Diego Bellavia

Can multiple previous treatment-requiring rejections affect biventricular myocardial function in heart transplant recipients? A two-dimensional speckle-tracking study

a Cardiology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS— ISMETT (IstitutoMediterraneo per i Trapianti e Terapie ad alta Specializzazione), Via Tricomi 5, 90127 Palermo, Italy b Cardiac Surgery and Heart Transplantation Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS— ISMETT (IstitutoMediterraneo per i Trapianti e Terapie ad alta Specializzazione), Via Tricomi 5, 90127 Palermo, Italy c Research Office, IRCCS — ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione), Via Tricomi 5, 90127 Palermo, Italy d University of Liege Hospital, GIGA Cardiovascular Sciences, Department of Cardiology, Heart Valve Clinic, CHU Sart Tilman, Liege, Belgium

Mitral Regurgitation Grading in the Operating Room: A Systematic Review and Meta-analysis Comparing Preoperative and Intraoperative Assessments During Cardiac Surgery

OBJECTIVEnTo assess differences in mitral regurgitation (MR) grade between the preoperative and the intraoperative evaluations.nnnDESIGNnSystematic review and meta-analysis of 6 observational studies found from MEDLINE and EMBASE.nnnSETTINGnCardiac surgery.nnnPARTICIPANTSnOne hundred thirty-seven patients.nnnINTERVENTIONnComparison between the preoperative MR assessment and the intraoperative evaluation conducted under general anesthesia (GA), with or without hemodynamic matching (HM) (artificial increase of afterload).nnnMEASUREMENTS AND MAIN RESULTSnThe primary outcome was the difference between the preoperative and intraoperative MR grade under GA-only or after-HM. Secondary analyses addressed differences according to effective regurgitant orifice area (EROA), regurgitant volume (RVol), color-jet area, and vena contracta width. Risk of MR underestimation was found under GA-only (SMD: 0.55; 95% confidence interval [CI], 0.31-0.79, p < 0.00001), but not after-HM (SMD: -0.16; 95% CI, -0.46 to 0.13, p = 0.27). Under GA-only, EROA had a trend toward underestimation (p = 0.07), RVol was reliable (p = 0.17), while reliance on color-jet area and vena contracta width incur risk of underestimation (both p = 0.003). After HM, EROA accurately reflected preoperative MR (p = 0.68) while RVol had a trend toward overestimation (p = 0.05). The overall reported incidence of misdiagnoses was slightly more common under GA-only (mean 48%, 39% underestimation, 9% overestimation; range: 32%-57%) than after-HM (mean 41%, 12% underestimation, 29% overestimation; range: 33%-50%). Only the minority of misdiagnoses were clinically relevant: underestimation was around 10% (both approaches), but 18% had clinically significant overestimation after-HM as compared with 3% under GA-only.nnnCONCLUSIONSnIntraoperative assessment under GA-only significantly underestimated MR. A more accurate intraoperative evaluation can be obtained with afterload manipulation, although HM strategy carries high risk of clinically significant overestimation.

Shear stress alterations in the celiac trunk of patients with a continuous-flow left ventricular assist device as shown by in-silico and in-vitro flow analyses

BACKGROUNDnThe use of left ventricular assist devices (LVADs) to treat advanced cardiac heart failure is constantly increasing, although this device leads to high risk for gastrointestinal bleeding.nnnMETHODSnUsing in-silico flow analysis, we quantified hemodynamic alterations due to continuous-flow LVAD (HeartWare, Inc., Framingham, MA) in the celiac trunk and major branches of the abdominal aorta, and then explored the relationship between wall shear stress (WSS) and celiac trunk orientation. To assess outflow from the aortic branch, a 3-dimensional-printed patient-specific model of the celiac trunk reconstructed from an LVAD-supported patient was used to estimate echocardiographic outflow velocities under continuous-flow conditions, and then to calibrate computational simulations. Moreover, flow pattern and resulting WSS values were computed for 5 patients with LVAD implantation.nnnRESULTSnPeak WSS values were estimated on the 3 branches of the celiac trunk and the LVAD cannula. The mean WSSs demonstrated that the left gastric artery underwent the highest WSS of 9.08 ± 5.45 Pa, with an average flow velocity of 0.57 ± 0.25 m/s compared with that of other vessel districts. The common hepatic artery had a less critical WSS of 4.58 ± 1.77 Pa. A positive correlation was found between the celiac trunk angulation and the WSS stress just distal to the ostium of the celiac trunk (R = 0.9), which may increase vulnerability of this vessel to bleeding.nnnCONCLUSIONSnAlthough further studies are needed to confirm these findings in a larger patient cohort, computational flow simulations may enhance the information of clinical image data and may have an application in clinical investigations of hemodynamic changes in LVAD-supported patients.

