Early postoperative hemodynamic instability after heart transplantation - incidence and metabolic indicators.

BACKGROUND: Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study's primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon. METHODS: Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) < 60 mmHg) combined with a high inotrope score (> 10). Data for long-term mortality were obtained from the population registration office. RESULTS: PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) µg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) µg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034). CONCLUSIONS: Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients.

Stenotic Bicuspid and Tricuspid Aortic Valves　- Micro-Computed Tomography and Biological Indices of Calcification.

BACKGROUND: Valve calcification is well estimated by ex-vivo micro-computed tomography (micro-CT). The objective of this study was to investigate the associations between micro-CT findings and biological indices of calcification in aortic stenosis (AS), as well as differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).Methods and Results:Aortic valves and plasma were obtained from patients undergoing valve surgery. Valves were dissected and underwent micro-CT, genetic analyses, and calcium content assessment. Plasma levels of calcification markers were measured. Forty-two patients with isolated severe AS, including 22 with BAV, were studied. BAV patients had a lower median CT value (140.0 [130.0-152.0] vs. 157.0 [147.0-176.0], P=0.002) and high-density calcification (HDC) fraction (9.3 [5.7-23.3] % vs. 21.3 [14.3-31.2] %, P=0.01), as compared with TAV. Calcification fraction (CF) correlated with AS severity (measured as maximal transvalvular pressure gradient [r=0.34, P=0.03], maximal flow velocity [r=0.38, P=0.02], and indexed aortic valve area [r=-0.37, P=0.02]). For TAV patients only, mRNA expression of integrin-binding sialoprotein correlated with CF (r=0.45, P=0.048), and the receptor activator of the nuclear factor κ-B ligand transcript correlated with HDC corrugation (r=0.54, P=0.01). CONCLUSIONS: TAV patients with AS present more mineralized calcifications in micro-CT than BAV subjects. The relative volume of calcifications increases with the AS severity. In TAV patients, upregulated expression of genes involved in osteoblastogenesis in AS correlates with leaflet mineralization in micro-CT.

Minimally invasive direct coronary artery bypass (MIDCAB) ­ safety assessment in own material.

Introduction: Minimally invasive direct coronary artery bypass (MIDCAB) allows achieving similar safety and efficacy, with markedly reduced post-operative length of stay when compared to conventional surgical revascularization. Despite promising results, a small number of minimally invasive procedures are performed in Poland. The aim of the study is to assess short- and long-term outcome of MIDCAB revascularization in order to evaluate the safety of the procedure. Materials and Methods: Retrospective observational study analyzing 38 consecutive patients who underwent MIDCAB procedure between 2014 to 2016 in the Department of Cardiovascular Surgery and Transplantology at the John Paul II Hospital, Kraków. Perioperative data was obtained from patient medical records and the median follow-up period valued 17.3 months. Results: No postoperative deaths and only 1 case of postoperative myocardial infarction were observed. Throughout the follow-up period, the survival rate and freedom from MACCE rate valued 100%, with only 1 case of repeated revascularization. Conclusions: Minimally invasive revascularization is a safe procedure which can be performed with excellent short- and long-term outcome in low-risk patients.

Prothrombotic State in Patients With a Left Atrial Appendage Thrombus of Unknown Origin and Cerebrovascular Events.

