Incidence of late-acquired stent malapposition of drug eluting stents with second generation permanent and biodegradable polymer coatings-A prospective, randomized comparison using optical coherence tomography.

OBJECTIVES AND BACKGROUND: Polymer coatings of drug-eluting stents (DES) may induce allergic reactions and inflammation, resulting in late-acquired stent malapposition (LASM) with the risk of stent thrombosis. This study evaluated, if biodegradable polymer (BP) reduces the incidence of LASM compared to permanent polymer (PP) after treatment with newer generation DES. METHODS AND RESULTS: Fifty patients with 59 lesions were randomized (2:1) to elective treatment with second generation PP-DES (n = 32, 39 stents), either Everolimus-eluting or Zotarolimus-eluting stents, or with BP-DES (Biolimus-eluting stents [BES]; n = 18, 20 stents) and underwent optical coherence tomography directly after implantation and after 1 year. After implantation acute stent malappositions (ASM) were documented in 30 stents (51%) distributed to 22 stents treated with PP-DES (56%) and 8 with BP-DES (40%; n.s.). After 1 year, late stent malappositions (LSM) were detected in 14 stents (24 %); ASM persisted (APSM) in 9 stents after one year (7 PP-DES-18%, 2 BES-10%), whereas ASM resolved in 21 stents. In addition, LASM was documented in nine stents including five stents without and four stents with additional APSM. All LASM were located in PP-DES (n = 9; 23%), none in BP-DES (P = 0.022). Compared to the reference lumen area, in-stent lumen area of stents without LASM was smaller due to neointimal hyperplasia (P = 0.021), whereas in-stent lumen area at maximum LASM of stents with LASM was larger due to positive remodeling (P = 0.002). CONCLUSIONS: In conclusion the use of BP-DES reduced the occurrence of LASM due to positive remodeling compared to second generation PP-DES.

Mechanical properties of the everolimus-eluting bioresorbable vascular scaffold compared to the metallic everolimus-eluting stent.

BACKGROUND: Everolimus-eluting bioresorbable vascular scaffolds (BVS) represent an innovative treatment option for coronary artery disease. Clinical and angiographic results seem promising, however, data on its immediate procedural performance are still scarce. The aim of our study was to assess the mechanical properties of BVS by Optical Coherence Tomography (OCT) in clinical routine. METHODS: Post-implantation OCT images of 40 BVS were retrospectively compared to those of 40 metallic everolimus-eluting stents (EES). Post-procedural device related morphological features were assessed. This included incidences of gross underexpansion and the stent eccentricity index (SEI, minimum/maximum diameter) as a measure for focal radial strength. RESULTS: Patients receiving BVS were younger than those with EES (54.0 ± 11.2 years versus 61.7 ± 11.4 years, p = 0.012), the remaining baseline, vessel and lesion characteristics were comparable between groups. Lesion pre-dilatation was more frequently performed and inflation time was longer in the BVS than in the EES group (n = 34 versus n = 23, p = 0.006 and 44.2 ± 12.8 versus 25.6 ± 8.4 seconds, p < 0.001, respectively). There were no significant differences in maximal inflation pressures and post-dilatation frequencies with non-compliant balloons between groups. Whereas gross device underexpansion was not significantly different, SEI was significantly lower in the BVS group (n = 12 (30 %) versus n = 14 (35 %), p = 0.812 and 0.69 ± 0.08 versus 0.76 ± 0.09, p < 0.001, respectively). There was no difference in major adverse cardiac event-rate at six months. CONCLUSION: Our data show that focal radial expansion was significantly reduced in BVS compared to EES in a clinical routine setting using no routine post-dilatation protocol. Whether these findings have impact on scaffold mid-term results as well as on clinical outcome has to be investigated in larger, randomized trials.

Inter-patient variability of platelet reactivity in patients treated with prasugrel and ticagrelor.

