Aspirin hypersensitivity: a practical guide for cardiologists.

Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.

Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Acute coronary syndrome in very elderly patients-a real-world experience.

Very elderly population constitutes an increasingly larger proportion of patients admitted for acute coronary syndromes (ACS). Notably, age represents both a proxy of frailty and an exclusion criterion in clinical randomized trials, which probably contributes to lack of data and undertreatment of real-world elderly patients. The aim of the study is to describe patterns of treatment and outcome of very elderly patients with ACS. All consecutive patients aged ≥ 80 years old (yo) admitted between January 2017 and December 2019 with ACS were included. The primary endpoint was in-hospital occurrence of major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, new onset cardiogenic shock, definite/probable stent thrombosis, and ischemic stroke. The secondary endpoints were in-hospital incidence of Thrombolysis in Myocardial Infarction (TIMI) major/minor bleedings, contrast-induced nephropathy (CIN), six-month all-cause mortality, and unplanned readmission. One hundred ninety-three patients (mean age 84.1 ± 3.5 yo, 46% females) were included, of whom 86 (44.6%), 79 (40.9%), and 28 (14.5%) presented with ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA), respectively. The vast majority of patients received an invasive strategy, with 92.7% undergoing coronary angiography and 84.4% to percutaneous coronary intervention (PCI). Aspirin was administered to 180 (93.3%) patients, clopidogrel to 89 (46.1%) patients, and ticagrelor to 85 (44%) patients. In-hospital MACE occurred in 29 patients (15.0%), whereas 3 (1.6%) and 12 patients (7.2%) experienced in-hospital TIMI major and TIMI minor bleeding, respectively. Of the overall population, 177 (91.7%) were discharged alive. After discharge, 11 patients (6.2%) died of all-cause death, whereas 42 patients (23.7%) required a new hospitalization within six months. Invasive strategy of ACS in elderly patients seems safe and effective. Six-month new hospitalization appears inevitably related to age.

The r'-Wave Algorithm: A New Diagnostic Tool to Predict the Diagnosis of Brugada Syndrome after a Sodium Channel Blocker Provocation Test.

A diagnosis of Brugada syndrome (BrS) is based on the presence of a type 1 electrocardiogram (ECG) pattern, either spontaneously or after a Sodium Channel Blocker Provocation Test (SCBPT). Several ECG criteria have been evaluated as predictors of a positive SCBPT, such as the ß-angle, the α-angle, the duration of the base of the triangle at 5 mm from the r'-wave (DBT- 5 mm), the duration of the base of the triangle at the isoelectric line (DBT- iso), and the triangle base/height ratio. The aim of our study was to test all previously proposed ECG criteria in a large cohort study and to evaluate an r'-wave algorithm for predicting a BrS diagnosis after an SCBPT. We enrolled all patients who consecutively underwent SCBPT using flecainide from January 2010 to December 2015 in the test cohort and from January 2016 to December 2021 in the validation cohort. We included the ECG criteria with the best diagnostic accuracy in relation to the test cohort in the development of the r'-wave algorithm (ß-angle, α-angle, DBT- 5 mm, and DBT- iso.) Of the total of 395 patients enrolled, 72.4% were male and the average age was 44.7 ± 13.5 years. Following the SCBPTs, 24.1% of patients (n = 95) were positive and 75.9% (n = 300) were negative. ROC analysis of the validation cohort showed that the AUC of the r'-wave algorithm (AUC: 0.92; CI 0.85-0.99) was significantly better than the AUC of the ß-angle (AUC: 0.82; 95% CI 0.71-0.92), the α-angle (AUC: 0.77; 95% CI 0.66-0.90), the DBT- 5 mm (AUC: 0.75; 95% CI 0.64-0.87), the DBT- iso (AUC: 0.79; 95% CI 0.67-0.91), and the triangle base/height (AUC: 0.61; 95% CI 0.48-0.75) (p < 0.001), making it the best predictor of a BrS diagnosis after an SCBPT. The r'-wave algorithm with a cut-off value of ≥2 showed a sensitivity of 90% and a specificity of 83%. In our study, the r'-wave algorithm was proved to have the best diagnostic accuracy, compared with single electrocardiographic criteria, in predicting the diagnosis of BrS after provocative testing with flecainide.

When to set anticoagulant therapy in asymptomatic AF? looking for a cut-off duration.

