Altered Left Ventricular Geometry and Torsional Mechanics in High Altitude-Induced Pulmonary Hypertension: A Three-Dimensional Echocardiographic Study.

BACKGROUND: Changes in left ventricular (LV) torsion have been related to LV geometry in patients with concomitant long-standing myocardial disease or pulmonary hypertension (PH). We evaluated the effect of acute high altitude-induced isolated PH on LV geometry, volumes, systolic function, and torsional mechanics. METHODS: Twenty-three volunteers were prospectively studied at low altitude and after the second (D3) and third night (D4) at high altitude (4,559 m). LV ejection fraction, multidirectional strains and torsion, LV volumes, sphericity, and eccentricity were derived by speckle-tracking on three-dimensional echocardiographic data sets. Pulmonary pressure was estimated from the transtricuspid pressure gradient (TRPG), LV preload from end-diastolic LV volume, and transmitral over mitral annular E velocity (E/e'). RESULTS: At high altitude, oxygen saturation decreased by 15%-20%, heart rate and cardiac index increased by 15%-20%, and TRPG increased from 21 ± 2 to 37 ± 9 mm Hg (P < .01). LV volumes, preload, ejection fraction, multidirectional strains, and sphericity remained unaffected, but diastolic (1.04 ± 0.07 to 1.09 ± 0.09 on D3/D4, P < .05) and systolic (1.00 ± 0.06 to 1.08 ± 0.1 [D3] and 1.06 ± 0.07 [D4], P < .05) eccentricity slightly increased, indicating mild septal flattening. LV torsion decreased from 2.14 ± 0.85 to 1.34 ± 0.68 (P < .05) and 1.65 ± 0.54 (P = .08) degrees/cm on D3/D4, respectively. Changes in torsion showed a weak inverse relationship to changes in systolic (r = -0.369, P = .013) and diastolic (r = -0.329, P = .032) eccentricity but not to changes in TRPG, heart rate or preload. CONCLUSIONS: High-altitude exposure was associated with mild septal flattening of the LV and reduced ventricular torsion at unchanged global LV function and preload, suggesting a relation between LV geometry and torsional mechanics.

Ticagrelor induced systemic inflammatory response syndrome.

BACKGROUND: Ticagrelor is a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12. Possible adenosine-mediated effects of ticagrelor on inflammation are complex and incompletely understood. To our knowledge, ticagrelor-induced systemic inflammatory response syndrome (SIRS) has not yet been described. CASE PRESENTATION: We report the case of an 84 years old patient presenting with SIRS subsequent to initiation of ticagrelor after implantation of two drug eluting stents. A broad diagnostic work-up for alternative causes and therapeutic measures were unrevealing. Discontinuation of the agent was followed by rapid improvement in clinical and laboratory signs of SIRS. CONCLUSIONS: After exclusion of other causes, ticagrelor needs to be considered as a possible causative agent for SIRS. Due to the widespread use of ticagrelor, clinicians should be aware of this possible adverse drug reaction.

How reliable are left ventricular ejection fraction cut offs assessed by echocardiography for clinical decision making in patients with heart failure?

We aimed to study the potential influence of the variability in the assessment of echocardiographically measured left ventricular ejection fraction (LVEF) on indications for the implantation of internal cardioverter defibrillator and/or cardiac resynchronization devices in heart failure patients. TIME-CHF was a multicenter trial comparing NT-BNP versus symptom-guided therapy in patients aged ≥60 years. Patients had their LVEF assessed at the recruiting centre using visual assessment, the area-length or biplane Simpson's method. Echocardiographic data were transferred to the study core-lab for re-assessment. Re-assessment in the core-lab was done with biplane Simpson's method, and included an appraisal of image quality. 413 patients had the LVEF analyzed at the recruiting centre and at the core lab. Image quality was optimal in 191 and suboptimal in 222. Overall, the correlation between LVEF at the recruiting centres and at the core-lab was good, independent of image quality (R² = 0.62). However, when a LVEF ≤30 % or ≥30 % was used as a cut-off, about 20 % of all patients would have been re-assigned to having either a LVEF above or below the cut-off, this proportion was not significantly influenced by image quality. We conclude that correlation between LVEF assessed by different centres based on the same ultrasound data is good, regardless of image quality. However, one fifth of patients would have been re-assigned to a different category when using the clinically important cut-off of 30 %.