The aim of this study was to evaluate the distribution of platelet reactivity values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 200 patients treated with prasugrel or ticagrelor. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) in the maintenance phase of treatment with prasugrel or ticagrelor. Only 3% of patients in the prasugrel group and 2% of study participants in the ticagrelor group had high on treatment platelet reactivity (HTPR). The majority of patients displayed low on treatment platelet reactivity (LTPR; prasugrel: 69%; ticagrelor: 64%). The pharmacodynamic effect was similar in patients treated with prasugrel and ticagrelor: the median level of ADP-induced platelet aggregation was 15U (interquartile range IQR 9-21U) under prasugrel treatment and 17U (IQR 8-24U) under ticagrelor treatment (p=0.370). In conclusion, our study suggests that there is some degree of variability in ADP-induced platelet aggregation under treatment with prasugrel and ticagrelor.

Comparison of magnetic wire navigation with the conventional wire technique for percutaneous coronary intervention of chronic total occlusions: a randomised, controlled study.

Wire crossing of a chronic total coronary occlusion (CTO) is time consuming and limited by the amount of contrast agent and time of radiation exposure. Magnetic wire navigation (MWN) might accelerate wire crossing by maintaining a coaxial vessel orientation. This study compares MWN with the conventional approach for recanalization of CTOs. Forty symptomatic patients with CTO were randomised to MWN (n = 20) or conventional approach (n = 20) for antegrade crossing of the occlusion. In the intention-to-treat analysis, MWN showed a shorter crossing time (412 versus 1131 s; p = 0.001), and, consequently, lower usage of contrast agent (primary endpoint 42 versus 116 ml; p = 0.01), and lower radiation exposure (dose-area product: 29 versus 80 Gy*cm(2); p = 0.002) during wire crossing compared to the conventional approach. Accordingly, in the per-protocol analysis, the wire-crossing rate was, in trend, higher using the conventional approach (17 of 31) compared to MWN (9 of 28; p = 0.08). The use of MWN for revascularisation of CTOs is feasible and reduces crossing time, use of contrast agent, and radiation exposure. However, due to a broader selection of wires, the conventional approach enables wire crossing in cases failed by MWN and seems to be the more successful choice.

Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents in patients with multivessel coronary artery disease compared to coronary artery bypass surgery five-years after intervention.

OBJECTIVES: Cost-effectiveness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES), and coronary artery bypass surgery (CABG) was analyzed in patients with multivessel coronary artery disease over a 5-year follow-up. BACKGROUND: DES implantation reducing revascularization rate and associated costs might be attractive for health economics as compared to CABG. METHODS: Consecutive patients with multivessel DES-PCI (n = 114, 3.3 ± 1.2 DES/patient) or CABG (n = 85, 2.7 ± 0.9 grafts/patient) were included prospectively. Primary endpoint was cost-benefit of multivessel DES-PCI over CABG, and the incremental cost-effectiveness ratio (ICER) was calculated. Secondary endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE), including acute myocardial infarction (AMI), all-cause death, revascularization, and stroke. RESULTS: Despite multiple uses for DES, in-hospital costs were significantly less for PCI than CABG, with 4551 €/patient difference between the groups. At 5-years, the overall costs remained higher for CABG patients (mean difference 5400 € between groups). Cost-effectiveness planes including all patients or subgroups of elderly patients, diabetic patients, or Syntax score >32 indicated that CABG is a more effective, more costly treatment mode for multivessel disease. At the 5-year follow-up, a higher incidence of MACCE (37.7% vs. 25.8%; log rank P = 0.048) and a trend towards more AMI/death/stroke (25.4% vs. 21.2%, log rank P = 0.359) was observed in PCI as compared to CABG. ICER indicated 45615 € or 126683 € to prevent one MACCE or AMI/death/stroke if CABG is performed. CONCLUSIONS: Cost-effectiveness analysis of DES-PCI vs. CABG demonstrated that CABG is the most effective, but most costly, treatment for preventing MACCE in patients with multivessel disease.

Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial.