The incidence of atrial fibrillation (AF) is progressively increasing, in line with the aging of the population and with the increase in chronic diseases. The care burden of the disease and above all to its consequences (i.e. ischaemic stroke and heart failure) significantly impacts the various health systems with forecasts of exponential increase in the near future. Clinical forms of AF, i.e. those diagnosed with electrocardiogram, have a clear correlation with systemic embolic events and also with a reduction in survival. Thromboembolic prophylaxis in these patients, with anticoagulant drugs, has in fact been shown to greatly reduce the incidence of ischaemic stroke and improve survival. In recent decades, the widespread use of therapeutic intra-cardiac devices, which allow constant and continuous monitoring of myocardial electrical activity, is bringing to light a large number of atrial high rate episodes (AHREs), which are not associated with clinical manifestation. The incidence of these findings grows linearly with the duration of the observation. More independent studies have shown that AHREs are associated with a risk of stroke that is higher (about double) than controls but significantly lower than in patients with manifest AF. However, taking into consideration patients with ischaemic stroke and wearers of implantable devices, no temporal correlation emerged between the incidence of the ischaemic episode and arrhythmia. The presence of AHRE is associated with an approximately six-fold increase in the incidence of clinical AF but only a minority of these patients meet the criteria for prescribing anticoagulation. Pending the publication of the studies still in progress, the European Society of Cardiology guidelines for the treatment of AF recommend considering the initiation of anticoagulant therapy in patients with long-lasting AHRE (> 24 h) associated with a high embolic risk. In patients with episodes of shorter duration (1-24 h), especially if with high burden, anticoagulant therapy can be considered in case of very high embolic risk (e.g. secondary prevention, CHADVASc ≥ 3).

ANMCO position paper on antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Follow-up strategies and individual risk profile after percutaneous coronary intervention: The prospective post percutaneous coronary intervention registry.

BACKGROUND: A multidisciplinary consensus document (MCD) provided a follow-up strategy after percutaneous coronary intervention (PCI) based on individual risk profiles: A, high; B, intermediate; and C, low. AIM: To assess patterns of follow-up after PCI and to evaluate the potential reduction of cardiologic examinations with the application of the MCD. METHODS: The post-PCI registry was carried out at 31 Italian Hospitals and included consecutive patients undergoing PCI. We collected cardiologic consults (CC), noninvasive stress tests (ST), and echocardiograms (EC) actually performed at 12 months and we compared them with the expected by the MCD. RESULTS: We included 1,113 patients (58% with acute coronary syndrome) that underwent 1,567 CC, 398 ST, and 612 EC. The performed CC and ST were significantly lower compared to the expected, respectively [1.6 (95% CI, 1.5-1.7) vs. 1.9 (95% CI, 1.8-2.0), and 0.40 (95% CI, 0.4-0.5) vs. 0.61 (95% CI, 0.6-0.7), p < .001]; the performed EC were significantly higher [0.6 (95% CI, 0.6-0.7) vs. 0.3 (95% CI, 0.3-0.37), p < .001]. Patients at moderate low risk had an excess of noninvasive tests whereas patients at higher risk received less examinations than the expected. The individual risk profile was an independent predictor of increased number of cardiac examination in patients at intermediate and low risk [profile B, OR 2.56 (95%CI 1.38-4.75); profile C, OR 27.00 (95%CI 8.13-89.62), p < .001]. CONCLUSION: In real world patients undergoing PCI, the intensity of follow-up at 12 months appeared not based on individual risk profile, with a higher numbers of examinations, particularly EC, performed in low risk subjects.

Atrial fibrillation in advanced renal failure: are there alternative solutions to warfarin-dicumarol?

Patients with atrial fibrillation (AF) and chronic renal failure (CRF) represent a growing population in epidemiological terms since both conditions increase with advancing age. The association of AF and CRF is burdened with a poor prognosis and with a high risk of adverse events, both ischaemic and haemorrhagic. Oral anticoagulant therapy, in these patients, is more problematic, especially due to the concomitant increased risk of bleeding. The use of direct oral anticoagulants (DOACs) in patients with non-severe renal insufficiency appears to be safe and effective. Since all currently available DOACs are at least partially eliminated by the kidney (dabigatran is the direct anticoagulant with the highest rate of renal elimination, approximately 80%), periodic monitoring of renal function is recommended to evaluate possible need for dosage adjustment. In patients with advanced renal insufficiency, the use of DOAC appears controversial, given the small number of clinical studies that have tested its efficacy and safety. It is known, however, that oral anticoagulation therapy with vitamin K antagonists (VKAs) is associated with an increase in nephropathy and renal-vascular calcification. From this point of view, therapy with DOAC could be more advantageous than VKAs. Data from clinical studies would seem to show that the use of dabigatran and rivaroxaban in these patients may lead to a reduction in the inevitable deterioration of renal function.

