Intraoperative Beat-to-Beat Pulse Transit Time (PTT) Monitoring via Non-Invasive Piezoelectric/Piezocapacitive Peripheral Sensors Can Predict Changes in Invasively Acquired Blood Pressure in High-Risk Surgical Patients.

BACKGROUND: Non-invasive tracking of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP, respectively) and to detect SBPIBP fluctuations. METHODS: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson's correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). RESULTS: Significant correlations between 1/PTT and SBPIBP were found for PES (r = 0.64) and PCS (r = 0.55) (p < 0.01), as well as MAPIBP/DBPIBP for PES (r = 0.6/0.55) and PCS (r = 0.5/0.45) (p < 0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease (0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). CONCLUSIONS: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus, PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

Measurement of multiple cytokines for discrimination and risk stratification in patients with Chagas' disease and idiopathic dilated cardiomyopathy.

Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.

Preserved autonomic regulation in patients undergoing transcatheter aortic valve implantation (TAVI): a prospective, comparative study.

Heart rate and blood pressure variability as well as baroreflex sensitivity (BRS) lead to additional insights on the patients' prognosis after cardiovascular events. The following study was performed to assess the differences in the postoperative recovery of the autonomic regulation after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Fifty-eight consecutive patients were enrolled in a prospective study; 24 underwent TAVI and 34 SAVR. BRS was calculated according to the Dual Sequence Method, heart rate variability (HRV) was evaluated using standard linear as well as nonlinear parameters. HRV and BRS parameters were reduced after surgery in patients with SAVR only (meanNN: p<0.001, sdNN: p<0.05, Shannon: p<0.01, BRS: p<0.01), while these indexes were preserved in patients after TAVI. Simultaneously, an increased complexity of blood pressure (BP) in SAVR patients (fwShannon: p<0.001, fwRenyi4: p<0.001), but not in TAVI patients was recorded. In this study we were able to demonstrate for the first time that, in contrast to patients undergoing conventional open surgery, there are fewer alterations of the cardiovascular autonomic system in patients with TAVI.

Amino-terminal fragment of C-type natriuretic peptide precursor and C-type natriuretic peptide do not correlate in patients with Chagas disease: role for neutral endopeptidase.

Atrial and B-type natriuretic peptides (ANP and BNP), but not C-type natriuretic peptide (CNP), have been identified to be diagnostic and prognostic markers in Chagas disease (CD). Although ANP and BNP excessively rise in patients with CD, increase in CNP is just minor. Our study aimed to investigate the mechanisms leading to CNP insensitivity to heart failure (HF) stimuli. Amino-terminal fragment of CNP precursor (NT-proCNP) and activity of neutral endopeptidase (NEP) were quantified to monitor CNP generation and degradation, respectively. Blood samples were collected from patients with CD and control healthy subjects. NT-proCNP concentrations were significantly lower in patients with CD without systolic dysfunction compared with healthy subjects. Despite a trend toward increase with rising heart failure clinical severity, it was significantly correlated with left ventricular ejection fraction and other echocardiographic parameters. As shown for CNP before, NT-proCNP could not predict mortality and heart transplant. Importantly, it had no statistical correlation with CNP. Additionally, NEP activity was significantly increased in New York Heart Association III and IV patients with HF but was positively correlated with CNP concentration. Our data demonstrates that generation of CNP is not enhanced under HF condition like CD. Thus, CNP rise by severe HF is caused by its less degradation that is independent of NEP activity.

Depression of cardiovascular autonomic function is more pronounced after mitral valve surgery: evidence for direct trauma.

The analysis of baroreflex sensitivity (BRS) and heart rate variability (HRV) leads to additional insights into patients' prognosis after cardiovascular events. The following study was performed to assess the differences in the post-operative recovery of autonomic regulation after mitral valve (MV) and aortic valve (AV) surgery with a heart-lung machine. Among the 43 consecutive male patients enrolled in a prospective study, 26 underwent isolated AV surgery and 17 isolated MV surgery. Blood pressure as well as ECG signals were recorded the day before, 24 hours after and one week after surgery. BRS was calculated according to the dual sequence method, and HRV was calculated using standard linear as well as nonlinear parameters. There were no major differences between the two groups in the pre-operative values. At 24 hours a comparable depression of HRV and BRS in both groups was observed, while at 7 days there was partial recovery in AV patients, which was absent in MV patients: p(AV versus MV)<0.001. While the response of the autonomic system to surgery is similar in AV and MV patients, there is obviously a decreased ability to recover in MV patients, probably attributed to traumatic lesions of the autonomic nervous system by opening the atria. Ongoing research is required for further clarification of the pathophysiology of this phenomenon and to establish strategies to restore autonomic function.

Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion.