CONTEXT: Thrombus embolization during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy. OBJECTIVE: To determine whether bolus intracoronary abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. DESIGN, SETTING, AND PATIENTS: Between November 28, 2009, and December 2, 2011, 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion undergoing primary PCI with bivalirudin anticoagulation were randomized in an open-label, 2 x 2 factorial design to bolus intracoronary abciximab delivered locally at the infarct lesion site vs no abciximab and to manual aspiration thrombectomy vs no thrombectomy. INTERVENTIONS: A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6 F aspiration catheter. MAIN OUTCOME MEASURES: Primary end point: infarct size (percentage of total left ventricular mass) at 30 days assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab vs no abciximab groups (pooled across the aspiration randomization); major secondary end point: 30-day infarct size in the aspiration vs no aspiration groups (pooled across the abciximab randomization). RESULTS: Evaluable cMRI results at 30 days were present in 181 and 172 patients randomized to intracoronary abciximab vs no abciximab, respectively, and in 174 and 179 patients randomized to manual aspiration vs no aspiration, respectively. Patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [IQR, 7.4-31.3 g]; n = 184, vs 24.0 g [IQR, 12.1-34.2 g]; n = 175; P = .03) but not abnormal wall motion score (median, 7.0 [IQR, 2.0-10.0]; n = 188, vs 8.0 [IQR, 3.0-10.0]; n = 184; P = .08). Patients randomized to aspiration thrombectomy vs no aspiration had no significant difference in infarct size at 30 days (median, 17.0% [IQR, 9.0%-22.8%]; n = 174, vs 17.3% [IQR, 7.1%-25.5%]; n = 179; P = .51), absolute infarct mass (median, 20.3 g [IQR, 9.7-31.7 g]; n = 178, vs 21.0 g [IQR, 9.1-34.1 g]; n = 181; P = .36), or abnormal wall motion score (median, 7.5 [IQR, 2.0-10.0]; n = 186, vs 7.5 [IQR, 2.0-10.0]; n = 186; P = .89). CONCLUSION: In patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin anticoagulation, infarct size at 30 days was significantly reduced by bolus intracoronary abciximab delivered to the infarct lesion site but not by manual aspiration thrombectomy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00976521.

Facilitated PCI in patients with ST-elevation myocardial infarction.

BACKGROUND: We hypothesized that percutaneous coronary intervention (PCI) preceded by early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or with abciximab alone (abciximab-facilitated PCI) would improve outcomes in patients with acute ST-segment elevation myocardial infarction, as compared with abciximab administered immediately before the procedure (primary PCI). METHODS: In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximab-facilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization. RESULTS: A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P=0.01 and P=0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P=0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P=0.49). CONCLUSIONS: Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228 [ClinicalTrials.gov].)

2020 update of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGHTG) on the position statement of the ÖKG and ÖGHTG for transcatheter aortic valve implantation 2011.

This position statement is an update to the 2011 consensus statement of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGTHG) for transfemoral transcatheter aortic valve implantation.Due to a number of recently published studies, broadening of indications and recommendations of medical societies and our own national developments, the ÖKG and the ÖGHTG wish to combine the 2017 ESC/EACTS guidelines for the management of valvular heart disease with a national position paper and to focus on certain details for the application in Austria. Thus, this position statement serves as a supplement and further interpretation of the international guidelines.

Transcatheter aortic valve replacement (TAVR) leads to an increase in the subendocardial viability ratio assessed by pulse wave analysis.

