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.

Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review.

Cardiovascular conditions in the spectrum of acute coronary syndromes are characterized by sex differences with regard to pathophysiology, risk factors, clinical presentation, invasive and pharmacologic treatment, and outcomes. This review delves into these differences, including specific subsets like myocardial infarction with non-obstructed coronary arteries or Spontaneous Coronary Artery Dissection, and alternative diagnoses like Takotsubo cardiomyopathy or myocarditis. Moreover, practical considerations are enclosed, on how a sex-specific approach should be integrated in clinical practice: in fact, personal history should focus on female-specific risk factors, and hormonal status and hormonal therapy should be assessed. Moreover, physical and psychological stressors should be investigated, particularly in the event of Spontaneous Coronary Artery Dissection or Takotsubo cardiomyopathy.

[Proposal to improve the patient journey for women's cardiovascular prevention]. / Proposta di miglioramento del percorso di prevenzione cardiovascolare della donna.

The relevance of gender medicine in cardiovascular prevention is still underestimated, and there is a lack of viable women-specific preventive, diagnostic, and therapeutic strategies. To ensure women have equal access to cardiovascular prevention, cardiovascular disease risk stratification needs to consider gender-specific factors related to women reproductive cycle phases together with the different impact that traditional risk factors have on men and women. The aim of this document is to improve the patient journey for cardiovascular risk prevention in women, enhancing the importance of a multidisciplinary approach and the role of the various professional figures involved, starting with the general practitioner, as the main actor of the first risk stratification. The goal of the proposed patient journey is to ensure effective risk assessment of cardiovascular disease in women, by raising attention on the risk factors related to different hormonal phases and to bridge the sex and gender gap in cardiovascular prevention. We hope that this journey can be implemented as uniformly as possible in clinical practice throughout Italy.

[Gender discrepancy: time to implement gender-based clinical management]. / Position paper ANMCO: Differenze di genere nell'approccio farmacologico cardiovascolare.

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.

[Gender cardiology: focus on clinical and pathophysiological peculiarities in women with long COVID syndrome]. / Cardiologia di genere: il punto su peculiarità cliniche e fisiopatologiche nelle donne nel long COVID.

Long COVID is a clinical syndrome characterized by the persistence or development of symptoms due to COVID-19 at least 12 weeks after initial infection. More than 200 different symptoms have been ascribed to long COVID, the most common being fatigue, shortness of breath, and muscle weakness. Women have a three-fold higher risk of being diagnosed with long COVID, and the symptoms more often described are persistent weakness, chest pain, altered smell and taste, palpitations or muscle pain, as well as neurological, gastrointestinal and rheumatologic symptoms. Long COVID features are influenced by immune function, endothelial dysfunction and sex hormones. Moreover, it leads to systemic dysfunction, so various therapeutic strategies have been explored and still different trials are ongoing, mainly regarding anticoagulation and immuno-modulators. Nowadays the most quoted interventions are focused rehabilitation programs and pharmacological selected treatments in specifical cases. The aim of this review will be focusing the clinical and pathophysiological sex-related peculiarities to understand the different long COVID phenotypes and possibly address a better tailored approach and treatment.

Lights and Shadows of Clinical Applications of Cardiac Scintigraphy with Bone Tracers in Suspected Amyloidosis.

Radionuclide bone scintigraphy is the cornerstone of an imaging-based algorithm for accurate non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). In patients with heart failure and suggestive echocardiographic and/or cardiac magnetic resonance imaging findings, the positive predictive value of Perugini grade 2 or 3 myocardial uptake on a radionuclide bone scan approaches 100% for the diagnosis of ATTR-CA as long as there is no biochemical evidence of a clonal dyscrasia. The technetium-labelled tracers that are currently validated for non-invasive diagnosis of ATTR-CA include pyrophosphate (99mTc-PYP); hydroxymethylene diphosphonate (99mTc-HMDP); and 3,3-diphosphono-1,2-propanodicarboxylate (99mTc-DPD). Although nuclear scintigraphy has transformed the contemporary diagnostic approach to ATTR-CA, a number of grey areas remains, including the mechanism for binding tracers to the infiltrated heart, differences in the kinetics and distribution of these radiotracers, differences in protocols of image acquisition worldwide, the clinical significance of extra-cardiac uptake, and the use of this technique for prognostic stratification, monitoring disease progression and assessing the response to disease-modifying treatments. This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers in order to offer practical information for the interpretation of nuclear images by physicians involved in the care of patients with this ATTR-CA.

