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Nils Kucher

Publications and source records attributed to Nils Kucher.

35 records · Page 2Linked to original sources
PubMed2004

International normalized ratio increase before warfarin-associated hemorrhage: brief and subtle.

OBJECTIVE: To determine the relationship between serial international normalized ratios (INRs) in patients who have been undergoing long-term anticoagulation and the onset of warfarin-associated bleeding complications. METHODS: The study cohort consisted of 2391 patients treated in the Anticoagulation Service at Brigham and Women's Hospital, Boston, Mass, from April 1999 through July 2003. For each patient with a bleeding event, we selected 2 controls who were matched for age, sex, indication for warfarin therapy, and duration of enrollment in our Anticoagulation Service. RESULTS: Warfarin-related hemorrhage occurred in 32 patients (1.3%). The mean +/- SD INRs at the time of the bleeding event or matched patient's event date (5.9 +/- 5.9 vs 2.3 +/- 0.7; P<.001) and the mean+/-SD last INRs before the bleeding event or matched patient's event date (3.0 +/- 1.2 vs 2.1 +/- 0.8; P<.001) were higher in the patients than in the controls. The last INRs before the bleeding event were obtained an average of 11.6 +/- 17.8 (mean +/- SD) days before the event in the patients and 18.3 +/- 28.0 (mean +/- SD) days before the matched date in the controls (P = .22). The mean second-to-last INRs were similar in both groups (2.8 +/- 2.1 vs 2.3 +/- 0.8; P = .11). When the INRs were plotted in relation to the time before the onset of bleeding, a marked increase in the patients' INRs was observed shortly before the bleeding began. CONCLUSIONS: Serial INRs are poor predictors of hemorrhagic events. There appears to be only a brief warning period during which a slightly elevated INR predicts an imminent bleeding event.

Adult↗
PubMed2004

Upper-extremity deep vein thrombosis: a prospective registry of 592 patients.

BACKGROUND: Upper-extremity deep vein thrombosis (UEDVT) occurs spontaneously or sometimes develops as a complication of pacemaker use, long-term use of a central venous catheter (CVC), or cancer. METHODS AND RESULTS: To improve our understanding of UEDVT, we compared the demographics, symptoms, risk factors, prophylaxis, and initial management of 324 (6%) patients with central venous catheter (CVC)-associated UEDVT, 268 (5%) patients with non-CVC-associated UEDVT, and 4796 (89%) patients with lower-extremity DVT from a prospective US multicenter DVT registry. The non-CVC-associated UEDVT patients were younger (59.2+/-18.2 versus 64.2+/-16.9 years old; P<0.0001), less often white (65% versus 73%; P<0.01), leaner (body mass index [BMI] 26.8+/-7.1 versus 28.5+/-7.3 kg/m2; P<0.001), and more likely to smoke (19% versus 13%; P=0.02) than the lower-extremity DVT patients. By way of propensity analysis and multivariable logistic regression analysis, we determined that an indwelling CVC was the strongest independent predictor of UEDVT (odds ratio [OR], 7.3; 95% confidence interval [CI], 5.8 to 9.2). An age of <67 years, a BMI of <25 kg/m2, and hospitalization were the independent predictors of non-CVC-associated UEDVT. Most (68%) UEDVT patients were evaluated while they were inpatients. Only 20% of the 378 UEDVT patients who did not have an obvious contraindication to anticoagulation received prophylaxis at the time of diagnosis. CONCLUSIONS: UEDVT risk factors differ from the conventional risk factors for lower-extremity DVT. Our findings identify deficiencies in our current understanding and the prophylaxis of UEDVT and generate hypotheses for future research efforts.

Adolescent↗
PubMed2004

Medication errors associated with anticoagulant therapy in the hospital.

