Assessment of aortic line of elasticity using polynomial regression analysis.

BACKGROUND: The aim of this study was to assess the sigmoid line of elasticity in the human aorta. METHODS AND RESULTS: The pressure-diameter relation was measured in the descending aorta in 120 subjects. In an additional group of 6 subjects, transient vena caval occlusion produced 5 sets of pressure-diameter data. We found that the best fit curve of the pooled pressure-diameter data was a third-order polynomial. A polynomial equation was used to calculate the sigmoid line of elasticity in the entire population and after the administration of diltiazem (15 patients) or enalaprilat (10 patients). The sigmoid line of elasticity was significantly different with respect to age (P<0.001), history of hypertension (P<0.004), and hypercholesterolemia (P<0.02). The difference between the transition point and the peak systolic pressure was increased in normal subjects compared with patients (P<0.0001). The sigmoid line shifted leftward and upward with diltiazem, but it remained unchanged with enalaprilat. During an average of 3 years of follow-up, 19 of 88 patients developed stroke (n=4), unstable angina (n=8), acute myocardial infarction (n=4), or acute pulmonary edema (n=3). CONCLUSIONS: This approach provides a quantitative evaluation of the aortic line of elasticity, which can differentiate the intrinsic from the extrinsic aortic elastic properties. Furthermore, it is a powerful and independent risk factor for cardiovascular events.

Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin.

BACKGROUND: Proinflammatory cytokines released by injured endothelium facilitate interaction of endothelial cells with circulating leukocytes and thus may contribute to development and progression of atherosclerosis. We investigated whether cytokines and C-reactive protein (CRP) are indicative of myocardial ischemia or of diseased vessels and whether they are influenced by aspirin treatment in patients with chronic stable angina. METHODS AND RESULTS: Plasma macrophage colony stimulating factor (MCSF), IL-1b, IL-6, and CRP were measured in 60 stable patients after 48-hour Holter monitoring and in 24 matched controls. All patients had angiographic documentation of disease and positive exercise ECGs. Patients with ischemia on Holter monitoring (n=40) received aspirin or placebo in a 6-week, randomized, double blind, crossover trial. Blood sampling was repeated at the end of each treatment phase (3 weeks). Compared to controls, patients had more than twice median MCSF (800 versus 372 pg/mL), IL-6 (3.9 versus 1.7 pg/mL), and CRP (1.25 versus 0.23 mg/L) levels (P<0.01 for all comparisons). MCSF was related to ischemia on Holter monitoring (P<0.01), to low ischemic threshold during exercise (P<0.01), and together with IL-1b to number of diseased vessels (P<0.05). MCSF, IL-6, and CRP were all reduced after 6 weeks of aspirin treatment (P<0.05). CONCLUSIONS: These findings suggest that cytokines are associated with both ischemia and anatomic extent of disease in patients with stable angina. Reduced cytokine and CRP levels by aspirin may explain part of aspirin's therapeutic action.

Closed relation between carotid and ascending aortic atherosclerosis in cardiac patients.

BACKGROUND: Carotid atherosclerosis and aortic atherosclerosis are both associated with coronary artery disease and cerebral thromboembolism. However, the relationship between asymptomatic carotid and aortic atherosclerosis is not well known. METHODS AND RESULTS: Sixty-two consecutive cardiac patients (mean age 57 years) without a history of atherosclerotic cardiovascular disease who were referred for transesophageal echocardiography were included. By means of a high-resolution ultrasound technique, normal carotid arteries were found in 12 patients (19.4%), whereas 15 patients (24. 2%) had increased intima-media thickness, and the remaining 35 patients (56.5%) had atherosclerotic plaques (intima-media thickness >/=1.3 mm). Transesophageal echocardiography characterized ascending aortic intimal morphology as normal in 1 patient (1.6%), as thickening in 22 patients (35.5%), and as atherosclerotic plaques in 39 patients (62.9%). Patients with both carotid and aortic plaques were older compared with patients without plaques; also, a higher percentage of patients with carotid and aortic plaques suffered from hypertension and diabetes mellitus compared with patients without plaques (P:<0.001). The incidence of carotid plaques was 74.3% (29 of 39 patients) in the subgroup with aortic plaques; there was a stepwise increase in the percentage of patients with carotid plaques among the patients with increasing grades of aortic atherosclerosis. Furthermore, the incidence of ascending aortic plaques was 82.8% (29 of 35 patients) in the subgroup with carotid plaques. Regression analysis revealed that age and carotid plaques were independently related to the presence of aortic plaques. In the entire study population, the presence of carotid plaques had a high positive predictive value (83%), an acceptable sensitivity (75%) and specificity (74%), and a relatively low negative predictive value (63%) for the presence of aortic plaques. CONCLUSIONS: In cardiac patients without clinical evidence of atherosclerotic cardiovascular disease, a high prevalence of combined aortic and carotid plaques were detected. The presence of carotid plaque reflects the presence of aortic plaque, whereas the absence of carotid plaque may not reflect the absence of aortic plaque.

Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: A new method of detection by application of a special thermography catheter.

BACKGROUND: Activated macrophages play an important role in the pathogenesis of acute ischemic syndromes. It has been postulated that detection of heat released by activated inflammatory cells of atherosclerotic plaques may predict plaque rupture and thrombosis. Previous ex vivo studies have shown that there is thermal heterogeneity in human carotid atherosclerotic plaques. METHODS AND RESULTS: To measure the temperature of human arteries in vivo, we developed a catheter-based technique. Ninety patients (45 with normal coronary arteries, 15 with stable angina [SA], 15 with unstable angina [UA], and 15 with acute myocardial infarction [AMI]) were studied. The thermistor of the thermography catheter has a temperature accuracy of 0.05 degrees C, a time constant of 300 ms, and a spatial resolution of 0.5 mm. Temperature was constant within the arteries of the control subjects, whereas most atherosclerotic plaques showed higher temperature compared with healthy vessel wall. Temperature differences between atherosclerotic plaque and healthy vessel wall increased progressively from SA to AMI patients (difference of plaque temperature from background temperature, 0. 106+/-0.110 degrees C in SA, 0.683+/-0.347 degrees C in UA, and 1. 472+/-0.691 degrees C in AMI). Heterogeneity within the plaque was shown in 20%, 40%, and 67% of the patients with SA, UA, and AMI, respectively, whereas no heterogeneity was shown in the control subjects. CONCLUSIONS: Thermal heterogeneity within human atherosclerotic coronary arteries was shown in vivo by use of a special thermography catheter. This heterogeneity is larger in UA and AMI, suggesting that it may be related to the pathogenesis.

Increased temperature of malignant urinary bladder tumors in vivo: the application of a new method based on a catheter technique.

PURPOSE: The aim of this study was to investigate the existence of any thermal difference between malignant tumors and inflammatory benign lesions of the human urinary bladder and to determine whether it correlates with tumor angiogenesis quantification. PATIENTS AND METHODS: A new method, developed in our institute, is introduced to detect temperature in human urinary bladder, in vivo. This method is based on a thermography catheter. We calculated the differences of the temperature of the solid tumor and of a normal area (Delta T) on 20 subjects (mean age, 72.5 years; 95% confidence interval [CI], 68.5 to 76.4). According to the biopsy histology, Eight (40%) patients had benign tumors, and 12 (60%) had malignant tumors. RESULTS: We found significant differences of Delta T between patients with benign and malignant tumor (P <.001). Also, differences were found for the mean values of angiogenesis level between malignant and benign tumors (P =.0261), and a moderated positive correlation was estimated between the degree of angiogenesis and Delta T (P =.02). Based on logistic regression analysis, we found that a 1-degree increase of Delta T triples the odds of a patient having a malignant tumor (odds ratio = 2.91; 95% CI, 1.97 to 7.78; P <.001), adjusted for the degree of angiogenesis (P =.0236) and the grade of tumor (P <.001). A threshold point of Delta T = 0.7 degrees C was determined, with sensitivity 83% and specificity 75%. CONCLUSION: These findings suggest that the calculated difference of temperature between normal tissue and neoplastic area could be a useful criterion in the diagnosis of malignancy in tumors of the human urinary bladder.