BACKGROUND AND PURPOSE: We hypothesized that formation of left atrial appendage (LAA) thrombi of unknown origin is associated with altered fibrin clot properties and blood hypercoagulability. METHODS: In a case-control study, we investigated 32 patients with a history of LAA thrombus after successful anticoagulant treatment versus 32 control subjects matched for age, sex, and diabetes mellitus. All subjects had previous ischemic stroke, transient ischemic attack, or migraine associated with patent foramen ovale. Patients with documented atrial fibrillation were excluded. We determined plasma fibrin clot permeability, fibrinolytic efficiency, thrombin generation, platelet and endothelial markers. Stroke or transient ischemic attack were assessed during a median follow-up of 74 (range 19-98) months. RESULTS: Compared with controls, patients with LAA thrombus more frequently were smokers (43.8% versus 18.8%) and had 20% prolonged clot lysis time, lower plasminogen (-14%), and higher plasminogen activator inhibitor-1 (+17%), thrombin-antithrombin complexes (+17%), CD40 ligand (+30%), P-selectin (+29%), and von Willebrand factor (+30%, all P<0.05). Occurrence of LAA thrombus was predicted by von Willebrand factor (ß=0.038, P=0.004), plasminogen (ß=-0.048, P=0.01), plasminogen activator inhibitor-1 (ß=-0.161, P=0.03), and clot permeability (ß=-1.076, P=0.03). During follow-up, cerebrovascular events occurred in 10 (33.33%) of the 30 available patients in the LAA thrombus group, including 7 (23.3%) with recurrent LAA thrombus and 4 (13.33%) with documented atrial fibrillation. Recurrent LAA thrombus was associated with lower baseline Ks and higher thrombin generation, fibrinogen, plasminogen activator inhibitor-1, and soluble CD40 ligand (all P<0.05). CONCLUSIONS: Prothrombotic blood alterations could be involved in the LAA thrombus formation in patients without documented atrial fibrillation and are associated with increased risk of stroke or transient ischemic attack during follow-up.

Ultrasonographic caval indices do not significantly contribute to predicting fluid responsiveness immediately after coronary artery bypass grafting when compared to passive leg raising.

BACKGROUND: Appropriate fluid management is one of the most important elements of early goal-directed therapy after cardiothoracic surgery. Reliable determination of fluid responsivenss remains the fundamental issue in volume therapy. The purpose of the study was to assess the usefulness of dynamic IVC-derived parameters (collapsibility index, distensibility index) in comparison to passive leg raising, in postoperative fluid management in mechanically ventilated patients with left ventricular ejection fraction ≥ 30 %, immediately after elective coronary artery bypass grafting. METHODS: Prospective observational case series study including 35 patients with LVEF ≥ 30 %, undergoingelective coronary artery bypass grafting was conducted. Transthoracic echocardiography, passive leg raising and intravenous administration of saline were performed in all study subjects. Dynamic parameters derived from ultrasonographic assessment of the IVC diameter (collapsibility index-CI and distensibility index-DI), cardiac output RESULTS: There were 24 (68.57 %) responders in the study population. There were no statistical differences between the groups in relation to: clinical parameters, pre- and postoperative LVEF, fluid balance and CVP. Change in cardiac output after passive leg raising correlated significantly with that after the volume expansion (p=0.000, r=0.822). Dynamic IVC derivatives were slightly higher in fluid responders, however this trend did not reach statistical significance. None of the caval indices correlated with fluid responsiveness. CONCLUSION: Dynamic IVC-derived parameters do not predict fluid responsiveness in mechanically ventilated patients with preserved ejection fraction immediately after elective coronary artery bypass grafting. Passive leg raising is not inferior to volume expansion in differentiating between fluid responders and nonresponders. Immediate fluid challenge after CABG is safe and well tolerated.

Effectiveness and Validity of Sonographic Upper Airway Evaluation to Predict Difficult Laryngoscopy.

OBJECTIVES: Our objective was to evaluate the effectiveness of 9 airway sonographic parameters imaged from the submandibular view as predictors of difficult laryngoscopy. Additionally, we aimed to evaluate the validity of the models of combined sonographic and clinical tests in predicting difficult laryngoscopy. METHODS: This study analyzed a sample of 199 patients who were categorized as having easy (grades 1 and 2) or difficult (grades 3 and 4) laryngoscopy during general anesthesia with endotracheal intubation based on the laryngoscopic criteria of Cormack and Lahane (Anaesthesia 1984; 39:1105-1111). Nine sonographic parameters imaged from the submandibular view, including the hyomental distance in neutral and extended positions, hyomental distance ratio, tongue cross-sectional area, tongue width, tongue volume, tongue thickness-to-oral cavity height ratio, and floor of the mouth muscle cross-sectional area and volume, were analyzed. The validity of the models encompassing combined screening tests was assessed. RESULTS: Twenty-two patients (11.1%) were categorized as having difficult laryngoscopy. Statistically significant differences between patients with difficult and easy laryngoscopy were noted for 5 of 9 parameters. The diagnostic validity profiles showed poor sensitivity (9.1%-42.9%) and positive predictive value (4.5%-66.7%), but good specificity (71.8%-97.7%) and negative predictive value (87.1%-94.5%). The combination of tests improved the diagnostic validity profile (area under the curve, 0.852). CONCLUSIONS: Sonographic predictors may help identify patients with difficult laryngoscopy. Individual measures have unsatisfactory diagnostic profiles. The models based on combined tests have improved diagnostic value.

