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A role of the potent and long-acting vasoconstrictor peptide endothelin-1 and the pathophysiology of chronic human heart failure has been postulated based upon indirect evidence such as elevated plasma endothelin-1 levels and their with the degree of hemodynamic impairment. The advent of specific of endothelin-1 receptor antagonists has provided the opportunity not only to directly evaluate its pathophysiological role but also to assess its potential role as a new approach to heart failure therapy. This brief review summarizes the evidence linking endothelin-1 to the pathophysiology of chronic heart failure and the clinical results obtained in patients during acute, intravenous and more prolonged, oral administration with bosentan, a mixed ET(A)/ET(B)-receptor antagonist. Bosentan acutely and during short-term oral therapy markedly improved hemodynamics in patients in addition to standard heart failure therapy, including an ACE-inhibitor. These effects were associated with a reduced responsiveness of the renin-angiotensin system to diuretic therapy and reduced basal plasma aldosterone levels. Although the hemodynamic and neurohumoral profile of short-term bosentan therapy looks promising for the treatment of patients with chronic heart failure appropriate trials will have to be performed to document clinical benefit during long-term therapy. Finally, the question remains open whether mixed endothelin-1 receptor antagonists like bosentan will have similar effects as compared to antagonists which block the ET(A) receptor only. [ABSTRACT FROM AUTHOR]

We studied acute (day 1) and long-term (day 14) effects of endothelin (ET) receptor blockade with the mixed ET(A/B) antagonist bosentan (1 g twice daily; n = 18) or placebo (n = 12) on plasma angiotensin II and aldosterone in 30 patients with symptomatic chronic heart failure taking angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Hormones were determined before and 3 hours after morning doses of diuretics and digoxin and the double-blind study drug, respectively, on days 1 and 14. On day 1, angiotensin II increased from 16.1+/-17.9 to 27.6+/-5.6 ng/L (p <0.05) with bosentan and similarly with placebo (15.5+/-9.3 and 36.0+/-49.1 ng/L, p = 0.06) after the morning dose of diuretics and digoxin. Aldosterone tended to increase from 322+/-239 to 362+/-254 pmol/L (bosentan) and from 271+/-70 to 297+/-136 pmol/L (placebo). On day 14, before drug intake, angiotensin II was unchanged compared with day 1 in both groups. However, aldosterone was lower than on day 1 with bosentan (213+/-124 vs. 322+/-239 pmol/L, p<0.05) and remained below baseline values 3 hours after drug intake, whereas it was unchanged with placebo. Thus, short-term ET(A/B) receptor antagonism decreases basal aldosterone secretion independently of angiotensin II, suggesting that ET participates in the regulation of aldosterone in patients already treated with angiotensin-converting enzyme inhibitors and diuretics. [ABSTRACT FROM AUTHOR]

The role of aortic diameter on the occurrence of type A dissection was investigated in 73 patients with dilated ascending aorta at the lime of pre-operative evaluation. Using transthoracic echocardiography for diagnosis and measurements, 54 patients were identified with type A dissection (group 1) and 19 without dissection (group 2). The true mean aortic diameters were identical (6·0±1·3 cm in group 1 and 6·4±1·4 cm in group 2; mean±SD; ns) as were the indexed aortic diameters (ratio of diameter/body surface area; 3·2±0·8 cm . m2 and 3·4±0·7cm m respectively; ns). However, the individual diameters showed a pronounced scatter in both groups (range from 3·6±11·0 cm). Of the 73 patients, 66 had surgery (47/54 with and 19/19 without dissection) and seven patients were treated medically. Emergency surgery was performed in 45/66 patients (all with acute type A dissection) andelective repair in 21/66 (19 without and two with chronic type A dissection). In-hospital mortality was 18% in the emergency group, 5% in the elective group and 57% in the medical group. It is concluded that patients with dilated ascending aorta have a substantial incidence of acute dissection. Their clinical course is unpredictable; acute dissection occurs in some, and in others the ascending aorta continues to enlarge without dissection. Because patients with dissection often arrive too late for elective repair andhave to be operated on as emergencies with a higher operative risk, we recommend elective surgery before the diameter of the ascending aorta has reached 6 cm. [ABSTRACT FROM PUBLISHER]

