Digital densitometric determination of relative coronary flow distributions.

In clinical cardiology, stenosis in a coronary artery is measured on the basis of visual assessment. The reading of coronary arteriograms leads, however, to large inter- and intra-observer variability. Image analysis and computer assistance result in a more consistent assessment, but this approach is mainly based upon static geometric parameters, such as diameter reduction of a segment of the stenosed artery. A more functional, physiological measurement is thus desirable. This can be realised by measuring the difference between the normal coronary blood flow and the increased flow under hyperaemic conditions, yielding the so-called coronary flow reserve (CFR). In clinical practice, however, this method is difficult and time-consuming. A less demanding approach is reported, in which relative flow distributions are determined densitometrically from digital angiograms acquired under basal and hyperaemic conditions. The proposition is that, if the relative flow distribution in hyperaemic state differs from that during rest, the functional severity of a stenosis downstream from the bifurcation can be indicated. The new approach is validated by comparing the results of a theoretical model for steady flow with a flow phantom experiment for steady and pulsatile flow. The obtained flow ratios correlate very well, both in steady and pulsatile flow, with correlation coefficients exceeding 0.95.

Acute hemodynamic effects and preload-dependent cardiovascular profile of the partial phosphodiesterase inhibitor nanterinone in patients with mild to moderate heart failure.

Nanterinone (UK-61,260) is a novel positive inotropic and balanced-type vasodilating drug, only partially based on phosphodiesterase III inhibition. Preliminary data from controlled studies suggest satisfactory long-term efficacy and safety. As its acute hemodynamic effects in humans are unknown, an oral dose of 2 mg nanterinone was studied in 14 patients with heart failure (NYHA class II-III) on chronic diuretic and angiotensin-converting enzyme (ACE) inhibitor treatment. Before the study, patients were on a 2 g salt-balanced diet, and they received their last medication 16 hours before each study day. Hemodynamic measurements were carried out before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours after administration of the study drug. All patients received placebo and nanterinone on 2 consecutive days. Following nanterinone, systemic vascular resistance decreased immediately from 1699 +/- 82 (mean +/- SEM) at baseline to 1368 +/- 80 at 1 hour. Changes persisted for 12 hours. Concomitantly, there was an immediate and significant fall in pulmonary wedge pressure to 38% of baseline at 1.5 hours, together with a 20% reduction in pulmonary artery pressure. Heart rate remained unchanged and arterial pressures showed only a short, significant decrease. Cardiac index rose significantly from 2.28 +/- 0.15 at baseline to a highest value of 2.65 +/- 0.14 1/min/m2 at 1 hour. Changes persisted for 3 hours. Placebo had no effect on these variables. As, in view of its potential venodilating properties, hemodynamic improvement by nanterinone may depend on pre-existing left ventricular filling pressure, patients were subsequently grouped according to baseline pulmonary wedge pressure of > 12 mmHg (H-PCWP) and < or = 12 mmHg (L-PCWP). Cardiac index improved by 26% in H-PCWP and by 17% in L-PCWP (NS). In contrast, PCWP fell more markedly in H-PWCP than in L-PCWP (40% and 23%, respectively, p < 0.05). Thus, oral nanterinone results in a significant acute hemodynamic improvement and is well tolerated. Although changes in left ventricular filling pressure are more pronounced in patients with elevated pre-existing PCWP, cardiac pump function improves equally in patients with normal or low left ventricular filling pressure at baseline.

Three-dimensional densitometric reconstruction and visualization of stenosed coronary artery segments.

In this paper we report results from an ongoing study about the diagnostic benefits of three-dimensional (3D) visualization and quantification of stenosed coronary artery segments. Biplane angiographic images do not provide enough information for the exact reconstruction of the coronary arteries. Therefore, a priori information about the 3D shape to be reconstructed must be incorporated into the reconstruction algorithm. One approach is to assume a circular cross-section of the coronary artery. Hence, the diameter is estimated from the contours of the vessel in both projections. Another approach is based on densitometry and searches for a solution of the reconstruction problem close to the previously reconstructed adjacent slice. In this paper we apply contour information as well as the densitometrical profiles of the two orthogonal vessel projections. We present a new probabilistic densitometric reconstruction algorithm, which extends the correct handling of the stochastic properties of the density profiles into the network flow based reconstruction algorithm. The reconstructed coronary segment is visualized in three dimensions. In order to assess the accuracy of the reconstruction, the method is applied to tubes with artificial obstruction of known geometry, modeling coronary artery stenoses. These catheter tubes are filled with normal iodine contrast material. The results of the reconstruction and visualization are discussed with respect to clinical usefulness.