The impact of COVID-19 on myocardial infarctions, strokes and out-of-hospital cardiopulmonary arrests: an observational retrospective study on time-sensitive disorders in the Friuli Venezia Giulia region (Italy).

The COVID-19 global pandemic has changed considerably the way time-sensitive disorders are treated. Home isolation, people's fear of contracting the virus and hospital reorganisation have led to a significant decrease in contacts between citizens and the healthcare system, with an expected decrease in calls to the Emergency Medical Services (EMS) of the Friuli-Venezia Giulia (FVG) region. However, mortality in clinical emergencies like acute ST-elevation myocardial infarction (STEMI), stroke and out-of-hospital cardiopulmonary arrest (OHCA) remained high. An observational retrospective cross-sectional study was carried out in FVG, taking into account the period between March 1, 2020, and May 31, 2020, the first wave of the COVID-19 pandemic, and comparing it with the same period in 2019. The flow of calls to the EMS was analysed and COVID-19 impact on time-sensitive disorders (STEMIs, ischemic strokes and OHCPAs) was measured in terms of hospitalisation, treatment and mortality. Despite a -8.01% decrease (p value ˂0.001) in emergency response, a 10.89% increase in calls to the EMS was observed. A lower number of advanced cardiopulmonary resuscitations (CPR) (75.8 vs 45.2%, p=0.000021 in April) and ROSC (39.1 vs 11.6%, p=0.0001 in April) was remarked, and survival rate dropped from 8.5 to 5%. There were less strokes (-27.5%, p value=0.002) despite a more severe onset of symptoms at hospitalisation with NHISS˃10 in 38.47% of cases. Acute myocardial infarctions decreased as well (-20%, p value=0.05), but statistical significances were not determined in the variables considered and in mortality. Despite a lower number of emergency responses, the number of calls to the EMS was considerably higher. The number of cardiac arrests treated with advanced CPR (ALS) was lower, but mortality was higher. The number of strokes decreased as well, but at the time of hospitalisation the clinical picture of the patient was more severe, thus affecting the outcome when the patient was discharged. Finally, STEMI patients decreased; however, no critical issues were observed in the variables taken into account, neither in terms of response times nor in terms of treatment times.

Women at heart: Introducing gender cardio-oncology.

As cardio-oncology imposed itself as the reference specialty for a comprehensive cardiovascular approach to all patients with cancer, a more specific and careful cardiac evaluation of women entering their journey into cancer care is needed. Gender medicine refers to the study of how sex-based biological and gender-based socioeconomic and cultural differences influence people's health. Gender-related aspects could account for differences in the development, progression, and clinical signs of diseases as well as in the treatment of adverse events. Gender also accounts for major differences in access to healthcare. As for medicine and healthcare in general, gender-related characteristics have gained significance in cardio-oncology and should no longer be neglected in both clinical practice and research. We aimed to review the most relevant cardiovascular issues in women related to the cardio-oncology approach to offer a specific gender-related point of view for clinicians involved in the care process for both cancer and cardiovascular disease.

[ANMCO Position paper: Cardiovascular disease in women - prevention, diagnosis, treatment and organization of care]. / Position paper ANMCO: Malattie cardiovascolari nella donna ­ prevenzione, diagnosi, terapia e organizzazione delle cure.