Effects of pacing-induced and balloon coronary occlusion ischemia on left atrial function in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to compare left atrial (LA) function in 16 patients with distal left anterior descending (LAD) and in 16 patients with proximal left circumflex (LCx) coronary artery stenosis at rest and immediately after pacing-induced tachycardia (LAD-pacing [P] and LCx-P) or coronary occlusion (LAD-CO and LCx-CO). BACKGROUND: During left ventricular (LV) ischemia, compensatory augmentation of LA contraction enhances LV filling and performance. The left atrium is supplied predominantly by branches arising from the LCx. Therefore, we hypothesized that one mechanism for the loss of atrial contraction may be ischemic LA dysfunction. METHODS: Left ventricular and LA pressure-area relations were derived from simultaneous double-tip micromanometer pressure recordings and automatic boundary detection echocardiograms. RESULTS: Immediately after pacing or after coronary occlusion, LV end-diastolic pressure, LV relaxation, LA mean pressure and LV stiffness significantly increased in all patients. However, the area of the A loop of the LA pressure-area relation, representing the LA pump function, significantly decreased in groups LCx-P and LCx-CO (from 14+/-3 to 9+/-2, and from 16+/-4 to 9+/-2 mm Hg.cm2, respectively, p < 0.05), whereas it increased in groups LAD-P and LAD-CO (from 12+/-3 to 54+/-10, and from 16+/-3 to 49+/-8 mm Hg.cm2, respectively, p < 0.001). CONCLUSIONS: In patients with LAD stenosis, LV supply or demand ischemia is associated with enhanced LA pump function. However, in patients with proximal LCx stenosis who develop the same type and degree of ischemia, LA branches might have been affected, rendering the LA ischemic and unable to increase its booster pump function.

Basal and flow-mediated nitric oxide production by atheromatous coronary arteries.

OBJECTIVES: This study assessed the effects of inhibition of nitric oxide synthesis on epicardial human coronary arteries and on coronary flow velocity during baseline conditions and during atrial pacing. BACKGROUND: Epicardial coronary artery dilation occurs in response to an increase in heart rate. It is not known whether the dilation of both angiographically normal and diseased epicardial coronary arteries during atrial pacing is nitric oxide dependent in humans. METHODS: The effects of an intracoronary infusion (4 mumol/min for 8 min) of NG-monomethyl-L-arginine (LNMMA), an inhibitor of nitric oxide synthesis, was studied in 16 patients with coronary artery disease and in 6 patients with normal coronary arteriograms. In all patients atrial pacing was performed during normal saline and during LNMMA infusion. the lumen diameter of epicardial coronary arteries was assessed by quantitative angiography, and changes in blood flow velocity were measured with a Doppler catheter. RESULTS: During saline infusion a significant increase in the lumen diameter of the proximal (p < 0.05) and distal (p < 0.01) segments of both normal and diseased arteries occurred during atrial pacing. No significant lumen diameter changes occurred in either group when atrial pacing was performed during LNMMA infusion. Stenosis diameter decreased during LNMMA infusion but did not change with atrial pacing either during saline infusion or during LNMMA infusion. The mean percent change in coronary blood flow with atrial pacing was less (p < 0.05) during LNMMA infusion than during saline infusion in both groups. CONCLUSIONS: These findings confirm that epicardial coronary artery dilation induced by pacing is nitric oxide dependent. Nitric oxide production contributes to the vasomotor tone of coronary resistance vessels. Nitric oxide is produced at the site of atheromatous stenosis but is unaffected by pacing.

Coronary artery distensibility in diabetic patients with simultaneous measurements of luminal area and intracoronary pressure: evidence of impaired reactivity to nitroglycerin.

OBJECTIVES: This study investigated whether noninsulin dependent diabetes mellitus (NIDDM) adversely affects the elastic properties of the coronary arteries in patients with coronary artery disease (CAD) and NIDDM. BACKGROUND: Attenuated vascular smooth muscle dilation to exogenous donors of nitric oxide, such as nitroglycerin, has been observed with forearm blood flow studies in patients with NIDDM. METHODS: Twenty patients with CAD and NIDDM (diabetics), and 20 patients with only CAD (nondiabetics) were evaluated. Intracoronary ultrasound (ICUS) imaging with simultaneous intracoronary pressure (P2) recordings were performed at the imaging site with 0.014 in fiber-optic high fidelity pressure monitoring wire. The same wire was used as guide wire for the ICUS catheter. Sites with less than 50% luminal stenosis by ICUS were studied. Recordings were done before and after 300 microg of intracoronary nitroglycerin (IC-NTG). Electrocardiographic tracings recorded simultaneously with ICUS images were used for timing. Systolic and diastolic cross-sectional lumen area (CSLA) and coronary artery distensibility (C-DIST) were measured, C-DIST = [(systolic CSLA-diastolic CSLA)/[(intracoronary pulse pressure) x (diastolic CSLA)]] x 1,000. RESULTS: Diabetics had smaller CSLA (diabetics = 8.6 +/- 0.6 mm2, nondiabetics = 11.5 +/- 0.5 mm2, p < 0.01). Although C-DIST was similar before IC-NTG in the two groups, it became significantly lower in diabetics after IC-NTG (diabetics C-DIST = 3.02 +/- 0.14 mm Hg(-1), nondiabetics C-DIST = 4.21 +/- 0.15 mm Hg(-1), p < 0.01). Degrees of circumference involved, total plaque burden and composition were similar in both groups. CONCLUSIONS: Noninsulin dependent diabetes mellitus reduces C-DIST after IC-NTG administration.

