Secundum atrial septal defect is associated with reduced survival in adult men.

AIMS: The identification of sex differences in the prognosis of adults with a secundum atrial septal defect (ASD2) could help tailor their clinical management, as it has in other cardiovascular diseases. We investigated whether disparity between the sexes exists in long-term outcome of adult ASD2 patients. METHODS AND RESULTS: Patients with ASD2 classified as the primary defect were selected from the Dutch national registry of adult congenital heart disease. Survival stratified by sex was compared with a sex-matched general population. In a total of 2207 adult patients (mean age at inclusion 44.8 years, 33.0% male), 102 deaths occurred during a cumulative follow-up of 13 584 patient-years. Median survival was 79.7 years for men and 85.6 years for women with ASD2. Compared with the age- and sex-matched general population, survival was lower for male, but equal for female patients (P = 0.015 and 0.766, respectively). Logistic regression analyses showed that men had a higher risk of conduction disturbances (OR = 1.63; 95% CI, 1.22-2.17) supraventricular dysrhythmias (OR = 1.41; 1.12-1.77), cerebrovascular thromboembolic events (OR = 1.53; 1.10-2.12), and heart failure (OR = 1.91; 1.06-3.43). CONCLUSION: In contrast to women, adult men with an ASD2 have worse survival than a sex-matched general population. Male patients also have a greater risk of morbidity during adult life. Sex disparity in survival and morbidity suggests the need for a sex-specific clinical approach towards these patients.

Intra- and interobserver reliability in measuring aortic root rotation with cardiac magnetic resonance imaging.

Background: The rotational position of the aortic root (AoR) is of substantial clinical interest as it has been associated with severe aortic complications, such as aortic dissections. We described a cardiac magnetic resonance (CMR)-based method for measuring AoR rotation and evaluated the reliability of measurements. Methods: CMR was used for measuring AoR rotation in 50 consecutive healthy subjects. Intra- and interobserver reliability were assessed by comparing repeated measurements by the same analyst and by three independent analysts. The angles of the non-coronary sinus (NCS), right coronary sinus (RCS), and left coronary sinus (LCS) were measured relative to the interatrial septum (IAS). The angle between IAS and posterior atrial wall was measured to examine the reliability of the IAS as a key anatomical landmark. Intra- and interobserver agreement were determined using intraclass correlation coefficients (ICCs). Results: Images of 47/50 (94%) subjects were analyzed; three were excluded due to insufficient image quality. The mean ± standard deviation (SD) AoR rotation angles of NCS, RCS, and LCS were 25.9°±12.9°, 37.5°±15.2°, and 97.0°±13.1°, respectively. For measurements of AoR rotation, both intraobserver [NCS: ICC =0.94, 95% confidence interval (CI): 0.88-0.96; RCS: ICC =0.93, 95% CI: 0.87-0.96; LCS: ICC =0.91, 95% CI: 0.84-0.95] and interobserver agreement (NCS: ICC =0.90, 95% CI: 0.84-0.94; RCS: ICC =0.86, 95% CI: 0.77-0.92; LCS: ICC =0.87, 95% CI: 0.80-0.92) were excellent. The IAS angle was 79.2°±8.9°; its intraobserver agreement was somewhat higher (ICC =0.94, 95% CI: 0.88-0.96) than the interobserver agreement (ICC =0.76, 95% CI: 0.63-0.85). Conclusions: The present study in healthy subjects reports a CMR-based approach for measuring AoR rotation. CMR allows to quantify AoR rotation with excellent intra- and interobserver agreement.

Relationship between infarct tissue characteristics and left ventricular remodeling in patients with versus without early revascularization for acute myocardial infarction as assessed with contrast-enhanced cardiovascular magnetic resonance imaging.