MR-imaging of the thoracic aorta: 3D-ECG- and respiratory-gated bSSFP imaging using the CLAWS algorithm versus contrast-enhanced 3D-MRA.

OBJECTIVE: To compare a contrast-enhanced 3D angiography (CE-3D-MRA) with the ECG- and respiratory gated 3D balanced steady state free precession (bSSFP) sequence using the CLAWS algorithm (3D-bSSFP-CLAWS) with respect to acquisition time, image quality, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). METHODS: 14 patients (4 women, mean age ± SD: 52 ± 18) with known or suspected thoracic aortic disease were imaged on a 1.5T scanner with both sequences. Two readers scored image quality of predefined levels of the thoracic aorta. Acquisition time, SNR and CNR were calculated for each examination. RESULTS: Image quality achieved with the 3D-bSSFP-CLAWS was scored significantly better than with the CE-3D-MRA for the aortic annulus (P = 0.003), the sinuses of Valsalva (P = 0.001), the proximal coronary arteries (P = 0.001) and the sinotubular junction (P = 0.001). Effective acquisition time for the 3D-bSSFP-CLAWS and corrected acquisition time (corrected for imaging parameters) was significantly longer compared to the CE-3D-MRA (P = 0.004 and P = 0.028). SNR and CNR were significantly higher for the CE-3D-MRA (P = 0.007 and P = 0.001). CONCLUSIONS: Providing the highest scan efficiency for a given breathing pattern, image quality for the proximal ascending aorta achieved with the 3D-bSSFP-CLAWS is significantly superior in contrast to the CE-3D-MRA.

Cardiovascular magnetic resonance imaging for diagnosis and clinical management of suspected cardiac masses and tumours.

AIMS: To evaluate the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging from a risk-stratification and therapeutic-management perspective in patients with suspected cardiac tumours. METHODS AND RESULTS: Cardiovascular magnetic resonance exams of 41 consecutive patients (aged 61 ± 14 years, 21 men) referred for evaluation of a suspected cardiac mass were reviewed for tumour morphology and signal characteristics in various unenhanced and contrast-enhanced sequences. Cardiovascular magnetic resonance-derived diagnosis and treatment were compared with clinical outcome and histology in patients undergoing surgery or autopsy (n = 20). In 18 of 41 patients, CMR excluded masses or reclassified them as normal variants; all were treated conservatively. In 23 of 41 patients, CMR diagnosed a neoplasm (14 'benign', 8 'malignant', and 1 'equivocal'); 18 of these patients were operated on, 2 managed conservatively, and 3 by palliation. During follow-up of 705 (inter-quartile range 303-1472) days, 13 patients died. No tumour-related deaths occurred in conservatively managed patients. Patients with a CMR-based diagnosis and treatment of benign tumour had a similar survival as patients without detectable tumour. Compared with histology, CMR correctly classified masses as 'benign or malignant' in 95% of the cases. Tumour perfusion, invasiveness, localization, and pericardial fluid were valuable to distinguish between malignant and benign tumours. Soft tissue contrast and signal intensity patterns in various sequences were valuable for excluding neoplastic lesions and helped to obtain tissue characterization at the histological level in selected tumour cases, respectively. CONCLUSION: Comprehensive CMR provides a confident risk-stratification and clinical-management tool in patients with suspected tumours. Patients where CMR excludes tumours can be managed conservatively.

Copeptin and risk stratification in patients with acute dyspnea.

