In patients with aortic stenosis increased flow-mediated dilation is independently associated with higher peak jet velocity and lower asymmetric dimethylarginine levels.

BACKGROUND: Recently, it has been shown that endothelial dysfunction and aortic stenosis (AS) share several risk factors. Endothelial function represents a crucial factor for the regulation of vascular tonus and its malfunction influences the formation of thrombosis and inflammation. However, the role of endothelial dysfunction in AS remains unclear. METHODS: Echocardiographic, clinical, and laboratory data of 34 patients (age 74.5 ± 7.9 years, 20 men) with at least moderate AS (peak jet velocity 3.8 ± 0.8 m/s) were collected. In all patients, endothelial function was determined by brachial artery flow-mediated dilation (FMD). Patients with rheumatic or endocarditic valve disease, bicuspid valves, a left ventricular ejection fraction of ≤40%, and coronary artery disease were excluded. Sixteen volunteers (age 69.3 ± 9.4 years, 10 men) without valve disease served as controls. RESULTS: Patients with AS had a trend toward a lower FMD than controls with a comparable risk profile (5.4% ± 3.6% vs 7.4% ± 4.1%, P = .1). Univariate correlates of FMD in patients with AS were peak jet velocity, medication with angiotensin-converting enzyme inhibitor, diabetes, diastolic blood pressure, and asymmetric dimethylarginine. Backward elimination identified peak jet velocity (ß = 0.51, P = .001), and asymmetric dimethylarginine (ß = -0.45, P = .003) as independent predictors of FMD in multivariate analysis. CONCLUSIONS: In patients with AS, we found a strong positive relation between the peak jet velocity and a higher FMD. This effect might be mediated by nitric oxide release due to turbulent poststenotic blood flow or the rising transvalvular gradient, and the increasing pulse pressure may be counteracted by a parallel increase in FMD.

Echocardiographic evaluation of left ventricular filling pressures validated against an implantable left ventricular pressure monitoring system.

BACKGROUND: Aim of this study was to assess the ability of different echocardiographic indices to evaluate left ventricular (LV) filling pressures in patients with reduced LV function. METHODS: In 5 patients scheduled for aortocoronary bypass surgery, a telemetric intraventricular pressure sensor was implanted. Over 6 months, these patients underwent a total of 21 echocardiographic examinations with a simultaneous recording of left ventricular mean (LVMDP) and end-diastolic pressure (LVEDP). The following echocardiographic parameters were extracted from the transmitral flow profile: early (E) and late (A) diastolic flow velocity, deceleration time of the E-wave (DT) and the isovolumic relaxation time (IVRT). Early diastolic velocity of the mitral ring (E') was recorded using pulsed-wave tissue Doppler echocardiography. RESULTS: All patients were in NYHA class III and mean ejection fraction was 30%. E correlated only moderately with LVMDP (r =-0.60, P = 0.003), but revealed the highest area under the receiver operating characteristic curve for the prediction of an elevated LVMDP > 12 mmHg (AUC = 0.94, sensitivity of 92% and specificity of 86%, cut-off value 7.5 cm/s). E/A > 1 predicted LVEDP > 15 mmHg with a sensitivity of 87% and a specificity of 80%. E/E' was not correlated with LVMDP or LVEDP. CONCLUSION: Although linear correlation between echocardiographic parameters and diastolic LV pressures reached statistical significance, the correlation coefficients were low. However, in these patients with severely reduced LV function due to ischemic heart disease conventional echocardiographic parameters of transmitral flow showed higher predictive values for elevated LV filling pressures than E/E'.

A Pilot Study on the Association of Mitochondrial Oxygen Metabolism and Gas Exchange During Cardiopulmonary Exercise Testing: Is There a Mitochondrial Threshold?

Background: Mitochondria are the key players in aerobic energy generation via oxidative phosphorylation. Consequently, mitochondrial function has implications on physical performance in health and disease ranging from high performance sports to critical illness. The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) allows in vivo measurements of mitochondrial oxygen tension (mitoPO2). Hitherto, few data exist on the relation of mitochondrial oxygen metabolism and ergospirometry-derived variables during physical performance. This study investigates the association of mitochondrial oxygen metabolism with gas exchange and blood gas analysis variables assessed during cardiopulmonary exercise testing (CPET) in aerobic and anaerobic metabolic phases. Methods: Seventeen volunteers underwent an exhaustive CPET (graded multistage protocol, 50 W/5 min increase), of which 14 were included in the analysis. At baseline and for every load level PpIX-TSLT-derived mitoPO2 measurements were performed every 10 s with 1 intermediate dynamic measurement to obtain mitochondrial oxygen consumption and delivery (mito V . O2, mito D . O2). In addition, variables of gas exchange and capillary blood gas analyses were obtained to determine ventilatory and lactate thresholds (VT, LT). Metabolic phases were defined in relation to VT1 and VT2 (aerobic:

Non-invasive Assessment of Mitochondrial Oxygen Metabolism in the Critically Ill Patient Using the Protoporphyrin IX-Triplet State Lifetime Technique-A Feasibility Study.

The imbalance of oxygen delivery and oxygen consumption resulting in insufficient tissue oxygenation is pathognomonic for all forms of shock. Mitochondrial function plays an important role in the cellular oxygen metabolism and has been shown to impact a variety of diseases in the intensive care setting, specifically sepsis. Clinical assessment of tissue oxygenation and mitochondrial function remains elusive. The in vivo protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) allows the direct, non-invasive measurement of mitochondrial oxygen tension (mitoPO2) in the human skin. Our recently established measurement protocol for the Cellular Oxygen Metabolism (COMET) Monitor, a novel device employing the PpIX-TSLT, additionally allows the evaluation of oxygen consumption (mitoVO2) and delivery (mitoDO2). In the intensive care setting, these variables might provide new insight into mitochondrial oxygen metabolism and especially mitoDO2 might be a surrogate parameter of microcirculatory function. However, the feasibility of the PpIX-TSLT in critically ill patients has not been analyzed systematically. In this interim study analysis, we evaluated PpIX-TSLT measurements of 40 patients during the acute phase of sepsis. We assessed (a) potential adverse side effects of the method, (b) the rate of analyzable measurements, (c) the stability of mitoPO2, mitoVO2, and mitoDO2, and (d) potential covariates. Due to excessive edema in patients with sepsis, we specifically analyzed the association of patients' hydration status, assessed by bioimpedance analysis (BIA), with the aforementioned variables. We observed no side effects and acquired analyzable measurements sessions in 92.5% of patients (n = 37/40). Different measures of stability indicated moderate to good repeatability of the PpIX-TSLT variables within one session of multiple measurements. The determined limits of agreement and minimum detectable differences may be helpful in identifying outlier measurements. In conjunction with signal quality they mark a first step in developing a previously unavailable standardized measurement quality protocol. Notably, higher levels of hydration were associated with lower mitochondrial oxygen tension. We conclude that COMET measurements are viable in patients with sepsis. To validate the clinical and diagnostic relevance of the PpIX-TSLT using the COMET in the intensive care setting, future studies in critically ill patients and healthy controls are needed.