Can the optimal type of stent be predicted based on clinical risk factors? A subgroup analysis of the randomized BASKET-PROVE trial.

BACKGROUND: The randomized BASKET-PROVE study showed no significant differences between sirolimus-eluting stents (SES), everolimus-eluting stents (EES), and bare-metal stents (BMS) with respect to the primary end point, rates of death from cardiac causes, or myocardial infarction (MI) at 2 years of follow-up, in patients requiring stenting of a large coronary artery. Clinical risk factors may affect clinical outcomes after percutaneous coronary interventions. We present a retrospective analysis of the BASKET-PROVE data addressing the question as to whether the optimal type of stent can be predicted based on a cumulative clinical risk score. METHODS: A total of 2,314 patients (mean age 66 years) who underwent coronary angioplasty and implantation of ≥1 stents that were ≥3.0 mm in diameter were randomly assigned to receive SES, EES, or BMS. A cumulative clinical risk score was derived using a Cox model that included age, gender, cardiovascular risk factors (hypercholesterolemia, hypertension, family history of cardiovascular disease, diabetes, smoking), presence of ≥2 comorbidities (stroke, peripheral artery disease, chronic kidney disease, chronic rheumatic disease), a history of MI or coronary revascularization, and clinical presentation (stable angina, unstable angina, ST-segment elevation MI). RESULTS: An aggregate drug-eluting stent (DES) group (n = 1,549) comprising 775 patients receiving SES and 774 patients receiving EES was compared to 765 patients receiving BMS. Rates of death from cardiac causes or nonfatal MI at 2 years of follow-up were significantly increased in patients who were in the high tertile of risk stratification for the clinical risk score compared to those who were in the aggregate low-mid tertiles. In patients with a high clinical risk score, rates of death from cardiac causes or nonfatal MI were lower in patients receiving DES (2.4 per 100 person-years, 95% CI 1.6-3.6) compared with BMS (5.5 per 100 person-years, 95% CI 3.7-8.2, hazard ratio 0.45, 95% CI 0.26-0.80, P = .007). However, they were not significantly different between receivers of DES and BMS in patients in the low-mid risk tertiles. CONCLUSIONS: This exploratory analysis suggests that, in patients who require stenting of a large coronary artery, use of a clinical risk score may identify those patients for whom DES use may confer a clinical advantage over BMS, beyond lower restenosis rates.

Tradeoff between bleeding and stent thrombosis in different dual antiplatelet therapy regimes: Importance of case fatality rates and effective treatment durations.

BACKGROUND: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined. METHODS: Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models. RESULTS: Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period; P = .145) but an inconsistent pattern for MB (interaction DAPT/period; P < .001 for TIMI major and P = .046 for BARC ≥ 3), with more MB occurring during months 7 to 12 with prolonged DAPT. Considering observed case fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST deaths and the excess of 5 MB deaths resulted in an expected benefit of 22 survivors/10,000 patients treated over 2 years with prolonged DAPT. CONCLUSION: Despite overall low event rates, prolonged DAPT was associated with more MB during months 7 to 12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST versus MB, 12- versus 6-month DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials.

Drug-eluting versus bare-metal stents in large coronary arteries.

BACKGROUND: Recent data have suggested that patients with coronary disease in large arteries are at increased risk for late cardiac events after percutaneous intervention with first-generation drug-eluting stents, as compared with bare-metal stents. We sought to confirm this observation and to assess whether this increase in risk was also seen with second-generation drug-eluting stents. METHODS: We randomly assigned 2314 patients needing stents that were 3.0 mm or more in diameter to receive sirolimus-eluting, everolimus-eluting, or bare-metal stents. The primary end point was the composite of death from cardiac causes or nonfatal myocardial infarction at 2 years. Late events (occurring during months 7 to 24) and target-vessel revascularization were the main secondary end points. RESULTS: The rates of the primary end point were 2.6% among patients receiving sirolimus-eluting stents, 3.2% among those receiving everolimus-eluting stents, and 4.8% among those receiving bare-metal stents, with no significant differences between patients receiving either drug-eluting stent and those receiving bare-metal stents. There were also no significant between-group differences in the rate of late events or in the rate of death, myocardial infarction, or stent thrombosis. Rates of target-vessel revascularization for reasons unrelated to myocardial infarction were 3.7% among patients receiving sirolimus-eluting stents, 3.1% among those receiving everolimus-eluting stents, and 8.9% among those receiving bare-metal stents. The rate of target-vessel revascularization was significantly reduced among patients receiving either drug-eluting stent, as compared with a bare-metal stent, with no significant difference between the two types of drug-eluting stents. CONCLUSIONS: In patients requiring stenting of large coronary arteries, no significant differences were found among sirolimus-eluting, everolimus-eluting, and bare-metal stents with respect to the rate of death or myocardial infarction. With the two drug-eluting stents, similar reductions in rates of target-vessel revascularization were seen. (Funded by the Basel Cardiovascular Research Foundation and the Swiss National Foundation for Research; Current Controlled Trials number, ISRCTN72444640.).

