Gender Differences in Takotsubo Syndrome.

BACKGROUND: Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized. OBJECTIVES: The aim of the present study is to describe TTS sex differences. METHODS: TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger. RESULTS: In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52). CONCLUSIONS: Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review.

The coronavirus disease 2019 (COVID-19), a deadly pandemic that has affected millions of people worldwide, is associated with cardiovascular complications, including venous and arterial thromboembolic events. Viral spike proteins, in fact, may promote the release of prothrombotic and inflammatory mediators. Vaccines, coding for the spike protein, are the primary means for preventing COVID-19. However, some unexpected thrombotic events at unusual sites, most frequently located in the cerebral venous sinus but also splanchnic, with associated thrombocytopenia, have emerged in subjects who received adenovirus-based vaccines, especially in fertile women. This clinical entity was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia, probably caused by cross-reacting anti-platelet factor-4 antibodies activating platelets. For this reason, the regulatory agencies of various countries restricted the use of adenovirus-based vaccines to some age groups. The prevailing opinion of most experts, however, is that the risk of developing COVID-19, including thrombotic complications, clearly outweighs this potential risk. This point-of-view aims at providing a narrative review of epidemiological issues, clinical data, and pathogenetic hypotheses of thrombosis linked to both COVID-19 and its vaccines, helping medical practitioners to offer up-to-date and evidence-based counseling to their often-alarmed patients with acute or chronic cardiovascular thrombotic events.

Cardiac injury following immunization with mRNA SARS-CoV-2 vaccines

Aims Cardiac involvement as myocarditis and/or pericarditis is now recognized as a rare but possible adverse event following SARS-CoV-2 mRNA vaccines. In this brief report we describe a series of four subjects: three of them with myocarditis and one with pericarditis probably due to hypersensitivity and developed in temporal association with COVID-19 mRNA vaccination. Methods and results During last summer, we observed a series of four young Caucasian male [median (range) age, 25 (18–32) years] presenting to the Emergency Department with severe acute chest pain within few days after second dose COVID-19 mRNA vaccine administration [median (range), 3 (2–5) days]. All of these were previously healthy and fitness males. All patients had abnormal electrocardiogram (EKG) and three of them had elevated high sensitive cardiac I troponin (hs-cTnI) levels. These latter three were diagnosed as having myocarditis and undergone cardiac magnetic resonance imaging (CMR). None had acute or prior COVID-19 or pulmonary disease on chest X-ray. Moreover, ischaemic injury, other infections, adverse drug reactions or any autoimmune diseases were excluded by appropriate tests. All patients underwent ecocardiography which showed preserved ejection fraction and no wall motion abnormalities and it excluded coronary origin abnormalities in each patient. The hospital course was uneventful for all four patients and they were discharged within few days of hospitalization [median (range), 6 (3–8) days] after a conservative treatment. The four patients met CDC criteria for probable myocarditis and pericarditis. To date, it is recognized a possible clinical correlation between cardiac injury and SARS-CoV-2 mRNA vaccination. The following elements support this hypothesis: (i) short time lapse between vaccine administration and symptoms onset;(ii) onset after the second dose suggesting an immune-mediated pathogenesis needing a previous sensibilization;(iii) exclusion of other possible damage causes (ischaemia, infections, other immune-mediated diseases, toxicity). In particular, we did not perform coronary angiography given the low pre-test probability of coronary heart disease. Although compending a small sample, our report includes a patient series with clinical features similar to those frequently encountered into other papers: i.e. a prevalence in young males without risk factors;symptoms onset within few days second dose administration;an eventful clinical course. This benign course, seen in the majority of cases in literature, raises the question of the need for specific therapy or an empirical one for symptoms control only. Our report suggest that possible cardiac involvement can range from isolated pericarditis to myocarditis with significant hs-cTnI raise and signs of acute inflammation at CMR or even a myocardial injury with a mild hs-cTnI raise in absence of pathological signs at CMR. This latter case suggests also a possible cardiac injury with subclinical course. Conclusions To date, we are observing a temporal association linking mRNA SARS-CoV-2 vaccines administration and cardiac involvement. According to the majority of papers, our experience suggests an acute benign course of such cardiac involvement;a longer follow-up will also reveal a long-term benign course or conversely the presence of any sequelae. Clinicians should adequately inform patients when receiving vaccine to ensure prompt symptoms recognition and consequently put in place the best management of myocarditis/pericarditis. Finally, it is important to keep in mind that the benefits of vaccines far outweigh the risks.

