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Aims: In pressure overload left ventricular (LV) hypertrophy, gender-related differences in global LV systolic function have been previously reported. The goal of this study was to determine regional systolic function of the left ventricle in male and female patients with hypertensive heart disease., Methods and Results: Regional LV function was analyzed from multiplane transesophageal echocardiography with three-dimensional (3D) reconstruction of the left ventricle. In 24 patients (13 males and 11 females), four parallel (2 basal and 2 apical) equidistant short axis cross-sections from base to apex were obtained from the reconstructed LV. In each short axis 24 wall-thickness measurements were carried out at 15 degrees intervals at end-diastole and end-systole. Thus, a total of 192 measurements were obtained in each patient. Wall thickening was calculated as difference of end-diastolic and end-systolic wall thickness, and fractional thickening as thickening divided by end-diastolic thickness. Fractional thickening and wall stress were inversely related to end-diastolic wall thickness in both, males and females. Females showed less LV systolic function when compared to males (p<0.001). However, when corrected for wall stress, which was higher in females, there was no gender difference in systolic function., Conclusion: There are regional differences in LV systolic function in females and males which are directly related to differences in wall stress. Thus, gender-related differences in LV regional function are load-dependent and not due to structural differences.

Aims: Intravascular inflammatory events during ischaemia/reperfusion injury following coronary angioplasty alter and denudate the endothelium of its natural anticoagulant heparan sulfate proteoglycan (HSPG) layer, contributing to myocardial tissue damage. We propose that locally targeted cytoprotection of ischaemic myocardium with the glycosaminoglycan analogue dextran sulfate (DXS, MW 5000) may protect damaged tissue from reperfusion injury by functional restoration of HSPG., Methods and Results: In a closed chest porcine model of acute myocardial ischaemia/reperfusion injury (60 min ischaemia, 120 min reperfusion), DXS was administered intracoronarily into the area at risk 5 min prior to reperfusion. Despite similar areas at risk in both groups (39+/-8% and 42+/-9% of left ventricular mass), DXS significantly decreased myocardial infarct size from 61+/-12% of the area at risk for vehicle controls to 39+/-14%. Cardioprotection correlated with reduced cardiac enzyme release creatine kinase (CK-MB, troponin-I). DXS abrogated myocardial complement deposition and substantially decreased vascular expression of pro-coagulant tissue factor in ischaemic myocardium. DXS binding, detected using fluorescein-labelled agent, localized to ischaemically damaged blood vessels/myocardium and correlated with reduced vascular staining of HSPG., Conclusion: The significant cardioprotection obtained through targeted cytoprotection of ischaemic tissue prior to reperfusion in this model of acute myocardial infarction suggests a possible role for the local modulation of vascular inflammation by glycosaminoglycan analogues as a novel therapy to reduce reperfusion injury.

Aims: To investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis., Methods and Results: Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent thrombosis was acute in 10 (11%), subacute in 61 (64%), and late in 24 (25%) patients. Procedural and clinical outcomes of emergency PCI for treatment of stent thrombosis were investigated. Emergency PCI was successful in 86 (91%), complicated by death in 2 (2%), and coronary artery bypass grafting in 2 (2%) patients. Myocardial infarction occurred in 77 (81%) patients with a peak creatine kinase level of 1466+/-1570 U/L. Left ventricular ejection fraction declined from 0.54+/-0.19 prior to 0.48+/-0.16 (P<0.05) at the time of stent thrombosis after emergency PCI. A 6 month major adverse clinical events comprised death (11%), reinfarction (16%), and recurrent stent thrombosis (12%) after emergency PCI. Multivariable logistic regression analysis identified the achievement of TIMI 3 flow (OR=0.1, CI 95% 0.01-0.54, P<0.001) and diameter stenosis <50% (OR=0.06, CI 95% 0.01-0.32, P<0.001) during emergency PCI to be independently associated with a reduced risk of cardiac death. Recurrent stent thrombosis was independently predicted by the omission of abciximab (OR=4.3, CI 95% 1.1-17.5)., Conclusion: Emergency PCI for treatment of stent thrombosis effectively restores vessel patency and flow. Patients presenting with stent thrombosis are at risk for recurrent myocardial infarction and recurrent stent thrombosis.

Background: The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia., Methods: Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow., Results: Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA., Conclusions: Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand.

Background: To test the hypothesis that troponin I and echocardiography have an incremental prognostic value in patients with pulmonary embolism (PE)., Methods and Results: In 91 patients with acute PE, echocardiography was performed within 4h of admission. Troponin I levels were obtained on admission and 12h thereafter. The 0.06 microg/l troponin I cut-off level was identified as the most useful, high-sensitivity cut-off level for the prediction of adverse outcome by receiver operating characteristic analysis with a sensitivity and specificity of 86%, respectively. Twenty-eight (31%) patients had elevated troponin I levels (4.9+/-3.8 microg/l). Twenty-one (23%) patients had adverse clinical outcomes including in-hospital death in five, cardiopulmonary resuscitation in four, mechanical ventilation in six, pressors in 14, thrombolysis in 14, catheter fragmentation in three, and surgical embolectomy in three. The area under the receiver operating characteristic curve from multivariate regression models for predicting adverse outcome without troponin I and echocardiography (0.765), with troponin I (0.890) or echocardiography alone (0.858), and the combination of both tests (0.900) was incremental. Three-month survival rate was highest in patients with both a normal troponin I level and a normal echocardiogram (98%). Positive predictive value for adverse clinical outcomes of the combination of echocardiography and troponin I was higher (75% (95%CI 55-88%)) compared with each test alone (echocardiography: 41%, 95% CI 28-56%; troponin I: 64%, 95% CI 46-79%)., Conclusions: While troponin I measurements added most of the prognostic information for identifying high-risk patients, a normal echocardiogram combined with a negative troponin I level was most useful to identify patients at lowest risk for early death.