BACKGROUND: Pulse wave analysis (PWA) is a useful tool for non-invasive assessment of central cardiac measures as subendocardial perfusion (Subendocardial Viability Ratio, SEVR) or contractility (dP/dtmax). The immediate influence of transcatheter aortic valve replacement (TAVR) on these indices has not been investigated yet. METHODS: We prospectively enrolled 40 patients presenting with severe aortic stenosis receiving TAVR. Central pressure curves were derived from radial and carotid sites using PWA up to 2 days before and 7 days after TAVR. Parameters were compared between peripheral measurement sites. Changes in SEVR, dP/dtmax and in indices of vascular stiffness were assessed. Additionally, association of these variables with clinical outcome was evaluated during a 12-month follow-up. RESULTS: Central waveform parameters were comparable between measurement sites. SEVR, but not dP/dtmax, augmentation Index (AIx) or augmentation pressure height (AGPH) correlated significantly with disease severity reflected by peak transvalvular velocity and mean transvalvular pressure gradient over the aortic valve (Vmax, ΔPm) [r = -0.372,p = 0.029 for Vmax and r = -0.371,p = 0.021 for ΔPm]. Vmax decreased from 4.5m/s (IQR:4.1-5.0) to 2.2m/s (IQR:1.9-2.7), (p<0.001). This resulted in a significant increase in SEVR [135.3%(IQR:115.5-150.8) vs. 140.3%(IQR:123.0-172.5),p = 0.039] and dP/dtmax [666mmHg(IQR:489-891) vs. 927mmHg(IQR:693-1092),p<0.001], and a reduction in AIx [154.8%(IQR:138.3-171.0) vs. 133.5%(IQR:128.3-151.8),p<0.001] and AGPH [34.1%(IQR:26.8-39.0) vs. 25.0%(IQR 21.8-33.7),p = 0.002], confirming the beneficial effects of replacing the stenotic valve. No association of these parameters could be revealed with outcome. CONCLUSIONS: PWA is suitable for assessing coronary microcirculation and contractility mirrored by SEVR and maxdP/dt in the setting of aortic stenosis. PWA parameters attributed to vascular properties should be interpreted with caution.

Correlates and prognostic impact of new-onset heart failure after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: insights from the INFUSE-AMI trial.

BACKGROUND: The determinants and significance of early (30-day) heart failure symptoms after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) remain unclear. We investigated the clinical and imaging correlates of early post-discharge heart failure in patients with STEMI, and evaluated its impact on clinical outcomes. METHODS: Patients from the INFUSE-AMI trial were categorized according to New York Heart Association (NYHA) functional classification at their 30-day visit (NYHA class ≥2 versus 1). Independent correlates of NYHA class ≥2 were determined by multivariable logistic regression. A landmark analysis beyond 30 days was performed to assess the impact of 30-day NYHA class ≥2 on 1-year risk of death or hospitalization for heart failure. RESULTS: Among 402 patients enrolled in the INFUSE-AMI trial with data on NYHA class at 30 days, 76 (18.9%) had NYHA class ≥2. Independent correlates of 30-day NYHA class ≥2 were age, Killip class ≥2 at presentation, heart rate at presentation, intraprocedural no-reflow, and 30-day infarct size (% total ventricular mass). After adjustment for infarct size, patients with NYHA class ≥2 remained at higher risk of death or hospitalization for heart failure at 1-year follow-up compared to those in NYHA class 1 (11.8% vs. 2.8%, adjusted hazard ratio 3.78, 95% confidence interval 1.16-12.22, P=0.03). CONCLUSIONS: Clinical, procedural, and imaging variables predict the development of clinical heart failure after primary percutaneous coronary intervention in patients with STEMI. Early post-discharge heart failure symptoms identify a high-risk patient cohort for subsequent heart failure hospitalization and death, independent of infarct size. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT00976521.

Effect of Smoking on Infarct Size and Major Adverse Cardiac Events in Patients With Large Anterior ST-Elevation Myocardial Infarction (from the INFUSE-AMI Trial).