Feasibility and accuracy of bedside transthoracic echocardiography in diagnosis of acute proximal aortic dissection.

STUDY OBJECTIVE: The purpose of the present study was to establish the accuracy of transthoracic echocardiography (TTE) in diagnosis of acute type A aortic dissection in comparison to computed tomography (CT), with reference to the intraoperative image. METHODS: The retrospective analysis included 178 patients referred to the cardiac surgery unit in our center due to acute type A dissection between 01-01-2008 and 31-12-2013, who underwent both TTE and CT. Intraoperative image was considered as a reference. RESULTS: Statistical analysis did not show any significant differences between computed tomography and echocardiography in the detection of the proximal aortic dissection. In patients with aortic valve abnormalities, procedure of choice was replacement by a composite graft (77,59%), whereas patients with a normal image of aortic valve were more likely to have the valve sparing procedure (50,88%). The R-Spearman statistics shows a strong positive correlation between maximum diameter of ascending aorta measured by TTE and CT (cc 0.869) and TTE and intraoperative measurement (cc 0.844). CONCLUSION: Our data confirm that transthoracic echocardiography is a reliable method for diagnosis of proximal aortic dissection. TTE provides a reliable value of maximum diameter of the ascending aorta in comparison to both CT and direct intraoperative measurement. Moreover, transthoracic echocardiography gives the additional information that influences the operative technique of choice and identifies the high-risk patients (cardiac tamponade, severe aortic dilatation, severe aortic regurgitation). Our retrospective analysis confirms the pivotal role of TTE in the evaluation of the patients with suspected proximal aortic dissection in emergency room setting.

Validity of a 5-minute focused echocardiography with A-F mnemonic performed by non-echocardiographers in the management of patients with acute chest pain.

STUDY OBJECTIVE: To validate the practicality of focused echocardiography with A-F mnemonic performed by non-specialists in patients with suspected acute coronary syndrome (ACS). DESIGN: This prospective observational study was conducted in the Emergency Room within 12 months period. Study population consisted of consecutive patients with preliminary diagnosis of an ACS. The following data were analyzed: demographics, clinical condition, medical history, ECG, transthoracic echocardiography (TTE) and levels of cardiac necrotic markers. TTE was performed within the first 15 minutes after the admission by the resident on-call. TTE images were interpreted and reported with mnemonic A-F. All studies were recorded and reviewed within 24 hours by the cardiologist. RESULTS: 1312 consecutive patients were enrolled to the study. TTE with A-F mnemonic revealed: RWMAs in 82.87% patients with confirmed ACS, other significant cardiac pathologies were found in 2.21% in ACS and 46.52% in non-ACS groups respectively. On the basis of these findings, 20 (1.92%) ACS and 29 (10.62%) non-ACS group patients underwent target operative treatment. Survey showed that both echocardiographic image acquisition and its interpretation with A-F mnemonic, took less than 5 minutes in 95% of cases. Residents found A-F mnemonic algorithm simple and useful. No differences were found in key findings between TTE performed by resident and the cardiologist. CONCLUSION: Focused echocardiography with A-F mnemonic allows both confirmation of acute myocardial ischemia and detection of the other life-threatening cardiac conditions resulting in proper bedside decision of directed treatment. Mnemonic based TTE enables reliable examination by properly trained residents.

Reliability of focused cardiac ultrasound by novice sonographer in preoperative anaesthetic assessment: an observational study.