Anticoagulation in hospitalized patients is frequently associated with medication errors. To determine the extent and severity of this problem, we reviewed consecutively reported, anticoagulation-related medication errors over a 3-year period. We identified 130 medication errors. There were 1.67 medication errors for every 1,000 patients treated with anticoagulants. These were most often associated with unfractionated heparin (66.2%), followed by warfarin (21.5%), low-molecular-weight heparin (9.2%), argatroban (1.5%), and lepirudin (1.5%). There were no deaths attributed to any anticoagulant medication errors, but 6.2% of patients required medical intervention and 1.5% needed prolonged hospitalization. Medication errors frequently occur with anticoagulant therapy in hospitalized patients.

Anticoagulants↗
PubMed2004

Time trends in warfarin-associated hemorrhage.

The annual incidence of warfarin-related bleeding at Brigham and Women's Hospital increased from 0.97/1,000 patient admissions in the first time period (January 1995 to October 1998) to 1.19/1,000 patient admissions in the second time period (November 1998 to August 2002) of this study. The proportion of patients with major and intracranial bleeding increased from 20.2% and 1.9%, respectively, in the first time period, to 33.3% and 7.8%, respectively, in the second.

Adult↗
PubMed2004

The effect of excessive anticoagulation on mortality and morbidity in hospitalized patients with anticoagulant-related major hemorrhage.

BACKGROUND: We aimed to determine the effect of excessive anticoagulation on morbidity and mortality in hospitalized patients with major anticoagulant-associated hemorrhage. METHODS: We prospectively identified 101 consecutive inpatients admitted to Brigham and Women's Hospital with major bleeding occurring during administration of warfarin sodium, unfractionated heparin (UFH), or low-molecular-weight heparin (LMWH). RESULTS: Fifty patients had excessive and 51 had nonexcessive anticoagulation. The overall mortality at 60 days was 26% (13/50) in the excessive group compared with 10% (5/51) in the nonexcessive group (P =.03). Excessive warfarin therapy was associated with an increased 60-day mortality (P =.049), in contrast to excessive anticoagulation with UFH or LMWH alone (P =.27) or UFH or LMWH as a "bridge" to warfarin therapy (P =.10). Multivariate regression identified excessive anticoagulation as an independent predictor of 60-day mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 1.39-12.49; P =.01), along with intracranial hemorrhage (adjusted HR, 6.16; 95% CI, 1.75-21.67; P =.005) and active cancer (adjusted HR, 3.79; 95% CI, 1.13-12.70; P =.03). Excessive anticoagulation was also a significant predictor of the combined nonfatal end point of stroke, myocardial infarction, hypotension, critical anemia, and surgical or angiographic intervention at 30 days (HR, 2.17; 95% CI, 1.25-3.78; P =.006). CONCLUSION: In a cohort of patients with anticoagulation-associated hemorrhage, excessive anticoagulation contributed independently to increased morbidity and mortality.

Adult↗
PubMed2004

Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism.

BACKGROUND: We investigated the prognostic role of right ventricular enlargement on multidetector-row chest CT in acute pulmonary embolism (PE). METHODS AND RESULTS: We studied 63 patients with CT-confirmed PE who underwent echocardiography within the ensuing 24 hours. Adverse clinical events, defined as 30-day mortality or the need for cardiopulmonary resuscitation, mechanical ventilation, pressors, rescue thrombolysis, or surgical embolectomy, were present in 24 patients. We performed off-line CT measurements of right and left ventricular dimensions (RV(D), LV(D)) with axial and 2-dimensional reconstructed 4-chamber (4-CH) views. The proportion of patients with RV(D)/LV(D)>0.9 on the axial view was similar in patients with (70.8%) and those without adverse events (71.8%; P=0.577). In contrast, RV(D)/LV(D)>0.9 on the 4-CH view was more common in patients with (80.3%) than without (51.3%; P=0.015) adverse events. The area under the curve of RV(D)/LV(D) from the axial and 4-CH views for predicting adverse events was 0.667 and 0.753, respectively. Sensitivity and specificity of RV(D)/LV(D)>0.9 for predicting adverse events were 37.5% and 92.3% on the axial view and 83.3% and 48.7% on the reconstructed 4-CH view, respectively. RV(D)/LV(D)>0.9 on the 4-CH view was an independent predictor for adverse events (OR, 4.02; 95% CI, 1.06 to 15.19; P=0.041) when adjusted for age, obesity, cancer, and recent surgery. CONCLUSIONS: Right ventricular enlargement on the reconstructed CT 4-CH views predicts adverse clinical events in patients with acute PE. Ventricular CT measurements obtained from 4-CH views are superior to those from axial views for identifying high-risk patients.