Effects of menopause on aortic root function in hypertensive women.

OBJECTIVES: This study sought to determine whether the natural decrease in sex hormones that occurs during menopause in hypertensive women plays a role in aortic root stiffness. BACKGROUND: The effect of menopause-induced sex hormone deprivation on aortic root function is not known; however, it is of special interest in hypertensive subjects, whose aortic elastic properties are already compromized. METHODS: Eighteen women with essential hypertension were followed-up for 3 years, during which time they went through menopause (group A) and were compared with 22 age-matched hypertensive women with normal menses (group B) and 20 hypertensive men (group C). Blind echocardiographic tracings and simultaneous blood pressure measurements were obtained after at least 30 medication-free days, both at baseline and 3.5 years later. RESULTS: Aortic root function tended to be aggravated in both groups B and C, but not significantly so, with no between-group differences (p = NS), whereas it deteriorated in group A. Thus, in menopausal hypertensive subjects, aortic root systolodiastolic percent change decreased (from 6.7% to 4.9%, p < 0.0001 [p = 0.002 vs. group B; p = 0.006 vs. group C]); cross-sectional compliance decreased (from 18 to 13 cm2/mm Hg, p < 0.0001 [p = 0.002 vs. group B; p = 0.03 vs. group C]); Peterson's elastic modulus increased (from 1.2 to 1.9 dynes/cm2, p = 0.0006 [p = 0.003 vs. group B; p = 0.005 vs. group C]); aortic stiffiness index increased (from 7.0 to 10.8, p = 0.0008 [p = 0.004 vs. group B; p = 0.007 vs. group C]); and aortic root distensibility decreased (from 1.8 to 1.2 dynes/cm2, p < 0.0001 [p = 0.0003 vs. group B; p = 0.007 vs. group C]). Serum lipids did not change significantly in any group (p = NS). CONCLUSIONS: In hypertensive women, the effect of menopause on the elastic properties of the aortic root is abrupt and devastating.

Increased local temperature in human coronary atherosclerotic plaques: an independent predictor of clinical outcome in patients undergoing a percutaneous coronary intervention.

OBJECTIVES: We investigated the midterm clinical significance of human coronary atherosclerotic plaques temperature after a successful percutaneous coronary intervention. BACKGROUND: Previous studies have shown an increased temperature in human atherosclerotic plaques. However, the prognostic significance of atherosclerotic plaque temperature in patients undergoing a successful percutaneous intervention is unknown. METHODS: We prospectively investigated the relation between the temperature difference (deltaT) between the atherosclerotic plaque and the healthy vessel wall and event-free survival among 86 patients undergoing a successful percutaneous intervention. Temperature was measured by a thermography catheter, as previously validated. The study group consisted of patients with effort angina (EA) (34.5%), unstable angina (UA) (34.5%) and acute myocardial infarction (AMI) (30%). RESULTS: The deltaT increased progressively from EA to AMI (0.132 +/- 0.18 degrees C in EA, 0.637 +/- 0.26 degrees C in UA and 0.942 +/- 0.58 degrees C in AMI). The median clinical follow-up period was 17.88 +/- 7.16 months. The deltaT was greater in patients with adverse cardiac events than in patients without events (deltaT: 0.939 +/- 0.49 degrees C vs. 0.428 +/- 0.42 degrees C; p < 0.0001). The deltaT was a strong predictor of adverse cardiac events during the follow-up period (odds ratio 2.14, p = 0.043). The threshold of the deltaT value, above which the risk for an adverse cardiac event was significantly increased, was 0.5 degrees C. The incidence of adverse cardiac events in patients with deltaT > or = 0.5 degrees C was 41%, as compared with 7% in patients with deltaT < 0.5 degrees C (p < 0.001). CONCLUSIONS: Increased local temperature in atherosclerotic plaques is a strong predictor of an unfavorable clinical outcome in patients with coronary artery disease undergoing percutaneous interventions.

