Grill, Diane E.

Background— Cardiac troponin T (cTnT) and B-type natriuretic peptide (BNP) have been used to estimate prognosis in heart failure; however, most studies have evaluated decompensated patients with single measurements. To determine if there are advantages to serial measurements, we evaluated stable chronic heart failure patients every 3 months for 2 years. Methods and Results— A cohort of 190 New York Heart Association class III–IV heart failure patients was prospectively enrolled from June 2001 to January 2004. Primary end points were death, cardiac transplantation, or hospitalization. At study enrollment cTnT was <0.01 ng/mL in 87 (45.8%) patients, 0.01 to 0.03 ng/mL in 50 (26.3%) patients, and >0.03 ng/mL in 53 (27.9%) patients. An increase in cTnT above normal (<0.01 ng/mL) carried a 3.4-fold increased risk ( P =0.019). Further increases (≥20%) from an elevated level worsened the overall risk (hazard ratio, 5.09; P <0.001). BNP was elevated (>95th percentile for age and gender normal population) in 122 (64.2%) patients. An elevation of BNP from normal at any time during the study was associated with a poor outcome, but, once elevated, further changes in BNP (increases or decreases) remained associated with the same risk (hazard ratio, 5.09; P <0.001). Combined elevations of cTnT (>0.03 ng/mL) and BNP defined the highest risk group (hazard ratio, 8.58; P <0.001). Conclusions— Elevations of cTnT or BNP from normal detected at any time during clinical follow-up in ambulatory patients with chronic heart failure are highly associated with an increased risk of events. Further increases in cTnT contribute to additional risk. Combined elevations of cTnT and BNP contribute the highest risk. The ability to monitor changes by serial measurements adds substantially to the assessment of risk in this patient population.

Background— The impact of aortic prosthesis-patient mismatch (P-PtM) on long-term survival is unclear. Methods and Results— Between 1985 and 2000, 388 patients at Mayo Clinic in Rochester, Minn, underwent aortic valve replacement (AVR) with 19- or 21-mm St Jude Medical prostheses and had transthoracic echocardiography within 1 year after AVR. Mean age of patients was 62±13 years; 69% were female. Prosthesis effective orifice area (EOA) was derived from the continuity equation. P-PtM was classified as severe (indexed EOA ≤0.60 cm 2 /m 2 ), moderate (0.60 cm 2 /m 2 <indexed EOA≤0.85 cm 2 /m 2 ), or not hemodynamically significant (indexed EOA >0.85 cm 2 /m 2 ). P-PtM was severe in 66 patients (17%), moderate in 168 (43%), and not hemodynamically significant in 154 (40%). Patients with severe P-PtM had a significantly larger body surface area ( P <0.0001), higher mean gradient ( P <0.0001), lower preoperative ( P <0.0001) and postoperative ( P <0.0001) ejection fractions, and lower stroke volume ( P <0.0001) and more often received a 19-mm prosthesis ( P =0.0008) than patients with moderate or no hemodynamically significant mismatch. For patients with severe mismatch, 5-year survival rates (72±6%) and 8-year survival rates (41±8%) were significantly less than for patients with moderate mismatch (80±3% and 65±5%; P =0.026) or no hemodynamically significant mismatch (85±3% and 74±5%; P =0.002). On multivariate analysis after adjustment for other predictors of outcome, severe mismatch was associated with higher mortality (hazard ratio 2.18; 95% confidence interval 1.24 to 3.85; P =0.007) and higher incidence of congestive heart failure (hazard ratio 3.1; 95% confidence interval 1.3 to 7.4; P =0.009) than no hemodynamically significant mismatch. Conclusions— Severe P-PtM is an independent predictor of higher long-term mortality and congestive heart failure in patients with small St Jude Medical aortic valve prostheses. For patients undergoing AVR who are at risk of severe mismatch, every effort should be made to use a larger prosthesis or to consider a prosthesis with a larger EOA.

AbstractImmunoglobulin light chain amyloidosis (AL) is characterized by a clonal expansion of plasma cells within the bone marrow. Gene expression analysis was used to identify a unique molecular profile for AL using enriched plasma cells (CD138+) from the bone marrow of 24 patients with AL and 28 patients with multiple myeloma (MM) and 6 healthy controls. Class prediction analysis (PAM) revealed a subset of 12 genes, which included TNFRSF7 (CD27), SDF-1, and PSMA2, that distinguished between these 2 groups with an estimated and observed accuracy of classification of 92%. This model was validated with an independent dataset of 11 patients with AL and 12 patients with MM with 87% accuracy. Differential expression for the most discriminant genes in the 12-gene subset was validated using quantitative real-time polymerase chain reaction and protein expression analysis, which upheld the observations from the micro-array expression data. Functional analyses using a novel network mapping software revealed a number of potentially significant pathways that were dysregulated in patients with AL, with those regulating proliferation, apoptosis, cell signaling, chemotaxis, and migration being substantially represented. This study provides new insight into the molecular profile of clonal plasma cells and its functional relevance in the pathogenesis of light chain amyloidosis.

Abstract Motivation: Our goal was to develop a normalization technique that yields results similar to cyclic loess normalization and with speed comparable to quantile normalization. Results: Fastlo yields normalized values similar to cyclic loess and quantile normalization and is fast; it is at least an order of magnitude faster than cyclic loess and approaches the speed of quantile normalization. Furthermore, fastlo is more versatile than both cyclic loess and quantile normalization because it is model-based. Availability: The Splus/R function for fastlo normalization is available from the authors.

Background — In patients undergoing percutaneous coronary intervention (PCI) in the modern era, the incidence and prognostic implications of acute renal failure (ARF) are unknown. Methods and Results — With a retrospective analysis of the Mayo Clinic PCI registry, we determined the incidence of, risk factors for, and prognostic implications of ARF (defined as an increase in serum creatinine [Cr] >0.5 mg/dL from baseline) after PCI. Of 7586 patients, 254 (3.3%) experienced ARF. Among patients with baseline Cr <2.0, the risk of ARF was higher among diabetic than nondiabetic patients, whereas among those with a baseline Cr >2.0, all had a significant risk of ARF. In multivariate analysis, ARF was associated with baseline serum Cr, acute myocardial infarction, shock, and volume of contrast medium administered. Twenty-two percent of patients with ARF died during the index hospitalization compared with only 1.4% of patients without ARF ( P <0.0001). After adjustment, ARF remained strongly associated with death. Among hospital survivors with ARF, 1- and 5-year estimated mortality rates were 12.1% and 44.6%, respectively, much greater than the 3.7% and 14.5% mortality rates in patients without ARF ( P <0.0001). Conclusions — The overall incidence of ARF after PCI is low. Diabetic patients with baseline Cr values <2.0 mg/dL are at higher risk than nondiabetic patients, whereas all patients with a serum Cr >2.0 are at high risk for ARF. ARF was highly correlated with death during the index hospitalization and after dismissal.