Determinants of Carotid Wall Echolucency in a Cohort of European High Cardiovascular Risk Subjects: A Cross-Sectional Analysis of IMPROVE Baseline Data.

Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima-media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM. Plaque-GSM and IM-GSM were measured in subjects from the IMPROVE study cohort (aged 54-79, 46% men) recruited in five European countries. Plaque-GSM was measured in subjects who had at least one IMTmax ≥ 1.5 mm (n = 2138), whereas IM-GSM was measured in all subjects included in the study (n = 3188). Multiple regression with internal cross-validation was used to find independent predictors of plaque-GSM and IM-GSM. Plaque-GSM determinants were plaque-size (IMTmax), and diastolic blood pressure. IM-GSM determinants were the thickness of plaque-free common carotid intima-media complex (PF CC-IMTmean), height, systolic blood pressure, waist/hip ratio, treatment with fibrates, mean corpuscular volume, treatment with alpha-2 inhibitors (sartans), educational level, and creatinine. Latitude, and pack-yearscode were determinants of both plaque-GSM and IM-GSM. The overall models explain 12.0% of plaque-GSM variability and 19.7% of IM-GSM variability. A significant correlation (r = 0.51) was found between plaque-GSM and IM-GSM. Our results indicate that IM-GSM is a weighty risk marker alternative to plaque-GSM, offering the advantage of being readily measurable in all subjects, including those in the early phases of atherosclerosis where plaque occurrence is relatively infrequent.

See It Best: A Propensity-Matched Analysis of Ultrasound-Guided versus Blind Femoral Artery Puncture in Balloon-Expandable TAVI.

Background: Currently, transcatheter aortic valve implantation (TAVI) is the standard procedure recommended for patients over 75 years of age with symptomatic aortic valve stenosis. Percutaneous transfemoral (TF) access is the main route used to perform the procedure. Among periprocedural complications, access-related ones are the most frequent, potentially leading to prolonged in-hospital stays and transfusions. Methods: We performed a retrospective analysis of prospectively collected data on consecutive patients undergoing TF-TAVI with the latest generation balloon-expandable transcatheter valve between 2013 and 2022. Results: A total of 600 patients were analyzed, differentiating the population between ultrasound-guided and blind common femoral artery puncture. Valve Academic Research Consortium 3 (VARC-3)criteria were used to report at 30 days and follow-up. In our propensity-matched comparison of the two groups, we found a strong reduction in access-related complications in the echo-guided group, particularly in terms of reduction of major and minor bleedings. We also found a significant trend in reduction of local complications, such as pseudoaneurysms, hematomas, arterio-venous fistulas, dissection of the femoral or iliac arteries, and stenosis. Conclusions: Although there is a lack of consensus on the role of ultrasound-guided puncture, we found better outcomes for patients having an echo-guided puncture of the main access, particularly with regard to access-related complications, early mobilization, and early discharge home.

The heart-mind relationship in women cardiovascular primary prevention: the role of depression, anxiety, distress and Type-D personality in the 10-years cardiovascular risk evaluation.

Introduction: Cardiovascular diseases are the leading cause of death among women. Prevention programmes underscore the need to address women-specific risk factors. Additionally, mental well-being is a significant aspect to consider when grappling with cardiovascular disease in women, particularly depression, anxiety, distress, and personality traits. This study aimed to create "at-risk" psychological profiles for women without prior cardiovascular disease history and to evaluate the association between anxiety, depression, distress, and Type-D personality traits with increased cardiovascular risk over 10 years. Methods: 219 women voluntarily participated in the "Monzino Women's Heart Centre" project for primary prevention and early diagnosis of cardiovascular diseases. Psychological profiles were developed utilising cluster analysis. Results: The primary finding indicating that belonging to the "at-risk" psychological cluster was associated with a surge in the 10-year cardiovascular risk prediction score, despite the number of comorbid risk factors (Psychological "at-risk" cluster: ß = .0674; p = .006; Risk factors: ß = .0199; p = .242). Conclusions: This finding suggests that psychological well-being of women should be assessed from the very beginning of cardiovascular prevention programmes.