Left ventricular (LV) remodeling following myocardial infarction (MI) is the result of complex interactions between various factors, including presence or absence of early revascularization. The impact of early revascularization on the relationship between infarct tissue characteristics and LV remodeling is incompletely known. Therefore, we investigated in patients with versus without successful early revascularization for acute MI potential relations between infarct tissue characteristics and LV remodeling with contrast-enhanced (CE) cardiovascular magnetic resonance (CMR). Patients with versus without successful early revascularization underwent CE-CMR for tissue characterization and assessment of LV remodeling including end-diastolic and end-systolic volumes, LV ejection fraction, and wall motion score index (WMSI). CE-CMR images were analyzed for infarct tissue characteristics including core-, peri- and total-infarct size, transmural extent, and regional scar scores. In early revascularized patients (n = 46), a larger area of infarct tissue correlated significantly with larger LV dimensions and a more reduced LV function (r = 0.39-0.68; all P ≤ 0.01). Multivariate analyses identified peri-infarct size as the best predictor of LV remodeling parameters (R(2 )= 0.44-0.62). In patients without successful early revascularization (n = 47), there was no correlation between infarct area and remodeling parameters; only peri-infarct size versus WMSI (r = 0.33; P = 0.03) and transmural extent versus LVEF (r = -0.27; P = 0.07) tended to be related. A correlation between infarct tissue characteristics and LV remodeling was found only in patients with early successful revascularization. Peri-infarct size was found to be the best determinant of LV remodeling. Our findings stress the importance of taking into account infarct tissue characteristics and success of revascularization when LV remodeling is studied.

[Myocardial Infarction and resuscitation of an adolescent: consequences of an unexplained disease]. / Myocardinfarct en reanimatie bij een adolescent.

BACKGROUND: Morbus Kawasaki is defined by unexplained fever combined with at least 4 out of 5 classic symptoms: bilateral conjunctivitis, polymorphic exanthema, strawberry tongue and red swollen lips, extremity changes and cervical lymphadenopathy. However, these symptoms do not always occur completely or simultaneously. CASE DESCRIPTION: An 18-year old man was admitted after an out of hospital cardiac arrest caused by an occluded aneurysmatic LAD, which was treated with a percutanious coronary intervention. Coronary angiogram however also revealed coronary aneurysms of all coronaries, identifying an episode of unexplained fever and vasculitis 4 years prior as Morbus Kawasaki. CONCLUSION: Echocardiogram, CTA and MRA can reveal coronary malformations and thus identify M. Kawasaki when there is an incomplete M. Kawasaki. An early diagnosis and treatment with high dose aspirin and intravenous immunoglobulines is essential to reduce the risk of cardiovascular complications later in life.

Hepatocellular carcinoma and the Fontan circulation: Clinical presentation and outcomes.

BACKGROUND: Fontan-associated liver disease (FALD) is universal in patients with a Fontan circulation. Hepatocellular carcinoma (HCC) is one of its severe expressions, and, though rare, frequently fatal. The purpose of this study was to describe the clinical presentation, risk factors, and outcomes of HCC in patients with a Fontan circulation. METHODS: A multicenter case series of Fontan patients with a diagnosis of HCC formed the basis of this study. The case series was extended by published cases and case reports. Clinical presentation, tumor characteristics, laboratory and hemodynamic findings as well as treatment types and outcomes, were described. RESULTS: Fifty-four Fontan patients (50% female) with a diagnosis of HCC were included. Mean age at HCC diagnosis was 30 ± 9.4 years and mean duration from Fontan surgery to HCC diagnosis was 21.6 ± 7.4 years. Median HCC size at the time of diagnosis was 4 cm with a range of 1 to 22 cm. The tumor was located in the right hepatic lobe in 65% of the patients. Fifty-one percent had liver cirrhosis at the time of HCC diagnosis. Fifty percent of the patients had no symptoms related to HCC and alpha-fetoprotein was normal in 26% of the cases. Twenty-six patients (48%) died during a median follow-up duration of 10.6 (range 1-50) months. CONCLUSIONS: HCC in Fontan patients occurs at a young age with a 1-year survival rate of only 50%. Meticulous liver surveillance is crucial to detect small tumors in the early stage.

Three cases of hepatocellular carcinoma in Fontan patients: Review of the literature and suggestions for hepatic screening.

