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This position statement is an update to the 2011 consensus statement of the Austrian Society of Cardiology (OKG) and the Austrian Society of Cardiac Surgery (OGTHG) 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 OKG and the OGHTG 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.

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.

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

Background and aim Automated image recognition based on machine learning methods was proven to be feasible in several medical imaging applications recently. Beside image classification methods to categorize input images for example into healthy or suspicious, image segmentation allows accurate localization of pathologies and thereby facilitates a wide area of applications. Because of the unique composition of every machine learning problem the applicability of image segmentation methods for detecting coronary pathologies in optical coherence tomography images remains unclear. Furthermore, the prediction accuracy of deep learning methods usually depends on vast amounts of training data which are often not available for particular medical questions. Therefore special strategies need to be applied to achieve satisfying results with smaller training datasets. We aimed to investigate the applicability of machine learning methods for plaque detection in coronary OCT images, especially considering the challenge of a small training dataset. Methods Originating from a dataset of 104 OCT frames containing calcified plaques, we performed image preprocessing using a custom build OCT image processing software to crop the luminal part as well as the areas outside the circular OCT signal to reduce entropy. Furthermore, plaques were identified and marked by an experienced OCT analyst, drawing plaque-enclosing polygonal masks using the same software. We also performed common image augmentation strategies, primarily applying rotation and zoom operations. Subsequently, we split the samples randomly into training, validation and test datasets (80:10:10%). To train the segmentation model, we fed the training and validation samples into an U-Net Convolutional Neuronal Network implementation with domain-specific adaptions using the RMSprop optimizer based on the publicly available PyTorch library. Results After 50 training epochs, we could achieve a prediction accuracy of 74.4% with the current configuration measured by the Sørensen–Dice coefficient comparing the similarity of the predicted plaque masks with the ground truth samples (figure 1 illustrates an exemplary comparison between predicted and ground truth plaque masks). Exemplary projection of a predicted mask Conclusion We were able to show that image segmentation based on machine learning strategies is a feasible way for automated plaque detection in coronary OCT imaging even based on small training datasets. Larger training datasets are necessary to raise prediction accuracy.

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162 ; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138 ; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571 )

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.

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.

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.

Die koronare Herzkrankheit (KHK; Synonym: coronary artery disease – CAD; stable ischemic heart disease – SIHD) ist definiert als Manifestation der arteriellen Verschlusskrankheit in den Herzkranzgefasen. Durch den Prozess der Arteriosklerose kommt es zur Bildung sogenannter Plaques, wodurch es zur Einengung des Gefaslumens kommt. Dies hat eine Minderdurchblutung des Herzmuskels zur Folge und fuhrt zu einem in Relation zum Sauerstoffverbrauch verminderten Sauerstoffangebot der Herzmuskelzelle. Man unterscheidet zwischen einer stabilen KHK, welche typischerweise durch das Leitsymptom der Angina pectoris (AP) charakterisiert ist, und der instabilen KHK, welche als akutes koronares Syndrom (Abb. 1) bezeichnet wird und den akuten Myokardinfarkt (ST-Elevations-Infarkt: STEMI, nicht-ST-Elevations-Infarkt: NSTEMI) bis zur instabilen Angina pectoris inkludiert. Open image in new window Abb. 1 Akutes Koronarsyndrom. (Kuch B. et al. J Kardiologie. 2003;10(3):103–6) Koronare Herzkrankheit: Erkrankung der arteriosklerotisch veranderten Koronargefase In der folgenden Ubersicht soll die stabile KHK abgehandelt werden. Es wird in der folgenden Ubersicht immer wieder auf Guidelines bzw. Klassen der Empfehlung und Evidenzlevels von diagnostischen Hilfsmitteln, Interventionen und Therapien eingegangen. Hier eine kurze Beschreibung: Klasse I: wird empfohlen Klasse IIa: Evidenz und Expertenmeinung widerspruchlich, Sachlage spricht aber eher fur Nutzen und Wirksamkeit Klasse IIb: wird eher nicht empfohlen Klasse III: wird nicht empfohlen, moglicherweise schadlich Evidenzlevel A: Daten aus mehreren randomisierten, klinischen Studien Evidenzlevel B: Daten aus einer einzigen randomisierten, klinischen Studie Evidenzlevel C: Expertenmeinung, Fallstudien, retrospektive Studien

