Contemporary Meta-Analysis of Extended Direct-Acting Oral Anticoagulant Thromboprophylaxis to Prevent Venous Thromboembolism.

BACKGROUND: Medically ill patients remain at risk of venous thromboembolism for up to 6 weeks after hospital discharge due to factors such as immobilization and inflammation. METHODS: We conducted a meta-analysis and systematic review of Phase III randomized controlled trials comparing extended use of direct oral anticoagulation (DOAC) post discharge for venous thromboembolism prophylaxis with placebo. RESULTS: The primary efficacy outcome (composite of venous thromboembolism and mortality) occurred in 373/13,099 patients in the DOAC group (2.9%) and 477/13,309 patients in the placebo group (3.6%), with an odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.69-0.91). The secondary efficacy outcome (nonfatal symptomatic venous thromboembolism) occurred in 75/15,573 patients in the DOAC group (0.48%) and 120/15,599 in the placebo group (0.77%) with an OR of 0.62 (95% CI, 0.47-0.83). The primary safety outcome (major bleeding) occurred in 90/15,474 patients in the DOAC group (0.58%) and in 47/15,418 patients in the placebo group (0.3%) with an OR of 1.92 (95% CI, 1.35-2.73). The secondary safety (clinically relevant nonmajor bleeding) outcome occurred in 333/15,474 patients in the DOAC group (2.2%) and 191/15,418 patients in the placebo group (1.2%) with an OR of 1.75 (95% CI, 1.46-2.1). The extended use of venous thromboembolism prophylaxis post discharge results in decreased venous thromboembolism events but increased bleeding risk. Our cost-effective analysis of extended DOAC use vs placebo showed superiority of the DOAC group. CONCLUSION: In conclusion, given the mortality benefit and cost benefit, extended thromboprophylaxis is a beneficial strategy to efficiently reduce the risk of venous thromboembolism.

Meta-Analysis Comparing the Efficacy, Safety, and Cost-Benefit of Direct Acting Oral Anticoagulants Versus Enoxaparin Thromboprophylaxis to Prevent Venous Thromboembolism Among Hospitalized Patients.

Venous thromboembolism (VTE) is a potentially fatal complication of hospitalization. Thromboprophylaxis using subcutaneous low molecular weight heparin (LMWH) can result in local irritation, pain, and ecchymoses, leading to nonadherence. Direct acting oral anticoagulants (DOACs) are an alternative, but their efficacy and safety for short-term inpatient-only use versus LMWH, in medically hospitalized patients, has not been rigorously assessed. We performed a systematic review with meta-analyses and exploratory cost effectiveness analysis of Phase III randomized controlled trials comparing DOACs to LMWH for VTE prophylaxis to determine the risk and benefit of each. The primary efficacy end point (composite of total VTE and any-cause mortality) occurred in 1,321 of 10,978 (11.4%) of patients receiving DOAC prophylaxis and 1,084 of 10,600 (10.2%) with LMWH (odds ratio [OR] 0.84; 95% confidence interval [CI] 0.63 to 1.13). The primary safety end point (composite of major bleeding and clinically relevant bleeding) occurred in 519 of 16,131 (3.2%) of patients receiving DOACs and 381 of 14,616 (2.6%) with LMWH (OR 1.12; 95%CI 0.83 to 1.53). Subgroup analyses for efficacy (n = 9,233) and safety (n = 12,584) was conducted on patients randomized to Apixaban or LMWH. The primary efficacy end point occurred in 294 of 4618 (6.4%) patients on Apixaban and 383 of 4615 (8.3%) on Enoxaparin (OR 0.82; 95% CI 0.55 to 1.24). Major and clinically relevant bleeding occurred in 157 of 6278 (2.50%) and 185 of 6,306 (2.9%), respectively (OR 0.86; 95% CI 0.58 to 1.26). Exploratory cost effectiveness analysis suggested that Apixaban compared with Enoxaparin thromboprophylaxis could result in long-term cost savings. In conclusion, this systematic review of randomized controlled trials and meta-analysis, stratified by type of patients and drug, indicates noninferiority of DOACs in efficacy, safety, and cost for short-term VTE thromboprophylaxis among patients hospitalized for medical illness.