BACKGROUND: Use of preoperative echocardiography may help to identify patients with increased cardiac risk, who may benefit from modification of perioperative plan. The objective of our study was to evaluate the reliability of preoperative focused cardiac ultrasound (FoCUS) performed by an anaesthetist with basic ultrasound training and its impact on patient's management. METHODS: The prospective observational study was conducted in 159 adult patients, scheduled for elective operations. Cardiac ultrasound was performed by one anaesthetist with a limited experience of FoCUS. A simple, mnemonic scheme was used for the final reporting of each study. The same scheme was used by a cardiologist who produced an independent report based on digital video loops stored in the machine memory. Anaesthetists in-charge made final perioperative plan. Comparative analysis of anaesthetist and cardiologist performed ultrasound report was made. The incidence of modification of initial perioperative plan resulting from FoCUS report was analyzed. RESULTS: The average time required to complete the examination was 182 s 95% CI [173-190]. Images of quality adequate to answer all questions from the scheme were obtained in 97.5% (155/159) of patients. There was strong agreement between the anaesthetist and the cardiologist in 97.8% (2274/2325) of the examined categories. In two categories (global and regional left ventricle contractility impairment) statistically significant discrepancies between both diagnosticians were confirmed (p McNemar <0.04). When compared with the cardiologist's assessment the agreement of the anesthetist's diagnosis had sensitivity of 0.84, specificity 0.99, positive predictive value 0.78 and negative predictive value 0.99. Kappa statistics showed good agreement between both examining doctors (κ = 0.797). Based on ultrasound findings, the preliminary anaesthetic plan was changed in relation to 20.8% (33/159) of patients. CONCLUSIONS: An anaesthetist with limited training in FoCUS can perform a reliable preoperative examination which alters the perioperative management.

New diastolic cardiomyopathy in patients with severe accidental hypothermia after ECMO rewarming: a case-series observational study.

INTRODUCTION: Accidental hypothermia is a condition associated with significant morbidity and mortality. Hypothermia has been reported to affect left ventricular systolic and diastolic function. However, most of the data come from animal experimental studies. AIM OF THE STUDY: The purpose of the present study was to assess the impact of severe accidental hypothermia on systolic and diastolic ventricular function in patients treated using veno-arterial extracorporeal membrane oxygenation (ECMO). METHODS: We prospectively assessed nine hypothermic patients (8 male, age 25-78 years) who were transferred to the Severe Accidental Hypothermia Center and treated with ECMO. Transthoracic echocardiography was performed on admission (in patients without cardiac arrest) and on discharge from ICU after achieving cardiovascular stability. Cardiorespiratory stability and full neurologic recovery was achieved in all patients. RESULTS: Biomarkers of myocardial damage (CK, CKMB, hsTnT) were significantly elevated in all study patients. Admission echocardiography performed in patients in sinus rhythm, revealed moderate-severe bi-ventricular systolic dysfunction and moderate bi-ventricular diastolic dysfunction. Discharge echocardiography showed persistent mild bi-ventricular diastolic dysfunction, although systolic function of both ventricles returned to normal. Discharge echocardiography in patients admitted with cardiac arrest showed normal (5 patients) or moderately impaired (1 patient) global LV systolic function on discharge. However, mild or moderate LV diastolic dysfunction was observed in all 6 patients. Discharge RV systolic function was normal, whereas mild RV diastolic dysfunction was present in these patients. CONCLUSION: After severe accidental hypothermia bi-ventricular diastolic dysfunction persists despite systolic function recovery in survivors treated with ECMO.

Bedside ultrasonographic measurement of the inferior vena cava fails to predict fluid responsiveness in the first 6 hours after cardiac surgery: a prospective case series observational study.

OBJECTIVE: To assess validity of respiratory variation of inferior vena cava (IVC) diameter to predict fluid responsiveness and guide fluid therapy in mechanically ventilated patients during the first 6 hours after elective cardiac surgery. DESIGN: Prospective observational case series study. SETTING: Single-center hospital. PATIENTS: 50 consecutive patients undergoing elective cardiac surgery. INTERVENTIONS: Transthoracic bedside echocardiography. MEASUREMENTS AND MAIN RESULTS: Parameters derived from ultrasonographic assessment of the IVC diameter (collapsibility index [CI], distensibility index [DI], and IVC/aorta index). In the whole study group, change in fluid balance correlated with change in IVC maximum diameter (p = 0.034, r = 0.176). IVC-CI and IVC-DI correlated with IVC/aorta index. A weak correlation between central venous pressure (CVP) and IVC-derived parameters (IVC-CI and IVC-DI) was noticed. Despite statistical significance (p<0.05), all observed correlations expressed low statistical power (r<0.21). There were no statistically significant differences between fluid responders and nonresponders in relation to clinical parameters, CVP, ultrasound IVC measurement, and IVC-derived indices. CONCLUSION: Dynamic IVC-derived parameters (IVC-CI, IVC-DI, and IVC/aorta index) and CVP are not reliable predictors of fluid responsiveness in the first 6 hours after cardiac surgery. Complexity of physiologic factors modulating cardiac performance in this group may be responsible for the difficulty in finding a plausible monitoring tool for fluid guidance. Bedside ultrasonographic measurement of IVC is unable to predict fluid responsiveness in the first 6 hours after cardiac surgery.

