Reactivation of coagulation after stopping infusions of recombinant hirudin and unfractionated heparin in unstable angina and myocardial infarction without ST elevation: results of a randomized trial. OASIS Pilot Study Investigators. Organization to Assess Strategies for Ischemic++ Syndromes.

AIMS: To compare effects of heparin and hirudin on biochemical markers of coagulation. METHODS AND RESULTS: Patients (n=395) with unstable angina or myocardial infarction without ST elevation were randomized to a 72-h infusion of one of three regimens: unfractionated heparin (bolus of 5000 IU followed by an infusion of 1200 IU. h(-1)), low-dose hirudin (HBW 023; 0.2 mg. kg(-1)bolus followed by 0.10 mg. kg(-1). h(-1)) or medium-dose hirudin (0.4 mg. kg(-1)bolus followed by 0.15 mg. kg(-1). h(-1)). Infusions were adjusted to maintain an activated partial thromboplastin time of between 60-100 s. Activated partial thromboplastin time, prothrombin fragment 1.2 (F1.2), thrombin antithrombin III complex and D-dimer were measured before, during and after the infusion. Median activated partial thromboplastin time was similar in the two groups early on, but was significantly lower in the heparin group than in the combined hirudin group 48 h after starting the infusion (53 s and 75 s, respectively;P<0.001), and 6 h after stopping (31 s and 46 s, respectively;P<0.001). Median F1.2 levels were not significantly different between the groups during the infusion. Median thrombin antithrombin III levels in the heparin and hirudin groups were 2.8 microg. l(-1)and 2.3 microg. l(-1), respectively, at 6 h (P<0.001), and 3.0 microg. l(-1)and 2.3 microg. l(-1), respectively, at 48 h (P<0.001). Median D-dimer levels were 320 ng. ml(-1)and 260 ng. ml(-1)48 h after starting the infusion in the heparin and hirudin groups, respectively (P<0.001), and 415 ng. ml(-1)and 280 ng. ml(-1), respectively (P<0.001) 6 h after stopping. D-dimer levels were significantly elevated above baseline values in both groups 24-48 h after stopping the infusions. CONCLUSIONS: The greater reduction of thrombin antithrombin III and D-dimer during the hirudin infusion supports the hypothesis that hirudin is a more potent antithrombin agent than heparin. Increased D-dimer levels after stopping heparin or hirudin suggest that there is an ongoing pro-coagulant state. These results point to the greater efficacy of hirudin in preventing early clinical events (death, myocardial infarction and refractory ischaemia) compared with heparin that have been observed in large randomized trials. Persistent activation of coagulation afterstopping infusions in our study suggests that a longer course of antithrombotic treatment may be needed to pacify the thrombus.

Echocardiography and excision of lipomatous hypertrophy of the interatrial septum.

We present a case of massive lipomatous hypertrophy of the interatrial septum, in which transesophageal echocardiography was used to guide surgical resection. Tissue removal was undertaken without entering either the left or right atrium, thereby obviating the need for atrial septal reconstruction.

Early experience with stentless versus stented valves.

BACKGROUND: The Toronto stentless porcine valve (SPV) was designed to improve hemodynamics after aortic valve replacement by maximizing available flow area in comparison to stented valves (STD). METHODS: To assess possible hemodynamic differences between STD and SPV, 59 patients undergoing isolated aortic valve replacement (+/-coronary artery bypass graft) were prospectively evaluated by preoperative and 3- to 6-month postoperative echocardiography. Among these, 23 patients received a STD, whereas 36 received the Toronto SPV. RESULTS: The mean size (mm) of SPV implanted was larger (SPV, 26.6+/-2.1; STD, 24.0+/-2.9; P=0.0002). Patients receiving STD valves were older and had a higher prevalence of coronary artery disease and congestive heart failure. There were no preoperative differences in left ventricular mass index (g/mo2), peak or mean pressure gradients (mmHg), effective orifice area (cm2), extent of fractional shortening (%), or velocity of circumferential shortening (cf/sec). ANOVA demonstrated a significant reduction in left ventricular mass index at 3 to 6 months (P=.0001) but no differences in left ventricular mass index regression between groups (STD, -28.8+/-37.5; SPV, -31.2+/-32.4; P=.36). Effective orafice area was increased postoperatively (P=.0001), particularly among SPV cases (STD, 1.5+/-0.4; SPV, 1.9+/-0.7; P=.01). Postoperative left ventricular mass index and mean pressure gradient were reduced (P=.0001) but did not differ between groups. Fractional shortening and velocity of circumferential shortening were greater in the SPV patients at 3 to 6 months after aortic valve replacement (P=.0004 and .0001, respectively), and an interactive effect was seen between time and prosthetic group (P=.0028 and .032, respectively). CONCLUSIONS: In a consecutive series of patients, we identified no hemodynamic differences between STD and SPV, although ventricular function improved after SPV. Because of the nonrandomized nature of the study, selection bias may have accounted for some of the observed results. A prospective, randomized trial is necessary to determine the hemodynamic advantages, if any, of the SPV valve.

Left ventricular mass regression early after aortic valve replacement.

