Right ventricular diastolic dysfunction in patients with anticardiolipin antibodies and antiphospholipid syndrome.

OBJECTIVE: To evaluate the prevalence of diastolic dysfunction in patients with anticardiolipin antibodies (aCL) and to examine whether the antiphospholipid syndrome (APS) is associated with diastolic dysfunction independently of valvular abnormalities and systolic dysfunction. METHODS: Pulsed, continuous, colour Doppler echocardiography was performed in 179 subjects, of whom 15 were excluded from the analysis because of systolic dysfunction or severe valvular disease. The remaining 164 subjects included 29 patients with primary APS, 26 patients with secondary APS (APS in the presence of systemic lupus erythematosus (SLE)), and 30 patients with SLE and aCL but without APS; 43 patients with SLE without aCL and 36 normal volunteers served as control groups. RESULTS: The groups compared differed significantly in all measures of right ventricular function. There was a gradation of increasing diastolic function impairment as manifested by prolonged deceleration time (DT) and isovolumic relaxation time (IVRT) across the groups of patients with SLE without aCL, SLE with aCL, secondary APS, and primary APS. Differences in left ventricular diastolic function measures were less prominent. In regression analysis, DT increased by 19.6 ms (p=0.002) in the presence of primary APS and by 20.1 ms (p=0.038) in the presence of pulmonary hypertension. The titre of IgG aCL was the strongest predictor of a prolonged IVRT. CONCLUSION: Diastolic dysfunction, in particular of the right ventricle-that is, independent of valvular disease and systolic dysfunction, is a prominent feature of APS and may be related to the pathogenesis of the syndrome.

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension.

BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.

Fibrinolytic/hemostatic variables in arterial hypertension: response to treatment with irbesartan or atenolol.

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (beta1-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned to atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin, tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were determined before and after 6 months of therapy. Age, gender distribution, body mass index, lipid profile, and baseline values of the measured markers were similar in both groups. Baseline values for systolic and diastolic blood pressure, as well as the reduction after treatment, were not significantly different between the two groups. Treatment with irbesartan was associated with a significant decrease in the levels of all the parameters. Similar findings were observed in the atenolol group, except for factor XII and tissue factor pathway inhibitor levels, which were not significantly decreased in this group. The reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and thrombomodulin was significantly greater in the irbesartan than in the atenolol group. In conclusion, the results indicated that, despite an equally controlled blood pressure, 6-month therapy with irbesartan was associated with a more favorable modification of hemostatic/fibrinolytic status than atenolol.

Resistance to activated protein C and FV leiden mutation in patients with a history of acute myocardial infarction or primary hypertension.

This study was designed to investigate both resistance to activated protein C (APC-R) and the factor FV Q506 mutation incidence in patients with a history of acute myocardial infarction (AMI) and patients with primary hypertension (PH), a high-risk group for arterial thrombosis. Eighty patients with a history of AMI (group A), 160 patients with a history of PH (group B), and 124 age-matched controls without arterial disease (group C) were studied. APC-R was determined using the Coatest APC Resistance Kit of Chromagenix, Sweden. The prevalence of the FV Q506 mutation was estimated by DNA analysis (Bertina method). The prevalence of the FV Q506 mutation was 20%, 13.75%, and 8% in groups A, B, and C, respectively (A v C P = .0466). The prevalence of APC-R was 47.5% in group A v 13% in group C (P < .0001) and 36.25% in group B v 13% in group C (P < .0001). The response to activated protein C expressed as mean value +/- SD was 2.05 +/- 0.33 in group A v 2.56 +/- 0.46 in group C (P < .05) and 2 +/- 0.22 in group B v 2.56 +/- 0.46 in group C (P < .05). These findings suggest that patients with a history of AMI or PH have a significantly increased incidence of both APC-R and FV Q506 mutation compared with the control group. These findings support the hypothesis that these anticoagulant defects may be risk factors for arterial thrombosis.

Elevated plasma immunoreactive leptin levels preexist in healthy offspring of patients with essential hypertension.