Aims: A simple management strategy is required for patients with acute pulmonary embolism which allows a rapid and reliable diagnosis in order to start timely and appropriate treatment., Methods and Results: Two hundred and four consecutive patients with suspected pulmonary embolism were managed according to a standardized protocol based on the clinical pretest probability and the initial haemodynamic presentation (shock index=heart rate divided by systolic blood pressure). Patients with a high pretest probability and a positive shock index (> or =1) (n=21) underwent urgent transthoracic echocardiography. Based on the presence or absence of right ventricular dysfunction, reperfusion treatment was initiated immediately. Patients with a negative shock index (<1) (n=183) underwent diagnostic evaluation including pretest probability, D-dimer, and spiral computed tomography (CT) as first-line tests. Echocardiography was performed only when a central pulmonary embolism was found in the spiral CT(n=33). According to our strategy, 98 patients met the diagnostic criteria of pulmonary embolism: 75 patients (all shock index <1) were treated with heparin alone, 16 (seven had a shock index > or =1) with thrombolysis, four (all shock index > or =1) with catheter fragmentation, and three (all shock index > or =1) with surgical embolectomy. The all-cause mortality rate at 30 days was 5%, and at 6 months 11%. Right ventricular dysfunction on baseline echocardiography was not associated with a higher mortality rate at 6 months (logrank 2.4, P=0.12)., Conclusions: The novel management strategy for patients with suspected pulmonary embolism resulted in a rapid diagnosis and treatment with a low 30-day mortality. In patients with pulmonary embolism and a positive shock index, time-consuming imaging tests can be avoided to reduce the risk of sudden death and not to delay reperfusion therapy.

Aims: Restenosis after percutaneous coronary angioplasty remains an important limitation of this procedure. This study evaluates whether elevated total plasma homocysteine levels contribute to the development of restenosis after coronary angioplasty., Methods and Results: Two hundred and five patients were recruited after successful angioplasty of at least one coronary stenosis (> or =50%). End-points were restenosis (> or =50%) and a composite of major adverse cardiac events. Of the 205 patients, 183 (89.3%) underwent 6 months angiographic follow-up. Patients with restenosis had significantly higher homocysteine levels than those without (10.9+/- 3.9 micromol x l(-1) vs 9.3+/-3.8 micromol x l(-1), P<0.01). Homocysteine levels were significantly correlated to follow-up diameter stenosis (r=0.24, P=0.0001), especially in small vessels (<3 mm) treated with balloon angioplasty only (r=0.40, P<0.0005). Late lumen loss at follow-up was significantly smaller with homocysteine levels below 9 micromol x l(-1) (0.62+/-0.82 mm vs 0.90+/-0.77 mm, P<0.01). Restenosis rate (25.3% vs 50.0%, P<0.001) and major adverse cardiac events (15.7% vs 28.4%, P<0.05) were also significantly lower in patients with homocysteine levels below 9 micromol x l(-1). Multivariate analysis did not weaken these findings., Conclusion: Total plasma homocysteine is a strong predictor of restenosis and major adverse cardiac events after coronary angioplasty. Thus, plasma homocysteine appears to be an important cardiovascular risk factor influencing outcome after successful coronary angioplasty., (Copyright 2001 The European Society of Cardiology.)

Objective: Immunosuppressive agents have been proposed to reduce neointimal hyperplasia in synthetic vascular grafts. Thus, the purpose of the present study was to evaluate the safety and efficacy of rapamycins (systemic vs. local vs. oral administration) and mycophenolate mofetil (MMF) to reduce intimal hyperplasia in infrarenal synthetic vascular grafts of the rat., Methods: Fifty-four Wistar rats (250 g) completed the study after a synthetic vascular graft (ePTFE, Gore-tex, 2 mm diameter, 10 mm length) was implanted end-to-end in the infrarenal aorta. The animals were divided into three groups: group 1 consisted of 12 control animals, group 2 consisted of 37 rats receiving rapamycins, either per os (RAD, 1.5 or 3 mg/kg), intraperitoneally (RPM, 1.5 or 3 mg/kg) or locally (RPM soaking of the graft); and in group 3 (n=5), MMF (40 mg/kg) was administered orally. The animals were followed weekly with weight controls and signs of toxicity for 30 (n=37) and 60 (n=17) days, respectively. All animals were sacrificed and underwent histological examination at completion of the study., Results: All animals survived in groups 1 and 3, but five died in group 2. The weight gain was normal in all groups, except for the subgroup 2a receiving high dose rapamycins orally. All rats in group 3 suffered from diarrhea, whereas animals receiving high dose rapamycins showed toxic signs (hair loss, wound healing problems). Histological examination showed a significant increase in intimal hyperplasia in group 1 (0.03+/-0.01 and 0.14+/-0.05 microm after 30 and 60 days, respectively; P<0.01). Rapamycins in either application or dosage had no significant effect on intimal hyperplasia., Conclusions: Local or systemic administration of rapamycins has no effect on intimal hyperplasia in synthetic vascular grafts. In contrast, toxic signs with weight loss were observed in animals treated with high dose rapamycins, but not in those treated with MMF. Thus, in the rat model, immunosuppression with rapamycins or MMF cannot be recommended for the prevention of intimal hyperplasia in the synthetic vascular graft model.