We sought to investigate the effect of smoking on infarct size (IS) and major adverse cardiac events (MACE) in patients with large anterior ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Participants from the Intracoronary Abciximab and Aspiration Thrombectomy in Patients with Large Anterior Myocardial Infarction study were categorized according to smoking status (current or previous smoking vs no history of smoking). The primary imaging outcome was cardiac magnetic resonance imaging-assessed IS of left ventricular mass (%) at 30 days. The primary clinical outcome was the rate of MACE at 30 days and 1 year, defined as the composite of death, reinfarction, new-onset heart failure, or rehospitalization. Of 447 patients enrolled in Intracoronary Abciximab and Aspiration Thrombectomy in Patients with Large Anterior Myocardial Infarction, 271 (60.6%) were current or past smokers. Compared with nonsmokers, smokers were almost 10 years younger and had a lower prevalence of clinical co-morbidities. Smokers had better procedural success and angiographic reperfusion compared with nonsmokers. At 30 days, there were no differences between smokers and nonsmokers in median IS (16.8% vs 17.4%, p = 0.67) or metrics of left ventricular function. By multivariable linear regression analysis, smoking was not significantly associated with IS at 30 days (beta coefficient: 0.83, p = 0.42). At 1 year, smokers had lower crude rates of MACE (7.6% vs 15%, p = 0.01). After multivariable adjustment, there were no significant differences in 1-year MACE between smokers and nonsmokers (adjusted hazard ratio 0.73, 95% CI 0.40 to 1.33, p = 0.30). In conclusion, smoking history had no significant effect on IS at 30 days. Although current or previous smokers had lower rates of 1-year MACE than those with no history of smoking, adjustment for baseline characteristics rendered this association nonsignificant. These findings support the hypothesis that the smoker's paradox is largely attributable to differences in demographic and clinical baseline risk, rather than differences in IS after primary percutaneous coronary intervention.

Outcome after Elective Percutaneous Coronary Intervention Depends on Age in Patients with Stable Coronary Artery Disease - An Analysis of Relative Survival in a Multicenter Cohort and an OCT Substudy.

BACKGROUND: Age is a strong predictor of survival in patients with coronary artery disease. In elder patients with increasing co-morbidities percutaneous coronary intervention (PCI) is associated with more complications and worse outcome. The calculation of relative survival rates adjusts for the "background" mortality in the general population by correcting for age and gender. We analyzed if elder patients after elective PCI have a worse relative survival compared to younger patient groups. METHODS: A total of 8,342 patients who underwent elective PCI at two high volume centers between 1998 and 2009 were analyzed. RESULTS: The survival of our patients after PCI (observed survival) was slightly lower compared to the general population (expected survival) resulting in a slightly decreasing relative survival curve. In a multivariate Cox regression model age amongst others was a strong predictor of survival. Stratifying patients according to their age the relative survival curves of younger patients (Quartile 1: <58 years; 2,046 patients), elder patients (Quartile 3: 66-73 years; 2,090 patients) and very old patients (Quartile 4: >73 years; 2,307 patients) were similar. The relative survival of mid-aged patients (Quartile 2: 58-65 years; 1,899 patients) was better than that of all other patient groups. The profile of cardiovascular risk factors differs between the various groups resulting in different composition and burden of coronary plaques in an optical coherence tomography sub-study. CONCLUSION: Patients after elective PCI have a slightly worse long-term survival compared to the age- and sex-matched general population. This is also true for different groups of age except for mid-aged patients between 58 and 63 years. Elder patients between 66 and 73 years and above 73 years have a similar relative survival compared to younger patients below 58 years, and might therefore have similar benefit from elective PCI.

Contribution of nicotine to acute endothelial dysfunction in long-term smokers.

