Diane E. Wallis

Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia.

PURPOSE The complications of heparin-induced thrombocytopenia include thrombosis and death. The purpose of the study was to determine whether early heparin cessation can prevent these outcomes. SUBJECTS AND METHODS We performed a retrospective analysis of consecutive patients with heparin-induced thrombocytopenia diagnosed by platelet aggregometry. Demographic, clinical, and laboratory findings were compared in patients by whether heparin treatment was stopped early (< or = 48 hours) or late (>48 hours) after the onset of thrombocytopenia, as well as between patients with and without thrombosis. Thrombocytopenia was defined as a 50% decline in baseline platelet counts or an absolute platelet count < 100,000/mm3. RESULTS Of the 113 patients, 38% developed thrombosis and 27% died. One-half of patients had thrombosis diagnosed >24 hours after heparin cessation. No difference in thrombosis or mortality was found in the 40 patients with early heparin cessation [mean (+/-SD) time of cessation 0.7 +/- 0.6 days] compared with the 73 patients with late heparin cessation (5 +/- 3 days). Thrombosis >24 hours after heparin cessation occurred in 61% of the patients in the early group and in 40% of the late group (P = 0.17). In a multivariate analysis, only a lower nadir of the platelet count (percent of baseline) was associated with thrombosis. Neither thrombosis nor the time to heparin cessation were associated with mortality. CONCLUSIONS Early heparin cessation was not effective in reducing morbid events in patients with heparin-induced thrombocytopenia. Treatment strategies other than heparin cessation alone should be considered in patients with this condition.

Peripartum cardiomyopathy: Clinical, hemodynamic, histologic and prognostic characteristics

Peripartum cardiomyopathy is defined as left ventricular dilation and failure, first developing during the third trimester of pregnancy or in the first 6 months postpartum. In an effort to characterize this syndrome in a middle class population, 14 consecutive patients with peripartum cardiomyopathy underwent a detailed history and physical examination, right heart catheterization, M-mode and two-dimensional echocardiography, radionuclide ventriculography and right ventricular endomyocardial biopsy. These patients were then observed with sequential noninvasive studies to determine prognostic indicators. Eight (57%) of these 14 patients were primiparous and an equal number first presented with heart failure concomitant with or immediately before the onset of labor. When these women were compared with 55 patients with idopathic dilated cardiomyopathy, only mean age at onset of symptoms (28.7 ± 5.7 versus 48.2 ± 13.6 years, p Seven (50%) of the patients with peripartum cardiomyopathy had dramatic improvement within 6 weeks of follow-up, and 6 (43%) died. Survivors had a higher ejection fraction (22.8 ± 11.7 versus 10.6 ± 1.5%, p

Segmental wall motion abnormalities in dilated cardiomyopathy: A common finding and good prognostic sign

Fifty patients with idiopathic dilated cardiomyopathy were separated into two groups based on the presence of segmental or diffuse left ventricular wall motion abnormalities by radionuclide ventriculography. Investigation included a history and physical examination, electrocardiogram, chest X-ray film, M-mode echocardiogram, coronary angiogram and right ventricular endomyocardial biopsy. Patients with histologic evidence of myocarditis were excluded. Sixty-four percent of the patients had segmental and 36% had diffuse wall motion abnormalities. The group with segmental abnormalities showed significant differences in age (52.5 +/- 10.7 versus 37.8 +/- 14.6 years, p less than 0.001), New York Heart Association functional class III to IV (56 versus 89%, p less than 0.01), pulmonary capillary wedge pressure (14 +/- 9 versus 26 +/- 9 mm Hg, p less than 0.001), left ventricular end-diastolic dimension measured on echocardiogram (67 +/- 8 versus 77 +/- 11 mm, p less than 0.001), cardiac index (2.6 +/- 0.6 versus 2.0 +/- 0.5 liters/min per m2, p less than 0.01) and ejection fraction by radionuclide ventriculography (20 +/- 7 versus 13 +/- 5%, p less than 0.001). Patients with diffuse wall motion abnormalities had poorer histologic findings based on myocardial cell hypertrophy and nuclear changes (p less than 0.01) and a higher short-term mortality with a 1 year survival rate of 50% compared with 90% in patients with segmental wall motion abnormalities by life-table analysis (p less than 0.05). When data were reanalyzed excluding those patients with complete left bundle branch block, no significant change in any variable was detected. Segmental wall motion abnormalities, even when left bundle branch block is excluded, are common in dilated cardiomyopathy in the absence of coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient bundle branch block following use of hypothermic cardioplegia in coronary artery bypass surgery: High incidence without perioperative myocardial infarction

Hypothermic cardioplegia (HCP) is a method commonly used for myocardial preservation at the time of aortic cross-clamping during coronary artery bypass grafting (CABG). This study assessed the frequency and significance of transient bundle branch block (BBB) in 50 patients undergoing CABG using HCP compared to 61 controls. All patients had normal QRS complexes on preoperative ECG. CLinical, hemodynamic, and operative data were similar in both groups. Seventeen (34%) of the HCP group and four (6%) of the controls developed postoperative BBB (p less than 0.001). These changes were transient in all but three patients in the HCP group. None of the HCP patients with transient BBB had evidence of perioperative myocardial infarction. Clinical and operative parameters did not provide prediction of development of transient BBB. This study demonstrates that transient BBB in the immediate post-CABG period occurs commonly with the use of HCP and does not indicate myocardial necrosis.

