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Aims To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure (HF) and preserved LVEF ( HFpEF). Methods and results Patients with HFpEF (LVEF >45%; n = 123) and HF with reduced LVEF (HFrEF; LVEF ≤45%; n = 499) with age ≥60 years, NYHA class ≥ II, and elevated NT-proBNP (>400 ng/L or >800 ng/L depending on age) were randomized to medical therapy titrated only to reduce symptoms to NYHA ≤II (symptom-guided) or also to reduce NT-proBNP below the inclusion threshold (NT-proBNP-guided) during a 6-month period. Patients were followed for an additional 12 months. Despite similar treatment escalation, NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF. Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF (P = 0.02), while survival and HF hospitalization-free survival did not differ. Among HFpEF patients, NT-proBNP reduction and symptom relief were similar in the symptom-guided (n = 59) and NT-proBNP-guided (n = 64) group despite more aggressive treatment in the NT-proBNP-guided group. In contrast to effects in HFrEF, NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF, with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival, 0.03 for survival, and 0.01 for HF hospitalization-free survival. Conclusions Outcomes in HFpEF were not better than in HFrEF, and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF. These preliminary findings suggest that, in contrast to HFrEF, NT-proBNP-guided therapy may not be beneficial in HFpEF. Trial registration ISRCTN43596477. [ABSTRACT FROM AUTHOR]

Objectives: To assess independent predictors of stent thrombosis (ST) in an all-comer trial. Methods: This is an observational case-control study based on a retrospective analysis of the Basel Stent Kosten Effektivitäts Trial (BASKET) (n = 826). Patients with ST were compared to controls with regard to baseline parameters. Multivariate models were performed to identify independent predictors of ST. Results: At 36 months, there were 53 (6.4%) patients with ST, 17 (32%) of whom had early ST and 36 (68%) of whom had late/very late ST. Patients with ST were at a higher cardiovascular risk but received lower doses of statins than the controls (n = 212). Stents in ST patients were longer, had more overlap and were not as well expanded, with significantly more remaining stenoses than the stents in the controls. Multivariable analysis revealed interventions in saphenous vein grafts, malapposed stents, an overlap >3 mm, complex coronary anatomy and treatment with low-dose/no statins as risk factors for ST, while interventions in saphenous vein grafts, underexpanded or malapposed stents, a history of myocardial infarction and treatment with low-dose/no statins were risk factors for late ST. Conclusions: The use of statins might have a protective effect against ST. This observation is new, hypothesis-generating and should be evaluated in an adequately powered randomized trial. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims NT-proBNP-guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT-proBNP-guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT-proBNP-guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) was assessed. Methods and results A total of 495 chronic HF patients, aged ≥60, with an LVEF ≤45%, NYHA class ≥II, randomized to NT-proBNP-guided or symptom-guided therapy and ≥1 month follow-up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18-month trial period. A total of 5212 AEs were noted, 433 of them serious. NT-proBNP-guided therapy led to a higher up-titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient-year 4.7 (2.8–9.4) vs. 5.4 (2.7–11.4), P = 0.69; number of severe AEs/patient-year 0.7 (0–2.7) vs. 1.3 (0–3.9), P = 0.21] similar to that of symptom-guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co-morbidities were associated with AEs and interacted with the safety profile of NT-proBNP-guided therapy: positive effects were more frequent in younger and less co-morbid patients whereas potential negative effects—although small and related to non-severe AEs only—were only seen in the older and more co-morbid patients. Conclusions NT-proBNP-guided therapy is safe in elderly and highly co-morbid HF patients. Trial registration ISRCTN43596477 [ABSTRACT FROM AUTHOR]

Aims Up to 50% of patients with heart failure (HF) may suffer from severe cognitive impairment (SCI), but longitudinal studies are sparse, and effects of changes in HF severity on cognitive function are unknown. Therefore, we assessed the prevalence of SCI in HF patients, its relationship with HF severity, its effects on morbidity and mortality, and the relationship between changes in HF severity and cognitive function. Methods and results We included 611 patients from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) and assessed cognitive function [Hodkinson Abbreviated Mental Test (AMT)] in relation to severity of HF (NYHA class, NT-proBNP) at baseline and 18 months (n = 382) and effects on hospitalization-free survival and mortality. SCI (i.e. AMT score ≤7) was present in 9.2% of patients at baseline, but only 20% of them had a diagnosis of dementia. Prevalence of SCI remained stable during follow-up. SCI was present at baseline more often in NYHA IV patients compared with NYHA II [odds ratio 2.94; 95% confidence interval (CI) 1.15–7.51, P = 0.025], but it was not related to NT-proBNP levels. SCI was related to higher mortality (hazard ratio 1.53, 95% CI 1.02–2.30, P = 0.04), but not hospitalization-free survival. Changes in HF severity were not significantly related to changes in cognitive function. Conclusion SCI is a frequent, but often unrecognized finding in HF patients, but the influence of HF severity and its changes on cognitive function were less than hypothesized. Trial registration ISRCTN43596477 [ABSTRACT FROM AUTHOR]

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia. [Copyright &y& Elsevier]

Objectives: This study sought to define the importance of 5-year coronary artery disease (CAD) progression after successful stenting. Background: Safety concerns regarding first-generation drug-eluting stents mandate 5-year follow-up studies. However, only limited data exist on the long-term importance of CAD progression relative to late stent–related problems. Methods: This study followed for 5 years, 428 consecutive patients randomized to drug-eluting versus bare-metal stents with successful stenting documented by freedom from symptoms/events and no ischemic perfusion defects (PDs) after 6 months. Rest/stress scintigraphic scans were repeated after 60 months. Late events and new PDs in areas remote from stented vessels indicated CAD progression. Results: During follow-up, 110 of 428 (25.7%) patients had 150 clinical events: 43 patients (10%) died, 36 (8.4%) suffered a myocardial infarction, and 71 (16.6%) needed repeat revascularization. Event rates were lower in remote versus target-vessel areas (9.8% vs. 14.3%, p = 0.019). Remote myocardial infarction and repeat revascularization accounted for 46 of 124 (37.1%) nonfatal events and were similar for both stent types. Five-year scintigraphic studies in patients without follow-up events showed 23.3% new PDs, 71% of which were asymptomatic. Remote defects accounted for 37.5% PDs and were similar for both stent types. Conclusions: Even 5 years after stenting, target-vessel events and/or new PDs remained more frequent than CAD progression assessed by remote events and/or new PDs. Still, remote events accounted for almost 40% of all events with a similar rate of additional new PDs, often silent, and independent of stent type. This documents the importance of CAD progression and stresses the need to differentiate remote from target-vessel events/PDs in long-term stent safety studies. (Basel Stent Kosten-Effektivitäts Trial [BASKET]; ISRCTN75663024) [Copyright &y& Elsevier]