BACKGROUND: Plasma leptin levels and plasma insulin levels have been found to be elevated in patients with essential hypertension (EH) and have been suggested to be components of the metabolic syndrome. Increased heart rate (HR) may predict the development of EH in normal or borderline-hypertensive individuals. The aim of our study was to test the hypothesis that elevated plasma leptin and insulin levels as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP) and increased resting HR preexist in the healthy offspring of patients with EH. METHODS AND RESULTS: Twenty-six (12 male, 14 female) healthy offspring of hypertensive patients, mean age 16 +/- 2.5 years and body mass index (BMI) of 21.5 +/- 2.8 kg/m(2) (group A), and 30 (14 male, 16 female) healthy offspring of normotensive patients, mean age 17 +/- 2.3 years and BMI of 21.9 +/- 2.4 kg/m(2) (group B), were studied. (The two groups were matched for sex, age, and BMI). Mean SBP, DBP, resting HR, plasma leptin, and plasma insulin levels (radioimmunoassay method) were determined in the whole study population. Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (120 +/- 12 vs 112 +/- 9.5 mm Hg, 77 +/- 9 vs 72 +/- 7 mm Hg, 79 +/- 8 vs 75 +/- 5 beats/min, P <.01, P <.05, and P <.05, respectively). Plasma leptin and insulin levels were significantly higher in group A than in group B (9 +/- 5.06 vs 5.6 +/- 2.5 ng/mL and 20.11 +/- 11.3 vs 14.8 +/- 5.2 microIU/mL, P <.01 and P <.05, respectively). CONCLUSIONS: Our findings support the hypothesis that hyperleptinemia, hyperinsulinemia, and elevated blood pressure and resting HR preexist in the healthy offspring of patients with EH.

Changes in phasic coronary blood flow velocity profile and relative coronary flow reserve in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: In this study, we both investigated coronary flow velocity in hypertrophic obstructive cardiomyopathy (HOCM) and tested the hypothesis of differing coronary flow reserve (CFR) of coronary arteries perfusing left ventricular regions with nonuniform myocardial hypertrophy by measuring the relative CFR. METHODS AND RESULTS: Coronary flow velocity was assessed in left anterior descending coronary (LAD) and left circumflex (LCX) arteries in 18 patients with HOCM and marked hypertrophy only in the ventricular septum, in 13 patients without obstruction (HCM), and in 9 age- and sex-matched normal subjects at rest, during rapid atrial pacing, and after dobutamine infusion (5 to 30 microg/kg per minute). Relative CFR was estimated as the ratio between absolute CFR of the LAD and absolute CFR of the LCX (LAD/LCX(CF)). At the peak of rapid atrial pacing and during dobutamine stress, LAD/LCX(CF) was reversed in HOCM patients (from 1.25+/-0.11 to 0.82+/-0.07 and 0.79+/-0.06, respectively), whereas it remained unchanged in control subjects (from 1.0+/-0.1 to 1.0+/-0.05 and 1.0+/-0.05, respectively; P<.001). In HCM patients, LAD/LCX(CF) at rest was 1.10+/-0.11, whereas during rapid atrial pacing and dobutamine stress, it was 0.92+/-0.08 and 0.90+/-0.09, respectively. Relative CFR was 0.62+/-0.05 in HOCM patients and 1.05+/-0.05 (P<.001) in normal subjects. There was an inverse correlation between relative CFR and peak systolic outflow tract gradient (r2=.74, P<.001). CONCLUSIONS: Regional distribution of hypertrophy in some patients with HOCM resulted in regional impairment of coronary flow. Relative CFR can be used to estimate regional disturbances of coronary flow and may help in patient selection for new interventional therapeutic techniques.

Changes in phasic coronary blood flow velocity profile in relation to changes in hemodynamic parameters during stress in patients with aortic valve stenosis.

BACKGROUND: Alterations in phasic coronary flow profile have been demonstrated at rest in patients with aortic valve stenosis (AVS) but have never been studied under conditions of hemodynamic stress. METHODS AND RESULTS: Thirty-four patients with significant pure AVS (21 with exertional symptoms [group 1], 13 asymptomatic [group 2]) and 9 control subjects (group 3), all with normal coronary arteries, were studied successively at rest, during rapid atrial pacing, and after dobutamine infusion (5 to 30 micrograms.kg-1.min-1 i.v.) by proximal left anterior descending (LAD) intracoronary Doppler flow velocimetry concomitant with hemodynamic measurements. Systolic retrograde coronary flow velocity (CFV) was recorded only in patients with AVS, and its resting peak value was positively correlated with peak aortic pressure gradient (APG) (r = .63, P < .001). In group 1, there was lower aortic valve area (0.58 +/- 0.10 versus 0.75 +/- 0.08 cm2, P < .001) and higher resting APG and peak systolic retrograde CFV than in group 2, and also higher resting peak diastolic and mean CFV than in groups 2 and 3. In the two AVS groups, there were no changes from rest in APG and retrograde CFV at peak pacing rate; however, these parameters increased concomitantly and significantly at peak dobutamine stress. The ratio of the resting systolic to diastolic CFV curve area was inversely correlated with mean APG (r = -.54, P < .001); it was significantly lower in group 1 than in groups 2 and 3 (0.19 +/- 0.07 versus 0.29 +/- 0.10 and 0.30 +/- 0.04, respectively, both P < .005) and increased at peak pacing (group 1, to 0.29 +/- 0.14; group 2, to 0.39 +/- 0.12; group 3, to 0.38 +/- 0.07; all P < .001). At peak dobutamine stress, it decreased in patients with AVS (group 1, to 0.05 +/- 0.05; group 2, to 0.08 +/- 0.03; both P < .001) but did not change in group 3 (0.25 +/- 0.05). From rest to peak dobutamine stress, in both AVS groups there was increased retrograde systolic (group 1, 441 +/- 483%; group 2, 681 +/- 356%; both P < .001), decreased total systolic (group 1, -66 +/- 25%, P < .001; group 2, -19 +/- 24%; P = NS), and increased diastolic (group 1, 33.4 +/- 31.7%; group 2, 197.7 +/- 105.1%; both P < .001; group 1 versus group 2, P < .001) CFV curve area. In contrast, group 3 showed comparable increases in both systolic (143.5 +/- 44.4%) and diastolic (197.1 +/- 75.2%) CFV area (both P < .001). The stress-induced increases in the mean CFV and blood flow exceeded or were comparable with the concomitant increases in the estimated myocardial metabolic demand in groups 2 and 3 but were significantly lower in group 1. CONCLUSIONS: Stress-induced changes in LAD phasic CFV profile differ significantly between patients with and without AVS. In AVS, these changes are closely related to the concomitant stress-induced changes in hemodynamic parameters.

