Faculty Bibliography

In patients with hypertension, heart failure, or coronary artery disease (CAD), obese patients have been shown to have a lower cardiac event rate compared with normal weight counterparts. This phenomenon has been termed the "obesity paradox." We sought to determine whether the obesity paradox exists in a cohort of patients referred for stress echocardiography. We evaluated 4,103 patients with suspected CAD (58 +/- 13 years; 42% men) undergoing stress echocardiography (52% exercise and 47% dobutamine). Patients were divided into 3 groups on the basis of body mass index (BMI): 18.5 to 24.9, 25 to 29.9, and >30 kg/m(2). During the follow-up of 8.2 +/- 3.6 years, there were 683 deaths (17%). Myocardial ischemia was present in 21% of the population. Myocardial ischemia was more prevalent in patients with a BMI of 18.5 to 24.9 kg/m(2) (26%) than those with a BMI of 25 to 29.9 kg/m(2) (21%) and >30 kg/m(2) (18%). Patients with a BMI of >30 kg/m(2) had the lowest death rate (1.2%/year) compared with those with a BMI of 25 to 29.9 kg/m(2) (1.75%/year) and 18.5 to 24.9 kg/m(2) (2.9%/year; p <0.001). After adjusting for significant clinical variables including exercise capacity, patients with higher BMI (>30 kg/m(2) and 25 to 29.9 kg/m(2)) had less risk of mortality compared with those with a BMI of 18.5 to 24.9 kg/m(2) (hazard ratio 0.58, 95% confidence interval 0.47 to 0.72, p <0.0001 and hazard ratio 0.69, 95% confidence interval 0.57 to 0.82, p <0.0001, respectively). In conclusion, higher survival rate in patients with higher BMI as previously described in patients with hypertension, heart failure, and CAD extends to patients with suspected CAD referred for stress echocardiography, independent of exercise capacity.

BACKGROUND: It is becoming increasingly recognized that manifestations of congenital heart disease (CHD) extend beyond the cardiovascular system. The factors contributing to renal dysfunction in patients with CHD are multifactorial, with acute kidney injury (AKI) at time of cardiac surgery playing a major role. AKI is often diagnosed based on changes in serum creatinine and estimated glomerular filtration rate (eGFR). Such measurements are often late and imprecise. Recent data indicate that urinary biomarkers interleukin-18 (IL-18) and neutrophil gelatinase-associated lipocalin (NGAL) are earlier markers of AKI. We sought to determine the efficacy of urinary IL-18 and NGAL for detecting early AKI in patients undergoing surgical pulmonary valve replacement (PVR). METHODS: Twenty patients presenting for surgical PVR with a history of previous repair of a conotruncal anomaly were enrolled. Preoperative clinical data were measured and urine samples and serum creatinine were collected at 6, 12, 24, and 72 hours post bypass. Urine was evaluated for NGAL and IL-18. AKI was determined using the Risk, Injury, Failure, Loss and End Stage Renal Disease (RIFLE) classification system. RESULTS: Using the RIFLE classification system, seven patients (35%) were found to have AKI defined as a drop in the eGFR or an increase in serum creatinine. All seven patients with AKI had marked increase from preoperative baseline in urine IL-18 (sixfold) and NGAL (26-fold). Using NGAL and IL-18, AKI was detected at 6 hours postoperatively, resulting in AKI being identified 12-36 hours prior to detection by conventional methods. No preoperative predictors for AKI were identified. CONCLUSION: Both NGAL and IL-18 are early predictive biomarkers of AKI, and both increase in tandem after surgical PVR. Importantly, both rise before an increase in creatinine or a decrease in eGFR is present. Monitoring both biomarkers may allow for earlier detection and subsequent interventions to prevent AKI at time of surgery for CHD.

OBJECTIVE: Recent data indicate that patients after the Fontan procedure are at risk for significant liver dysfunction; however, the prevalence and extent of liver disease in the Fontan population remains unknown. Furthermore, limited data exist in regard to screening for liver disease in adult Fontan patients. We sought to determine the prevalence of liver disease in adult patients following the Fontan procedure using computed tomography (CT) and serum biomarkers of liver fibrosis. DESIGN: Adult Fontan patients underwent screening for liver disease as part of their annual evaluation. Screening consisted of laboratory evaluation and dual-phase liver CT scan. Laboratory evaluation included analysis of liver function, viral hepatitis serologies, and FibroSURE panel (LabCorp), a test that analyzes the results of serum biomarkers to provide a quantitative surrogate marker for liver fibrosis. RESULTS: Sixteen patients, mean age 30.3 (range 20-41) years, were enrolled in the study. Mean length of follow-up from time of Fontan palliation was 20.5 (range 11-33) years. No patients had serologic evidence of viral hepatitis or synthetic liver dysfunction. Twelve patients (75%) had abnormal FibroSURE scores, seven (44%) had elevated FibroSURE scores predictive of Metavir fibrosis stage F2 or greater on liver biopsy, and one (6%) had a FibroSURE score predictive of cirrhosis on biopsy. All 16 patients had abnormal radiologic liver findings identified on CT, including heterogeneous enhancement in 11 (69%), varices in six (38%), and liver nodules in five patients (31%). Length of time since Fontan surgery correlated significantly with an elevated FibroSURE score (P = .05) and having more CT scan abnormalities (P = .04). CONCLUSIONS: Liver fibrosis detected by serum biomarkers and dual phase CT scan is common in adult patients following the Fontan procedure. Further studies are needed to determine the long-term clinical significance of these findings.

The use of stress echocardiography has undergone considerable evolution in the past 3 decades. Although stress echocardiography was first introduced as a noninvasive diagnostic tool for determining the presence or absence of coronary artery disease (CAD), it later served a prognostic role as well. The importance of stress echocardiography in risk stratification and prognosis is substantially undervalued by clinicians. The identification of patients at risk for future cardiac events has become a primary objective in noninvasive evaluation of patients with suspected or known CAD. In particular, the ability of stress echocardiography to identify patients at low (< 1%), intermediate (1%-5%), or high (> 5%) risk for future cardiac events is essential to decision making in patient management. Moreover, previous studies have conclusively demonstrated the incremental prognostic value of stress echocardiography over clinical and treadmill exercise data in predicting future cardiac events. This article presents a primarily single-center experience of retrospective and observational studies that address the current role of stress echocardiography and summarize its use for risk stratification, prognosis, and determining clinical outcomes, as well as cost-effective integration of such information in patient management decision making

Mass spectrometry is a powerful technique for the identification of proteins at nanogram quantities. However, some degree of sample preparation prior to mass spectrometry is required, and silver-stained protein gel samples are most problematic. Here we report our strategy to obtain peptide mass profiles from silver-stained protein gel samples from one- or two-dimensional gels by destaining prior to enzymatic digestion. This study demonstrates that by using the destaining method, the sensitivity and quality of mass spectra is increased for matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometric analysis, permitting more proteins to be identified by peptide mass database analysis