PreScheck Team Study: prehabilitation clinic as an effective patient management tool in elective cardiac surgery.

INTRODUCTION: The main purpose of the study was to assess the impact of preoperative interdisciplinary assessment by the PreScheck Team on optimization of the final selection for elective cardiac surgery. MATERIAL AND METHODS: This is a single-centre prospective observational study. The examined population consisted of 933 adult patients planned for cardiac surgery. After the exclusion of urgent operations, the study group consisted of 288 patients planned for elective cardiac surgery within 3 months from 1.01.2023 with PreScheck assessment (PreScheck Team group 2) and a control group of 311 patients scheduled for elective cardiac surgery between 1.03.2022 and 30.06.2022 (4 months), without preoperative interdiscipli-nary assessment (No PreScheck Team group 2). RESULTS: Fifty-two patients (18.06%) from the study group were finally excluded from the surgery on the scheduled date. In 46 patients (88.46%) the temporary or permanent exclusion from surgery was a result of PreScheck Team assessment. In the control group 42 patients (13.5%) did not undergo surgery on the scheduled date. Twenty-seven of those patients (8.97%) were permanently excluded from cardiac surgery after admission to the hospital and required additional tests before the final clinical decision, with total hospitalization time of 146 days. CONCLUSIONS: Pre Surgery Check (PreScheck) Team is an original concept that combines classical preoperative assessment and an outpatient prehabilitation clinic. The approach we are proposing here should be a complementary stage in the process of selection for elective cardiac surgery, in addition to the Heart Team recommendation. This two-step decision-making enables real individual risk assessment, selection of the most suitable intervention and better use of medical resources.

Right ventricular-pulmonary arterial coupling in patients with implanted left ventricular assist devices.

OBJECTIVE: Both the right ventricular (RV) contractile function and pulmonary arterial (PA) pressure influence clinical outcomes in patients supported with left ventricular assist devices (LVADs), but the impact of RV-PA coupling is unknown. This study aimed to determine the prognostic impact of RV-PA coupling in patients with implanted LVADs. METHODS: Patients with implanted third-generation LVADs were retrospectively enrolled. The RV-PA coupling was assessed preoperatively by the ratio of RV free wall strain (RVFWS) derived from speckle-tracking echocardiography and noninvasively measured peak RV systolic pressure (RVSP). The primary end point was a composite of all-cause mortality or right heart failure (RHF) hospitalization. Secondary end points consisted of all-cause mortality at a 12-month follow-up and RHF hospitalization. RESULTS: A total of 103 patients were screened, and 72 with good RV myocardial imaging were included. The median age was 57 years; 67 patients (93.1%) were men, and 41 (56,9%) had dilated cardiomyopathy. A receiver-operating characteristic analysis (AUC 0.703, 51.5% sensitivity, 94.9% specificity) was used to identify the optimal cutoff point (0.28%/mmHg) for the RVFWS/TAPSE threshold. Nineteen subjects (26.4%) had advanced RV-PA uncoupling. Event rates were estimated using the Kaplan-Meier method showing a strong association with an increased risk for the primary end point of death or RHF hospitalization (89.47% vs. 30.19%, p < 0.001). A similar observation applied to all-cause mortality (47.37% vs. 13.21%, p = 0.003) and RHF hospitalization (80.43% vs. 20%, p < 0.001). CONCLUSIONS: An advanced RV dysfunction assessed by RV-PA coupling may serve as a predictor of adverse outcomes in patients with implanted LVADs.

The Role of Extracorporeal Membrane Oxygenation ECMO in Accidental Hypothermia and Rewarming in Out-of-Hospital Cardiac Arrest Patients-A Literature Review.

