Noninvasive Assessment in Takotsubo Syndrome: A Diagnostic Challenge.

Takotsubo syndrome (TTS) is a clinical syndrome characterized by a transient left ventricular dysfunction whose diagnosis can be challenging due to its resemblance to acute myocardial infarction (AMI). Despite the growing recognition of TTS, acute complications and long-term mortality rates are comparable to those observed in AMI patients. In this context, a systematic diagnostic approach is imperative for an accurate patient assessment, with due consideration of the distinctive characteristics and optimal timing of each imaging modality. Coronary angiography with ventriculography may be reserved for cases presenting with ST-segment elevation, whereas in all other cases, the use of multimodality noninvasive imaging allows for a comprehensive evaluation of typical diagnostic features and detection of acute complications while also providing prognostic insights. The aim of this review is to evaluate the current research on non-invasive modalities and to propose a diagnostic algorithm that will facilitate the identification and management of TTS.

Cancer and Heart Failure: Dangerous Liaisons.

Cancer and heart failure (HF) are increasingly relevant worldwide, both from an epidemiologic and clinical point of view. This review aims to explore the relationship between cancer and HF by underscoring risk factors and disclosing the cardiotoxic effects of the current chemotherapy agents. We also deal with the current evidence on the diagnosis and management of HF related to cancer therapy. Finally, we will address the main gaps in knowledge and future perspectives in this field.

Impact of Newly Diagnosed Cancer on Bleeding Events in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants.

BACKGROUND: In patients with atrial fibrillation (AF), the association between cancer and cardioembolic or bleeding risk during oral anticoagulant therapy still remains unclear. PURPOSE: We aimed to assess the impact of cancer present at baseline (CB) or diagnosed during follow-up (CFU) on bleeding events in patients treated with direct oral anticoagulants (DOACs) for non-valvular AF (NVAF) compared with patients without CB or CFU, respectively. METHODS: All consecutive patients with NVAF treated with DOACs for stroke prevention were enrolled between January 2017 and March 2019. Primary outcomes were bleeding events or cardiovascular death, non-fatal stroke and non-fatal myocardial infarction, and the composite endpoint between patients with and without CB and between patients with and without CB. RESULTS: The study population comprised 1170 patients who were followed for a mean time of 21.6 ± 9.5 months. Overall, 81 patients (6.9%) were affected by CB, while 81 (6.9%) were diagnosed with CFU. Patients with CFU were associated with a higher risk of bleeding events and major bleeding compared with patients without CFU. Such an association was not observed between the CB and no CB populations. In multivariate analysis adjusted for anemia, age, creatinine, CB and CFU, CFU but not CB remained an independent predictor of overall and major bleeding (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.8-3.89, p < 0.001; HR 3.02, 95% CI 1.6-3.81, p = 0.001, respectively). CONCLUSION: During follow-up, newly diagnosed primitive or metastatic cancer in patients with NVAF taking DOACs is a strong predictor of major bleeding regardless of baseline hemorrhagic risk assessment. In contrast, such an association is not observed with malignancy at baseline. Appropriate diagnosis and treatment could therefore reduce the risk of cancer-related bleeding.

Spectrum of electrocardiographic abnormalities in a large cohort of cardiac masses.

BACKGROUND: Cardiac masses represent a heterogeneous clinical scenario. Potential electrocardiographic (ECG) red flags of malignancy remain to be investigated. OBJECTIVES: The purpose of this study was to describe the spectrum of ECG abnormalities in a large cohort of cardiac masses and to evaluate potential red flags suggestive of malignancy. METHODS: This was an observational cohort study of 322 consecutive patients with a cardiac mass and available ECG at Bologna University Hospital. All masses were diagnosed by histologic examination or, in the case of cardiac thrombi, by radiologic resolution after proper anticoagulant therapy. Multivariable regression analysis was used to assess potential predictors of malignancy among ECG abnormalities. All-cause mortality at follow-up was evaluated. RESULTS: Of 322 patients, 98 (30.4%) had malignant tumors. Compared with patients with benign masses, those with malignant tumors exhibited a higher heart rate, right-axis deviation, greater depolarization, repolarization abnormalities, and bradyarrhythmia at presentation. Regarding specific ECG features, a higher heart rate on admission (P = .014), bradyarrhythmias (P = .009), ischemic-like repolarization abnormalities (ST-segment deviation, both depression and elevation, and negative T-wave; P <.001), low voltages (P = .001), and right-axis deviation (P = .025) were identified as independent predictors of malignancy. Considering these specific ECG alterations, a malignancy-oriented ECG was associated with higher mortality at follow-up (median 20.7 months). CONCLUSION: ECG frequently is abnormal in cases of malignant cardiac tumors. Some specific ECG changes are strongly suggestive for malignancy and type of infiltration.