[Important classifications and scores in cardiology]. / Wichtige Stadieneinteilungen und Scores in der Kardiologie.

Classifications and scores play a fundamental role in clinical cardiology. While classification systems may help to quantify symptoms and stages of disease, specific scores enable risk stratification and may facilitate decision-making in various cardiac disorders. The present article reviews some of the most frequently used cardiologic classifications and scores. Frequently used classification systems are the NYHA classification for staging patients with cardiac diseases according to their symptoms and functional capacity, and the CCS classification for grading the severity of symptoms in patients with stable angina pectoris. The Killip classification represents a simple clinical tool to estimate mortality risk in patients with acute coronary syndromes. While there is no controversy about the acute management of patients with STEMI - i. e. reperfusion therapy by fibrinolysis or, preferably, primary percutaneous coronary intervention - the diagnostic and therapeutic strategy in patients with NSTE-ACS depends on their individual risk. Various scores have been developed for early risk stratification in patients with NSTE-ACS. Of these, the TIMI risk score and the GRACE score are the most frequently used. Prevention of thromboembolic events represents a primary therapeutic goal in patients with atrial fibrillation. In affected patients, scores such as the CHA2DS2-VASc-Score and the HAS-BLED score are helpful in assessing individual risk of thromboembolic and bleeding complications. Herewith, these scores aid in decision-making for anticoagulation and, thereby, improve prognosis of patients with atrial fibrillation.

Drug-eluting stents compared with bare metal stents improve late outcome after saphenous vein graft but not after large native vessel interventions.

OBJECTIVES: To define long-term efficacy of different stent types in saphenous vein graft (SVG) interventions. METHODS: In BASKET (Basel Stent Cost Effectiveness Trial), major adverse cardiac events (MACE), i.e. cardiac death, myocardial infarction and symptom-driven target vessel revascularization (TVR) were assessed after 18 months comparing drug-eluting stents (DES) versus bare metal stents (BMS), and SVG and large native vessels (> or =3.0 mm). RESULTS: Large vessel interventions were performed in 605 patients. Patients with SVG interventions (n = 47, 8%) were older and had more often hypertension, prior myocardial infarction, prior revascularization and multivessel disease and less frequent ST-elevation myocardial infarction than patients with large native vessel interventions (n = 558, 92%). Stent number and length were higher in SVG than in large native vessel interventions. Baseline characteristics were similar for DES and BMS. In SVG stenting, long-term outcome was better in DES- than in BMS-treated patients (MACE 21 vs. 62%, p = 0.007, mainly due to TVR 18 vs. 46%, p = 0.045), but for large native vessel stenting, no significant difference was noted (MACE: 13 vs. 16%, p = 0.40). CONCLUSIONS: Among patients with SVG disease, treatment with DES resulted in a better long-term outcome than treatment with BMS. In contrast, no DES benefit was found in similarly sized native vessels regarding MACE.

Drug-eluting or bare-metal stents for large coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: study protocol and design.

