Prospective study of early atropine use in dobutamine stress echocardiography.

AIMS: Dobutamine stress echocardiography is a time-consuming test, often requiring atropine at the end of the protocol to achieve target heart rate (HR). We examined whether earlier administration of atropine in appropriate patients would shorten test time and increase the likelihood of achieving peak HR. METHODS: Two hundred and seventy consecutive patients were randomized prospectively to conventional or early atropine protocols. Of these, 120 patients with an inadequate HR response [mid-30 microg/kg/min HR<100 (age <50) or <90 (age >50); or mid-40 microg/kg/min stage HR<120 (age <50) or <110 (age >50)] were included in the analysis. The remaining patients were used in a model to define which patients are likely to require atropine. RESULTS: The 61 patients receiving early-atropine had decreased test-time relative to the 59 not receiving early-atropine (17:05 vs. 18:24 min:sec, P=0.014) accompanied by a 10% reduction in total dobutamine dose (P=0.008). Their HR at end of 40 microg/kg/min was 123+/-18 vs. 105+/-17 respectively, P<0.0001. Only 7% of the early-atropine group failed to reach target HR vs. 15% not receiving early-atropine. By multivariate analysis, age (P<0.0001), HR at end of 30 microg/kg/min stage (P<0.0001), beta-blocker use (P=0.009) and baseline HR (P=0.04) were predictors of need for atropine. CONCLUSION: Giving atropine early in appropriate patients can reduce test times without an increase in side effects. Our model enables accurate prediction of these patients.

A pilot study on the hemodynamic effect of short-term ursodeoxycholic acid therapy in patients with stable liver cirrhosis.

OBJECTIVE: Total serum bile acid concentrations are elevated in individuals with liver disease. Ursodeoxycholic acid (UDCA) therapy in such patients results in a further significant rise in plasma levels to the extent that it becomes the major circulating bile acid. In laboratory animals, bile acids, such as taurocholic acid, have also been shown to possess a diuretic-like action, as they can promote diuresis, natriuresis, and kaliuresis by inhibiting tubular sodium reabsorption. The aim of the present study was to assess the effect of 1 month's UDCA therapy on cardiovascular function in cirrhotic patients. METHODS: Two groups of patients with cirrhosis were studied, six with primary biliary cirrhosis (PBC) and six with postnecrotic liver cirrhosis (PNC). Cardiovascular function was assessed by determination of blood pressure, heart rate, and by two-dimensional and pulsed Doppler echocardiography. RESULTS: In PBC patients, 1 month's treatment with UDCA significantly reduced diastolic volume without changing systolic, diastolic, and mean blood pressures, heart rate, systolic and stroke volumes, ejection fraction, cardiac output, and systemic vascular resistance. In PNC patients, UDCA significantly reduced cardiac output, with a tendency to reduce left ventricular volumes, without any changes in systolic, diastolic, and mean blood pressures. CONCLUSIONS: UDCA caused reductions in diastolic volume in the PBC patients and cardiac output in the PNC patients. Such reductions are not unlike that seen in individuals treated with diuretics. This diuretic-like action deserves further study, particularly in cirrhotic patients who are also being treated with diuretics or show evidence of cardiac myopathy.

Long-term follow-up of patients with severe rheumatic tricuspid stenosis.

BACKGROUND: Tricuspid stenosis is a part of the chronically rheumatic heart. Although rare, when tricuspid stenosis does occur, it occurs in the setting of coexistent mitral and aortic valve disease. The natural course of patients with severe tricuspid stenosis is not well defined. The aim of this study is to present close follow-up of patients with chronic rheumatic heart disease and severe tricuspid stenosis. METHODS AND RESULTS: We retrospectively studied 13 patients (11 women and 2 men) with severe tricuspid stenosis who were followed closely for 6 to 31 years. The mean tricuspid pressure gradient ranged from 3 to 9 mm Hg. Twelve patients underwent surgery for mitral and/or aortic valve lesions without complications. Concomitant tricuspid valve surgery was performed on six patients: two De Vega procedures, two Kay plications, and two implantations of Carpentier rings. All these also had leaflet commissurotomy. After surgery, the mean tricuspid gradient decreased in three patients, did not change in two, and increased in one. All 13 patients were treated with diuretics, digoxin, warfarin, and spirinolactone or ACE inhibitors. On their last follow-up visit, every patient had increased jugular venous pressure. Hepatomegaly was found in 6 of 13, leg edema in 4 of 13, and ascites in 1 of 13. CONCLUSIONS: Most tricuspid stenos patients are women with severe mitral and aortic valve disease. After successful repair of the mitral or aortic valve, and regardless of the type of tricuspid valve surgery, severe tricuspid stenosis was found to be very well tolerated by all the patients over many years of follow-up.