Acute Disease↗
PubMed2004

Comparison of efficacy, safety, and cost of low-molecular-weight heparin with continuous-infusion unfractionated heparin for initiation of anticoagulation after mechanical prosthetic valve implantation.

We compared the efficacy, safety, and impact on postoperative hospital length of stay and inpatient hospital costs of low-molecular-weight heparin with that of unfractionated heparin as a "bridge" to achieving therapeutic levels of anticoagulation with warfarin in patients with newly implanted prosthetic heart valves. The patients who received low-molecular-weight heparin had a shorter length of stay and decreased postoperative costs compared with the control subjects receiving unfractionated heparin.

Anticoagulants↗
PubMed2004

Giant anastomotic pseudoaneurysm complicating aortic xenograft replacement.

A 74-year-old woman was referred for investigation of a 2-week history of progressive dyspnea. Her medical history included an aortic valve replacement with a stentless bioprosthesis followed 13 months later by the replacement of the aortic root with a porcine xenograft. Transesophageal echocardiography revealed a giant circular pseudoaneurysm of the aortic xenograft with compression of the prosthetic aortic valve and concomitant severe aortic regurgitation. Dehiscence of the proximal graft anastomosis was also diagnosed, and a possible distal anastomotic dehiscence was suspected. The latter turned out intraoperatively to be an almost complete dehiscence of the right coronary artery. The patient died intraoperatively.

Aged↗
PubMed2004

Warfarin dosing and cytochrome P450 2C9 polymorphisms.

Two cytochrome P450 2C9 (CYP2C9) polymorphisms, CYP2C9*2 and *3, metabolize warfarin inefficiently. We assessed the extent to which these polymorphisms explain very low warfarin dose requirements and hemorrhagic complications after excluding non-genetic determinants of warfarin dosing. In this retrospective observational study, 73 patients with stable warfarin doses for > or =1 month and International Normalized Ratios (INR) of 2.0-3.0 were enrolled from our Anticoagulation Clinic. Seventeen patients required < or =2 mg (low-dose), 41 required 4-6 mg (moderate-dose), and 15 required > or =10 mg (high-dose) of daily warfarin. CYP2C9 genotyping was assessed by PCR amplification and restriction enzyme digestion analysis of DNA isolated from circulating leukocytes. The CYP2C9 polymorphisms independently predicted low warfarin requirements after adjusting for Body Mass Index, age, acetaminophen use, and race (OR 24.80; 95% CI 3.83-160.78). At least one polymorphism was present in every patient requiring < or =1.5 mg of daily warfarin, and 88%, 37%, and 7% of the low-, moderate-, and high-dose groups, respectively. All homozygotes and compound-heterozygotes for the variant alleles were in the low-dose group. Rates of excessive (INR>6.0) anticoagulation (and bleeding) were 4.5 (6.0), 7.9 (7.9), and 14.7 (0) per 100 patient-years in the wild-types, heterozygotes, and compound heterozygotes/homozygotes, respectively. In conclusion, CYP2C9*2 or *3 compound heterozygotes and homozygotes have low warfarin requirements even after excluding liver disease, excessive alcohol or acetaminophen consumption, low body weight, advancing age, and drug interactions. These polymorphisms increase the rate of excessive anticoagulation, but this risk does not appear to be associated with higher bleeding rates when anticoagulation status is closely monitored.

Adult↗
PubMed2003

Prognostic role of brain natriuretic peptide in acute pulmonary embolism.