BACKGROUND: Regression of left ventricular hypertrophy is an important and well-recognized salutary effect of aortic valve replacement. The earliest evidence of left ventricular mass regression after aortic valve replacement and the influence of prosthesis type are not well known, and were the focus of this study. METHODS: Transthoracic echocardiography was used to measure left ventricular mass index preoperatively and before discharge in 57 consecutive patients undergoing isolated aortic valve replacement (with or without coronary artery bypass grafting). RESULTS: Three patients were excluded from the study because of inability to obtain accurate M-mode echocardiographic images for left ventricular mass measurement preoperatively (1) or postoperatively (2). Of the remaining 54 patients, mechanical bileaflet valves were used in 19, stented tissue bioprostheses were implanted in 15, and a stentless porcine bioprosthesis was chosen for 20. Postoperative echocardiograms were obtained 4.9 +/- 2.3 days after aortic valve replacement (range, 2 to 9 days). A two-way repeated-measures analysis of variance demonstrated a significant reduction of left ventricular mass index before discharge (preoperative 141.4 +/- 45.2 g/m2, postoperative 127.5 +/- 32.8 g/m2; p = 0.0005) but no differences between prostheses. CONCLUSIONS: Left ventricular mass regression begins early after aortic valve replacement, probably because of reduction of transvalvular gradients and left ventricular wall stress. At least in the very early postoperative period, the type of prosthesis does not influence the extent of mass regression.

Overtreatment of hypertension in the community?

Some patients currently receiving therapy for uncomplicated, mild to moderate essential hypertension may have been started on medication because of transient increases in office blood pressure (BP) or because of "white coat hypertension." As a consequence, many patients who do not have persistent hypertension may be receiving therapy for this diagnosis. This possibility was examined by discontinuing medication in 98 patients without target organ damage who were receiving longterm antihypertensive therapy under the care of their family physician in the community. Development of hypertension was based upon an increase in the patient's ambulatory BP (mm Hg) to > or = 160/95 recorded during usual daily activities. Evidence of early target organ damage was sought by using echocardiography to measure changes in left ventricular mass during the period off therapy. In the 50 patients who remained off treatment for 1 year, mean ambulatory BP increased (P < .001 from baseline (128 +/- 2/76 +/- 1) to 139 +/- 1/82 +/- 1 at 1 year, but remained lower (P < .001) than corresponding office readings performed by the patient's family physician (baseline: 138 +/- 2/83 +/- 1; 1 year: 150 +/- 2/89 +/- 1). At 1 year, ambulatory BP was < 150/90 and < 140/90 in 41 and 21 patients, respectively. Withdrawal of therapy did not produce any changes in left ventricular mass index (g/m2) with the mean value at 1 year (104 +/-3) being similar to baseline (103 +/- 3). Of the remaining patients, 35 redeveloped hypertension and 13 restarted therapy for reasons unrelated to BP. Many patients with treated, uncomplicated, mild to moderate hypertension may tolerate withdrawal of antihypertensive drug therapy without developing persistent hypertension or any increase in left ventricular mass.

Prevalence of white coat effect in treated hypertensive patients in the community.

Patients receiving drug therapy for hypertension in the tertiary care setting frequently exhibit higher office readings compared to ambulatory blood pressure values (white coat effect). In this study, the prevalence of a white coat effect was determined in an unselected population of 147 hypertensive patients receiving treatment from their family physicians in the community. The proportion of patients with a white coat effect (defined as office - ambulatory blood pressure > or = 20/10 mm Hg) was significantly (P < .001) higher when based upon the family physician's routine blood pressure readings (91/147), compared to special readings taken by the family physician for the study (54/147) or readings taken by a research nurse (30/147). There was a higher correlation (P < .05) between the ambulatory systolic blood pressure and the nurse's readings (r = 0.62) or special physician's readings (r = 0.55) v the routine physician's readings (r = 0.34). Left ventricular mass index as measured by echocardiography correlated (P < .01) with the special physician (r = 0.27), nurse (r = 0.23), and ambulatory systolic blood pressure readings (r = 0.24), but not with the routine physician's readings (r = 0.06). A white coat effect is frequently present in treated hypertensive patients when blood pressure is recorded by family physicians in routine clinical practice.

Reproducibility of nurse-measured, exercise and ambulatory blood pressure and echocardiographic left ventricular mass in borderline hypertension.

OBJECTIVE: To compare the short-term reproducibility of four diagnostic tests: resting blood pressure, exercise blood pressure, non-invasive daytime ambulatory blood pressure and echocardiographic left ventricular mass. DESIGN: Blinded, prospective test-retest (reliability) study. SETTING: Hypertension research units in two teaching hospitals. PARTICIPANTS: Six normal volunteers and 22 patients with untreated borderline to mild hypertension, mean age 44 years. MAIN OUTCOME MEASURES: The intraclass correlation coefficient (RI) and standard deviation of the difference (SDD) between visits. MAIN RESULTS: The mean blood pressures and left ventricular mass did not differ between visits. Concordance between visits reached RI = 0.86 systolic/0.66 diastolic for ambulatory blood pressure and RI = 0.85 systolic/0.64 diastolic for nurse-measured random-zero sphygmomanometer resting blood pressure. The respective variabilities were SDD = 9/8 and 8/8 mmHg. Submaximal exercise systolic blood pressure (SBP) and echo left ventricular mass showed excellent reliability. Echo left ventricular mass and resting SBP or ambulatory SBP were significantly more reproducible than resting diastolic blood pressure (DBP) or ambulatory DBP. CONCLUSIONS: Despite averaging many readings within each day, clinically important between-visit variations in ambulatory blood pressure remained. The between-visit variability of daytime ambulatory blood pressure was similar to that of resting blood pressure when carefully measured by a research nurse. The echo left ventricular mass appears to be more reproducible over the short term than the current diagnostic standard for hypertension, the resting DBP.