Background: Feasibility of transfemoral (TF) transcathteter aortic valve replacement (TAVR) is limited by the smallest diameter, the calcification and tortuosity of the iliofemoral access vessels. The use of the Portico system without delivery sheath results in significantly lower profile delivery system compared to standard technique. We herein report our single center experience, feasibility and safety of such an approach., Methods: The Portico valve was implanted sheathless in 81 high-risk patients with severe aortic stenosis utilizing percutaneous femoral access. Mean minimal diameter of the ileo-femoral arterial access was 7.06 ± 1.89 mm. In most cases a multidetector computed tomography was performed before the intervention to assess the feasibility of vascular access and for aortic annulus measurements. The vascular access site was preclosed using two ProGlide suture systems., Results: Device implantation was successful 98.7% of patients. Valve recapturing and repositioning as well as valve-in-valve deployment was performed in only one case (1.2%). There were no infarctions, 2 strokes (2.4%) and 2 acute kidney failure (2.4%), 1 major vascular complication1 (1.2%) 4 major bleedings (4.9%), 11 conductions disturbances and relative pace-maker implantations (14.2%). The mean gradient decreased from 42.3 ± 17 to 6.3 ± 2.78 mm Hg. Paravalvular regurgitation as assessed by TTE at discharge was absent or trivial in 19 patients, mild in 60 and moderate 1. Thirty-day mortality was 2.4%., Conclusions: Sheathless use of the Portico valve is feasible and appears to be safe, with excellent rates of complications and mortality in the short-term. Such an approach has the potential to further expand feasibility of TF TAVR to patients with severe peripheral arterial disease. Feasibility in patients with smaller femoral access and more challenging anatomy has to be proven in further studies. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Aims: The use of left atrial appendage (LAA) occluders in atrial fibrillation is increasing. There are few data on the comparison between transesophageal echocardiography (TEE) and computed tomography (MDCT) assessing peridevice flow and outcome of electrical cardioversion (ECV) in these patients., Methods and Results: Single-center prospective registry from 2009 to 2015 including all LAA occluders to analyze success and complications during implantation and follow-up. Patients having ≥1 ECV were further analyzed. TEE was performed during implantation and at 6 weeks. In a subgroup of 77 patients, we compared MDCT with TEE at 6 weeks. Overall, 135 patients (69 ± 9 years; 70% male; CHA 2 DS 2 -VASc score: 3.6 ± 1.4; HAS-BLED score: 2.5 ± 0.6) received a LAA occluder (Watchman, n = 73; ACP-1, n = 59; Amulet, n = 3; PVI + LAA occluder, n = 91; and LAA occluder only, n = 44). Device implantation was successful in 131 (97%). Eight patients (5.9%) had major periprocedural complications (ischemic stroke/transient ischemic attacks, n = 4, tamponade, n = 2, device thrombosis, n = 2, Dressler syndrome, n = 1). The periprocedural complication rate was similar between concomitant procedure and LAA occluder only (8/91 vs. 5/44; P = 0.6). Twelve patients (9%) died (procedure-related, n = 2; 1%) during follow-up of 44 months (IQR: 43). MDCT (n = 77) at 6 weeks showed similar peridevice flow compared to TEE (TEE: 1.5 ± 1.9 mm vs. MDCT: 1.1 ± 2.2 mm, P = 0.25). Thromboembolic events occurred in 3 patients (CVA, n = 1; TIA, n = 2) during follow-up. In total, 41 ECV were performed in 26 patients (1.6 ± 0.9/patient), 13 months (IQR: 24) after implantation (<1 month: n = 8). No ECV-related clinical complications were observed., Conclusion: LAA occlusion is feasible with an acceptable safety profile and few events during long-term follow-up. ECV after LAA occlusion is feasible. MDCT could help to evaluate peridevice flow., (© 2017 Wiley Periodicals, Inc.)