Background— Whether intralesional abciximab administration and thrombus aspiration confer clinical benefits to patients undergoing primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction is controversial. Methods and Results— A total of 452 patients with ST-segment–elevation myocardial infarction caused by proximal or mid left anterior descending artery occlusion undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation were randomized in a 2×2 factorial design to bolus abciximab delivered locally at the infarct lesion site versus no abciximab and to manual thrombus aspiration versus no aspiration. Treatment with intralesional abciximab, thrombus aspiration, or both therapies compared with no active therapy before stent implantation resulted in lower 1-year rates of death (4.5% versus 10.4%; P =0.03), severe heart failure (4.2% versus 10.3%; P =0.02), and stent thrombosis (0.9% versus 3.8%; P =0.046). Between 30 days and 1 year of follow-up, treatment with intralesional abciximab compared with no abciximab was associated with a lower rate of death (1.4% versus 4.9%; P =0.04) and composite major adverse ischemic events (3.3% versus 7.8%; P =0.04), with nonsignificantly different overall 1-year rates of mortality, composite ischemic events, and heart failure–related events. Thrombus aspiration compared with no aspiration was associated with lower rates of new-onset severe heart failure between 30 days and 1 year (0.9% versus 4.5%; P =0.02) and of rehospitalization for heart failure from randomization to 1 year (0.9% versus 5.4%; P =0.0008), with nonsignificantly different rates of mortality. Conclusions— Intralesional abciximab and thrombus aspiration may have long-term benefits in patients with anterior ST-segment–elevation myocardial infarction presenting early after symptom onset and undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00976521.

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.

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

Objectives The aim of this landmark exploratory analysis, ATLANTIC-H 24 , was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study. Background The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). Methods The ATLANTIC-H 24 analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥70% ST-segment elevation resolution, and clinical endpoints over the first 24 h. Results Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. Conclusions The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580 ])

AIMS ST-elevation acute coronary syndrome (STE-ACS) is characterised by compromised blood flow at the epicardial and microvascular levels. Endothelin-1 (ET-1) is a mediator of microvascular dysfunction and adverse cardiac remodelling. We hypothesised that administration of an endothelin type A (ETA) receptor antagonist (BQ-123; Clinalfa, Laufelfingen, Switzerland) may protect microvascular function. METHODS AND RESULTS In this proof-of-concept, randomised, double-blind, placebo-controlled trial, patients with posterior-wall STE-ACS (n=57) were randomly assigned to receive intravenous BQ-123 at 400 nmol/minute or placebo over 60 minutes, starting at the onset of primary percutaneous coronary intervention (PCI). Time to myocardial contrast wash-in of the infarcted segment assessed by first-pass perfusion cardiac magnetic resonance imaging was the primary efficacy endpoint. Secondary endpoints included enzymatic infarct size and left ventricular ejection fraction (LVEF). In patients randomised to BQ-123 we observed shorter microvessel perfusion delays six days after PCI (1.8 sec [0.7-3.4] versus 3.3 sec [2.3-5.4] in placebo-treated patients, p=0.005). The treatment group demonstrated smaller enzymatic infarct sizes (p=0.014). All patients were alive at six months, with an LVEF of 63% (58-69) in patients randomised to BQ-123 and 59% (51-66) in placebo-treated patients (p=0.047). CONCLUSIONS Administration of an ETA receptor blocker during primary PCI in patients with STE-ACS is safe and may improve tissue-level perfusion and LVEF.

Taxus™ stent implantations with the aim of complete revascularization can be safe for patients with multivessel disease. The Austrian Multivessel Taxus Stent (AUTAX) registry including patients with post-percutaneous coronary intervention lesions provides additional information to the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) study.