Hemodynamic, neurohumoral, and myocardial energetic effects of pimobendan, a novel calcium-sensitizing compound, in patients with mild to moderate heart failure.

In contrast to cyclic AMP-dependent positive inotropes, the calcium-sensitizer and partial phosphodiesterase (PDE) inhibitor pimobendan may induce beneficial effects in heart failure. However, its effect on relaxation, myocardial energetics and neurohormones are unknown. Twelve patients with heart failure, New York Heart Association (NYHA) classification II-III, due to ischemic cardiomyopathy, were studied for 1 h after they received 5 mg pimobendan intravenously (i.v.). Pimobendan progressively reduced systemic resistance and left ventricular end-diastolic pressure (LVEDP) (22 and 50%, respectively) and improved isovolumetric contractility and relaxation parameters by 30% (all p < 0.05 vs. control). LV end-diastolic and end-systolic volumes (LVEDV, LVESV) decreased significantly by 20 and 19%, respectively. Cardiac output (CO) increased by 17% due to a simultaneous increase in heart rate (HR) from 75 +/- 3 to 86 +/- 5 beats/min (mean +/- SEM, p < 0.05). Pimobendan did not change coronary hemodynamics, but myocardial O2 extraction and consumption were decreased significantly by 18 and 20%, respectively. Catecholamines, angiotensin II (AII), and aldosterone levels did not change significantly. In contrast, arterial and coronary venous renin increased significantly from 57 +/- 17 and 53 +/- 14.7 microM/h at control to 69 +/- 20 and 69 +/- 20 microM/h, respectively, 60 min after pimobendan administration. Simultaneously, cardiac renin uptake at baseline (0.449 +/- 0.185 mumol/min) changed to release (-0.071 +/- 0.145 mumol/min, p < 0.05). Serious side effects did not occur. Thus, pimobendan had progressive positive inotropic and lusitropic effects, diminished preload and afterload despite modest stimulation of plasma renin activity (PRA), and reduced systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute systemic and antiischemic effects of epanolol in patients with coronary artery disease.

Antiischemic effects of beta 1-blocking agents are based on intrinsic negative inotropic and chronotropic properties. Partial beta 1-agonistic activity, although useful in preserving cardiac function, may counteract such antiischemic properties by modulating the intrinsic negative cardiac effects of beta-blockade. To investigate the acute hemodynamic and antiischemic profile of epanolol, a cardioselective beta 1-antagonist and partial agonist, 20 patients with left coronary artery disease underwent two incremental atrial pacing tests, 45 minutes before (APST I) and 15 minutes after (APST II) 4 mg intravenous epanolol, administered over 5 minutes. Additional measurements were carried out at 1, 3, 5, 10, and 15 minutes after epanolol, at basal and fixed heart rates. Epanolol immediately reduced heart rate with a maximum of 10% at 15 minutes and decreased contractility (Vmax) by 7% (both p < .05), whereas cardiac output fell temporarily by 9% (p < .05). Other hemodynamic parameters did not change, except for a significant 11% reduction in myocardial oxygen demand. Despite comparable pacing conditions, both the double product and contractility decreased significantly less during APST II, resulting in a 17% lower myocardial oxygen consumption (p < .05). Myocardial ischemia was markedly reduced, indicated by normalization of lactate metabolism [lactate extraction 16 +/- 7% vs. -7 +/- 8% (APST I)], less ST depression (21%), and modulation of LV end-diastolic pressure postpacing (all p < .05 vs. APST I), whereas angina was absent or less in 14 patients. None of the patients reported an adverse effect. Thus, under resting conditions intravenous epanolol induces moderate, short-lasting negative chronotropic and inotropic effects, but does not alter cardiac pump function or vascular resistance, reflecting its additional beta 1-agonistic properties. Alternatively, during pacing it still reduces ischemia through negative inotropic effects and diminishes myocardial oxygen demand, reflecting its beta 1-antagonistic profile.

A severed pacemaker lead entrapped in a hepatic vein.

Complete lead fracture is a uncommon phenomenon in cardiac pacing. Recently we encountered a patient with a severed lead at routine pacemaker follow-up visit. In this case report, the typical ECG changes and noninvasive pacemaker measurements are discussed. The chest roentgengram showed the position of the proximal part of the lead, but this technique could not establish the exact position of the distal part of the lead. Ultrasound recording of the upper abdomen demonstrated that the distal part of lead was entrapped in the great hepatic vein. Since this position was stable with one end in the right ventricular apex and the other end in a hepatic vein, no further action was undertaken to remove this part of lead. The proximal part of the lead and the pulse generator were explanted. So far the clinical course of the patient has been uneventful. Strategies to remove severed leads are discussed based on a review of the literature.