Non-stenotic fibro-calcific aortic valve as a predictor of myocardial infarction recurrence.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk. OBJECTIVES: To stratify subgroups of AMI patients with specific probabilities of recurrent AMI and to evaluate the importance of AVSc in this setting. METHODS: Consecutive AMI patients (n = 2530) were admitted at Centro Cardiologico Monzino (2010-2019) and followed up for 5 years. Patients were divided into study (n = 1070) and test (n = 966) cohorts. Topological data analysis (TDA) was used to stratify patient subgroups, while Kaplan-Meier and Cox regressions analyses were used to evaluate the significance of baseline characteristics. RESULTS: TDA identified 11 subgroups of AMI patients with specific baseline characteristics. Two subgroups showed the highest rate of reinfarction after 5 years from the indexed AMI with a combined hazard ratio (HR) of 3.8 (95%CI: 2.7-5.4) compared to the other subgroups. This was confirmed in the test cohort (HR = 3.1; 95%CI: 2.2-4.3). These two subgroups were mostly men, with hypertension and dyslipidemia, who exhibit higher prevalence of AVSc, higher levels of high-sensitive c-reactive protein and creatinine. In the year-by-year analysis, AVSc, adjusted for all confounders, showed an independent association with the increased risk of reinfarction (odds ratio of ∼2 at all time-points), in both the study and the test cohorts (all p < 0.01). CONCLUSIONS: AVSc is a crucial variable for identifying AMI patients at high risk of recurrent AMI and its presence should be considered when assessing the management of AMI patients. The inclusion of AVSc in risk stratification models may improve the accuracy of predicting the likelihood of recurrent AMI, leading to more personalized treatment decisions.

We wanted to understand the factors that make some acute myocardial infarction (AMI) patients more likely to experience recurrent infarction after leaving the hospital. Specifically, we asked whether a heart valve condition called non-stenotic aortic valve fibro-calcific remodeling (AVSc) could be a crucial factor. Our study used advanced data analysis techniques, including topological data analysis (TDA), to explore this question. We unveil that AVSc is indeed a significant predictor of recurrent infarction in AMI patients. Our findings suggest that the presence of aortic valve remodeling should be taken into account when assessing the risk of recurrent AMI and managing these patients.

Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Taking a walk on the heart failure side: comparison of metabolic variables during walking and maximal exertion.

AIMS: Although cardiopulmonary exercise testing (CPET) is the gold standard to assess exercise capacity, simpler tests (i.e., 6-min walk test, 6MWT) are also commonly used. The aim of this study was to evaluate the relationship between cardiorespiratory parameters during CPET and 6MWT in a large, multicentre, heterogeneous population. METHODS: We included athletes, healthy subjects, and heart failure (HF) patients of different severity, including left ventricular assist device (LVAD) carriers, who underwent both CPET and 6MWT with oxygen consumption measurement. RESULTS: We enrolled 186 subjects (16 athletes, 40 healthy, 115 non-LVAD HF patients, and 15 LVAD carriers). CPET-peakV̇O2 was 41.0 [35.0-45.8], 26.2 [23.1-31.0], 12.8 [11.1-15.3], and 15.2 [13.6-15.6] ml/Kg/min in athletes, healthy, HF patients, and LVAD carriers, respectively (P < 0.001). During 6MWT they used 63.5 [56.3-76.8], 72.0 [57.8-81.0], 95.5 [80.3-109], and 95.0 [92.0-99.0] % of their peakV̇O2, respectively. None of the athletes, 1 healthy (2.5%), 30 HF patients (26.1%), and 1 LVAD carrier (6.7%), reached a 6MWT-V̇O2 higher than their CPET-peakV̇O2. Both 6MWT-V̇O2 and walked distance were significantly associated with CPET-peakV̇O2 in the whole population (R2 = 0.637 and R2 = 0.533, P ≤ 0.001) but not in the sub-groups. This was confirmed after adjustment for groups. CONCLUSIONS: The 6MWT can be a maximal effort especially in most severe HF patients and suggest that, in absence of prognostic studies related to 6MWT metabolic values, CPET should remain the first method of choice in the functional assessment of patients with HF as well as in sport medicine.

