Flow-Mediated Vasodilation Predicts Outcome in Patients With Chronic Heart Failure Comparison With B-Type Natriuretic Peptide

ObjectivesThe aim of this study was to assess the predictive potency of impaired endothelium-dependent flow-mediated vasodilation (FMD) in patients with chronic heart failure (CHF).BackgroundChronic heart failure is associated with reduced FMD; the prognostic impact of this observation is unknown.MethodsSeventy-five ambulatory CHF patients (United Network of Organ Sharing [UNOS] status 2) with a left ventricular ejection fraction (LVEF) ≤30%, despite optimized medical therapy (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, 100%; beta-blocker, 81%), were evaluated. Using high-resolution ultrasound, FMD of the brachial artery was assessed in addition to other neurohormonal, clinical, and hemodynamic variables. Age, gender, New York Heart Association (NYHA) functional class, LVEF, hemodynamic variables, B-type natriuretic peptide (BNP) levels, medical therapy, cardiovascular risk factors, and FMD were analyzed for prediction of the combined end point conversion to UNOS status 1 or death in a multivariate Cox model.ResultsUp to three years, 21 patients (28%) converted to UNOS status 1, and 6 patients (8%) died. Univariate risk factors for the combined end point were log BNP (p = 0.0032), FMD (p = 0.0033), NYHA functional class (p = 0.0132), beta-blocker therapy (p = 0.0367), and mean blood pressure (p = 0.0406). In the multivariate analysis, only FMD (p = 0.0007), log BNP (p = 0.0032), and mean blood pressure (p = 0.0475) were independently related to the combined end point. In the Kaplan-Meier plot, significantly more patients with FMD <6.8% (median) reached the combined end point, as compared with patients with FMD >6.8% (p = 0.004).ConclusionsIn CHF, impaired FMD is a strong, independent predictor of conversion to UNOS status 1 or death

Noninvasive tests of vascular function and structure: Why and how to perform them

Background Early atherosclerosis involves the endothelium of many arteries. Information about peripheral arterial anatomy and function derived from vascular imaging studies such as brachial artery reactivity (BAR) and carotid intima media thickness (IMT) may be pertinent to the coronary circulation. The prevention and early treatment of atherosclerosis is gaining more attention, and these tests might be used as indications or perhaps guides to the effectiveness of therapy, but their application in clinical practice has been limited. This review seeks to define the anatomy and pathophysiology underlying these investigations, their methodology, the significance of their Findings, and the issues that must be resolved before their application. Methods The literature on BAR and IMT is extensively reviewed, especially in relation to clinical use. Results Abnormal flow-mediated dilation is present in atherosclerotic vessels, is associated with cardiovascular risk factors, and may be a marker of preclinical disease. Treatment of known atherosclerotic risk Factors has been shown to improve flow-mediated dilation, and some data suggest that vascular responsiveness is related to outcome. Carotid IMT is associated with cardiovascular risk factors, and increased levels can predict myocardial infarction and stroke. Aggressive risk factor management can decrease IMT. Conclusions BAR and IMT ate functional and structural markers of the atherosclerotic process. The clinical use of BAR has been limited by varying reproducibility and the influence by exogenous factors, but IMT exhibits less variability. A desirable next step in the development of BAR and IMT as useful clinical tools would be to show an association of improvement in response to treatment with improvement in prognosis

Interplay between genetic and clinical variables affecting platelet reactivity and cardiac adverse events in patients undergoing percutaneous coronary intervention.

Several clinical and genetic variables are associated with influencing high on treatment platelet reactivity (HTPR). The aim of the study was to propose a path model explaining a concurrent impact among variables influencing HTPR and ischemic events. In this prospective cohort study polymorphisms of CYP2C19*2, CYP2C19*17, ABCB1, PON1 alleles and platelet function assessed by Multiple Electrode Aggregometry were assessed in 416 patients undergoing percutaneous coronary intervention treated with clopidogrel and aspirin. The rates of major adverse cardiac events (MACE) were recorded during a 12-month follow up. The path model was calculated by a structural equation modelling. Paths from two clinical characteristics (diabetes mellitus and acute coronary syndrome (ACS)) and two genetic variants (CYP2C19*2 and CYP2C19*17) independently predicted HTPR (path coefficients: 0.11 0.10, 0.17, and -0.10, respectively; p<0.05 for all). By use of those four variables a novel score for prediction of HTPR was built: in a factor-weighted model the risk for HTPR was calculated with an OR of 3.8 (95%CI: 3.1-6.8, p<0.001) for a score level of ≥1 compared with a score of <1. While MACE was independently predicted by HTPR and age in the multivariate model (path coefficient: 0.14 and 0.13, respectively; p<0.05), the coexistence of HTPR and age ≥75 years emerged as the strongest predictor of MACE. Our study suggests a pathway, which might explain indirect and direct impact of variables on clinical outcome: ACS, diabetes mellitus, CYP2C19*2 and CYP2C19*17 genetic variants independently predicted HTPR. In turn, age ≥75 years and HTPR were the strongest predictors of MACE