Acute effect of captopril administration on baroreflex sensitivity in patients with acute myocardial infarction.

Depressed baroreflex sensitivity (BRS) after acute myocardial infarction (AMI) is considered an indication of decreased vagal and/or increased sympathetic tone. To determine the effect of angiotensin converting enzyme inhibitors (ACEI) on BRS after AMI we studied 27 patients with a first Q wave AMI, no signs of heart failure and no history of arterial hypertension or diabetes mellitus. An additional group of 10 patients with the same clinical characteristics served as controls. On the 5th day after the onset of AMI, three consecutive boluses of phenylephrine were given intravenously and baseline BRS was taken as the mean slope of the linear regression lines of RR intervals over systolic blood pressure. QT interval was also measured and corrected according to Bazett's formula (QTc). Consequently, a single oral dose of captopril 50 mg or placebo was given to treatment or control group patients, respectively; BRS and QTc were reassessed 1 h later. One hour after captopril administration BRS increased from 5.95 +/- 2.80 to 9.14 +/- 3.46 ms.mmHg-1 (P < 0.0001); QTc increased from 414 +/- 46 to 425 +/- 46 ms (P < 0.0001), systolic blood pressure decreased from 125 +/- 19 to 115 +/- 15 mmHg (P = 0.0002), while heart rate did not change significantly. Baseline BRS was correlated only with age (r = -0.74, P < 0.0001). In the control group, 1 h after placebo, no difference was observed in any variable compared to baseline. Captopril appears to improve BRS immediately in the early phase of AMI.

45,X Turner syndrome with normal ovarial function and multiple malformations of the aorta.

We present a case of a female patient with monosomy of X chromosome in peripheral lymphocytes and skin fibroblasts, normal ovarian function and associated multiple congenital abnormalities of the aorta: bicuspid aortic valve, dilatation of the ascending aorta and multiple cystic structures of the aortic wall, complicated by endarteritis. We review the literature on fertile women with 45,X karyotype and the possible pathogenetic mechanisms of the aortic defects described as 'cystic medial necrosis of the aorta'.

Relation between changes in blood flow of the contralateral coronary artery and the angiographic extent and function of recruitable collateral vessels arising from this artery during balloon coronary occlusion.

OBJECTIVES: The purpose of this study was to investigate changes in the magnitude of blood flow through the contralateral coronary artery in relation to the development of recruitable collateral vessels arising from this artery to supply a balloon-occluded coronary vessel. BACKGROUND: Recruitable collateral vessels have been shown to emerge suddenly to supply an occluded coronary artery, but their physiologic effect cannot always be predicted angiographically. METHODS: Twenty-four patients were studied during four successive balloon dilations for single left anterior descending coronary artery stenosis. Before and during each balloon occlusion, blood flow in the proximal right coronary artery was measured by intracoronary Doppler flow velocimetry and quantitative coronary angiography. Estimates of chest pain and ST segment elevation were also obtained. RESULTS: Fourteen patients developed angiographically visible recruitable collateral vessels (high grade in 6 [group III], low grade in 8 [group II]), whereas 10 patients (group I) did not. During the four successive balloon occlusions, the right coronary artery flow showed transient reproducible increases in group III (first occlusion 66.4 +/- 36.8%, fourth occlusion 64 +/- 23.9%, all p = 0.036), progressive increases in group II (from first occlusion 17.9 +/- 26.6% [p = 0.08] to fourth occlusion 60.4 +/- 35.9% [p = 0.014]) and no significant changes in group I. Between the first and the fourth occlusion, the severity of chest pain and the magnitude of ST segment elevation declined significantly in group II but did not change in groups I and III. CONCLUSIONS: During balloon coronary artery occlusion, the transient appearance of recruitable collateral vessels is associated with a transient increase in blood flow through the collateral donor artery. This increase in coronary flow appears to reflect collateral function better than the angiographic assessment, especially in patients with poor collateral vessel recruitment.

