Gail E. Peterson

Analysis of the Impact of Early Surgery on In-Hospital Mortality of Native Valve Endocarditis Use of Propensity Score and Instrumental Variable Methods to Adjust for Treatment-Selection Bias

Background— The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study sought to evaluate valve surgery compared with medical therapy for NVE and to identify characteristics of patients who are most likely to benefit from early surgery. Methods and Results— Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure. Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] versus 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] −5.9%, P<0.001). With a combined instrument, the instrumental-variable–adjusted ARR in mortality associated with early surgery was −11.2% (P<0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR −10.9% for quintiles 4 and 5, P=0.002) and those with paravalvular complications (ARR −17.3%, P<0.001), systemic embolization (ARR −12.9%, P=0.002), S aureus NVE (ARR −20.1%, P<0.001), and stroke (ARR −13%, P=0.02) but not those with valve perforation or congestive heart failure. Conclusions— Early surgery for NVE is associated with an in-hospital mortality benefit compared with medical therapy alone.

Venous thrombosis in patients with short- and long-term central venous catheter-associated Staphylococcus aureus bacteremia*

Objective: Infection and thrombosis are important complications of intravascular catheters. The purpose of this study was to determine the incidence of thrombosis in patients with central venous catheter–associated Staphylococcus aureus bacteremia and the utility of physical examination for diagnosing upper extremity or neck venous thrombosis. Design: Prospective observational cohort. Setting: Tertiary care facility. Patients: In all, 65 consecutive patients with catheter-associated S. aureus bacteremia with central venous catheters of the internal jugular, brachial, or subclavian veins were eligible for participation. Intervention: From July 1999 through August 2004, enrolled patients underwent physical examination and ultrasonography independently to identify the presence of catheter-associated thrombosis. Study ultrasonograms were interpreted blindly using defined criteria. Outcomes were defined at 12-wk follow-up. Measurements and Main Results: A total of 48 patients were enrolled. By ultrasonography, definite or possible thrombosis was present in 34 of 48 patients (71%) in this cohort. Death or recurrent bacteremia occurred in 11/34 (32%) infected patients with thrombosis and two of 14 (14%) infected patients without thrombosis (p = .29). Sensitivity of all physical examination findings, either alone or in combination, was low (≤24%). Only engorged veins upon hand elevation and the presence of multiple physical examination abnormalities were specific (100% each). Conclusions: Thrombosis is a common complication of central venous catheter–associated S. aureus bacteremia. Patients with central venous catheter–associated S. aureus bacteremia should undergo ultrasonography to detect thromboses even if the physical examination is normal.

Transesophageal Echocardiography Clinical Indications and Applications

Case: A 36 year-old woman without significant past medical history was admitted with left-sided hemiparesis. Imaging studies confirmed a right middle cerebral artery (MCA) stroke with normal carotid arteries. Transesophageal echocardiogram (TEE) showed right heart enlargement and a large secundum atrial septal defect (ASD) (Figure 1). Using TEE guidance, an ASD occluder device was placed without complication (Figure 2). Figure 1. This short-axis TEE view taken along the interatrial septum includes the left atrium, interatrial septum, and the right atrium. The color flow Doppler demonstrates left to right flow across an ASD. This figure can be viewed as a moving image online (see Movie I). Figure 2. An interatrial septal closure device is positioned across the ASD using TEE guidance. Both sides of the device are in position. The left atrium is at the top of the screen. No abnormal color flow was seen around the device. This figure may be viewed as a movie clip online (see Movie II). The use and indications for transesophageal echocardiography have expanded since its introduction over a decade ago.1,2 The suggested approach for a TEE examination is given in Table 1. As illustrated in the case above, TEE is used not only as a diagnostic tool but also as a monitoring adjunct for operative and percutaneous cardiac procedures (Table 2). The short distance between the transducer and the heart allows for the use of increased frequency transducers, yielding better spatial resolution and superior performance. Although major complications of TEE are rare (<0.02%), insertion and manipulation of the TEE probe can result in oral, esophageal, or pharyngeal trauma and arrhythmias, along with complications of conscious sedation. Because inaccurate acquisition and interpretation of images can lead to improper clinical decisions, experienced operators are essential to the success of TEE. View this table: TABLE 1. Suggested Approach …