Differentiating thrombus from pannus formation in obstructed mechanical prosthetic valves: an evaluation of clinical, transthoracic and transesophageal echocardiographic parameters.

OBJECTIVES: We sought to determine the clinical and echocardiographic parameters that differentiate thrombus from pannus formation as the etiology of obstructed mechanical prosthetic valves. BACKGROUND: Distinction of thrombus from pannus on obstructed prosthetic valves is essential because thrombolytic therapy has emerged as an alternative to reoperation. METHODS: We analyzed clinical, transthoracic and transesophageal echocardiography (TEE) data in 23 patients presenting with 24 obstructed prosthetic valves and compared the findings to pathology at surgery. RESULTS: Fourteen valves had thrombus and 10 had pannus formation. Patients with thrombus had a shorter duration from time of valve insertion to malfunction, shorter duration of symptoms, but similar New York Heart Association functional class at the time of operation. Patients with thrombus had a lower rate of adequate anticoagulation (21% vs. 89%; p=0.0028). Pannus formation was more common in the aortic position (70% vs. 21%; p=0.035). Abnormal prosthetic valve motion was detected by TEE in all cases with thrombus formation but in 60% with pannus (p=0.0198). Thrombi were larger than pannuses (total length 2.8+/-2.47 cm vs. 1.17+/-0.43 cm; p=0.038). This was mostly due to extension of thrombi into the left atrium in prosthetic mitral valves. Thrombi appeared as a soft mass on the valve in 92% of cases, whereas 29% of pannuses had a soft echo density (p= 0.007). Ultrasound video intensity ratio, derived as the videointensity of the mass to that of the prosthetic valve, was lower in the thrombus group (0.46+/-0.14 vs. 0.71+/-0.17, p=0.006). A videointensity ratio of <0.70 had a positive predictive value of 87% and a negative predictive value of 89% for thrombus. Duration from onset of symptoms to reoperation of <1 month separated thrombus from pannus formation. The best objective clinical parameter for prediction of thrombus was inadequate anticoagulation, whereas the best TEE parameters were qualitative and quantitative ultrasound intensity of the mass. The presence of either inadequate anticoagulation or a soft mass by TEE improved the predictive power of either parameter alone and was similar to that of ultrasound videointensity ratio. CONCLUSIONS: Duration of symptoms, anticoagulation status and qualitative and quantitative ultrasound intensity of the mass obstructing a mechanical prosthetic valve can help differentiate pannus formation from thrombus and may therefore be of value in refining the selection of patients for thrombolytic therapy of prosthetic valve obstruction.

Stents wrapped in autologous vein: an experimental study.

OBJECTIVES: A new type of coated stent, consisting of a conventional stent covered by an autologous vein graft, was developed at our institution. BACKGROUND: Coated stents are under investigation to address stenting limitations. However, experimental implantation of coated stents covered by autologous tissue has not been reported. METHODS: An autologous vein graft was removed and carefully prepared. Subsequently, a Palmaz stent was covered by the vein graft both internally and externally. Twenty-seven stents were implanted in the normal iliac arteries of 27 pigs weighing 18 to 33 kg. In 15 of the pigs, 15 noncoated Palmaz stents were implanted in the contralateral artery; these animals served as the control group. The animals were followed up angiographically for a period ranging from 7 days to 6 months. At the time of death, the stented segments were removed, and histomorphometric analysis was performed. RESULTS: Autologous vein graft-coated stent preparation and implantation was feasible and uncomplicated. In both stents, angiographic follow-up revealed the absence of thrombosis, except for two cases of subacute thrombosis in the control group. The thickness of the intimal layer was greater in the coated stents and seems to be due to the existence of the internal vein layer ([mean +/- SD] 0.57 +/- 0.12 vs. 0.27 +/- 0.13 mm, p = 0.001). The arterial media of the coated stent segments was thinner than that in the control group (0.14 +/- 0.03 vs. 0.18 +/- 0.01 mm, p = 0.02). CONCLUSIONS: The autologous vein graft-coated stent seems to be nonthrombogenic, and only minimal hyperplasia was observed in the pigs. Further studies are needed to explore the efficacy of this technique in humans.

Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin.