Pertinence of myocardial perfusion imaging in octogenarians.

AIM: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the elderly population. Atypical presentation, reduced activity levels, and comorbidity often confound the diagnosis. We studied the use of stress myocardial perfusion imaging (MPI) in octogenarians. METHODS: We retrospectively reviewed the medical records of all patients with both MPI and coronary angiogram within 6 months from 1998 to 2008. Sixty veterans under the age of 60 years who underwent both cardiac procedures served as controls. RESULTS: We evaluated 53 patients, predominantly men, with mean age of 85 +/- 2.5 yrs. Chest pain (68%) was the most common reason for requesting the stress test. Risk factors included diabetes 44%, hypertension 93%, smoking 48%, hyperlipidemia 93%, and peripheral vascular disease 40%. All patients had an abnormal myocardial perfusion scan. Reversible defects were present in 91% with the following distribution: mild 26%, moderate 39%, severe 15% and multiple defects 11%. Fixed defects were present in 44% of the patients. Analysis of both studies in the 53 patients revealed complete (43), partial (7) and no correlation (3) between the MPI defects and culprit lesions identified on the coronary angiogram. Positive predictive value and accuracy of the myocardial perfusion scan in detection of the disease was 98%. Follow up ranged from 1 to 10 years during which 19 patients died, and 7 deaths were cardiac. CONCLUSION: Myocardial perfusion imaging in octogenarians is as accurate in diagnosing CAD as it is in younger people.

B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events.

BACKGROUND: Detection of heart failure (HF) in stable outpatients can be difficult until an overt event occurs. This study sought to determine whether the combination of B-type natriuretic peptide (BNP) and impedance cardiography (ICG) could be used in a nonacute clinical setting to risk stratify and predict HF-related events in stable outpatients. METHODS AND RESULTS: Patients undergoing routine outpatient echocardiography underwent ICG and BNP testing and were followed for one year for HF-related events (Emergency Department [ED] visit or hospitalization due to HF or all-cause death). A total of 524 patients were analyzed, resulting in 57 HF-related events; 16 ED visits, 17 hospitalizations, and 24 all-cause deaths. Using Cox regression analyses, BNP and systolic time ratio index (STRI) by ICG proved to be the strongest predictors of future HF-related events. Patients with a BNP >100 pg/ml and STRI >0.45 sec(-1) had a significantly lower event-free survival rate than those with a high BNP and low STRI (67% versus 89%, P=.001). In patients with LV dysfunction only, if both BNP and STRI values were high, the relative risk of a HF-related event increased by 12.5 (95 % C.I. 4.2-36.7), when compared with patients with a low BNP and low STRI (P<.001). CONCLUSIONS: In a nonacute clinical setting, both BNP and ICG testing can provide unique predictive power of long-term HF-related events in a stable cohort of patients with and without LV dysfunction.

Unexplained hypotension: the spectrum of dynamic left ventricular outflow tract obstruction in critical care settings.

OBJECTIVE: To illustrate the clinical and hemodynamic abnormalities caused by dynamic left ventricular outflow tract obstruction (LVOTO) in critical care setting. DESIGN: We reviewed cases referred to Cardiology with echocardiographic evidence of LVOTO and their clinical presentations. We present those cases where LVOTO can transiently occur without hypertrophic cardiomyopathy when inotropic agents are used for hypotension. MEASUREMENTS AND MAIN RESULTS: Five women in the 50-70 age range and prior history of hypertension presented with various symptoms like chest discomfort, fatigue, dizziness, atrial fibrillation, and hypotension. An ejection systolic murmur was noted most often in the left third intercostal space and ECG revealed ST-T wave abnormalities. LVOTO caused by mitral systolic anterior motion was detected by echocardiography and catheterization excluded acute coronary disease. In critical care setting, LVOTO can occur due to apical ballooning syndrome, coronary disease, medications, volume depletion, and valvular abnormalities. Because this condition mimics acute coronary syndrome or other etiologies of hypotension in medical and surgical intensive care units, appropriate treatment can be delayed. Nonhypertrophic cardiomyopathy LVOTO usually responds well to fluid replacement, beta blockers, and medication changes. CONCLUSIONS: LVOTO should be suspected especially in women presenting with hypotension and systolic murmur in critical care settings. Clinical acumen and timely echocardiography are required to effectively counter this transient but potentially lethal problem.