The Fontan procedure has been used since 1971 as a palliative treatment for various (functionally) univentricular hearts. The systemic venous blood flows passively to the pulmonary arteries, without passing through a functional ventricle. This results in chronic systemic venous congestion, which may lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. This review discusses possible screening modalities for liver fibrosis and cirrhosis in the Fontan population and proposes a screening protocol. We suggest starting screening for progression of fibrosis and cirrhosis in collaboration with the hepatologist circa 10 years after Fontan completion. The screening programme will consist of a yearly evaluation of liver laboratory tests in conjunction with imaging of the liver with ultrasound or MRI every two years. In case of liver fibrosis or cirrhosis, (reversible) causes should be ruled out (e.g. obstruction in the Fontan circuit). In case of severe fibrosis or cirrhosis, other complications of portal hypertension should be evaluated and screening for hepatocellular carcinoma is required on a regular (6-12 months) basis. As regards hepatocellular carcinoma, treatment should be discussed in a multidisciplinary team, before deciding a treatment modality.

Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology.

AIMS: To describe the outcomes of pregnancy in women with pulmonary hypertension. METHODS AND RESULTS: In 2007 the European Registry on Pregnancy and Heart Disease was initiated by the European Society of Cardiology. Consecutive patients with all forms of cardiovascular disease, presenting with pregnancy, were enrolled with the aim of investigating the pregnancy outcomes. This subgroup of the cohort included 151 women with pulmonary hypertension (PH) either diagnosed by right heart catheterization or diagnosed as possible PH by echocardiographic signs, with 26% having pulmonary arterial hypertension (PAH), in three subgroups: idiopathic (iPAH), associated with congenital heart disease (CHD-PAH), or associated with other disease (oPAH), and 74% having PH caused by left heart disease (LHD-PH, n = 112). Maternal mean age was 29.2 ± 5.6 years and 37% were nulliparous. Right ventricular systolic pressure was <50 mmHg in 59.6% of patients, 50-70 mmHg in 28.5% and >70 mmHg in 11.9%. In more than 75% of patients, the diagnosis of PH had been made before pregnancy. Maternal death up to 1 week after delivery occurred in five patients (3.3%), with another two out of 78 patients who presented for follow-up (2.6%), dying within 6 months after delivery. The highest mortality was found in iPAH (3/7, 43%). During pregnancy, heart failure occurred in 27%. Caesarean section was performed in 63.4% (23.9% as emergency). Therapeutic abortion was performed in 4.0%. Complications included miscarriage (5.6%), fetal mortality (2%), premature delivery (21.7%), low birth weight (19.0%), and neonatal mortality (0.7%). CONCLUSION: Mortality in this group of patients with various forms of PH was lower than previously reported as specialized care during pregnancy and delivery was available. However, maternal and fetal mortality remains prohibitively high in women with iPAH, although this conclusion is restricted by limited numbers. Early advice on contraception, pregnancy risk and fetal outcome remains paramount.

Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.

Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.

Differential localisation of the renin-angiotensin system in de-novo lesions and in-stent restenotic lesions in in-vivo human coronary arteries.

OBJECTIVE: Different components of the renin-angiotensin system (RAS) have been demonstrated in atherosclerotic plaques. However, the involvement of the RAS in in-stent restenosis is not clear. We studied the differential immunolocalisation of angiotensin converting enzyme (ACE) and the angiotensin II type 1 (AT1) receptor in de-novo stenotic lesions and in-stent restenotic lesions in human coronary arteries. METHODS: Using a pullback atherectomy catheter, biopsies from de-novo coronary lesions (n=19) and in-stent restenotic lesions (n=19) were obtained. The biopsies were immunostained for vascular smooth muscle cells (VSMCs), macrophages, ACE and the AT1 receptor. RESULTS: In biopsies from de-novo stenotic lesions ACE-positive macrophages were more numerous than in in-stent restenotic lesions (P=0.002). Moreover, in the latter lesions, ACE-positive macrophages decreased when the time interval of stent implantation was longer. On the other hand, in-stent restenotic lesions contained predominantly young VSMCs, which abundantly expressed AT1 receptors. CONCLUSIONS: Lesional ACE expression is not a prominent feature of in-stent restenotic lesions. In contrast, AT1 receptors are abundantly expressed on young VSMCs. In de-novo lesions ACE and AT1 receptors were found on macrophages and VSMCs, which were present in all specimens.