Leukocyte cell population data as potential markers of COVID-19 disease characterization.

Background: The usefulness of leukocyte cell population data (CPD) is currently being investigated. In COVID-19 pandemic several reports showed the clinical importance of hematological parameters. Our study aimed to assess CPDs in Sars CoV-2 patients as new disease markers. Methods: From February to April 2020 (1st wave) 540 and from September to December 2020 (2nd wave) 2821 patients respectively were enrolled. SARS CoV-2 infection diagnosis was carried out by Multiplex rRT-PCR from nasopharyngeal swabs. CPDs were detected by XN 2000 hematology analyzer (Sysmex Corporation). A comparison between two disease waves was performed. Additionally, C-reactive protein (CRP) and lactate dehydrogenase (LDH) were assayed. Results: CPDs were classified into: cell complextity, DNA/RNA content and abnormal sized cells. We detected parameters increased from the reference population for all cell types for both 1st and 2nd wave (p<0.05). However, in the 2nd vs 1st wave 5 CPDs vs 9 CPDs were found. In addition we observed higher CPD values of the 1st compared to 2nd wave: (NE-SFL) (p<0.001), (LY-Y) (p<0.0001), (LY-Z) (p<0.0001), (MO-X) (p<0.0001), (MO-Y) (p<0.0001). These findings were confirmed by the higher concentrations of CRP and LDH in the 1st vs 2nd wave: 17.3 mg/L (8.5-59.3) vs 6.3 mg/L (2.3-17.6) (p<0.001) and 241.5 IU/L (201-345) vs 195 IU/L (174-228) (p< 0.001) (median, interquartile range) respectively. Conclusions: CPDs showed increased cell activation in 1st wave patients confirmed by clinical and biochemical data, associated with worse clinical conditions. Results highlighted the CPDs as disease characterization markers or useful for a risk model.

Circulating Small Extracellular Vesicles Reflect the Severity of Myocardial Damage in STEMI Patients.

Circulating small extracellular vesicles (sEVs) contribute to inflammation, coagulation and vascular injury, and have great potential as diagnostic markers of disease. The ability of sEVs to reflect myocardial damage assessed by Cardiac Magnetic Resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) is unknown. To fill this gap, plasma sEVs were isolated from 42 STEMI patients treated by primary percutaneous coronary intervention (pPCI) and evaluated by CMR between days 3 and 6. Nanoparticle tracking analysis showed that sEVs were greater in patients with anterior STEMI (p = 0.0001), with the culprit lesion located in LAD (p = 0.045), and in those who underwent late revascularization (p = 0.038). A smaller sEV size was observed in patients with a low myocardial salvage index (MSI, p = 0.014). Patients with microvascular obstruction (MVO) had smaller sEVs (p < 0.002) and lower expression of the platelet marker CD41-CD61 (p = 0.039). sEV size and CD41-CD61 expression were independent predictors of MVO/MSI (OR [95% CI]: 0.93 [0.87-0.98] and 0.04 [0-0.61], respectively). In conclusion, we provide evidence that the CD41-CD61 expression in sEVs reflects the CMR-assessed ischemic damage after STEMI. This finding paves the way for the development of a new strategy for the timely identification of high-risk patients and their treatment optimization.

The cardiopulmonary exercise test in the prognostic evaluation of patients with heart failure and cardiomyopathies: the long history of making a one-size-fits-all suit.

Cardiopulmonary exercise test (CPET) has become pivotal in the functional evaluation of patients with chronic heart failure (HF), supplying a holistic evaluation both in terms of exercise impairment degree and possible underlying mechanisms. Conversely, there is growing interest in investigating possible multiparametric approaches in order to improve the overall HF risk stratification. In such a context, in 2013, a group of 13 Italian centres skilled in HF management and CPET analysis built the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score, based on the dynamic assessment of HF patients and on some other instrumental and laboratory parameters. Subsequently, the MECKI score, initially developed on a cohort of 2716 HF patients, has been extensively validated as well as challenged with the other multiparametric scores, achieving optimal results. Meanwhile, the MECKI score research group has grown over time, involving up to now a total of 27 centres with an available database accounting for nearly 8000 HF patients. This exciting joint effort from multiple HF Italian centres allowed to investigate different HF research field in order to deepen the mechanisms underlying HF, to improve the ability to identify patients at the highest risk as well as to analyse particular HF categories. Most recently, some of the participants of the MECKI score group started to join the forces in investigating a possible additive role of CPET assessment in the cardiomyopathy setting too. The present study tells the ten-year history of the MECKI score presenting the most important results achieved as well as those projects in the pipeline, this exciting journey being far to be concluded.