OBJECTIVES: The purpose of this study was to examine the genotype-phenotype relation with respect to penetrance, age and severity of expression, disease progression and prognosis in a recessively inherited arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: Naxos disease is a recessively inherited ARVC caused by a mutation in the gene encoding plakoglobin (cell adhesion protein) in which the cardiac phenotype is associated with palmoplantar keratoderma and woolly hair. METHODS: Twelve families with Naxos disease underwent cardiac and molecular genetic investigation. Serial cardiac assessment with annual resting 12-lead and 24-h ambulatory electrocardiogram (ECG) and two-dimensional echocardiography was performed during 1 to 16 years, median 7 +/- 6 years in all 78 surviving members. RESULTS: Twenty-eight surviving members were homozygous and 40 were heterozygous for the mutation. All adults who were homozygous (n = 26) fulfilled the diagnostic criteria for ARVC, the youngest by the age of 13 years. In eight who were heterozygous, minor ECG or echocardiographic abnormalities were observed. Of the 26 subjects who were affected homozygotes, 92% showed ECG abnormalities, 92% ventricular arrhythmias, 100% right ventricular structural alterations and 27% left ventricular involvement. During follow-up (10 +/- 6 years), 16 (62%) developed structural progression, 12 (46%) arrhythmic events and 7 (27%) heart failure. The annual disease-related and sudden death mortality was 3% and 2.3%, respectively. CONCLUSIONS: Autosomal recessive ARVC caused by a mutation in plakoglobin was 100% penetrant by adolescence. Affected subjects who were homozygous experienced progressive disease with adverse prognosis. A minority of subjects who were heterozygous showed minor ECG/echocardiographic changes, but clinically significant disease did not develop.

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.

Effects of balloon mitral valvuloplasty on left atrial function in mitral stenosis as assessed by pressure-area relation.

OBJECTIVES: This study sought to investigate the changes induced on the pressure-area relation of the left atrium in patients with mitral stenosis after percutaneous balloon mitral valvuloplasty. BACKGROUND: Left atrial (LA) function is influenced by changes in LA afterload. The latter is increased in mitral stenosis as a result of increased resistance to blood flow imposed by the stenotic mitral valve. METHODS: We studied the effects of acute alterations of LA afterload induced by retrograde nontransseptal balloon mitral valvuloplasty (RNBMV) on LA function in patients with mitral stenosis. LA pressure-area relations were obtained in 15 patients with mitral stenosis (8 with sinus rhythm, 7 with atrial fibrillation) before and after valvuloplasty, as well as in 15 normal subjects. LA pressure was recorded by a catheter-tipped micromanometer introduced retrogradely into the left atrium while LA area was recorded simultaneously using acoustic quantification. The areas of the A and V loops of the pressure-area relation as well as the LA chamber stiffness constant were calculated. RESULTS: Balloon valvuloplasty resulted in a significant increase in mitral valve area (p < 0.001) and a substantial reduction of the mean transmitral pressure gradient (p < 0.001) and mean LA pressure (p < 0.001). The area of the A loop in patients with sinus rhythm and the area of the V loop in those with atrial fibrillation increased significantly after completion of the procedure (p < 0.001). Furthermore, LA stiffness decreased in both groups. CONCLUSIONS: After RNBMV, there is a significant increase in LA pump function in patients with sinus rhythm, a significant increase in LA reservoir function in patients with atrial fibrillation and a significant reduction in LA stiffness in all patients. Marked alterations of the configuration of the LA pressure-area relation occur immediately after successful RNBMV in patients with mitral stenosis.

Assessment of left atrial pressure-area relation in humans by means of retrograde left atrial catheterization and echocardiographic automatic boundary detection: effects of dobutamine.