Objectives The multicenter AUTAX (Austrian Multivessel TAXUS-Stent) registry investigated the 2-year clinical/angiographic outcomes of patients with multivessel coronary artery disease after implantation of TAXUS Express stents (Boston Scientific, Natick, Massachusetts), in a “real-world” setting. Background The AUTAX registry included patients with 2- or 3-vessel disease, with/without previous percutaneous coronary intervention (PCI) and concomitant surgery. Methods Patients (n = 441, 64 ± 12 years, 78% men) (n = 1,080 lesions) with possible complete revascularization by PCI were prospectively included. Median clinical follow-up was 753 (quartiles 728 to 775) days after PCI in 95.7%, with control angiography of 78% at 6 months. The primary end point was the composite of major adverse cardiac (nonfatal acute myocardial infarction [AMI], all-cause mortality, target lesion revascularization [TLR]) and cerebrovascular events (MACCE). Potential risk factor effects on 2-year MACCE were evaluated using Cox regression. Results Complete revascularization was successful in 90.5%, with left main PCI of 6.8%. Rates of acute, subacute, and late stent thrombosis were 0.7%, 0.5%, and 0.5%. Two-year follow-up identified AMI (1.4%), death (3.6%), stroke (0.2%), and TLR (13.1%), for a composite MACCE of 18.3%. The binary restenosis rate was 10.8%. The median of cumulative SYNTAX score was 23.0 (range 12.0 to 56.5). The SYNTAX score did not predict TLR or MACCE, due to lack of scoring of restenotic or bypass stenoses (29.8%). Age (hazard ratio [HR]: 1.03, p = 0.019) and acute coronary syndrome (HR: 2.1, p = 0.001) were significant predictors of 2-year MACCE. Incomplete revascularization predicted death or AMI (HR: 3.84, p = 0.002). Conclusions With the aim of complete revascularization, TAXUS stent implantations can be safe for patients with multivessel disease. The AUTAX registry including patients with post-PCI lesions provides additional information to the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) study. (Austrian Multivessel TAXUS-Stent Registry; NCT00738686)

Objective: To explore the morphological and functional effect of selective and non-selective endothelin (ET)-receptor blockade in coronary artery disease (CAD). Design: Prospective randomised controlled trial. Setting: University hospital. Patients: 26 patients with stable CAD. Interventions: Intracoronary infusion (30 minutes) of the ET-A receptor blocker BQ-123 (40 nmol/min, group A, n = 13) alone or with the ET-B receptor blocker BQ-788 (10 nmol/min, group AB, n = 13) as well. Main outcome measures: Fractional flow reserve (FFR), coronary flow reserve (CFR) and intramyocardial resistance (IMR) by PressureWire, mean arterial blood pressure (MAP), minimal lumen diameter (MLD) and average angiographic lumen diameter (mean LD) of the target vessel before and after intracoronary infusion of ET antagonists. Concentrations of C-terminal pro-endothelin-1 (CT-proET1) in arterial blood were determined before and after infusion. Results: Mean MLD, mean LD, FFR, CFR, IMR and MAP remained unaffected by ET-receptor blockade in both groups; their changes were comparable. Concentrations of CT-proET-1 increased by 6.2 (SD 5.9) pmol/l (95% CI 1.2 to 11.1 pmol/l; p = 0.022) in group A and by 4.1 (SD 4.3) pmol/l (95% CI 1.1 to 7.2 pmol/l; p = 0.014) in group AB. Conclusions: We found a broad variety of individual haemodynamic responses to ET-receptor antagonists with an overall neutral effect after an infusion period of 30 minutes despite an overall effective blockade of ET-receptors. Prolonged infusion time may be needed to cause a more distinct vasomotor response. Trial registration number: NCT00427232.

Udgivelsesdato: 2008-May-22 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].)

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.