BACKGROUND: Based on a subgroup analysis of 18-month BAsel Stent Kosten Effektivitäts Trial (BASKET) outcome data, we hypothesized that very late (> 12 months) stent thrombosis occurs predominantly after drug-eluting stent implantation in large native coronary vessel stenting. METHODS: To prove or refute this hypothesis, we set up an 11-center 4-country prospective trial of 2260 consecutive patients treated with > or = 3.0-mm stents only, randomized to receive Cypher (Johnson & Johnson, Miami Lakes, FL), Vision (Abbott Vascular, Abbott Laboratories, IL), or Xience stents (Abbott Vascular). Only patients with left main or bypass graft disease, in-stent restenosis or stent thrombosis, in need of nonheart surgery, at increased bleeding risk, without compliance/consent are excluded. All patients are treated with dual antiplatelet therapy for 12 months. The primary end point will be cardiac death/nonfatal myocardial infarction after 24 months with further follow-up up to 5 years. RESULTS: By June 12, 229 patients (10% of the planned total) were included with a baseline risk similar to that of the same subgroup of BASKET (n = 588). CONCLUSIONS: This study will answer several important questions of contemporary stent use in patients with large native vessel stenting. The 2-year death/myocardial infarction-as well as target vessel revascularization-and bleeding rates in these patients with a first- versus second-generation drug-eluting stent should demonstrate the benefit or harm of these stents compared to cobalt-chromium bare-metal stents in this relevant, low-risk group of everyday patients. In addition, a comparison with similar BASKET patients will allow to estimate the impact of 12- versus 6-month dual antiplatelet therapy on these outcomes.

Bosentan preserves endothelial function in mice overexpressing APP.

This study was designed to test the hypothesis that Alzheimer's disease (AD) is associated with endothelial dysfunction and that chronic endothelin-1 antagonism preserves endothelial function in mice overexpressing the AD amyloid precursor protein (APP). Three groups of mice were studied: C57BL/6 (normal control, n = 6), transgenic mice overexpressing APP (Tg2576, n = 5), and Tg2576 mice fed Bosentan (100 mg/(kg day)(-1)), a combined endothelin A and B receptor antagonist, for 4 months (Tg2576+Bosentan, n = 5). Mice were sacrificed at the age of 7 months. In vitro, the endothelium-dependent aortic vasorelaxation was significantly attenuated in Tg2576 mice as compared to C57BL/6 and Tg2576+Bosentan mice. In contrast, Tg2576+Bosentan and C57BL/6 mice showed similar endothelium-dependent aortic vasorelaxation. Similarly, endothelium-dependent carotid vasorelaxation was significantly attenuated in Tg2576 mice compared to C57BL/6 and Tg2576+Bosentan mice. There was no difference between the three groups in the response to nitroprusside. The current study demonstrates the presence of endothelial dysfunction in both carotid and aortic arteries in mice overexpressing APP and suggests a pathophysiological role for the endogenous endothelin system in AD.

Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitäts Trial (BASKET).

BACKGROUND: No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice. METHODS: The Basel stent cost-effectiveness trial (BASKET) included 826 consecutive patients treated with angioplasty and stenting for 1281 de-novo lesions, irrespective of indication for angioplasty. Patients were randomised to one of two DES (Cypher, n=264; Taxus, n=281) or to a cobalt-chromium-based BMS (Vision, n=281) and followed up for 6 months for occurrence of major adverse cardiac events and costs. Analysis was by intention-to-treat. The primary endpoint was cost-effectiveness after 6 months, with effectiveness defined as reduction of major adverse cardiac events. FINDINGS: Cardiac death, myocardial infarction, or target vessel revascularisation occurred in 39 of 544 (7.2%) patients with DES and 34 of 280 (12.1%) with BMS (odds ratio 0.56, 95% CI 0.35-0.91; p=0.02), without significant differences between the two DES. Total costs at 6 months were higher with DES (mean 10,544, SD 6849) than with BMS (9639, 9067; p<0.0001); higher stent costs of DES were not compensated for by lower follow-up costs. Incremental cost-effectiveness ratio of DES compared with BMS to avoid one major event was 18,311, and costs per quality-adjusted life-year gained were more than 50 000. Subgroup analyses showed that DES were more cost-effective for elderly patients in specific high-risk groups. INTERPRETATION: In a real-world setting, use of DES in all patients is less cost effective than in studies with selected patients. Use of these stents could be restricted to patients in high-risk groups.

Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events.