Aims: Circular irrigated radiofrequency ablation using the nMARQ catheter has recently been introduced for the treatment of atrial fibrillation (AF). The aim of this study is to report the safety and efficacy of catheter ablation using this technology in patients with paroxysmal and persistent AF., Methods and Results: The data of a prospective registry describing the experience of a single operator using this technology on 327 consecutive patients were analysed. The mean procedure time was 69 ± 22 min for paroxysmal AF (n = 228) and 75 ± 23 min for persistent AF (n = 97). Follow-up was available for 206 (63%) patients for 6 ± 5 months (range 1-23, median 3.3). Single procedure success off antiarrhythmic drugs was 75% in paroxysmal AF and 52% in persistent AF. Including the 5% redo cases and those on antiarrhythmic medication, freedom from AF was documented in 90 and 83% of paroxysmal and persistent AF patients, respectively. There were no serious complications in the first 325 patients, but the last two consecutive patients (0.6%) developed atrio-oesophageal fistulas and had a fatal outcome. The catheter has been recalled from market., Conclusion: The nMARQ catheter is a highly effective tool for treatment of paroxysmal and persistent AF. Nevertheless, the occurrence of life-threatening oesophageal fistulas is of major concern and requires further investigation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: For successful cardiac resynchronisation therapy (CRT) a spatial and electrical separation of right and left ventricular electrodes is essential. The spatial distribution of electrical delays within the coronary sinus (CS) tributaries has not yet been identified., Objective: Electrical delays within the CS are described during sinus rhythm (SR) and right ventricular pacing (RVP). A coordinate system grading the mitral ring from 0° to 360° and three vertical segments is proposed to define the lead positions irrespective of individual CS branch orientation., Methods: In 13 patients undergoing implantation of a CRT device 6±2.5, (median 5) lead positions within the CS were mapped during SR and RVP. The delay to the onset and the peak of the local signal was measured from the earliest QRS activation or the pacing spike. Fluoroscopic positions were compared to localizations on a nonfluoroscopic electrode imaging system., Results: During SR, electrical delays in the CS were inhomogenous in patients with or without left bundle branch block (LBBB). During RVP, the delays increased by 44±32 ms (signal onset from 36±33 ms to 95±30 ms; p<0.001, signal peak from 105±44 ms to 156±30 ms; p<0.001). The activation pattern during RVP was homogeneous and predictable by taking the grading on the CS ring into account: (% QRS) = 78-0.002 (grade-162)(2), p<0.0001. This indicates that 78% of the QRS duration can be expected as a maximum peak delay at 162° on the CS ring., Conclusion: Electrical delays within the CS vary during SR, but prolong and become predictable during RVP. A coordinate system helps predicting the local delays and facilitates interindividual comparison of lead positions irrespective of CS branch anatomy.

Purpose: Optimal atrioventricular delay (AVD) setting for cardiac resynchronisation therapy, i.e. biventricular pacing in patients with heart failure, remains a formidable challenge. Thus, the purpose of this study was to evaluate the effects of different AVD on inter- and intra-ventricular resynchronisation using phase histograms of radionuclide ventriculography (RNV)., Methods: In 17 consecutive patients (mean age 64 +/- 6 years), RNV was performed 236 +/- 350 days after pacemaker implantation for cardiac resynchronisation therapy. Images were acquired during atrial pacing at 80 bpm and during biventricular pacing with AVD ranging from 80 to 160 ms. Inter-ventricular dyssynchrony was measured by the delay between the mean phase angles of the left and right ventricles. Intra-ventricular dyssynchrony was measured by the standard deviation (SD) of left ventricular phase histograms., Results: Left ventricular (LV) ejection fraction (EF) was inversely correlated to LV dyssynchrony (SD of LV phase histogram, R = -0.82, p < 0.0001). However, the increase in LVEF by biventricular pacing (mean +4.4 +/- 4%) showed only modest correlation to the resulting resynchronisation effect (characterised by a -13 +/- 8 degrees decrease in LV phase histogram SD, R = -0.38, p < 0.0001)., Conclusion: RNV is helpful in optimising pacing parameters for resynchronisation therapy. Varying AVD did not have a major impact on intra- or inter-ventricular resynchronisation. Thus, the benefit of AVD-based LVEF optimisation seems to result from atrioventricular resynchronisation.