Accidental hypothermia, defined as an unintentional drop of the body core temperature below 35 °C, is one of the causes of cardiocirculatory instability and reversible cardiac arrest. Currently, extracorporeal life support (ECLS) rewarming is recommended as a first-line treatment for hypothermic cardiac arrest patients. The aim of the ECLS rewarming is not only rapid normalization of core temperature but also maintenance of adequate organ perfusion. Veno-arterial extracorporeal membrane oxygenation (ECMO) is a preferred technique due to its lower anticoagulation requirements and potential to prolong circulatory support. Although highly efficient, ECMO is acknowledged as an invasive treatment option, requiring experienced medical personnel and is associated with the risk of serious complications. In this review, we aimed to discuss the clinical aspects of ECMO management in severely hypothermic cardiac arrest patients.

Nutritional Risk Assessment and Adverse Events in Patients Undergoing Left Ventricular Assist Device Implantation-A Retrospective Cohort Study Using Hospital Information System.

Clinical or subclinical malnutrition occurs in 30% to 70% of patients with advanced heart failure and increases the risk of postoperative adverse events. The main objective of this study was to assess the nutritional status of patients prior to left ventricular assist device (LVAD) implantation using different methods of malnutrition assessment and to evaluate the relationship between nutritional status and postoperative adverse events. A retrospective cohort study included 120 patients aged 26-74 years referred for LVAD surgery. Preoperative nutritional status (NRS-2002-Nutritional Risk Score 2002, NRI-Nutritional Risk Index, PNI-Prognostic Nutritional Index; TLC-total lymphocyte count) and postoperative adverse events were assessed. Moderate to severe malnutrition was found in 55.8%, 43.3%, 40.0%, and 20% of all patients, respectively, according to the PNI, NRI, TLC, and NRS-2002 scores. Patients with a TLC < 1200 cells/m3 had a higher risk of postoperative acute renal failure [hazard ratio (HR): 2.5; 95% confidence interval (95% CI): 1.01-6.3] and death during the observation period [HR = 2.1; 95% CI: 1.2-3.5]. Moderate to severe malnutrition was also associated with a significantly increased risk of in-hospital death [for the NRI score, HR = 4.9 (95% CI: 1.1-22.0); for the PNI score, HR = 5.0 (95% CI: 1.1-22.3)]. In conclusion, moderate to severe malnutrition prior to LVAD implantation has been identified as a risk factor for postoperative acute renal failure and mortality. Assessment of nutritional risk may improve patient selection and early initiation of nutritional support.

Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory mediator involved in atherosclerosis. Since aortic valve stenosis (AVS) is regarded as an atherosclerosis-like inflammatory disease, we sought to investigate whether AVS is associated with elevated Lp-PLA2. METHODS: Plasma Lp-PLA2 levels were determined in 48 consecutive patients with severe AVS without atherosclerotic vascular disease and compared with the values obtained in 48 controls matched for age, sex and cardiovascular risk factors. RESULTS: Lp-PLA2 was higher in AVS than in controls (242.3±50.4 vs. 151.9±28.1 ng/mL, p<0.0001). Lp-PLA2 correlated inversely with aortic valve area (AVA) (r=-0.53; p=0.0001) and positively with mean pressure gradient (PG) (r=0.32; p=0.029). In multivariable analysis C-reactive protein (CRP) (OR=1.42; 95% CI 0.95-2.1; p=0.09) and AVA (OR=0.003; 95% CI 0.00004-0.23; p<0.01) were independently associated with Lp-PLA2 above a mean of 242 ng/mL. After adjustment for CRP, AVA was the only independent predictor of Lp-PLA2 in AVS patients (p<0.001). CONCLUSIONS: This study is the first to show that AVS is characterized by increased plasma Lp-PLA2 levels associated with the severity of AVS, which suggests active involvement of Lp-PLA2 in the pathogenesis of AVS.

Acute myocardial infarction reparation/regeneration strategy using Wharton's jelly multipotent stem cells as an 'unlimited' therapeutic agent: 3-year outcomes in a pilot cohort of the CIRCULATE-AMI trial.

