Bioactive adrenomedullin for assessment of venous congestion in heart failure.

AIMS: Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive haemodynamic and population-based studies. METHODS AND RESULTS: Normal reference ranges for bio-ADM were derived from a community-based cohort (n = 5060). Correlations with haemodynamic data were explored in a cohort of HF patients undergoing right heart catheterization (n = 346). Mortality and decision cutoffs for bio-ADM was explored in a cohort of patients presenting in the ER with acute dyspnoea (n = 1534), including patients with decompensated HF (n = 570). The normal reference range was 8-39 pg/mL. The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mean right atrial pressure (mRAP) and pulmonary arterial wedge pressure (PAWP) was 0.74 (95% CI = 0.67-0.79) and 0.70 (95% CI = 0.64-0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95% CI = 0.68-0.79] and 0.68 [95% CI = 0.61-0.75]). Bio-ADM correlated with (mRAP, r = 0.55) while NT-proBNP correlated with PAWP. Finally, a bio-ADM decision cutoff of 39 pg/mL associated with 30 and 90 day mortality and conferred a two-fold increased odds of HF diagnosis, independently from NT-proBNP. CONCLUSIONS: Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.

Preoperative Assessment of Endothelial Function for Prediction of Adverse Events After Cardiovascular Surgery.

BACKGROUND: Cardiovascular surgery is one of the highest risk procedures in the field of surgery. Preoperative assessment of endothelial function has been reported as useful for predicting postoperative adverse events (AEs). The aim of this study was to investigate the relationship between endothelial function assessed by reactive hyperemia index (RHI) and AEs after cardiovascular surgery.Methods and Results:A prospective observational study of 197 patients who underwent cardiovascular surgery was conducted. RHI was measured before the surgery. The primary endpoint was a composite of postoperative death, reoperation, stroke, newly required dialysis, deep sternum infection, and prolonged ventilation within 30 days. The secondary endpoint was new-onset atrial fibrillation (AF) within 30 days. Following cardiovascular surgery, 19 patients (9.6%) had AEs. New-onset AF was documented in 42 (25.9%) of 162 patients without a prior history of AF. In the receiver-operating characteristic curve analysis, RHI significantly predicted AEs (area under the curve [AUC] 0.67, best cutoff value 1.64, P=0.03), whereas RHI did not predict new-onset AF (AUC 0.53, P=0.93). Patients with RHI ≤1.64 had more AEs than those with RHI >1.64 (16.3% vs. 4.5%, P=0.005). Multiple logistic regression analysis showed the number of surgical procedures and RHI ≤1.64 as significant predictors of AEs. CONCLUSIONS: Preoperative endothelial dysfunction assessed by RHI was associated with postoperative AEs in patients with cardiovascular surgery.

A novel technique for the assessment of preoperative cardiovascular risk: reactive hyperemic response to short-term exercise.

BACKGROUND: Perioperative vascular function has been widely studied using noninvasive techniques that measure reactive hyperemia as a surrogate marker of vascular function. However, studies are limited to a static setting with patients tested at rest. We hypothesized that exercise would increase reactive hyperemia as measured by digital thermal monitoring (DTM) in association to patients' cardiometabolic risk. METHODS: Thirty patients (58 ± 9 years) scheduled for noncardiac surgery were studied prospectively. Preoperatively, temperature rebound (TR) following upper arm cuff occlusion was measured before and 10 minutes after exercise. Data are presented as means ± SD. Statistical analysis utilized ANOVA and Fisher's exact test, with P values <0.05 regarded as significant. RESULTS: Following exercise, TR-derived parameters increased significantly (absolute: 0.53 ± 0.95 versus 0.04 ± 0.42°C, P=0.04, and % change: 1.78 ± 3.29 versus 0.14 ± 1.27 %, P=0.03). All patients with preoperative cardiac risk factors had a change in TR (after/before exercise, ΔTR) with values falling in the lower two tertiles of the study population (ΔTR <1.1%). CONCLUSION: Exercise increased the reactive hyperemic response to ischemia. This dynamic response was blunted in patients with cardiac risk factors. The usability of this short-term effect for the preoperative assessment of endothelial function warrants further study.

Assessment of the long-term reproducibility of baseline and dobutamine-induced myocardial blood flow in patients with stable coronary artery disease.