Distal embolization during primary percutaneous coronary intervention (PCI) occurs in at least 15% of patients and is a strong predictor of more extensive myocardial damage and a poor prognosis. Several devices are designed to evacuate the intracoronary thrombus or to prevent distal embolization. The Proxis device is a proximal embolic protection system that completely blocks antegrade flow during PCI. It may prevent distal embolization during recanalization of thrombotic coronary occlusion and thus improve outcome. We created a registry of 172 patients with ST-segment elevation myocardial infarction who underwent primary PCI with proximal embolic protection and aspiration. The mean ST-segment elevation resolution (STR) at 1 hour was 77.7%+/- 15.2; STR was greater than 50% in 94% and greater than 70% in 72% of patients. The 1-year cumulative major adverse cardiac and cerebrovascular events rate was 10.5%. The overall mortality at 1 year was 2.3%.

Aims: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS)., Methods and Results: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset., Conclusion: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.

Background: Crossing chronic total occlusions (CTO) of coronary arteries continues to challenge interventional cardiologists. A clinical study was undertaken in four European centers to examine the feasibility of using the new CROSSER system that utilizes high-frequency mechanical vibration to penetrate atherosclerotic plaque material to cross CTOs in patients where conventional guidewire techniques had failed. The objective of the study was to determine whether the CROSSER system could safely cross such CTOs., Patients and Methods: A total of 55 CTO lesions in 53 patients were treated in two clinical phases: (1) Phase 1 feasibility study (30 CTOs), with a primary focus on device safety; and (2) Phase 2 pivotal study (25 CTOs) using an improved version of the device, with a primary focus on effectiveness., Results: The primary endpoint of device efficacy and the secondary endpoint of clinical success were both 76% (19 of 25) in the pivotal study phase. No major adverse cardiac events of death, Q-wave myocardial infarction or target lesion revascularization (by either coronary artery bypass graft surgery or percutaneous coronary intervention) were observed through 30-day follow up. No coronary perforation or pericardial tamponade occurred., Conclusions: The CROSSER system is a safe device that can cross many occlusions after a conventional guidewire failure. With additional refinement and improvements to the device, this success rate could be further increased.

Different embolic protection devices have been introduced for endovascular interventions: filters or balloon occlusion and aspiration systems. Despite widening use in a variety of vascular beds and clinical syndromes, little is known about the particulate burden liberated from different vascular beds and caught by different protection devices. We performed histologic and morphometric analyses of particulate debris captured during stenting of degenerated saphenous vein bypass grafts and native coronary arteries during acute myocardial infarction or during elective intervention and carotid arteries to assess the relative performance of different protection devices. We analyzed 232 interventions (90 saphenous vein bypass grafts, 77 native coronary arteries, and 65 carotid arteries) with 4 different devices (65 FilterWires, 99 Interceptors, 41 GuardWires, and 27 Proxis catheters) using the RapidVue particle analyzer. No difference in embolic volume retrieved was demonstrated between devices in saphenous vein bypass grafts and carotid interventions. A smaller volume of particulate debris was retrieved by the GuardWire compared with the FilterWire and the Proxis catheter in native coronary artery interventions. The Interceptor and the GuardWire captured more smaller particles than did the FilterWire or Proxis catheter. During saphenous vein bypass graft or carotid intervention, different embolic protection strategies were performed similarly. In native coronary artery stenting, however, proximal embolic protection retrieved larger amounts of debris than did distal filters or occlusion devices. These data may allow greater tailoring of embolic protection device development and application in specific anatomic locales.