Background: A pooled analysis in cardiogenic shock due to acute coronary syndromes is desirable to assess the effect of early revascularization (ERV) across all ages and a wide spectrum of disease severity. Methods: Only two randomized controlled trials (RCT), i.e. SMASH and SHOCK, met the inclusion criteria and were combined for a pooled analysis using individual patient data ( n == 348). Results: SMASH patients ( n == 54, 16%) had more severe disease than SHOCK patients ( n == 294, 84%). After adjustment for age, anoxic brain damage, non-inferior myocardial infarction, prior coronary artery bypass graft surgery, renal failure, systolic blood pressure, and selection for coronary angiography, one-year mortality was similar (relative risk SHOCK versus SMASH 0.87, 95% CI: 0.61--1.25). Relative risk of one-year death for ERV versus initial medical stabilization was 0.82 (95% CI: 0.70--0.96). There was no significant difference in the treatment effect by age (≤≤75 years relative risk at one year 0.79, 95% CI: 0.63--0.99; > 75 years relative risk at one year 0.93, 95% CI: 0.56--1.53; interaction P == 0.10). Conclusions: Only two RCT have been published emphasizing the difficulty of enrolling critically ill patients. Despite large differences in shock severity, ERV benefit is similar across all ages and not significantly different for the elderly. [ABSTRACT FROM AUTHOR]

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.) N Engl J Med 2010;363:2310-9. [ABSTRACT FROM AUTHOR]

Background: Drug-eluting stents (DESs) are associated with late stent thromboses, but the exact mechanism of action is unknown. Objective: The goal of this article was to assess the clinical interaction of glycoprotein IIb/IIIa inhibitors (GPIs) with different stent and vessel types in unselected patients undergoing percutaneous coronary intervention (PCI). Methods: This was a predefined retrospective analysis of the randomized controlled Basel Stent Kosten Effektivitats Trial (BASKET), which compared DES with bare-metal stents (BMSs) in patients undergoing PCI. Patients were compared for major adverse clinical events in relation to GPI use (abciximab and tirofiban) after 18 months. In a subgroup analysis prespecified in the study protocol, specific regard was given to angiographic groups at different risk levels for late events (high-risk vessels [ie, small vessels with a diameter <3.0 mm and saphenous vein grafts], and low-risk vessels [ie, large native vessels ≥3.0 mm]). Baseline differences between patients with or without GPI use were identified and incorporated into a multivariable Cox proportional hazards regression analysis if different at a <0.05 level. Results: A total of 826 patients (650 males, 176 females) were enrolled in BASKET; 301 (36%) received GPI therapy. Of these 301 patients, 255 (85%) received abciximab and 46 (15%) received tirofiban. After 18 months, the rate of cardiac death and nonfatal myocardial infarction was higher in patients with GPI use than in those without GPI use (35/301 [12%] vs 32/525 [6%]; P = 0.005). In patients undergoing PCI in anatomically low-risk vessels and receiving GPI therapy, there was a higher rate of cardiac death and nonfatal myocardial infarction at 18 months with a DES versus a BMS (22/151 [15%] vs 3/66 [5%]; P = 0.033). In patients undergoing PCI in anatomically low-risk vessels and without GPI therapy, there was no significant difference for cardiac death and nonfatal myocardial infarction (DES vs BMS, 11/207 [5%] vs 6/134 [4%]). In the multivariable analysis, GPI use (hazard ratio = 2.93; 95% CI, 1.53-5.63; P = 0.001) and age (hazard ratio = 1.034 per year increase; 95% CI, 1.008-1.062; P = 0.012) remained the only significant independent predictors of outcome. Interaction of stent type and GPI use was significant (P = 0.006). Conclusions: This retrospective analysis of the BASKET data found that GPIs and DESs used in patients with large native vessels may have an adverse interaction in terms of late stent thromboses. However, large prospective studies are needed to confirm these findings. [Copyright &y& Elsevier]

Abstract: Background: The incidence of coronary artery disease (CAD) in totally asymptomatic patients with myocardial ischemia during stress testing is unknown. Methods: 54 patients with asymptomatic myocardial ischemia participated in the Swiss Interventional Study on Silent Ischemia type I (SWISSI I). Asymptomatic myocardial ischemia was verified by bicycle ergometry and stress imaging (echocardiography or scintigraphy). Findings from coronary angiographies in the course of the study constituted the main outcome. Results: Of the 54 study participants, 29 patients (53.7%) underwent coronary angiography. CAD was found in 27 of 29 patients (93.1%). In those 27 patients with CAD, 9 patients (33.3%) suffered from single vessel disease, 9 patients (33.3%) from two vessel disease, and 9 patients (33.3%) from triple vessel disease. Two patients showed left main coronary artery stenosis. Conclusion: This study shows a high incidence of relevant CAD among totally asymptomatic patients with myocardial ischemia during stress testing. Previously healthy subjects with exercise-induced ST-segment depression at check-up examinations, even if asymptomatic, should have further diagnostic evaluation. [Copyright &y& Elsevier]

The occurrence of sudden cardiac death (SCD) in patients with silent ischemia after myocardial infarction (MI) and the factors facilitating SCD are unknown. This study aimed to determine the factors facilitating SCD in patients with silent ischemia after MI. In the Swiss Interventional Study on Silent Ischemia Type II (SWISSI II), 201 patients with silent ischemia after MI were randomized to percutaneous coronary intervention (PCI) or medical management. The main end point of the present analysis was SCD. Multivariable regression models were used to detect potential associations between baseline or follow-up variables and SCD. During a mean follow-up of 10.3 ± 2.6 years, 12 SCDs occurred, corresponding to an average annual event rate of 0.6%. On multivariate regression analysis, the decline in the left ventricular ejection fraction (LVEF) during follow-up was the only independent predictor of SCD (p = 0.011), other than age; however, the baseline LVEF was not. The decline in LVEF was greater in patients receiving medical management than in those who had received PCI (p <0.001), as well as in patients with residual myocardial ischemia or recurrent MI compared with patients without these findings (p = 0.038 and p <0.001, respectively). Compared with medical management, PCI reduced the rate of residual myocardial ischemia (p <0.001) and recurrent MI (p = 0.001) during follow-up. In conclusion, patients with silent ischemia after MI are at a substantial risk of SCD. The prevention of residual myocardial ischemia and recurrent MI using PCI resulted in better long-term LVEF and a reduced SCD incidence. [Copyright &y& Elsevier]