Neurohumoral activation during acute myocardial ischaemia. Effects of ACE inhibition.

ACE inhibition may be useful in several manifestations of ischaemic heart disease, such as heart failure due to ischaemic cardiomyopathy. Recent evidence suggests that these effects may also be present in normotensive patients with ischaemic heart disease without heart failure. Theoretically, converting-enzyme inhibition, through coronary and systemic vasodilating effects and negative inotropic properties, should have a favourable effect on the myocardial oxygen supply/demand ratio and, hence, affect the incidence and severity of myocardial ischaemia. It is doubtful, however, whether these cardiac and extracardiac properties of ACE inhibitors really underlie its potential antiischaemic effects, at least in the average patient with ischaemic heart disease without concomitant heart failure and hypertension. Recent animal and human studies indicate that converting-enzyme inhibitors may modulate myocardial ischaemia by reducing ischaemia-induced circulating neurohumoral activation. It has been shown that, depending on the severity of ischaemia, the circulating renin-angiotensin system may become activated together with an increase in circulating catecholamine levels. ACE inhibition suppresses this neuroendocrine stimulation during ischaemia and modulates subsequent systemic and, presumably, also coronary vasoconstriction. In addition to these effects on circulating neurohormones, ACE inhibition could affect myocardial ischaemia through a number of local actions, e.g. modulation of tissue (cardiac) angiotensin II formation and bradykinin breakdown, stimulation of prostaglandin synthesis and, in the use of sulphydryl compounds, by affecting EDRF formation. Whether ACE inhibitors have clear antiischaemic effects in all clinical conditions is uncertain. Their efficacy to limit exercise-induced ischaemia has been questioned. In contrast, pacing-induced ischaemia in patients at rest is clearly prevented by ACE inhibition. This differential effect may be related to a more pronounced difference in circulating neurohormones during exercise per se. It also suggests that ACE inhibitors may be particularly useful as (additional) antiischaemic therapy in patients with angina at rest, e.g. unstable angina and the acute phase of myocardial infarction.

Acute hemodynamic and antiischemic properties of intravenous bepridil in coronary artery disease.

The acute hemodynamic and antiischemic effects of intravenous bepridil (3 mg/kg/5 minutes followed by 1 mg/kg/hour) were studied in 19 patients with coronary artery disease under basal conditions and during 2 identical pacing stress tests 30 minutes before (pace test I) and 15 minutes after (pace test II) onset of infusion. Bepridil immediately decreased coronary and systemic vascular resistance (26 and 17%, respectively). This resulted in a 19 and 21% reduction in left ventricular systolic and mean aortic pressures and a 15% increase in coronary flow and stroke index (p less than 0.05 vs control for each). These vasodilating effects were short lasting, persisting for 5 minutes after the bolus infusion, followed by significant reductions in heart rate (15%) and contractility (10%) and a temporary 46% increase in left ventricular filling pressure. During both pace tests heart rate, contractility, coronary flow and myocardial O2 consumption were comparable. In contrast, bepridil prevented the significant increase in systemic resistance and mean aortic pressure observed during pace test I (11 and 15%, respectively). Subsequently, myocardial O2 demand was significantly less during pacing after bepridil, due to an 11% reduction in left ventricular systolic pressure (p less than 0.05 vs control and pacing test II vs I). This resulted in marked antiischemic effects: normalization of lactate extraction and reduction in ST-segment depression (-14 +/- 7 vs 3 +/- 6% and 0.2 +/- 0.02 vs 0.13 +/- 0.02 mV, respectively, pace test I vs II, p less than 0.05), and in less or no angina in 18 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute antiischaemic properties of high dosages of intravenous diltiazem in humans in relation to its coronary and systemic haemodynamic effects.