OBJECTIVES: The aim of this study was to determine whether nicotine, a constituent of cigarette smoke, contributes to acute endothelial dysfunction after smoking one cigarette. BACKGROUND: Animal studies suggest that nicotine might cause an impairment of endothelium-dependent vasodilation via an increase in oxidative stress. METHODS: Sixteen healthy smokers were entered into a randomized, observer-blinded crossover study comparing the effects of nicotine nasal spray (1-mg nicotine) and cigarette smoke (1-mg nicotine, 12 mg tar) on vascular reactivity in the brachial artery. Using high-resolution ultrasound, flow-mediated dilation (FMD) and endothelium-independent, nitroglycerin-induced dilation were assessed at baseline and 20 min after the administration of nicotine (spray or cigarette). RESULTS: In response to similar increases in nicotine serum levels, FMD values declined from 10.2 +/- 4.4% to 6.7 +/- 4.0% after the spray (mean difference: -3.6 +/- 2.0%, 95% confidence interval: -4.6; -2.5, p < 0.0001) and from 9.4 +/- 3.8% to 4.3 +/- 2.8% after the cigarette (-5.1 +/- 2.6%, -6.5; -3.7, p < 0.0001). Nitroglycerin-induced dilation remained similar within both periods. Performing a period effect analysis of variance, a significant influence on FMD was found for the mode of administration (p = 0.017) and the baseline value (p = 0.021). The effect on FMD was more pronounced after the cigarette than after the spray (estimated average effect difference: 1.9% FMD). Oxidation parameters did not increase significantly after nicotine spray or tobacco exposure. CONCLUSIONS: These results demonstrate that nicotine alone causes acute endothelial dysfunction, although to a lesser extent than smoking a cigarette of the same nicotine yield. However, the precise mechanisms by which nicotine leads to this altered vascular reactivity remain unclear.

Vascular dysfunction after coarctation repair is related to the age at surgery.

BACKGROUND: Despite repair of aortic coarctation, hypertension is frequent in adults and premature coronary and cerebrovascular disease remain of concern. Persistent impairment of arterial dilation has been suspected to contribute to abnormal blood pressure regulation. We tested the hypothesis that arterial reactivity is more likely to be impaired in patients corrected at older age. METHODS: We studied changes in brachial artery diameter in response to reactive hyperemia (FMD) and to nitroglycerin (NMD) in 36 patients and 25 controls. Depending on their age at surgery, patients were divided in group A (surgery <9 years) and group B (surgery > or =9 years). RESULTS: Cholesterol levels and percentage of smokers were similar in patients and controls, but 16 patients had arterial hypertension compared to none of the controls. Endothelium-dependent vasodilation, FMD, and endothelium-independent vasodilation, NMD, were significantly impaired in patients vs. controls (8.2+/-6.2% vs. 13.0+/-5.1%, p<0.001 and 12.9+/-8.0% vs. 18.8+/-9.2%, p<0.01, respectively), both, in hypertensives (8.3+/-6.0%, p<0.01 and 11.8+/-6.0%, p<0.05) and in normotensives (8.1+/-6.5% p<0.01 and 13.8+/-9.3%, p<0.05). However, FMD and NMD in patients of group A did not significantly differ from that in controls (10.0+/-6.7% n.s. and 15.0+/-7.6% n.s.), whereas they were lowest in patients of group B (5.5+/-4.3%, p<0.0001 and 9.6+/-7.7% p<0.001). CONCLUSIONS: Persistent impairment of FMD and NMD after repair of coarctation is more likely to be present in patients corrected at older age. It may be an important contributor to abnormal blood pressure regulation and late morbidity and mortality.

Pressure-controlled intermittent coronary sinus occlusion (PICSO) in acute ST-segment elevation myocardial infarction: results of the Prepare RAMSES safety and feasibility study.

AIMS: Pressure-controlled intermittent coronary sinus occlusion (PICSO) may improve myocardial perfusion after pPCI. We evaluated the safety and feasibility of PICSO after pPCI for STEMI, and explored its effects on infarct size and myocardial function. METHODS AND RESULTS: Thirty patients were enrolled following successful pPCI of a left anterior descending coronary artery culprit lesion for anterior STEMI, in whom PICSO for 90 minutes was attempted. Infarct size and myocardial function were assessed by cardiovascular magnetic resonance (CMR) at two to five days and four months post pPCI. An independent core laboratory selected matched historical control patients with CMR data for comparison. PICSO was initiated in 19 patients (63%), and could be maintained for 90 (±2) minutes in 12 patients (40%). Major adverse safety events occurred in one patient (3%). Comparing all PICSO-treated patients to matched controls demonstrated no significant differences in infarct size or myocardial recovery. However, infarct size reduction from two to five days to four months was greater for patients successfully treated with PICSO compared with matched controls (41.6±8.2% vs. 27.7±9.9%, respectively; p=0.04). CONCLUSIONS: PICSO is safe in the setting of STEMI, although feasibility was limited. Administration of sufficient PICSO therapy may be associated with enhanced myocardial recovery during follow-up, warranting further evaluation of this novel therapy.