Context: It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy.Objective: To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy.Design, Setting, and Patients: Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008.Intervention: Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy).Main Outcome Measures: Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires.Results: Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction)Conclusion: Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment.Trial Registration: isrctn.org Identifier: ISRCTN43596477. [ABSTRACT FROM AUTHOR]

Background: Few studies describe recent changes in the incidence, treatment, and outcomes of cardiogenic shock.Objective: To examine temporal trends in the incidence, therapeutic management, and mortality rates of patients with the acute coronary syndrome (ACS) and cardiogenic shock, and to assess associations of therapeutic management with death and cardiogenic shock developing during hospitalization.Design: Analysis of registry data collected among patients admitted to hospitals between 1997 and 2006.Setting: 70 of the 106 acute cardiac care hospitals in Switzerland.Patients: 23 696 adults with ACS enrolled in the AMIS (Acute Myocardial Infarction in Switzerland) Plus Registry.Measurements: Cardiogenic shock incidence; treatment, including rates of percutaneous coronary intervention; and in-hospital mortality rates.Results: Rates of overall cardiogenic shock (8.3% of patients with ACS) and cardiogenic shock developing during hospitalization (6.0% of patients with ACS and 71.5% of patients with cardiogenic shock) decreased during the past decade (P < 0.001 for temporal trend), whereas rates of cardiogenic shock on admission remained constant (2.3% of patients with ACS and 28.5% of patients with cardiogenic shock). Rates of percutaneous coronary intervention increased among patients with cardiogenic shock (7.6% to 65.9%; P = 0.010), whereas in-hospital mortality decreased (62.8% to 47.7%; P = 0.010). Percutaneous coronary intervention was independently associated with lower risk for both in-hospital mortality in all patients with ACS (odds ratio, 0.47 [95% CI, 0.30 to 0.73]; P = 0.001) and cardiogenic shock development during hospitalization in patients with ACS but without cardiogenic shock on admission (odds ratio, 0.59 [CI, 0.39 to 0.89]; P = 0.012).Limitations: There was no central review of cardiogenic shock diagnoses, and follow-up duration was confined to the hospital stay. Unmeasured or inaccurately measured characteristics may have confounded observed associations of treatment with outcomes.Conclusion: Over the past decade, rates of cardiogenic shock developing during hospitalization and in-hospital mortality decreased among patients with ACS. Increased percutaneous coronary intervention rates were associated with decreased mortality among patients with cardiogenic shock and with decreased development of cardiogenic shock during hospitalization. [ABSTRACT FROM AUTHOR]

Background: Few studies describe recent changes in the incidence, treatment, and outcomes of cardiogenic shock. Objective: To examine temporal trends in the incidence, therapeutic management, and mortality rates of patients with the acute coronary syndrome (ACS) and cardiogenic shock, and to assess associations of therapeutic management with death and cardiogenic shock developing during hospitalization. Design: Analysis of registry data collected among patients admitted to hospitals between 1997 and 2006. Setting: 70 of the 106 acute cardiac care hospitals in Switzerland. Patients: 23 696 adults with ACS enrolled in the AMIS (Acute Myocardial Infarction in Switzerland) Plus Registry. Measurements: Cardiogenic shock incidence; treatment, including rates of percutaneous coronary intervention; and in-hospital mortality rates. Results: Rates of overall cardiogenic shock (8.3% of patients with ACS) and cardiogenic shock developing during hospitalization (6.0% of patients with ACS and 71.5% of patients with cardiogenic shock) decreased during the past decade (P < 0.001 for temporal trend), whereas rates of cardiogenic shock on admission remained constant (2.3% of patients with ACS and 28.5% of patients with cardiogenic shock). Rates of percutaneous coronary intervention increased among patients with cardiogenic shock (7.6% to 65.9%; P = 0.010), whereas in-hospital mortality decreased (62.8% to 47.7%; P = 0.010). Percutaneous coronary intervention was independently associated with lower risk for both in-hospital mortality in all patients with ACS (odds ratio, 0.47 [95% CI, 0.30 to 0.73]; P = 0.001) and cardiogenic shock development during hospitalization in patients with ACS but without cardiogenic shock on admission (odds ratio, 0.59 [CI, 0.39 to 0.89]; P = 0.012). Limitations: There was no central review of cardiogenic shock diagnoses, and follow-up duration was confined to the hospital stay. Unmeasured or inaccurately measured characteristics may have confounded observed associations of treatment with outcomes. Conclusion: Over the past decade, rates of cardiogenic shock developing during hospitalization and in-hospital mortality decreased among patients with ACS. Increased percutaneous coronary intervention rates were associated with decreased mortality among patients with cardiogenic shock and with decreased development of cardiogenic shock during hospitalization. [ABSTRACT FROM AUTHOR]

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 (≥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. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels forthe US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial.comparisons between stents with indirect evidence from othertrials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes. [ABSTRACT FROM AUTHOR]