Objectives The aim of this study was to assess the predictive potency of impaired endothelium-dependent flow-mediated vasodilation (FMD) in patients with chronic heart failure (CHF). Background Chronic heart failure is associated with reduced FMD; the prognostic impact of this observation is unknown. Methods Seventy-five ambulatory CHF patients (United Network of Organ Sharing [UNOS] status 2) with a left ventricular ejection fraction (LVEF) ≤30%, despite optimized medical therapy (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, 100%; beta-blocker, 81%), were evaluated. Using high-resolution ultrasound, FMD of the brachial artery was assessed in addition to other neurohormonal, clinical, and hemodynamic variables. Age, gender, New York Heart Association (NYHA) functional class, LVEF, hemodynamic variables, B-type natriuretic peptide (BNP) levels, medical therapy, cardiovascular risk factors, and FMD were analyzed for prediction of the combined end point conversion to UNOS status 1 or death in a multivariate Cox model. Results Up to three years, 21 patients (28%) converted to UNOS status 1, and 6 patients (8%) died. Univariate risk factors for the combined end point were log BNP (p = 0.0032), FMD (p = 0.0033), NYHA functional class (p = 0.0132), beta-blocker therapy (p = 0.0367), and mean blood pressure (p = 0.0406). In the multivariate analysis, only FMD (p = 0.0007), log BNP (p = 0.0032), and mean blood pressure (p = 0.0475) were independently related to the combined end point. In the Kaplan-Meier plot, significantly more patients with FMD 6.8% (p = 0.004). Conclusions In CHF, impaired FMD is a strong, independent predictor of conversion to UNOS status 1 or death.

ObjectivesThe aim of this study was to determine whether nicotine, a constituent of cigarette smoke, contributes to acute endothelial dysfunction after smoking one cigarette.BackgroundAnimal studies suggest that nicotine might cause an impairment of endothelium-dependent vasodilation via an increase in oxidative stress.MethodsSixteen 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).ResultsIn 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.ConclusionsThese 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.

Introduction: The polymers releasing the drug of first-generation drug-eluting stents (DES) may induce allergic reactions and inflammation, resulting in late-acquired stent malapposition (LASM) with uncoverage of struts, and risk of stent thrombosis. The incidence and predictors of LASM in DES with different polymers designed to improve biocompatibility are unknown. Methods: Fifty patients with 59 lesions of interest were randomized to elective treatment with Everolimus-eluting stents (EES; n=17, 20 lesions)], Zotarolimus-eluting stents (ZES; n=15, 19 lesions), and Biolimus-eluting stents (BES; n=18, 20 lesions) and underwent optical coherence tomography after implantation and after one year. Results: After implantation 29 early stent malappositions (ESM) were documented in 29 lesions (49% of lesions), distributed to 11 lesions treated with EES (55%), 11 with ZES (58%), and 7 with BES (35%; n.s.). After one year 14 late stent malappositions (LSM) in 14 lesions (24%) were detected; nine ESM persisted (EPSM) after one year (1 EES, 6 ZES, 2 BES), whereas 20 ESM resolved. In addition, 9 LASM were documented (5 LASM in early well-apposed Stents, 4 LASM in Stents which also have EPSM). LASM was present in 7 hydrophilic polymer-coated ZESs (37%), in 2 fluoropolymer-coated EESs (10%), and in none of the biodegradable polymer-coated BESs (p=0.003). Independent predictors of LASM were the vessel treated (RCA as vessel with high motion; p Conclusion: The incidence of ESM and EPSM were similar, whereas the incidence of LASM was different in second-generation DES with different polymers. Biodegradable polymer prevented LASM, stent locations with significant vessel movement (RCA) enhanced LASM.