In Vitro Resistance to Thrombin-Induced Platelet Microbicidal Protein in Isolates of Staphylococcus aureus from Endocarditis Patients Correlates with an Intravascular Device Source

Platelet microbicidal proteins (PMPs) are small antimicrobial peptides secreted by mammalian platelets. In vitro resistance of Staphylococcus aureus strains to PMPs correlates with more extensive disease in experimental infective endocarditis (IE). To determine whether this same relationship exists in human S. aureus IE, we evaluated the in vitro PMP susceptibility phenotype of isolates from 58 prospectively-identified patients with definite S. aureus IE. On multivariate analyses, patients with S. aureus IE complicating an infected intravascular device were significantly more likely to have IE caused by a PMP-resistant strain (P=.0193). No correlations were detected between in vitro PMP resistance among S. aureus strains and the severity of human IE. This work supports the concept that in vitro PMP resistance in clinical S. aureus strains is associated with important clinical characteristics of S. aureus endovascular infections in vivo.

Prevalence and Correlates of Left Ventricular Hypertrophy in the African American Study of Kidney Disease Cohort Study

African Americans with hypertensive renal disease represent a high-risk population for cardiovascular events. Although left ventricular hypertrophy is a strong predictor of adverse cardiac outcome, the prevalence and associated factors of left ventricular hypertrophy in this patient population are not well described. The African American Study of Kidney Disease Cohort Study is a prospective, observational study that is an extension of the African American Study of Kidney Disease randomized clinical trial that was conducted from 1994 to 2001 in African Americans with hypertension and mild-to-moderate renal dysfunction. Echocardiograms and 24-hour ambulatory blood pressure monitoring were performed at the baseline visit of the cohort. Of 691 patients enrolled in the cohort study, 599 patients had interpretable baseline echocardiograms and ambulatory blood pressure data. Left ventricular hypertrophy was defined using a cut point for left ventricular mass index >49.2 g/m2.7 in men and >46.7 m/m2.7 in women. The majority of patients had left ventricular hypertrophy (66.7% of men and 73.9% of women). In a multiple regression analysis, higher average day and nighttime systolic blood pressure, younger age, and lower predicted glomerular filtration rate were associated with left ventricular hypertrophy, but albuminuria was not. These data demonstrate a striking prevalence of left ventricular hypertrophy in the African American Study of Kidney Disease Cohort and identify potential targets for prevention and therapeutic intervention in this high-risk patient population.

Propionibacterium endocarditis: A case series from the International Collaboration on Endocarditis Merged Database and Prospective Cohort Study

Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis Merged Database (ICE-MD) and Prospective Cohort Study (ICE-PCS), and compared the results to 28 cases previously reported in the literature. In the ICE database, 11 of 15 patients were male with a mean age of 52 y. Prosthetic valve endocarditis occurred in 13 of 15 cases and 3 patients had a history of congenital heart disease. Clinical findings included valvular vegetations (9 patients), cardiac abscesses (3 patients), congestive heart failure (2 patients), and central nervous system emboli (2 patients). Most patients were treated with β-lactam antibiotics alone or in combination for 4 to 6 weeks. 10 of the 15 patients underwent valve replacement surgery and 2 patients died. Similar findings were noted on review of the literature. The results of this paper suggest that risk factors for Propionibacterium endocarditis include male gender, presence of prosthetic valves and congenital heart disease. The clinical course is characterized by complications such as valvular dehiscence, cardiac abscesses and congestive heart failure. Treatment may require a combination of medical and surgical therapy.

