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.

Surgical Ventricular Restoration for Ischemic Heart Failure: A Glance at a Real-World Population.

Surgical ventricular restoration (SVR) has repeatedly been suggested as a viable therapeutic strategy for ischemic heart failure (HF) patients, although the survival benefit is still debated. We investigated a real-world population treated with SVR in a single center with high case volumes. From July 2001 to June 2017, 648 patients (111 females) underwent SVR; coronary surgery was performed in 582 patients. Data were analyzed by dividing the population into two groups: Group I (371 patients operated between July 2001 and December 2007) and Group II (277 patients operated between January 2008 and June 2017). At baseline, Group I patients were more symptomatic for angina (47.4% versus 19.4%, p < 0.0001) and less symptomatic for HF (NYHA class III/IV, 46.3% versus 57%, p = 0.0071). The end-diastolic volume (106 mL/m2 versus 118.3 mL/m2, p < 0.0001) and the end-systolic volume (70.5 mL/m2 versus 81.5 mL/m2, p < 0.0001) were lower in Group I. The presence of 3-vessel coronary artery disease (CAD) was higher in Group I (73.3% versus 59.2%, p < 0.0001). Thirty-day mortality (6.64%) was similar in the two groups (p = 0.4475). The Kaplan−Meier estimate for all-cause mortality for the entire population was 13% at 2 years, 19.2% at 4 years and 36.6% at 8 years, and the probability was not different between groups (Log-rank = 0.11). In a real-world ischemic HF population, SVR may be carried out with favorable results; in patients with worse LV remodeling and less extensive CAD, SVR showed a trend toward a better outcome.

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.

Prognostic value of natriuretic peptides and restrictive filling pattern before surgical ventricular restoration.

OBJECTIVE: Both increased natriuretic peptide levels and restrictive filling pattern (RFP) are important risk predictors in patients with heart failure. The aim of this study was to examine the role of the combined use of natriuretic peptide and RFP for the prognostic stratification of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration in the Biomarker Plus study. METHODS: A total of 186 patients (aged 64 ± 10 years) underwent echocardiographic study and N-terminal pro-B-type natriuretic peptide assay at baseline (before surgical ventricular restoration). Patients were divided into 4 groups depending on baseline diastolic filling pattern (RFP/no RFP) and N-terminal pro-B-type natriuretic peptide level (less than or greater than or equal to the upper tertile value of 2003 ŋg/L). RFP was defined as E/A ratio ≥2. All-cause death or heart failure hospitalizations within 36-month follow-up were analyzed. RESULTS: Despite similar ejection fraction, volumes, and mass, the 4 groups presented distinct clinical and structural pattern of presurgical ventricular restoration ventricular remodeling and significantly different clinical outcome after surgical unloading. During follow-up, 67 patients died or were hospitalized for heart failure (36%). High N-terminal pro-B-type natriuretic peptide levels and RFP, considered individually, were significantly associated with outcome (P < .0001). The combination of both was associated with the highest adjusted hazard of adverse events (hazard ratio, 3.63; 95% CI, 1.73-7.6; P < .0001). CONCLUSIONS: The simultaneous use of 2 markers, 1 biological and 1 echocardiographic, may allow better prognostic stratification and characterization of the distinct structural and clinical phenotypes in a population of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration. This approach could be useful in the decision-making process to guide treatment choices in patients with ischemic cardiomyopathy.

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.

Comparable outcomes between genders in patients undergoing surgical ventricular reconstruction for ischaemic heart failure.