The acute effect of minocycline on the pericardium: experimental and clinical findings.

STUDY OBJECTIVES: To evaluate the acute effect of minocycline on the pericardium in the experimental animal and in the human with malignant pericardial disease. DESIGN: A prospective study in open-chest dogs and in humans. SETTING: Experimental surgery laboratory, medical school; coronary care unit, university hospital. METHODS: Twenty-three open-chest dogs were divided into four groups according to the solution injected intrapericardially: (1) minocycline, 5 mg/kg; (2) minocycline, 10 mg/kg; (3) normal saline solution, 100 mL, followed by minocycline, 10 mg/kg; (4) a mixture of 50 mL of the dog's own blood mixed ex vivo with minocycline, 10 mg/kg to evaluate the effect of rising pH of minocycline solution. The extent of myocardial injury is evaluated by measuring ST-T segment deviation in six standard bipolar leads and in three unipolar electrograms recorded over the left ventricular pericardial surface. The pH of the various minocycline solutions is measured. Nine consecutive patients with malignant cardiac tamponade receiving minocycline intrapericardially are evaluated for the appearance of chest pain and ECG changes. RESULTS: Minocycline (5 and 10 mg/kg) caused marked, transient ST-T segment deviation in all dogs, whether or not saline solution was previously injected into the pericardial sac. Prior mixing of minocycline with blood markedly increased the acidic pH of the minocycline solution and significantly reduced the extent of ST-T segment deviation. Four of nine patients had chest pain during minocycline injection. None had ST-T segment changes. CONCLUSION: Minocycline causes a marked, transient injury to the epicardial-pericardial surface. Our animal and in vitro studies indicate that this acute injury is probably partly related to the acidic pH of the minocycline solution. Our experimental findings suggest that this minocycline-induced injury may be reduced by raising the pH of the solution either ex vivo (eg, by mixing minocycline with previously withdrawn pericardial fluid) or in vivo (eg, by leaving 200 to 300 mL of pericardial fluid prior to minocycline injection). Limited experience in the human with malignant cardiac tamponade indicates that intrapericardial minocycline is usually well tolerated, although severe chest pain may appear.

Cardiac valvular vegetations in cancer patients: a prospective echocardiographic study of 200 patients.

PURPOSE: Nonbacterial thrombotic endocarditis can complicate various malignancies and may cause morbidity and mortality mainly as a result of systemic embolism. The antemortem diagnosis of nonbacterial thrombotic endocarditis is rare. The purpose of our study was to assess the frequency, echocardiographic characteristics, and clinical correlation of nonbacterial thrombotic endocarditis in cancer patients. PATIENTS AND METHODS: A prospective echocardiographic screening of 200 nonselected ambulatory patients with solid tumors was performed. Patients were evaluated for evidence of thromboembolic events and for plasma D-dimer levels. A cohort of 100 consecutive patients without overt heart disease referred to echocardiography for the detection of an occult arterial embolic source served as a control group. It consisted of 52 males and 48 females, median age 60 years. RESULTS: The study group included 87 women and 113 men, median age 64 years (range 21 to 91). The frequent malignancies were lymphoma (26%), carcinoma of the gastrointestinal tract (20%), and carcinoma of the lung (16%). Cardiac valvular vegetations were found in 38 patients (19%) compared with only in 2 patients in the control group (2%, P < 0.001). Vegetations were found on the mitral or on the aortic valve in 19 and 18 patients, respectively. Isolated tricuspid valve vegetation was found in 1 patient. Valvular lesions were mostly common in patients with carcinoma of the pancreas (3 of 6, 50%), carcinoma of the lung (9 of 32, 28%), and lymphoma (10 of 52, 19%). Thromboembolism was diagnosed in 22 (11%) patients (12 deep vein thrombosis, 4 emboli to extremities, 2 cerebrovascular accidents, and 4 "silent" segmental left ventricular wall motion abnormalities on echocardiography). Thromboembolism was noticed in 9 of 38 patients (24%) with vegetations compared with 13 of 162 patients without vegetations (8%; P = 0.013). Plasma D-dimer level was examined in a subgroup of 170 patients. D-dimer level was increased in 19 of 21 patients (90%) with thromboembolism compared with 76 of 149 patients without thromboembolism (51%; P = 0.001). CONCLUSIONS: This study demonstrated a high prevalence of cardiac valvular lesions in patients with solid tumors. Vegetations were associated with thromboembolism. Plasma D-dimer level was significantly increased in patients with thromboembolism.