The use of B-type natriuretic peptide to assess volume status in patients with end-stage renal disease.

BACKGROUND: Although B-type natriuretic peptide (BNP) levels correlate with volume overload in congestive heart failure, its usefulness in patients with renal dysfunction has been questioned. A simple test to estimate volume overload and assist in the management of dry weight in hemodialysis (HD) patients would be useful. METHODS: Thirty-nine patients--aged 64 +/- 2 years (mean +/- SEM), male-female ratio of 37:2--undergoing HD thrice weekly for at least 30 days were studied. Samples were collected at the start and end of each of 3 consecutive HD sessions. Pre- and postsession weights and blood pressures were recorded. Left ventricular ejection fractions were obtained from echocardiograms performed within 1 year of enrollment. The first session was the dialysis session after a 72-hour interdialytic period, whereas the second and third sessions were after a 48-hour period. Plasma volume changes were measured in a subset of 13 patients. RESULTS: Pre- and postdialysis BNP levels for each of the 3 sessions were 434 and 343 pg/mL, 347 and 231 pg/mL, and 249 and 202 pg/mL, respectively. The values for body weights were 82.6 +/- 3.6 and 78.6 +/- 3.5 kg, 81.5 +/- 3.6 and 78.2 +/- 3.5 kg, and 81.5 +/- 3.46 and 78.3 +/- 3.5 kg, respectively. The values of mean systolic blood pressures were 150 +/- 4 and 134 +/- 3 mm Hg, 142 +/- 4 and 134 +/- 4 mm Hg, and 142 +/- 4 and 131 +/- 4 mm Hg, respectively. The values for mean diastolic blood pressures were 81 +/- 2.5 and 70 +/- 2.4 mm Hg, 74 +/- 2.4 and 72.1 +/- 2.2 mm Hg, and 76 +/- 2.9 and 72 +/- 2.9 mm Hg, respectively. There was no correlation between changes in intradialytic BNP values and other measured parameters. Plasma volume changed minimally during dialysis. CONCLUSIONS: Values of BNP are elevated in patients with end-stage renal disease and decline after each dialysis session. Over the course of a week, BNP levels gradually declined irrespective of changes in weight or blood pressure. The lack of correlation between changes in BNP and changes in measured clinical parameters is partly explained by a lack of a significant change in plasma volume. The highest BNP values were seen in patients with systolic dysfunction.

B-type natriuretic peptide (BNP) levels and ethnic disparities in perceived severity of heart failure: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study of BNP levels and emergency department decision making in patients presenting with shortness of breath.

BACKGROUND: Previous studies have shown that in patients presenting to the emergency department (ED) with heart failure, there is a disconnect between the perceived severity of congestive heart failure (CHF) by physicians and the severity as determined by B-type natriuretic peptide (BNP) levels. Whether ethnicity plays a role in this discrepancy is unknown. METHODS AND RESULTS: The Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) was a 10-center trial of 464 patients seen in the ED with acute dyspnea and BNP level higher than 100 pg/mL on arrival. Physicians were blinded to BNP levels. Patients were followed for 90 days after discharge. A total of 151 patients identified themselves as white (32.5%) and 294 as black (63.4%). Of these, 90% were hospitalized. African Americans were more likely to be perceived as New York Heart Association class I or II than whites (P = .01). Blacks who were discharged from the ED had higher median BNP levels than whites who were discharged (1293 vs. 533, P = .004). The median BNP of blacks who were discharged was actually higher than the median BNP of blacks who were admitted (1293 vs. 769, P = .04); the same did not hold true for whites. BNP was predictive of 90-day outcome in both blacks and whites; however, perceived severity of CHF, race, and ED disposition did not contribute to the prediction of events. CONCLUSION: In patients presenting to the ED with heart failure, the disconnect between perceived severity of CHF and severity as determined by BNP levels is most pronounced in African Americans.

Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study.

OBJECTIVES: The study purpose was to examine "gray zone" B-type natriuretic peptide (BNP) levels (100-500 pg/mL) in terms of associated clinical factors, perceived severity, and outcomes in patients with established congestive heart failure (CHF). BACKGROUND: Although gray zone BNP levels may have diagnostic ambiguity, the implications of these levels in patients with an established diagnosis of CHF have not been examined. METHODS: REDHOT was a national prospective study in which 464 patients seen in the emergency department with dyspnea had BNP levels drawn. Entrance criteria included a BNP > 100 pg/mL; however, physicians were blinded to the actual BNP level. Patients were followed up for 90 days. RESULTS: Thirty-three percent had gray zone BNP levels. There was no difference in perceived New York Heart Association class (P = .32) or admission rates (P = .76) between the gray zone and non-gray zone groups; 62% of patients with a gray zone BNP were identified as class III or IV CHF. Despite this perceived severity, the 90-day event rate was lower in the gray zone group (19.2% vs 32.9%, respectively, P = .002). Although patients in the gray zone had more symptoms of concomitant pulmonary disease, multivariate analysis could not demonstrate any variable that worsened the prognosis of patients with a gray zone BNP level. CONCLUSIONS: In patients with established CHF, those with gray zone BNP levels have a better prognosis than those with non-gray zone levels despite being perceived by physicians as having New York Heart Association class III or IV CHF.

Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients.

BACKGROUND: Patients with hypertension are at high risk for the development of left ventricular dysfunction (LVD). Echocardiography is considered to be the gold standard for diagnosis of LVD; but its cost, complexity, and availability prevents its use for frequent evaluation. Brain natriuretic peptide (BNP) and N-terminal BNP (NT-BNP) can identify heart failure in dyspneic patients. Impedance cardiography (ICG) is a noninvasive method of measuring hemodynamic and electromechanical timing parameters. The objective of this study was to determine the ability of BNP, NT-BNP, and ICG to detect the presence of LVD in patients with hypertension. METHODS: A convenience sample of subjects undergoing echocardiography who had a history of hypertension or current systolic blood pressure >/=140 mm Hg were enrolled and retrospectively evaluated. Patients with known LVD were excluded. Diagnosis of LVD was determined by the presence of systolic or diastolic dysfunction, valvular or wall motion abnormalities, or left ventricular hypertrophy. RESULTS: A total of 193 subjects were enrolled: 189 men and four women, age 68.8 +/- 11.7 years. Multivariate regression analysis of history and symptoms, BNP, and ICG parameters identified significant predictor variables for LVD including cardiac index (P = .005), left cardiac work index (P = .008), BNP (P = .017), arrhythmia (P = .023), angina (P = .034), and systemic vascular resistance (P = .048). Receiver operating characteristic (ROC) analysis determined the area under the ROC curve (AUC) of BNP (0.60), NT-BNP (0.67), ICG velocity index (0.66), composite ICG (0.66), ICG combined with BNP (0.70), and ICG combined with NT-BNP (0.73). CONCLUSIONS: In this high-risk hypertensive population, BNP, NT-BNP, and ICG were useful to identify the presence of LVD. The use of ICG with natriuretic peptide testing may improve the ability to detect LVD.

Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath.

