Rheumatic and Degenerative Mitral Stenosis: From an Iconic Clinical Case to the Literature Review.

Mitral stenosis (MS) poses significant challenges in diagnosis and management due to its varied etiologies, such as rheumatic mitral stenosis (RMS) and degenerative mitral stenosis (DMS). While rheumatic fever-induced RMS has declined in prevalence, DMS is rising with aging populations and comorbidities. Starting from a complex clinical case of DMS, the aim of this paper is to review the literature on mitral stenosis by analyzing the available tools and the differences in terms of diagnosis and treatment for rheumatic and degenerative stenosis. Emerging transcatheter techniques, such as transcatheter mitral valve replacement (TMVR) and lithotripsy-facilitated percutaneous mitral commissurotomy (PMC), represent promising alternatives for DMS patients deemed unfit for surgery. In particular, intravascular lithotripsy (IVL) has shown potential in facilitating percutaneous interventions by fracturing calcific deposits and enabling subsequent interventions. However, larger prospective studies are warranted to validate these findings and establish IVL's role in DMS management. To further enhance this technique, research could focus on investigating the long-term outcomes and durability of mitral lithotripsy, as well as exploring its potential in combination with PMC or TMVR.

[Management of patent foramen ovale in non-cardiac surgery]. / Gestione della pervietà del forame ovale nella chirurgia non cardiaca.

Patent foramen ovale (PFO) is a remnant of normal fetal anatomy which may persist into adulthood, mostly asymptomatic. In some adults, PFO may result in a potential for shunting venous thromboembolism to the arterial circulation; less frequently it can cause interatrial, right-to-left shunting of deoxygenated blood. The pathogenesis of several medical conditions is related to the presence of PFO. Some randomized clinical trials have shown evidence of benefit for device closure as compared with medical therapy in patients with cryptogenic stroke. The literature reported several cases of carbon dioxide embolism during general laparoscopic surgery and sometimes stroke after laparoscopic or neurosurgery but there are neither prospective studies addressing these issues, nor randomized clinical trials assessing the effectiveness of pharmacotherapy or interventional procedures at decreasing risk. The European position paper suggests routine monitoring in non-cardiac surgery of patients with a PFO and no actual indications for closure. This article aims to further stratify the risk of periprocedural stroke and paradoxical embolism in this category of patients.

Valve-in-valve transcatheter aortic valve implantation: The issues behind crossing a bioprosthesis.

Valve-in-valve transcatheter aortic valve implantation (ViV TAVI) is rapidly arising as a safe and effective alternative to redo-surgery in the treatment of bioprostheses deterioration. While scientific community is currently focusing its attention on the most common limitations related to this procedure, such as the risk of coronary obstruction and patient-prosthesis mismatch, data regarding the first step of a ViV TAVI, the crossing of a degenerated bioprosthesis, are still lacking. The aim of this review is to analyze the available information about bioprosthesis crossing, to show the inherent challenges encountered by interventional cardiologists during valve crossing and to describe the current strategies to perform a correct crossing.

Patients younger than 70 undergoing transcatheter aortic valve implantation: Procedural outcomes and mid-term survival.