Intrapericardial minocycline sclerosis for malignant pericardial effusion.

STUDY OBJECTIVE: To evaluate the effectiveness and safety of minocycline hydrochloride (minocycline) intrapericardially in patients with malignant pericardial effusion. DESIGN: Consecutive patients admitted to the hospital during a 32-month period received intrapericardial minocycline. SETTING: A 900-bed university hospital. PATIENTS: Fourteen consecutive patients with malignant pericardial effusion. INTERVENTION: Following percutaneous insertion of a pericardial drain, minocycline was administered at a dosage of 10 mg/kg every 48 h until fluid drainage stopped or until further therapy was deemed necessary. MEASUREMENTS: Complications associated with therapy, total minocycline requirements, immediate and late failure of therapy, and clinical and echocardiographic follow-up of at least 6 months. RESULTS: Mean amount of minocycline administered was 1.9 +/- 1.0g given in 2.4 divided doses. Total drainage time was 5.4 +/- 2.5 days. Recurrence of malignant pericardial effusion was seen in only 1 of 14 patients. Death occurred in 10 patients due to severe metastatic disease in all. Minocycline instillation was associated with severe chest pain in seven patients, and with ECG changes suggesting pericardial or subepicardial injury in two patients. CONCLUSION: (1) Intrapericardial minocycline instillation is very effective in preventing recurrence of malignant pericardial effusion. (2) Minocycline is irritative to the pericardium and may cause severe chest pain with transient ECG changes, suggesting pericardial or subepicardial injury.

Missed diagnosis of severe symptomatic aortic stenosis.

Patients with angina pectoris and congestive heart failure with a systolic murmur should be suspected of having significant AS. These patients are frequently women with atrial fibrillation and no left ventricular hypertrophy criteria on the electrocardiogram. Echocardiography with calculation of the aortic valve area is indicated in all these patients.

Digital subtraction myocardial contrast echocardiography: design and application of a new analysis program for myocardial perfusion imaging.

Myocardial contrast echocardiography may provide important physiologic information on myocardial perfusion. Most current analysis programs use manual frame grabbing and selecting of the area of interest. This is time-consuming and not highly reproducible. A system for automatic analysis of myocardial contrast echocardiographic studies was developed and evaluated. The program acquires an electrocardiographically gated sequence of end-diastolic images with a frame grabber in a personal computer. The baseline image is subtracted and the videodensity versus time contrast curve parameters are calculated on-line. Fast color-coded analysis is done automatically with a running square window that covers the entire image. A second mode of contrast analysis allows manual selection of multiple regions of interest. The program was evaluated with contrast echo data from open-chest dogs and two demonstrative patients. This myocardial contrast analytic package is an inexpensive, rapid, flexible, convenient, and reproducible on-line method that facilitates myocardial contrast echocardiographic analysis.

Septal/free wall curvature ratio: a noninvasive index of pulmonary arterial pressure.