OBJECTIVES: The purpose of this study was to examine the relationships among B-type natriuretic peptide (BNP) levels within the diagnostic range, perceived congestive heart failure (CHF) severity, clinical decision making, and outcomes of the CHF patients presenting to emergency department (ED). BACKGROUND: Since BNP correlates with the presence of CHF, disease severity, and prognosis, we hypothesized that BNP levels in the diagnostic range offer value independent of physician decision making with regard to critical outcomes in emergency medicine. METHODS: The Rapid Emergency Department Heart failure Outpatient Trial (REDHOT) study was a 10-center trial in which patients seen in the ED with shortness of breath were consented to have BNP levels drawn on arrival. Entrance criteria included a BNP level >100 pg/ml. Physicians were blinded to the actual BNP level and subsequent BNP measurements. Patients were followed up for 90 days after discharge. RESULTS: Of the 464 patients, 90% were hospitalized. Two-thirds of patients were perceived to be New York Heart Association (NYHA) functional class III or IV. The BNP levels did not differ significantly between patients who were discharged home from the ED and those admitted (976 vs. 766, p = 0.6). Using logistic regression analysis, an ED doctor's intention to admit or discharge a patient had no influence on 90-day outcomes, while the BNP level was a strong predictor of 90-day outcome. Of admitted patients, 11% had BNP levels <200 pg/ml (66% of which were perceived NYHA functional class III or IV). The 90-day combined event rate (CHF visits or admissions and mortality) in the group of patients admitted with BNP <200 pg/ml and >200 pg/ml was 9% and 29%, respectively (p = 0.006). CONCLUSIONS: In patients presenting to the ED with heart failure, there is a disconnect between the perceived severity of CHF by ED physicians and severity as determined by BNP levels. The BNP levels can predict future outcomes and thus may aid physicians in making triage decisions about whether to admit or discharge patients. Emerging clinical data will help further refine biomarker-guided outpatient therapeutic and monitoring strategies involving BNP.

Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus.

OBJECTIVES: We hypothesized that B-type natriuretic peptide (BNP) levels can predict cardiac mortality in diabetic patients. BACKGROUND: Detection of cardiovascular disease in diabetics can be difficult until overt events occur. METHODS: A total of 482 diabetics (majority male with type 2 diabetes) at the Veterans Affairs Medical Center San Diego were divided into two groups: 1) referred patients for echocardiogram on the basis of clinical suspicion of cardiac dysfunction (referred [R], n = 180); 2) patients randomly selected from the diabetic clinic without any suspicion of cardiac dysfunction (not referred [N-R], n = 302). We examined cardiac events and all-cause mortality in relation to initial BNP levels during the follow-up. RESULTS: A total of 71 (14.7%) patients died during this period: 52 of 180 (29%) in the R group (30 of 52 [58%] cardiac, 10 of 52 [19%] non-cardiac, 2 of 52 [4%] renal, 10 of 52 [19%] unknown cause) and 19 of 302 (6%) in N-R group (6 of 19 [32%] cardiac). The median BNP level in the R and N-R groups who died of cardiac, non-cardiac, and unknown cause was 537 and 87, 80 and 53, and 343 and 38 pg/ml, respectively. The receiver-operating characteristic (ROC) values for mortality in two groups in relation to BNP revealed the area under the curve to be 0.720 and 0.691, respectively (p < 0.01 in both). Among commonly used prognostic indicators in diabetics, only the ROC for triglycerides was significant. The most accurate cut-point in both the N-R group (87%) and R group (61%) was 120 pg/ml of BNP. Cox regression analysis showed BNP to be the most significant predictor of all-cause mortality in the R group. There was a marked decrease in survival in the patient group with BNP >120 pg/ml. CONCLUSIONS: B-type natriuretic peptide appears to be a reliable predictor of future cardiac and all-cause mortality in diabetic patients.

A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction.

