Dario Calderone

Scopus Publications

Acurate Neo2 for valve-in-valve treatment of degenerated 3F Enable sutureless bioprosthetic valve in nonagenarian patient: a case report
Andres Agustin Vecchia, Giuseppe Migliaro, Paolo Cioffi, Dario Calderone, and Giuseppe Verolino
Oxford University Press (OUP)
Abstract Background Sutureless bioprosthetic valves (SBVs) are engineered to enable a less invasive surgical valve replacement procedure in patients at high surgical risk. Valve degeneration is a relatively common occurrence across all types of surgical valves, including SBVs. Valve-in-valve (ViV) procedures are increasingly becoming the preferred treatment for many cases of valve degeneration due to their minimally invasive nature and favourable long-term outcomes. However, the specific structural characteristics of SBVs present challenges for ViV procedures, and the evidence on this subject remains limited. Case summary A 91-year-old man was admitted to our hospital presenting with dyspnoea due to severe aortic regurgitation in a degenerated 3F Enable sutureless valve. Valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) was successfully performed using a self-expanding Acurate Neo2 valve, yielding good haemodynamic results without overt interaction between the prosthesis. A 6-month follow-up echocardiogram confirmed excellent valve performance. Discussion ViV-TAVI is a well-established treatment for bioprosthetic valve failure in high-risk patients. However, sutureless valve degeneration presents a challenging scenario for ViV procedures, with only a limited number of cases performed using the Acurate platform. In this case, we demonstrated the technical feasibility of ViV using the Acurate system in a less explored surgical sutureless bioprosthesis.


Antithrombotic strategies for preventing graft failure in coronary artery bypass graft
Maria Sara Mauro, Simone Finocchiaro, Dario Calderone, Carla Rochira, Federica Agnello, Lorenzo Scalia, and Davide Capodanno
Springer Science and Business Media LLC
AbstractCoronary artery bypass graft (CABG) procedures face challenges related to graft failure, driven by factors such as acute thrombosis, neointimal hyperplasia, and atherosclerotic plaque formation. Despite extensive efforts over four decades, the optimal antithrombotic strategy to prevent graft occlusion while minimizing bleeding risks remains uncertain, relying heavily on expert opinions rather than definitive guidelines. To address this uncertainty, we conducted a review of randomized clinical trials and meta-analyses of antithrombotic therapy for patients with CABG. These studies examined various antithrombotic regimens in CABG such as single antiplatelet therapy (aspirin or P2Y12 inhibitors), dual antiplatelet therapy, and anticoagulation therapy. We evaluated outcomes including the patency of grafts, major adverse cardiovascular events, and bleeding complications and also explored future perspectives to enhance long-term outcomes for CABG patients. Early studies established aspirin as a key component of antithrombotic pharmacotherapy after CABG. Subsequent randomized controlled trials focused on adding a P2Y12 inhibitor (such as clopidogrel, ticagrelor, or prasugrel) to aspirin, yielding mixed results. This article aims to inform clinical decision-making and guide the selection of antithrombotic strategies after CABG.


Percutaneous coronary interventions for aneurysmatic right coronary artery in acute coronary syndrome: RIGHTMARE registry outcomes
Giulio Piedimonte, Enrico Cerrato, Cristina Rolfo, Ivan J. Nunez Gil, Lorenzo Azzalini, Riccardo Mangione, Francesco Maiellaro, Alberto Boi, Donovan Riganelli, Andrea Sardone,et al.
Elsevier BV



Clinical Performance of the Gore Septal Occluder in Patent Foramen Ovale Closure in Different Septal Anatomies: 1-Year Results from a Single-Center Experience
Giuseppe Verolino, Dario Calderone, Mara Gavazzoni, Davide Sala, and Paolo Sganzerla
MDPI AG
Background: PFO (Patent foramen ovale) is a common defect that affects about 25% of the population. Although its presence is asymptomatic in the majority of the cases, the remaining part becomes overt with different symptoms, including cryptogenic stroke. PFO closure is currently a widely available procedure in complex anatomy, with Amplatzer PFO Occluder (APO) being the most commonly used tool. However, the performance of another device, the GORE Septal Occluder (GSO), has not been completely explored with regard to different septal anatomies. Methods: From March 2012 to June 2020, 118 consecutive patients with an indication of PFO closure were treated using the GSO system, included in a prospective analysis, and followed. After 12 months, every patient underwent transcranial Doppler ultrasound to evaluate the effectiveness of treatment. Results: Of 111 patients evaluated, 107 showed effective PFO closure (96.4%), and 4 showed a residual shunt (3.6%). To better evaluate the device performance, the overall population was sorted into two clusters based on the echocardiographic characteristics. The main difference between groups was for PFO width (4.85 ± 1.8 vs. 2.9 ± 1 mm, p < 0.001) and PFO tunnel length (12.6 ± 3.8 vs. 7.2 ± 2, p < 0.001), allowing complex and simple anatomies to be identified, respectively. Regardless of the aforementioned cluster, the GSO performance required to reach an effective closure was independent of anatomy type and the chosen device size. Conclusion: The GSO device showed a high closure rate at 1-year follow-up in patients, with at least one anatomical factor of complexity of PFO irrespective of the level of complexity itself.