ANMCO POSITION PAPER: Role of intra-aortic balloon pump in patients with acute advanced heart failure and cardiogenic shock.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.

Considerations on the use of MitraClip in the treatment of mitral regurgitation.

Mitral regurgitation (MR) is, by occurrence, the second most common valvular heart disease in the Western world, with a significant impact on prognosis and mortality. A significant number of patients with significant mitral incompetence cannot be submitted to conventional surgery due to high surgical risk. The need for an adequate therapeutical strategy prompted the development of innovative endovascular techniques. Among them, the MitraClip percutaneous system, mimicking the 'edge-to-edge' surgical technique introduced by Alfieri in 2003 has emerged as the treatment of choice in patients not suitable for conventional surgery. Since its introduction, this procedure has been effectively carried out in more than 35 000 patients. The evidences from the first randomized clinical trial, EVEREST II, suggested that the MitraClip system is effective in improving survival and quality of life in patients with severe MR. Further randomized trials, MITRA-FR and COAPT, added some more information, showing that an appropriate patient selection, close attention to the specific anatomical characteristics of the mitral valve, and adequate experience of the centre providing the treatment, are important determinants of the outcome of the procedure.

De-escalation therapy after acute coronary syndrome: is it reasonable to switch from prasugrel (or ticagrelor) to clopidogrel early?

Dual antiplatelet treatment (DAPT) is the treatment of choice to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) treated with percutaneous interventions (PCIs). The availability of different P2Y12 inhibitors set the stage for costum made DAPT, as to achieve the highest profile of safety and efficacy. The de-escalation therapy for the newer and more powerful antiplatelet drugs, such as ticagrelor and prasugrel, to clopidogrel, is a strategy for patients with recent ACS, unfit for continuing DAPT for their high risk of bleeding, or side effects, or socio-economic reasons, but without a prohibitive ischaemic risk. There is a need for compelling clinical evidences able to provide the clinical cardiologist with the necessary information to decide the best antiplatelet strategy for each individual patient.

Consensus Document ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: Long-term Antiplatelet Therapy in Patients with Coronary Artery Disease.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be difficult to identify the ideal patient profile which could safely reduce or prolong the DAPT duration in daily clinical practice. The aim of this consensus document is to review contemporary literature on optimal DAPT duration, and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

Antiplatelet therapy and outcome in patients undergoing surgery following coronary stenting: Results of the surgery after stenting registry.

OBJECTIVES: The aim of the present study was to define the feasibility and clinical impact of complying with national consensus recommendations on perioperative management of antiplatelet therapy in patients with coronary stents undergoing cardiac and noncardiac surgery. BACKGROUND: There are limited evidence-based recommendations on the perioperative management of antiplatelet therapy in stented patients undergoing surgery. METHODS: The recommendations provided by the national consensus document were applied in a multicenter, prospective registry of consecutive patients with prior coronary stenting undergoing any type of surgery at 19 hospitals in Italy. The primary end-point was in-hospital net adverse clinical events (NACE) represented by the composite of all-cause death, myocardial infarction, probable/definite stent thrombosis and Bleeding Academic Research Consortium (BARC) grade ≥3 bleeding. Patients were followed for 30 days. RESULTS: A total of 1,082 patients were enrolled. Adherence to consensus recommendations occurred in 85% of the cases. Perioperative aspirin and dual antiplatelet therapy were maintained in 69.7 and 10.5% of the cases, respectively. In-hospital NACE rate was 12.7%, being significantly higher in patients undergoing cardiac surgery (36.3% vs. 7.3%, P < 0.01), mainly due to BARC 3 bleeding events (32.3%). At 30 days, MACE rates were similar (3.5% vs. 3.5%, P = NS) in patients undergoing cardiac and noncardiac surgery, whereas BARC ≥3 bleeding events were significantly higher with cardiac surgery (36.3% vs. 5.6%, P < 0.01). CONCLUSIONS: The results of this registry demonstrate the safety and feasibility of applying a national consensus document on the perioperative management of antiplatelet therapy in stented patients undergoing surgery. © 2016 Wiley Periodicals, Inc.