BACKGROUND: Stroke, mainly attributable to atherothrombotic disease, represents a leading cause of disability and death in the Western world. Endothelial dysfunction, which is considered a key factor in atherogenesis, is associated with an increased risk of cardiovascular events. However, the magnitude of the association between coronary endothelial dysfunction (CED) and cerebrovascular events is unknown. This study was performed to investigate the association between CED and cerebrovascular events. METHODS AND RESULTS: We studied 503 patients without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing by intracoronary acetylcholine infusion. Patients were divided according to the presence (n=305) or absence (n=198) of CED, and medical records were examined for the occurrence of ischemic or hemorrhagic stroke or transient ischemic attack either before (prevalent) or after (incident) coronary endothelial function testing. Among the study population, a total of 25 cerebrovascular events were documented, 22 in patients with CED (15 prevalent) and 3 in patients without (all prevalent) (P=0.008). Multivariable logistic regression, which included traditional cerebrovascular disease-related risk factors, identified the presence of CED as the single strongest factor associated with cerebrovascular events (OR, 4.32; 95% CI, 1.26 to 14.83). Kaplan-Meier analysis indicated that patients with CED had a significantly higher cumulative cerebrovascular event rate than those without (P=0.04). CONCLUSIONS: Presence of CED in patients without obstructive CAD is independently associated with an increased risk of cerebrovascular events. Thus, detection of this early stage of atherosclerosis may provide important information to identify patients who benefit from aggressive preventive strategies.

Enhanced external counterpulsation for ischemic heart disease: what's behind the curtain?

Enhanced external counterpulsation (EECP) has been shown to reduce angina and to improve objective measures of myocardial ischemia in patients with refractory angina. Prospective clinical studies and large treatment registries suggest that a course of EECP is associated with prolongation of the time to exercise-induced ST-segment depression and resolution of myocardial perfusion defects, as well as with enhanced exercise tolerance and quality of life. With a growing knowledge base supporting the safety and beneficial clinical effects associated with EECP, this therapy can be considered a valuable treatment option, particularly in patients who have exhausted traditional revascularization methods and yet remain symptomatic despite optimal medical care. However, although the concept of external counterpulsation was introduced almost four decades ago, and despite growing evidence supporting the clinical benefit and safety of this therapeutic modality, little is firmly established regarding the mechanisms responsible for the beneficial effects associated with this technique. Suggested mechanisms contributing to the clinical benefit of EECP include improvement in endothelial function, promotion of coronary collateralization, enhancement of ventricular function, peripheral effects similar to those observed with regular physical exercise, and nonspecific placebo effects. This review summarizes the current evidence for a contribution of these mechanisms to the clinical benefit associated with EECP.

Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia.

OBJECTIVES: We investigated the value of reactive hyperemia peripheral arterial tonometry (RH-PAT) as a noninvasive tool to identify individuals with coronary microvascular endothelial dysfunction. BACKGROUND: Coronary endothelial dysfunction, a systemic disorder, represents an early stage of atherosclerosis; RH-PAT is a technique to assess peripheral microvascular endothelial function. METHODS: Using RH-PAT, digital pulse volume changes during reactive hyperemia were assessed in 94 patients without obstructive coronary artery disease and either normal (n = 39) or abnormal (n = 55) coronary microvascular endothelial function; RH-PAT index, a measure of reactive hyperemia, was calculated as the ratio of the digital pulse volume during reactive hyperemia divided by that at baseline. RESULTS: Average RH-PAT index was lower in patients with coronary endothelial dysfunction compared with those with normal coronary endothelial function (1.27 +/- 0.05 vs. 1.78 +/- 0.08: p < 0.001). An RH-PAT index <1.35 was found to have a sensitivity of 80% and a specificity of 85% to identify patients with coronary endothelial dysfunction. CONCLUSIONS: Digital hyperemic response, as measured by RH-PAT, is attenuated in patients with coronary microvascular endothelial dysfunction, suggesting a role for RH-PAT as a noninvasive test to identify patients with this disorder.

Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering.

UNLABELLED: OBJECTIVES; This study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia. BACKGROUND: Simvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown. METHODS: Pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated. RESULTS: Total and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05). CONCLUSIONS: These findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering.

Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease.

