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INTRODUCTION: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear. METHODS: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death. RESULTS: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15 days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P = 0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50 × 103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50 mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P = 0.05). CONCLUSIONS: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death.

Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission.We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ± 13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all P 0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78).In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs—in terms of quality of life—in European countries.

In patients with heart failure (HF), the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Biomarker Study Group of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with HFrEF because most studies on cardiac remodelling focused on this setting.

[Abstract] Aims: To perform a comprehensive characterization of acute heart failure (AHF) with preserved (HFpEF), versus mildly reduced (HFmrEF) versus reduced ejection fraction (HFrEF). Methods and results: Of 5951 participants in the ESC HF Long-Term Registry hospitalized for AHF (acute coronary syndromes excluded), 29% had HFpEF, 18% HFmrEF, and 53% HFrEF. Hospitalization reasons were most commonly atrial fibrillation (more in HFmrEF and HFpEF), followed by ischaemia (HFmrEF), infection (HFmrEF and HFpEF), worsening renal function (HFrEF), and uncontrolled hypertension (HFmrEF and HFpEF). Hospitalization characteristics included lower blood pressure, more oedema and higher natriuretic peptides with lower ejection fraction, similar pulmonary congestion, more mitral regurgitation in HFrEF and HFmrEF and more tricuspid regurgitation in HFrEF. In-hospital mortality was 3.4% in HFrEF, 2.1% in HFmrEF and 2.2% in HFpEF. Intravenous diuretic (∼80%) and nitrate (∼15%) use was similar but inotrope use greater in HFrEF (16%, vs. HFmrEF 7.4% vs. HFpEF 5.3%). Weight loss and estimated glomerular filtration rate improvement were greater in HFrEF, whereas reduction in natriuretic peptides was similar. Over 1 year post-discharge, events per 100 patient-years (95% confidence interval) in HFrEF versus HFmrEF versus HFpEF were: all-cause death 22 (20-24) versus 17 (14-20) versus 17 (15-20); cardiovascular (CV) death 12 (10-13) versus 8.6 (6.6-11) versus 8.4 (6.9-10); non-CV death 2.4 (1.8-3.1) versus 3.3 (2.1-4.8) versus 4.5 (3.5-5.9); all-cause hospitalization 48 (45-51) versus 35 (31-40) versus 42 (39-46); HF hospitalization 29 (27-32) versus 19 (16-22) versus 17 (15-20); and non-CV hospitalization 7.7 (6.6-8.9) versus 9.6 (7.5-12) versus 15 (13-17). Conclusion: In AHF, HFrEF is more severe and has greater in-hospital mortality. Post-discharge, HFrEF has greater CV risk, HFpEF greater non-CV risk, and HFmrEF lower overall risk.

Aims Physical activity (PA) is important in patients with heart failure (HF) to improve health outcomes. The adherence to PA is low, and therefore, novel approaches are necessary to increase PA. We aimed to determine the difference in PA in patients with HF who have access to exergaming compared to patients who received motivational support and to explored predictors of a clinically relevant change in non-sedentary time between baseline and 3 months. Methods and results In total, 64 patients (mean age 69 ± 9 years, 27% female) wore an accelerometer 1 week before and 1 week after the intervention. Data were analysed using logistic regression analysis. Patients spent 9 h and 43 min (±1 h 23 min) during waking hours sedentary. There were no significant differences in PA between patients who received an exergame intervention or motivational support. In total, 30 of 64 patients achieved a clinically relevant increase in non-sedentary time. Having grandchildren [odds ratio (OR) 7.43 P = 0.03], recent diagnosis of HF (OR 0.93 P = 0.02), and higher social motivation (OR 2.31 P = 0.03) were independent predictors of a clinically relevant increase of non-sedentary time. Conclusion Clinicians should encourage their patients to engage in alternative approaches to improve PA and reduce sedentary habits. Future exergaming interventions should target individuals with chronic HF who have low social motivation and a low level of light PA that may benefit most from exergaming. Also (non-familial), intergenerational interaction is important to enabling patients in supporting patients in becoming more active.

©The European Society of Cardiology 2020. Article reuse guidelines : sagepub.com/journals-permissions, Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and ‘modern’ cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.

