Cardiac tamponade masking pulmonary embolism.

This report describes a patient admitted with shortness of breath due to cardiac tamponade, which masked concomitant pulmonary embolism that was diagnosed only after right heart pressures failed to decrease after successful pericardiocentesis. The patient was found to have widely metastatic adenocarcinoma of colon (with metastases to pericardium) and a paraneoplastic syndrome of deep vein thrombosis.

Exacerbated tamponade: deterioration of cardiac function by lowering excessive arterial pressure in hypertensive cardiac tamponade.

Patients with cardiac tamponade usually have significant hypotension; hypertension is rare. Before administering any medication during tamponade one must consider the complex physiology and compensatory mechanisms of cardiac compression [1]. We observed both an accentuation of pulsus paradoxus and retrospectively recognized fluctuations of left-ventricular function after progressively rising arterial blood pressure had been lowered.

Heart disease and hypertension in severe obesity: the benefits of weight reduction.

Severe obesity is associated with abnormalities of cardiac structure and function. These include an increased cardiac workload and ventricular hypertrophy. Hypertension in combination with severe obesity seriously burdens the heart because the increased preload and afterload compound cardiac work. Weight reduction induced by gastric operations for severe obesity is associated with resolution of hypertension, reduction in ventricular wall thickness and cardiac chamber size, as well as improved systolic function. Additional data are needed to predict when in the course of development of obese cardiomyopathy the changes in contractile function become irreversible. Additionally, the impact of coronary artery disease on the progression of obese cardiomyopathy and the effects of surgical weight reduction on cardiac structure and function need to be further clarified. Studies of the association between obesity, its treatment, and modification of cardiovascular risk are a major focus of preventive cardiology today.

Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group.

A multicenter double-blind, randomized, placebo-controlled trial of oral enoximone, a phosphodiesterase inhibitor, was conducted in 102 outpatients (50 receiving enoximone and 52 receiving placebo) with moderate to moderately severe congestive heart failure. All were on a long-term regimen of digoxin and diuretics without vasodilators and converting enzyme inhibitors. Symptom score was obtained, and exercise testing was performed monthly for 4 months. There were no differences between groups in symptoms or exercise duration at the end of 4 months. A subgroup undergoing analysis of oxygen consumption with measurement of anaerobic threshold during exercise showed an increase (p less than 0.05) in anaerobic threshold at 1 month with enoximone. (2.7 +/- 0.8 ml O2/kg/min) compared with placebo (-0.8 +/- 1.2 ml O2/kg/min). This improvement was not sustained at 4 months (0.5 +/- 1.7 ml O2/kg/min with enoximone and 0.2 +/- 1.5 ml O2/kg/min with placebo). The dropout rate was significantly higher (p less than 0.02) with enoximone (46%) than with placebo (25%). Adverse effects other than death were slightly, but not significantly, higher with enoximone (32%) than with placebo (22%). During therapy, five deaths occurred in the enoximone group, and none occurred in the placebo group (p less than 0.05). Two deaths were sudden, two were from progressive congestive heart failure, and one was from acute myocardial infarction. With intention-to-treat analysis and inclusion of patients who were removed from therapy because of lack of study drug effect, 10 deaths occurred in the enoximone group, and three occurred in the placebo group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of hemodynamic tolerance from a 24-hour intravenous infusion of fenoldopam mesylate in congestive heart failure.

To determine the maintenance of pharmacodynamic effects of fenoldopam mesylate, a dopamine-1 agonist, the invasive hemodynamic profiles of 33 patients with New York Heart Association functional class III to IV congestive heart failure were examined. Fenoldopam mesylate was initiated at 0.1 micrograms/kg/min and titrated to a cardiac index greater than or equal to 25% above baseline. Upon achievement of optimal hemodynamics, maintenance infusion was begun (mean dose 0.6 micrograms/kg/min). Fenoldopam mesylate (baseline vs maximal effect) decreased systemic vascular resistance by 37% (p less than 0.001), left ventricular filling pressure by 16% (p less than 0.05) and mean arterial pressure by 11% (p less than 0.05), with an associated augmentation in cardiac index and stroke volume index by 27% (p less than 0.001). Attenuation of hemodynamic effect (maximal effect vs time) was noted in cardiac index (14% p less than 0.001), systemic vascular resistance (13% p less than 0.05) and stroke volume index (13% p less than 0.05). None of the parameters exhibited complete attenuation to baseline values. Fenoldopam mesylate improves cardiac output and lowers systemic vascular resistance with relative attenuation of pharmacodynamic effect during a 24-hour intravenous infusion.

Interdependence of the left and right ventricles in health and disease.