Transcatheter aortic valve replacement (TAVR) leads to an increase in the subendocardial viability ratio assessed by pulse wave analysis.

BACKGROUND:Pulse wave analysis (PWA) is a useful tool for non-invasive assessment of central cardiac measures as subendocardial perfusion (Subendocardial Viability Ratio, SEVR) or contractility (dP/dtmax). The immediate influence of transcatheter aortic valve replacement (TAVR) on these indices has not been investigated yet. METHODS:We prospectively enrolled 40 patients presenting with severe aortic stenosis receiving TAVR. Central pressure curves were derived from radial and carotid sites using PWA up to 2 days before and 7 days after TAVR. Parameters were compared between peripheral measurement sites. Changes in SEVR, dP/dtmax and in indices of vascular stiffness were assessed. Additionally, association of these variables with clinical outcome was evaluated during a 12-month follow-up. RESULTS:Central waveform parameters were comparable between measurement sites. SEVR, but not dP/dtmax, augmentation Index (AIx) or augmentation pressure height (AGPH) correlated significantly with disease severity reflected by peak transvalvular velocity and mean transvalvular pressure gradient over the aortic valve (Vmax, ΔPm) [r = -0.372,p = 0.029 for Vmax and r = -0.371,p = 0.021 for ΔPm]. Vmax decreased from 4.5m/s (IQR:4.1-5.0) to 2.2m/s (IQR:1.9-2.7), (p<0.001). This resulted in a significant increase in SEVR [135.3%(IQR:115.5-150.8) vs. 140.3%(IQR:123.0-172.5),p = 0.039] and dP/dtmax [666mmHg(IQR:489-891) vs. 927mmHg(IQR:693-1092),p<0.001], and a reduction in AIx [154.8%(IQR:138.3-171.0) vs. 133.5%(IQR:128.3-151.8),p<0.001] and AGPH [34.1%(IQR:26.8-39.0) vs. 25.0%(IQR 21.8-33.7),p = 0.002], confirming the beneficial effects of replacing the stenotic valve. No association of these parameters could be revealed with outcome. CONCLUSIONS:PWA is suitable for assessing coronary microcirculation and contractility mirrored by SEVR and maxdP/dt in the setting of aortic stenosis. PWA parameters attributed to vascular properties should be interpreted with caution

Outcome after Elective Percutaneous Coronary Intervention Depends on Age in Patients with Stable Coronary Artery Disease - An Analysis of Relative Survival in a Multicenter Cohort and an OCT Substudy.

Age is a strong predictor of survival in patients with coronary artery disease. In elder patients with increasing co-morbidities percutaneous coronary intervention (PCI) is associated with more complications and worse outcome. The calculation of relative survival rates adjusts for the "background" mortality in the general population by correcting for age and gender. We analyzed if elder patients after elective PCI have a worse relative survival compared to younger patient groups.A total of 8,342 patients who underwent elective PCI at two high volume centers between 1998 and 2009 were analyzed.The survival of our patients after PCI (observed survival) was slightly lower compared to the general population (expected survival) resulting in a slightly decreasing relative survival curve. In a multivariate Cox regression model age amongst others was a strong predictor of survival. Stratifying patients according to their age the relative survival curves of younger patients (Quartile 1: 73 years; 2,307 patients) were similar. The relative survival of mid-aged patients (Quartile 2: 58-65 years; 1,899 patients) was better than that of all other patient groups. The profile of cardiovascular risk factors differs between the various groups resulting in different composition and burden of coronary plaques in an optical coherence tomography sub-study.Patients after elective PCI have a slightly worse long-term survival compared to the age- and sex-matched general population. This is also true for different groups of age except for mid-aged patients between 58 and 63 years. Elder patients between 66 and 73 years and above 73 years have a similar relative survival compared to younger patients below 58 years, and might therefore have similar benefit from elective PCI