INTRODUCTION: Based on recent data, the indication for transcatheter aortic valve implantation (TAVI) is expanding to individuals at lower surgical risk, who are generally younger than subjects historically treated for severe aortic stenosis. Indeed, younger patients have traditionally been under-represented in current TAVI literature. The aim of the present study is to report about clinical features, procedural outcomes and mid-term outcomes of patients younger than 70 who underwent TAVI in a single high-volume center. MATERIALS AND METHODS: Consecutive patients younger than 70 years of age who underwent TAVI for severe, symptomatic aortic stenosis between 2007 and 2019 at a single, tertiary referral center have been included in this retrospective study. Procedural and mid-term outcomes were analyzed, comparing 1st generation with 2nd generation devices. RESULTS: Between 2007 and 2019, 1740 TAVI procedures were performed in our center. Among these, one hundred twenty-nine (7.4%) patients were younger than 70 years at the time of the intervention and were included in the present analysis. Fifty-eight patients (45%) were implanted with a 1st generation prosthesis while seventy-one patients (55%) were implanted with a 2nd generation device. Reasons which lead to a transcatheter approach in this population were: previous CABG (27.9%); porcelain aorta (24%); severe left ventricular systolic dysfunction (21.7%); prior chest radiation (19.4%); severe lung disease (8.5%); hemodynamic instability (7.0%); advanced liver disease (4.6%) and active cancer (3.9%). Overall device success rate was 89%, with no differences among 1st and 2nd generation devices. Threeyears all-cause mortality was 34%, with no difference among the two groups. Low incidence of aortic-valve re-intervention was observed at mid-term follow-up (late valve re-intervention = 2.3%). CONCLUSIONS: TAVI in young patient with appropriate indication for intervention is a safe procedure, associated with low rate of in hospital mortality and low rate of severe complications both with 1st and with 2nd generation devices. When considering long term durability, more data are needed; in our case series long-term follow up shows a good survival and also an extremely low rate of valve re-intervention.

Downstream or upstream administration of P2Y12 receptor blockers in non-ST elevated acute coronary syndromes: study protocol for a randomized controlled trial.

BACKGROUND: The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors-ticagrelor and prasugrel-currently recommended by the guidelines. STUDY DESIGN: DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. CONCLUSIONS: The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618837 . Registered on 1 December 2015.

Residual SYNTAX Score and One-Year Outcome in Elderly Patients With Acute Coronary Syndrome.

BACKGROUND: The residual burden of coronary artery disease after percutaneous coronary intervention (PCI) has been associated with worse ischemic outcome. However, data are conflicting in elderly patients. The aim of our study was to verify the incremental value of the residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (rSS) over clinical variables and baseline SYNTAX score (bSS) in predicting 1-year mortality or cardiovascular events. METHODS: A post hoc analysis of data collected in the Elderly-ACS 2 multicenter randomized trial was performed. We included 630 patients aged > 75 years with multivessel coronary disease undergoing PCI for acute coronary syndrome (ACS). The primary outcome was a composite of death, recurrent myocardial infarction, and stroke at 1-year follow up. Change in c-statistic and standardized net benefit were used to evaluate the incremental value of the rSS. RESULTS: Event rates were significantly higher in patients with incomplete revascularization (rSS > 8). When the rSS was included in a core Cox regression model containing age, previous myocardial infarction, and ACS type, the hazard ratio for patients with score values > 8 was 2.47 (95% confidence interval, 1.51-4.06). However, the core model with rSS did not increase the c-statistic compared with the core model with the bSS (from 0.69 to 0.70) and gave little incremental value in the standardized net benefit. CONCLUSIONS: In elderly patients with ACS with multivessel disease undergoing PCI, incomplete revascularization was associated with worse outcome at 1-year follow-up. However, there was no clear incremental value of the rSS in the prediction of 1-year adverse outcome compared with a model including clinical variables and bSS.