ANMCO-SIMEU Consensus Document: in-hospital management of patients presenting with chest pain.

Chest pain is a common general practice presentation that requires careful diagnostic assessment because of its diverse and potentially serious causes. However, the evaluation of acute chest pain remains challenging, despite many new insights over the past two decades. The percentage of patients presenting to the emergency departments because of acute chest pain appears to be increasing. Nowadays, there are two essential chest pain-related issues: (i) the missed diagnoses of acute coronary syndromes with a poor short-term prognosis; and (ii) the increasing percentage of hospitalizations of low-risk cases. It is well known that hospitalization of a low-risk chest pain patient can lead to unnecessary tests and procedures, with an increasing trend of complications and burden of costs. Therefore, the significantly reduced financial resources of healthcare systems induce physicians and administrators to improve the efficiency of care protocols for patients with acute chest pain. Despite the efforts of the Scientific Societies in producing statements on this topic, in Italy there is still a significant difference between emergency physicians and cardiologists in managing patients with chest pain. For this reason, the aim of the present consensus document is double: first, to review the evidence-based efficacy and utility of various diagnostic tools, and, second, to delineate the critical pathways (describing key steps) that need to be implemented in order to standardize the management of chest pain patients, making a correct diagnosis and treatment as uniform as possible across the entire country.

ANMCO/GICR-IACPR/SICI-GISE Consensus Document: the clinical management of chronic ischaemic cardiomyopathy.

Stable coronary artery disease (CAD) is a clinical entity of great epidemiological importance. It is becoming increasingly common due to the longer life expectancy, being strictly related to age and to advances in diagnostic techniques and pharmacological and non-pharmacological interventions. Stable CAD encompasses a variety of clinical and anatomic presentations, making the identification of its clinical and anatomical features challenging. Therapeutic interventions should be defined on an individual basis according to the patient's risk profile. To this aim, management flow charts have been reviewed based on sustainability and appropriateness derived from recent evidence. Special emphasis has been placed on non-pharmacological interventions, stressing the importance of lifestyle changes, including smoking cessation, regular physical activity, and diet. Adherence to therapy as an emerging risk factor is also discussed.

A multidisciplinary consensus document on follow-up strategies for patients treated with percutaneous coronary intervention.

The number of percutaneous coronary interventions (PCI) is increasing worldwide. Follow-up strategies after PCI are extremely heterogeneous and can greatly affect the cost of medical care. Of note, clinical evaluations and non-invasive exams are often performed to low risk patients. In the present consensus document, practical advises are provided with respect to a tailored follow-up strategy on the basis of patients' risk profile. Three strategies follow-up have been defined and types and timing of clinical and instrumental evaluations are reported. Clinical and interventional cardiologists, cardiac rehabilitators, and general practitioners, who are in charge to manage post-PCI patients, equally contributed to the creation of the present document.

Impact of baseline hemorrhagic risk on the benefit of bivalirudin versus unfractionated heparin in patients treated with coronary angioplasty: a meta-regression analysis of randomized trials.

BACKGROUND: Bivalirudin significantly reduces 30-day major and minor bleeding compared with unfractionated heparin (UFH), while resulting in similar or lower rates of ischemic events in both patients with stable and unstable coronary disease undergoing percutaneous coronary intervention. We performed a meta-analysis of randomized trials to evaluate the impact of bivalirudin compared with UFH, with or without glycoprotein IIb/IIIa receptor inhibitors (GPI), on the rates of mortality, myocardial infarction (MI), and major bleeding. METHODS: We searched electronic databases for randomized controlled trials with >100 patients comparing bivalirudin (±provisional GPI) with UFH with either routine or provisional GPI in patients undergoing percutaneous coronary intervention. The principal efficacy end points were mortality and MI within 30 day, whereas major bleeding was the principal safety end point. We assessed the benefit of bivalirudin for each efficacy end point relative to the baseline bleeding risk, using the control (UFH) major bleeding rate as proxy for that risk. RESULTS: A total of 12 randomized trials that enrolled 33,261 patients were included. Overall, there was no significant difference in mortality and MI between bivalirudin monotherapy and UFH (±GPI), whereas major bleeding was significantly lower with bivalirudin. Bivalirudin reduced major and minor bleeding across the entire bleeding risk spectrum. CONCLUSIONS: Bivalirudin significantly reduces major and minor bleeding regardless of the estimated baseline hemorrhagic risk.

Anderson-Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement.

Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.