OBJECTIVES: The goal of this study was to examine the effect of enhanced external counterpulsation (EECP) on endothelial function. BACKGROUND: Enhanced external counterpulsation improves symptoms and exercise tolerance in patients with symptomatic coronary artery disease (CAD). However, the exact mechanisms by which this technique exerts its clinical benefit are unclear. METHODS: Reactive hyperemia-peripheral arterial tonometry (RH-PAT), a noninvasive method to assess peripheral endothelial function by measuring reactive hyperemic response in the finger, was performed in 23 patients with refractory angina undergoing a 35-h course of EECP. In each patient RH-PAT measurements were performed before and after the first, at midcourse, and the last EECP session. In addition, RH-PAT response was assessed one month after completion of EECP therapy; RH-PAT index, a measure of reactive hyperemia, was calculated as the ratio of the digital pulse volume during reactive hyperemia divided by that at rest. RESULTS: Enhanced external counterpulsation led to symptomatic improvement (>/=1 Canadian Cardiovascular Society class) in 17 (74%) patients; EECP was associated with a significant immediate increase in average RH-PAT index after each treatment (p < 0.05). In addition, average RH-PAT index at one-month follow-up was significantly higher than that before EECP therapy (p < 0.05). When patients were divided by their clinical response, RH-PAT index at one-month follow-up increased only in those patients who experienced clinical benefit. CONCLUSIONS: Enhanced external counterpulsation enhances peripheral endothelial function with beneficial effects persisting at one-month follow-up in patients with a positive clinical response. This suggests that improvement in endothelial function may contribute to the clinical benefit of EECP in patients with symptomatic CAD.

Influence of revascularization on long-term outcome in patients > or =75 years of age with diabetes mellitus and angina pectoris.

Little is known about the effect of revascularization in patients > or =75 years of age with symptomatic coronary artery disease (CAD) and diabetes mellitus (DM) for whom periprocedural risk and overall mortality are increased. Therefore, we examined the 301 patients of the Trial of Invasive versus Medical therapy in the Elderly with symptomatic CAD (TIME) with special regard to diabetic status. Patients were randomized to an invasive versus optimized medical strategy. The median follow-up was 4.1 years (range 0.1 to 6.9). Patients with DM (n = 69) had a greater incidence of hypertension (73% vs 58%, p = 0.03), > or =2 risk factors (93% vs 46%, p <0.01), previous heart failure (22% vs 12%, p = 0.04), and previous myocardial infarction (59% vs 43%, p = 0.02), and a lower left ventricular ejection fraction (48% vs 54%, p = 0.02) than did patients without DM. Mortality was greater in patients with DM than in those without DM (41% vs 25%, p = 0.01; adjusted hazard ratio 1.86, p = 0.01). Revascularization improved the overall survival rate from 61% (no revascularization) to 79% (p <0.01; adjusted hazard ratio 1.68, p = 0.03), an effect similarly observed in patients with and without DM. The event-free survival rate was 11% in nonrevascularized patients with DM compared with 40% in nonrevascularized patients without DM and 41% and 53% in revascularized patients with and without DM, respectively (p <0.01). Angina severity and antianginal drug use were similar for patients with and without DM, but those with DM performed worse in daily activities and physical functioning. In conclusion, elderly diabetic patients with chronic angina have a worse outcome than those with DM but benefit similarly from revascularization regarding symptom relief and long-term outcome. However, physical functioning related to daily activities is reduced in those with DM and may need special attention.

Endothelial dysfunction: a marker of atherosclerotic risk.

Endothelial dysfunction is a systemic disorder and a key variable in the pathogenesis of atherosclerosis and its complications. Current evidence suggests that endothelial status is not determined solely by the individual risk factor burden but rather, may be regarded as an integrated index of all atherogenic and atheroprotective factors present in an individual, including known as well as yet-unknown variables and genetic predisposition. Endothelial dysfunction reflects a vascular phenotype prone to atherogenesis and may therefore serve as a marker of the inherent atherosclerotic risk in an individual. In line with this hypothesis, dysfunction of either the coronary or peripheral vascular endothelium was shown to constitute an independent predictor of cardiovascular events, providing valuable prognostic information additional to that derived from conventional risk factor assessment. Interventions like risk factor modification and treatment with various drugs, including statins and angiotensin-converting enzyme inhibitors, may improve endothelial function and thereby, potentially prognosis. Hence, given its reversibility and granted the availability of a diagnostic tool to identify patients at risk and to control the efficacy of therapy in clinical practice, endothelial dysfunction may be an attractive primary target in the effort to optimize individualized therapeutic strategies to reduce cardiovascular morbidity and mortality.