CONTEXTE: Le fardeau résiduel de la coronaropathie après une intervention coronarienne percutanée (ICP) a été associé à de moins bons résultats sur le plan ischémique. Les données recueillies chez les patients âgés sont toutefois contradictoires. Cette étude avait donc pour objectif de valider la valeur ajoutée du score SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) résiduel (SSr) par rapport aux paramètres cliniques et au score SYNTAX initial (SSi) pour prédire la mortalité à 1 an et les manifestations cardiovasculaires. MÉTHODOLOGIE: Une analyse a posteriori des données de l'étude multicentrique avec répartition aléatoire Elderly-ACS 2 a été effectuée. Pour ce faire, 630 patients âgés de plus de 75 ans, atteints d'une coronaropathie multitronculaire et ayant subi une ICP pour traiter un syndrome coronarien aigu (SCA) ont été retenus. Le critère d'évaluation principal était composé du décès, de l'infarctus du myocarde récurrent et de l'accident vasculaire cérébral (AVC) au moment du suivi à 1 an. La variation de la statistique C et le bénéfice net normalisé ont servi à évaluer la valeur ajoutée du SSr. RÉSULTATS: Les manifestations étaient significativement plus fréquentes chez les patients dont la revascularisation était incomplète (SSr > 8). Lorsque le SSr a été pris en compte dans un modèle de régression de Cox de base ayant pour facteurs l'âge, les antécédents d'infarctus du myocarde et le type de SCA, le rapport des risques instantanés pour les patients ayant un score > 8 était de 2,47 (intervalle de confiance à 95 % : 1,51-4,06). L'intégration du SSr dans le modèle de base n'a toutefois pas donné lieu à une statistique C plus élevée que celle du SSi (0,70 vs 0,69) et conférait peu de valeur ajoutée sur le plan du bénéfice net normalisé. CONCLUSIONS: Chez les patients âgés présentant un SCA et une atteinte multitronculaire, et subissant une ICP, la revascularisation incomplète a été associée à de moins bons résultats au moment du suivi à 1 an. Le SSr n'a toutefois pas été clairement associé à une valeur ajoutée pour prédire une issue défavorable à 1 an comparativement à un modèle reposant sur des paramètres cliniques et le SSi.

Characteristics and Outcome of Patients ≥75 Years of Age With Prior Coronary Artery Bypass Grafting Admitted for an Acute Coronary Syndrome.

The prognostic role of previous coronary artery bypass (CABG) in elderly patients admitted to hospital for an acute coronary syndrome (ACS) is unclear. Therefore, the aim of this study was to compare the prognosis of patients aged ≥75 years admitted for an ACS with or without previous history of CABG. The primary outcome of the study was a composite of overall mortality, recurrent nonfatal myocardial infarction, nonfatal stroke, and rehospitalization for heart failure at 1-year follow-up. We included 2,253 ACS patients, aged 81 (78 to 85) years enrolled in 3 multicenter studies (the Italian Elderly ACS study, the LADIES ACS study, and the Elderly ACS 2 randomised trial) - 178 (7.9%) with previous CABG, 2,075 (92.1%) without. Patients with previous CABG had a higher burden of cardiovascular risk factors, lower ejection fraction, and higher creatinine values on admission. However, both at univariate analysis and after adjustment for the most relevant covariates (sex, age, previous myocardial infarction, type of ACS, left ventricular ejection fraction, and serum creatinine on admission), previous CABG did not show any statistically significant association with 1-year outcome (adjusted hazard ratio 0.85; 95% confidence interval 0.61 to 1.19; p = 0.353). In conclusion, our study suggests that elderly ACS patients with previous CABG have worse basal clinical characteristics. Nevertheless, in a broad cohort of patients mostly treated with percutaneous coronary intervention during the index event, previous CABG did not confer independent additional risk of major adverse cardiovascular events at 1-year follow-up.

Impact of Ascending Aorta Dilation on Mid-Term Outcome After Transcatheter Aortic Valve Implantation.

BACKGROUND: Severe aortic stenosis (AS) is often associated with ascending aorta dilation (AAD). AAD is amenable to surgical correction combined with aortic valve replacement. Transcatheter aortic valve implantation (TAVI) might represent a valid therapeutic option in these patients when AAD correction Is not indicated. The aim of the present study is to evaluate the impact of concomitant AAD on early and mid-term outcomes after TAVI for symptomatic severe AS. METHODS: This is a single-center observational study including patients undergoing transfemoral TAVI. All patients with previous surgery on the left ventricular outflow tract, aortic valve, or ascending aorta (except coronary artery bypass graft surgery) were excluded from the analysis. Patients undergoing TAVI for congenital aortic valve defects or subjects in whom a computed tomography (CT) scan was not available were excluded from the analysis. Ascending aortas were measured on CT scans using appropriate multiplanar reconstructions. Ascending aortas were qualified as dilated if the measurement was >40 mm. Study outcomes were death from any cause, significant paravalvular leaks (PVLs), and new permanent pacemaker (PPM) implant. RESULTS: The final population consisted of 680 subjects, 61% females, mean age 82 ± 7 years. One hundred subjects (15%) had AAD. No differences in terms of significant PVL or PPM implantation were found between subjects with or without AAD (P>.99 and P=.13, respectively). At a median follow-up of 498 ± 216 days, no significant difference in terms of mortality was found between subjects with or without AAD (P=.78). CONCLUSIONS: AAD does not appear to impact the mid-term outcomes in a cohort of subjects undergoing TAVI.

Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low-Dose Prasugrel or Clopidogrel.

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( Padj<0.001) without a difference in ADBRs ( Padj=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( Padj<0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( Padj<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.

A comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization: Design and rationale of the randomized Elderly-ACS 2 study.

BACKGROUND: Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding. STUDY DESIGN: The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75mg in patients older than 74years with ACS (either ST- or non-ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score). CONCLUSION: The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503).

The role of early contrast-enhanced chest computed tomography in the aetiological diagnosis of patients presenting with cardiac tamponade or large pericardial effusion.

AIMS: The role of chest computed tomography (CT) is not well defined for either diagnosis or management of pericardial disease. The aim of this study was to evaluate the added value of early chest CT in the diagnostic workup for patients presenting with cardiac tamponade or large pericardial effusion of unknown aetiology as the first manifestation of disease. METHODS AND RESULTS: We performed CT scan on 55 patients with pericardial effusion as defined above, undergoing echo-guided pericardiocentesis. We compared the success rate in making diagnosis and/or staging the underlying disorder of three sequential workups, including, respectively, (i) clinical presentation, inflammatory markers, chest X-ray imaging, (ii) all of the above and pericardial fluid analysis, and (iii) all of the above and chest CT. We were able to make diagnosis in 53 patients (96%): the major cause of effusion was malignancy (38%). Clinical and biochemical data were not able to differentiate non-tumour from tumour patients. CT revealed pathological findings in all patients with malignancy: tumour mass in 15/21 (71%) and pathological lymphadenopathy in the remaining 6 cases. The workup including CT provided a significantly higher diagnostic yield than the other two workups (P < 0.0001), both in the overall population and in the two subgroups of neoplastic (Npl) and non-Npl patients. CONCLUSION: In all patients with cardiac tamponade or large pericardial effusion, CT was useful either in identifying the underlying disease or in excluding other potential causes of pericardial effusion. We conclude that chest CT is a very useful non-invasive diagnostic tool to identify and stage pericardial diseases.

[From the coronary care unit to the intensive cardiac care unit: the evolution of the Cardiovascular Department of a tertiary center]. / Dalla unità di cura coronarica alla terapia intensiva cardiologica: l'evoluzione del Dipartimento Cardiovascolare dell'Ospedale di Lecco.