BACKGROUND: Although echocardiography is the gold standard test for suspected left ventricular dysfunction, its cost and availability limits its use as a routine screening tool. The high negative predictive value of B-natriuretic peptide (BNP) in dyspneic patients suggests its possible utility in screening patients prior to echocardiography. Determining an appropriate BNP level below which the need for echocardiography is precluded would be valuable. We hypothesized that a fixed plasma BNP level of 20 pg/mL and simple clinical parameters are an effective pre-echocardiographic screening tool for left ventricular dysfunction. METHODS: Two hundred and two patients at a Veterans Administration facility with symptoms suggestive of heart disease (male to female ratio 193:9, mean age 65 years) were screened prior to echocardiography. Patients with known cardiac dysfunction were excluded. RESULTS: BNP levels of > or =20 pg/mL were 79% sensitive and 44% specific in screening for any abnormality of ventricular function. The negative predictive value was 69%. When broken down into categories of dysfunction, the cutoff point of 20 pg/mL had a better negative predictive value for those with systolic dysfunction (96%) or systolic plus diastolic dysfunction (100%) if patients with diastolic dysfunction were excluded. The majority of patients with falsely low BNP levels (<20 pg/mL with positive echocardiographic findings) had mild diastolic dysfunction, with 3 patients exhibiting mild systolic dysfunction. CONCLUSIONS: BNP may be a useful screening tool for left ventricular dysfunction in patients with history suggestive of heart disease and be used to assist in forming a pretest probability, which in turn could greatly assist in appropriateness of patient referral and in optimization of drug therapy.

Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery.

OBJECTIVES: The purpose of the present study was to assess whether preoperative and postoperative B-type natriuretic peptide (BNP) levels could be used as predictors of postoperative complications and outcomes in patients after open-heart surgery. BACKGROUND: A variety of multifactor indexes have been proposed for preoperative risk assessment of patients undergoing cardiac surgery, but they have shown limited ability and utility in accurately predicting postoperative complications, hospital stay, and mortality. METHODS: Subjects consisted of 98 male patients (63 +/- 9.1 years) undergoing open-heart surgery at the San Diego Veterans Administration Health System during a 19-month period. B-type natriuretic peptide levels were analyzed, and postoperative data recorded. RESULTS: There was a higher preoperative BNP level in patients requiring the use of intra-aortic balloon pumps (IABPs) (mean BNP = 387 +/- 112 pg/ml vs. 181 +/- 25 pg/ml), in patients who died within one year (357 +/- 93 pg/ml vs. 184 +/- 26 pg/ml), and in patients with postoperative hospital stays of 10 days or more (307 +/- 68 pg/ml vs. 179 +/- 27 pg/ml). Receiver operating characteristic curves demonstrated preoperative BNP levels as predictors of postoperative IABP use, hospital stay 385 pg/ml predict the postoperative complications and one-year mortality after heart surgery. Postoperatively, elevated peak BNP levels and elevated change to peak BNP levels were associated with prolonged hospital stay and mortality within one year.

Portable chest radiographs in the intensive care units: referral patterns and estimated cumulative radiation exposures.

The objective of this article was to determine the frequency of referrals for portable chest radiographs from medical and (noncardiac) surgical intensive care units (NICU and SICU) and their respective stepdown units (NICA and SICA). Additionally, the cumulative entrance skin exposure (ESE) using an ion chamber was determined. We retrospectively reviewed the medical records of all adult patients admitted to the MICU, SICU, MICA, and SICA at a tertiary referral center during a 6-month interval. The duration of stay and the number of portable chest radiographs were determined for each patient. The measured ESEs from all portable radiography units ranged from 5 to15 mR (average: 10mR). The cumulative radiation exposure for each patient was calculated. There were 567 patients admitted to the units: 146 surgical and 421 medical. Their ages ranged from 15 to 87 years. The duration of stay varied from 1 to 68 days. A total of 3,794 portable chest radiographs were obtained. The number of radiographs per patient varied from 1 to 94. The number of radiographs and the corresponding cumulative radiation doses were as follows: 406 patients (72%) had fewer than five radiographs (<50 mR); 76 (13%) had five to 10 radiographs (<100 mR); 35 (6%) had 11 to 20 (<200 mR); and 50 (9%) had more than 20 chest radiographs (>200 mR). The cumulative ESE ranged from 10 to 940 mR. It exceeded 450 mR in only nine (1.5%) patients. Most (73%) patients undergoing intensive care undergo fewer than five radiographs during their stay in the units. Patient exposure from portable chest radiographs in this population is less than the average annual exposure from background radiation in the USA (450-500 mR), and is much less than the average annual exposure from teratogenic radiation.