Efficacy and Safety of Aspirin for Primary Cardiovascular Risk Prevention in Younger and Older Age: An Updated Systematic Review and Meta-analysis of 173,810 Subjects from 21 Randomized Studies
Dario Calderone, Antonio Greco, Salvatore Ingala, Federica Agnello, Gabriele Franchina, Lorenzo Scalia, Sergio Buccheri, and Davide Capodanno
Georg Thieme Verlag KG
Abstract Aims The efficacy and safety of aspirin for primary cardiovascular disease (CVD) prevention is controversial. The aim of this study was to investigate the efficacy and safety of aspirin in subjects with no overt CVD, with a focus on age as a treatment modifier. Methods and Results Randomized trials comparing aspirin use versus no aspirin use or placebo were included. The primary efficacy outcome was all-cause death. The primary safety outcome was major bleeding. Secondary ischemic and bleeding outcomes were explored. Subgroup analyses were conducted to investigate the consistency of the effect sizes in studies including younger and older individuals, using a cut-off of 65 years. A total of 21 randomized trials including 173,810 individuals at a mean follow-up of 5.3 years were included. Compared with control, aspirin did not reduce significantly the risk of all-cause death (risk ratio: 0.96; 95% confidence interval: 0.92–1.00, p = 0.057). Major adverse cardiovascular events were significantly reduced by 11%, paralleled by significant reductions in myocardial infarction and transient ischemic attack. Major bleeding, intracranial hemorrhage, and gastrointestinal bleeding were significantly increased by aspirin. There was a significant age interaction for death (p for interaction = 0.007), with aspirin showing a statistically significant 7% relative benefit on all-cause death in studies including younger patients. Conclusion The use of aspirin in subjects with no overt CVD was associated with a neutral effect on all-cause death and a modest lower risk of major cardiovascular events at the price of an increased risk in major bleeding. The benefit of aspirin might be more pronounced in younger individuals.


Short Duration of DAPT Versus De-Escalation After Percutaneous Coronary Intervention for Acute Coronary Syndromes
Claudio Laudani, Antonio Greco, Giovanni Occhipinti, Salvatore Ingala, Dario Calderone, Lorenzo Scalia, Federica Agnello, Marco Legnazzi, Maria Sara Mauro, Carla Rochira,et al.
Elsevier BV



Transcatheter treatment of severe aortic stenosis in patients with complex coronary artery disease: case series and proposed therapeutic algorithm
Francesco Soriano, Claudio Montalto, Dario Calderone, Stefano Nava, Giuseppe Esposito, Francesco Saia, Jacopo A Oreglia, and Lars Søndergaard
Oxford University Press (OUP)
Abstract Background Patients with severe aortic stenosis (AS) and complex coronary artery disease with a clinical indication to both transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) pose a clinical dilemma since it is unclear which lesion should be treated first and careful planning is required. Case summary We report two cases of AS with complex PCI (ASCoP) features. In the first one, easy coronary cannulation with an Acurate Neo2 valve and commissural alignment was predicted; therefore, TAVI was performed first, and subsequently complex high-risk PCI of the left main was performed in the same procedure but without the burden of ongoing severe AS. In the second case, complex coronary cannulation after TAVI with an Evolut PRO valve was predicted; therefore, balloon aortic valvuloplasty and Impella placement were performed first to allow for complex, high-risk multivessel PCI and subsequent TAVI. In both cases, a single-stage approach was preferred to reduce the use of large-bore arterial access with possible consequent adverse events. Discussion In this case series, we illustrate a possible approach to the treatment of ASCoP patients. In such complex cases, a thorough preprocedural planning is mandatory, and clinical decision-making should be centred upon the predicted chance of cannulation of coronary arteries after TAVI.