Angiotensin receptors in the cardiovascular system.

The angiotensin II receptors mediate the effects of the renin-angiotensin system, which has an important role in cardiovascular (patho)physiology. Four types of angiotensin receptors are known, of which the type 1 (AT1) and the type 2 (AT2) receptors are the most important. Stimulation of the AT1 receptor leads to a cascade of signalling pathways in several cell types, which finally leads to processes such as vasoconstriction, inflammation and proliferation. These processes are of great importance in various cardiovascular diseases, including hypertension, atherosclerosis and ventricular hypertrophy. The AT2 receptor is expressed mainly in the fetal stage. In adults, the AT2 receptor is minimally expressed under normal circumstances. Its role in the adult cardiovascular system is not well established, but its effects seem to oppose those of the AT1 receptor. This overview discusses the pathophysiological role of the angiotensin II receptors in various cardiovascular diseases with the emphasis on the signal transduction of the AT1 and the AT2 receptors.

Evidence of myocardial scarring and microvascular obstruction on cardiac magnetic resonance imaging in a series of patients presenting with myocardial infarction without obstructed coronary arteries.

Patients with acute chest pain, electrocardiographic ST-elevation and significant elevation of cardiac troponin but without obstructive coronary artery disease represent a diagnostic and therapeutic dilemma. Cardiac magnetic resonance imaging (CMR) can elucidate underlying alternative causes of troponin elevation including detection of (minor) myocardial infarction (MI) by identifying myocardial scarring as delayed enhancement. Of 77 patients, who were admitted between March 2009 and December 2012 with electrocardiographic (ECG) and biochemical evidence of acute MI without obstructive coronary artery disease, 45 patients underwent CMR that showed in 11/77 (14%) late gadolinium enhancement (LGE), compatible with myocardial scarring. We analyzed clinical, echocardiographic, and CMR data of these patients. Elevated troponin I levels were observed in all patients (median 1.3 ng/l, IQR 0.44-187) with median peak creatinine phosphokinase of 485 U/l (IQR 234-618). Echocardiographic wall motion abnormalities were detected in 8/11 (73%) patients; in 75% of these segments, ECG abnormalities were observed in corresponding leads. CMR detected LGE in the inferior (4/11), the inferolateral (5/11), the inferoseptal (2/11), the anterior (3/11), apical (3/11) and in the lateral segments (2/11). In addition, in all but two patients, these segments matched ECG abnormalities in corresponding leads. CMR identified microvascular obstruction in 4/11 (36%) patients. Patients with clinical, ECG, and biochemical signs of acute MI but unobstructed coronary arteries may have CMR-detectable myocardial scars. Information on myocardial scarring may help to make the diagnosis and draw therapeutic consequences. This case series underlines the value of contrast-enhanced CMR for myocardial tissue characterization.

Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification.

BACKGROUND: The aging congenital heart disease (CHD) population is prone to develop a variety of sequelae, including pulmonary arterial hypertension (PAH). Previous prevalence estimates are limited in applicability due to the use of tertiary centers, or database encoding only. We aimed to investigate the contemporary prevalence of PAH in adult CHD patients, using a nationwide population. METHODS: A cross-sectional study was performed, using the population-based Dutch CONgenital CORvitia (CONCOR) registry. All patients born with a systemic-to-pulmonary shunt, thereby at risk of developing PAH, were identified. From this cohort, a random sample was obtained and carefully reviewed. RESULTS: Of 12,624 registered adults with CHD alive in 2011, 5,487 (44%) were at risk of PAH. The random sample consisted of 1,814 patients (mean age 40 ± 15 years) and 135 PAH cases were observed. PAH prevalence in patients born with a systemic-to-pulmonary shunt was 7.4%. The prevalence of PAH after corrective cardiac surgery was remarkably high (5.7%). Furthermore, PAH prevalence increased with age, from 2.5% under 30 years until 35% in the eldest. PAH prevalence in the entire CHD population was 3.2%. Based on 3000 per million adult CHD patients in the general population, we can assume that PAH-CHD is present in 100 per million. CONCLUSIONS: This new approach using a nationwide CHD population reports a PAH prevalence of 3.2% in CHD patients, and 100 per million in the general adult population. Especially in patients after shunt closure and the elderly, physicians should be aware of PAH-CHD, to provide optimal therapeutic and clinical care.