INTRODUCTION: The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of Copeptin, the C-terminal part of the vasopressin prohormone alone and combined to N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea. METHODS: We conducted a prospective, observational cohort study in the emergency department of a university hospital and enrolled 287 patients with acute dyspnea. RESULTS: Copeptin levels were elevated in non-survivors (n = 29) compared to survivors at 30 days (108 pmol/l, interquartile range (IQR) 37 to 197 pmol/l) vs. 18 pmol/l, IQR 7 to 43 pmol/l; P < 0.0001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.83 (95% confidence interval (CI) 0.76 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for Copeptin, NT-proBNP and BNP, respectively (Copeptin vs. NTproBNP P = 0.21; Copeptin vs. BNP P = 0.002). When adjusted for common cardiovascular risk factors and NT-proBNP, Copeptin was the strongest independent predictor for short-term mortality in all patients (HR 3.88 (1.94 to 7.77); P < 0.001) and especially in patients with acute decompensated heart failure (ADHF) (HR 5.99 (2.55 to 14.07); P < 0.0001). With the inclusion of Copeptin to the adjusted model including NTproBNP, the net reclassification improvement (NRI) was 0.37 (P < 0.001). An additional 30% of those who experienced events were reclassified as high risk, and an additional 26% without events were reclassified as low risk. CONCLUSIONS: Copeptin is a new promising prognostic marker for short-term mortality independently and additive to natriuretic peptide levels in patients with acute dyspnea.

[Noninvasive diagnostic of coronary artery disease]. / Die nichtinvasive Bilddiagnostik der koronaren Herzkrankheit.

Noninvasive imaging of coronary artery disease has extensively evolved during the last decade. Today, at least four imaging techniques with excellent image quality such as echocardiography, myocardial perfusion scintigraphy and PET, cardiac magnetic resonance and cardiac CT are widely available in order to estimate the risk for future ischemic events, to corroborate the suspected diagnosis of coronary artery disease, to demonstrate the extent and localisation of myocardial ischemia, to diagnose myocardial infarction and measure it's size, to identify the myocardium at risk during acute ischemia, to differentiate between viable and nonviable myocardium and thereby provide the basis for indications of revascularisations, to follow revascularized patients over long time, to assess the risk for sudden cardiac death and the development of heart failure after myocardial infarction and to depict atheromatosis and atherosclerosis of the coronary artery tree. Echocardiography is the most widely used imaging method in cardiology. It provides excellent information on morphology and function of nearly all cardiac structures. Stress echocardiography has been proven to be a reliable tool for the demonstration of myocardial ischemia and for the acquisition of prognostic data. Newer ultrasound techniques may further improve investigator dependence and thereby reproducibility. The completeness of echocardiography will always depend on acoustic windows, which are given in a specific patient. Myocardial perfusion scintigraphy provides the largest database especially on prognosis in coronary artery disease. It has been the <> for the depictions of ischemic and infarcted myocardium. Radiation exposure will always be an issue. Newer hybrid techniques combining nuclear methods with cardiac CT may add arguments, which will be needed for clinical decision-making. Cardiac magnetic resonance has evolved as an important tool in the diagnosis of cardiovascular diseases. It is investigator independent, does not apply any biologically hazardous energy and has the largest potential for tissue characterization due to its high contrast resolution. It therefore is an excellent technique to investigate all the aspects of coronary artery disease. Its availability is increasing, however in order to fully utilize its large potential an optimal collaboration among -specialist (cardiologists, radiologists, physicists) is mandatory. Cardiac CT has evolved as an excellent method for the depiction of the coronary arteries. Due to its high spatial and time resolution it provides high quality luminography of the coronaries and newer technique are also -investigating plaque composition of diseased coronary arteries. Overestimation of coronary artery stenosis in calcified vessels is an inherent problem of the technique and the risk of radiation exposure has to be weighted against the benefit of non-invasively depicting the coronary arteries. It will be the future task of all specialists in this field to define the most efficient and cost-effective way to apply these excellent techniques for the investigation of all the different aspects of patients with coronary artery disease.

Immediate and sustained blood pressure lowering by urocortin 2: a novel approach to antihypertensive therapy?