Cardiovascular diseases are still the main cause of death among women despite the improvements in treatment and prognosis achieved in the last 30 years of research. The determinant factors and causes have not been completely identified but the role of "gender" is now recognized. It is well known that women tend to develop cardiovascular disease at an older age than men, and have a high probability of manifesting atypical symptoms not often recognized. Other factors may also co-exist in women, which may favor the onset of specific cardiac diseases such as those with a sex-specific etiology (differential effects of estrogens, pregnancy pathologies, etc.) and those with a different gender expression of specific and prevalent risk factors, inflammatory and autoimmune diseases and cancer. Whether the gender differences observed in cardiovascular outcomes are influenced by real biological differences remains a matter of debate.This ANMCO position paper aims at providing the state of the research on this topic, with particular attention to the diagnostic aspects and to care organization.

Novelties in Therapy of Chronic Heart Failure.

In recent decades, considerable advances have been made in the treatment of heart failure. The main target of heart failure therapy is the inhibition of the sympathetic nervous system and renin-angiotensin-aldosterone system. The angiotensin receptor blockers represent a breakthrough in the treatment of heart failure with a demonstrated effect on reduction of cardiovascular events. However, new perspectives derive from latest drugs developed for diabetes, iron deficiency, and hyperkalemia. New frontiers are also opened to the development of neurohormonal therapies, antagonists of inflammatory mediators, inotropic agents, and cell-based treatments.

Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Although oral P2Y12 inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined. OBJECTIVES: The purpose of this study was to compare downstream and upstream oral P2Y12 inhibitors administration strategies in patients with non-ST-segment elevation acute coronary syndrome undergoing invasive treatment. METHODS: We performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit). RESULTS: We randomized 1,449 patients to downstream or upstream oral P2Y12 inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: -0.46; 95% repeated confidence interval: -2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment). CONCLUSIONS: Downstream and upstream oral P2Y12 inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y12 Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837).

Heterogeneity of clinical presentation in Tako-Tsubo syndromes: the prevalence of normal segmental wall motion and normal ECG pattern.

AIM: The aim of this study is to report the heterogeneity of clinical presentation in Tako-Tsubo syndrome (TTS), including a significant prevalence of normal ECG and echocardiographic patterns in a series of consecutive patients from a single center. METHODS AND RESULTS: From our database we selected a total of 168 cases of TTS. A total of 140 of these (Group A); 14 men (10%), mean age 60.3 years, range 39-87; 126 women (90%), mean age 66.1 years, range 43-93; matched the following reported criteria: typical stenocardic pain immediately following an emotional acute stress, or acute medical or surgical event within the preceding 12 h; acute rise and fall of troponin release; absence of significant coronary disease at coronary angiography. ECG findings at presentation ranged from T wave abnormalities (41 cases, 29.3%) to ST elevation (52 cases, 37.1%) and ST depression (11 cases, 7.9%), whereas in 36 cases (25.7%) the ECG was normal. Echocardiography at presentation showed akinesia of the total apical or medium-apical segments in 74 patients (53%), whereas it showed akinesia of left ventricular wall segments in other locations in 30 patients (21%) and even normal regional wall motion and thickening in 36 patients (26%). We described also a series of 13 female patients (mean age 70.2 years; age range 45-85 years) (Group B) who did not complain of chest pain at presentation, but showed a classical Tako-Tsubo evolution of wall motion abnormalities at echocardiography. Finally we selected 15 female patients (mean age 69.3 years; age range 49-89 years) (Group C) who formally did not report acute stress immediately preceding their presentation to the hospital for chest pain. They showed a classical Tako-Tsubo evolution of wall motion abnormalities at echocardiography and only one case of normal ECG pattern at presentation. CONCLUSION: In this series of acute TTS, a wide variability of ECG and echocardiographic patterns are observed, ranging from ST elevation with coexisting segmental wall motion abnormalities of the typical TTS to a clinical presentation characterized by normal ECG and normal segmental wall motion pattern.

Cardiac imaging in patients with arterial hypertension.