Physiology of exercise and heart failure treatments: cardiopulmonary exercise testing as a tool for choosing the optimal therapeutic strategy.

In the last decades, the pharmacological treatment of heart failure (HF) become more complex due to the availability of new highly effective drugs. Although the cardiovascular effects of HF therapies have been extensively described, less known are their effects on cardiopulmonary function considered as a whole, both at rest and in response to exercise. This is a 'holistic' approach to disease treatment that can be accurately evaluated by a cardiopulmonary exercise test. The aim of this paper is to assess the main differences in the effects of different drugs [angiotensin-converting enzyme (ACE)-inhibitors, Angiotensin II receptor blockers, ß-blockers, Angiotensin receptor-neprilysin inhibitors, renal sodium-glucose co-transporter 2 inhibitors, iron supplementation] on cardiopulmonary function in patients with HF, both at rest and during exercise, and to understand how these differences can be taken into account when choosing the most appropriate treatment protocol for each individual patient leading to a precision medicine approach.

Activities of daily living in heart failure patients and healthy subjects: when the cardiopulmonary assessment goes beyond traditional exercise test protocols.

Heart failure (HF) patients traditionally report dyspnoea as their main symptom. Although the cardiopulmonary exercise test (CPET) and 6 min walking test are the standardized tools in assessing functional capacity, neither cycle ergometers nor treadmill maximal efforts do fully represent the actual HF patients' everyday activities [activities of daily living (ADLs)] (i.e. climbing the stairs). New-generation portable metabolimeters allow the clinician to measure task-related oxygen intake (VO2) in different scenarios and exercise protocols. In the last years, we have made considerable progress in understanding the ventilatory and metabolic behaviours of HF patients and healthy subjects during tasks aimed to reproduce ADLs. In this paper, we describe the most recent findings in the field, with special attention to the relationship between the metabolic variables obtained during ADLs and CPET parameters (i.e. peak VO2), demonstrating, for example, how exercises traditionally thought to be undemanding, such as a walk, instead represent supramaximal efforts, particularly for subjects with advanced HF and/or artificial heart (left ventricular assist devices) wearers.

This article summarizes the most recent evidence on the cardiometabolic behaviours of a full spectrum of heart failure (HF) patients of different severity during their daily life activities (i.e. walking, making a bed, and taking the stairs).Heart failure patients experience symptoms (mostly dyspnoea) during daily activities that sometimes represent maximal or supramaximal exercises for them, particularly for the most severe patients.Measuring metabolic parameters (O2 intake, ventilation, and CO2 production) through appropriate devices during these activities provides a better understanding of the pathophysiological mechanisms underlying HF patients' symptoms and their adaptation. This can lead to the detection of new parameters that can become novel patient-centred prognostic markers or therapeutic targets for drugs and rehabilitation treatments.

Prognostic Impact of Percutaneous Coronary Intervention in Older Patients Hospitalized with Acute Myocardial Infarction: Real-World Findings from the Lombardy Health Database.