Is diuretic withdrawal safe in patients with heart failure and reduced ejection fraction? A retrospective analysis of our outpatient cohort

Although diuretics are essential to optimize volume status in patients with heart failurewith reduced ejection fraction (HFrEF) [1], safety and benefits of prolonged diuretic treatment are uncertain, in particular on patients with chronic and compensated HFrEF. In facts, diuretics can increase the neuro-humoral activation in HFrEF [2], determine electrolyte disturbances [3] and acute renal insufficiency [4]. On the contrary, Hopper et al. identified seven studies of diuretic withdrawal (DW) in stable chronic HF, in which clinical decompensation wasmore frequent in theDWgroup [5]. Our hypothesiswas that diuretic therapy could be safely suspended in patients with HFrEF after adequate therapeutic neuro-hormonal antagonism [6]. Therefore, we retrospectively analyzed our cohort of HFrEF outpatients with a twofold aim: first, to asses if DW is safe in patients with HFrEF and second, to identify clinical, biochemical or echocardiographic parameters associated to DW among HFrEF patients regularly followed-up at our outpatients clinic. The studywas conducted in our tertiary level HF clinical center. All ambulatory patients referred from November 2011 through September 2014 at our centerwere considered for recruitment. Exclusion criteria were as follows: (I) hospitalization for HF within 30 days before ambulatory evaluation, (II) myocardial revascularization and/or resynchronization therapy within 180 days before ambulatory visit, (III) congenital heart disease, (IV) severe valve heart disease. Overall, 216 consecutive clinically stable HFrEF patients (ejection fraction HF ≤ 35%) were evaluated for retrospective enrollment. Among them, 26 patientswere excluded, since theywere not takingdiuretics. Eventually, 190 patients were recruited and stratified according to diuretics continuation: no withdrawal group (NWG), N = 169 (89%), and diuretics withdrawal group (WG) N= 21 (11%) (Fig. 1S in supplementary materials). Furosemide was the only diuretic used. Patients were assessed at baseline visit. Medical history, physical exam, 12-lead electrocardiogram and laboratory analysis comprehensive of N-terminal pro brain natriuretic peptides (NT-proBNP) and highly sensitive troponin essay were obtained. To assess the safety of DW, furosemide dose in WG was tapered down (steps of 25 mg) at each visit usually at the sixth month re-evaluation, according to the following criteria: 1) no symptomsor signs of congestionwere evident at the clinical assessment and 2) NT-proBNP trend was in downturn. A standard 2-Dimensional and Doppler transthoracic echocardiogram was performed at baseline visit and repeated in case of worsening clinical conditions. Baseline

In Silico Shear and Intramural Stresses are Linked to Aortic Valve Morphology in Dilated Ascending Aorta

OBJECTIVE/BACKGROUNDnThe development of ascending aortic dilatation in patients with bicuspid aortic valve (BAV) is highly variable, and this makes surgical decision strategies particularly challenging. The purpose of this study was to identify new predictors, other than the well established aortic size, that may help to stratify the risk of aortic dilatation in BAV patients.nnnMETHODSnUsing fluid-structure interaction analysis, both haemodynamic and structural parameters exerted on the ascending aortic wall of patients with either BAV (nxa0=xa021) or tricuspid aortic valve (TAV; nxa0=xa013) with comparable age and aortic diameter (42.7xa0±xa05.3xa0mm for BAV and 45.4xa0±xa010.0xa0mm for TAV) were compared. BAV phenotypes were stratified according to the leaflet fusion pattern and aortic shape.nnnRESULTSnSystolic wall shear stress (WSS) of BAV patients was higher than TAV patients at the sinotubular junction (6.8xa0±xa03.3xa0N/m2 for BAV and 3.9xa0±xa01.3xa0N/m2 for TAV; pxa0=xa0.006) and mid-ascending aorta (9.8xa0±xa03.3xa0N/m2 for BAV and 7.1xa0±xa02.3xa0N/m2 for TAV; pxa0=xa0.040). A statistically significant difference in BAV versus TAV was also observed for the intramural stress along the ascending aorta (e.g., 2.54xa0×xa0105xa0±xa00.32xa0×xa0105xa0N/m2 for BAV and 2.04xa0×xa0105xa0±xa00.34xa0×xa0105xa0N/m2 for TAV; pxa0<xa0.001) and pressure index (0.329xa0±xa00.107 for BAV and 0.223xa0±xa00.139 for TAV; pxa0=xa0.030). Differences in the BAV phenotypes (i.e., BAV type 1 vs. BAV type 2) and aortopathy (i.e., isolated tubular vs. aortic root dilatations) were associated with asymmetric WSS distributions in the right anterior aortic wall and right posterior aortic wall, respectively.nnnCONCLUSIONnThese findings suggest that valve mediated haemodynamic and structural parameters may be used to identify which regions of aortic wall are at greater stress and enable the development of a personalised approach for the diagnosis and management of aortic dilatation beyond traditional guidelines.