Recently, novel corticotropin-releasing factor-related peptides, named urocortin 1, 2, and 3, and a distinct cardiac and peripheral vascular receptor (corticotropin-releasing factor receptor 2) were described being part of a peripheral corticotropin-releasing factor system modulating cardiovascular function in response to stress. Vasorelaxation and blood pressure lowering have been reported after acute administration of these peptides. No data are available on the acute and chronic effects of urocortin 2 on blood pressure in models of arterial hypertension. To test these effects, hypertensive salt-sensitive and normotensive salt-resistant Dahl rats were randomly assigned to twice-daily applications of urocortin 2 or vehicle for 5 weeks. Blood pressure, heart rate, and left ventricular dimension and function were recorded at baseline, after initial application, and, together with cardiac and aortic expression of urocortin 2 and its receptor, after 5 weeks of treatment. Urocortin 2 significantly reduced blood pressure in hypertensive rats without affecting heart rate. Long-term urocortin 2 treatment in hypertensive rats induced sustained blood pressure reduction and diminished the development of hypertension-induced left ventricular hypertrophy and the deterioration of left ventricular contractile function. Corticotropin-releasing factor receptor 2 expression was preserved despite chronic stimulation by urocortin 2. In conclusion, our study shows that, in an animal model of arterial hypertension, urocortin 2 has immediate and sustained blood pressure-lowering effects. Beneficial effects on blood pressure, left ventricular dimension, and function, together with preserved receptor expression, suggest that corticotropin-releasing factor receptor 2 stimulation by urocortin 2 may represent a novel approach to the treatment of arterial hypertension.

Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial.

OBJECTIVES: The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention. BACKGROUND: FX06, a naturally occurring peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury. METHODS: In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers. FX06 or matching placebo was given as intravenous bolus at reperfusion. Infarct size was assessed 5 days after myocardial infarction by late gadolinium enhanced cardiac magnetic resonance imaging. Secondary outcomes included size of necrotic core zone and microvascular obstruction at 5 days, infarct size at 4 months, left ventricular function, troponin I levels, and safety. RESULTS: There were no baseline differences between groups. On day 5, there was no significant difference in total late gadolinium enhanced zone in the FX06 group compared with placebo (reduction by 21%; p = 0.207). The necrotic core zone, however, was significantly reduced by 58% (median 1.77 g [interquartile range 0.0, 9.09 g] vs. 4.20 g [interquartile range 0.3, 9.93 g]; p < 0.025). There were no significant differences in troponin I levels (at 48 h, -17% in the FX06 group). After 4 months, there were no longer significant differences in scar size. There were numerically fewer serious cardiac events in the FX06-treated group, and no differences in adverse events. CONCLUSIONS: In this proof-of-concept trial, FX06 reduced the necrotic core zone as one measure of infarct size on magnetic resonance imaging, while total late enhancement was not significantly different between groups. The drug appears safe and well tolerated. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury [F.I.R.E.]; NCT00326976).

Routine echocardiography after radiofrequency ablation: to flog a dead horse?

AIMS: Radiofrequency ablation (RFA) is frequently used to treat sustained arrhythmias. One major complication is pericardial effusion-tamponade. Therefore, many centres perform echocardiography after interventions, but data on necessity of such routine procedures are scarce. METHODS AND RESULTS: We included 510 patients with RFA and compared echocardiographic results acquired before and <24 h after intervention. We defined pericardial effusion as 'small', if <10 mm in diastole, 'moderate' if >10 mm, 'large' if >20 mm, or tamponade (>20 mm with haemodynamic compromise). Age was 55 +/- 16 years, 40% were females. Thirty-five percentage underwent RFA for atrioventricular nodal re-entrant tachycardia (AVNRT), 28% for atrial flutter, 15% for atrial fibrillation (AF), 12% for Wolff-Parkinson-White (WPW) syndrome, and 10% for different other arrhythmias. In 16 patients (3.2%), small asymptomatic effusions were detected. The only moderate effusion was suspected due to procedure circumstances. Radiofrequency ablation for AF had a higher incidence compared to AVNRT and flutter (P = 0.001 and <0.0001, respectively) or to WPW syndrome (P = 0.06). CONCLUSION: Numbers of significant pericardial effusion as detected by routine echocardiography were low (3.6%) and clinically relevant effusions absent. We thus recommend performing echocardiography after RFA only, if effusion is suspected clinically or if RFA was performed for AF, due to the high incidence of effusions with this type of ablation.

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.