Background: Diastolic dysfunction with delayed relaxation and abnormal passive elastic properties has been described in patients with severe pressure overload hypertrophy. The purpose of this study was to evaluate the time course of rotational motion of the left ventricle in patients with aortic valve stenosis using myocardial tagging., Methods: Myocardial tagging is a non-invasive method based on magnetic resonance which makes it possible to label ('tag') specific myocardial regions. From the motion of the tag's cardiac rotation, radial displacement and translational motion can be determined. In 12 controls and 13 patients with severe aortic valve stenosis systolic and diastolic wall motion was assessed in an apical and basal short axis plane., Results: The normal left ventricle performs a systolic wringing motion around the ventricular long axis with clockwise rotation at the base (-4.4+/-1.6 degrees) and counter-clockwise rotation at the apex (+6.8+/-2.5 degrees) when viewed from the apex. During early diastole an untwisting motion can be observed which precedes diastolic filling. In patients with aortic valve stenosis systolic rotation is reduced at the base (-2.4+/-2.0 degrees; P<0.01) but increased at the apex (+12.0+/-6.0 degrees; P<0.05). Diastolic untwisting is delayed and prolonged with a decrease in normalized rotation velocity (-6.9+/-1.1 s(-1)) when compared to controls (-10.7+/-2.2 s(-1); P<0.001). Maximal systolic torsion is 8.0+/-2.1 degrees in controls and 14.1+/-6.4 degrees (P<0.01) in patients with aortic valve stenosis., Conclusions: Left ventricular pressure overload hypertrophy is associated with a reduction in basal and an increase in apical rotation resulting in increased torsion of the ventricle. Diastolic untwisting is delayed and prolonged. This may explain the occurrence of diastolic dysfunction in patients with severe pressure overload hypertrophy.

The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosis.

To evaluate gender-related differences in left ventricular (LV) structure and function in aortic stenosis, LV biplane cineangiography, micromanometry and endomyocardial biopsies were carried out in 56 patients with aortic stenosis and normal coronary arteries. Patients were divided into males (M: n = 35), and females (F: n = 21). Sixteen normal subjects 8 M, 8 F) served as haemodynamic controls. Control biopsy data were obtained from six pre-transplantation donor hearts (3 M and 3 F). LV systolic function was evaluated by ejection fraction and its relationship to mean systolic circumferential wall stress, diastolic function by the time constant of LV pressure decay, peak filling rates and passive myocardial stiffness constant. Biopsy samples were evaluated for interstitial fibrosis, muscle fibre diameter and volume fraction of myofibrils. In a subset of 27 consecutive patients, biopsy samples were evaluated with a morphometric-morphological method, for total collagen volume fraction, endocardial fibrosis and the extension and thickness of orthogonal collagen fibres (cross-hatching). In patients with aortic stenosis, aortic valve area, aortic valve resistance and mean aortic pressure gradient were comparable in males and females, whereas end-systolic and end-diastolic volumes were larger in males than females. Ejection fraction was lower (56%) in males than females (64%) (P < 0.05); 20 of 35 males and four of 21 females had depressed systolic contractility when assessed with regard to the relationship ejection fraction-mean systolic stress (P < 0.01). Myocardial stiffness constant was higher in males than in females (P < 0.01). Nine of 14 males and two of 13 females had endocardial fibrosis (P < 0.009), whereas increased cross-hatching (> 1.5 grade) was present in 11 males and four females with aortic stenosis (P < 0.01). An abnormal collagen architecture was present in 13/14 males and 5/13 females (P < 0.002). In aortic stenosis, males have a depressed systolic function and abnormal passive elastic properties when compared to females with valve lesions of similar severity. Changes in collagen architecture may account, at least in part, for these differences.

Left ventricular (LV) failure can be divided into systolic and diastolic dysfunction. The former is characterized by a reduced ejection fraction and an enlarged LV chamber, the latter by an increased resistance to filling with increased filling pressures. Systolic dysfunction is clinically associated with left ventricular failure in the presence of marked cardiomegaly, while diastolic dysfunction is accompanied by pulmonary congestion together with a normal or only slightly enlarged ventricle. Echocardiography is currently the most relevant technique for non-invasive differentiation of the two forms. Systolic dysfunction is easily assessable by estimation of global ejection fraction and regional wall motion. Diastolic dysfunction can be diagnosed indirectly by means of a normal or nearly normal ejection fraction and and changes of the mitral filling pattern in the context of LV failure. For an exact determination of diastolic dysfunction LV catheterization is required. Systolic dysfunction treatment is well defined, consisting of ACE inhibitors, followed by diuretics and digitalis. Calcium channel blockers are usually contraindicated. Diastolic dysfunction therapy is more dependent on the underlying disease. Calcium channel blockers, ACE inhibitors or beta-blockers are first line drugs in most instances: diuretics can be added with increasing symptoms. Digitalis should be avoided, except in atrial fibrillation, to control heart rate.