Argatroban Therapy for Heparin-Induced Thrombocytopenia in Acutely Ill Patients:

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction to heparin therapy. To evaluate clinical outcomes and effects of argatroban therapy in acutely ill HIT patients. Retrospective analysis. Hospital in-patient. Acutely ill patients with clinically diagnosed HIT from previous multicenter, historically controlled studies of argatroban therapy in HIT. Argatroban, adjusted to maintain activated partial thromboplastin times 1.5 to 3 times baseline, or historical control therapy (ie, no direct thrombin inhibition). We identified 488 patients who received argatroban (N = 390; mean dose of 1.9 µg/kg/min for a mean 6 days) or historical control therapy (N = 98) for HIT. The primary all-cause composite endpoint of death, amputation, or new thrombosis within 37 days occurred in 133 (34.1%) argatroban-treated patients and 38 (38.8%) controls (P = .41). Argatroban, versus control, significantly reduced the primary thrombosis-related composite endpoint of death because of thrombosis, amputation secondary to ischemic complications of HIT, or new thrombosis (17.7% vs 30.6%, P = .007). Significant reductions also occurred in new thrombosis and death because of thrombosis. Major bleeding was similar between groups (7.7% vs 8.2%; P = .84). Adverse outcomes were more likely to occur in patients who were initially diagnosed with HIT and thrombosis, had undergone cardiac surgery, were not white, or had more severe thrombocytopenia. In acutely ill HIT patients, argatroban, versus historical control, provides effective antithrombotic therapy without increasing major bleeding. Patients with more severe thrombocytopenia or HIT-related thrombosis on HIT diagnosis have a poorer prognosis, emphasizing the importance of prompt recognition/ treatment of HIT in acutely ill patients.

Significance of Electrocardiographic ST Elevation During Coronary Artery Bypass Surgery

The aim of this study was to determine the significance of new electrocardiographic (ECG) ST elevation during coronary artery bypass surgery. Multilead ECGs were recorded intraoperatively approximately every 3 min on 105 patients. Cases of new ST elevation were divided into ischemic and those considered to be due to nonischemic causes such as cooling during cardiopulmonary bypass (CPB), defibrillation, new cardiac conduction abnormalities, and pericarditis. The myocardial fraction of creatine kinase (CK-MB) > or = 25 IU/L was considered to be indicative of myocardial injury. Both patients who had ischemic ST elevation prior to CPB and all seven patients who had ST elevation in temporal association with the administration of protamine had peak CK-MB > or = 25 IU/L. One patient with peak CK-MB > or = 25 IU/L did not have ST elevation and was considered to have injury during CPB. Two of these ten patients had Q wave myocardial infarctions (MIs). For the detection of patients with peak CK-MB > or = 25 IU/L, the sensitivity of ischemic ST elevation was 90% and the specificity was 100%. A history of MI prior to surgery and a history of Type I diabetes were associated with peak CK-MB > or = 25 IU/L (P < 0.05).

Transesophageal echocardiographic assessment of the contribution of intrinsic tissue thickness to the appearance of a thick mitral valve in patients with mitral valve prolapse.

OBJECTIVES This prospective, blinded transesophageal echocardiographic study was performed to determine the relative contributions of leaflet redundancy and overlap versus intrinsic tissue thickening as mechanisms for the apparent increase in diastolic thickness of the mitral valve. BACKGROUND Increased diastolic thickness of the mitral valve has been identified as an echocardiographic feature that predicts subsequent adverse sequelae in patients with mitral valve prolapse (MVP). METHODS Eleven patients with clinical and transthoracic echocardiographic evidence of MVP and 11 age-matched control subjects underwent protocol transesophageal echocardiography to image the mitral valve in two orthogonal planes and to measure its thickness in systole and diastole. RESULTS Maximal diastolic width of the slack, unloaded anterior leaflet was significantly greater in patients with MVP than in control subjects (mean +/- SD: 0.64 +/- 0.20 cm vs. 0.30 +/- 0.04 cm, p < 0.001). Similarly, diastolic posterior leaflet width was greater in patients with MVP (0.67 +/- 0.39 cm vs. 0.31 +/- 0.06 cm, p < 0.01). In contrast, minimal systolic width of the distended pressure-loaded mitral valve was not significantly different between patients with MVP and control subjects for either the anterior (0.22 +/- 0.05 cm vs. 0.20 +/- 0.04 cm, p = NS) or the posterior (0.25 +/- 0.07 cm vs. 0.24 +/- 0.05 cm, p = NS) leaflets. The percent change in leaflet width from diastole to systole (% delta W), an index of the contribution of dynamic factors (e.g., leaflet redundancy and overlap) to the apparent increase in diastolic leaflet thickness, was significantly greater in patients with MVP than in control subjects for both the anterior (% delta W 62 +/- 13% vs. 34 +/- 16%, p < 0.001) and the posterior (% delta W 54 +/- 19% vs. 22 +/- 21%, p < 0.005) leaflets. CONCLUSIONS The apparent increase in diastolic mitral leaflet thickness in patients with MVP versus control subjects is largely attributable to dynamic factors such as leaflet redundancy, overlap and deformation. During diastole, when the mitral leaflets are slack and unstressed, the leaflets appear markedly thickened in patients with MVP. In contrast, during systole, when developed intraventricular pressure distends the leaflets, causing them to stretch and balloon into the left atrium, the intrinsic tissue thickness is much less than that measured in diastole. These findings have important implications for the morphologic criteria used to diagnose MVP and the potential pathophysiologic mechanisms for adverse sequelae in this syndrome.