Antiplatelet therapy after noncardioembolic ischemic stroke or transient ischemic attack
Lorenzo Scalia, Dario Calderone, and Davide Capodanno
Informa UK Limited
ABSTRACT Introduction Antiplatelet therapy is key to prevent recurrences in patients with an acute or prior non-cardioembolic stroke or transient ischemic attack (TIA). The narrow balance between the risks of ischemic recurrence and major bleeding is a relevant clinical dilemma in this population. Areas covered This review covers the current evidence on antiplatelet therapy for patients with non-cardioembolic stroke or TIA. Randomized controlled trials of antithrombotic strategies for patients with these conditions were searched in Pubmed/Medline from 1970 to 2022. Expert opinion Numerous randomized controlled trials have defined the current indications to the use of antiplatelet drugs for patients with non-cardioembolic ischemic stroke or TIA. For the management of these subjects, single antiplatelet therapy with aspirin or clopidogrel, or the combination of aspirin and dipyridamole, is usually recommended. After an acute stroke or TIA, a short course of dual antiplatelet therapy with aspirin in combination with clopidogrel or ticagrelor should be considered. The risk of bleeding might be higher with ticagrelor, but a direct comparison with clopidogrel is not available in this setting. The introduction of newer strategies, such as dual-pathway inhibition with aspirin and a direct oral anticoagulant (including emerging factor XI inhibitors under clinical development) may open a new research avenue in this challenging area.


Determinants of Popularity and Natural History of Social Media Accounts in Interventional Cardiology
Paolo D’Arrigo, Antonio Greco, Antonio Gabriele Franchina, Salvatore Ingala, Rocco Paolo Milluzzo, Dario Calderone, Federica Agnello, Marco Legnazzi, Giovanni Occhipinti, Lorenzo Scalia,et al.
Elsevier BV



Appraising the contemporary role of aspirin for primary and secondary prevention of atherosclerotic cardiovascular events
Dario Calderone, Salvatore Ingala, Maria Sara Mauro, Dominick J. Angiolillo, and Davide Capodanno
Informa UK Limited
ABSTRACT Introduction Although the role of aspirin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) has been disputed, its use in secondary ASCVD prevention is well established. Recent trials of primary prevention do not suggest a significant net benefit with aspirin, whereas accruing evidence supports adopting aspirin-free strategies in the context of potent P2Y12 inhibition for the secondary prevention of selected patients undergoing percutaneous coronary intervention. Areas covered This updated review aims at summarizing and appraising the pharmacological characteristics and the contemporary role of aspirin for the primary and secondary prevention of ASCVD. Expert opinion Recent trials and metanalyses in the context of primary prevention highlighted a modest reduction in ischemic events with aspirin use, counterbalanced by a significant increase in bleeding events. However, ongoing studies on cancer prevention could modify the current paradigm of the unfavorable benefit-risk ratio of aspirin in patients with no overt ASCVD. Conversely, aspirin use is crucial for secondary ASCVD prevention, both in chronic and acute coronary syndromes. Nevertheless, after a brief period of dual antiplatelet therapy, patients at high bleeding risk may benefit from discontinuation of aspirin if a P2Y12 inhibitor is used, hence reducing the bleeding risk with no rebound in thrombotic events.


Acute coronary syndrome with spontaneous coronary artery dissection: Which therapeutic option for a different pathophysiology?
Dario Calderone and Davide Capodanno
Oxford University Press (OUP)
Abstract Spontaneous coronary artery dissection (SCAD) has been recognized as an emergent cause of acute coronary syndrome (ACS), myocardial infarction, and sudden death. Patients mostly affected by SCAD are individuals without or with few cardiovascular risk factors, particularly young women, thus suggesting a clearly different pathophysiology than the more common atherosclerosis. Present research efforts outlined an improved characterization of the prevalence, natural history, and clinical outcome of SCAD. Intracoronary imaging has been an important asset in this condition, providing an improved diagnostic and therapeutic understanding. Current evidences suggest not only that this condition is more common than previously thought but also that the clinical management could be distinctly different from ACS secondary to atherosclerosis. Both medical and interventional treatment should consider the different cause of ACS, as well as the clinical stability of the patient, taking into account that the risk of recurrence is particularly high, predominantly during the first few days after the acute event. Stemming from new scientific evidences in terms of pathophysiology, clinical approach, therapy strategies, and follow-up of SCAD, it is important to identify spontaneous coronary dissection in the differential diagnosis of ACS.