The effects of early captopril treatment on left ventricular volumes and function in patients with and without depressed global ejection fraction after acute myocardial infarction.

To determine the effects of captopril on left ventricular volumes and function in patients with and without depressed ventricular function following acute myocardial infarction (AMI) we studied 78 patients with a first Q wave AMI and no clinical evidence of heart failure. All patients underwent radionuclide ventriculography (RVG) on the 4th day after admission and were then randomly assigned to receive conventional treatment alone (36 patients, control group) or with the addition of oral captopril, 25 mg three times daily (42 patients, captopril group). RVG was repeated one month after the baseline examination. After one month the left ventricular ejection fraction (LVEF) significantly increased in the captopril group (from 43.2 +/- 1.3 to 50.9 +/- 1.6%, P < 0.001) and remained relatively unchanged in the control group (from 47 +/- 1.3 to 49.2 +/- 1.7%, P = ns). In the captopril group the subgroup of patients with a baseline LVEF < 45% demonstrated a significant decrease in end-systolic volume index (ESVI) (from 53.3 +/- 3.2 to 42.4 +/- 2.8 ml. m-2, P < 0.002) and a highly significant improvement in LVEF (from 36.3 +/- 1.3 to 49.6 +/- 1.8%, P < 0.00005). In the control group, LVEF also increased in those in whom it was < 45% (from 38 +/- 1.4 to 42 +/- 2.4%, P < 0.01), but the increase was less than that in the captopril group (P < 0.01), mainly due to an increase in end-diastolic volume index (EDVI) (from 78.2 +/- 4.6 to 84.6 +/- 12.3 ml.m-2, P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous pulmonary valvuloplasty in an octogenarian with calcific pulmonary stenosis.

We describe a patient in whom calcific pulmonary vascular stenosis was diagnosed at the age of 84 years. Valve stenosis was relieved by percutaneous transluminal pulmonary valvuloplasty. To our knowledge, PTPV performed at this age has not been previously reported.

Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril.

PURPOSE: This prospective study was performed to evaluate the response of the cardiopulmonary vasculature to two vasodilators in patients with systemic sclerosis and either minimal or no central hemodynamic abnormalities. PATIENTS AND METHODS: Twenty patients with systemic sclerosis, Raynaud's phenomenon (19 of 20 patients), and clinically normal cardiac function underwent right heart catheterization. Rest and exercise hemodynamic measurements, including cardiac output by thermodilution, were performed before and after oral administration of nifedipine 20 mg and captopril 25 mg. RESULTS: Half of the patients had normal hemodynamics (Group A); the other half (Group B) had abnormal baseline elevations in pulmonary vascular resistance and four of them showed "borderline" pulmonary arterial hypertension. Group A, with significantly shorter disease duration compared with Group B, responded poorly to nifedipine and captopril. However, Group B had significant decreases in pulmonary vascular resistance (from 148 +/- 20 to normal levels of 94 +/- 21 dynes.second.cm-5) and pulmonary mean pressure in response to nifedipine treatment but not to captopril. CONCLUSION: These observations show a short-term beneficial effect of nifedipine in the cardiopulmonary vasculature of patients with systemic sclerosis and suggest that a potentially reversible vasoconstrictive element is included in the vascular lesion of this disorder.

Autonomic neuropathy in leprosy.

The integrity of the autonomic control of the cardiovascular system was studied in 21 patients with lepromatous leprosy and in ten normal people using several simple tests based on cardiovascular reflexes. Impairment of both parasympathetic and sympathetic function was demonstrated in the lepromatous patients.

Sinus node coronary arteries studied with angiography.

Coronary angiograms of 309 consecutive patients undergoing coronary angiography were reviewed to investigate the blood supply to the sinus node area. Blood was supplied from the right coronary artery in 59% of cases, from the left coronary artery in 38%, and from both coronary arteries in 3%. The posterior sinus node artery was demonstrated in 32 patients (27% of the 119 patients with the sinus node artery originating from the left circumflex and 10.5% of all patients).