We describe the case of a 45-year-old male smoker who presented with an acute anterior wall myocardial infarction and a platelet count on admission of 1030000/mm3. Emergent coronary angiography revealead left anterior wall akinesia caused by a spontaneously resolved thrombosis of the left anterior descending artery with residual stenosis. Primary percutaneous coronary angioplasty and stenting were performed. Postangioplasty course was uneventful. He was diagnosed with essential thrombocythemia based on the findings of marked thrombocytosis of 1,030,000/mm3, splenomegaly and numerous clumping giant megakaryocytes on bone marrow biopsy. In addition to standard therapy with aspirin, heparin, betablocking agent, ACE-inhibitor and statine he received additional anti-platelet therapy with Clopidogrel. Cytoreductive therapy was not necessary.

Positional anomalies of the heart are rare and are seldom found during routine physical examinations. We describe the case of a 25-yr-old Swiss airline pilot candidate whose aeromedical examination was normal except that an unusual ECG raised suspicion, leading to a diagnosis of dextrocardia with a normal arrangement of atria and abdominal viscera. This diagnosis in a pilot candidate should raise concern because a high percentage of such individuals have congenital heart defects. Further tests were conducted to rule out associated cardiac malformations, conduction anomalies, or rhythm disturbances. Testing also excluded other associated diseases such as primary ciliary dyskinesia and Kartagener's syndrome. Dextrocardia is not listed as a disqualifying condition in the applicable aeromedical regulations (Joint Aviation Authorities Medical Manual, Joint Aviation Requirements-Flight Crew Licensing guidelines). Therefore, after demonstrating that there were no physical, hemodynamic, or electrophysiological abnormalities, the candidate was allowed to enroll in civilian pilot training without restrictions.

Objectives: The purpose of this prospective study was to investigate the impact of the gender of physicians and patients on the accuracy of diagnosing coronary artery disease (CAD) based on the patient history only., Methods: Screening involved 1082 consecutive patients undergoing coronary angiography for suspected CAD. Known CAD was an exclusion criterion. The inclusion criteria were met by 144 patients (47 females). All patients were inverviewed by both an experienced male cardiologist (n=6) and an experienced female cardiologist (n=5), who had to state before coronary angiography if CAD was present relying solely on the patient interview. Eligible subjects also answered a questionnaire. Diagnostic performance to assess the presence or absence of CAD by history taking by male and female cardiologists, exercise testing, patient self-assessment, and the questionnaire were compared., Results: Coronary angiography showed significant CAD in 20 females (43%) and 70 males (72%). Diagnostic accuracy was not different between male (79%) and female (79%) cardiologists and comparable to the results of exercise testing (74%) but better than self-assessment by the patients (65%, p=0.01) or a questionnaire (68%, p=0.01). The accuracy of female physicians was better in men than in women (85% vs. 66%, p=0.01). The specificity of male physicians tended to be better in women than in men (74% vs. 59%, p=0.25). Female cardiologists overestimated the presence of CAD in women (specificity 48% vs. 74%, p=0.04)., Conclusions: The female cardiologists did not assess women more accurately than did their male colleagues. The diagnostic accuracy of these male and female cardiologists was quite good. However, both tend to assess patients of the opposite gender more specifically. There may be an impact of the gender of the physician on the accuracy of diagnosis of CAD by history taking.