Hypertension is considered the major modifiable risk factor for cardiovascular disease. Conventional echocardiography is the most common and used imaging technique and can detect anatomical and functional changes easily in a real-time, quick, noninvasive and relatively inexpensive manner. Other imaging techniques, such as magnetic resonance imaging and 3-D echocardiography gained an increasing role in selected patients, as well as the study of arterial stiffness, also using ultrasonographic echo-tracking methods. This review analyzes the role of echocardiography and other imaging techniques in the evaluation of the cardiovascular effects of hypertension.

The Ventricular-Arterial Coupling: From Basic Pathophysiology to Clinical Application in the Echocardiography Laboratory.

The interplay between cardiac function and arterial system, which in turn affects ventricular performance, is defined commonly ventricular-arterial coupling and is an expression of global cardiovascular efficiency. This relation can be expressed in mathematical terms as the ratio between arterial elastance (EA) and end-systolic elastance (EES) of the left ventricle (LV). The noninvasive calculation requires complicated formulae, which can be, however, easily implemented in computerized algorithms, allowing the adoption of this index in the clinical evaluation of patients. This review summarizes the up-to-date literature on the topic, with particular focus on the main clinical studies, which range over different clinical scenarios, namely hypertension, heart failure, coronary artery disease, and valvular heart disease.

Tako-tsubo cardiomyopathy: insights from a community hospital.

AIMS: To describe the actual incidence, prevalence among acute coronary syndrome patients and rate of recurrences of tako-tsubo cardiomyopathy in an emergency department of a community hospital. METHODS: We report the in-hospital and long-term clinical course (7.5 years follow-up) of 25 consecutive tako-tsubo cardiomyopathy patients (mean age 66.8 ±â€Š11.76 years; F/M: 21/4) admitted to a community hospital (referring population: 97,000 inhabitants). RESULTS: The incidence rate of tako-tsubo cardiomyopathy was 0.03 cases per 1000 person-years; the prevalence was 3.0% among those with acute coronary syndrome and 7.6% among ST elevation myocardial infarction patients. Clinical presentations included mainly chest pain (n = 16, 64%) and dyspnea (n = 3, 12%). Precipitating conditions were emotional (n = 10, 40%), physical stress (n = 5, 20%) or both (n = 1, 4%); no stressors were recorded in nine patients (36%). Two patients died during hospitalization (8%). At the end of follow-up (mean time: 960.24 ± 724.34 days), all patients (n = 23) were alive and no major cardiovascular events were observed. Five patients had recurrences (22%). The mean time of recurrence was 105.4 ± 82.92 days and the clinical presentation was less severe compared with the first event: ECG had less ST involvement, ejection fraction was higher and cardiac injury biomarkers were lower. CONCLUSIONS: In our population incidence and prevalence of tako-tsubo cardiomyopathy among acute coronary syndrome patients, as well as the recurrence rate of tako-tsubo cardiomyopathy, were higher than previously reported, suggesting that probably this syndrome often passes undiagnosed.

[Patent foramen ovale and cardiovascular stroke: the eternal dilemma]. / Forame ovale pervio e ictus cardioembolico: l'eterno dilemma.

Ischemic stroke is one of the leading causes of mortality and the most important determinant of disability in developed countries. Its association with patent foramen ovale is one of the more controversial issues of the literature, also because paradoxical embolism is frequently a diagnosis of suspicion. Up to now, no clinical randomized studies unequivocally demonstrated the causality of this association. Comparing international guidelines there are substantial differences in clinical recommendations among scientific societies, which confirm the uncertainty surrounding this field. Actually, the superiority of transcatheter percutaneous closure over medical therapy alone is not confirmed, partially as a consequence of significant variability in the inclusion criteria, technical approach, peri- and post-procedural therapy among different studies. Moreover, the procedure is very recent and very few studies report prospective data about the safety and effectiveness of patent foramen ovale closure at long-term follow-up. A careful assessment of both clinical characteristics of patients and anatomical features of patent foramen ovale is very helpful to drive a personalized choice for the individual patient. On the basis of the available evidence, this review re-examines the impact of patent foramen ovale in the etiology of cryptogenic cerebrovascular events as well as the advantages and disadvantages of different treatment modalities, waiting for more scientific consensus.