BACKGROUND: Substantial changes have occurred over time in the diagnoses, procedures and characteristics of patients admitted to coronary care units (CCU). Following the introduction of cardiac surgery activity in our hospital in December 2009, the aim of this study was to evaluate the changes in activity, processes of care and outcomes of patients consecutively admitted to our CCU after the reorganization of the Cardiovascular Department. METHODS: All 1674 consecutive patients admitted to the CCU from January 2009 to December 2010 were enrolled in this retrospective registry. RESULTS: In 2010, the number of patients referred from other hospitals or wards significantly increased (from 17.2% to 28.3%; p<0.001). Significant was also the increase of patients with ST-elevation myocardial infarction (n=190 to n=230, p<0.001), shock (n=20 to n=50, p<0.001), pulmonary edema (n=47 to n=64, p<0.05), cardiac arrest (n=2 to n=8, p<0.05), aortic dissection (n=0 to n=12; p<0.001). Conversely, the number of patients admitted for acute coronary syndromes without ST-segment elevation and GRACE risk score <140 significantly decreased (n=169 to n=52, p<0.001). In parallel, a significant increase in the use of intra-aortic balloon pump (2.0% to 5.6%, p<0.001), continuous hemofiltration (0.3% to 3.1%, p>0.001), non-invasive ventilation (5.6% to 10.5%, p<0.001) and mechanical ventilation (0% to 4.1%, p<0.001) was observed. Intensive care devices were more frequently used in the subgroups affected by shock, acute coronary syndromes without ST-segment elevation and GRACE risk score >200, and heart failure. Interestingly, despite the increase in high-risk clinical conditions the intra-CCU mortality did not change (3.1 vs 2.9%). CONCLUSIONS: Patients admitted to the CCU have high-risk acute clinical conditions. A model based on the sharing of cardiological, cardiac anesthesiological and surgical expertise is effective in increasing admission appropriateness and improving standards of care in a short period of time.

Anti-inflammatory action of apoptotic cells in patients with acute coronary syndromes.

OBJECTIVES: Atherosclerotic plaques contain both apoptotic cells and phagocytes. Apoptotic cells are known to exert an anti-inflammatory effect. Little is known on their action in patients with acute coronary syndromes. METHODS AND RESULTS: We challenged mononuclear phagocytes from the peripheral blood of patients with acute coronary syndromes (n=20) and healthy controls (n=30) with lipopolysaccharide (LPS, 100ng/ml) or peptidoglycan (PGN, 20microg/ml) in the presence or in the absence of apoptotic cells. After 24h, mononuclear phagocytes from patients with acute coronary syndromes produced more TNFalpha and IL-10 than controls; moreover, they were significantly more susceptible to the anti-inflammatory action of apoptotic cells. Apoptotic cells were more effective in ACS patients with C-reactive protein levels <3mg/l than in patients with CRP levels >3mg/l. CONCLUSIONS: Patients with acute coronary syndromes and low circulating C-reactive protein levels are more sensitive to the anti-inflammatory action of apoptotic cells: this suggests the existence of an enhanced anti-inflammatory feedback circuit, which could contribute to protect from plaque instability.

Clinical outcomes after unrestricted implantation of everolimus-eluting stents.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of unrestricted everolimus-eluting stent (EES) implantation in a contemporary cohort of real-world patients. BACKGROUND: The randomized SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trials have evaluated the performance of EES, resulting in their approval by the Food and Drug Administration, but data regarding unselected usage, including off-label indications are lacking. METHODS: Consecutive patients treated with EES (either PROMUS, Boston Scientific Corp., Natick, Massachusetts, or XIENCE-V, Abbott Vascular Devices, Santa Clara, California) between October 2006 and February 2008 were analyzed. End points were cardiac death, myocardial infarction (MI), ischemic-driven target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac events (MACE) (a composite of cardiac death, MI, TLR) during follow-up. RESULTS: We identified 345 patients (573 lesions) treated with EES. The majority of patients (71.9%) were treated for > or =1 off-label or untested indication. Clinical follow-up was completed in 99%. At a median follow-up of 378 days (interquartile range 334 to 473), MACE occurred in 36 (10.6%) patients, TLR in 27 (7.9%), MI in 7 (2.1%), and cardiac death in 7 (2.1%). Definite and probable ST was observed in 3 (0.9%) cases. Off-label EES implantation was not associated with a statistically significant increased risk of MACE (12.2% vs. 6.3%, p = 0.17), TLR (9.3% vs. 4.2%, p = 0.18), or ST (0.8% vs. 1.1%, p = 1.0). On multivariable analysis, previous bypass surgery (p = 0.002) and diabetes (p = 0.03) were associated with MACE. CONCLUSIONS: In unrestricted daily practice, EES were implanted predominantly for off-label indications and associated with a relative low rate of MACE and TLR.