BACKGROUND: Rapid, noninvasive, and accurate prognostic assessment with an inexpensive cardiac biomarker is an appealing approach for patients with acute pulmonary embolism (PE). METHODS AND RESULTS: We measured at the time of admission the plasma level of plasma brain natriuretic peptide (BNP) to determine its utility in prognosticating the clinical course of 73 consecutive patients with acute PE. We used a prespecified BNP cut-off level (<90 pg/mL) for the prediction of the absence of a major adverse cardiovascular event, defined as any of the following: death, cardiopulmonary resuscitation, mechanical ventilation, or use of pressors, thrombolysis, catheter fragmentation, or surgical embolectomy. In the 20 (27%) patients with adverse events, median BNP (194.2, range 3.7 to 1201.1 pg/mL) was higher than in patients with a benign course (39.1, range 1.0 to 1560.0 pg/mL; P<0.001). However, 3 patients with adverse outcomes had low BNP levels on admission: 1 death, BNP 52 pg/mL; 1 patient with prolonged cardiopulmonary resuscitation, BNP 3.7 pg/mL; and 1 patient undergoing rescue thrombolysis, BNP 75 pg/mL. Sensitivity, specificity, and negative and positive predictive value of BNP levels <90 pg/mL for absence of adverse outcomes were 85% (64% to 95%), 75% (62% to 85%), 93% (95% CI 81% to 98%), and 57% (39% to 73%), respectively. The optimal BNP cut-off level, identified by receiver operating characteristic analysis, was <50 pg/mL. CONCLUSIONS: Low BNP levels do not guarantee an uncomplicated hospital course in patients with acute PE, using a "congestive heart failure" cut-off level of 90 pg/mL. A lower cut-off level of <50 pg/mL identifies 95% of patients with a benign clinical course.

Acute Disease↗
PubMed2003

Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism.

BACKGROUND: The role of pro-brain natriuretic peptide (proBNP) for the prediction of clinical outcome has not been examined in patients with acute pulmonary embolism (PE). METHODS AND RESULTS: ProBNP levels were measured in 73 patients with acute PE within 4 hours of admission. Adverse clinical outcome was defined as in-hospital death or the need for at least 1 of the following: cardiopulmonary resuscitation, mechanical ventilation, pressors, thrombolysis, catheter fragmentation, or surgical embolectomy. In the 53 patients with a benign clinical outcome, proBNP (median 121, range 16 to 34 802 pg/mL) was lower than in 20 patients with adverse clinical outcome (median 4250, range 92 to 49 607 pg/mL; P<0.0001). The negative predictive value of proBNP levels <500 pg/mL to predict adverse clinical outcome was 97% (95% confidence interval 84 to 99). ProBNP remained an independent predictor for adverse clinical outcome (odds ratio 14.6; 95% confidence interval 1.5 to 139.0; P=0.02) after adjusting for severity of PE (submassive/massive), troponin T levels >0.01 ng/mL, age >70 years, gender, and history of congestive heart failure. CONCLUSIONS: Low proBNP levels predict an uneventful hospital course in patients with acute PE. A proBNP level <500 pg/mL identifies patients who will be potential candidates for an abbreviated hospital length of stay or care on a completely outpatient basis.

Acute Disease↗
PubMed2003

QR in V1--an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism.

AIMS: To test the hypothesis that Qr in V(1)is a predictor of pulmonary embolism, right ventricular strain, and adverse clinical outcome. METHODS AND RESULTS: ECG's from 151 patients with suspected pulmonary embolism were blindly interpreted by two observers. Echocardiography, troponin I, and pro-brain natriuretic peptide levels were obtained in 75 patients with pulmonary embolism. Qr in V(1)(14 vs 0 in controls; p<0.0001) and ST elevation in V(1)> or =1 mV (15 vs 1 in controls; p=0.0002) were more frequently present in patients with pulmonary embolism. Sensitivity and specificity of Qr in V(1)and T wave inversion in V(2)for predicting right ventricular dysfunction were 31/97% and 45/94%, respectively. Three of five patients who died in-hospital and 11 of 20 patients with a complicated course, presented with Qr in V(1). After adjustment for right ventricular strain including ECG, echocardiography, pro-brain natriuretic peptide and troponin I levels, Qr in V(1)(OR 8.7, 95%CI 1.4-56.7; p=0.02) remained an independent predictor of adverse outcome. CONCLUSIONS: Among the ECG signs seen in patients with acute pulmonary embolism, Qr in V(1)is closely related to the presence of right ventricular dysfunction, and is an independent predictor of adverse clinical outcome.