The effect of atrial contraction on cardiac function is reviewed in patients with dual chamber and rate-responsive ventricular pacemakers. The question posed was is there any haemodynamic, clinical or prognostic advantage of AV synchrony in dual chamber pacemakers in comparison to rate-responsive ventricular pacemakers? Optimal AV delay in dual chamber pacing favours cardiac performance at rest, while during exercise the increase in heart rate rather than AV synchrony influences cardiac performance and working capacity. However, there is little information on the benefit of maintained AV synchrony in patients' daily activities. Patients with pacemakers which maintain AV synchrony seem to have less morbidity and mortality than patients with ventricular stimulation alone, and there are comparable rates of complication in carriers of single and dual chamber pacemakers, the former showing problems with the pacemaker syndrome and the latter with atrial sensing and pacemaker-induced tachycardias. The disadvantage of dual chamber pacemakers are higher costs and time-consuming controls.

The effect of mechanical circulatory support on left ventricular (LV) function was evaluated during prolonged myocardial ischaemia. Regional wall thickening of a normal and an ischaemic LV region were determined in eight calves (mean body weight 76 kg) using pairs of ultrasonic crystals. LV end-diastolic (mmHg) and peak systolic (mmHg) pressure as well as maximum dP/dt (mmHg s-1) were calculated from LV high-fidelity pressure tracings. The left circumflex coronary artery was ligated proximally for 6 h and reperfused for 18 h. Circulatory support by the assist device was performed from the beginning of ischaemia to the end of the experiment. After a mean time of 4 h all animals showed ventricular fibrillation, which was converted successfully in six animals after a mean time interval of 5 h. Five animals survived after 24 h. The non-surviving animals had larger infarcts, greater creatine kinase release and a larger drop in cardiac output during ischaemia. Haemodynamic measurements were carried out after turning off the assist device. Inotropic stimulation with 0.68 mg.min-1 dopamine i.v. was performed at the end of the study. LV regional function showed systolic bulging during myocardial ischaemia. After 18 h of reperfusion, the ischaemic wall recovered and showed normal systolic wall thickening in the presence of an increased LV preload. LV relaxation was prolonged after reperfusion, suggesting diastolic dysfunction. It is concluded that mechanical circulatory support is effective in protecting myocardial function during prolonged ischaemia in approximately two-thirds of the animals, despite severe ischaemic ventricular dysfunction and intermittent ventricular fibrillation.

The accuracy of digital subtraction angiography (DSA) for determination of left ventricular (LV) systolic wall thickness and muscle mass was evaluated in 20 patients (mean age 50 +/- 11 years). Conventional LV angiograms were digitized and subtracted using a combined subtraction mode ('mask mode' and 'time interval difference' subtraction). Wall thickness and muscle mass were determined at end-diastole, after the first- and second-third of systole and at end-systole. M-mode echocardiography (Echo), which was obtained from beam selection of the two-dimensional echocardiogram and conventional angiography (LVA), served as reference techniques. Angiographic LV wall thickness and muscle mass were determined according to the technique of Rackley in both, right (RAO) and left (LAO) anterior oblique projections, whereas echocardiographic wall thickness was measured just below the mitral valve orthogonal to the posterior wall (= LAO equivalent). Percent wall thickening was calculated in all patients. LV end-diastolic wall thickness and muscle mass correlated well between DSA and LVA (LV end-diastolic wall thickness in LAO projection r = 0.72, biplane LV end-diastolic muscle mass r = 0.83), LV end-systolic wall thickness (1.44 vs 1.33 cm, P less than 0.05) and percent wall thickening (52 vs 42%, P less than 0.05) compared favourably between echocardiography and DSA but was significantly larger when echocardiographically measured than with DSA (LAO projection). DSA and echocardiography showed a good correlation in regard to LV end-diastolic and end-systolic wall thickness (correlation coefficient r = 0.89, standard error of estimate SEE = 0.15 cm or 13% of the mean value).(ABSTRACT TRUNCATED AT 250 WORDS)

In patients with aortic valve disease and normal coronary angiograms coronary reserve was determined by the coronary sinus thermodilution technique. Three groups of patients were studied: 37 preoperative patients; 18 different patients 12-52 months after aortic valve replacement and seven control subjects with no cardiac disease. Coronary flow ratio (dipyridamole/rest) was diminished in preoperative compared with postoperative patients (1.66 +/- 0.44 vs 2.22 +/- 0.85; P less than 0.05) as well as with controls (2.80 +/- 0.84; P less than 0.01), and corresponding coronary resistance ratio (dipyridamole/rest) was higher in preoperative patients than in both other groups (0.61 +/- 0.17 vs 0.48 +/- 0.14; P less than 0.05 vs 0.37 +/- 0.10; P less than 0.01). Differences in the flow ratio, but not in the resistance ratio, were significant (P less than 0.05) in patients after aortic valve replacement compared with controls. Total coronary sinus blood flow at rest was elevated in preoperative compared with both postoperative patients and controls (252 +/- 99 vs 169 +/- 63; P less than 0.01; vs 170 +/- 35 ml.min-1, P less than 0.05), whereas flows after maximal vasodilation did not differ among the three groups (416 +/- 184 vs 361 +/- 150 vs 488 +/- 235 ml.min-1). Postoperative patients showed a distinct, though not total regression of left ventricular angiographic muscle mass index and wall thickness. Nine of the 18 postoperative patients showed a normal coronary flow reserve and nine showed subnormal response. These two subgroups did not differ with respect to preoperative macroscopic and microscopic measures of hypertrophy. Thus in aortic valve disease, the reduced coronary vasodilator capacity is mainly due to an elevated coronary flow at rest, while the maximal coronary blood flow achieved is identical to that of postoperative patients and controls. With regression of left ventricular hypertrophy, flow at rest decreases and this leads to a distinct improvement of coronary flow reserve.