N-Terminal Prohormone Brain Natriuretic Peptide as a Predictor of Cardiovascular Disease and Mortality in Blacks With Hypertensive Kidney Disease: The African American Study of Kidney Disease and Hypertension (AASK)

Background— Higher levels of N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular disease (CVD) in several disease states, but few data are available in patients with chronic kidney disease or in blacks. Methods and Results— The African American Study of Kidney Disease and Hypertension trial enrolled hypertensive blacks with a glomerular filtration rate of 20 to 65 mL · min−1 · 1.73 m−2 and no other identified cause of kidney disease. NT-proBNP was measured with a sandwich chemiluminescence immunoassay (coefficient of variation 2.9%) in 994 African American Study of Kidney Disease and Hypertension participants. NT-proBNP was categorized as undetectable, low, moderate, or high. Proteinuria was defined as 24-hour urinary protein–creatinine ratio >0.22. A total of 134 first CVD events (CVD death or hospitalization for coronary artery disease, heart failure, or stroke) occurred over a median of 4.3 years. Participants with high NT-proBNP were much more likely to have a CVD event than participants with undetectable NT-proBNP after adjustment (relative hazard 4.0 [95% confidence interval [CI] 2.1 to 7.6]). A doubling of NT-proBNP was associated with a relative hazard of 1.3 (95% CI 1.0 to 1.6) for coronary artery disease, 1.7 (95% CI 1.4 to 2.2) for heart failure, 1.1 (95% CI 0.9 to 1.4) for stroke, and 1.8 (95% CI 1.4 to 2.4) for CVD death. The association of NT-proBNP with CVD events was significantly stronger (Pinteraction=0.05) in participants with than in those without proteinuria. Higher NT-proBNP was not associated with renal disease progression. Conclusions— These results suggest that elevated NT-proBNP levels are associated with higher CVD risk among blacks with hypertensive kidney disease. This association may be stronger in individuals with significant proteinuria.

Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults

Referral bias occurs because of the clustering of patients at tertiary care centers. This may result in the distortion of observed clinical manifestations of rare diseases. This analysis evaluates the effect of referral bias on the epidemiology of infective endocarditis (IE) in the International Collaboration on Endocarditis—Prospective Cohort Study (ICE-PCS). This is a prospective multicenter cohort study comparing transferred and non-transferred patients with IE. Factors independently associated with transfer status were evaluated using multivariable logistic regression. A total of 2,760 patients were included in the analysis, of which 1,164 (42.2%) were transferred from other medical centers. Transferred patients more often underwent surgery for IE (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1.9–3.2). They were also more likely to have complications such as stroke (OR = 1.5; 95% CI 1.3–1.9), heart failure (OR = 1.4; 95% CI 1.1–1.6), and new valvular regurgitation (OR = 1.3; 95% CI 1.1–1.6). The in-hospital mortality rates were similar in both groups. Patients with IE who require surgery and suffer complications are referred to tertiary hospitals more frequently than patients with an uncomplicated course. Hospital transfer has no obvious effect on the in-hospital mortality. Referral bias should be taken into consideration when describing the clinical spectrum of IE.

Relation of Level of B-Type Natriuretic Peptide With Outcomes in Patients With Infective Endocarditis

Elevated B-type natriuretic peptide (BNP) is a marker of poor outcomes in heart failure, acute coronary syndromes, and sepsis. Elevated cardiac troponin I (cTnI) is associated with adverse outcomes in infective endocarditis. It was hypothesized that elevated BNP would be associated with increased rates of morbidity and mortality in patients with infective endocarditis, particularly when combined with elevated cTnI. Consecutively enrolled patients in the International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) were evaluated at a single center. The association between elevated BNP and a composite outcome of death, intracardiac abscess, and central nervous system event and the individual components of the composite was determined. Similar analyses were performed in patients who had BNP and cTnI measured. Of 103 patients, 45 had BNP measured for clinical indications. The median BNP level was higher in patients with the composite outcome (1,498 vs 433 pg/ml, p = 0.03) and in those who died (2,150 vs 628 pg/ml, p = 0.04). Elevated BNP was significantly associated with the composite outcome (p <0.01) and intracardiac abscess (p = 0.02). Patients with elevation of BNP and cTnI had a significantly higher probability of the composite outcome (69%) than patients with either BNP or cTnI elevated (29%) or neither BNP nor troponin elevated (0%) (p for trend <0.01). In conclusion, these data demonstrate a significant association between elevated BNP alone and in combination with cTnI for serious outcomes in infective endocarditis and warrant prospective evaluation.

Relationship of Left Ventricular Hypertrophy and Diastolic Function With Cardiovascular and Renal Outcomes in African Americans With Hypertensive Chronic Kidney Disease

African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05–1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.