Aims There is still uncertainty on the management of patients with pheochromocytoma-induced CS (PICS), as only a few clinical cases have been reported. The aim of this study is to investigate the clinical presentation, management, and outcome of patients with PICS. Methods We collected retrospectively 18 patients without previously known pheochromocytoma with histologically proven PICS admitted to 8 European hospitals. Results Among the 18 patients with a mean age of 50 years, 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension crises and hypotension (72%). On echocardiography, mean left ventricular ejection fraction (LVEF) was 25% with an atypical-Takotsubo pattern (basal/midventricular) in 50%. Laboratory exams showed increased inflammatory markers, in particular, the mean white blood count was 21.9*109/L. Inotropes/vasopressors were started in all patients and a temporary mechanical circulatory support (t-MCS) was required in 11 (61.1%) patients. All patients underwent surgical removal of the pheochromocytoma but 4 (22.2%) on t-MCS. Echocardiogram (16/17 patients) revealed a mean LVEF of 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. Conclusions In patients with PICS, characteristically, an atypical Takotsubo pattern was observed in almost half of the cases. Although the use of exogenous catecholamine can be perceived as deleterious, we showed a fairly good mid-term prognosis with rapid improvement of LVEF in most, even if adrenalectomy often occurred on t-MCS.

Background β-blockers are one of the four recommended disease-modifying classes of drugs for the treatment of heart failure with reduced ejection fraction (HFrEF). Although their efficacy and prognostic role is unquestionable in the general population of HFrEF patients, the differences in their effect in relation to sex have not been yet investigated in detail. The present study analyzed a large, real-world, Italian population of HFrEF patients aiming to highlight any prognostic difference between males and females in relation to dose and β-selectivity of the ongoing β-blocker treatment. Methods Out of the 7900 HFrEF patients included in the MECKI score registry, we retrospectively analyzed those treated with β-blockers. We investigated the prognostic role of β-selectivity, dividing the population in assuming β1/β2-receptor blockers (carvedilol) vs. β1-selective blockers (bisoprolol, nebivolol or metoprolol), according to sex, and the prognostic role of daily carvedilol-equivalent β-blocker dose in relation to sex. The primary outcome of the study was the composite of all cause mortality, urgent heart transplant and LVAD implant analyzed at 5 years, both as raw data and after correction of potential confounders. Results 6784 HFrEF patients treated with β-blockers were analyzed (1215 females, 5569 males). Patients median follow-up was 4.05 years [1.72-7.47]: 4.37 [1.6-8.13] for females and 3.99 [1.75-7.3] for males (p=ns). According to β-selectivity no prognostic differences were found in the general population, as in female or males (Fig. 1 right panel). Stratification of patients according to β-blockers equivalent dose showed significant difference among groups: mortality decreases with increasing β-blockers dose in both males and females (Fig. 1, left panel), both at baseline and after adjustment for the main confounders (LVEF, age, peakVO2, systolic pressure, hemoglobin, rest heart rate; VE/VCO2 slope, etiology. ICD, MDRD). Conclusions In a large, real-life population of chronic HFrEF patients analyzed according to sex, no prognostic differences were found between stratifying for β-selectivity. A better outcome was observed in subjects receiving a high daily dose, independently from sex.

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

BackgroundEnterobius vermicularis (E. vermicularis) is a nematode that infects up to 200 million people worldwide, despite effective medications being available. Conventional diagnostic tests are hindered by low sensitivity and poor patient compliance. Furthermore, no biomolecular techniques are available for clinical application. The aim of this study was to develop a procedure specifically designed for clinical application to detect E. vermicularis by means of PCR.Materials and methodsTwo subject groups were taken into account: a group of 27 infected patients and a control group of 27 healthy subjects. A nested-PCR was performed on fecal samples to detect E. vermicularis. Due to the intrinsic difficulties of the fecal matrix, several countermeasures were adopted to ensure the efficient performance of the method: (a) a large amount of feces for the extraction process (20 g instead of 200 mg); (b) a combination of chemical and physical treatments to grind the fecal matrix; (c) an additional purification process for the negative samples after the first nested-PCR; and (d) the selection of a very specific target region for the PCR.ResultsDue to the lack of overlap with other organisms, a sequence of the 5S ribosomal DNA (rDNA) spacer region including the tract SL1 was chosen to design appropriate external and internal primers. The first nested-PCR detected E.vermicularis in 19/27 samples from infected patients. After further purification, 5/8 of the negative samples resulted positive at the second PCR. Conversely, all the samples from healthy controls resulted negative to both PCRs. Sensitivity and specificity of the method were, respectively, 88.9% and 100%.ConclusionThe results prove the high diagnostic accuracy of the proposed method, addressing and overcoming the challenges posed by both conventional tests and PCR-based approaches. Therefore, the method can be proposed for clinical application.

