Characterization of cardiovascular and cerebrovascular controls via spectral causality analysis in patients undergoing surgical aortic valve replacement during a three-month follow-up.

Objective.Aortic valve stenosis (AVS) induces left ventricular function adaptations and surgical aortic valve replacement (SAVR) restores blood flow profile across aortic valve. Modifications of cardiac hemodynamics induced by AVS and SAVR might alter cardiovascular (CV) and cerebrovascular (CBV) controls. The study aims at characterizing CV and CBV regulations one day before SAVR (PRE), within one week after SAVR (POST), and after a three-month follow-up (POST3) in 73 AVS patients (age: 63.9 ± 12.9 yrs; 48 males, 25 females) from spontaneous fluctuations of heart period (HP), systolic arterial pressure, mean arterial pressure and mean cerebral blood velocity.Approach.CV and CBV regulations were typified via a bivariate autoregressive approach computing traditional frequency domain markers and causal squared coherence (CK2) from CV and CBV variabilities. Univariate time and frequency domain indexes were calculated as well. Analyses were carried out in frequency bands typical of CV and CBV controls at supine rest and during active standing. A surrogate method was exploited to check uncoupling condition.Main results.We found that: (i) CV regulation is impaired in AVS patients; (ii) CV regulation worsens in POST; (iii) CV regulation recovers in POST3 and CV response to active standing is even better than in PRE; (iv) CBV regulation is preserved in AVS patients; (v) SAVR does not affect CBV control; (vi) parameters of the CBV control in POST3 and PRE are similar.Significance.CK2is particularly useful to characterize CV and CBV controls in AVS patients and to monitor of patient's evolution after SAVR.

Monitoring the Evolution of Asynchrony between Mean Arterial Pressure and Mean Cerebral Blood Flow via Cross-Entropy Methods.

Cerebrovascular control is carried out by multiple nonlinear mechanisms imposing a certain degree of coupling between mean arterial pressure (MAP) and mean cerebral blood flow (MCBF). We explored the ability of two nonlinear tools in the information domain, namely cross-approximate entropy (CApEn) and cross-sample entropy (CSampEn), to assess the degree of asynchrony between the spontaneous fluctuations of MAP and MCBF. CApEn and CSampEn were computed as a function of the translation time. The analysis was carried out in 23 subjects undergoing recordings at rest in supine position (REST) and during active standing (STAND), before and after surgical aortic valve replacement (SAVR). We found that at REST the degree of asynchrony raised, and the rate of increase in asynchrony with the translation time decreased after SAVR. These results are likely the consequence of the limited variability of MAP observed after surgery at REST, more than the consequence of a modified cerebrovascular control, given that the observed differences disappeared during STAND. CApEn and CSampEn can be utilized fruitfully in the context of the evaluation of cerebrovascular control via the noninvasive acquisition of the spontaneous MAP and MCBF variability.

Respiration is a Confounder of the Closed Loop Relationship Between Mean Arterial Pressure and Mean Cerebral Blood Flow.

This study tested the hypothesis that respiration (RESP) is a confounder or suppressor of the closed loop relationship responsible for the cerebrovascular dynamical interactions as assessed from spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow (MCBF). The evaluation was carried out in the information domain via transfer entropy (TE) estimated through a linear model-based approach comparing TE markers computed solely over MAP and MCBF series with TE indexes accounting for the eventual action of RESP over MAP and MCBF. We considered 11 patients (age: 76±5 yrs, 7 males) undergoing surgical aortic valve replacement (SAVR) at supine resting (REST) and during active standing (STAND) before and after SAVR surgery. The decrease of the predictive ability of MCBF to MAP when accounting for RESP compared to the one assessed when disregarding RESP suggested that RESP is a confounder of the link from MCBF to MAP along the Cushing reflex instead of being a suppressor. This result was more evident in POST when autonomic control was dramatically depressed and in an unchallenged condition such as REST. RESP did not affect significantly the link from MAP to MCBF along the pressure-to-flow relationship. Clarification of the type of RESP influence on the MAP-MCBF closed loop relationship could favor a deeper characterization of cerebrovascular interactions and the comprehension of cerebral autoregulation mechanisms.Clinical Relevance- This study suggests that respiration is a confounder of the closed loop relationship between MAP and MCBF, especially of the flow-to-pressure causal link. This result might open new possibilities in elucidating the mechanisms of cerebral autoregulation in healthy and pathological populations.

Evaluation of the impact of surgical aortic valve replacement on short-term cardiovascular and cerebrovascular controls through spontaneous variability analysis.

We assessed the effect of surgical aortic valve replacement (SAVR) on cardiovascular and cerebrovascular controls via spontaneous variability analyses of heart period, approximated as the temporal distance between two consecutive R-wave peaks on the electrocardiogram (RR), systolic, diastolic and mean arterial pressure (SAP, DAP and MAP) and mean cerebral blood flow (MCBF). Powers in specific frequency bands, complexity, presence of nonlinear dynamics and markers of cardiac baroreflex and cerebral autoregulation were calculated. Variability series were acquired before (PRE) and after (POST) SAVR in 11 patients (age: 76±5 yrs, 7 males) at supine resting and during active standing. Parametric spectral analysis was performed based on the autoregressive model. Complexity was assessed via a local nonlinear prediction approach exploiting the k-nearest-neighbor strategy. The presence of nonlinear dynamics was checked by comparing the complexity marker computed over the original series with the distribution of the same index assessed over a set of surrogates preserving distribution and power spectral density of the original series. Cardiac baroreflex and cerebral autoregulation were estimated by assessing the transfer function from SAP to RR and from MAP to MCBF and squared coherence function via the bivariate autoregressive approach. We found that: i) orthostatic challenge had no effect on cardiovascular and cerebrovascular control markers in PRE; ii) RR variance was significantly reduced in POST; iii) complexity of SAP, DAP and MAP variabilities increased in POST with a greater likelihood of observing nonlinear dynamics over SAP compared to PRE at supine resting; iv) the amplitude of MCBF variations and MCBF complexity in POST remained similar to PRE; v) cardiac baroreflex sensitivity decreased in POST, while cerebrovascular autoregulation was preserved. SAVR induces important changes of cardiac and vascular autonomic controls and baroreflex regulation in patients exhibiting poor reactivity of cardiovascular regulatory mechanisms, while cerebrovascular autoregulation seems to be less affected.