What is already known about this subject • Furosemide is an effective diuretic, but its absorption may be too slow to allow oral treatment in certain patients. What this study adds • In healthy volunteers, sublingual administration is associated with a higher Cmax, a higher bioavailability and a more accentuated initial natriuretic response than oral furosemide. Sublingual administration may offer advantages over oral administration of furosemide in certain clinical situations. Background In patients with decompensated heart failure, absorption of orally administered furosemide may be delayed, possibly leading to impaired pharmacodynamic effects. Sublingual administration may represent an alternative in such situations. Methods In a crossover study including 11 healthy men, 20 mg furosemide was administered intravenously, orally and sublingually on three different days. Pharmacokinetics and pharmacodynamics were assessed from repeated blood and urine samples. Results Compared with oral administration, sublingual administration was associated with 43% higher Cmax[difference 215 ng ml−1, 95% confidence interval (CI) 37, 392], a higher urinary recovery (8.9 vs. 7.3 mg, difference 1.6 mg, 95% CI 0.3, 2.9), an 28% higher AUC (difference 328 ng h−1 ml−1, 95% CI 24, 632) and a higher bioavailability of furosemide (59 vs. 47%, difference 12.0%, 95% CI −1.2, 25.2). Sodium excretion was higher after sublingual compared with oral administration (peak excretion rate 1.8 vs. 1.4 mmol min−1, P < 0.05), whereas urine volume did not differ significantly between the two application modes. In comparison, intravenous administration showed the expected more rapid and intense response. Conclusion Sublingually administered furosemide tablets differ in certain kinetic and dynamic properties from identical tablets given orally. Sublingual administration of furosemide may offer therapeutic advantages in certain groups of patients. [ABSTRACT FROM AUTHOR]

The article discusses the study on the importance of hemodynamic parameters in cardiogenic shock (CS). It shows that stroke volume index (SVI) and stroke work index (SWI) are the most powerful hemodynamic predictors of 30-day mortality in CS patients. It also notes that the early hemodynamic stability after initial medical stabilization should not delay revascularization since long term outcomes are superior with early vascularization.

This article presents the results of an 18 month study on the cost-effectiveness of drug-eluting stents in patients at high or low risk of major cardiac events. To assess the value of these medical devices, the authors looked at cost of the procedure and the rate of follow-up events which were usually vessel revascularisations avoided by placement of the stents. The study found that overall costs were higher for patients with drug-eluting stents over those with bare metal stents due to the higher price of the drug-eluting stent. If used in all patients, the drug-eluting stents would not be good value for the money. They are cost effective in patients who need small vessel or bypass graft stenting but not in those who need larger vessel stenting.

Objectives: Our purpose was to make a synthesis of the available evidence on the relative efficacy and safety of 2 drug-eluting stents (DES)—sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES)—in patients with coronary artery disease. Background: It is not known whether there are differences in late outcomes between the 2 most commonly used DES: SES and PES. Methods: Sixteen randomized trials of SES versus PES with a total number of 8,695 patients were included in this meta-analysis. A full set of individual outcome data from 5,562 patients was also available. Mean follow-up period ranged from 9 to 37 months. The primary efficacy end point was the need for reintervention (target lesion revascularization). The primary safety end point was stent thrombosis. Secondary end points were death and recurrent myocardial infarction (MI). Results: No significant heterogeneity was found across trials. Compared with PES, SES significantly reduced the risk of reintervention (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 to 0.87, p < 0.001) and stent thrombosis (HR 0.66; 95% CI 0.46 to 0.94, p = 0.02) without significantly impacting on the risk of death (HR 0.92; 95% CI 0.74 to 1.13, p = 0.43) or MI (HR 0.84; 95% CI 0.69 to 1.03, p = 0.10). Conclusions: Sirolimus-eluting stents are superior to PES in terms of a significant reduction of the risk of reintervention and stent thrombosis. The risk of death was not significantly different between the 2 DES, but there was a trend toward a higher risk of MI with PES, especially after the first year from the procedure. [Copyright &y& Elsevier]

This article presents a meta-analysis of outcomes associated with drug-eluting and bare-metal stents. The study sought to see if there was a difference in outcomes between the sirolimus-eluting stents, the paclitaxel-eluting stents and the bare-metal stents. The study found that mortality was similar in all three groups. In comparing sirolimus-eluting stents with bare-metal, the drug-eluting stents were associated with the lowest rate of myocardial infarction. The risk of late definite stent thrombosis was increased with the paclitaxel-eluting stents. The reduction in target lesion revascularisation was more pronounced with the sirolimus-eluting stents which leads the authors to conclude that sirolimus-eluting stents seem to be clinically better than the other two.

Context: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known.Objective: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI.Design, Setting, and Participants: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006.Interventions: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin.Main Outcome Measures: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up.Results: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up).Conclusion: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.Trial Registration: clinicaltrials.gov Identifier: NCT00387231. [ABSTRACT FROM AUTHOR]

This article presents a clinical trial on the effects of percutaneous coronary interventions (PCI) in silent ischemia after myocardial infarction (MI). The objective of the study was to determine if PCI, compared with drug therapy, improves long-term outcome of asymptomatic patients with silent ischemia after an MI. The conclusion of the trial was that among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1-or 2-vessel coronary arteries disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.

Background: Diabetes mellitus (DM), particularly if insulin-dependent, is a predictor of increased perioperative risk, whereas stringent metabolic control with insulin is beneficial in the critically ill. Methods: The impact of oral hypoglycemics (OH) vs. insulin on outcome was determined as a secondary retrospective analysis of a cohort study in patients with coronary artery disease (CAD) and DM undergoing major non-cardiac surgery. Primary end-point was 2-year all-cause mortality; secondary endpoints were perioperative myocardial ischemia and 2-year cardiac mortality. Results: Of 173 patients, DM was diagnosed in 42 (24%) based on pre-existing treatment with OH (15%) or insulin (9%). During follow-up, 40/173 (23%) patients died. All-cause mortality was similar in the non-diabetic (20%) and insulin groups (19%) but significantly higher in the OH group (42%; p = 0.025). Cardiac mortality tended to be higher in the OH group compared with the insulin and non-diabetic groups (27 vs. 19% and 11%, respectively; p = 0.066). Multivariate analysis revealed renal failure (odds ratio [OR] = 4.9, 95% confidence interval [CI] = 1.8–13.0), treatment with OH (OR = 3.3, 95% CI = 1.2–9.0), peripheral vascular surgery (OR = 2.7, 95% CI = 1.2–6.0), and prior diuretic therapy (OR = 2.6, 95% CI = 1.1–5.7) being independently associated with 2-year all-cause death. No difference existed in postoperative ischemia among the different groups. Conclusions: Long-term mortality after major non-cardiac surgery is elevated in patients with CAD and diabetes mellitus only if they are treated with OH, but not if they are treated with insulin. Further evaluation of the impact of perioperative anti-diabetic treatment on morbidity and mortality in CAD is warranted. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background The long-term effects of treatment with sirolimus-eluting stents, as compared with bare-metal stents, have not been established. Methods We performed an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents (mean follow-up interval, 12.1 to 58.9 months). The primary end point was death from any cause. Other outcomes were stent thrombosis, the composite end point of death or myocardial infarction, and the composite of death, myocardial infarction, or reintervention. Results The overall risk of death (hazard ratio, 1.03; 95% confidence interval [CI], 0.80 to 1.30) and the combined risk of death or myocardial infarction (hazard ratio, 0.97; 95% CI, 0.81 to 1.16) were not significantly different for patients receiving sirolimus-eluting stents versus bare-metal stents. There was a significant reduction in the combined risk of death, myocardial infarction, or reintervention (hazard ratio, 0.43; 95% CI, 0.34 to 0.54) associated with the use of sirolimus-eluting stents. There was no significant difference in the overall risk of stent thrombosis with sirolimus-eluting stents versus bare-metal stents (hazard ratio, 1.09; 95% CI, 0.64 to 1.86). However, there was evidence of a slight increase in the risk of stent thrombosis associated with sirolimus-eluting stents after the first year. Conclusions The use of sirolimus-eluting stents does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents. There is a sustained reduction in the need for reintervention after the use of sirolimus-eluting stents. The risk of stent thrombosis is at least as great as that seen with bare-metal stents [ABSTRACT FROM AUTHOR]