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

OBJECTIVE Serum calcium was found to be an independent, prospective risk factor for myocardial infarction. We have previously shown that altered arterial reactivity in the course of primary hyperparathyroidism, a disease characterized by hypercalcaemia, may predominantly involve the arterial media and not the endothelium as observed in patients with various stages of atherosclerosis. The present study was performed to test whether successful parathyroidectomy can improve vascular reactivity in patients with primary hyperparathyroidism. SUBJECTS AND DESIGN Endothelium-dependent, flow-mediated and endothelium-independent, nitroglycerin-induced dilatation were assessed by brachial artery ultrasound (7 MHz) in 18 patients with primary hyperparathyroidism (mean ± SD; age, 55.1 ± 12.6) prior to and 3 years after successful parathyroidectomy. RESULTS Parathyroidectomy resulted in significant decreases of PTH (242 ± 186 vs. 34 ± 24 ng/l, P = 0.0001) and serum calcium levels (2.8 ± 0.3 vs. 2.4 ± 0.1 mm/l, P = 0.00001) and in an increase of serum phosphate levels (0.78 ± 0.23 vs. 1.17 ± 0.18 mm/l, P = 0.00001). However, normalization of hormone and electrolyte levels did not lead to an improvement of flow-mediated dilatation (12.1 ± 3.1 vs. 11.0 ± 5.4&, P = 0.49) or nitroglycerin-induced dilatation (12.5 ± 3.1 vs. 13.2 ± 6.8%, P = 0.68) within the follow-up period. No changes were observed with respect to the risk factor profile, vessel size and blood flow. CONCLUSION These data suggest that restoration of normocalcaemia by parathyroidectomy cannot improve vascular reactivity in patients with primary hyperparathyroidism but may prevent further progression of vascular disease within this period of time.

In summary, this study shows that CRP levels do not correlate with the extent and severity of coronary narrowing assessed by angiography. Other mechanisms such as acute inflammation with plaque instability and rupture may explain the higher cardiovascular event rate in patients with elevated CRP levels. 1. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340

Patients with primary hyperparathyroidism (PHPT) and/or hypercalcemia are at increased risk for myocardial ischemia. Whether PHPT is associated with altered endothelium-dependent dilation, vascular smooth muscle cell function, or both is unknown. This study was performed to test the hypothesis that endothelium-dependent, flow-mediated dilation (FMD) and/or endothelium-independent, nitroglycerin-induced dilation (NMD) is impaired in the preclinical phase of vascular disease in patients with PHPT.Twenty-six PHPT patients (mean +/- SD; age 55 +/- 15 y, serum calcium 3.00 +/- 0.37 mmol/l, serum phosphate 0.79 +/- 0.21 mmol/l, iPTH 249 +/- 262 pg/ml) with no evidence of coronary artery disease (CAD) as well as 26 normocalcemic control subjects (CTL; age 51 +/- 12 y) were studied. FMD following reactive hyperemia and NMD after 0.8 mg nitroglycerin (NTG) were assessed in the brachial artery by using high resolution ultrasound (7 MHz).NMD was impaired in PHPT patients compared to CTL (11.9 +/- 3.9% vs. 15.6 +/- 5.7%; p = 0.012). FMD was similar in both study groups (11.6 +/- 4.6% vs. 12.6 +/- 4.9; NS). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98 +/- 0.19 vs 0.81 +/- 0.25, p = 0.0009). On multiple stepwise regression analysis serum calcium was independently associated with the FMD/NMD ratio (r = 0.34, p = 0.017).Endothelium-independent vasodilation is impaired in PHPT patients without clinical evidence of coronary artery disease compared to normocalcemic CTL, while endothelium-dependent dilation was similar in both study groups. Thus, altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed previously in patients with various stages of atherosclerosis.

Recent studies suggest prophylactic intraaortic balloon-pulsation (IABP) in patients undergoing coronary reperfusion therapy. However, variable effects of IABP on coronary blood flow are reported. It is suggested that augmentation of coronary flow is more effective in patients with a compromised hemodynamic status, which might have potential relevance in selecting IABP treatment in patients undergoing reperfusion therapy.