Angiogenic factors like placental growth factor and its antiangiogenic antagonist soluble fms-like tyrosine kinase 1 (sFlt1) are closely related to the pathogenesis of preeclampsia and intrauterine growth restriction. Because it is known that altered maternal sFlt1 and placental growth factor levels are detectable weeks before the onset of these pregnancy complications, it was the aim of the study to investigate the predictive value of these markers in high-risk second trimester pregnancies characterized by abnormal uterine perfusion. This prospective study includes 63 second trimester pregnant women with abnormal uterine perfusion. Twenty five of them developed a later complication (12 with preeclampsia, 11 with intrauterine growth restriction, and 2 with intrauterine death), whereas 38 had a normal course of pregnancy. Pregnancies with adverse pregnancy outcome showed in the second trimester significantly higher sFlt1 (1403.6+/-555 versus 451.8+/-42 pg/mL; P<0.05) and lower placental growth factor (139.6+/-24 versus 184.1+/-21 pg/mL) levels compared with those with normal outcome. These alterations were more pronounced in pregnancies with subsequent preeclampsia compared with intrauterine growth restriction and early onset diseases (delivery <34 weeks) compared with late-onset diseases. The combination of Doppler and sFlt1 increases the sensitivity of Doppler alone for iatrogenic preterm delivery from 64% up to 79% and the specificity from 63% up to 80%. Using both factors, sFlt1 and placental growth factor, early onset preeclampsia can be predicted with 83% sensitivity and 95% specificity. We conclude that the concurrent measurement of uterine perfusion and angiogenic factors allows an efficient prediction of early onset pregnancy complications, particularly preeclampsia.

Autonomic control in patients experiencing atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation (AF) occurs in 20-40% of patients after open heart surgery and leads to an increased morbidity and prolonged hospital stay. Earlier studies have demonstrated that depressed baroreflex function predicts mortality and major arrhythmic events in patients surviving myocardial infarction. Cardiac surgery per se leads to decreased baroreflex sensitivity (BRS) and heart rate variability (HRV). Hence, the present study was aimed at analyzing the impact of the cardiovascular autonomous system on the development of postsurgical AF. METHODS AND RESULTS: The study covered 51 patients who consecutively underwent aortic valve replacement, coronary artery bypass surgery, or combined procedures. Noninvasive blood pressure and ECG were recorded the day before and 24 hour after surgery. BRS, linear as well as nonlinear HRV parameters were calculated using established methods. Eighteen patients developed AF during the first postoperative week, while 33 remained in sinus rhythm (SR) throughout the observation period. Patients with postoperative (PostOp) AF exhibited a significantly reduced preoperative (PreOp) BRS in terms of bradycardic and tachycardic regulation (average delayed slope [ms/mmHg]: SR: PreOp: 9.83 +/- 3.26, PostOp: 6.02 +/- 2.29, Pre-Post: P < 0.001; AF: PreOp: 7.59 +/- 1.99, PostOp: 6.39 +/- 3.67, Pre-Post: P < 0.044; AF vs SR: PreOp: P < 0.01, PostOp: ns). In both groups, surgery caused a decrease of BRS and HRV. Analysis of nonlinear dynamics revealed a tendency toward decreased system complexity caused by the operation; this trend was significant in patients remaining in sinus rhythm. CONCLUSIONS: Patients experiencing postoperative AF obviously suffer from an impaired BRS before surgery already. These findings may be used to guide prophylactic antiarrhythmic therapy.

Large-scale dimension densities for heart rate variability analysis.

In this work, we reanalyze the heart rate variability (HRV) data from the 2002 Computers in Cardiology (CiC) Challenge using the concept of large-scale dimension densities and additionally apply this technique to data of healthy persons and of patients with cardiac diseases. The large-scale dimension density (LASDID) is estimated from the time series using a normalized Grassberger-Procaccia algorithm, which leads to a suitable correction of systematic errors produced by boundary effects in the rather large scales of a system. This way, it is possible to analyze rather short, nonstationary, and unfiltered data, such as HRV. Moreover, this method allows us to analyze short parts of the data and to look for differences between day and night. The circadian changes in the dimension density enable us to distinguish almost completely between real data and computer-generated data from the CiC 2002 challenge using only one parameter. In the second part we analyzed the data of 15 patients with atrial fibrillation (AF), 15 patients with congestive heart failure (CHF), 15 elderly healthy subjects (EH), as well as 18 young and healthy persons (YH). With our method we are able to separate completely the AF (rho (mu/ls) = 0.97 +/- 0.02) group from the others and, especially during daytime, the CHF patients show significant differences from the young and elderly healthy volunteers (CHF, 0.65 +/- 0.13; EH, 0.54 +/- 0.05; YH, 0.57 +/- 0.05; p < 0.05 for both comparisons). Moreover, for the CHF patients we find no circadian changes in rho (mu/ls) (day, 0.65 +/- 0.13; night, 0.66 +/- 0.12; n.s.) in contrast to healthy controls (day, 0.54 +/- 0.05; night, 0.61 +/- 0.05; p=0.002). Correlation analysis showed no statistical significant relation between standard HRV and circadian LASDID, demonstrating a possibly independent application of our method for clinical risk stratification.

Recurrence-plot-based measures of complexity and their application to heart-rate-variability data.

The knowledge of transitions between regular, laminar or chaotic behaviors is essential to understand the underlying mechanisms behind complex systems. While several linear approaches are often insufficient to describe such processes, there are several nonlinear methods that, however, require rather long time observations. To overcome these difficulties, we propose measures of complexity based on vertical structures in recurrence plots and apply them to the logistic map as well as to heart-rate-variability data. For the logistic map these measures enable us not only to detect transitions between chaotic and periodic states, but also to identify laminar states, i.e., chaos-chaos transitions. The traditional recurrence quantification analysis fails to detect the latter transitions. Applying our measures to the heart-rate-variability data, we are able to detect and quantify the laminar phases before a life-threatening cardiac arrhythmia occurs thereby facilitating a prediction of such an event. Our findings could be of importance for the therapy of malignant cardiac arrhythmias.