Albert Chiu

Arterial blood pressure responses to cell-free hemoglobin solutions and the reaction with nitric oxide

Changes in mean arterial pressure were monitored in rats following 50% isovolemic exchange transfusion with solutions of chemically modified hemoglobins. Blood pressure responses fall into three categories: 1) an immediate and sustained increase, 2) an immediate yet transient increase, or 3) no significant change either during or subsequent to exchange transfusion. The reactivities of these hemoglobins with nitric monoxide (⋅NO) were measured to test the hypothesis that different blood pressure responses to these solutions result from differences in ⋅NO scavenging reactions. All hemoglobins studied exhibited a value of 30 μm −1 s−1 for both⋅NO bimolecular association rate constants and the rate constants for ⋅NO-induced oxidation in vitro. Only the ⋅NO dissociation rate constants and, thus, the equilibrium dissociation constants varied. Values of equilibrium dissociation constants ranged from 2 to 14 pm and varied inversely with vasopressor response. Hemoglobin solutions that exhibited either transient or no significant increase in blood pressure showed tighter⋅NO binding affinities than hemoglobin solutions that exhibited sustained increases. These results suggest that blood pressure increases observed upon exchange transfusion with cell-free hemoglobin solutions can not be the result of ⋅NO scavenging reactions at the heme, but rather must be due to alternative physiologic mechanisms.

Serial Sampling of ST2 Predicts 90-Day Mortality Following Destabilized Heart Failure

BACKGROUND To prospectively determine the prognostic utility of serial sampling of the interleukin-1 receptor family member, ST2, for predicting 90-day mortality in patients with heart failure (HF) admitted to a Veteran Affairs Medical Center. METHODS AND RESULTS A total 150 patients hospitalized with acutely destabilized HF were followed at the Veteran Affairs Healthcare System in San Diego, CA. Multiple cardiac-related parameters were measured including ST2, B-type natriuretic peptide (BNP), NT-proBNP, and blood urea nitrogen (BUN). Plasma samples were collected at 6 time points between admission and discharge. Biomarker concentrations were correlated to survival at 90 days. Uni- and multivariate analyses were used to identify prognostic variables. From admission to discharge, percent change in ST2 was strongly predictive of 90-day mortality: those patients whose ST2 values decreased by 15.5% or more during the study period had a 7% chance of death, whereas patients whose ST2 levels failed to decrease by 15.5% in this time interval had a 33% chance of dying. CONCLUSIONS Percent change in ST2 concentrations during acute HF treatment is predictive of 90-day mortality and was independent of BNP or NT-proBNP levels. ST2 may provide clinicians with an additional tool for guiding treatment in patients with acute destabilized HF.

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.

PROSPECTIVE CRYOBALLOON DOSING STUDY BASED ON TIME-TO-ISOLATION

Background: Cryoballoon ablation is an effective treatment for Paroxysmal Atrial Fibrillation (PAF). Optimal dosing of the second-generation cryoballoon (CB2; Arctic Front AdvanceTM, Medtronic Inc) is still unclear. Time-to-effect (TTE) is the physiologic end-point when acute pulmonary vein signals

Prospective search for an optimal BNP level to screen patients with suspected left ventricular dysfunction

Objectives: We hypothesized that a fixed plasma B-naturetic peptide (BNP) level of 20pg/ml BNP and simple clinical parameters would be an effective pre-echocardiographic screening tool for LV dysfunction. Background: The importance of early detection of left ventricular dysfunction cannot be over emphasized, as the lead time gained with good management can improve symptoms, survival and quality of life drastically, while decreasing the burden of disease on society. Even though echocardiography is the gold standard for the evaluation of the suspected Left Ventricular dysfunction (LVD), the cost and availability of this procedure limits its use as a routine screening tool. On the other hand, availability of rapid BNP measurements along with its high negative predictive value in dyspneic patients suggests its possible utility in screening patients prior to echocardiography. Determining an appropriate BNP level below that would preclude the need for echocardiography (high negative predictive value) would be valuable (cost ratio of 1/20 (BNP/echocardiogram). Methods: 202 VA subjects with symptoms suggestive of heart disease (m:f 193:9 and mean age 65(22-100)) were screened before undergoing echocardiography. Patients with known cardiac dysfunction were excluded.Results: BNP levels of 20 pg/ml and below 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 cut point of 20 pg/ml had a better negative predictive value for those with systolic dysfunction (96%), or systolic plus diastolic dysfunction (100%). The negative predictive value for detecting any form of diastolic dysfunction was 73%. The majority of patients with false low BNP levels ( 20 pg/ml with positive echo findings) had mild diastolic dysfunction, with just 3 patients exhibiting systolic dysfunction, all of which were mild. Conclusions: There is no BNP level below which, would preclude echocardiography if suspicion of heart disease is high. In low risk patients or in those with limited access to echo, a BNP level below 20 pg/ml makes significant cardiac function unlikely.