BACKGROUND: Older patients are less likely to receive percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) compared to younger patients. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003-2018 by using the administrative Lombardy Health Database (Italy). METHODS: We considered all patients aged ≥75 years hospitalized with AMI (either STEMI or NSTEMI) from 2003 to 2018 in Lombardy. Patients were grouped according to whether they were treated or not with PCI during the index hospitalization. The primary outcome was in-hospital mortality. The secondary endpoints were 1-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI. RESULTS: 116,063 patients aged ≥75 years (mean age 83 ± 6; 48% males; 46% STEMI) were hospitalized with a primary diagnosis of AMI. Thirty-seven percent of them (n = 42,912) underwent PCI. The in-hospital mortality rate was significantly lower in PCI-treated patients (6% vs. 15%; p < 0.0001). One-year mortality and 1-year re-hospitalization for AHF/AMI were less frequent in PCI-treated patients (16% vs. 41% and 15% vs. 21%, respectively; p < 0.0001). The adjusted risks of the study endpoints were lower in PCI-treated patients: OR 0.37 (95% CI 0.36-0.39) for in-hospital mortality; HR 0.37 (95% CI 0.36-0.38) for 1-year mortality; HR 0.74 (95% CI 0.71-0.77) for 1-year re-hospitalization for AHF/AMI. Similar results were found in STEMI and NSTEMI patients considered separately. CONCLUSIONS: Our real-world data showed that in patients with AMI ≥ 75 years of age, PCI use is associated with lower in-hospital and 1-year mortality.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Looking into the Kinetics of NT-proBNP and sST2 Changes in Patients with Heart Failure Treated with Sacubitril/Valsartan: A Hint to Different Therapeutic Pathways.

BACKGROUND AND OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble interleukin 1 receptor-like 1 ST2 (sST2) are biomarkers used to grade heart failure with reduced ejection fraction (HFrEF) severity. Both are potential targets of HFrEF treatment, but the first is associated with the patient's hemodynamic status, while the second is more indicative of the inflammatory status and of myocardial fibrosis. The aim of this study was to assess the kinetics of these biomarkers after treatment with sacubitril/valsartan in HFrEF. METHODS: We analyzed blood samples of patients with HFrEF at baseline (before sacubitril/valsartan treatment), after 1, 2, and 3 months (respectively, after a month taking the 24/26 - 49/51 - 97/103 mg twice daily, or b.i.d., doses), and 6 months after the maximum-tolerated dose was reached (end study). RESULTS: We obtained samples from 72 patients with HFrEF (age 64.0 ± 10.5 years, 83% males). NT-proBNP and sST2 values progressively and significantly reduced to 37% and 16%, respectively, with a greater reduction for NT-proBNP (p < 0.001). Specifically, NT-proBNP reduced from 1144 [593-2586] pg/mL to 743 [358-1524] pg/mL and sST2 from 27.3 [20.5-35.0] ng/mL to 23.1 [15.9-30.7] ng/mL, p for trend < 0.001 in both cases. The reduction of the two biomarkers over time occurred with statistically significant different kinetics: deferred for sST2 and faster for NT-proBNP. No significant changes in renal function and potassium levels were recorded. CONCLUSION: These findings suggest that, in patients with HF, sacubitril/valsartan effects on the cardiovascular system share a double pathway: a first, hemodynamic, faster pathway and a second, non-hemodynamic anti-fibrotic, delayed one. Both likely contribute to the sacubitril/valsartan benefits in HFrEF.

Does the AVNeo valve reduce wall stress on the aortic wall? A cardiac magnetic resonance analysis with 4D-flow for the evaluation of aortic valve replacement with the Ozaki technique.

OBJECTIVES: Aortic valve neocuspidalization aims to replace the 3 aortic cusps with autologous pericardium pre-treated with glutaraldehyde, and it is a surgical alternative to the classical aortic valve replacement (AVR). Image-based patient-specific computational fluid dynamics allows the derivation of shear stress on the aortic wall [wall shear stress (WSS)]. Previous studies support a potential link between increased WSS and histological alterations of the aortic wall. The aim of this study is to compare the WSS of the ascending aorta in patients undergoing aortic valve neocuspidalization versus AVR with biological prostheses. METHODS: This is a prospective nonrandomized clinical trial. Each patient underwent a 4D-flow cardiac magnetic resonance scan after surgery, which informed patient-specific computational fluid dynamics models to evaluate WSS at the ascending aortic wall. The adjusted variables were calculated by summing the residuals obtained from a multivariate linear model (with ejection fraction and left ventricle outflow tract-aorta angle as covariates) to the mean of the variables. RESULTS: Ten patients treated with aortic valve neocuspidalization were enrolled and compared with 10 AVR patients. The aortic valve neocuspidalization group showed a significantly lower WSS in the outer curvature segments of the proximal and distal ascending aorta as compared to AVR patients (P = 0.0179 and 0.0412, respectively). WSS levels remained significantly lower along the outer curvature of the proximal aorta in the aortic valve neocuspidalization population, even after adjusting the WSS for the ejection fraction and the left ventricle outflow tract-aorta angle [2.44 Pa (2.17-3.01) vs 1.94 Pa (1.72-2.01), P = 0.02]. CONCLUSIONS: Aortic valve neocuspidalization hemodynamical features are potentially associated with a lower WSS in the ascending aorta as compared to commercially available bioprosthetic valves.