Coronary vasomotion plays an important role in the regulation of coronary perfusion at rest and during exercise. Normal coronary arteries show coronary vasodilation of the proximal (+20%) and distal (+40%) vessel segments during supine bicycle exercise. However, patients with coronary artery disease show exercise-induced vasoconstriction of the stenotic vessel segments. The exact mechanism of exercise-induced stenosis narrowing is not clear but might be related to a passive collapse of the disease-free vessel wall (Venturi mechanism), elevated plasma levels of circulating catecholamines, an insufficient production of the endothelium-derived vasorelaxing factor or increased platelet aggregation due to turbulent blood flow with release of thromboxane A2 and serotonin. Various vasoactive drugs, such as nitroglycerin and calcium antagonists, prevent exercise-induced stenosis vasoconstriction. An additive effect on coronary vasodilation of the stenotic vessel segment was observed after combination of nitroglycerin with diltiazem. Thus, exercise-induced stenosis narrowing plays an important role in the pathophysiology of myocardial ischaemia during dynamic exercise. The antianginal effect of vasoactive substances can be explained--besides the effect on pre- and afterload--by a direct action on coronary stenosis vasomotion.

In patients with hypertrophic cardiomyopathy (HCM), impaired left ventricular (LV) relaxation and diastolic filling have been reported. Therefore, we determined LV diastolic stiffness in nine patients with HCM before and 10 to 15 min after 0.15 mg/kg propranolol i.v. (group 1) and in six patients with HCM before and 10 to 15 min after 0.1 mg/kg verapamil i.v. (group 2). Simultaneous LV cineangiography and high-fidelity pressure measurements were performed in group 1 and simultaneous M-mode echocardiography and high-fidelity pressure measurements in group 2. Passive LV chamber stiffness was determined in group 1 from the diastolic pressure-volume data using an exponential three-parameter model: P = ae beta V + C, where P = pressure, alpha = intercept, beta = constant of chamber stiffness, V = volume and C = baseline pressure. Passive LV myocardial stiffness was estimated in group 2 from the diastolic stress-strain data using a viscoelastic model: sigma = alpha' (e beta' epsilon -1) + eta epsilon, where sigma = meridional wall stress, alpha = intercept, beta' = constant of myocardial stiffness, epsilon = midwall strain, eta = constant of myocardial viscosity and epsilon = strain rate. LV relaxation was assessed from the time constant of LV pressure decay (T) by plotting LV pressure versus negative dP/dt. LV diastolic filling was evaluated from peak and mean LV filling rate in group 1 and from peak and mean midwall lengthening rate in group 2. LV chamber and myocardial stiffness, respectively, remained unchanged before and after administration of propranolol (beta = 0.054 and 0.047) and verapamil (beta' = 14.8 and 12.6); however, the time constant of LV pressure decay T increased significantly in group 1 from 45 to 66 ms (P less than 0.05) and decreased significantly in group 2 from 53 to 43 ms (P less than 0.05). Parallel to the changes in LV isovolumic relaxation, mean LV diastolic filling rate decreased significantly in group 1 from 257 to 196 ml m-2 s-1 (P less than 0.025) and mean LV midwall lengthening rate increased significantly in group 2 from 2.37 to 4.31 cm/sec (P less than 0.05). It is concluded that LV diastolic stiffness remains unchanged in patients with HCM after propranolol and verapamil. LV relaxation and mean diastolic filling, however, are impaired in patients with HCM following propranolol but are improved after verapamil. Thus, the beneficial effect of verapamil on diastolic mechanics is related to improved relaxation and diastolic filling rather than to changes in LV diastolic stiffness.

Coronary vasomotion is an important determinant of myocardial perfusion in patients with angina pectoris, and it influences not only normal but also stenotic coronary arteries. The ability of a stenotic coronary artery to change its size is dependent on the presence of a normal musculo-elastic wall segment within the stenosis (i.e., eccentric stenosis). Coronary vasoconstriction of normal and stenotic coronary arteries has been reported by Brown and coworkers (Circulation 1984; 70: 18-24) during isometric exercise. The effect of dynamic exercise on coronary vasomotion was evaluated in one group of 13 patients with ischaemia-like symptoms and normal coronary arteries (group 1) and in a second group of 12 patients with coronary artery disease with exercise-induced angina pectoris (group 2). Luminal area of a normal and a stenotic vessel segment was determined by biplane quantitative coronary arteriography at rest, during supine bicycle exercise and 5 min after administration of 1.6 mg sublingual nitroglycerin. Coronary sinus blood flow was measured in group 1 at rest and after 0.5 mg kg-1 intravenous dipyridamole using coronary sinus thermodilution. Coronary flow reserve was calculated from coronary sinus flow after dipyridamole divided by coronary sinus flow at rest. In group 1, coronary vasodilation of the large (i.e., proximal) and the small (i.e., distal) coronary arteries was observed during exercise in seven patients (subgroup A). However, in the remaining six patients (subgroup B) coronary vasoconstriction of the small arteries (-24%, P less than 0.001) was found during exercise, whereas the large vessels showed coronary vasodilation (+26%, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