Arrhythmias, Cardiac↗
PubMed2003

Incremental prognostic value of troponin I and echocardiography in patients with acute pulmonary embolism.

BACKGROUND: To test the hypothesis that troponin I and echocardiography have an incremental prognostic value in patients with pulmonary embolism (PE). METHODS AND RESULTS: In 91 patients with acute PE, echocardiography was performed within 4h of admission. Troponin I levels were obtained on admission and 12h thereafter. The 0.06 microg/l troponin I cut-off level was identified as the most useful, high-sensitivity cut-off level for the prediction of adverse outcome by receiver operating characteristic analysis with a sensitivity and specificity of 86%, respectively. Twenty-eight (31%) patients had elevated troponin I levels (4.9+/-3.8 microg/l). Twenty-one (23%) patients had adverse clinical outcomes including in-hospital death in five, cardiopulmonary resuscitation in four, mechanical ventilation in six, pressors in 14, thrombolysis in 14, catheter fragmentation in three, and surgical embolectomy in three. The area under the receiver operating characteristic curve from multivariate regression models for predicting adverse outcome without troponin I and echocardiography (0.765), with troponin I (0.890) or echocardiography alone (0.858), and the combination of both tests (0.900) was incremental. Three-month survival rate was highest in patients with both a normal troponin I level and a normal echocardiogram (98%). Positive predictive value for adverse clinical outcomes of the combination of echocardiography and troponin I was higher (75% (95%CI 55-88%)) compared with each test alone (echocardiography: 41%, 95% CI 28-56%; troponin I: 64%, 95% CI 46-79%). CONCLUSIONS: While troponin I measurements added most of the prognostic information for identifying high-risk patients, a normal echocardiogram combined with a negative troponin I level was most useful to identify patients at lowest risk for early death.

Acute Disease↗
PubMed2003

Role of blood coagulation factor XIII in patients with acute pulmonary embolism. Correlation of factor XIII antigen levels with pulmonary occlusion rate, fibrinogen, D-dimer, and clot firmness.

In patients with acute pulmonary embolism (PE), pulmonary occlusion rate is directly related to D-dimer and inversely related to fibrinogen levels. The role of coagulation factor XIII (FXIII) levels in acute venous thromboembolism is not known. A total of 120 consecutive patients with suspected PE and VIDAS D-dimer levels >500 micro g/L were investigated by helical computed tomography (CT). Pulmonary occlusion rate was assessed by CT using the modified Miller index. D-dimer, fibrinogen, and FXIII A- and B-subunit antigen levels were taken on admission. Thrombelastography (TEG) was performed in a subset of patients (n = 12). The 71 patients with PE had lower FXIII A-subunit levels than the 49 patients with excluded PE (78.6 +/- 24.5% vs. 91.3+/-28.8%, p=0.01). In both groups, FXIII A-subunit was inversely related to D-dimer levels. FXIII A-subunit correlated with fibrinogen levels in patients with PE but not in patients without PE. FXIII A-subunit decreased with increasing pulmonary occlusion rate. The risk of PE was increased in the presence of A-subunit levels < 60% (OR 7.0 [95% CI 1.4-35.3], p = 0.019). Clot firmness determined by TEG was lower in patients with PE than in patients without PE. In patients with PE, circulating FXIII A-subunit is decreased compared to patients with suspected but excluded PE. The higher the clot burden within the pulmonary arteries the lower the FXIII antigen. In these patients, direct relation of FXIII A-subunit to fibrinogen levels argues for significant consumption of these coagulation factors in PE. This consumption of FXIII can also be detected by a global coagulation test like TEG.

Acute Disease↗
PubMed2002

Validation of six noninvasive Doppler methods for the assessment of left ventricular filling pressure.