Complexity and Nonlinearities of Short-Term Cardiovascular and Cerebrovascular Controls after Surgical Aortic Valve Replacement.

We assessed the effect of surgical aortic valve replacement (SAVR) on cardiovascular and cerebrovascular controls with particular attention to their complexity and presence of nonlinear behaviors via the analysis of spontaneous variability of heart period (HP), systolic and diastolic arterial pressure (SAP and DAP) and mean cerebral blood flow (MCBF). Variability series were acquired before (PRE) and after (POST) SAVR in 12 patients (age: 76±4.7 yrs, 7 males) at rest in supine position and during active standing. Complexity was assessed via a local nonlinear prediction approach exploiting the k-nearest neighbor strategy. The presence of nonlinear dynamics was checked by comparing the complexity marker computed over the original series with the distribution of values assessed over 100 surrogates preserving distribution and power spectral density of the original series but with random phases. We found that: i) HP variance was significantly reduced in POST; ii) the complexity of SAP and DAP variabilities increased in POST with a greater likelihood of observing nonlinear dynamics over SAP compared to PRE at supine rest; iii) the amplitude of MCBF fluctuations and its complexity in POST remained similar to PRE. SAVR induces important changes of the cardiac and vascular autonomic controls, while cerebrovascular regulation seems to be less affected.

Clinical Course of COVID-19 Infection in Patients Urgently Operated of Cardiac Surgical Procedures.

OBJECTIVE: The aim of this study was to describe the clinical course of a consecutive series of patients operated of urgent cardiac surgery during COVID-19 outbreak. BACKGROUND: In Italy, COVID outbreak has mostly occurred in the metropolitan area of Milan, and in the surrounding region of Lombardy, and previously "conventional" hospitals were converted into COVID spokes to increase ICU beds availability, and to allow only urgent CS procedures. METHODS: Among urgent CS patients (left main stenosis with unstable angina, acute endocarditis, valvular regurgitation with impending heart failure), 10 patients (mean age = 57 ± 9 years), despite a negative admission triage, developed COVID-pneumonia postoperatively, at a median of 7 days after CS. RESULTS: Patients showed typical lymphopenia, higher prothrombotic profile, and higher markers of inflammation (ferritin and interleukin-6 values). At the zenith of pulmonary distress, patients presented with severe hypoxia (median PaO2/FIO2 ratio = 116), requiring advanced noninvasive ventilation (Venturi mask and continuous positive airway pressure) in the majority of cases. All patients were treated with hydroxychloroquine, azithromycin, and low-molecular-weight heparin at anticoagulant dose. Overall in-hospital mortality was 10% (1/10), peaking 25% in patients who developed COVID pneumonia immediately after CS. The remaining patients, with late infection, were all discharged home without oxygen support, at a median of 25 days after symptom onset. CONCLUSIONS: As postoperative mortality in case of COVID pneumonia is not negligible, meticulous rules (precise triage, safe hospital path, high level of protection for health-care teams, prompt diagnosis of suspicious symptoms) should be strictly followed in patients undergoing CS during COVID pandemic. The role of therapies alternative to CS should be further assessed.

Anaemia as an inflammation-mediated condition during chronic heart failure. Possible role of fibrinogen.

BACKGROUND: In patients with chronic heart failure (CHF) anaemia is a common finding and may worsen clinical conditions. Moreover, CHF itself could be involved in the pathogenesis of anaemia. Early studies suggested a pathogenic role of inflammation mediators. OBJECTIVES: The objectives of the study were to assess the relationship between CHF and haemoglobin (Hgb) plasma levels, and to investigate a possible link between fibrinogen plasma levels and anaemia. METHODS: This retrospective study included consecutively hospitalized patients with CHF and left ventricular ejection fraction (LVEF) < 50%. Patients without signs or symptoms of CHF and with LVEF > or = 50% were selected as controls. Patients with secondary anaemia were excluded. RESULTS: 257 patients (72% men) with CHF and 224 controls (65% men) were studied.The average +/- SD of Hgb in CHF patients was 12.38 +/- 1.98 g/dl vs. 13.43 +/- 1.64 g/dl in controls (P < 0.0001). A total of 69 patients (26.7%) had both CHF and anaemia. Plasma fibrinogen concentration was higher in the patients compared with the control subjects (364.83 +/- 123.76 mg/dl vs. 343.44 +/- 135.43 mg/dl; respectively; P = 0.013). Patients with anaemia showed a significantly higher plasma fibrinogen concentration compared to those without anaemia (400.57 +/- 132.36 mg/dl vs. 351.72 +/- 118.13 mg/dl; P = 0.0059). Stepwise logistic regression analysis showed that female gender, creatinine plasma levels, and fibrinogen plasma levels were independently associated with anaemia. No significant relationship between fibrinogen and creatinine plasma concentration was found. CONCLUSION: Anaemia is common in CHF patients and it is associated with heart failure severity.The increase of fibrinogen plasma levels in CHF patients seems to confirm that chronic inflammation is involved in the pathogenesis of anaemia.