In 14 patients (pts) with aortic valve disease (AVD) left ventricular (LV) relaxation was assessed by the time constant (T) of LV pressure (tipmanometer) fall before and 19 months after successful aortic valve replacement (AVR). 12 control pts (CO) were studied by the same technique. Preoperative LV ejection fraction in AVD (64%) and in CO (69%) did not differ. In AVD T was increased (60 ms) as compared to the CO (38 ms, P less than 0.05). During handgrip (HG) there was a similar increase of LV peak systolic pressure (LVSP), heart rate and peak measured contractile element velocity of shortening in AVD and in the CO. LV end-diastolic pressure varied minimally in both groups. T decreased during handgrip in CO (38 to 33 ms, P less than 0.01) and remained unchanged in AVD. Following AVR T at rest decreased insignificantly to 52 ms, but remained increased (P less than 0.025) as compared with CO. During postoperative HG however, a decrease to 47 ms (P less than 0.05) was noted. Postoperative angiographic LV muscle mass (105 g/m2) and LVSP at rest (137 mmHg) remained elevated (P less than 0.02) as compared to CO (72 g/m2; 119 mmHg). It is concluded that (1) in AVD with normal ejection performance LV relaxation at rest is prolonged and the reaction of relaxation to HG is abnormal despite preserved contractile response, (2) following AVR the response of LV relaxation to HG becomes normal and (3) elevated postoperative T at rest appears to be related to residual hypertrophy and probably also to the still increased LVSP rather than to intrinsic disturbances of myocardial relaxation.

Left ventricular (LV) volume was determined simultaneously by monoplane cineangiocardiography and conductivity using a multielectrode conductance catheter at rest and during pressure loading in seven mongrel dogs (mean body weight 22 kg). LV volumes were calculated frame-by-frame (75 frames s-1) by angiocardiography and matched with instantaneous volumes obtained by conductivity. There was an excellent correlation between the two techniques at rest (correlation coefficient, r = 0.96) and during pressure loading (r = 0.92) when the data of each dog were pooled. The standard error of estimate of the mean angiographic volume was 4%. The slope of the regression analysis showed a small but significant (P less than 0.01) decrease from 0.365 at rest to 0.289 during pressure loading, whereas the intercept remained unchanged (24 versus 26 ml). Since no calibration for parallel conductivity of the surrounding tissue was performed, LV end-systolic volume was significantly over- and LV ejection fraction significantly underestimated whereas LV end-diastolic volume was estimated correctly by the conductance technique. It is concluded that LV end-diastolic volume can be determined accurately by the conductance technique in dogs. However, LV end-systolic volume is significantly over- and ejection fraction significantly underestimated. Since there is a good correlation between angiocardiography and conductivity, exact determination of LV volumes and ejection fraction is feasible using a correction factor. The change in slope of the regression equation between angiocardiography and conductivity suggests a change in conductivity of the surrounding tissue during pressure loading which limits the application of the conductance catheter to stable haemodynamic situations or calls for repeated calibrations by an independent technique during acute interventions.

The effect of intracoronary and intravenous propranolol on coronary vasomotion was evaluated in 28 patients with coronary artery disease. Luminal area of a normal and a stenotic coronary vessel segment was determined at rest, during submaximal bicycle exercise and 5 min after 1.6 mg sublingual nitroglycerin administered at the end of the exercise test involving biplane quantitative coronary arteriography. Patients were divided into three groups: group 1 (n = 12) served as the control group, group 2 consisted of 10 patients with intracoronary administration of 1 mg propranolol and group 3 of six patients with intravenous administration of 0.1 mg kg-1 propranolol prior to the exercise text. In the control group there was coronary vasodilation (+23%, P less than 0.01) of the normal and coronary vasoconstriction (-29%, P less than 0.001) of the stenotic vessel segment during bicycle exercise. After sublingual administration of 1.6 mg nitroglycerin there was vasodilation of normal (+40%, P less than 0.001 vs rest) and stenotic (+12%, NS vs rest) vessel segments. In group 2 intracoronary propranolol was not accompanied by a change in coronary vessel area but both normal (+13%, P less than 0.05) and stenotic (+22%, P less than 0.05) vessel segments showed coronary vasodilation during bicycle exercise. After sublingual nitroglycerin there was further vasodilation of both normal (+31%, P less than 0.001 vs rest) and stenotic (+45%, P less than 0.01 vs rest) arteries. In group 3 intravenous administration of propranolol was associated with a decrease in coronary luminal area of both normal (-24%, P less than 0.001) and stenotic (-31%, P less than 0.001) vessel segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular (LV) wall thickness and muscle mass are important measures of LV hypertrophy. In 24 patients LV end-diastolic wall thickness and muscle mass were determined (two observers) by digital subtraction angiocardiography (DSA) and conventional LV angiocardiography (LVA). Wall thickness was determined over the anterolateral wall of the left ventricle according to the technique of Rackley (method 1) or by planimetry (method 2). Seventeen patients were studied at rest and seven during dynamic exercise. Wall thickness correlated well between LVA and DSA; the best correlations were obtained by a combined subtraction mode using either method 1 or 2 (method 1, r greater than or equal to 0.80; method 2, r greater than or equal to 0.75). The standard error of estimate of the mean (SEE) was slightly lower for method 2 (less than or equal to 10%) than for method 1 (less than or equal to 13%). DSA significantly overestimated wall thickness by 5-7% with method 1 and underestimated by 12-14% with method 2. Muscle mass correlated well between LVA and DSA; the SEE was less than or equal to 15% for method 1 and less than or equal to 12% for method 2. Overestimation of muscle mass by DSA was 7-11% with method 1 and underestimation was 13-15% with method 2. It is concluded that LV wall thickness can be determined accurately by DSA with an SEE ranging between 10 and 13%. Determination of LV muscle mass is slightly less accurate and the SEE is slightly larger ranging between 13 to 17%. With method 1, wall thickness and muscle mass were overestimated and with method 2 underestimated.

