Fisiopatologia del danno da riperfusione nell'infarto miocardico acuto: strategie farmacologiche e interventistiche per la sua prevenzione

L’infarto acuto rappresenta la prima causa di morte nei paesi industrializzati. La strategia terapeutica di scelta è rappresentata in acuto dalla terapia riperfusiva, da effettuarsi tramite angioplastica o fibrinolisi. La riperfusione tuttavia determina anche una serie di effetti a livello cellulare che comportano un danneggiamento dei miociti, determinando quello che viene chiamato “danno da riperfusione”. La manifestazione più importante di questo danno è il “fenomeno del no-reflow”, ovvero il mancato ripristino di flusso dopo riapertura della coronaria, che è responsabile di un minor recupero funzionale del miocardio e quindi di un aggravamento del danno causato dall’infarto. Data la rapidità con cui si instaura questo fenomeno e la irreversibilità del danneggiamento cellulare, appare più opportuno cercare di prevenire questo fenomeno piuttosto che curarlo. Le strategie per cercare di minimizzare questo fenomeno sono varie, sia di tipo interventistico che farmacologico. Negli ultimi anni alcuni studi hanno messo in evidenza i benefici del postcondizionamento, ovvero di una serie di brevi sequenze ischemia/riperfusione effettuate subito dopo la riapertura del vaso tramite PCI. L’altra strategia molto sperimentata è quella farmacologica, tramite somministrazione di adenosina. Le ultime evidenze sottolineano come, mentre la somministrazione intravenosa non determina un miglioramento dell’outcome clinico del paziente, la somministrazione intracoronarica in infusione è efficace nel ridurre l’area infartuata e migliorare il recupero funzionale del paziente. Lo studio qui proposto, denominato OSCAR, partendo da queste evidenze si propone di confermare la validità delle due tecniche sopra descritte e confrontarle tra di loro per evidenziare un eventuale vantaggio di una delle due

Bicuspid Valve Sizing for Transcatheter Aortic Valve Implantation: The Missing Link

Transcatheter aortic valve implantation (TAVI) is a well-recognized and established therapy for severe aortic stenosis, with expanding indications toward younger patients with low surgical risk profile. As bicuspid aortic valve (BAV) affects ~1-2% of the population, it may be speculated that an increasing number of patients with degenerated BAV may eventually need TAVI during the course of the disease. On the other hand, BAV represents a challenge due to its peculiar anatomical features and the lack of consensus on the optimal sizing strategy. The aim of this paper is to review the peculiar aspects of BAV and to discuss and compare the currently available sizing methods. Special attention is given to the role of pre-procedural imaging, mostly with multislice computed tomography, and to the aspects that operators should evaluate in order to ensure an optimal procedural planning and avoid procedural-related complications

Valutazione a lungo termine dei pazienti trattati mediante impianto di scaffold riassorbibile

Le malattie cardiovascolari rappresentano la prima causa di mortalità nei paesi industrializzati, e tra queste la cardiopatia ischemica è la patologia più rappresentata. Attualmente il gold standard del trattamento sia in acuto che in cronico è rappresentato dall’angioplastica coronarica con impianto di stents. Gli stents hanno conosciuto una rapida evoluzione tecnologica nel corso degli anni, passando dai primi modelli costituiti da una semplice rete metallica, ai più evoluti stents medicati a rilascio di farmaco o ai recentissimi stents con polimero riassorbibile. Tuttavia la struttura metallica è sempre stata presente in tutte le generazioni di dispositivi. Questo predispone a quello che è l’aspetto debole dell’angioplastica coronarica, ovvero il rischio di trombosi tardiva dello stent, rischio che è progressivo e permane per tutta la vita del paziente. Per ovviare a questo ed ad altri inconvenienti legati alla permanenza di un corpo estraneo all’interno dell’organismo, sono stati sviluppati dei dispositivi completamente riassorbibili, che hanno la capacità di sostenere il vaso nelle fasi successive all’angioplastica, rilasciare il farmaco e poi, in un tempo variabile, scomparire completamente, annullando di fatto il rischio di trombosi tardiva. Questi dispositivi, che sono già stati testati su alcune migliaia di pazienti, hanno mostrato ottimi risultati sia a breve che a lungo termine. Come tutte le nuove tecnologie tuttavia, i primi studi tendono a includere paziente altamente selezionati, per esempio escludendo i pazienti con sindrome coronarica acuta nel caso degli stent riasssorbibili (BVS). Scopo di questo studio è quindi di valutare l’efficacia in acuto e a lungo termine dell’impianto di BVS in una popolazione “all-comers” afferente al laboratorio di emodinamica, e in particolare di valutare l’efficacia clinica e strumentale ad un follow up di 1 e 2 anni