UNLABELLED: Although physical exercise is the preferred stimulus for cardiac stress testing, pharmacologic agents are useful in patients who are unable to exercise. Previous studies have demonstrated short-term repeatability of exercise and adenosine stress, but little data exist regarding dobutamine (Dob) stress or the long-term reproducibility of pharmacologic stressors in coronary artery disease (CAD) patients. PET allows accurate, noninvasive quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The aim of the study was to investigate the long-term reproducibility of Dob stress on MBF and CFR in CAD patients using PET. METHODS: Fifteen patients with chronic stable angina and angiographically proven CAD (>70% stenosis in at least 1 major coronary artery) underwent PET with (15)O-labeled water and Dob stress at baseline (time [t] = 0) and after 24 wk (t = 24). MBF at rest and MBF during Dob stress were calculated for the whole left ventricle, the region subtended by the most severe coronary artery stenosis (Isc), and remote myocardium subtended by arteries with minimal or no disease (Rem). Reproducibility was assessed using the Bland-Altman (BA) repeatability coefficient and was also expressed as a percentage of the mean value of the 2 measurements (%BA). RESULTS: Dob dose (30 +/- 11 vs. 031 +/- 11 microg/kg/min; P = not significant [ns]) and peak Dob rate.pressure product (20,738 +/- 3,947 vs. 20,047 +/- 3,455 mm Hg x beats/min; P = ns) were comparable at t = 0 and t = 24. There was no significant difference in resting or Dob MBF (mL/min/g) between t = 0 and t = 24 for the whole left ventricle (1.03 +/- 0.19 vs. 1.10 +/- 0.20 and 2.02 +/- 0.44 vs. 2.09 +/- 0.57; P = ns for both), Isc (1.05 +/- 0.24 vs. 1.10 +/- 0.26 and 1.79 +/- 0.53 vs. 1.84 +/- 0.62; P = ns for both), or Rem (1.03 +/- 0.23 vs. 1.10 +/- 0.26 and 2.27 +/- 0.63 vs. 2.26 +/- 0.63; P = ns for both) territories. Global (1.98 +/- 0.40 vs. 1.90 +/- 0.46; P = ns) and regional CFR (Isc: 1.65 +/- 0.40 vs. 1.67 +/- 0.47, and Rem: 2.25 +/- 0.57 vs. 2.06 +/- 0.51; P = ns) were reproducible. The BA repeatability coefficients (and %BA) for MBF in ischemic and remote territories were 0.3 (28%) and 0.26 (24%) at rest and 0.49 (27%) and 0.58 (26%) during Dob stress. CONCLUSION: In patients with clinically stable CAD, Dob induces reproducible changes in both global and regional MBF and CFR over a time interval of 24 wk. The reproducibility of MBF and CFR with Dob was comparable with the short-term repeatability reported for adenosine and physical exercise in healthy subjects.

Echocardiographic assessment of LV mass in rabbits: models of pressure and volume overload hypertrophy.

We describe a method for the noninvasive measurement of left ventricular mass in small animals using two-dimensionally guided M-mode echocardiography. We compared echocardiographic cross-sectional area (CSA) and cubed-based volumetric indexes of left ventricular (LV) mass with postmortem wet weight in renovascular hypertension-induced pressure overload (group I) and acute aortic insufficiency-induced volume overload (group II) models of ventricular hypertrophy. CSA and cubed echocardiographic indexes correlated well with wet weight from a combination of group I and II animals and their controls (r = 0.89, P < 0.001 for both groups). Separate analyses of groups I and II also demonstrated significant relationships between mass indexes and wet weight using CSA and cubed formulas, respectively, in both pressure (r = 0.57, P = 0.01 and r = 0.71, P < 0.001) and volume (r = 0.90 and r = 0.89, P < 0.001) overload models. Echocardiographically predicted LV mass derived from cubed and CSA regression formulas was 89 and 56% sensitive for pressure overload hypertrophy in group I and 100% sensitive (both cubed and CSA methods) for volume overload hypertrophy in group II. Cubed and CSA mass regression formulas were 60 and 80% specific for hypertrophy in group I and 100 and 90% specific in group II. Normalization of predicted LV mass for body weight added little to the overall technique accuracy with measured sensitivities of 83 and 75% and specificities of 92 and 77%, respectively, for cubed and CSA methods. Two-dimensionally guided M-mode echocardiography provides a reasonably accurate method of LV mass determination in rabbits with pressure- or volume-overloaded ventricles.