Coronary-cameral fistulas in adults: Acquired types (second of two parts).

Acquired coronary artery fistulas (CCFs) are infrequently detected during conventional coronary angiography. To delineate the characteristics of congenital (first part) and acquired (second part) CCFs in adults, a PubMed search was conducted for papers dealing with congenital or acquired CCFs. None of the publications describing patients with coronary-vascular fistulas were included. Papers dealing with pediatric subjects were excluded. From the world literature, a total of 243 adult patients were selected who had congenital (n = 159/243, 65%) and acquired (n = 84/243, 35%) CCFs. Among the acquired types (n = 72, 85.7%) were traumatic (iatrogenic (n = 65/72, 90%), accidental (n = 7/72, 10%) and (n = 12, 14.3%) spontaneously developing in relation to severe coronary atherosclerosis or myocardial infarction. A high incidence of spontaneous resolution of iatrogenic CCFs resulting from endomyocardial biopsy or following post-septal myectomy was reported. Spontaneous CCFs associated with myocardial ischemia or infarction resolved completely in 8% of the subjects. Early surgical intervention was the treatment of choice in acquired traumatic accidental CCFs. The congenital types are addressed in a previous issue of this journal (first part). In this review (second of two parts, part II), we describe the acquired coronary-cameral fistulas.

Infarct tissue characterization in implantable cardioverter-defibrillator recipients for primary versus secondary prevention following myocardial infarction: a study with contrast-enhancement cardiovascular magnetic resonance imaging.

Knowledge about potential differences in infarct tissue characteristics between patients with prior life-threatening ventricular arrhythmia versus patients receiving prophylactic implantable cardioverter-defibrillator (ICD) might help to improve the current risk stratification in myocardial infarction (MI) patients who are considered for ICD implantation. In a consecutive series of (ICD) recipients for primary and secondary prevention following MI, we used contrast-enhanced (CE) cardiovascular magnetic resonance (CMR) imaging to evaluate differences in infarct tissue characteristics. Cine-CMR measurements included left ventricular end-diastolic and end-systolic volumes (EDV, ESV), left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and mass. CE-CMR images were analyzed for core, peri, and total infarct size, infarct localization (according to coronary artery territory), and transmural extent. In this study, 95 ICD recipients were included. In the primary prevention group (n = 66), LVEF was lower (23 ± 9% vs. 31 ± 14%; P < 0.01), ESV and WMSI were higher (223 ± 75 ml vs. 184 ± 97 ml, P = 0.04, and 1.89 ± 0.52 vs. 1.47 ± 0.68; P < 0.01), and anterior infarct localization was more frequent (P = 0.02) than in the secondary prevention group (n = 29). There were no differences in infarct tissue characteristics between patients treated for primary versus secondary prevention (P > 0.6 for all). During 21 ± 9 months of follow-up, 3 (5%) patients in the primary prevention group and 9 (31%) in the secondary prevention group experienced appropriate ICD therapy for treatment of ventricular arrhythmia (P < 0.01). There was no difference in infarct tissue characteristics between recipients of ICD for primary versus secondary prevention, while the secondary prevention group showed a higher frequency of applied ICD therapy for ventricular arrhythmia.

Efficacy of antiarrhythmic drugs in adults with congenital heart disease and supraventricular tachycardias.