Since the publication of Bernheim's report it has been clear that the anatomic and functional integrity of each ventricle is an important determinant of the functional characteristics of the other ventricle. How the ventricles interact in health and disease has been of interest to many investigators. This article reviews and considers the structure and function of each ventricle as an independent subunit and as a unified pumping system in the healthy state and in various disease states.

Pulmonary angiography in the diagnosis of pulmonary embolism.

In patients in whom there is clinical suspicion of pulmonary thromboembolic disease, because of the risk of inadequate treatment, definitive radiologic evaluation should be carried out. Of the diagnostic procedures available, conventional pulmonary angiography has the greatest sensitivity and specificity in the detection of pulmonary embolism or other pulmonary vascular disease. Pulmonary angiography is indicated for patients with an indeterminate lung scan, for those with a high-probability lung scan in whom confirmation is necessary because of high risk for bleeding complications from anticoagulation, if embolism is massive and embolectomy is contemplated, if thrombolytic therapy or vena cava interruption is considered or if there is significant clinical evidence for an alternative diagnosis as well as for those with low-probability scans with a high degree of clinical suspicion and to complete a workup in patients with pulmonary hypertension. Refinements in the technique have simplified and expanded its application. The hemodynamic evaluation with right-heart catheterization before and after pulmonary angiography plays an important role in the choice of treatment of pulmonary embolism. In patients with multiple bilateral lobar or segmental perfusion defects, performance of right and left pulmonary arteriography in the right and left posterior oblique projections should be carried out. In the presence of additional pulmonary hypertension, the lung in which perfusion is most abnormal is selected first for angiography with a low bolus contrast dose. The angiographic criteria for the diagnosis of pulmonary embolism are intraluminal vascular filling defects or an abrupt cutoff of a large vessel. For selective opacification of lobar pulmonary branches occlusion pulmonary angiography is helpful. The mortality of pulmonary angiography in experienced centers is approximately 0.3%. Complications may include cardiac perforation in up to 1% and subendocardial injury in less than 0.2%. In patients with pulmonary embolism but no pulmonary hypertension, treatment with heparin for ten to 14 days should be followed by coumadin anticoagulation for at least three to six months. For obstruction of greater than or equal to 50% of the pulmonary vascular cross-sectional area and pulmonary hypertension thrombolytic therapy should be given and insertion of an inferior caval filter can be considered. In those with more than 75% pulmonary vascular obstruction and corresponding hemodynamic derangement, pulmonary artery embolectomy or thrombolytic therapy should be carried out.4

The comparative effects of ionic versus nonionic agents in cardiac catheterization.

Although all contrast media that are used in ventriculography and coronary arteriography have some adverse effects, clinical and laboratory experiences with nonionic contrast media have provided evidence of the lower toxicity and better tolerability associated with these agents. A review of comparative studies of nonionic and ionic contrast media is presented. The nephrotoxic and cardiotoxic effects of ionic contrast agents are discussed. The advantages of the nonionic agent, iohexol, are outlined, and guidelines for its use are suggested.

How effective is digitalis in the treatment of congestive heart failure?

The evidence suggests that digitalis glycosides do indeed improve ventricular performance through a sustained but moderate positive inotropic effect. This effect is more marked in failing than in nonfailing myocardium. The clinical studies suggest a moderate salutary effect in patients with chronic CHF who are in sinus rhythm. The drug can be given safely to patients with CAD and in combination with other medications when the physician is aware of those factors leading to increased sensitivity to digitalis.

Pulmonary artery pseudoaneurysm. A potential complication of pulmonary artery catheterization.

A 70-year-old woman with pulmonary hypertension due to severe chronic obstructive pulmonary disease and long-standing mitral stenosis developed hemoptysis and a right upper lobe infiltrate during manipulation of a balloon-tipped flow-directed pulmonary artery catheter. Hemoptysis resolved spontaneously over several minutes, and the right upper lobe infiltrate cleared over several weeks, during which time a new right upper lobe nodule became apparent. Angiography disclosed the presence of a late-filling well-circumscribed saccular pseudoaneurysm. This was obliterated with an acute infiltrate with or without hemoptysis in the area subtended by a flow-director pulmonary artery catheter, and particularly when it is associated with manipulation of that catheter, the differential diagnosis should include pulmonary artery perforation as well as infarction. If the patient survives the episode, the possibility that a pseudoaneurysm has formed must be actively entertained and aggressively evaluated, since pseudoaneurysm is a potentially fatal lesion that is treatable.

Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy.