Outcomes of renin- angiotensin-aldosterone systemblockers in patients with COVID-19: A systematic review andmeta-analysis
Antonio Greco, Sergio Buccheri, Paolo D’Arrigo, Dario Calderone, Federica Agnello, Marco Monte, Rocco Paolo Milluzzo, Antonio Gabriele Franchina, Salvatore Ingala, and Davide Capodanno
Oxford University Press (OUP)
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently reached the pandemic level. COVID-19 is associated with higher case fatality in patients with comorbidities, including those with arterial hypertension or other cardiovascular diseases. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are extensively used for different clinical indications. It has been hypothesized that the use of ACEIs/ARBs may negatively impact on the clinical outcomes of COVID-19 patients by affecting the expression of angiotensinconverting enzyme 2 aminopeptidase (ACE-2), the human receptor for SARS-CoV-2. Accruing evidence is available that does not show a higher risk with ACEIs/ARBs in patients with COVID-19. However, available studies have limited statistical power to detect signals of increased mortality. In this context, a metaanalysis provides more precise estimates of the direction and strength of association between the use of ACEIs/ARBs and prognosis. Few meta-analyses have been published that do not show an increase in death with ACEIs/ARBs. However, new studies are now available that suggest the opportunity for an update. This meta-analysis complies with the MOOSE (Meta-analyses Of Observational Studies in Epidemiology) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and its protocol is registered in the PROSPERO database (CRD42020185053). We searched PubMed, Scopus, and web sources up to 7 June 2020 for studies reporting data on the association between ACEI/ARB use and clinical outcomes in patients with COVID-19. No language restrictions were used. The primary outcome of interest was all-cause death (inhospital or within 28 days from symptom onset). The secondary outcome of interest was severe disease due to SARS-CoV-2. Where available, we extracted both the raw number of events and the adjusted risk estimates (e.g. multivariable or propensity score adjusted). When needed, the corresponding authors of the included studies were contacted, and one of them provided additional data that were not available in the original publication. Data quality of the included studies was evaluated using the Newcastle Ottawa scale (NOS). Data were pooled using inversevariance weighted random-effects models. The between-study heterogeneity was calculated according to the DerSimonian and Laird method. The Hartung–Knapp method was used for adjustment of the estimates and confidence intervals (CIs). Publication bias was assessed using the Begg and Mazumdar test. Pooled estimates are presented as odds ratios (ORs) with the 95% CI. A total of 175 studies were screened at the title and abstract level, and 14 were finally included (13 with observational design and one interim analysis of a randomized clinical trial), encompassing 10 127 patients. Most patients were in their sixth decade, with age ranging across studies between 45 and 86 years. Hypertension was the only indication for ACEIs/ARBs in 8 studies out of 14. All-cause mortality was reported in 13 studies (n = 10 014) while severe disease was reported in 9 studies (n = 1675). The quality of the included studies ranged from low to high (average NOS score 5.5, range 3–8). In the unadjusted analysis, the use of ACEIs/ARBs was not associated with an increased risk of all-cause death (OR 0.95, 95% CI 0.57–1.58; Figure 1A) or severe disease (OR 0.88, 95% CI 0.60–1.31). The results were consistent in a sensitivity analysis restricted to studies with NOS score >_5. A leave-one-out sensitivity analysis showed that none of the studies overly influenced the magnitude and significance of the summary estimate (Figure 1B). There were no concerns for publication bias (Pvalue >0.05). We did not identify an increased risk of early death or severe disease associated with the use of ACEIs/ARBs. These findings support the recommendation of major international cardiovascular societies on the importance of continuing ACEIs/ARBs during the COVID-19 outbreak. Although no conclusions can be drawn on the benefit of ACEIs/ARBs in COVID-19, our results support the safety of the uninterrupted use of ACEIs/ARBs. In addition, since these drugs provide clear benefits in patients with cardiovascular diseases, their preventive discontinuation during COVID-19 should be discouraged.