Hemostatic system in Takotsubo patients at long-term follow-up: A hidden activation?

BACKGROUND: Takotsubo cardiomyopathy (TTS) has long been considered a benign condition, despite recurrent events and long-term adverse outcomes are often reported. Endothelial damage, blood hyperviscosity, and platelet activation described in acute phase persist in long-term follow-up; however, TTS pathophysiology is still not fully understood. Here, we explored the hemostatic system at a median of 3.1 years after TTS to uncover additional long-lasting changes in these patients. METHODS: We assessed hemostatic parameters in women with TTS (n = 23) or coronary artery disease (CAD; n = 31) and in control women (n = 26) age-matched, by thromboelastographic analysis, prothrombin time (PT) and partial thromboplastin time (aPTT) coagulation assays and microparticle exposing Tissue Factor (MP-TF). Functional fibrinogen and fibrin polymerization were analyzed by Clauss method and spectrophotometry, respectively. Platelet reactivity was evaluated by light transmission aggregometry, whereas plasminogen activator inhibitor-1 (PAI-1) and brain-derived neurotrophic factor (BDNF) were measured by ELISA kit. RESULTS: Compared with control subjects, TTS patients exhibit an accelerated clot formation, higher percentage of fibrin polymerization and higher PAI-1 levels. Compared with CAD, TTS patients showed sustained residual platelet activation but decreased functional fibrinogen, fibrin polymerization and MP-TF levels, prolonged aPTT and a marked BDNF increase. CONCLUSIONS: The long-term activation of hemostatic system observed in TTS patients compared to control subjects suggests a persistent humoral abnormality that may be related to the propensity for TTS recurrence. The higher residual platelet activity observed in TTS than in CAD patients invites investigation on TTS-tailored antiplatelet therapy potentially needed to prevent TTS adverse outcomes.

Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y12 and Link to Residual Platelet Reactivity.

BACKGROUND: ADP-induced platelet activation leads to cell surface expression of several proteins, including TF (tissue factor). The role of ADP receptors in platelet TF modulation is still unknown. We aimed to assess the (1) involvement of P2Y1 and P2Y12 receptors in ADP-induced TF exposure; (2) modulation of TFpos-platelets in anti-P2Y12-treated patients with coronary artery disease. Based on the obtained results, we revisited the intracellular localization of TF in platelets. METHODS: The effects of P2Y1 or P2Y12 antagonists on ADP-induced TF expression and activity were analyzed in vitro by flow cytometry and thrombin generation assay in blood from healthy subjects, P2Y12-/-, and patients with gray platelet syndrome. Ex vivo, P2Y12 inhibition of TF expression by clopidogrel/prasugrel/ticagrelor, assessed by VASP (vasodilator-stimulated phosphoprotein) platelet reactivity index, was investigated in coronary artery disease (n=238). Inhibition of open canalicular system externalization and electron microscopy (TEM) were used for TF localization. RESULTS: In blood from healthy subjects, stimulated in vitro by ADP, the percentage of TFpos-platelets (17.3±5.5%) was significantly reduced in a concentration-dependent manner by P2Y12 inhibition only (-81.7±9.5% with 100 nM AR-C69931MX). In coronary artery disease, inhibition of P2Y12 is paralleled by reduction of ADP-induced platelet TF expression (VASP platelet reactivity index: 17.9±11%, 20.9±11.3%, 40.3±13%; TFpos-platelets: 10.5±4.8%, 9.8±5.9%, 13.6±6.3%, in prasugrel/ticagrelor/clopidogrel-treated patients, respectively). Despite this, 15% of clopidogrel good responders had a level of TFpos-platelets similar to the poor-responder group. Indeed, a stronger P2Y12 inhibition (130-fold) is required to inhibit TF than VASP. Thus, a VASP platelet reactivity index <20% (as in prasugrel/ticagrelor-treated patients) identifies patients with TFpos-platelets <20% (92% sensitivity). Finally, colchicine impaired in vitro ADP-induced TF expression but not α-granule release, suggesting that TF is open canalicular system stored as confirmed by TEM and platelet analysis of patients with gray platelet syndrome. CONCLUSIONS: Data show that TF expression is regulated by P2Y12 and not P2Y1; P2Y12 antagonists downregulate the percentage of TFpos-platelets. In clopidogrel good-responder patients, assessment of TFpos-platelets highlights those with residual platelet reactivity. TF is stored in open canalicular system, and its membrane exposure upon activation is prevented by colchicine.

