%; P < 0.001). These trends persisted for patients without hypertension and those who had complete revascularization. CONCLUSIONS: Successful percutaneous coronary revascularization did not substantially supplant the use of antianginal medications, which were commonly used despite the marked improvement in anginal status. This may reflect reluctance to alter therapy once symptoms of angina subside. Guidelines on continued medical therapy after percutaneous coronary revascularization are needed.

Abciximab administration and outcome after intracoronary stent implantation.

Although adjunctive abciximab therapy improves outcome after angioplasty or atherectomy, there are few data demonstrating its benefit for intracoronary stent implantation. We characterized patients receiving abciximab for stent placement in our practice and determined the impact of abciximab on outcome. Abciximab was introduced to our practice in April 1995 for percutaneous revascularization. Demographic, clinical, and angiographic variables that were independently associated with the use of abciximab for stent placement through 1996 (abciximab era) were examined. We then examined among all patients receiving stents from 1992 through 1996 (preabciximab and abciximab eras) whether the use of abciximab was independently associated with improved outcome (death, nonfatal Q-wave myocardial infarction, coronary bypass surgery, or target vessel percutaneous revascularization) in the hospital and at 30 days. The 30-day event rate was 7% for those who did or did not receive abciximab. The following characteristics were independently associated with the use of abciximab for stent placement in the abciximab era: thrombus before stent placement (chi-square 50.5), > or =2 stents implanted (chi-square 10.8), stent in venous graft (chi-square 7.4), calcific lesion (chi-square 5.8), and hypertension (chi-square 5.5). Among all patients receiving stents in the preabciximab and abciximab eras (n=1,859), the presence of these characteristics was independently associated with worse outcome. Abciximab, however, did not improve outcome in the hospital (odds ratio [95% confidence interval]=0.96 [0.58 to 1.58]) or at 30 days (0.87 [0.53 to 1.41]), even after adjusting for these characteristics. Abciximab for stent placement was used in high-risk patients in our practice but was not associated with improved outcome.

The role of myocardial revascularization preceding noncardiac surgery.

Of about 6.7 million Americans who have coronary artery disease, approximately 700,000 undergo various noncardiac operations annually in the United States. Perioperative cardiac complications remain the leading cause of morbidity and mortality not related to the primary operative procedure; the mechanisms of perioperative ischemia and infarction are unclear. Currently, clinicians, using a combination of clinical and laboratory findings, can estimate the risk of noncardiac surgical procedures with a high degree of precision, but much less is known about the preferred approach to patient management after noninvasive risk stratification. Coronary angiography and revascularization are frequently recommended for those determined by functional tests to be at moderate and high risk, but the risks of revascularization are often substantially higher among these patients. No randomized, controlled trials exist to guide patient management. Quantitative decision analysis based on published nonrandomized data suggests that coronary angiography with selective myocardial revascularization should be performed to reduce the risk of noncardiac surgery only if the risk of noncardiac surgery is greater than 5% and the risk of coronary angiography with selective revascularization is less than 3%. On the other hand, if independent indications exist for myocardial revascularization, it should generally be performed before the noncardiac operation.

Smokers undergoing percutaneous coronary revascularization present with fewer narrowings in the target coronary artery.

Among patients undergoing percutaneous coronary revascularization, cigarette smoking remained associated with fewer lesions in the target artery even after adjusting for age, extent of coronary artery disease, diabetes mellitus, and hypertension. These findings support the hypothesis that smokers have less active, yet more active, coronary artery disease.

Cardiac risk of noncardiac surgery: influence of coronary disease and type of surgery in 3368 operations. CASS Investigators and University of Michigan Heart Care Program. Coronary Artery Surgery Study.

BACKGROUND: The influence of prior coronary artery bypass surgery (CABG) versus medical therapy for reducing the risk of postoperative cardiac complications after noncardiac surgery continues to be debated. To further clarify this controversy we studied 24,959 participants in the Coronary Artery Surgery Study (CASS) database with suspected coronary disease by identifying those who required noncardiac surgery during more than 10 years of follow-up. METHODS AND RESULTS: CASS registry enrollees were either treated with CABG or medical therapy after initial entry. During follow-up, patients who required noncardiac operations were evaluated for hospital death or out-of-hospital death within 30 days of noncardiac surgery and nonfatal postoperative myocardial infarction (MI). At a mean follow-up of 4.1 years, 3368 patients underwent noncardiac surgery, with abdominal (36%), urologic (21%), orthopedic (15%), and vascular being most common. Abdominal, vascular, thoracic, and head and neck surgery each had a combined MI/death rate among patients with nonrevascularized coronary disease >4%. Among 1961 patients undergoing higher-risk surgery, prior CABG was associated with fewer postoperative deaths (1.7% versus 3.3%, P=.03) and MIs (0.8% versus 2.7%, P=.002) compared with medically managed coronary disease. Contrariwise, 1297 patients undergoing urologic, orthopedic, breast, and skin operations had mortality of <1% regardless of prior coronary treatment. Prior CABG was most protective in patients with advanced angina and/or multivessel coronary artery disease. CONCLUSIONS: In patients with known coronary artery disease, noncardiac surgeries involving the thorax, abdomen, vasculature, and head and neck are associated with the highest cardiac risk, which is reduced among patients with prior CABG.