Introduction: CIRCULATE-AMI (NCT03404063), a cardiac magnetic resonance imaging (cMRI) infarct size-reduction-powered double-blind randomized controlled trial (RCT) of standardized Wharton jelly multipotent stem cells (WJMSCs, CardioCell Investigational Medical Product) vs. placebo (2 : 1) transcoronary transfer on acute myocardial infarction (AMI) day ~5-7, is preceded by safety and feasibility evaluation in a pilot study cohort (CIRCULATE-AMI PSC). Aim: To evaluate WJMSC transplantation safety and evolution of left ventricular (LV) remodeling in CIRCULATE-AMI PSC. Material and methods: In 10 consecutive patients (32-65 years, peak CK-MB 533 ±89 U/l, cMRI-LVEF 40.3 ±2.7%, cMRI-infarct size 20.1 ±2.8%), 30 × 106 WJMSCs were administered using a novel cell delivery-dedicated, coronary-non-occlusive method (CIRCULATE catheter). Other treatment was guideline-based. Results: WJMSC transfer was safe and occurred in the absence of coronary (TIMI-3 in all) or myocardial (corrected TIMI frame count (cTFC) 45 ±8 vs. 44 ±9, p = 0.51) flow deterioration or troponin elevation. By 3 years, 1 patient died from a new, non-index territory AMI; there were no other major adverse cardiovascular and cerebrovascular events (MACCE) and no adverse events that might be related to WJMSCs. cMRI infarct size was reduced from 33.2 ±7.6 g to 25.5 ±6.4 g at 1 year and 23.1 ±5.6 g at 3 years (p = 0.03 vs. baseline). cMRI, SPECT, and echo showed a consistent, statistically significant increase in LVEF at 6-12 months (41.9 ±2.6% vs. 51.0 ±3.3%, 36.0 ±3.9% vs. 44.9 ±5.0%, and 38.4 ±2.5% vs. 48.0 ±2.1% respectively, p < 0.01 for all); the effect was sustained at 3 years. Conclusions: CIRCULATE-AMI PSC data suggest that WJMSC transcoronary application ~5-7 days after large AMI in humans is feasible and safe and it may be associated with a durable LVEF improvement. CIRCULATE-AMI RCT will quantify the magnitude of LV adverse remodeling attenuation with CardioCell/placebo administration.

Hemodynamic Effects of Ultrasound-Assisted, Catheter-Directed, Very Low-Dose, Short-Time Duration Thrombolysis in Acute Intermediate-High Risk Pulmonary Embolism (from the EKOS-PL Study).

Ultrasound-assisted, catheter-directed, low-dose thrombolysis (USAT) at an average alteplase dose of 20 mg infused over 12 to 24 hours reversed right ventricular disfunction and improved pulmonary hemodynamics in intermediate-high-risk pulmonary embolism patients. As bleeding risk increases with the thrombolytic dose, establishing a minimal effective USAT dosing regimen is of clinical importance. We aimed to investigate hemodynamic effects and safety of a very low-alteplase-dose USAT of 10 mg administered within 5 hours. We included 12 consecutive intermediate-high-risk pulmonary embolism patients with symptoms duration of <14 days and proximal thrombi location in pulmonary arteries. Pulmonary Embolism Response Team decision-based fixed, bilateral ultrasound-assisted alteplase infusions at the rate of 1mg/hour/catheter for 5 hours through EKOS system catheters were made. The primary efficacy measure was the change in invasive systolic and mean pulmonary arteries pressure, and in cardiac index from USAT start to termination. Safety measures were 180-day all-cause death or cardiopulmonary decompensation and bleeding complications. The systolic pulmonary arteries pressure and mean pulmonary arteries pressure decreased from 53 (45.5 to 59) to 37.5 (27.5 to 40.5) mm Hg (p = 0.02) and from 29.5 (27.5 to 32) to 21.5 (15.5 to 25) mm Hg (p = 0.02), respectively. The cardiac index increased from 1.6 (1.5 to 1.8) to 2.2 (1.9 to 2.4) l/min/m2, (p = 0.02). No deaths, decompensations, or need for therapy intensification occurred. There was 1 episode of access-site bleeding, which subsided after conservative management. No intracranial hemorrhages appeared. In conclusion, reduced dose and duration USAT improved pulmonary hemodynamics and cardiac function leading to cardiopulmonary stabilization in intermediate-high risk pulmonary embolism patients at a low periprocedural risk.