In aortic valve stenosis, concentric hypertrophy develops which is characterized by a reduced end-diastolic radius-to-wall thickness ratio (r/h) with an essentially normal cavity shape. As long as the product of (r/h) and LV systolic pressure remains constant, hypertrophy is appropriate. An increase in the product, which represents an increase in wall stress signals inadequate LV hypertrophy. Although at first glance, massive LV hypertrophy appears favourable for the maintenance of a normal LV ejection fraction in aortic stenosis, data from 23 studies of the literature have shown an inverse relationship between ejection fraction and LV angiographic mass m-2 (r = -0.59). Both a degree of hypertrophy inadequate to keep systolic wall stress within normal limits and a reduction of LV contractility may explain the depression of ejection fraction when LV angiographic mass is sizeably increased. Conversely, a normal ejection fraction in aortic stenosis may not be indicative of normal systolic myocardial function under all circumstances. In the presence of mildly reduced contractility, a normal ejection fraction may be maintained by the use of preload reserve. Assessment of myocardial structure from LV endomyocardial biopsies revealed no differences in muscle fibre diameter, interstitial fibrosis and volume fraction of myofibrils between patients with aortic stenosis having a normal and those with a depressed ejection fraction. Preoperative ejection fraction is a poor predictor of postoperative survival, whereas markedly increased preoperative angiographic mass and end-systolic volume have been reported to predict an unsatisfactory postoperative outcome characterized by either death or poor LV function.

The vasodilatory effect of diltiazem and nitroglycerin on the large epicardial coronary arteries was evaluated in 26 patients with coronary artery disease. The luminal area of a normal and a stenotic coronary artery was determined at rest, after intracoronary administration of diltiazem, during submaximal exercise as well as 5 min after 1.6 mg sublingual nitroglycerin using biplane quantitative coronary arteriography. Twelve patients with no pretreatment prior to the exercise test served as group 1 (controls) and 14 patients with intracoronary administration of 2 to 3 mg diltiazem prior to the exercise test as group 2. Normal vessel: In the control group luminal area increased significantly during exercise (+23%, P less than 0.01) and after sublingual administration of nitroglycerin (+40%, P less than 0.001). In group 2 luminal area increased after intracoronary administration of diltiazem (+19%, P less than 0.01), during bicycle exercise (+23%, P less than 0.001) and after sublingual administration of nitroglycerin (+39%, P less than 0.001). Stenotic vessel: In the control group luminal area decreased significantly (-29%, P less than 0.001) during bicycle exercise but increased after sublingual administration of nitroglycerin at the end of the exercise test (+12%, NS vs. rest). In group 2 intracoronary administration of diltiazem was associated with a mild increase in stenosis area (+11%, P less than 0.05). There was a further increase in stenosis area during bicycle exercise (+23%, P less than 0.001 vs. rest) and after sublingual nitroglycerin (+32%, P less than 0.001). Coronary vasodilation of the stenotic segment was, however, significantly more pronounced after sublingual nitroglycerin in group 2 than 1 (+32% versus 12%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasomotion was evaluated in eight patients (age 50 +/- 8 years) with coronary disease before and 3.3 +/- 1.9 months after successful percutaneous transluminal coronary angioplasty (PTCA). Luminal area of a normal and a stenotic coronary artery was determined before and after PTCA using biplane quantitative coronary arteriography. Patients were studied at rest, during supine bicycle exercise and 5 min after 1.6 mg sublingual nitroglycerin. Workloads before and after PTCA were identical. Percentage diameter stenosis decreased from 78% to 24% (P less than 0.001) after PTCA. Mean pulmonary artery pressure increased during exercise from 21 to 40 mmHg (P less than 0.001) before and from 19 to 34 mmHg (P less than 0.001) after PTCA. Peak exercise pulmonary artery mean pressure was significantly (P less than 0.05) lower after PTCA. Normal coronary arteries showed a minimal increase in mean luminal area before (+2%; NS) as well as after (+6%; NS) PTCA. Nitroglycerin produced dilation of the normal vessel segment to a similar extent pre- (+27%; P less than 0.001) and post- (+31%; P less than 0.001) PTCA. In contrast, stenotic vessel segments showed coronary vasoconstriction during exercise before PTCA (-28%; P less than 0.01); after PTCA, exercise-induced vasoconstriction of the diseased segment was minimal (-4%; NS). Nitroglycerin was associated with vasodilation of the stenotic vessel segment before (+17%; NS) as well as after (+26%; P less than 0.005) PTCA. Thus, exercise-induced coronary vasoconstriction of stenotic coronary arteries is observed before as well as after PTCA, but vasoconstriction after PTCA is significantly less than before PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular volumes were determined by means of digital subtraction cineangiocardiography (DSA) which was performed in the right anterior oblique projection after contrast agent injection into the superior vena cava. Monoplane end-diastolic (EDV), end-systolic volumes (ESV), and ejection fraction (EF) were calculated using the 'area-length' method and were compared with the same parameters obtained by conventional left ventricular cineangiocardiography. A first group of 20 patients was studied at rest and a second group of 10 patients during bicycle exercise at a work load of 64 watts during 2 min, by DSA and conventional cineangiocardiography. Three different subtraction modes were evaluated: (1) mask mode subtraction (MMS), (2) time interval difference (TID) method and (3) a combination of MMS and TID called MMS + TID method. With the MMS method good correlations were obtained for EDV, ESV and EF at rest (r greater than 0.91) and during exercise (r greater than 0.91). The TID method showed only moderate correlations for patients at rest (r greater than 0.86) and during exercise (r greater than 0.79). Similar results as with MMS were achieved by the combined method (MMS + TID) at rest (r greater than 0.91) and during exercise (r greater than 0.91). Interobserver variability indicated a high reproducibility for all methods except for TID during exercise. It is concluded that DSA is an accurate technique for left ventricular volume determination not only at rest but also during exercise. The best results are obtained with MMS or MMS + TID methods, while left ventricular contour detection is easier and more convenient with MMS + TID.