Long-term benefits and limitations of combined antianginal drug therapy in elderly patients with symptomatic chronic coronary artery disease.

BACKGROUND: Chronic angina is a common and disabling disorder in the elderly. Combined antianginal drug treatment represents the mainstay of therapy in this population. However, there is a paucity of data regarding the effect of this strategy on long-term outcome in the elderly. METHODS: To assess the long-term effect of combined antianginal drug therapy in elderly individuals, we performed a long-term follow-up analysis of all 148 patients of the Trial of Invasive versus Medical therapy in Elderly (TIME) patients with chronic symptomatic coronary-artery disease assigned to an optimized medical therapy strategy. Angina severity, measures of quality of life (QOL), and survival were assessed after a median of 3.7 (0.1-6.9) years. RESULTS: At baseline, patients were 79.8 +/- 3.5 years old with Canadian Cardiovascular Society (CCS) class angina 3.0 +/- 0.7 despite the use of 2.4 +/- 0.6 antianginal drugs. Although antianginal drugs were increased to 2.8 +/- 0.9 (P < .01), 63 (43%) patients needed revascularization for refractory symptoms during the first year of observation (REVASC). At baseline, REVASC patients had more frequently CCS class 4 angina (37% vs 20%, P < 0.05) but reported less prior heart failure (5% vs 20%, P < 0.01), fewer prior cerebral events (3% vs 13%, P < .05) and a lower rate of two or more comorbidities (10% vs 33%, P < .01) than patients on continued drug therapy (DRUG). At long-term follow-up, angina severity was still higher in DRUG compared to REVASC patients (CCS class, 1.8 +/- 1.6 vs 1.0 +/- 1.4, P < .05) despite more antianginal drugs (2.1 +/- 1.1 vs 1.5 +/- 1.0, P < .01), whereas measures of QOL had improved similarly in both groups. In addition, long-term mortality was significantly higher in DRUG than in REVASC patients (38% vs 13%, P < .01). CONCLUSION: Combined antianginal drug therapy successfully relieved symptoms in most elderly patients with chronic angina but failed to do so in 43%. Patients who needed revascularization for refractory symptoms reported less angina, despite lower drug use during long-term follow-up and had a better long-term survival. Thus, the widely used strategy to increase antianginal drug therapy in elderly patients instead of evaluating them for revascularization should be reconsidered.

Coronary stent infection: a rare but severe complication of percutaneous coronary intervention.

During the last two decades, the number of percutaneous coronary interventions (PCI) has steadily increased in Switzerland, as has the use of coronary stents. However, reports of coronary stent infections are very rare. In the present article we review all published cases of coronary stent infections. All patients presented with symptoms of infection within the first four weeks after PCI. Clinical hallmarks of stent infection were fever and chest pain. Blood cultures were positive in all patients. Despite the use of intravenous antibiotics in all except one patient and surgical drainage of the infectious focus in the majority of affected individuals mortality was high (40%). Thus, coronary stent infection, although exceedingly rare, represents a life-threatening complication and should be considered in the differential diagnosis of patients presenting with fever during the first few weeks after PCI.

Endothelin type A receptor antagonism restores myocardial perfusion response to adenosine in experimental hypercholesterolemia.

Experimental hypercholesterolemia is characterized by increased endothelin-1 (ET-1) activity and is associated with an attenuated myocardial perfusion response and an inappropriate increase in coronary microvascular permeability during episodes of increased myocardial demand. This study was designed to determine the effect of chronic selective ET type A (ET(A)) receptor antagonism on coronary vascular response to simulated cardiac stress in experimental hypercholesterolemia. Twenty-one pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC), and HC diet plus ABT-627, a selective ET(A) receptor antagonist, (HC+ABT-627). After 12 weeks, cardiac electron beam computed tomography (EBCT) was performed before and during intravenous infusion of adenosine, and myocardial perfusion (ml/min per g) and coronary microvascular permeability index (arbitrary units) were calculated. Basal myocardial perfusion was similar in all groups (N: 0.91+/-0.10; HC: 0.95+/-0.08; HC+ABT-627: 1.03+/-0.09; P=0.64). Adenosine infusion led to a significant increase in myocardial perfusion in the N (1.32+/-0.15; P<0.001) but not in the HC (0.95+/-0.07) group. However, in the HC+ABT-627 group, adenosine also significantly increased myocardial perfusion (1.33+/-0.12; P=0.001). Basal permeability index did not differ between the groups (N: 1.56+/-0.13; HC: 1.34+/-0.19; HC+ABT-627: 1.62+/-0.10; P=0.38). Adenosine infusion significantly increased permeability index in HC pigs (2.29+/-0.22; P<0.001) but not in N (1.71+/-0.21) and HC+ABT-627 (1.82+/-0.08) pigs. We conclude that chronic selective ET(A) receptor antagonism preserves myocardial perfusion response and coronary microvascular integrity during episodes of increased myocardial demand in experimental hypercholesterolemia, indicating an important role for the endogenous endothelin system in this disorder.