State-of-the-Art Review : Heparin-induced Thrombocytopenia and Thrombosis Syndrome

Manuscript received February 2, 1998; accepted February 11, 1998. Address correspondence and reprint requests to Dr. Diane E. Wallis, Loyola University Medical Center, Bldg. 104, Room 3369, 2160 South First Avenue, Maywood, IL 60153, U.S.A. Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) are recognized as devastating immunemediated complications of heparin therapy. Due to the ubiquitous use of unfractionated heparin, the reported HIT prevalence of 2% to 3% is a significant concern, as affected patients with HIT may suffer death and morbidity due to complications such as limb loss, myocardial, cerebral or visceral infarction, and thromboembolism. In this review, the pathophysiology, clinical expression, diagnosis, laboratory investigation, and treatment will be discussed.

Safety and efficacy of esmolol for unstable angina pectoris

Esmolol is a rapidly metabolized cardioselective beta-adrenergic blocker that provides steady state beta-adrenergic blockade when administered by continuous intravenous infusion. To determine the efficacy of esmolol in the management of unstable angina, 23 patients with known coronary artery disease, who averaged 3.7 +/- 2.7 daily episodes of chest pain at rest, were randomized to receive either a continuous infusion of esmolol (n = 12) or oral propranolol (n = 11), as an adjunct to concomitant antianginal therapy. Patients with systolic blood pressure less than 110 mm Hg, heart rate less than 60 beats/min or known contraindications to beta blockade were excluded. Esmolol was titrated in a step-wise fashion from 2 to 24 mg/min at 5-minute intervals up to a 30% reduction in heart rate and systolic blood pressure double-product. The propranolol dose was increased every 6 hours by 50 to 100% to achieve a similar reduction in heart rate and blood pressure. When compared with their 24-hour baseline periods, both groups achieved a significant reduction in episodes of chest pain, from 4.6 +/- 3.3 to 1.4 +/- 1.5 in the esmolol group (p less than 0.02) and 2.6 +/- 1.4 to 1.0 +/- 1.5 in the propranolol group (p less than 0.02) during the subsequent study period. The cardiac event rate and incidence of drug side effects were similar between the 2 groups; however, side effects seen with esmolol did not require treatment after drug discontinuation. Thus, maximally tolerated beta blockade is an effective therapy for unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Esmolol on the Ventricular Fibrillation Threshold

The effect of esmolol on the ventricular fibrillation threshold (VFT) was determined in 11 open-chest dogs anesthetized with sodium pentobarbital. Since changes in VFT by antiarrhythmic drugs have been shown to depend on the method used to test vulnerability to fibrillation, two methods were studied. The vulnerable period was scanned with a train of pulses (100 Hz, 4 ms, 20 pulses) in nine experiments and a single pulse (10 ms) in eight experiments. Following control measurements, esmolol was administered as an intravenous bolus of 500 micrograms/kg followed by a continuous infusion of 300 micrograms/kg/min. After 15 min of infusion, the adequacy of beta-blockade was tested by the administration of 0.5 micrograms/kg of isoproterenol. Isoproterenol increased the heart rate by only 18 +/- 2 beats/min following esmolol administration which was significantly less than the control response (79 +/- 7 beats/min, p less than 0.01). Although the VFT measured with the single-pulse technique did not change in response to esmolol (14.1 +/- 1.1 mA vs. 14.3 +/- 1.2 mA), the VFT measured with the train-of-pulses technique significantly increased (3.7 +/- 0.5 mA to 14.5 +/- 2.8 mA, p less than 0.01). Twenty minutes after discontinuing esmolol, the VFT measurements were repeated and did not differ from control values with either technique. The increase in heart rate in response to isoproterenol also returned to control values (80 +/- 6 beats/min). The results suggest that the ability of esmolol to raise VFT as measured by the train-of-pulses technique is due to beta-adrenergic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)