Aim: Diagnosis of early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC) with minimal structural abnormalities is challenging. The purpose of this study was to assess the value of repeated cardiac magnetic resonance imaging (CMR) in patients referred for right ventricular arrhythmias and clinical suspicion of ARVC. Methods and Results: Prospective follow-up study of 18 patients (8 females) studied with CMR for suspected ARVC. Patients with implanted defibrillators (ICD) were excluded. Mean follow-up was 37 ± 16 (12–59) months. Patients were assigned to 2 categories (ARVC likely or ARVC unlikely) according to a CMR-score based on right ventricular abnormalities. Clinical follow-up revealed no disease progression in 17 patients (94%). In 1 patient, an ICD was implanted because of disease progression. Of 9 patients with initial findings suggestive of ARVC, follow-up CMR remained positive in 3 and was diagnosed as normal in 6, mainly due to the inability to confirm the presence of fatty infiltrates at follow-up (5 of 6 patients). Initially, 9 patients had a normal CMR and 8 of those remained normal during follow-up. Conclusion: Repeated CMR after an average follow-up of 3 years was normal in 6 of 9 patients with clinical findings consistent with early stages of ARVC at the time of baseline CMR. Thus, CMR diagnosis of early stage ARVC is difficult and should be made with caution. [ABSTRACT FROM AUTHOR]

Summary 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 &z.euro;10 544, SD 6849) than with BMS (&z.euro;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 &z.euro;18 311, and costs per quality-adjusted life-year gained were more than &z.euro;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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Little is known about the effect of revascularization in patients ≥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), ≥2 risk factors (93% vs 46%, p &#60;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 &#60;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 &#60;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. [Copyright &y& Elsevier]

Objectives: We aimed to compare the hemodynamic effects of right-atrial-paced (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac resynchronization therapy (CRT). Background: Cardiac resynchronization therapy improves hemodynamics in patients with severe heart failure and left ventricular (LV) dyssynchrony. However, the impact of active right atrial pacing on resynchronization therapy is unknown. Methods: Seventeen CRT patients were studied 10 months (range: 1 to 46 months) after implantation. At baseline, the programmed atrioventricular delay was optimized by timing LV contraction properly at the end of atrial contraction. In both modes the acute hemodynamic effects were assessed by multiple Doppler echocardiographic parameters. Results: Compared to DDD pacing, VDD pacing resulted in much better improvement of intraventricular dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 ± 83 ms vs. DDD 145 ± 95 ms; p = 0.001), whereas the interventricular mechanical delay (difference between onset of pulmonary and aortic outflow) did not differ (VDD 20 ± 21 ms vs. DDD 18 ± 17 ms; p = NS). Furthermore, VDD pacing significantly prolonged the rate-corrected LV filling period (VDD 458 ± 123 ms vs. DDD 371 ± 94 ms; p = 0.0001) and improved the myocardial performance index (VDD 0.60 ± 0.18 vs. DDD 0.71 ± 0.23; p &#60; 0.01). Conclusions: Our findings suggest that avoidance of right atrial pacing results in a higher degree of LV resynchronization, in a substantial prolongation of the LV filling period, and in an improved myocardial performance. Thus, the VDD mode seems to be superior to the DDD mode in CRT patients. [Copyright &y& Elsevier]

Study objectives: To test the short- and long-term performance of a simple algorithm to detect or rule out acute coronary artery disease (CAD) in patients referred with acute chest pain (CP). Design: Prospective, multicenter study with 30-day and 1-year follow-ups. Setting: Emergency and coronary care units of two university hospitals and four affiliated teaching hospitals in a suburban region of northern Switzerland. Patients: One hundred sixty-one consecutive patients referred with acute CP with a high CAD risk profile underwent exercise testing (ET) within 24 h if results of two troponin tests and ECG remained normal within 6 h. The patients were discharged if ET results were negative or underwent angiography if the results were positive. Measurements and results: The primary end point was survival free of death, myocardial infarction (MI), and acute coronary syndrome, as well as the correct diagnosis of CAD in need of revascularization. Failure of the algorithm included events not predicted and false-positive ET results. Symptom-limited ET was performed in 142 patients, and stress imaging was performed in 17 patients. Discharge within 24 h was possible in 76%. Angiography in 21 patients showed no CAD in 4 patients, whereas revascularization was necessary in 17 patients. During follow-up, three patients had an MI (one fatal) and two patients had unstable angina, for an event rate of 3.1%/yr. Overall sensitivity of the algorithm to detect CAD was 71%, whereby six of seven false-positive ET results were due to exercise-induced CP without ECG changes. More importantly, the negative predictive value was 96.4%, indicating that this simple algorithm failed to identify only 3.6% of patients at risk for future events. Conclusions: Discharge within 24 h after onset of acute CP in high-risk CAD patients is safe, irrespective of CAD history, if ECG findings remain unchanged and troponin test results are normal within 6 h, and if results of adequate ET are negative. [ABSTRACT FROM AUTHOR]