Effects of bisoprolol fumarate on left ventricular size, function, and exercise capacity in patients with heart failure: analysis with magnetic resonance myocardial tagging.

BACKGROUND: Recent data suggest that beta-blockers can be beneficial in subgroups of patients with chronic heart failure (CHF). For metoprolol and carvedilol, an increase in ejection fraction has been shown and favorable effects on the myocardial remodeling process have been reported in some studies. We examined the effects of bisoprolol fumarate on exercise capacity and left ventricular volume with magnetic resonance imaging (MRI) and applied a novel high-resolution MRI tagging technique to determine myocardial rotation and relaxation velocity. METHODS: Twenty-eight patients (mean age, 57 +/- 11 years; mean ejection fraction, 26 +/- 6%) were randomized to bisoprolol fumarate (n = 13) or to placebo therapy (n = 15). The dosage of the drugs was titrated to match that of the the Cardiac Insufficiency Bisoprolol Study protocol. Hemodynamic and gas exchange responses to exercise, MRI measurements of left ventricular end-systolic and end-diastolic volumes and ejection fraction, and left ventricular rotation and relaxation velocities were measured before the administration of the drug and 6 and 12 months later. RESULTS: After 1 year, heart rate was reduced in the bisoprolol fumarate group both at rest (81 +/- 12 before therapy versus 61 +/- 11 after therapy; P <.01) and peak exercise (144 +/- 20 before therapy versus 127 +/- 17 after therapy; P <.01), which indicated a reduction in sympathetic drive. No differences were observed in heart rate responses in the placebo group. No differences were observed within or between groups in peak oxygen uptake, although work rate achieved was higher (117.9 +/- 36 watts versus 146.1 +/- 33 watts; P <.05) and exercise time tended to be higher (9.1 +/- 1.7 minutes versus 11.4 +/- 2.8 minutes; P =.06) in the bisoprolol fumarate group. A trend for a reduction in left ventricular end-diastolic volume (-54 mL) and left ventricular end-systolic volume (-62 mL) in the bisoprolol fumarate group occurred after 1 year. Ejection fraction was higher in the bisoprolol fumarate group (25.0 +/- 7 versus 36.2 +/- 9%; P <.05), and the placebo group remained unchanged. Most changes in volume and ejection fraction occurred during the latter 6 months of treatment. With myocardial tagging, insignificant reductions in left ventricular rotation velocity were observed in both groups, whereas relaxation velocity was reduced only after bisoprolol fumarate therapy (by 39%; P <.05). CONCLUSION: One year of bisoprolol fumarate therapy resulted in an improvement in exercise capacity, showed trends for reductions in end-diastolic and end-systolic volumes, increased ejection fraction, and significantly reduced relaxation velocity. Although these results generally confirm the beneficial effects of beta-blockade in patients with chronic heart failure, they show differential effects on systolic and diastolic function.

Successful treatment of symptomatic coronary endothelial dysfunction with enhanced external counterpulsation.

Enhanced external counterpulsation (EECP) is a valuable therapeutic option for patients with coronary artery disease and refractory angina. Although the exact mechanisms by which this technique exerts favorable effects remain unclear, improvement in endothelial function is considered a potential mechanism contributing to the clinical benefit associated with EECP. We describe a young woman with severely symptomatic coronary endothelial dysfunction in the absence of obstructive coronary artery disease who experienced a dramatic and sustained reduction in symptoms in response to a standard 35-hour course of EECP.