Long-term outcomes after intracoronary Beta-irradiation for in-stent restenosis in bare-metal stents.

OBJECTIVE: We sought to characterize the long-term outcomes of patients undergoing intracoronary brachytherapy using Beta- irradiation (Beta-BT). BACKGROUND: Beta-BT is effective in reducing angiographic restenosis as well as target vessel revascularization (TVR) in patients with in-stent restenosis (ISR) after bare-metal stenting (BMS). METHODS: 81 consecutive patients undergoing Beta-BT for ISR (irradiated length 32 [32-54] mm) after BMS in native vessels (n = 79) or saphenous vein grafts (n = 2) between 2001 and 2003 were followed. Major cardiac events (MACE), including cardiac death, nonfatal myocardial infarction (MI), and TVR occurring > 1 year or > 1 year were assessed 5.2 (4.4-5.6) years after the index procedure. RESULTS: During the entire follow-up period, the total MACE rate was 49.4%. Within the first year and at > 1 year, MACE rates were 25.9% and 23.5%, cardiac death occurred in 2.4% and 6.2%, and nonfatal MI in 6.2% and 12.3% for annual cardiac death/MI rates of 8.7% at < 1 year and 4.1% thereafter. TVR was required in 19% at < 1 year and in 16% of patients later on. The only independent predictor of MACE occurring < 1 year was an irradiated vessel length > 32 mm (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.10-6.78; p = 0.03). The best, albeit not statistically significant, predictor of MACE occurring at > 1 year was the presence of diabetes mellitus (OR 2.49, 95% CI 0.94-6.57; p = 0.07). CONCLUSIONS: Patients undergoing Beta-BT for ISR after BMS carry a substantial risk of MACE also beyond the first year, with annual cardiac death and nonfatal MI rates of 1.5% and 2.9% up to 5 years postprocedure.

Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats.

Persistent Nuclear Factor-kappaB (NF-kappaB) activation is hypothesized to contribute to myocardial injuries following ischemia-reperfusion. Because inhibition or control of NF-kappaB signaling in the heart probably confers cardioprotection, we determined the potency of the NF-kappaB inhibitor dimethyl fumarate (DMF) in cardiovascular cells, and determined whether administration of DMF translates into beneficial effects in an animal model of myocardial infarction. In rat heart endothelial cells (RHEC), we analysed inhibitory effects of DMF on NF-kappaB using shift assay and immunohistofluorescence. In in vivo experiments, male Sprague Dawley rats undergoing left coronary artery occlusion for 45 min received either DMF (10 mg/kg body weight) or vehicle 90 min before ischemia as well as immediately before ischemia. After 120 min of reperfusion, the hearts were stained with phthalocyanine blue dye and triphenyltetrazolium chloride. Additionally, acute hemodynamic and electrophysiologic effects of DMF were determined in dose-response experiments in isolated perfused rat hearts. DMF inhibited TNF-alpha-induced nuclear entry of NF-kappaB in RHEC. In in vivo experiments, myocardial infarct size was significantly smaller in rats that had received DMF (20.7%+/-9.7% in % of risk area; n=17) than in control rats (28.2%+/-6.2%; n=15). Dose-response experiments in isolated perfused rat hearts excluded acute hemodynamic or electrophysiologic effects as mechanisms for the effects of DMF. DMF inhibits nuclear entry of NF-kappaB in RHEC and reduces myocardial infarct size after ischemia and reperfusion in rats in vivo. There was no indication that the beneficial effects of DMF were due to acute hemodynamic or electrophysiologic influences.

Value and limitations of target-vessel ischemia in predicting late clinical events after drug-eluting stent implantation.