Abstract: Nanotechnology promises new avenues to medical diagnosis and treatment. Of special interest are injectable nanovehicles that are programmable towards specific targets, are able to evade the immune defense, and are versatile enough to be suited as carriers of complex functionality. Biotin-functionalized (poly(2-methyloxazoline)–b-poly(dimethylsiloxane)–b-poly(2-methyloxazoline) triblock copolymers were self-assembled to form nanocontainers, and biotinylated targeting ligands were attached by using streptavidin as a coupling agent. Specifically, fluorescence-labeled nanocontainers were targeted against the scavenger receptor A1 from macrophages, an important cell in human disease. In human and transgenic cell lines and in mixed cultures, receptor-specific binding of these generic carriers was followed by vesicular uptake. Low nonspecific binding supported the “stealth” properties of the carrier while cytotoxicity was absent. This versatile carrier appears promising for diagnostic or therapeutic medical use. [Copyright &y& Elsevier]

Background: Post-stress ejection fraction (EF), end-diastolic (EDV) and end-systolic (ESV) volumes by gated myocardial perfusion SPECT (MPS) are well validated, reproducible and of prognostic significance. However, little is known about the impact of percutaneous coronary intervention (PCI) on left ventricular volumes and remodeling. Methods: Thirty-eight patients who underwent MPS before and 6 months after PCI were evaluated. MPS were interpreted deriving summed stress (SSS), rest (SRS) and difference (SDS=SSS-SRS; extent of ischemia) scores. EF, EDV and ESV were generated by QGS™. Pre-PCI MPS were compared to post-PCI MPS. Results: Single vessel disease was present in 63% of patients. PCI of one vessel was performed in 82% of patients. After 6 months, SSS (10.6±6.3 vs. 2.8±4.3, p<0.001) and SDS (8.2±5.6 vs. 1.4±2.3, p<0.001) had improved; however, EF did not change significantly (55±10 vs. 57±13, p=ns). Still, EDV (105±25 ml vs. 96±25 ml, p=0.006) and ESV (49±19 ml vs. 41±18 ml, p=0.001) were significantly reduced. Conclusion: Results of MPS documented the beneficial effect of PCI on symptoms and extent of ischemia. In addition, the findings showed a significant decrease in ESV and EDV after PCI as compared to pre-PCI findings which points to a positive effect on left ventricular remodeling even in the absence of significant changes in EF. [Copyright &y& Elsevier]

Study objectives: To define the prognostic value of stress testing (STRT) in patients ≥75 years of age. Design: Multicenter prospective randomized trial. Setting: Tertiary care centers. Patients: Two hundred ninety-two patients of the Trial of Invasive vs Medical Treatment of Elderly Patients aged ≥75 years with chronic angina despite receiving two or more antianginal drugs were prospectively observed for 1 year. Intervention: STRT (88% exercise ECG; 12% pharmacologic stress imaging) was performed if possible, and ischemia was diagnosed using current guidelines. Death for any reason and nonfatal myocardial infarction were outcome events. Results: Patients who could perform STRT (148 patients) were younger, had a lower risk profile, received less medication, and had less severe angina than patients who could not perform STRT (144 patients). The 1-year mortality rate was only 1.4% in patients with negative STRT results (72 patients) compared to 5.3% in patients with positive STRT results (76 patients) and 13.7% in patients who had not undergone STRT due to unstable symptoms (95 patients). The corresponding 1-year rates of death/infarction were 2.8%, 15.8%, and 26.3%, respectively. After adjustment for baseline differences, mortality rates were no longer significantly different. However, compared to patients with negative STRT results, infarction and death/infarction rates remained higher in patients with provocable ischemia (hazard ratio [HR], 8.9 [p = 0.04]; HR, 6.1 [p = 0.02], respectively) and in patients without STRT due to unstable angina (HR, 11.8 [p = 0.02]; HR, 8.6 [p = .004], respectively). Conclusions: STRT in elderly patients is feasible and provides important prognostic information for their future management. Patients with negative STRT results after receiving therapy have a good prognosis, and their conditions may be managed conservatively. [ABSTRACT FROM AUTHOR]

: ObjectivesThe aim of this study was to determine whether perioperative measurements of heart rate variability (HRV) and cardiac troponin I (cTnI) add additional prognostic information to established risk scores for first-year mortality in patients at risk of coronary artery disease (CAD) undergoing major noncardiac surgery.: BackgroundIn cardiac-risk patients undergoing major noncardiac surgery, the short- and long-term prognoses are mainly influenced by perioperative cardiac complications. Heart rate variability and cTnI are important prognostic markers in patients with congestive heart failure and myocardial infarction.: MethodsIn a prospective study, 173 patients with CAD or at high risk of CAD undergoing major noncardiac surgery were followed up for one year. The main outcome measure was all-cause mortality. In addition to clinical parameters and established risk scores, HRV and cTnI were assessed perioperatively.: ResultsTwenty-eight (16%) patients died within one year. Multivariate logistic regression analysis revealed three findings that were independently associated with death within the first year after surgery: the revised cardiac risk index (odds ratio 6.2 [95% confidence interval 1.6 to 25], depressed HRV before induction of anesthesia (16.2 [2.8 to 94]), and elevation of cTnI on postoperative day 1 or 2 (9.8 [3.0 to 32]).: ConclusionDepressed HRV before induction of anesthesia and elevated cTnI postoperatively are independent and powerful predictors of one-year mortality for patients at risk of CAD undergoing major noncardiac surgery and add incremental prognostic information to established risk scores that only consider preoperative information. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to describe the core laboratory angiographic findings of “SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK” (SHOCK) trial participants and to determine the relationship of angiographic parameters to one-year survival.: BackgroundIn the SHOCK trial, emergency revascularization improved one-year survival of patients with cardiogenic shock compared with initial medical stabilization including thrombolysis and intraaortic balloon counterpulsation.: MethodsCoronary angiography was performed by protocol in 147 of 152 (97%) patients in the emergency revascularization (ERV) group and by clinical selection in 100 of 150 (67%) patients in the initial medical stabilization (IMS) group. Of the other 50 IMS patients, 45 of 50 (90%) died rapidly and did not undergo angiography.: ResultsLeft ventricular ejection fraction was correlated with one-year survival in both treatment groups (p < 0.001). In the IMS group, the hazard ratio for death was 2.59 (95% confidence interval 1.47 to 4.58, p = 0.001) per diseased vessel (0/1 vs. 2 vs. 3). In the ERV group, the hazard ratio for death per diseased vessel was 1.11 (95% confidence interval 0.79 to 1.56, p = 0.559). Multivariate analysis of the angiography cohort (without regard for left ventriculogram measurements) identified initial Thrombolysis in Myocardial Infarction flow grade (p = 0.032), number of diseased vessels (for IMS patients only, p = 0.024), and culprit vessel (p = 0.004) as independent correlates of one-year survival, even after adjustment for key clinical factors. In the smaller cohort with left ventricular ejection fraction measured (n = 97), ejection fraction and culprit vessel remained independently correlated with survival.: ConclusionsFor patients in cardiogenic shock, left ventricular function and culprit vessel were independent correlates of one-year survival. [Copyright &y& Elsevier]