OBJECTIVES: This study sought to validate and apply a new method for obtaining the left atrial (LA) pressure-area relation. BACKGROUND: In physiologic investigations, the pressure-area relation is the most accurate and representative index of LA hemodynamic status. METHODS: We applied real-time two-dimensional echocardiographic imaging with automatic boundary detection to estimate LA area changes. To obtain LA pressure, a catheter-tipped micromanometer was introduced retrogradely into the left atrium using a steerable cardiac catheter developed at our institution. Twenty-five patients (11 normal subjects, 7 patients with an enlarged left atrium due to heart failure, 7 patients with atrial fibrillation) were studied before and after dobutamine administration. From the LA pressure-area relation, the area of the A loop (the first counterclockwise loop) and the V loop (the second clockwise loop), the pressure-minimal area relation and the LA passive elastic chamber stiffness constant were measured. RESULTS: Normalized pressure-minimal area relation was highly linear and sensitive to changes in inotropic state (normal subjects: from 0.96 to 1.27 mm Hg/cm2, p < 0.01; patients with heart failure: from 0.59 to 0.68 mm Hg/cm2, p = NS; patients with atrial fibrillation: from 0.80 to 1.06 mm Hg/cm2, p < 0.05). The LA stroke work index was accurately calculated, and a very good correlation was found with LA preload. LA stroke work index was lower in patients with heart failure (3.9 +/- 0.8 cm2 x mm Hg, p < 0.001), whereas the LA stiffness constant was increased in patients with heart failure (0.801 +/- 0.097 cm(-2), p < 0.01) and atrial fibrillation (0.796 +/- 0.091 cm(-2), p < 0.01) compared with normal subjects (stroke work index 7.3 +/- 1.9 cm2 x mm Hg, stiffness constant 0.623 +/- 0.107 cm(-2), respectively). In addition, increased inotropic state after dobutamine administration resulted in improved LA pump function (stroke work index) in normal subjects (from 10.2 +/- 0.9 to 13.8 +/- 1.9 cm2 x mm Hg, p < 0.001) and patients with heart failure (from 4.3 +/- 0.4 to 7.6 +/- 0.4 cm2 x mm Hg, p < 0.001), as well as in decreased stiffness constant in all groups of patients (normal subjects: from 0.712 +/- 0.141 to 0.473 +/- 0.089 cm(-2); patients with heart failure: from 0.896 +/- 0.181 to 0.494 +/- 0.093 cm(-2); patients with atrial fibrillation: from 0.779 +/- 0.145 to 0.467 +/- 0.086 cm(-2), p < 0.001). CONCLUSIONS: The method described here is both safe and reproducible for obtaining the LA pressure-area relation. LA function is impaired in patients with heart failure and in those with atrial fibrillation and may be acutely improved with inotropic agents in both normal and diseased atria.

Retrograde nontransseptal balloon mitral valvuloplasty: immediate results and intermediate long-term outcome in 441 cases--a multicenter experience.

OBJECTIVES: Our aim was to present the immediate and intermediate long-term results of the application of retrograde nontransseptal balloon mitral valvuloplasty (RNBMV) in four cooperating centers from Greece and India. BACKGROUND: RNBMV is a purely transarterial method of balloon valvuloplasty, developed with the aim to avoid complications associated with transseptal catheterization. Only single-center experience with RNBMV has been previously reported. METHODS: The procedure was attempted in 441 patients with symptomatic mitral stenosis (320 women, 121 men, mean age [+/-SD] 44+/-11 years, mean echocardiographic score [+/-SD] 7.7+/-2.0) from 1988 to 1996. Three hundred eighty-five patients with successful immediate outcome were followed clinically for a mean [+/-SD] of 3.5+/-1.9 (range, 0.5-9.1) years. RESULTS: A technically successful procedure was achieved in 388 (88%) cases. The echocardiographic score (p < 0.001), male gender (p=0.005), preprocedural mitral regurgitation (p=0.007) and previous surgical commissurotomy (p=0.029) were unfavorable predictors of immediate outcome. Complications included death (0.2%), severe mitral regurgitation (3.4%) and injury of the femoral artery (1.1%). Event-free (freedom from cardiac death, mitral valve surgery, repeat valvuloplasty and NYHA class > II symptoms) survival rates (+/-SEM) were 100%, 96.9+/-0.9%, 89.8+/-1.9% and 75.5+/-5.5% at 1, 2, 4 and 9 years, respectively. The echocardiographic score (p < 0.001), NYHA class (p=0.008) and postprocedural mitral valve area (p=0.009) were significant independent predictors of intermediate long-term outcome. CONCLUSIONS: Multicenter experience indicates that RNBMV is a safe and effective technique for the treatment of symptomatic mitral stenosis. As with the transseptal approach, patients with favorable mitral valve anatomy derive the greatest immediate and intermediate long-term benefit from this procedure.

The controversial role of serum uric acid in essential hypertension: relationships with indices of target organ damage.