The leftward septal shift, a well-recognized feature of pulmonary hypertension, was used to quantify right ventricular pressure in 16 patients with pulmonary hypertension and 11 control patients, all with normal left ventricular function. Pulmonary pressure was calculated from the tricuspid regurgitation jet and left ventricular pressure was taken by arm cuff measurements. Short-axis echocardiographic images were obtained and the midwall curvatures of the septum and the left ventricular free wall were measured for each frame from end diastole to end systole and averaged. The septal/free-wall curvature ratio (CR) was 0.37 +/- 0.19 in the study group compared with 0.79 +/- 0.06 in the control group (p < 0.0001). A tight relationship between the CR and the transseptal/transmural pressure ratio (CR = 0.057 + 0.89 x transseptal/transmural pressure ratio; r = 0.98; p < 0.001) was obtained by linear regression. Given the systolic arterial pressure, the pulmonary systolic pressure is given by: systolic arterial pressure x (1.064-1.12 x CR). Therefore the CR can be used as a noninvasive index that reflects the level of pulmonary pressure in relationship to the systolic arterial pressure.

Cardiac involvement in patients with myeloproliferative disorders.

INTRODUCTION: To evaluate cardiac involvement in myeloproliferative disorders (MPD), two-dimensional and Doppler echocardiographic studies were performed in 30 patients with MPD. PATIENTS AND METHODS: There were 18 women and 12 men, with an age range from 35 to 76 years. Eighteen patients had polycythemia vera (PV), 8 had essential thrombocythemia (ET), and 4 had agnogenic myeloid metaplasia (AMM). RESULTS: Echocardiography revealed valvular lesions in 19 of 30 patients (63%) compared with only 1 of 22 patients (4.5%) in a control group of patients referred for echocardiography to exclude a cardiac source for idiopathic systemic thromboembolism (chi 2 = 13.39, p < 0.001, by chi 2 test with Yates' correction). Valvular lesions were found in 77% of patients with PV, 50% with ET, and 25% with AMM (p = NS). The aortic and mitral valves were the most commonly involved valves, and the most common echocardiographic lesion was leaflet thickening, which was found in 12 patients (40%), followed by vegetations, which were observed in 5 patients (16%). In their past history, 14 of 30 (47%) MPD patients had arterial or venous thrombosis or embolism. Twelve of 19 (63%) patients with valvular lesions had thromboembolism compared with only 2 of 11 (18%) patients without evidence of valvular lesions (chi 2 = 3.99, p < 0.05, by chi 2 test with Yates' correction). Pulmonary hypertension, unrelated to the severity of valvular disease and probably resulting from pulmonary venous occlusion, was found in four patients (13%). CONCLUSIONS: We conclude that the heart is frequently involved in patients with MPD, particularly when their past history is complicated by a thromboembolic event. Some patients have clinically significant valvular disease. Pulmonary hypertension is another relatively common finding in MPD patients. Echocardiography provides information of clinical significance in MPD patients. A larger number of patients is needed to determine whether the presence of valvular lesions is of prognostic significance and may herald future thromboembolic events.

Malignant pericardial tamponade.

We studied the clinical course and management of 27 patients with malignant pericardial tamponade seen in a single Medical Center over a 10 year period. Patients treated with repeat pericardial tap as their only mode of therapy had a high rate of recurrent tamponade (6 of 13 subjects) whereas most patients treated with drainage (either surgical or percutaneous) had sustained control of their pericardial effusion (achieved in 10/13 subjects). Intra-pericardial instillation of tetracycline or cyclophosphamide did not clearly improve the good results obtained with drainage alone. Extensive pericardiectomy was required in 2 patients only. Irrespective of the mode of therapy, survival was poor in patients with carcinoma of lung (N = 10) with a median survival of 30 days only vs. 135 days for patients with breast carcinoma (N = 10). Patients with malignant pericardial tamponade are best treated with immediate drainage. Percutaneous and sub-xiphoid surgical drainage are equally effective. Despite invasion of the pericardium by carcinoma, patients with a good oncologic prognosis may enjoy an appreciable survival with adequate quality of life following relief of tamponade.