Objectives: We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants.Background: There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors.Methods: Fifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily.Results: In hypertensive patients, the change in MBF (DeltaMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 +/- 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 +/- 0.27 and 0.63 +/- 0.17 vs. 0.14 +/- 0.18 ml/g/min; both p < or = 0.001). In smokers, DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 +/- 0.10, 0.54 +/- 0.13, 0.50 +/- 0.07 vs. -0.08 +/- 0.10 ml/g/min; all p < or = 0.001). In hypercholesterolemic patients, no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 +/- 0.14, 0.08 +/- 0.18, 0.02 +/- 0.19 vs. 0.08 +/- 0.16 ml/g/min; p = NS). The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p < or = 0.001).Conclusions: The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion. [ABSTRACT FROM AUTHOR]

: ObjectivesWe sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants.: BackgroundThere is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors.: MethodsFifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily.: ResultsIn hypertensive patients, the change in MBF (ΔMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 ± 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 ± 0.27 and 0.63 ± 0.17 vs. 0.14 ± 0.18 ml/g/min; both p ≤ 0.001). In smokers, ΔMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 ± 0.10, 0.54 ± 0.13, 0.50 ± 0.07 vs. −0.08 ± 0.10 ml/g/min; all p ≤ 0.001). In hypercholesterolemic patients, no improvement in ΔMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 ± 0.14, 0.08 ± 0.18, 0.02 ± 0.19 vs. 0.08 ± 0.16 ml/g/min; p = NS). The CPT-induced ΔMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p ≤ 0.001).: ConclusionsThe present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion. [Copyright &y& Elsevier]

Objectives: We sought to evaluate the incidence of silent ischemia versus symptomatic ischemia six months after percutaneous coronary intervention (PCI) and its impact on prognosis and to test the utility of myocardial perfusion single-photon emission computed tomography (SPECT), or MPS, for risk stratification in these patients.Background: Silent ischemia is frequent after PCI. However, little is known about silent ischemia and long-term outcome after PCI and stenting.Methods: In 356 consecutive patients with successful PCI and stenting and follow-up MPS after six months, long-term follow-up (4.1 +/- 0.3 years) was performed. The MPS images were interpreted by defining summed stress, rest, and difference scores (summed difference score [SDS] = extent of ischemia) and related to symptoms and outcome. Critical events included cardiac death, myocardial infarction, and target vessel revascularization.Results: Eighty-one patients (23%) had evidence of target vessel ischemia, which was silent in 62%. The only independent predictor of silent ischemia was SDS (odds ratio 0.64, p = 0.001). During follow-up, 67 critical events occurred. For patients with an SDS of 0, 1-4, and >4, the critical event rates were 17%, 29%, and 69%, respectively. Similarly, patients without ischemia, silent ischemia, and symptomatic ischemia had 17%, 32%, and 52% of critical events, respectively. Diabetes (relative risk 1.98, p = 0.03) and SDS (relative risk 1.2, p < 0.001) were independent predictors of critical events. The MPS image added incremental information for the prediction of critical events.Conclusions: Six months after PCI and stenting, 23% of patients had target vessel ischemia, which was silent in 62%. Silent ischemia predicted a worse outcome than did no ischemia and tended to have a better outcome than symptomatic ischemia. This was closely related to the extent of ischemia. The SDS added incremental value to pre-scan findings with respect to diagnosis and prognosis, indicating the utility of MPS for risk stratification after PCI and stenting. [ABSTRACT FROM AUTHOR]

: ObjectivesWe sought to evaluate the incidence of silent ischemia versus symptomatic ischemia six months after percutaneous coronary intervention (PCI) and its impact on prognosis and to test the utility of myocardial perfusion single-photon emission computed tomography (SPECT), or MPS, for risk stratification in these patients.: BackgroundSilent ischemia is frequent after PCI. However, little is known about silent ischemia and long-term outcome after PCI and stenting.: MethodsIn 356 consecutive patients with successful PCI and stenting and follow-up MPS after six months, long-term follow-up (4.1 ± 0.3 years) was performed. The MPS images were interpreted by defining summed stress, rest, and difference scores (summed difference score [SDS] = extent of ischemia) and related to symptoms and outcome. Critical events included cardiac death, myocardial infarction, and target vessel revascularization.: ResultsEighty-one patients (23%) had evidence of target vessel ischemia, which was silent in 62%. The only independent predictor of silent ischemia was SDS (odds ratio 0.64, p = 0.001). During follow-up, 67 critical events occurred. For patients with an SDS of 0, 1–4, and >4, the critical event rates were 17%, 29%, and 69%, respectively. Similarly, patients without ischemia, silent ischemia, and symptomatic ischemia had 17%, 32%, and 52% of critical events, respectively. Diabetes (relative risk 1.98, p = 0.03) and SDS (relative risk 1.2, p < 0.001) were independent predictors of critical events. The MPS image added incremental information for the prediction of critical events.: ConclusionsSix months after PCI and stenting, 23% of patients had target vessel ischemia, which was silent in 62%. Silent ischemia predicted a worse outcome than did no ischemia and tended to have a better outcome than symptomatic ischemia. This was closely related to the extent of ischemia. The SDS added incremental value to pre-scan findings with respect to diagnosis and prognosis, indicating the utility of MPS for risk stratification after PCI and stenting. [Copyright &y& Elsevier]