UNLABELLED: Drug-eluting stents reduce clinical events related to restenosis but may be complicated by late stent-thrombosis. Whereas assessment of target-vessel ischemia by myocardial perfusion scintigraphy identifies relevant restenosis noninvasively, it is unknown whether this technique may also predict late clinical events related to late stent-thrombosis and to restenosis after drug-eluting stent implantation. METHODS: All 826 patients treated with stenting between May 2003 and May 2004 were included in the Basel Stent Cost Effectiveness Trial (Basel Stent Kosten-Effektivitäts Trial, or BASKET) and randomized (2:1) to drug-eluting stents or bare metal stents. Myocardial scintigraphy was performed on 476 (64%) of 747 patients without major events after 6 mo. Patients were followed for 1 y for cardiac death, nonfatal myocardial infarction, and target-vessel revascularization due to restenosis or late stent-thrombosis. RESULTS: The rate of target-vessel ischemia in these patients was lower with drug-eluting stents than with bare metal stents (5.4% vs. 10.4%, P = 0.045), similar to the rates of symptom-driven target-vessel revascularization up to 6 mo (4.6% vs. 7.8%, P = 0.08). Ischemia was silent in 68%. During follow-up, patients with target-vessel ischemia had higher event rates than did patients without ischemia (32.4% vs. 6.1%, P < 0.001); however, ischemia did not predict late stent-thrombosis (0/11 cases). CONCLUSION: The rate of clinical restenosis assessed scintigraphically was lower with drug-eluting stents than with bare metal stents and paralleled that of symptom-driven target-vessel revascularization. Target-vessel ischemia independently predicted late clinical events related to restenosis but not to late stent-thrombosis.

Use of B-type natriuretic peptide outside of the emergency department.

In contrast to their established role in the evaluation of acute dyspnea in emergency department (ED) patients, applications of B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) in patients outside of the ED are less well defined. A PubMed-based electronic and hand search for articles dealing with BNP and NT-proBNP in settings other than the ED was performed. We found that currently available evidence is sufficient to support the use of BNP and NT-proBNP in four cardiovascular settings outside of the ED: i) evaluation of patients with suspected heart failure (HF) referred from primary care, ii) risk stratification in patients with HF, iii) risk stratification in stable coronary artery disease, and iv) risk stratification in pulmonary artery hypertension. Recent studies indicate that BNP and NT-proBNP might also be helpful in guiding therapy in patients with chronic HF. Despite active research in many additional fields, the use of BNP/NT-proBNP in other settings is not yet based on solid evidence and, therefore, seems not to be useful.

Cost-effectiveness of drug-eluting stents in patients at high or low risk of major cardiac events in the Basel Stent KostenEffektivitäts Trial (BASKET): an 18-month analysis.

BACKGROUND: Our aim was to determine whether drug-eluting stents are good value for money in long-term, everyday practice. METHODS: We did an 18-month cost-effectiveness analysis of the Basel Stent KostenEffektivitäts Trial (BASKET), which randomised 826 patients 2:1 to drug-eluting stents (n=545) or to bare-metal stents (281). We used non-parametric bootstrap techniques to determine incremental cost-effectiveness ratios (ICERs) of drug-eluting versus bare-metal stents, to compare low-risk (> or =3.0 mm stents in native vessels; n=558, 68%) and high-risk patients (<3.0 mm stents/bypass graft stenting; n=268, 32%), and to do sensitivity analyses by altering costs and event rates in the whole study sample and in predefined subgroups. Quality-adjusted life-years (QALYs) were assessed by EQ-5D questionnaire (available in 703/826 patients). FINDINGS: Overall costs were higher for patients with drug-eluting stents than in those with bare-metal stents (11,808 euros [SD 400] per patient with drug-eluting stents and 10,450 euros [592] per patient with bare-metal stents, mean difference 1358 euros [717], p<0.0001), due to higher stent costs. We calculated an ICER of 64,732 euros to prevent one major adverse cardiac event, and of 40,467 euros per QALY gained. Stent costs, number of events, and QALYs affected ICERs most, but unrealistic alterations would have been required to achieve acceptable cost-effectiveness. In low-risk patients, the probability of drug-eluting stents achieving an arbitrary ICER of 10,000 euros or less to prevent one major adverse cardiac event was 0.016; by contrast, it was 0.874 in high-risk patients. INTERPRETATION: If used in all patients, drug-eluting stents are not good value for money, even if prices were substantially reduced. Drug-eluting stents are cost effective in patients needing small vessel or bypass graft stenting, but not in those who require large native vessel stenting.

Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial.

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.