The antiischaemic properties of intravenous diltiazem in recommended therapeutic doses are disputed. In 17 patients with coronary artery disease the systemic and coronary haemodynamic effects of diltiazem were assessed during a high-dose infusion (0.4 mg kg-1 per 5 min, followed by 0.4 mg kg-1 per 10 min). In addition, its potential antiischaemic properties were investigated during identical pacing stress tests, 30 minutes before (P1) and immediately after diltiazem administration (P2). Diltiazem reduced left ventricular systolic pressure from 133 +/- 5 to 116 +/- 5 mmHg (P less than 0.005, means +/- SEM), persisting until after P2. It decreased systemic and coronary resistance by 32% (P less than 0.001) and 29% (P less than 0.005), respectively, with a sustained increase in cardiac output from 5.9 +/- 0.4 to 7.3 +/- 0.6 l min-1 (P less than 0.01), but a brief 20% rise in coronary flow (P less than 0.05), after the bolus infusion only. Heart rate, contractility, left ventricular filling pressure and myocardial O2 consumption remained unchanged. Despite high plasma levels (673 +/- 81 micrograms l-1) diltiazem was well tolerated. During identical maximal pacing rates diltiazem considerably reduced myocardial O2 demand (double product: 16.3 +/- 0.8 (P2) vs 21.1 +/- 1.1 (P1), P less than 0.005), due to an 18% decrease in left ventricular systolic pressure, resulting in diminished coronary flow and myocardial O2 consumption during P2 (14% and 15%, respectively, P less than 0.05 vs P1). Diltiazem also significantly reduced pacing-induced ischaemia, indicated by normalization of myocardial lactate extraction (1 +/- 8% (P2) vs -41 +/- 12% (P1), P less than 0.05), and left ventricular filling pressure (13 +/- 2 (P2) vs 27 +/- 3 mmHg (P1), P less than 0.01), less ST-segment depression (0.12 +/- 0.01 (P2) vs 0.24 +/- 0.02 mV (P1), P less than 0.01) and improved contractility (Vmax 59 +/- 5 (P2) vs 48 +/- 3 s-1 (P1), P less than 0.05). Angina was absent or less in 15 patients during pacing after diltiazem. Thus, diltiazem, in high dosages, induces continuing systemic but short lasting coronary vasodilation, improves pump function without negative chronotropic and inotropic effects and has pronounced antiischaemic properties, predominantly due to diminished myocardial O2 demand.

Dose related coronary and systemic haemodynamic effects of intravenous bepridil in patients with coronary artery disease.

The acute coronary and systemic haemodynamic effects of intravenous bepridil were investigated in 27 patients with coronary artery disease; 13 (group 1) received 2 mg kg-1 and 14 (group 2) 4 mg kg-1 over 5 min. An immediate systemic and coronary vasodilation occurred in both groups during and immediately after the infusion. Changes were dose-related with a maximal decrease in left ventricular (LV) systolic pressure of 11% (group 1) and 18% (group 2), in mean aortic pressure of 11% (group 1) and 19% (group 2), and in coronary resistance of 23% (group 1) and 41% (group 2). Coronary flow increased by 17% (group 1) and 47% (group 2) (all changes significantly different from control (C) values and between groups). Cardiac output, measured immediately after bepridil, was unaltered, although in group 2 stroke volume index increased (14%) and systemic resistance decreased (16%), both P less than 0.05 vs C. In group 2, heart rate (HR) and contractility initially increased (8% and 10%, respectively, P less than 0.05 vs C), secondary to the greater fall in afterload, followed by a significant reduction at 5 and 10 min after bepridil (9% and 10%, respectively), accompanied by a 36% increase in LV enddiastolic pressure (P less than 0.05 vs C). No such changes were observed in group 1, apart from a simultaneous decrease in HR (9%, P less than 0.05 vs C). Thus, in humans, a dose-related, biphasic haemodynamic pattern is observed with intravenous bepridil, consisting of an acute, short-lasting vasodilation, followed by late negative chronotropic and inotropic effects, which, with longterm bepridil administration, may be beneficial during myocardial ischaemic.

Temporal relation of changes in regional coronary flow and myocardial lactate and nucleoside metabolism during pacing-induced ischemia.

The temporal relation between myocardial lactate and hypoxanthine metabolism and regional changes in krypton-81m perfusion during pacing-induced ischemia was studied in 17 patients with coronary artery disease (CAD). During incremental atrial pacing, lactate production and hypoxanthine release occurred early and simultaneously, accompanied by ST-segment changes, but before angina and only few minutes after a significant (17%) reduction in krypton-81m perfusion in areas with more than 90% luminal diameter reduction. During maximal pacing heart rates, krypton-81m distribution decreased to 68 +/- 7% of control in areas with more than 90% diameter reduction and to 80 +/- 4% in 70 to 90% reduction (both p less than 0.05 vs control). Maximal lactate production occurred 15 seconds after pacing (extraction -15 +/- 7% vs 16 +/- 2% during control, p less than 0.05) and peak hypoxanthine release 1 minute after pacing (delta arteriovenous -2.64 +/- 0.8 microM vs 0.08 +/- 0.21 microM during control, p less than 0.05). Krypton-81m perfusion decreased in 20 of the 21 CAD areas. Angina, ST-segment changes, hemodynamic alterations and lactate production occurred in 15, 14, 9 and 15 patients, respectively. In contrast, hypoxanthine release was found in all cases. After pacing, lactate production and all general indexes of ischemia persisted for only 2 to 3 minutes. In contrast, krypton-81m perfusion was still significantly reduced 5 minutes after pacing and was only accompanied by hypoxanthine release (delta arteriovenous -1.41 +/- 0.6 microM, p less than 0.05 vs control).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous determination of regional myocardial blood flow with intracoronary krypton-81m in coronary artery disease.