Milrinone and dobutamine are positive inotropic agents with beneficial hemodynamic effects in patients with congestive heart failure. This study was undertaken to compare the effects of intravenous milrinone and dobutamine in patients with stable New York Heart Association class III or IV congestive heart failure and to test the hypothesis that intravenous milrinone is at least as beneficial as dobutamine in this setting. Seventy-nine patients were randomized to either dobutamine therapy at incremental doses of 2.5, 5, 7.5, 10, 12.5 and 15 micrograms/kg/min, or milrinone as a bolus of 50 or 75 micrograms/kg followed by an infusion of 0.5 to 1.0 micrograms/kg/min. Both agents significantly increased heart rate, cardiac index and stroke volume index and decreased pulmonary artery wedge pressure and systemic vascular resistance compared with baseline levels (p less than 0.01). During sustained infusion for 48 hours, no difference in hemodynamic effects was observed between the 2 drugs. Ventricular tachycardia occurred in 5 patients (3 taking milrinone, 2 taking dobutamine); 1 patient taking milrinone had ventricular fibrillation. Milrinone and dobutamine elicited similar beneficial hemodynamic results with relatively few adverse effects.

Pharmacokinetics of intravenous bepridil in patients with coronary disease.

The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing.

Preliminary experience with synchronized coronary sinus retroperfusion in humans.

Synchronized coronary sinus retroperfusion (SCSR) with arterial blood has been extensively tested in animals. This intervention offers temporary support to areas of ischemic myocardium while a method of definitive revascularization is being sought. The feasibility and safety of this procedure for patients with unstable angina was therefore tested. A No. 7F autoinflatable retroperfusion balloon catheter (USCI) was inserted percutaneously into the coronary sinus of the study patients. Arterial blood was obtained through a No. 8F catheter placed in the femoral artery. Arterial blood was infused in a retrograde fashion into the coronary venous system during cardiac diastole by means of a piston-driven pump that was electrocardiographically synchronized with the drainage of the venous system during systole. This procedure was performed in five patients with unstable angina refractory to maximum medical therapy. SCSR significantly decreased the frequency of anginal episodes and the requirement for antianginal medications. SCSR also provided time for patient stabilization before diagnostic cardiac catheterization or therapeutic intervention. This preliminary experience suggests that synchronized coronary sinus retroperfusion is a feasible and safe procedure. It can be performed at the bedside with no apparent adverse effects to the patient. Retroperfusion also appears to be effective in relieving ischemic symptoms as assessed by clinical parameters. Based on our preliminary experience, further delineation of its clinical applications is warranted.

Pharmacokinetics of the bipyridines amrinone and milrinone.

The pharmacokinetics of milrinone were studied in sequential ascending doses in New York Heart Association Class III and IV patients receiving oral and intravenous medication. The parameters determined after parenteral administration were estimated by fitting the plasma concentration data to an open two-compartment body model. After oral medication, regression-independent parameters were determined. After either oral or parenteral administration of milrinone, plasma levels were dose dependent and the drug had an apparent first-order terminal elimination half-life of approximately 2 hr. The apparent volume of distribution was approximately 400 to 500 ml/kg, and total body clearance was approximately 130 ml/kg/hr. These values obtained in patients receiving milrinone were compared with those obtained for milrinone in volunteers, as well as those noted with the other inotropic bipyridine, amrinone. Milrinone's elimination from the blood stream patients was slower that that in normal healthy subjects and faster than amrinone's elimination in patients with congestive heart failure. Milrinone's pharmacokinetic parameters in these patients were unchanged after approximately 30 days of continuous oral medication.

Pharmacokinetics and pharmacodynamics of milrinone in chronic congestive heart failure.

The acute hemodynamic effects and pharmacokinetics of bolus intravenous milrinone administration were assessed in 13 patients with severe congestive heart failure. Serial hemodynamics were measured and blood samples were obtained to determine plasma milrinone concentration and calculation of pharmacokinetic variables after administration of milrinone at 12.5, 25, 50 and 75 micrograms/kg, allowing at least 6 hours to elapse between consecutive milrinone doses. At each dose milrinone effected prompt but very short-lived increases in cardiac output and left ventricular stroke work and decreases in pulmonary artery pressure, right atrial pressure and systemic and pulmonary vascular resistance in a non-dose-dependent fashion. Pulmonary artery wedge pressure decreased in a dose-related manner. Heart rate increased significantly after the 75-micrograms/kg dose and mean arterial pressure decreased significantly only after the 50- and 75-micrograms/kg milrinone dose. The time-dependent decline in plasma milrinone concentration was biexponential and log linear, conforming to an open 2-compartment model of drug distribution and elimination. Mean plasma milrinone clearance (+/- standard error) was 0.15 +/- 0.03 liters/min/kg, volume of distribution was 0.35 +/- 0.02 liters/kg and mean elimination half-life was 1.7 hours.