Multislice computed tomography SYNTAX score for coronary artery disease evaluation prior to transcatheter aortic valve implantation

Background: Coronary computed tomography angiography (CCTA) is a useful tool for the evaluation of coronary anatomy prior to both surgical and transcatheter aortic valve implantation (TAVI). Multislice Computed Tomography (MSCT) SYNTAX score (SXscore) strongly correlates with the traditional angiographic SXscore, and the latter has proven to predict cardiovascular events in patients with coronary artery disease (CAD) referred to TAVI. Purpose: The aim of the study is to evaluate the feasibility and accuracy of the calculation of MSCT SXscore in TAVI patients, compared to the gold standard angiographic SXscore. Materials and methods: We evaluated 65 patients eligible for TAVI who underwent both CCTA and invasive coronary angiography (ICA) prior to valve replacement. CCTA was compared to ICA in terms of sensitivity, specificity, and positive and negative predictive values. CCTA performance was evaluated at 3 levels: patient level, vessellevel and segmentlevel. MSCT SXscore was calculated, when possible (i.e. only in fullyevaluable scans), and compared to the angiographic SXscore. Results: Overall CCTA diagnostic performance was good, with high sensitivity and negative predictive values (97.2% and 96.0%, respectively) and good agreement with ICA (k=0.81). As expected, specificity and positive predictive values were lower (82.8% and 87.5%, respectively). At vessellevel, the circumflex artery (CA) was more often misdiagnosed than the other arteries. We were able to calculate MSCT SXscore in 50/65 scans (76.9%). The correlation between MSCT and angiographic SXscore was excellent (Pearson's R=0.965, P<0.001). Conclusions: MSCT SXscore emerges as an interesting tool with strong agreement with angiographic SXscore, providing a noninvasive ambulatory alternative to assess CAD severity in TAVI patients

Evaluation of a Novel Method Using Computed Tomography to Predict New Onset of Atrial Fibrillation or Embolic Events after Transcatheter Aortic Valve Implantation: the Role of Hounsfield Unit Density Ratio in the Left Atrial Appendage

Backgrounds: Evaluation of left atrial appendage (LAA) with angio-computed tomography (CCTA) in order to predict new onset of atrial fibrillation (AF) or embolic events is a new upcoming topic. No previous reported studies are available in patients undergoing transcatheter aortic valve implantation (TAVI). Methods: We analyzed pre-procedural CCTA scans of 325 patients who underwent TAVI performing a linear coefficient of attenuation analyses with Hounsfield units (HU) in LAA. HU in LAA distal and proximal was calculated, as well as the ratio. A sensibility and specificity analyses was conducted in order to identify the optimal cutoff to predict new onset AF or embolic events after TAVI. Results: Patients were divided into 4 groups according to the presence of AF. Baseline clinical and echocardiographic features were similar except for a significantly higher STS score and mitral regurgitation severity in PRE-TAVI AF group (p=0.003 and p=0.002 respectively). HU analyses showed a statistical difference in measure performed in LAA distal and in the HU LAA distal/Proximal ratio, with the lowest value in patients with pre-TAVI AF (p<0.001 and p<0.001 respectively). The ROC analyses found 0.84 as the cut-off for to predict the composite endpoint of new AF or embolic events, with sensitivity of 51% and specificity of 52% (p=0.008). Conclusion: In patients with aortic stenosis (AS), use of LAA assessment with CCTA to predict embolic events or new onset AF is no efficacy and cannot be substituted clinical indications for prevention and therapy of embolic events

Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty

Background: Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. Methods: We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77-81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Results: Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574-1971 pg/mL vs. 775, 95% CI 600-950 pg/mL, respectively, p < 0.0001). Subjects in the upper GDF15 tertile were older (p = 0.004), with a more advanced NYHA functional class (p = 0.04) and a higher prevalence of impaired renal function (p = 0.004). Such patients also showed a higher frailty score (p = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain (p = 0.01) and a higher left ventricular mass (p = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9-1.1; p = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. Conclusions: GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients' frailty, independent of indices of left ventricular dysfunction

MicroRNAs distribution in different phenotypes of Aortic Stenosis

Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7-84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p = 0.003) and miRNA 133 (p = 0.03). LF condition was associated with higher levels of miRNA1 (p = 0.02) and miRNA21 (p = 0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p = 0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p = 0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes

Radial access for percutaneous coronary procedure: relationship between operator expertise and complications

Objective The aim of this study was to investigate (1) whether the learning curve of new catheterization laboratory operators increases the incidence of complications of transradial access during percutaneous coronary interventions and (2) whether manual compression with a two-step approach is safe and efficient for radial access hemostasis. Methods We performed a prospective study with all consecutive patients who underwent a coronary diagnostic or intervention procedure with radial access. The primary end point was a composite of pulseless radial artery of the wrist and hematoma evaluated after 24 hours. The secondary end point of efficacy was defined as the presence of bleeding or hematoma after 30 seconds. Results From March 2016 to June 2016, 150 consecutive patients, of whom 147 underwent coronary angiography and/or percutaneous coronary intervention through radial access, were included in the present study. The primary end point was present in 33%, but pulseless radial artery of the wrist was present only in 5.3%. We found that the incidence of primary end point was statistically different according to the number of puncture attempts, with a cutoff of two punctures with blood. The secondary end point of safety was present only in 4.7% of the cases. Conclusion Radial access is feasible and safe even if performed by training physicians. Manual compression with early evaluation after 30 seconds is a safe technique for managing the radial access after sheath removal

Impact of COVID-19 Pandemic on TAVR Activity: A Worldwide Registry

Background: The COVID-19 pandemic had a considerable impact on the provision of structural heart intervention worldwide. Our objectives were: 1) to assess the impact of the COVID-19 pandemic on transcatheter aortic valve replacement (TAVR) activity globally; and 2) to determine the differences in the impact according to geographic region and the demographic, development, and economic status of diverse international health care systems. Methods: We developed a multinational registry of global TAVR activity and invited individual TAVR sites to submit TAVR implant data before and during the COVID-19 pandemic. Specifically, the number of TAVR procedures performed monthly from January 2019 to December 2021 was collected. The adaptive measures to maintain TAVR activity by each site were recorded, as was a variety of indices relating to type of health care system and national economic indices. The primary subject of interest was the impact on TAVR activity during each of the pandemic waves (2020 and 2021) compared with the same period pre–COVID-19 (2019). Results: Data were received from 130 centers from 61 countries, with 14 subcontinents and 5 continents participating in the study. Overall, TAVR activity increased by 16.7% (2,337 procedures) between 2018 and 2019 (ie, before the pandemic), but between 2019 and 2020 (ie, first year of the pandemic), there was no significant growth (–0.1%; –10 procedures). In contrast, activity again increased by 18.9% (3,085 procedures) between 2020 and 2021 (ie, second year of the pandemic). During the first pandemic wave, there was a reduction of 18.9% (945 procedures) in TAVR activity among participating sites, while during the second and third waves, there was an increase of 6.7% (489 procedures) and 15.9% (1,042 procedures), respectively. Further analysis and results of this study are ongoing and will be available at the time of the congress. Conclusion: The COVID-19 pandemic initially led to a reduction in the number of patients undergoing TAVR worldwide, although health care systems subsequently adapted, and the number of TAVR recipients continued to grow in subsequent COVID-19 pandemic waves. Categories: STRUCTURAL: Valvular Disease: Aorti

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come