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Temporal
aspects of heparin-induced thrombocytopenia.
Reviewer: Rose Christopherson,
MD, PhD
Background: Heparin-induced thrombocytopenia (HIT) is a common antibody-mediated drug reaction. The temporal relation between HIT and previous or current heparin therapy was studied. Methods: The study population was 243 patients with serologically confirmed HIT. The time from the start of heparin therapy to onset of HIT was examined, as well as the persistence of heparin-dependent antibodies in patients' plasma. Either a platelet serotonin-release assay or an assay of anti-platelet factor 4 antibodies was used. Also, the course of 7 patients who had HIT previously and were later treated with heparin was examined. Results: Onset of HIT was 4 or more days after the start of heparin therapy in 170 patients (70 %). In the other 73 patients (30 %), the onset of HIT was rapid, with median time of onset 10.5 hours after initiation of heparin therapy. All of these patients had received heparin within 100 days prior to the beginning of the course of heparin therapy which resulted in HIT. Heparin-dependent antibodies in the sera of all patients fell to undetectable levels after a median of 50-85 days, depending on the assay used. None of the 7 patients who received heparin after the disappearance of heparin-dependent antibodies from HIT developed HIT a second time. Conclusions: The authors concluded that HIT can have a very rapid onset in patients who have received heparin within 100 days prior to beginning heparin therapy. However, heparin-dependent antibodies did not necessarily reoccur when a small subset of the study patients received heparin after the antibodies from the previous episode of HIT had disappeared. Comments: Among the 170 patients with more typical onset of HIT, only 16 had received heparin within 100 days previously. Forty-seven had definitely received heparin at some time prior to HIT, 49 may have had previous heparin therapy, and 74 were felt to be unlikely to have previously received heparin. The time of onset of HIT among these patients was not related to whether they had previously received heparin. The authors noted another report in which 10 patients with a history of HIT but with negative serological tests for heparin-dependent antibodies were given heparin in preparation for cardiac surgery. None of these patients developed HIT. This suggests that among patients with a history of HIT but with negative serologic tests for heparin-dependent antibodies, the risk of HIT is relatively low. However, this is based upon only 17 patients. The authors concluded that among such patients, there should be a compelling indication for giving heparin, such as cardiac or vascular surgery, and that the use of heparin should be limited to the surgical procedure, with another anticoagulant given afterward.
Ischemic mitral regurgitation; long-term outcome and
prognostic implications with quantitative Doppler assessment.
Reviewer: Mark A. Chaney, M.D
Myocardial infarction (MI) can initiate ischemic mitral regurgitation (IMR), which portends a poor prognosis in the acute and early phases following infarction. However, the prognostic implications of IMR during the chronic and late phases following infarction are poorly defined. These investigators analyzed 303 patients with previous (>16 days) MI (ECG Q-wave) who underwent transthoracic echocardio-graphy. 194 patients exhibited IMR whereas 109 patients did not. Both groups were similar in regards to age, sex, and ejection fraction. In IMR patients, regurgitant volume (RVol) and effective regurgitant orifice (ERO) area were 36 ± 24 mL/beat and 21 ± 12 mm2, respectively. At 5 year follow-up, total mortality and cardiac mortality for patients with IMR (62 ± 5% and 50 ± 6%, respectively) were higher than for those without IMR (39 ± 6% and 30 ± 5%, respectively) (both P < 0.001). In multivariate analysis, independent of all baseline characteristics (including age and ejection fraction), the adjusted relative risks of total and cardiac mortality associated with the presence of IMR and quantified degree of IMR (defined by RVol ³ 30mL and by ERO ³ 20 mm2) were high. The investigators conclude the presence of IMR in the chronic phase after MI is associated with excess mortality independent of baseline characteristics and degree of ventricular dysfunction. The mortality risk is related directly to the degree of IMR as defined by RVol and ERO. Thus, IMR detection and quantification provide important information for risk stratification and clinical decision making in the chronic post-MI phase. Comments: Mitral regurgitation due to acute complications of coronary
artery disease (IMR) and/or MI is a much different entity than that associated
with intrinsic valve disease (rheumatic disease). IMR in the acute phase of
MI is frequent (approximately 20% of patients) and likely is associated with
an adverse prognosis yet prognostic implications of IMR in the chronic post-MI
phase are uncertain. Previous investigations in this area are confounded by
problems involving characteristics of study patients (timing of MI) and methodology
of determining the degree of mitral regurgitation (angiography, echocardiography,
etc.). The aim of this investigation was to analyze, in the post-MI chronic
phase, the independent prognostic implications of IMR presence and degree, quantitatively
assessed by Doppler echocardiography. These investigators studied 303 patients
who experienced a Q-wave MI older than 16 days before baseline assessment with
transthoracic echocardiography. The 16-day criterion was based on studies that