Closed-loop stimulation (CLS) is a new sensor concept for rate adaptive pacing measuring changes in the unipolar right ventricular impedance, which correlates to changes of the right ventricular contractility and reflects the autonomic nervous innervation of the heart. Some patients do not tolerate the CLS mode because of inappropriate tachycardia, mainly related to postural changes. This study tested if the rate response of the CLS sensor is influenced not only by myocardial contractility but also by rapid changes in right ventricular filling. In 12 patients (10 men, median age 77 years) with a Biotronik Inos2 -CLS DDDR pacemaker and 14 controls (13 men, median age 59 years) head-up tilt and handgrip testing was performed to provoke rapid changes in pre- and afterload. Tilting the pacemaker patients resulted in a nonphysiological steep increase of the sensor rate (increase >20 beats/min, peak after 1 minute, return to baseline within 2–3 minutes), which was significantly different from the control group, showing only a slight rise in intrinsic heart rate immediately after tilting. Simultaneously to the rapid increase in sensor rate, the pacemaker patients showed a marked orthostatic decline of systolic blood pressure. During handgripping, heart rate and blood pressure curves were similar in both groups. In patients with this CLS pacemaker, rapid preload reduction during head-up tilting caused an overshooting sensor rate increase, reproducing the authors' clinical observation of postural pacemaker tachycardia in some patients. Consequently, they concluded that the rate response of the CLS pacing system can be inappropriately influenced by rapid shifts of blood volume, affecting right ventricular filling. (PACE 2003; 26[Pt. I]:1504–1510). [ABSTRACT FROM AUTHOR]

Objectives: We sought to assess the ability of a new noninvasive method to quantify atherosclerosis severity and to examine its power to predict cardiovascular events.Background: Drug prevention of cardiovascular events is effective but costly, leading to a debate about who should receive this treatment. Patient selection is often based on surrogate markers, but quantification of atherosclerosis severity is desirable.Methods: Atherosclerosis severity was quantified by determination of specific aortic wall elastance in transthoracic echocardiography, applying the biomechanics of pulse wave propagation. After validating the method in 52 patients by measuring aortic plaque burden in transesophageal echo directly, another 336 patients were prospectively studied by monitoring atherosclerotic events at one year and comparing the results with conventional risk stratification.Results: Specific aortic elastance was well correlated with plaque burden (p < 0.0001) and largely independent of confounding variables. Specific aortic elastance predicted the primary end point of "atherosclerotic death, myocardial infarction or stroke" at one year (p < 0.0002). Event rate at one year in the lowest specific elastance tertile was 1.8% (CI 0.0% to 4.3%), in the middle tertile 5.4% (CI 1.1% to 9.7%) and in the highest tertile 12.7% (CI 6.3% to 19%). Secondary end points supported these findings. Stepwise multivariate analysis identified specific aortic elastance, prior atherosclerotic events and left ventricular ejection fraction as independent risk predictors. Specific elastance was of incremental value to clinically identified variables.Conclusions: Bedside measurement of specific aortic elastance allows assessment of atherosclerosis severity. It predicts the risk for future atherosclerotic events beyond conventional risk factors, promising better targeting of pharmacologic prevention and improved cost effectiveness. [ABSTRACT FROM AUTHOR]

: ObjectivesWe sought to assess the ability of a new noninvasive method to quantify atherosclerosis severity and to examine its power to predict cardiovascular events.: BackgroundDrug prevention of cardiovascular events is effective but costly, leading to a debate about who should receive this treatment. Patient selection is often based on surrogate markers, but quantification of atherosclerosis severity is desirable.: MethodsAtherosclerosis severity was quantified by determination of specific aortic wall elastance in transthoracic echocardiography, applying the biomechanics of pulse wave propagation. After validating the method in 52 patients by measuring aortic plaque burden in transesophageal echo directly, another 336 patients were prospectively studied by monitoring atherosclerotic events at one year and comparing the results with conventional risk stratification.: ResultsSpecific aortic elastance was well correlated with plaque burden (p < 0.0001) and largely independent of confounding variables. Specific aortic elastance predicted the primary end point of “atherosclerotic death, myocardial infarction or stroke” at one year (p < 0.0002). Event rate at one year in the lowest specific elastance tertile was 1.8% (CI 0.0% to 4.3%), in the middle tertile 5.4% (CI 1.1% to 9.7%) and in the highest tertile 12.7% (CI 6.3% to 19%). Secondary end points supported these findings. Stepwise multivariate analysis identified specific aortic elastance, prior atherosclerotic events and left ventricular ejection fraction as independent risk predictors. Specific elastance was of incremental value to clinically identified variables.: ConclusionsBedside measurement of specific aortic elastance allows assessment of atherosclerosis severity. It predicts the risk for future atherosclerotic events beyond conventional risk factors, promising better targeting of pharmacologic prevention and improved cost effectiveness. [Copyright &y& Elsevier]

The ability to identify patients with severe coronary artery disease (CAD) by analysis of perfusion defects is limited. The lung/heart ratio (LHR) and transient ischaemic dilatation (TID) have been used for this purpose in thallium-201 scintigraphy. The value of these parameters in technetium-99m sestamibi single-photon emission tomography (SPET) imaging is controversial. In this study, therefore, we determined TID and LHR in a single-day rest/stress [sup 99m] Tc-sestamibi SPET perfusion protocol and compared these measurements with perfusion defect size (PDS) and angiographic severity of CAD. Severe CAD was defined as >75% left main coronary stenosis and/or >90% proximal left anterior descending artery stenosis and/or >90% proximal stenosis in the left circumflex and right coronary arteries. LHR was determined from a stress anterior planar image recorded ≤6 min after exercise. TID ratio was derived from automatically calculated left ventricular rest/stress volumes, and PDS was measured based on semi-automated computer software (CEqual). Diagnostic accuracy and predictive values were compared between 22 patients with severe and 98 patients without severe CAD. LHRs showed a higher sensitivity (73%) for the assessment of severe CAD as compared to PDS and TID ratio (41% and 23% respectively, P<0.01), whereas specificity was highest for TID ratio [95%, P<0.01 when compared to PDS (84%) and LHR (82%)]. It is concluded that increased LHR in [sup 99m] Tc-sestamibi myocardial perfusion imaging seems to yield good diagnostic accuracy in the detection of patients with severe CAD and may be derived from a single-day rest/stress study. [ABSTRACT FROM AUTHOR]