Prognostic values of genotyping and phenotyping for assessment of clopidogrel responsiveness have been shown in independent studies.To compare different assays for prediction of events during long-term follow-up.In this prospective cohort study polymorphisms of CYP2C19*2 and CYP2C19*17 alleles, vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay, multiple electrode aggregometry (MEA), cone and platelet analyser (CPA) and platelet function analyser (PFA-100) were performed in 416 patients undergoing percutaneous coronary intervention. The rates of events were recorded during a 12-month follow-up.Platelet aggregation by MEA predicted stent thrombosis (2.4%) better (c-index = 0.90; P0.001; sensitivity = 90%; specificity = 83%) than the VASP assay, CPA or PFA-100 (c-index0.70; P0.05; sensitivity70%; specificity70% for all) or even the CYP2C19*2 polymorphism (c-index0.56; P0.05; sensitivity = 30%; specificity = 71%). Survival analysis indicated that patients classified as poor responders by MEA had a substantially higher risk of developing stent thrombosis or MACE than clopidogrel responders (12.5% vs. 0.3%, P0.001, and 18.5% vs. 11.3%, P = 0.022, respectively), whereas poor metabolizers (CYP2C19*1/*2 or *2/*2 carriers) were not at increased risks (stent thrombosis, 2.7% vs. 2.5%, P0.05; MACE, 13.5% vs. 12.1%, P = 0.556). The incidence of major bleedings (2.6%) was numerically higher in patients with an enhanced vs. poor response to clopidogrel assessed by MEA (4% vs. 0%) or in ultra-metabolizers vs. regular metabolizers (CYP2C19*17/*17 vs. CYP2C19*1/*1; 9.5% vs. 2%). The classification tree analysis demonstrated that acute coronary syndrome at hospitalization and diabetes mellitus were the best discriminators for clopidogrel responder status. Phenotyping of platelet response to clopidogrel was a better predictor of stent thrombosis than genotyping.

Ein 63-jahriger Mann bricht beim Tennisspielen zusammen und bleibt reglos liegen. Die anwesenden Personen konnen keine Atmung feststellen und beginnen mit der Herz-Lungen-Wiederbelebung. Die sofort alarmierte Rettung trifft 12 min nach dem Kollaps ein und setzt die Reanimationsmasnahmen fort. Der EKG-Monitor zeigt Kammerflimmern, der Patient wird sofort defibrilliert und die Reanimation fortgesetzt. Kurz darauf ist ein Puls tastbar, das EKG zeigt einen Sinusrhythmus mit zahlreichen ventrikularen Extrasystolen. Der Patient wird daraufh in intubiert und analgosediert. Der angeforderte Notarzthubschrauber transportiert den Patienten ins Krankenhaus. Dort wird ein ausgedehnter Vorderwandinfarkt festgestellt; der Patient erhalt sofort eine PTCA mit Stentimplantation und wird fur weitere 24 h auf 33 °C gekuhlt. Wenige Tage nach dem Ereignis kann er ohne neurologisches Defi zit die Rehabi litation antreten.

OBJECTIVE To describe the case of an adult patient with swallow syncope after bypass surgery, possibly related to hypoxia. DESIGN Case report. SETTING University hospital, medical-cardiologic intensive care unit. PATIENT A 67-yr-old patient after second aortocoronary bypass operation for unstable angina. MAIN RESULTS After the patient managed to extubate himself, he was in a borderline respiratory condition with an oxygen mask. When drinking for the first time after extubation, asystole was observed coincidentally with interruption of oxygen insufflation. During the next days, similar events occurred during food ingestion or when drinking liquids after a fall of oxygen saturation. The bradyarrhythmia was readily reversible on administration of atropine and ventricular backup pacing via temporary pacing wires. After normalization of gas exchange, no more episodes of swallowing-associated asystole were observed and the patient was discharged without a permanent pacemaker. There was no esophageal or gastrointestinal disease. Pre- and postoperative PR and QRS durations were normal. CONCLUSION Extrinsic and transient mechanisms, rather than intrinsic conduction system disease, seem to have been operative in this case. It is suggested that hypoxia reinforced the vagal pharyngocardiac reflex as described in pediatric patients.