[Periprocedural myocardial injury and infarction after myocardial revascularization: incidence, clinical features and prognosis]. / Infarto e danno miocardico periprocedurali dopo rivascolarizzazione miocardica: incidenza, implicazioni cliniche e prognosi.

Myocardial revascularization, either percutaneous or surgical, is the cornerstone of chronic and acute ischemic coronary artery disease therapy. Periprocedural myocardial injury and infarction are possible complications of these procedures. Several pathogenetic mechanisms have been proposed in the setting of percutaneous (distal embolism, vasospasm, obstruction of a minor vessel) or surgical revascularization (prolonged ischemic time, early graft failure, arrhythmia or severe hypotension during the procedure). High-sensitivity cardiac troponins have emerged as the recommended biomarkers due to their important prognostic implications. However, data regarding diagnostic criteria, management and prognostic implications of these complications are lacking. The present review aims to provide an overview regarding the possible diagnostic criteria, management and prognostic role of periprocedural myocardial injury and infarction.

Performance of Prognostic Scoring Systems in MINOCA: A Comparison among GRACE, TIMI, HEART, and ACEF Scores.

Background: the prognosis of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is not benign; thus, prompting the need to validate prognostic scoring systems for this population. Aim: to evaluate and compare the prognostic performance of GRACE, TIMI, HEART, and ACEF scores in MINOCA patients. Methods: A total of 250 MINOCA patients from January 2017 to September 2021 were included. For each patient, the four scores at admission were retrospectively calculated. The primary outcome was a composite of all-cause death and acute myocardial infarction (AMI) at 1-year follow-up. The ability to predict 1-year all-cause death was also tested. Results: Overall, the tested scores presented a sub-optimal performance in predicting the composite major adverse event in MINOCA patients, showing an AUC ranging between 0.7 and 0.8. Among them, the GRACE score appeared to be the best in predicting all-cause death, reaching high specificity with low sensitivity. The best cut-off identified for the GRACE score was 171, higher compared to the cut-off of 140 generally applied to identify high-risk patients with obstructive AMI. When the scores were tested for prediction of 1-year all-cause death, the GRACE and the ACEF score showed very good accuracy (AUC = 0.932 and 0.828, respectively). Conclusion: the prognostic scoring tools, validated in AMI cohorts, could be useful even in MINOCA patients, although their performance appeared sub-optimal, prompting the need for risk assessment tools specific to MINOCA patients.

Predictive value of Killip classification in MINOCA patients.

BACKGROUND: Killip classification is a practical clinical tool for risk stratification in patients with acute myocardial infarction (AMI). However, its prognostic role in myocardial infarction with non-obstructive coronary artery (MINOCA) is still poorly explored. Our purpose was to evaluate the prognostic role of high Killip class in the specific setting of MINOCA and compare the results with a cohort of patients with obstructive coronary arteries myocardial infarction (MIOCA). METHODS: This study included 2455 AMI patients of whom 255 were MINOCA. We compared the Killip classes of MINOCA with those of MIOCA and evaluated the prognostic impact of a high Killip class, defined if greater than I, on both populations' outcome. Short-term outcomes included in-hospital death, re-AMI and arrhythmias. Long-term outcomes were all-cause mortality, re-AMI, stroke, heart failure (HF) hospitalization and the composite endpoint of MACE. RESULTS: Killip class >1 occurred in 25 (9.8%) MINOCA patients compared to 327 (14.9%) MIOCA cases. In MINOCA subjects, a high Killip class was associated with a greater in-hospital mortality (p = 0.002) and, at long term follow-up, with a three-fold increased mortality (p = 0.001) and a four-fold risk of HF hospitalization (p = 0.003). Among MINOCA, a high Killip class was identified as a strong independent predictor of MACE occurrence [HR 2.66, 95% CI (1.25-5.64), p = 0.01] together with older age and worse kidney function while in MIOCA population also left ventricular ejection fraction and troponin value predicted MACE. CONCLUSIONS: Killip classification confirmed its prognostic impact on short- and long-term outcomes also in a selected MINOCA population, which still craves for a baseline risk stratification.

Sex- and age-related differences in outcomes of patients with acute myocardial infarction: MINOCA vs. MIOCA.