Pacing-induced changes in regional coronary flow were studied continuously with krypton-81m by intracoronary infusion in 25 patients: 21 with 50% or greater diameter narrowing of 1 or more left coronary arteries (group I) and 4 with less than 50% diameter reduction of a left coronary artery (group II). No changes occurred in group II. In group I, krypton-81m perfusion decreased progressively in all areas with more than 70% diameter narrowing, with a simultaneous increase in normal regions. At the end of pacing during angina, krypton-81m perfusion was reduced to 81 +/- 4% of control in areas with 71 to 90% diameter reduction (n = 8) and to 69 +/- 6% in areas with more than 90% diameter narrowing (n = 15). In contrast, in regions with 50 to 70% diameter reduction changes were variable (decrease in 4 regions, increase in 2 and an unchanged distribution in 1 region). Krypton-81m perfusion decreased early, before general signs of ischemia in areas with more than 90% diameter reduction, whereas this decrease occurred later in regions with 71 to 90% diameter narrowing, concurrently with ST-segment changes but before anginal pain. Although all signs of ischemia had disappeared between 2 and 5 minutes after pacing, changes in krypton-81m distribution persisted in most areas for 5 to 15 minutes after pacing. It is concluded that the functional significance of coronary arterial narrowing can be assessed with a continuous intracoronary infusion of krypton-81m. Changes in regional distribution persisted after cessation of pacing-induced ischemia, indicating an ongoing decrease in regional myocardial blood flow.

[Coxiella burnetii as a possible cause of endocarditis in a 7-year old boy]. / Coxiella burnetii als mogelijke verwekker van endocarditis bij een 7-jarige jongen.

The case-history of a 7-year-old boy with endocarditis, myocarditis and pericarditis, possibly caused by Coxiella burnetii (Q-fever), is presented. As far as we know only one case of Q-fever endocarditis in a child is previously described in literature. That child had, contrary to our patient, a pre-existing valve abnormality. Q-fever was diagnosed after demonstration of a significant rise in titer of the antibodies against Coxiella burnetii in both the IgM and the IgG fractions. IgA antibodies, indicative for an endocarditis, were also demonstrated.

Acute hemodynamic and antiischemic effects of intravenous amiodarone.

The acute hemodynamic and antiischemic properties of amiodarone were investigated in 16 patients with more than 70% diameter reduction of a left coronary artery. Two successive atrial pacing stress tests (APST I and II) were performed, with an interval of 40 minutes in between, and amiodarone, 5 mg/kg/5 min, was infused 30 minutes after APST I. Hemodynamic changes during amiodarone administration consisted of a 20% decrease in left ventricular (LV) systolic pressure, a 13% decrease in systemic vascular resistance and an 18% decrease in stroke work. Coronary vascular resistance was reduced 19% and coronary sinus flow increased 23%. Despite a secondary 14% increase in heart rate, contractility decreased 21%, accompanied by a 45% increase in LV end-diastolic pressure, which persisted until APST II. Although most hemodynamic changes were observed only during the infusion, contractility and LV systolic pressure were still diminished at the beginning of APST II and remained so during pacing, resulting in a reduction in myocardial oxygen demand compared to APST I. Although overall myocardial oxygen consumption and coronary flow were equal during both pacing tests, amiodarone significantly reduced pacing-induced myocardial ischemia. Lactate metabolism remained normal during APST II (lactate extraction 12 +/- 3% vs -28 +/- 8% (APST I) at maximal pacing rates [p less than 0.05]), while ST-segment depression, LV end-diastolic pressure postpacing and angina were also significantly reduced during APST II. Thus, in humans, intravenous amiodarone reduces vascular resistance and contractility and inhibits pacing-induced myocardial ischemia, presumably by reducing myocardial oxygen demand.

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti-ischaemic properties are mainly based on a reduction of myocardial oxygen demand, rather than on an improvement in coronary flow. It is concluded then, that amiodarone has significant haemodynamic effects as manifested by an early reduction in vascular resistance and a late negative inotropic effect. Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone alone. The important anti-ischaemic properties of amiodarone appear to result primarily from these cardiovascular actions and the inherent reduction in myocardial oxygen demand.