Background Heart failure with preserved ejection fraction (HFpEF) diagnosis remains challenging, since several mechanisms (diastolic and systolic reserve abnormalities, chronotropic incompetence, ventricular or vascular stiffening, atrial dysfunction, pulmonary hypertension, impaired vasodilation, endothelial dysfunction, energetic abnormalities and autonomic dysfunction) play different roles in HFpEF development. European Society of Cardiology HF guidelines recently suggested a stepwise non-invasive diagnostic approach consisting of three steps: the first is clinical, the second includes echocardiographic and laboratory data (natriuretic peptides), named HFA-PEEF score, and finally, in case of inconclusive findings, diastolic stress echocardiography is recommended. On the other hand, in United States, another multiparametric score, named H2FPEF, has been proposed for HFpEF diagnosis, and including, in addition to echocardiographic parameters, also clinical data; thereby more applicable in the outpatient clinical arena. Purpose Whether there is a clinical overlap between the two scores (HFA-PEEF and H2FPEF) as well as whether the addition of clinical data to the HFA-PEEF could improve its ability to identify different HFpEF phenotypes is still an open issue and these were the aims of our study. Methods HFA-PEEF and H2FPEF scores were systematically applied on 1,156 consecutive subjects with preserved ejection fraction who undergone cardiovascular evaluation at the Cardiovascular Prevention Center of Fondazione Don Gnocchi & University of Parma. All subjects underwent cardiovascular risk assessment followed by echocardiography and cardiopulmonary exercise testing; due to the outpatient (non-acute) setting of the evaluation, natriuretic peptides assay was not performed. Clinical data and cardiovascular risk factors data were compared between different groups of HFpEF risk. Results According to H2FPEF score, low risk (75%) in 197 (17%); according to HFA-PEEF score, 675 (58%) had 0 or 1 point, 253 (22%) had 2 points and 230 (20%) had 3 or 4 points (moderate-to-high risk). Patients with higher HFA-PEEF score were older (p75 years to a 4.6-fold higher risk, HTN to a 3.6-fold higher risk (p Conclusions Although HFA-PEEF score does not include clinical data, patients with older age, atrial fibrillation, hypertension, hypertensive heart, diabetes, sedentary lifestyle and chronic coronary syndrome show a higher ESC risk of HFpEF. Funding Acknowledgement Type of funding sources: None.

Background Exercise intolerance evaluation in Heart failure with preserved ejection fraction (HFpEF) remains challenging, since several mechanisms (diastolic and systolic reserve abnormalities, low chronotropic reserve (CR), ventricular or vascular stiffening, atrial dysfunction, pulmonary hypertension, endothelial dysfunction, energetic abnormalities and autonomic dysfunction) play different roles. European Society of Cardiology HF guidelines recently suggested a stepwise non-invasive HFpEF diagnostic approach consisting of three steps: clinical, echocardiographic and laboratory data (natriuretic peptides), named HFA-PEEF Score, and finally, in case of inconclusive findings, diastolic stress echocardiography data. Cardiopulmonary exercise testing (CPET) may represent a promising further non-invasive diagnostic tool in HFpEF evaluation since allow to assess the presence of reduced functional capacity as well as to differentiate between cardiovascular, ventilatory or peripheral causes. Purpose Whether increased risk of HFpEF is associated with different and specific cardiopulmonary responses to exercise is still an open issue and this was the aim of our study. Methods 1.156 consecutive subjects with preserved ejection fraction undergoing cardiovascular evaluation at the Cardiovascular Prevention Center of Fondazione Don Gnocchi & University of Parma were enrolled. All subjects underwent cardiovascular evaluation and echocardiography, HFA-PEEF and H2FPEF Score assessment and cardiopulmonary exercise testing. Different cardiopulmonary response to exercise were compared between different groups of HFpEF risk. Results According to HFA-PEEF Score, 675 (58%) had 0 or 1 point, 253 (22%) had 2 points and 230 (20%) had 3 or 4 points (moderate-to-high risk). Patients with both higher HFA-PEEF and H2FPEF Score showed lower functional capacity, expressed as low peak V02 (p35) to a 2.4-fold higher risk (p Conclusions Different degrees HFpEF risk, estimated using both HFA-PEEF and H2FPEF score, are associated with different cardiopulmonary responses to exercise. High HFpEF risk patients show low functional capacity, cardiovascular and ventilator efficiency due to lower cardiac output at peak, despite preserved ejection fraction, associated to lower chronotropic response to exercise. Funding Acknowledgement Type of funding sources: None.