Prognosis of patients who develop acute renal failure during the first 24 hours of cardiogenic shock after myocardial infarction.

PURPOSE: Acute renal failure has important prognostic implications in critically ill patients, but the effects of acute renal failure on in-hospital mortality in the subset of patients with cardiogenic shock are not known. SUBJECTS AND METHODS: All consecutive patients who presented with acute coronary syndrome at our cardiovascular intensive care unit from 1993 to 2000 and who were in cardiogenic shock were enrolled. Acute renal failure was defined as a urine volume < 20 mL/h associated with an increase in serum creatinine level > or = 0.5 mg/dL or > 50% above the baseline value. RESULTS: There were 118 patients (83 men [70%]; mean [+/- SD] age, 66 +/- 10 years), 39 (33%) of whom developed acute renal failure within 24 hours after the onset of shock. In-hospital mortality was 87% (34/39) in patients with acute renal failure and 53% (42/79) in patients without acute renal failure (odds ratio [OR] = 6.0; 95% confidence interval [CI]: 2.1 to 17; P < 0.001). Other significant univariate predictors of mortality included the peak serum lactate level, epinephrine dose, and the maximum serum creatinine level. Multivariate logistic regression analysis identified acute renal failure as the only independent predictor of mortality. CONCLUSION: Acute renal failure was common in patients with cardiogenic shock and strongly associated with in-hospital mortality.

Endothelin receptor antagonists in cardiology clinical trials.

Endothelin-1 (ET-1) is enhanced and has been demonstrated to be a prognostic marker in patients with advanced stages of heart failure, acute ischaemic syndromes, myocardial infarction and pulmonary hypertension. Activation of the endothelin (ET) system is associated with adverse haemodynamic consequences in patients with congestive heart failure and results in coronary vasoconstriction in patients with coronary artery disease (CAD). Moreover, ET-1 raises blood pressure, induces vascular and myocardial hypertrophy and acts as the natural counterpart of nitric oxide (NO), which exerts vasodilating, antithrombotic and antiproliferative effects. This article reviews recently completed and ongoing clinical trials examining the effects of ET receptor antagonists in patients with heart failure, CAD, arterial hypertension and pulmonary hypertension.

Intracoronary brachytherapy with beta-radiation for the treatment of long diffuse in-stent restenosis.

OBJECTIVE: To assess the efficacy of intracoronary brachytherapy with beta-radiation (Sr/Y) for the treatment of long diffuse in-stent restenosis (ISR). METHODS: As recurrent ISR depends on intimal injury after coronary angioplasty, long in-stent restenotic lesions were defined as lesions with a treatment length >26 mm (lesion length >20 mm plus a treatment margin of 3 mm at each end). Seventy-eight patients with long ISR were treated at our institution with beta-brachytherapy after coronary angioplasty. Patients were irradiated with either an approximate dose of 12 Gy at 1 mm vessel wall depth or with 18 Gy at 1 mm vessel wall depth. Clinical follow-up was available for 69 patients and angiographic follow-up for 65 patients. Late lumen loss (LLL), binary restenosis (stenosis >50%), target lesion revascularization (TLR) and major adverse cardiac events (MACE) were assessed for a follow-up time of 6.6+/-2.2 months. RESULTS: Mean interventional treatment length was 46+/-18 mm. TLR was performed in all 23 patients with binary restenosis (33%). Death of cardiac cause was reported for two patients, one of whom did not undergo TLR. Thus, overall MACE rate was 35%. Recurrent ISR was significantly more frequent in patients with geographic miss. Comparison of the different radiation dose regimens revealed significantly lower LLL in patients irradiated with the higher dose (0.20+/-0.68 mm compared with 0.65+/-0.96 mm, P=0.03). CONCLUSION: Intracoronary brachytherapy with beta-radiation (Sr/Y) is a safe and effective therapeutic option for the reduction of recurrent ISR in long diffuse lesions. We recommend a high-dose irradiation with 18 Gy at 1 mm vessel wall depth.