[A&F: obstacles to implementing interventions in the health system.] / A&F: gli ostacoli nell'implementare interventi nel sistema sanitario.

Understanding how well a clinician or health care team is performing provides an essential foundation for improvement. If done well, Audit and Feedback (A&F) provides data in non-judgemental, motivating insights and leads to changes in clinical processes that benefit patients. This article will explore obstacles to optimizing the potential positive effects of A&F to improve patient care and outcomes by examining three interrelated steps in the process: the audit; the feedback; and the action. The audit requires data that will be perceived as both valid and actionable. Acquiring and using such data properly often requires partnerships. Feedback recipients need to know how to turn data into action. The A&F, therefore, should include components that direct the recipient toward feasible next steps to undertake the change that will lead to improvement. The proposed actions may be individual (learning new diagnostic or therapeutic strategies, trying a more patient-centered approach, etc.) or organizational (more proactive approaches often including the involvement of additional team members). The ability to turn feedback into action will depend on the culture of the recipient-group, and its level of experience with these change processes. Feedback facilitation or coaching may be useful for some groups or certain kinds of desired changes in practice. Inadequate leadership and support for health professionals, as they try to respond to A&F, is also often a barrier. Finally, with the final focus on the challenges of the individual Work Packages (WP) within the Easy-Net network program, the article focuses on what were the facilitating and hindering factors, the obstacles encountered, and the resistance to change overcome, useful considerations in support of the increasingly widespread implementation of A&F activities in our Healthcare System in the future.

Pre-TAVI aortic annulus sizing: comparison between manual and semi-automated new generation software measurements in operators with different experience.

OBJECTIVES: Aim of the study is to compare manual and semi-automatic measurements for aortic annulus assessment among different operators. METHODS: Eighty patients who underwent TAVI were retrospectively enrolled. The measurements manually performed by an experienced reader for aortic annulus (minimum and maximum diameters, perimeter, area), annulus-to-coronary ostia distance and time needed for the whole evaluation, were collected. The same operator (observer 1) and two less experienced readers (observer 2 and 3, with >5 years and 1 year of experience, respectively) assessed the same measurements using a semi-automatic software. Differences between manual and semi-automatic measurements, reading time and suggested valves size derived by CT were compared. RESULTS: Very good correlations were found between manual and software-aided measurements for aortic annulus area and perimeter in comparison with standard measurements for the three readers (ICC range 0.81-0.98). Good correlations were found for the distance with coronary ostia(0.75-0.79). The same area-derived prosthesis size for manual and semi-automatic measurements was selected in 96% of cases for observer 1; very good correlations were also found for observer 2 and 3 (ICC = 0.89 and 0.88, respectively). Using semi-automatic measurements, the mean time needed for CT images was significantly lower for observers 1 and 2 (1.50 and 1.72versus 3.14 min), respectively. CONCLUSIONS: Pre-TAVI CT using semi-automatic software allows accurate and reproducible measurements, reducing reconstruction time up to 50% and is reliable even for operators with different experience. ADVANCES IN KNOWLEDGE: The use of semi-automatic dedicated software for CT in TAVI planning is reliable even for operators without long time experience and allows accurate and reproducible measurements improving pre-TAVI workflow.