The aim of this study was to assess the predictive potency of impaired endothelium-dependent flow-mediated vasodilation (FMD) in patients with chronic heart failure (CHF).Chronic heart failure is associated with reduced FMD; the prognostic impact of this observation is unknown.Seventy-five ambulatory CHF patients (United Network of Organ Sharing [UNOS] status 2) with a left ventricular ejection fraction (LVEF)or =30%, despite optimized medical therapy (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, 100%; beta-blocker, 81%), were evaluated. Using high-resolution ultrasound, FMD of the brachial artery was assessed in addition to other neurohormonal, clinical, and hemodynamic variables. Age, gender, New York Heart Association (NYHA) functional class, LVEF, hemodynamic variables, B-type natriuretic peptide (BNP) levels, medical therapy, cardiovascular risk factors, and FMD were analyzed for prediction of the combined end point conversion to UNOS status 1 or death in a multivariate Cox model.Up to three years, 21 patients (28%) converted to UNOS status 1, and 6 patients (8%) died. Univariate risk factors for the combined end point were log BNP (p = 0.0032), FMD (p = 0.0033), NYHA functional class (p = 0.0132), beta-blocker therapy (p = 0.0367), and mean blood pressure (p = 0.0406). In the multivariate analysis, only FMD (p = 0.0007), log BNP (p = 0.0032), and mean blood pressure (p = 0.0475) were independently related to the combined end point. In the Kaplan-Meier plot, significantly more patients with FMD6.8% (median) reached the combined end point, as compared with patients with FMD6.8% (p = 0.004).In CHF, impaired FMD is a strong, independent predictor of conversion to UNOS status 1 or death.

Objective To assess the efficacy of intracoronary brachytherapy with β-radiation ( 9 0 Sr/ 9 0 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 β-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 β-radiation ( 9 0 Sr/ 9 0 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 18Gy at 1 mm vessel wall depth.

Background: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are rare. The present series describes the 24-h hemodynamic effects of levosimendan as add-on therapy in desperately ill patients with cardiogenic shock requiring catecholamines. Methods: Ten patients with cardiogenic shock received levosimendan as continuous infusion of 0.1 µg kg−1 min−1 for 24 h. The patients were otherwise unselected. Hemodynamic measurements were routinely performed at baseline (time 0) and at 1, 8, 16 and 24 h after start of levosimendan (LS) using a Swan-Ganz thermodilution catheter. Results: During the levosimendan infusion there was a significant increase in cardiac index from 1.8 ± 0.4 to 2.4 ± 0.6 L*min−1*m−2 (P = 0.023) and a significant decrease in systemic vascular resistance from 1559 ± 430 to 1109 ± 202 dyn*s*cm−5 (P = 0.001), respectively. Changes in catecholamine dose, and in systolic and diastolic blood pressure were not significant. Given the individual response to LS, 8/10 patients showed an increase in left ventricular stroke work index under reduced or roughly unchanged preload conditions after 8 h. Conclusion: This series shows that a LS infusion is feasible and able to improve hemodynamics in severely compromized, critically ill patients with cardiogenic shock requiring catecholamine therapy. Its potential advantages when compared with other inotropes are unclear. To clarify the potential role of LS in this clinical setting randomized controlled trials on hemodynamic and mortality endpoints are needed.

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.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 (surgery9 years) and group B (surgeryor =9 years).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%, p0.001 and 12.9+/-8.0% vs. 18.8+/-9.2%, p0.01, respectively), both, in hypertensives (8.3+/-6.0%, p0.01 and 11.8+/-6.0%, p0.05) and in normotensives (8.1+/-6.5% p0.01 and 13.8+/-9.3%, p0.05). 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%, p0.0001 and 9.6+/-7.7% p0.001).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.

The relation of peripheral flow-mediated vasodilation and coronary arterial calcium was studied in young patients with heterozygous familial hypercholesterolemia (FH) using high-resolution ultrasound and multi-detector computed tomography (MDCT). We found that peripheral flow mediated vasodilation, a precursor of atherosclerosis, is altered in young heterozygous patients with FH. This alteration occurs before coronary arterial or aortic root calcium can be detected by MDCT and is independently related to hypercholesterolemia.

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.

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.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 volume20 mL/h associated with an increase in serum creatinine levelor = 0.5 mg/dL or50% above the baseline value.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; P0.001). 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.Acute renal failure was common in patients with cardiogenic shock and strongly associated with in-hospital mortality.