The role of serum uric acid (SUA) in the context of adverse cardiovascular events in hypertensive subjects is controversial. Additionally, the relationship between SUA and indices of target organ damage is not well defined in this setting. Towards this end, we studied 842 consecutive nondiabetic patients with stage I-II essential hypertension (office blood pressure=148/95 mmHg, aged 53.4 years), referred to our outpatient hypertensive unit within a period of 4 years. According to the urinary albumin excretion (UAE), the study population was classified into those with microalbuminuria [MA(+), UAE=20-200 mg/24 h, n=222] and those without MA [MA (-), UAE< 20 mg/24 h, n=620]. Moreover, according to the presence of left ventricular hypertrophy (LVH) the participants were subdivided into two additional groups: [LVH (+), n=305 and LVH (-), n=537]. SUA levels were higher by 0.4 mg/dl, (P=0.04) in group MA (+) compared with the group MA (-), while no difference was observed between groups LVH (+) and LVH (-) (P=NS). In the entire population, SUA was correlated with body mass index (BMI) (r=0.17, P<0.001), waist/hip ratio (r=0.3, P<0.001), office systolic blood pressure (SBP) (r=0.14, P<0.05), triglycerides levels (r=0.25, P<0.001), UAE (r=0.35, P<0.001) and HDL (r=-0.26, P<0.001). Multiple regression analysis demonstrated that SUA was significantly related with BMI, office SBP and UAE (P<0.05). In conclusion, increased SUA levels are associated with MA but not with LVH in essential hypertensive subjects. Whether these inter-relationships may elucidate the clinical positioning of augmented SUA in this setting remains to be clarified in future studies.

Effects of oxyfedrin: a beta-adrenoreceptor stimulant, on infarct size following acute coronary artery ligation.

Regional left ventricular blood flow and the extent of myocardial ischaemia were studied after acute coronary artery occlusion in open-chest dogs before and after infusion of oxyfedrin, a beta-adrenergic stimulant. Regional blood flow was measured with radioactive tracer microspheres and local tissue injury was estimated by the S-T segment elevation in epicardial electrocardiograms. Animals receiving oxyfedrin were divided into two groups: 1 and 2. Oxyfedrin was infused intravenously in a dose of 0.80 to 0.94 mg.kg-1 in dogs of group 1 and 1.45 to 1.60 mg.kg-1 in dogs of group 2. The rate of infusion in the animals of both groups was 0.61 mg.min-1. Oxyfedrin caused further S-T segment elevation over ischaemic myocardium and increased the extent of ischaemic injury in group 1 dogs. Conversely, in this same group of dogs, the blood flow was unchanged in low flow regions ( less than 0.3 cm3.g-1.min-1) and increased in higher flow areas, inside the ischaemic region. In the animals of group 2, oxyfedrin caused further S-T segment elevation over ischaemic myocardium and increased the extent of ischaemic injury. Concomitantly, blood flow was significantly reduced both inside and outside the ischaemic region. These observations in dogs of group 1 (ie increased blood flow inside the ischaemic region by infusion of oxyfedrin, in flow zones higher than 0.3 cm3.g-1.min-1, with a further S-T segment elevation over ischaemic myocardium, and an increase in the extent of ischaemic injury) may be explained by a primary effect of oxyfedrin on oxygen demands with secondary changes in blood flow.

Antianginal drugs and relationship between epicardial ST segment depression and moderate regional myocardial blood flow reduction in experimental partial coronary artery occlusion.

STUDY OBJECTIVE: The aim of the study was to determine whether moderate reduction in regional myocardial blood flow is related to epicardial ST segment depression and to the changes in grade and extent induced in this variable by antianginal drugs. DESIGN: Blood flow through the anterior descending coronary artery was reduced to 25-30% of control in open chest dogs, using a cuff flow meter as a monitor, and glyceryl trinitrate, propranolol and nifedipine were infused 60 min later. Regional left ventricular blood flow was measured with 15 mu radioactive microspheres and electrocardiograms were recorded from the epicardial surface of the anterior left ventricular wall before and after administration of the drugs. EXPERIMENTAL SUBJECTS: 20 adult male greyhounds were used, weighing 19-24 kg. MEASUREMENTS AND RESULTS: Under control conditions there was a poor correlation between ST segment depression and regional flow. Neither glyceryl trinitrate nor nifedipine had any significant effect on ST segment depression in sites overlying zones with a flow range of 80-105% of normal flow. On the other hand, glyceryl trinitrate, but not nifedipine, decreased ST segment depression in sites overlying the central ischaemic zone (35-80% of control posterior wall flow). With propranolol, mean ST depression was decreased significantly in sites overlying the central ischaemic zone (35-80% of control flow), but not in sites overlying zones with flows ranging from 80-105% of normal. Propranolol reduced blood flow to all zones. CONCLUSIONS: Epicardial ST segment depression is unreliable for the quantitative exploration of the grade and extent of myocardial ischaemia.