The aim of this study was to assess costs and safety of immediate femoral sheath removal and closure with a suture-mediated closure device (Perclose, Menlo Park, CA) in patients undergoing elective (PCI). A total of 193 patients was prospectively randomized to immediate arterial sheath removal and access site closure with a suture-mediated closure device (SMC; n = 96) or sheath removal 4 hr after PCI followed by manual compression (MC; n = 97). In the SMC group, patients were ambulated 4 hr after elective PCI if hemostasis was achieved. In the MC group, patients were ambulated the day after the procedure. In addition to safety, total direct costs including physician and nursing time, infrastructure, and the device were assessed in both groups. Total direct costs were significantly (all P < 0.001) lower in the SMC group. Successful hemostasis without major complication was achieved in all patients. The time to achieve hemostasis was significantly shorter in the SMC group (7.1 +/- 3.4 vs. 22.9 +/- 14.0 min; P < 0.01) and 85% of SMC patients were ambulated on the day of intervention. Suture-mediated closure allows a reduction in hospitalization time, leading to significant cost savings due to decreased personnel and infrastructural demands. In addition, the use of SMC is safe and convenient to the patients., (Copyright 2002 Wiley-Liss, Inc.)

Recent advances in the recognition and the treatment of acute coronary syndromes (ACS) have lead to an improvement in patient survival and definition of newer guidelines. Current strategies for the treatment of patients with non-ST-elevation ACS include anti-ischemic and antiplatelet medications. While aspirin, beta-blockers, heparin and nitrates are still common practice, the advent of newer anticoagulants (low molecular weight heparins) and antiplatelet agents (glycoprotein llb/IIIa inhibitors and thienopyridines like ticlopidin and clopidogrel) and, possibly, aggressive lipid lowering with statins have added significant benefits to the treatment options with a better prognosis for these patients. Moreover, aggressive medical strategies seem to be justified not only in high-risk patients but also in those that undergo an early invasive approach.

Natriuretic peptides play an important role in water and salt homeostasis and in the regulation of the cardiovascular system. In recent years, exogenous administration of natriuretic peptides has primarily been used to improve our understanding of the role of natriuretic peptides. Also, it became evident that natriuretic peptides may be used therapeutically. Because of their peptide character, they cannot be administered orally and, therefore, may be used for short-term intravenous therapy only. In recent years, inhibitors of neutral endopeptidase, which degrades natriuretic peptides to inactive metabolites, have been investigated. This review focuses on the potential benefits of increasing natriuretic peptide levels, either through exogenous administration or inhibiting the degradation of endogenous natriuretic peptides.

A role of the potent and long-acting vasoconstrictor peptide endothelin-1 in the pathophysiology of chronic human heart failure has been postulated based on indirect evidence such as elevated plasma endothelin-1 levels, their correlation with the degree of hemodynamic impairment, and their predictive value for patient survival. The advent of specific of endothelin-1 receptor antagonists has provided the opportunity to directly evaluate its pathophysiologic role and assess its potential role as a new approach to heart failure therapy. This review summarizes the evidence linking endothelin-1 to the pathophysiology of chronic heart failure, and analyzes the clinical results obtained thus far in patients during acute intravenous, and more prolonged, oral administration of endothelin-1-receptor antagonists.

Endothelin-1 (ET-1) regulates vascular tone in congestive heart failure and modulates renal function. Its role in patients with normal left ventricular (LV) function and its renal effects are unclear. Cardiac and renal hemodynamics were studied in 24 patients with normal LV function and coronary arteries after single-dose, double-blind, randomized administration of TAK-044 (25, 50, or 100 mg, i.v.), an ET(A/B)-receptor antagonist, or placebo. Hemodynamics were monitored using Swan-Ganz and arterial catheters, and ET levels were measured. Renal function was assessed by clearance techniques. In the absence of a dose-response relation, TAK-044 patients were analyzed as a single group. Most hemodynamic effects occurred during the first 4 h. TAK-044 reduced mean arterial (-9.3 mm Hg, p < 0.001), pulmonary (-1.8 mm Hg, p = 0.01), and pulmonary capillary wedge pressure (-1.6 mm Hg, p < 0.001) between 30 min and 4 h. Mean reduction in systemic vascular resistance was 279 dyne/s/cm2 (p < 0.001), whereas heart rate increased 6.1 beats/min (p < 0.001) and cardiac index by 0.37 L/m2 (p = 0.01). Stroke volume index, right atrial pressure, and pulmonary vascular resistance did not change. TAK-044 increased renal plasma flow in proportion to the increase in cardiac output (+119 ml/min, 4 h after TAK-044; p < 0.05) and ET-1 levels (2.5-fold; p < 0.05). No serious side effects were noted. In patients with normal cardiac function, ET-receptor blockade causes vasodilation and reduces systemic but not pulmonary vascular resistance and increases cardiac index and renal plasma flow.