Interplay between genetic and clinical variables affecting platelet reactivity and cardiac adverse events in patients undergoing percutaneous coronary intervention.

Several clinical and genetic variables are associated with influencing high on treatment platelet reactivity (HTPR). The aim of the study was to propose a path model explaining a concurrent impact among variables influencing HTPR and ischemic events. In this prospective cohort study polymorphisms of CYP2C19*2, CYP2C19*17, ABCB1, PON1 alleles and platelet function assessed by Multiple Electrode Aggregometry were assessed in 416 patients undergoing percutaneous coronary intervention treated with clopidogrel and aspirin. The rates of major adverse cardiac events (MACE) were recorded during a 12-month follow up. The path model was calculated by a structural equation modelling. Paths from two clinical characteristics (diabetes mellitus and acute coronary syndrome (ACS)) and two genetic variants (CYP2C19*2 and CYP2C19*17) independently predicted HTPR (path coefficients: 0.11 0.10, 0.17, and -0.10, respectively; p<0.05 for all). By use of those four variables a novel score for prediction of HTPR was built: in a factor-weighted model the risk for HTPR was calculated with an OR of 3.8 (95%CI: 3.1-6.8, p<0.001) for a score level of ≥1 compared with a score of <1. While MACE was independently predicted by HTPR and age in the multivariate model (path coefficient: 0.14 and 0.13, respectively; p<0.05), the coexistence of HTPR and age ≥75 years emerged as the strongest predictor of MACE. Our study suggests a pathway, which might explain indirect and direct impact of variables on clinical outcome: ACS, diabetes mellitus, CYP2C19*2 and CYP2C19*17 genetic variants independently predicted HTPR. In turn, age ≥75 years and HTPR were the strongest predictors of MACE.

Dual non-responsiveness to antiplatelet treatment is a stronger predictor of cardiac adverse events than isolated non-responsiveness to clopidogrel or aspirin.

BACKGROUND: High platelet reactivity (HPR) under treatment with clopidogrel or aspirin is associated with adverse outcome. We aimed to investigate whether high platelet reactivity (HPR) to both aspirin and clopidogrel is a stronger predictor of adverse events compared to isolated HPR to clopidogrel or aspirin. METHODS: In this prospective cohort study platelet reactivity to adenosine diphosphate (ADP) and arachidonic acid (AA) was assessed by Multiple Electrode Aggregometry (MEA) in 403 patients undergoing percutaneous coronary intervention. The rates of the composite of cardiac adverse events (acute coronary syndrome, stent thrombosis, stroke, death and revascularization) were recorded during 12-month follow-up. RESULTS: The composite endpoint of cardiovascular adverse events occurred more often in patients with high platelet reactivity (HPR) to both agonists ADP and AA (37.5%) than in those with isolated HPR to ADP (33.3%), AA (25.6%) or without any HPR (18.6%; p=0.003). Classification tree analysis indicated that any HPR emerged as an independent predictor influencing outcome, which was associated with a 1.75 higher risk of cardiac adverse events (OR=1.75: 95%CI=1.1-2.9). Interestingly, the predictive value of HPR tended to be greater among patients with diabetes mellitus (OR=2.18; 95%CI=1.20-3.95). C-reactive protein and diabetes mellitus were independent predictors of high platelet reactivity to both agonists. CONCLUSIONS: Dual low responsiveness to clopidogrel and aspirin is a strong predictor of cardiac adverse events, especially in patients with diabetes mellitus, which underlines the need for personalized antiplatelet treatment.