indict the poor prognostic effect of IMR diagnosed within and not beyond 16
days after MI. Diagnosis of IMR was based on normal leaflets with an enlarged
annulus and was easily differentiated from organic regurgitation. Patients with
(n=194) and
Factors associated with prolonged mechanical ventilation
following coronary artery bypass surgery
Reviewer: KW Tim Park, MD
Background: In the U.S., nearly 600,000 coronary artery bypass graft (CABG) procedures are performed annually, with an average cost of more than $ 44,000 per case (American Heart Association update 1998). A significant fraction of the cost is due to the stay in the intensive care unit (ICU) and a common reason for prolonged ICU stay is prolonged mechanical ventilation. This paper examined the typical postoperative duration of mechanical ventilation after CABG at a busy regional referral center for cardiac surgery and identified factors associated with prolonged ventilation. Patients with preoperative renal failure were especially likely to receive prolonged ventilation, with more than 20 % of them receiving ventilation for 4 or more days. Previous cardiac surgery or placement of a permanent pacemaker or ACID, preoperative medical instability from cardiac or respiratory failure, urgent operation and concomitant valve surgery were additional risk factors for prolonged ventilation. There were not enough patients who underwent MID CAB to study the impact of this surgery on postoperative ventilation. When the STS score was included in the Cox regression analysis, the only variables other than the score that were associated with prolonged ventilation were the operative urgency and the patient's age. The STS score by itself would have underestimated the importance of the age and the operative urgency in predicting prolonged ventilation. Comments: The results of this study confirm the clinical impression that most CABG patients can be extubated within a day or two of the surgery and is qualitatively consistent with the STS National Cardiac Surgery Database that reported that the % of patients receiving ventilation > 1 day was 5.9 % in 1997. The fraction receiving prolonged ventilation might have been higher in the study cohort, because the study hospital was a referral center and the % of urgent operations may have been higher than the national average. In the study population, 5.9 % of the patients received ventilation for 4 or
more days. From the probability of ventilation curve in the paper, one can calculate
that these 5.9 % of the patients accounted for about a third of total ICU days
consumed by all the patients. Even if one discounted the fact that patients
who required prolonged ventilation were likely to require more labor- and resource-intensive
ICU care per each ICU day than patients who were The STS score was developed to predict the risk of death after cardiac surgery and was, by definition and derivation, a significant predictor of mortality after CABG. The fact that the STS score by itself was a significant independent predictor of prolonged postoperative ventilation suggested that measures to alter risks of prolonged ventilation will likely alter risks of death as well. Studies that prospectively alter risk factors of prolonged ventilation and death and document expected changes would need to be carried out.
Methods: The medical records of all 4,863 patients who underwent CABG in 1996-97 were retrospectively reviewed after discharge or death. The duration of mechanical ventilation was the number of calendar days from the end of surgery to extubation, with fractions of a day being rounded up. The following variables were noted: demographic factors, chronic and acute medical problems, previous cardiac interventions, type and urgency of the operation, the Society of Thoracic Surgery (STS) score, and perioperative mortality. Three types of the operation were recognized: CABG alone, CABG with a valve surgery, and minimally invasive CABG (MID CAB). The STS score was a predicted risk of mortality derived from a proprietary logistic regression equation using preoperative variables; the software that calculates the score from preoperative variables may be purchased from the STS. These variables were analyzed for their effect on continuing ventilation in a Cox proportional hazards regression model, with the time spent receiving ventilation taken as the "survival" time. P < 0.001 was considered significant to decrease the type I errors associated with testing multiple variables. Results: 88.8 % of the patients were extubated either on the day of
surgery or the next day. An additional 5.3 % was extubated on day 3, 4.2 % on
days 4 _ 14, and the remaining 1.7 % after day 14. Reintubation occurred in
3.2 % of the patients, more than 80 % of whom received ventilation for 4 or
more days. Tracheostomy was required for prolonged ventilation in 0.8 %. The
mortality rate was 1.95 % (95 out of 4,863); 66 of the 95 were ventilated for
4 or more days. Among demographic factors, prolonged ventilation was significantly
associated with female gender, age, and low body mass index (BMI). Although
age was significantly associated with prolonged ventilation, nearly 90 % of
even those > 75 years old were extubated in the first 3 postoperative days.
Whereas a low BMI (< 20 kg/m2) was associated with prolonged ventilation,
there was no increased risk with obesity, even morbid obesity. History of renal
failure, cardiomyopathy, valvular dysfunction, congestive heart failure, stroke,
or COPD, but not tobacco use or diabetes was associated with prolonged ventilation.
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