AIMS: The aim of the study is to evaluate the impact of sex on acute myocardial infarction (AMI) patients' clinical presentation and outcomes, comparing those with non-obstructive and obstructive coronary arteries (MINOCA vs. MIOCA). METHODS AND RESULTS: We enrolled 2455 patients with AMI undergoing coronary angiography from January 2017 to September 2021. Patients were divided according to the type of AMI and sex: male (n = 1593) and female (n = 607) in MIOCA and male (n = 87) and female (n = 168) in MINOCA. Each cohort was further stratified based on age (≤/> 70 years). The primary endpoint (MAE) was a composite of all-cause death, recurrent AMI, and hospitalization for heart failure (HF) at follow-up. Secondary outcomes included all-cause and cardiovascular death, recurrent AMI, HF re-hospitalization, and stroke. MINOCA patients were more likely to be females compared with MIOCA ones (P < 0.001). The median follow-up was 28 (15-41) months. The unadjusted incidence of MAE was significantly higher in females compared with males, both in MINOCA [45 (26.8%) vs. 12 (13.8%); P = 0.018] and MIOCA cohorts [203 (33.4%) vs. 428 (26.9%); P = 0.002]. Age was an independent predictor of MAE in both cohorts. Among MINOCA patients, females ≤70 years old had a higher incidence of MAE [18 (23.7%) vs. 4 (5.9%); P = 0.003] compared with male peers, mainly driven by a higher rate of re-hospitalization for HF (P = 0.045) and recurrence of AMI (P = 0.006). Only in this sub-group of MINOCA patients, female sex was an independent predictor of MAE (hazard ratio = 3.09; 95% confidence interval: 1.02-9.59; P = 0.040). MINOCA females ≤70 years old had worse outcomes than MIOCA female peers. CONCLUSION: MINOCA females ≤70 years old had a significantly higher incidence of MAE, compared with males and MIOCA female peers, likely due to the different pathophysiology of the ischaemic event. TRIAL REGISTRATION: Data were part of the ongoing observational study 'AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation' (ClinicalTrials.gov Identifier: NCT03883711).

Sex-Related Disparities in Cardiac Masses: Clinical Features and Outcomes.

BACKGROUND: Cardiac masses (CM) represent a heterogeneous clinical scenario, and sex-related differences of these patients remain to be established. PURPOSE: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. MATERIAL AND METHODS: The study cohort included 321 consecutive patients with CM enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause mortality at follow-up was evaluated. Multivariable regression analysis assessed the potential prognostic disparities between men and women. RESULTS: Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p = 0.02) than men. Regarding CM histotypes, females were affected by benign masses more frequently (with cardiac myxoma above all), while metastatic tumours were more common in men (p < 0.001). At presentation, peripheral embolism occurred predominantly in women (p = 0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, in multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignant tumours and peripheral embolism were independent predictors of mortality. CONCLUSIONS: In a large cohort of cardiac masses, a significant sex-related difference in histotype prevalence was found: Benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex did not influence prognosis in benign and malignant masses.

On the distribution functions of depletion interactions.

Molecular dynamics computer simulations were performed on model colloidal binary mixtures of two large and many small soft repulsive spheres. Depletion forces arise between the two large spheres, as a function of their distance, because of the nonadditivity of the volume they exclude to the small spheres. The probability distribution functions of both longitudinal and transverse component of the total force exerted by the small particles were calculated and generally turned out non-Gaussian. The distributions of the collective forces were analyzed in terms of the distribution of the force that a single small sphere exerts on a large sphere and of the number of the surrounding small spheres. The reconstructed function matches well the corresponding exact distribution. Residual correlation among small particles, combined with a relatively small number of neighbors, slows the approach to the Gaussian limit. In our fully repulsive model, the direct force between a large and a small sphere is a monotonic function of their distance. On these bases, we propose and successfully test an approach that relates the probability distribution function of the depletion forces to the large-sphere-small-sphere radial distribution function. This approach can be extended to experimental data of radial distribution function, thus allowing for an estimate of depletion force fluctuations in real colloidal mixtures.

Orientational dynamics in the isotropic phase of a calamitic liquid-crystal model.

We report a molecular dynamics simulation study on the isotropic phase of an idealized calamitic liquid crystal model with a length-to-width ratio of approximately 5-6. The study focuses on the characterization of single-particle and collective orientational dynamics on approaching the phase transition to the nematic phase. Recent experimental and simulation works have suggested that a power law behavior exists at relatively short times in the decay of the time derivative of the orientational correlation functions. Qualitatively, our simulation data are consistent with these findings. Both single-particle and collective time correlation function derivatives possess, in their respective log-log plots, a linear region at very short times, whose slope is essentially independent from the thermodynamic state. Nevertheless, the single-particle orientational correlation functions are better described by a function which is the sum of a fast exponential, an intermediate stretched-exponential and a slow exponential, while the collective orientational correlation functions are satisfactorily described by a sum of two exponentials, at higher density, or by just one exponential, at lower density.