[COVID-19, vaccines, and thrombotic events]. / COVID-19, vaccini ed eventi trombotici.

COVID-19, a deadly pandemic that has affected millions of people worldwide, is also associated with cardiovascular complications, such as venous and arterial thromboembolic events. The viral spike protein, in fact, may promote the release of prothrombotic and inflammatory mediators. Vaccines, coding for the spike protein, are the primary measure for preventing COVID-19. However, some unexpected thrombotic events at unusual sites, most frequently the cerebral venous and splanchnic districts, with associated thrombocytopenia, have emerged in subjects who received adenovirus-based vaccines, especially in fertile women. This clinical entity has been rapidly recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia, probably caused by cross-reacting antiplatelet factor 4 antibodies activating platelets. This prompted the regulatory agencies of various countries to restrict the use of adenovirus-based vaccines to specific age groups. The prevailing opinion of most experts, however, is that the risk of developing COVID-19 disease, including thrombosis, clearly outweighs this potential extremely low risk.This paper aims at providing a comprehensive review of epidemiological issues, clinical data and pathogenetic hypotheses of thrombosis linked to both COVID-19 and its vaccines, helping cardiologists to offer an up-to-date and evidence-based counseling to their often-alarmed patients with acute or chronic coronary syndromes.

[ANMCO Position paper: Use of sacubitril/valsartan in hospitalized patients with acute heart failure]. / Position paper ANMCO: Utilizzo di sacubitril/valsartan nel paziente ricoverato con scompenso cardiaco acuto.

Sacubitril/valsartan (S/V) has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms in chronic heart failure with reduced ejection fraction compared to enalapril. After 7 years since the publication of the results of PARADIGM-HF, further insight has been gained with potential new indications. Two prospective randomized multicenter studies (PIONEER-HF and TRANSITION) in patients hospitalized for acute heart failure (AHF) have shown an improved clinical outcome and biomarker profile as compared to enalapril, and good tolerability, safety and feasibility of initiating in-hospital administration of S/V. Furthermore, some studies have highlighted the favorable effects of S/V in attenuating adverse myocardial remodeling, supporting an early benefit after treatment. Observational data from non-randomized studies in AHF report that in-hospital and pre-discharge prescription of evidence-based drugs associated with better survival still remains suboptimal. Additionally, the COVID-19 pandemic has also negatively impacted on outpatient activities. Therefore, hospitalization, a real crossroads in the history of heart failure, must become a management and therapeutic opportunity for our patients. The objective of this ANMCO position paper is to encourage and facilitate early S/V administration in stabilized patients during hospitalization after an AHF episode, with the aim of improving care efficiency and clinical outcome.

ANMCO POSITION PAPER: Use of sacubitril/valsartan in hospitalized patients with acute heart failure.

Sacubitril/valsartan (S/V) has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms in chronic heart failure with reduced ejection fraction compared with enalapril. After 7 years since the publication of the results of PARADIGM-HF, further insight has been gained with potential new indications. Two prospective randomized multicentre studies (PIONEER-HF and TRANSITION) in patients hospitalized for acute heart failure (AHF) have shown an improved clinical outcome and biomarker profile as compared with enalapril, and good tolerability, safety, and feasibility of initiating in-hospital administration of S/V. Furthermore, some studies have highlighted the favourable effects of S/V in attenuating adverse myocardial remodelling, supporting an early benefit after treatment. Observational data from non-randomized studies in AHF report that in-hospital and pre-discharge prescription of evidence-based drugs associated with better survival still remain suboptimal. Additionally, the COVID-19 pandemic has also negatively impacted on outpatient activities. Therefore, hospitalization, a real crossroad in the history of heart failure, must become a management and therapeutic opportunity for our patients. The objective of this ANMCO position paper is to encourage and facilitate early S/V administration in stabilized patients during hospitalization after an AHF episode, with the aim of improving care efficiency and clinical outcome.

ANMCO POSITION PAPER: The reorganization of cardiology in times of the SARS-CoV-2 pandemic.