Objective To compare the rate-lowering effect of diltiazem and two amiodarone regimens in critically ill patients with recent-onset atrial tachyarrhythmias. Design Prospective, randomized, controlled study. Setting Medical cardiologic intensive care unit in a university hospital. Patients Sixty critically ill patients (Acute Physiology and Chronic Health Evaluation [APACHE] III score 70 +/- 30, age 67 +/- 10 yrs). Interventions Patients with atrial fibrillation (n = 57), atrial flutter (n = 2), or atrial tachycardia (n = 1, and a heart rate consistently >120 beats/min over 30 mins were randomly assigned to one of three intravenous treatment regimens. Group 1 received diltiazem in a 25-mg bolus followed by a continuous infusion of 20 mg/hr for 24 hrs, group 2 received amiodarone in a 300-mg bolus, and group 3 received amiodarone in a 300-mg bolus followed by 45 mg/hr for 24 hrs. Measurements and main results The primary study end point was a >30% rate reduction within 4 hrs. The secondary study end point was a heart rate 120 beats/min 4 hrs after study drug). The primary study end point was achieved in 14/20 (70%), 11/20 (55%), and 15/20 (75%) of patients in groups 1, 2, and 3, respectively (chi2 = 1.95, p =.38). Uncontrolled tachycardia was more frequently observed in group 2 (0/20, 9/29 [55%], and 1/20 [5%] of patients in groups 1, 2, and 3, respectively; chi2 = 17, p =.00016). In patients achieving tachycardia control, diltiazem showed a significantly better rate reduction (p =.0001 group 1 vs. group 3, p =.0001 over time; p =.0001 group 1 vs. group 2, p =.001 over time) when compared with the amiodarone groups. Premature drug discontinuation due to hypotension was required significantly more often in group 1 (6/20 [30%], 0/20, and 1/20 [5%] for groups 1, 2, and 3, respectively; chi2 = 10, p =.01). Conclusion Sufficient rate control can be achieved in critically ill patients with atrial tachyarrhythmias using either diltiazem or amiodarone. Although diltiazem allowed for significantly better 24-hr heart rate control, this effect was offset by a significantly higher incidence of hypotension requiring discontinuation of the drug. Amiodarone may be an alternative in patients with severe hemodynamic compromise.

Background —Chronic heart failure (CHF) is associated with impaired endothelium-dependent vasodilation and increased basal vascular tone due, in part, to elevated endothelin-1 plasma levels. In the present study, we investigated whether a reduction of vascular tone using an endothelin A receptor blocker attenuates the impairment of endothelium-dependent, flow-mediated vasodilation (FMD). Methods and Results —Twenty-one patients with CHF randomly received either the endothelin A receptor blocker LU 135252 (30 mg/d, n=7; 300 mg/d, n=7) or a placebo (n=7). Using high-resolution ultrasound, FMD and endothelium-independent, nitroglycerin-induced dilation of the brachial artery were assessed at baseline in the 21 patients with CHF and in 11 controls and after 3 weeks treatment in the 21 patients with CHF. FMD at baseline was impaired in all 21 patients with CHF (3.2±2%) when compared with the 11 controls (9.7±4.9%; P =0.0005). In comparison with baseline, FMD significantly improved after 3 weeks of treatment with LU 135252 in all 14 patients receiving it (from 3.0±2.0% to 4.9±2.9%; P =0.04), but FMD remained unchanged with placebo. Subgroup analysis, according to different dosages, revealed a significant increase of FMD compared with baseline (from 2.4±1.5% to 5.5±2.4%; P =0.03) in the patients treated with the low-dose (30 mg/d), whereas a high dose of 300 mg/d failed to increase FMD significantly. Improvement in the high-dose group, however, may have been masked by reduced vasodilator capacity due to a significant increase in vessel size (from 4.8±0.4 to 5.1±0.7 mm; P =0.03). Conclusions —These results suggest that endothelin A receptor blockade improves FMD in CHF patients.