Background: Prevention of distal embolisation during percutaneous coronary revascularisation may be necessary to reduce postinterventional morbidity and mortality., Methods and Results: We employed a newly developed emboli containment and retrieval system in native coronary arteries during percutaneous coronary angioplasty and stenting in 39 selected patients (mean age 58.9 +/- 10.1 years, 11 females) presenting with acute (n = 22; 8 LAD, 3 LCX, 11 RCA), subacute (n = 7; 2 LAD, 2 LCX, 3 RCA) or chronic (n = 6; 2 LAD, 4 RCA) total or subtotal occlusion of an infarct-related vessel, or with severe stenosis and symptoms of unstable angina (n = 4; 2 LAD, 2 RCA). Protection device-assisted angioplasty with stent implantation was uneventful in all patients with good angiographic results and normal postprocedural flow. Intermittent aggravation of anginal pain during inflation of the occlusive balloon (from 2.5 to a maximum of 25 minutes cumulative inflation time) was observed in 19 of the 36 conscious patients (7 with acute, 7 with subacute and 3 with chronic occlusion, and 2 with unstable angina), but caused neither interruption of distal occlusion nor haemodynamic instability. In 31 patients the aspirates contained visible debris. Histological analysis showed particles up to 12 mm in size, consisting of necrotic core, inflammatory cells, cholesterol debris, and old and fresh thrombi. In 8 patients the aspirated particles were too small to allow microscopic diagnosis or debris was absent., Conclusions: This preliminary report demonstrates the feasibility of using a protection device in native coronary arteries to prevent distal embolisation of particulate matter that is mobilised during percutaneous interventions. To the extent that this material contributes to the mechanisms of distal embolisation, noreflow and infarction, this device may help to reduce such complications. Appropriately designed trials are required to assess the clinical benefit of this system.

Background: Cardiac allograft vasculopathy after heart transplantation leads to an accelerated form of atherosclerosis with marked and often diffuse vessel wall changes that limit long-term survival. Previous studies showed contradictory results relating vessel wall changes to endothelial vasodilator response., Methods: A total of 30 cardiac transplant recipients were studied 3, 12, and 24 months after heart transplantation. Coronary angiography was performed at rest, during supine bicycle ergometry, and after 1.6 mg sublingual nitroglycerin. Coronary cross-sectional area (biplane coronary angiography) and coronary artery wall changes (intravascular ultrasound) were assessed and extent of intimal changes correlated to vasodilator responses to nitroglycerine and bicycle ergometry., Results: Intravascular ultrasound showed significant intimal thickening in 43, 64, and 58% of patients at 3, 12, and 24 months. Intimal thickening 3 months after transplantation was related to donor age (r=0.70, P<0.01) but did not predict progression of disease that manifested itself angiographically as a decrease in coronary cross-sectional area at 12 and 24 months (P<0.005) and significant coronary stenosis in 12% of patients after 24 months. Endothelium-independent vasodilatation after nitroglycerin (33+/-15, 44+/-20, and 43+/-24%) was normal. Endothelium-dependent, flow-induced vasodilatation during exercise was decreased (14+/-11, 18+/-14, and 16+/-17%) but did not correlate to intimal changes assessed by ultrasound., Conclusions: The study confirms the high incidence of intimal thickening after heart transplantation as assessed by intravascular ultrasound. Impaired exercise-induced vasodilatation suggests diminished bioavailability of endothelium-derived nitric oxide to physiological stimulation but the lack of relationship between coronary wall changes and this functional impairment suggests intermittent and presumably reversible endothelial injury in graft atherosclerosis.