AIMS: Female sex and heart failure (HF) are considered poor prognostic factors for surgery. We aimed to investigate the association between sex and surgical outcomes in patients with ischaemic HF undergoing surgical ventricular reconstruction and coronary artery bypass grafting. METHODS AND RESULTS: From July 2001 to June 2017, 648 patients [111 women (17%) and 537 men (83%)] were referred to our centre. Follow-up continued through June 2018. All patients underwent surgical ventricular reconstruction; coronary artery bypass grafting was performed in 582 patients (90%). Primary outcome was defined as all-cause mortality. Secondary outcome included all-cause mortality or all-cause hospitalization. Women were older (70 vs. 65 years, P < 0.0001) with lower body surface area (1.70 vs. 1.86 m2 , P < 0.0001). Women had more diabetes (36% vs. 24%, P = 0.005) and a higher New York Heart Association classification (Class III/IV 65.7% vs. 47.8%, P = 0.0006), without any significant difference in medical therapy except for a higher use of oral antidiabetic agents in women (P = 0.029). At baseline, the left ventricular (LV) end-diastolic volume index was significantly lower in women [median 107.06 (80.6-127.81) vs. 113. 04 (94.33-135.52) mL/m2 , P = 0.0078] but not the LV end-systolic volume index (ESVI) [median 73.45 (51.93-96.79) vs. 77.03 (60.33-95.71) mL/m2 , P = 0.1393] and the ejection fraction (median 31% vs. 32%, P = 0.150). Women had a higher rate of anterior remodelling (90.9% vs. 79.1%, P = 0.0129), without evidence of differences in mitral valve insufficiency (P = 0.761 for Grade 0 to 4) and mitral surgery (P = 0.810). After surgery, the percentage of reduction in LV ESVI was higher in women than in men (median ΔLV ESVI -42.06 vs. -31.99, P = 0.0003). Mortality within 30 days occurred in 43 patients (6.64%): 12 women (10.81%) and 31 men (5.77%, P = 0.0522). Over a median follow-up of 9.8 years, all-cause mortality occurred in 269 patients (41.64%), without significant difference between women (45.9%) and men (40.7%). There was no evidence of difference of all-cause death between sexes (log-rank = 0.2441). When considering mortality and first hospitalization as competing events, Gray's test showed no difference of cumulative incidence functions (all-cause hospitalization, all-cause death, and combined endpoint) according to sex (P = 0.909, P = 0.445, and P = 0.429, respectively). CONCLUSIONS: In this study, long-term outcomes for women and men with ischaemic HF undergoing complex cardiac surgery were equivalent. Albeit older and more symptomatic, women should not be denied this type of cardiac surgery.

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.

The Monitoring of Psychosocial Factors During Hospitalization Before and After Cardiac Surgery Until Discharge From Cardiac Rehabilitation: A Research Protocol.

Introduction: There is considerable evidence that psychosocial factors contribute to the etiology and prognosis of cardiac illness. Currently, in Italy, psychologists are only obligatory in the cardiac rehabilitation setting, although there are indications that patients could be experiencing distress also during other moments of hospitalization, such as on admission for cardiac surgery. Objective and Methods: The objective of this protocol is to gain more information about cardiac patients, specifically during the various moments of hospitalization for cardiac surgery, by collecting data at admission before cardiac surgery (t0), at admission to cardiac rehabilitation (t1), and at discharge (t2) at the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato hospital. A psychosocial questionnaire was constructed after consulting the relevant national and international guidelines. Patients admitted for cardiac surgery and attending a rehabilitation program will be evaluated by acquiring data about their civil status, religiosity, education and work capacity, social condition (including the presence and quality of intimate relationships and support received), previous psychological and psychiatric histories, psychological status, lifestyle (including questions on nutrition, smoking, alcohol, and substance abuse), adherence to therapy, quality of life (QoL), health perception, anxiety, and depression at t0. Health perception, anxiety, and depression are also measured at t1 and t2. Discussion and Conclusion: This study is an attempt to identify the recommended psychosocial variables which need to be monitored during cardiac patients' hospitalization for cardiac surgery, through to the completion of cardiac rehabilitation. After implementing this study at the IRCCS Policlinico San Donato, attempts will be made to create studies on a national and international level to generate more evidence regarding these variables, in order to create tailor-made interventions for these patients during these specific and delicate moments.

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.

Myocardial Revascularization for Patients With Diabetes: Coronary Artery Bypass Grafting or Percutaneous Coronary Intervention?

Patients affected by diabetes usually have extensive coronary artery disease. Coronary revascularization has a prominent role in the treatment of coronary artery disease in the expanding diabetic population. However, diabetic patients undergoing coronary artery bypass grafting or percutaneous coronary intervention experience worse outcomes than nondiabetic patients. Several studies comparing coronary artery bypass grafting vs percutaneous coronary intervention in subgroups of diabetic patients demonstrated a survival advantage and fewer repeat revascularization procedures with an initial surgical strategy. This review summarizes the current state of evidence comparing the effectiveness and safety of coronary artery bypass grafting and percutaneous coronary intervention in diabetic patients.

[New antithrombotic drugs in cardiovascular disease]. / Nuovi farmaci antitrombotici in patologia cardiovascolare.

During the past decades, a great bulk of studies have been undertaken to investigate the pathophysiologic mechanisms responsible for thrombus formation. As a consequence, different therapeutic strategies interfering at different levels of the coagulation process have been developed. Many of these compounds did not achieve full development, but others are presently available for the clinician. The present review paper will focus on these new therapeutic strategies developed in the last 10 years.