An updated drug profile of ticagrelor with considerations on the treatment of patients with coronary artery disease and diabetes mellitus
Dario Calderone, Davide Capodanno, and Dominick J. Angiolillo
Informa UK Limited
ABSTRACT Introduction Ticagrelor is an antiplatelet agent acting through direct and reversible competitive inhibition of the platelet P2Y12 receptor. While the clinical merits of ticagrelor in patients who experienced an acute coronary syndrome are widely accepted, its role in stable coronary artery disease is less established. Recently, large-scale trials of ticagrelor have been published in this setting, including a trial in patients with diabetes mellitus (DM). Areas covered This review aims to inform about recent findings on ticagrelor, by appraising the current body of evidence on its use in different clinical scenarios, particularly in DM, ranging from pharmacology to clinical outcomes and future directions. Expert opinion The results of the THEMIS trial, conducted in DM patients with stable coronary artery disease and no prior stroke or myocardial infarction, showed that although ticagrelor in addition to aspirin reduced the risk of ischemic events, this was associated with a parallel increase in bleeding complications. However, patients with history of percutaneous coronary intervention seemed to benefit more from adjunctive ticagrelor therapy. Careful bleeding and ischemic risk stratification remains crucial to define the best antithrombotic strategy for the individual patient.


Mechanisms of ST-segment elevation myocardial infarction in patients with atrial fibrillation, prior stenting and long-standing chronic coronary syndrome
Antonio Gabriele Franchina, Dario Calderone, Paolo D'Arrigo, Salvatore Ingala, Rocco Paolo Milluzzo, Antonio Greco, Marco Spagnolo, Corrado Tamburino, and Davide Capodanno
VM Media SP. zo.o VM Group SK
BACKGROUND The optimal antithrombotic regimen for patients with atrial fibrillation (AF) and chronic coronary syndromes beyond 1 year after percutaneous coronary intervention (PCI) is a matter of debate. For these patients, guidelines recommend oral anticoagulation (OAC) alone, but the risk of thrombotic complications remains a concern. The aim of this study was to characterize the incidence, presentation and use of antithrombotic therapy in patients with AF, prior stenting > 12 months and new ST-segment elevation myocardial infarction (STEMI). METHODS Consecutive patients were selected from an institutional registry over a 3-year period if they matched the following criteria: 1) STEMI undergoing primary PCI; 2) AF; 3) chronic coronary syndrome with prior stenting > 12 months. RESULTS Among 852 consecutive STEMI patients undergoing primary PCI, the prevalence of AF was 4.1%, and 6 (0.9%) patients met all the inclusion criteria. Substantial heterogeneity in antithrombotic treatment for these patients was noted (e.g., OAC alone, OAC plus a single antiplatelet agent, no antithrombotic therapy). In 50% of patients, the STEMI episode was linked to a previously stented lesion or documented plaque. CONCLUSIONS This case review illustrates the wide heterogeneity in antithrombotic pharmacotherapy among AF patients presenting with STEMI > 12 months after PCI. The underlying reason for STEMI is only partly related to disease progression or stent-related events. This finding suggests that multiple mechanisms of recurrence may be advocated, and are not only limited to antithrombotic therapy but may be explained by the natural history of coronary artery disease in remote vessels.


Aspirin for the primary prevention of cardiovascular disease: latest evidence
Davide Capodanno, Salvatore Ingala, Dario Calderone, and Dominick J. Angiolillo
Informa UK Limited
ABSTRACT Introduction: While the clinical merits of aspirin in secondary cardiovascular disease (CVD) prevention remain undisputed, its role in primary prevention is controversial. Recently, three trials of primary prevention reported neutral net benefit results or evidence of harm for aspirin in patients with no overt CVD. Areas covered: This article aims to inform clinical practitioners by appraising the current body of evidence on the use of aspirin for primary CVD prevention, ranging from general pharmacology to clinical outcomes and future directions. Expert opinion: Based on meta-analyses incorporating latest trials in the field of primary prevention, the modest reduction in ischemic events with aspirin, if any, is offset by a modest increase in nonfatal bleeding. Improved control of CVD risk factors and broader use of statins may have reduced the thrombotic complications of atherosclerosis, thus limiting the opportunity for aspirin to prevent clinical CVD events in the contemporary era. As such, decision-making about aspirin for primary prevention is challenging even when selected patients are considered and involves careful weighing of risks and benefits. Ongoing investigations conducted in patients with cancer could rapidly modify the current perception of the unfavorable benefit-risk ratio of aspirin in patients with no overt CVD.