Supraventricular tachycardias (SVTs) are a major cause of morbidity in adults with congenital heart disease (CHD). Few data exist on safety and efficacy of antiarrhythmic drugs in this population. Our aim was to determine the efficacy of antiarrhythmic drugs in adults with CHD and first-onset SVT on maintaining sinus rhythm after conversion. This was a multicenter retrospective study including adults with CHD and first-onset SVT from January 2008 to January 2011. First-onset SVT occurred in 92 of 7,171 patients without previous SVT (mean age 51 ± 16 years, 57% women). SVTs included atrial fibrillation and flutter in >80% of the patients. Most of these patients had septal defects (50%) and left-sided lesions (21%). The acute management of SVTs resulted in sinus rhythm in 83 patients, and 89% of these patients were instituted on oral antiarrhythmics to prevent SVT recurrence. After a mean follow-up of 2.5 ± 1.4 years, only 45% of the patients were free from SVT. Class III antiarrhythmics (85% sotalol and 15% amiodarone) were associated with a significantly lesser risk of SVT recurrence compared with all other antiarrhythmic drugs (hazard ratio 0.5, 95% confidence interval 0.27 to 0.96, p = 0.036). However, adverse effects of medication occurred in 22% of the patients, mainly in patients taking amiodarone. In conclusion, in adults with CHD and first-onset SVTs, class III antiarrhythmics are more efficacious in maintaining sinus rhythm after cardioversion than other antiarrhythmics. Sotalol may be considered as the first-choice therapy as this is associated with fewer adverse effects than amiodarone.

Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade?

Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endothelial dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme inhibitors (ACE-I) improve endothelial function in CHF, the effects of angiotensin II AT1-receptor blockers (ARB) are less well established. Therefore we compared the effects of the ACE-I lisinopril vs. the ARB candesartan on endothelial dysfunction in a rat model of CHF. CHF was induced by myocardial infarction (MI) after coronary ligation. Two weeks after MI, daily treatment with lisinopril (2 mg/kg) or candesartan cilexetil (1.5 mg/kg) was started. After 13 weeks, rats were sacrificed and endothelial function was determined by measuring acetylcholine (ACh)-induced vasodilation in aortic rings, with selective presence of the nitric oxide synthase (NOS)-inhibitor NG-monomethyl-L-arginine (L-NMMA) to determine the contribution of nitric oxide (NO). ACh-induced vasodilation was attenuated in untreated MI (-50%) compared with control rats. This was in part due to an impaired contribution of NO (-49%). Lisinopril and candesartan cilexetil fully normalised ACh-induced dilation, including the part mediated by NO. Chronic RAAS-blockade with lisinopril and candesartan cilexetil normalised endothelial function in CHF in a comparable way. The effect of both treatments included the increase of the NO-mediated dilation, further indicating the important role of oxidative stress in the relationship between the RAAS and endothelial dysfunction in CHF.

Functional antagonism of different angiotensin II type I receptor blockers in human arteries.

OBJECTIVES: To evaluate and compare the functional type and the degree of antagonism of the selective angiotensin II type 1 receptor blockers (ARB) losartan, EXP 3174 (the active metabolite of losartan), valsartan and candesartan in human internal mammary arteries. METHODS: Human internal mammary arteries were obtained as excess graft material during coronary bypass surgery. Vessels were prepared as rings and mounted in an organ bath in which vasoconstriction and -dilation can be measured. Concentration-response curves of angiotensin II-mediated vasoconstriction were measured in absence or presence of different concentrations of one of the ARBs. RESULTS: Losartan showed a rightward shift of the angiotensin II-mediated vasoconstriction, whereas addition of its metabolite EXP 3174 caused a decrease of the maximal effect of angiotensin II. Incubation with valsartan and candesartan also resulted in a decrease of the maximal effect. The inhibiting effects on the angiotensin II-mediated vasoconstriction by the highest concentration of EXP 3174, valsartan and candesartan did not differ significantly. CONCLUSION: In human internal mammary arteries, losartan acts as a surmountable antagonist. On the other hand, EXP 3174, valsartan and candesartan demonstrate an insurmountable type of antagonism. Furthermore, the inhibiting effects of EXP 3174, valsartan and candesartan in our study are equal in the highest concentrations.