Physiologic hypertrophy occurs as the result of exercise conditioning and is characterized by normal or supranormal left ventricular (LV) contractile function and reversibility of structural alterations. Whether hypertrophy produced by chronic abnormal loading can be termed 'physiologic' is a matter of debate because in experimental pressure overload hypertrophy normal in vivo ventricular function may be associated with abnormal in vitro function of the papillary muscles. In patients with moderate LV hypertrophy from aortic valve disease (angiographic mass less than 180 g/m2) ejection fraction (EF) is preserved, but at similar levels of afterload, when mass exceeds 180 g/m2, EF is depressed. Comparison of LV function with myocardial structure (endomyocardial biopsies) has shown that in patients with compensated LV function and those with left heart failure (EF less than 57%, LVEDP greater than 20 mm Hg and/or cardiac index less than 2.5 l/min/m2) interstitial fibrosis (IF) was increased to a similar extent (16 and 18%; normal less than 5%), whereas muscle fiber diameter (MFD; normal less than or equal to 20 mu) was larger (P less than 0.05) in the patients with failure (30 mu) than in those with preserved function (27 mu). Moreover patients with depressed postoperative function had a larger (P less than 0.01) preoperative MFD (35 mu) than those with normal postoperative function (30 mu). Seventeen months after successful aortic valve replacement IF increased (P less than 0.02) and MFD decreased (P less than 0.001) but did not become normal regardless whether postoperative function was normal or depressed. Thus in secondary hypertrophy myocardial structure is pathologic even in the presence of normal LV function and depressed function appears likely to be related to excessive fiber hypertrophy rather than to IF. Massive fiber hypertrophy heralds an unfavorable postoperative LV function and fibrosis is irreversible after surgical correction of the abnormal load.

Angiographic techniques have been used for the quantification of mitral or aortic and rarely tricuspid regurgitation. Mitral or aortic regurgitant volume per beat and the regurgitation fraction (fao and fm, respectively) are obtained from the angiographic determination of total left ventricular stroke volume (TSV) and forward stroke volume (FSV) estimated by a different technique. Although this procedure is generally accepted as the gold standard for quantification of left heart regurgitations, there are several limitations: In the presence of mitral and aortic regurgitation no separate quantification of fao and fm is feasible; heart rate at the time of determination of FSV (from Fick or dye dilution cardiac output) and of TSV (angio) may be different; there is a tendency to consistently overestimate stroke volume by angio techniques; repeated estimations of TSV by angio are influenced by the circulatory effects of the contrast dye. In contrast indicator dilution techniques, where upstream and downstream sampling allow the simultaneous estimation of forward and regurgitant flow, the accuracy of the determination of FSV is well established and repeated estimations of fao and fm are possible because the indicators do not have cardiovascular effects. These methods are, however, crucially dependent on thorough mixing of the regurgitant volume with the blood in the upstream chamber. In 23 patients with isolated aortic regurgitation there was a positive correlation between fao evaluated by thermodilution and fao determined by the biplane angio-Fick method (r = 0.59). fao by thermodilution averaged 0.40 and fao by angio-Fick 0.46 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)