OBJECTIVES: The aim of this study was to determine the accuracy of six noninvasive Doppler methods for assessing invasively derived left ventricular diastolic pressure (LVDP). BACKGROUND: To date, no studies have evaluated which of the various available Doppler methods are most reliable in determining LVDP in a consecutive patient population with different cardiac diseases. METHODS: LVDP was estimated by the following Doppler methods (M): (1) M1-the peak mitral regurgitant flow velocity (peak MR), (2) M2-the mitral regurgitant velocity at the time of aortic valve opening (MRAVO), (3) M3-the aortic regurgitant end-diastolic flow velocity (ARED), (4) M4-the ratio of the transmitral to mitral annular early diastolic velocity (ETM/EDTI), (5) M5-a transmitral flow velocity regression equation (RegrTM), and (6) M6-the difference of pulmonary venous and transmitral A wave duration (APV - ATM duration). For M1-M3, sphygmomanometric blood pressure was used to calculate LVDP. RESULTS: In 101 patients, the regression coefficient, standard error of estimate, and mean difference with confidence limits between Doppler and catheter-derived measurements were as follows: M1 (n = 46): r = 0.81 (P < 0.0001), 4.3 mmHg and 3.7 +/- 12.0 mmHg; M2 (n = 47): r = 0.79 (P < 0.0001), 5.4 mmHg and 1.1 +/- 11.2 mmHg; M3 (n = 20): r = 0.64 (P = 0.002), 7.8 mmHg and 4.6 +/- 17.6 mmHg; M4 (n = 50): r = 0.62 (P < 0.0001), 5.6 mmHg and 0 +/- 11.2 mmHg; M5 (n = 79): r = 0.24 (P = 0.03), 7.1 mmHg and - 0.1 +/- 16.8 mmHg; and M6 (n = 79): r = 0.22 (P = 0.05), 7.3 mmHg and 0 +/- 14.4 mmHg, respectively. CONCLUSIONS: The Doppler measurement of mitral regurgitant jets is most accurate method to estimate left ventricular filling pressure noninvasively.

Aged↗
PubMedDate not supplied

Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher.

BACKGROUND: The prognostic role of echocardiographic right ventricular (RV) dysfunction for predicting mortality in patients with acute pulmonary embolism and a preserved systemic arterial pressure remains controversial. METHODS: We evaluated 1035 patients with pulmonary embolism from the International Cooperative Pulmonary Embolism Registry who (1) presented with systolic systemic arterial pressure of 90 mm Hg or higher and (2) who underwent echocardiography within 24 hours of a diagnosis of pulmonary embolism, showing presence (n = 405) or absence (n = 630) of RV hypokinesis. The main outcome measure was the cumulative survival rate through 30 days in patients with and without RV hypokinesis. RESULTS: In patients with RV hypokinesis, the initial systolic systemic pressure was lower (125 +/- 22 mm Hg vs 131 +/- 22 mm Hg; P<.001), and the initial heart rate was higher (104 +/- 21 beats per minute vs 99 +/- 22 beats per minute; P<.001) than in patients without RV hypokinesis. Cancer was less often present (14.1% vs 22.5%, P = .001). The 30-day survival rates in patients with and without RV hypokinesis were 83.7% (95% confidence interval [CI], 79.3%-87.0%) and 90.6% (95% CI, 88.0%-92.6%), respectively (log-rank P value <.001). The univariate hazard ratio of RV hypokinesis for predicting 30-day mortality was 2.11 (95% CI, 1.41-3.16; P<.001). Right ventricular hypokinesis remained an independent predictor of 30-day mortality (hazard ratio, 1.94; 95% CI, 1.23-3.06) after adjusting for univariately significant predictors, including cancer, congestive heart failure, chronic lung disease, age older than 70 years, systolic arterial pressure of 100 mm Hg or lower, administration of thrombolytic therapy, and heart rate greater than 100 beats per minutes. CONCLUSION: Among patients with pulmonary embolism who present with a systolic arterial pressure greater than or equal to 90 mm Hg, echocardiographic RV hypokinesis is an independent predictor of early death.

Acute Disease↗