Endothelin (ET)-1 is a potent vasoconstrictor with growth promoting and mitogenic properties associated with various cardiovascular diseases (CVD) and has been found to be an important protagonist in congestive heart failure (CHF). The introduction of ET-1 receptor antagonists into the arena of clinical research has amplified our understanding of the ET system: the first human trials with acute and chronic inhibition of the ET system have shown promising results and confirm the findings from experimental models. The availability of oral compounds such as bosentan has raised the hope that these novel drugs might become a new therapeutic class of agents for the treatment of CVD and, in particular, of CHF. The question, however, remains whether the beneficial effects observed so far in patients with CHF go beyond simple hemodynamic improvements and whether these compounds improve long-term survival in these patients.

Coronary artery stenting has definitely been proven to improve results of percutaneous revascularisation in a large number of patients. Stenting reduces restenosis in large vessels above 3 mm diameter. Stenting has not solved the problem of restenosis but in spite of the inevitable in-stent restenosis due to neointimal proliferation seems to yield better long-term results than conventional PTCA. Adjunctive pharmacological treatment with aspirin and clopidogrel in combination with improved stent deployment techniques has reduced the incidence of subacute stent thrombosis. GP IIb/IIIa inhibition is a promising mean for the reduction of procedure related ischaemic events and complications not only with stent implantation but also with conventional PTCA. Other new devices may further influence the treatment choices of stenting versus conventional PTCA in the future. Novel approaches such as brachytherapy and molecular genetic approaches to reduce in-stent restenosis are currently being investigated but to date no conclusions can be drawn as to their future place in clinical practice. From a mechanistic standpoint it seems obvious to give all our efforts to protect patients with coronary atherosclerosis from loss of myocardium either with coronary artery bypass grafting or percutaneous revascularisation. As both approaches are palliative in nature, it may be useful to attempt percutaneous revascularisation in patients amenable to this therapy and thus obviate or delay the need for definitive revascularisation by coronary artery bypass grafting. At the end of this discussion we would like to remind that medical therapy for coronary artery disease is of utmost importance as all revascularisation procedures do not influence the underlying disease. Besides symptomatic relief of angina, treatment of heart failure, and other beneficial strategies to improve endothelial function, medical therapy with lipid lowering compounds together with risk factor control offers the possibility to delay progression of coronary artery disease.

Congestive heart failure is a complex disease that results from pumping failure of the cardiac muscle and adaptational processes of the cardiovascular system to correct for the reduced blood supply to the organism. It is associated with increased vasoconstriction and impaired vasodilation in response to physical activity. The elevated vasoconstrictor tone is caused by the activation of compensatory mechanisms including the sympathetic nervous system and stimulation of the release of neurohormones like angiotensin II, catecholamines, and vasopressin. Furthermore, the vascular endothelium is importantly involved in the regulation of vascular tone as it releases a variety of vasoactive substances that act locally and systemically. In congestive heart failure, there is a marked imbalance between the diminished release or the increased inactivation of vasodilators on the one hand, ie, nitric oxide, and the elevated production, release, or reduced inactivation of vasoconstrictors such as endothelin-1 on the other hand. In addition to its very potent vasoconstrictor effects, endothelin-1 possesses antinatriuretic and mitogenic properties that are a common feature of substances that are involved in development of the deleterious consequences that render congestive heart failure a lethal disease. The spectrum of action of the endothelin system and the advent of specific antagonists for its receptors have made this system a very interesting target for clinical research and possibly for future therapeutic approaches.