Three-dimensional parametric modeling of bicuspid aortopathy and comparison with computational flow predictions

Bicuspid aortic valve (BAV)-associated ascending aneurysmal aortopathy (namely bicuspid aortopathy) is a heterogeneous disease making surgeon predictions particularly challenging. Computational flow analysis can be used to evaluate the BAV-related hemodynamic disturbances, which likely lead to aneurysm enlargement and progression. However, the anatomic reconstruction process is time consuming so that predicting hemodynamic and structural evolution by computational modeling is unfeasible in routine clinical practice. The aim of the study was to design and develop a parametric program for three-dimensional (3D) representations of aneurysmal aorta and different BAV phenotypes starting from several measures derived by computed-tomography angiography (CTA). Assuming that wall shear stress (WSS) has an important implication on bicuspid aortopathy, computational flow analyses were then performed to estimate how different would such an important parameter be, if a parametric aortic geometry was used as compared to standard geometric reconstructions obtained by CTA scans. Morphologic parameters here documented can be used to rapidly model the aorta and any phenotypes of BAV. t-test and Bland-Altman plot demonstrated that WSS obtained by flow analysis of parametric aortic geometries was in good agreement with that obtained from the flow analysis of CTA-related geometries. The proposed program offers a rapid and automated tool for 3D anatomic representations of bicuspid aortopathy with promising application in routine clinical practice by reducing the amount of time for anatomic reconstructions.

In Vivo Strain Analysis of Dilated Ascending Thoracic Aorta by ECG-Gated CT Angiographic Imaging

Accurate assessment of aortic extensibility is a requisite first step for elucidating the pathophysiology of an ascending thoracic aortic aneurysm (ATAA). This study aimed to develop a framework for the in vivo evaluation of the full-field distribution of the aortic wall strain by imaging analysis of electrocardiographic- (ECG) gated thoracic data of 34 patients with ATAA. Seven healthy controls (i.e., non-aneurysmal aorta) from patients who underwent ECG-gated CT angiography for coronary artery diseases were included for comparison. To evaluate the systolic function, ECG-gated computed tomography (CT) angiography was used to generate patient-specific geometric meshes of the ascending aorta, and then to estimate both the displacement and strain fields using a mathematical algorithm. Results evidenced stiff behavior for the aneurysmal aorta compared with that of the healthy ascending aorta of the controls, with patients over 55xa0years of age displaying significantly lower extensibility. Moreover, the patient risk as quantified by the ratio of in vivo strain to the ruptured one increased significantly with increased systolic blood pressure, older age, and higher pressure-strain modulus. Statistical analysis also indicated that an increased pressure-strain modulus is a risk factor for ATAAs with bicuspid aortic valve, suggesting a different mechanism of failure in these patients. The approach here proposed for the in vivo evaluation of the aortic wall strain is simple and fast, with promising applicability in routine clinical imaging, and could be used to develop a rupture potential criterion on the basis of the aortic aneurysm extensibility.

Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality

Purpose: We describe an approach for anticoagulation and transfusions in veno-venous–extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, and their impact on mortality. Methods: Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO. Results: In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO [PRESERVE] score: 4, Interquartile range [IQR]: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction [RESP] score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval [CI]: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04). Conclusion: Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.

Biomechanical Determinants of Right Ventricular Failure in Pulmonary Hypertension

Pulmonary hypertension (PH) is a disease characterized by progressive adverse remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and load pressure on the right ventricle (RV), ultimately leading to RV failure. Invasive hemodynamic testing is the gold standard for diagnosing PH and guiding patient therapy. We hypothesized that lumped-parameter and biventricular finite-element (FE) modeling may lead to noninvasive predictions of both PH-related hemodynamic and biomechanical parameters that induce PH. We created patient-specific biventricular FE models that characterize the biomechanical response of the heart and coupled them with a lumped-parameter model that represents the systemic and pulmonic circulation. Simulations were calibrated by adjusting the pulmonary vascular resistance and myocardial contractility parameters through matching imaging data of ventricular chambers. Linear regression analysis demonstrated that the lumped-derived RV cardiac index (CI) was in good agreement with catheterization measurements collected from 10 patients with PH (R2 = 0.82; p < 0.001). Biventricular FE analysis revealed a paradoxical leftward shift of the interventricular septum, and this correlated with invasive measurements of pulmonary vascular resistances (R = 0.70; p = 0.048) as found by Pearson’s coefficient. A significant difference was noted for RV myocardial fiber stress in healthy control patients (4.5u2009±u20090.7 kPa) compared with that of patients with PH at either rest (30.1u2009±u200912.1 kPa; p = 0.005) or simulated exercise conditions (69.6u2009±u200924.8 kPa; p < 0.001), thus suggesting adverse RV remodeling. This approach may become a useful and versatile tool for noninvasively assessing RV impairment induced by PH and realistically predicting ventricular mechanics and interactions for an improved management of patients with PH.

Patients with bicuspid aortic valve are likely to receive an aortic valve prosthesis during prophylactic resection of their ascending aortic aneurysm

☆ All authors take responsibility for all aspects of the reli the data presented and their discussed interpretation. ⁎ Corresponding author at: Cardiac Surgery and Department for the Treatment and Study of Cardiothora Transplantation, Mediterranean Institute for Transplanta Therapies (ISMETT), Via Tricomi 5, 90127 Palermo, Italy. E-mail address: giuseppe.raffa78@gmail.com (G.M. Ra 1 Equal contribution as first author.