The COVID-19 pandemic represents an unprecedented event that has brought deep changes in hospital facilities with reshaping of the health system organization, revealing inadequacies of current hospital and local health systems. When the COVID-19 emergency will end, further evaluation of the national health system, new organization of acute wards, and a further evolution of the entire health system will be needed to improve care during the chronic phase of disease. Therefore, new standards for healthcare personnel, more efficient organization of hospital facilities for patients with acute illnesses, improvement of technological approaches, and better integration between hospital and territorial services should be pursued. With experience derived from the COVID-19 pandemic,new models, paradigms, interventional approaches, values and priorities should be suggested and implemented.

[ANMCO Position paper: Reorganization of cardiology in the era of the COVID-19 pandemic]. / Position paper ANMCO: Riorganizzazione della cardiologia in epoca di pandemia COVID-19.

The COVID-19 pandemic represents an unprecedented event that has brought deep changes in hospital facilities with reshaping of the health system organization, revealing inadequacies of current hospital and local health systems. When the COVID-19 emergency will end, further evaluation of the national health system, new organization of acute wards, and a further evolution of the entire health system will be needed to improve care during the chronic phase of disease. Therefore, new standards for healthcare personnel, more efficient organization of hospital facilities for patients with acute illnesses, improvement of technological approaches, and better integration between hospital and territorial services should be pursued. With experience derived from the COVID-19 pandemic, new models, paradigms, interventional approaches, values and priorities should be suggested and implemented.

ANMCO POSITION PAPER: The cardiological clinical activities in the transition phase of the COVID-19 pandemic

Infections by SARS CoV2 - COVID-19 became in a short time a worldwide health emergency. The present SARS-CoV-2 pandemic induced in a short time, an unprecedented impact on public health and on the pre-existing care pathways. In order to appropriately address this epidemiological emergency, urgent solutions were needed, such as remodelling or stopping hospitalization and deferrable clinical activities to avoid spreading the SARS-CoV-2 infection. After the first emergency lockdown phase, care pathways must guarantee healthcare to patients and preserve the safety of the healthcare personnel and of all the other subjects that refer to the cardiological surgeries. Rigorous prescriptive appropriateness of the requested exams with consequent reduction of unnecessary examinations is an essential requirement to preserve prioritized diagnostic and care pathways to patients in need, minimizing the risks connected to the SARS-CoV-2 contagion in hospitals. Telemedicine services represent a valid answer to cardiovascular disease patients’ need for care and assistance, including those in quarantine and voluntary isolation. These services successfully contribute to fight the spread of the virus guaranteeing at the same time therapy and support through remote services that must therefore be considered a resource to be implemented and enhanced. This document has to be used by the healthcare personnel working in hospitals and in district offices, if applicable, and aims at managing patients, in complete safety and considered not suspect/not probable (‘not at risk’) of SARS-CoV-2 infection, eligible for diagnostic activity and subsequent therapy in outpatient surgeries. In particular, this document provides indications for patient evaluation to prevent COVID-19 exposure, gives general indications on managing appointments and waiting rooms, on how to strictly adhere to environmental safety measures, on the proper use of Individual Protective Equipment (IPE). It also provides specific indications for outpatient service procedures, like electrocardiogram, cardiologic examination, cardiologic checkup, Dynamic Holter Electrocardiogram, Transthoracic Echocardiography, Echo Stress, Transoesophageal Echocardiography, Bike Ergometer stress test, Ergospirometry, Outpatient Checkup of implantable electronic cardiac devices.

ANMCO POSITION PAPER: The management of suspect or confirmed COVID-19 patients needing urgent electrophysiology and/or electrostimulation procedures

The aim of this document is the management and organization of patients in need of urgent access to electrophysiology (EP) and pacing procedures during the COVID-19 emergency. Specifically, non-deferrable procedures or irreplaceable with a drug therapy prior to the resolution of the COVID-19 virus emergency [pacemaker (PM) implant/replacement/urgent defibrillator (implantable cardioverter-defibrillator, ICD) or arrhythmic storm or other indication of non-deferrable ablation]. The pacing and electrophysiological procedures urgent as they may be, less and less frequently represent situations of emergency, therefore for almost all cases, it is possible to perform a swab test to determine the positivity to COVID-19 of the patient. In cases where this is not possible, due to situations of emergency, the recommendations and procedures we have indicated are advisable, if not mandatory, in order to avoid the spreading of the virus to healthcare personnel and other patients.