Estimating maximum work rate during cardiopulmonary exercise testing from the six-minute walk distance in patients with heart failure.

Background: Exercise is recommended for patients with chronic heart failure (CHF) and its intensity is usually set as a percentage of the maximal work rate (MWR) during cardiopulmonary exercise testing (CPX) or a symptom-limited incremental test (SLIT). As these tests are not always available in cardiac rehabilitation due to logistic/cost constraints, we aimed to develop a predictive model to estimate MWR at CPX (estMWR@CPX) in CHF patients using anthropometric and clinical measures and the 6-min walk test (6 MWT), the most widely used exercise field test. Methods: This is a multicentre cross-sectional retrospective study in a cardiac rehabilitation setting. Six hundred patients with HF in New York Heart Association (NYHA) functional class I-III underwent both CPX and 6 MWT and, through multivariable linear regression analysis, we defined several predictive models to define estMWR@CPX. Results: The best model included 6 MWT, sex, age, weight, NYHA class, left ventricular ejection fraction (LVEF), smoking status and chronic obstructive pulmonary disease COPD (adjusted R2 = 0.55; 95% LoA -39 to 33 W). When LVEF was excluded as a predictor, the resulting model performed only slightly worse (adjusted R2 = 0.54; 95% LoA -42 to 34 W). Only in 34% of cases was the percentage difference between estMWR@CPX and real MWR@CPX <10% in absolute value. EstMWR@CPX tended to overestimate low values and underestimate high values of true MWR@CPX. Conclusions: Our results showed a lack of accuracy in the predictive model evaluated; therefore, for an accurate prescription of cycle-ergometer exercise training, it is necessary to assess MWR by CPX or SLIT.

Incremental prognostic value of functional impairment assessed by 6-min walking test for the prediction of mortality in heart failure.

Natriuretic peptides (NP) are recognized as the most powerful predictors of adverse outcomes in heart failure (HF). We hypothesized that a measure of functional limitation, as assessed by 6-min walking test (6MWT), would improve the accuracy of a prognostic model incorporating a NP. This was a multicenter observational retrospective study. We studied the prognostic value of severe functional impairment (SFI), defined as the inability to perform a 6MWT or a distance walked during a 6MWT < 300 m, in 1696 patients with HF admitted to cardiac rehabilitation. The primary outcome was 1-year all-cause mortality. After adjusting for the baseline multivariable risk model-including age, sex, systolic blood pressure, anemia, renal dysfunction, sodium level, and NT-proBNP-or for the MAGGIC score, SFI had an odds ratio of 2.58 (95% CI 1.72-3.88; p < 0.001) and 3.12 (95% CI 2.16-4.52; p < 0.001), respectively. Adding SFI to the baseline risk model or the MAGGIC score yielded a significant improvement in discrimination and risk classification. Our data suggest that a simple, 6MWT-derived measure of SFI is a strong predictor of death and provide incremental prognostic information over well-established risk markers in HF, including NP, and the MAGGIC score.

Taking a walk on the heart failure side: comparison of metabolic variables during walking and maximal exertion.

AIMS: Although cardiopulmonary exercise testing (CPET) is the gold standard to assess exercise capacity, simpler tests (i.e., 6-min walk test, 6MWT) are also commonly used. The aim of this study was to evaluate the relationship between cardiorespiratory parameters during CPET and 6MWT in a large, multicentre, heterogeneous population. METHODS: We included athletes, healthy subjects, and heart failure (HF) patients of different severity, including left ventricular assist device (LVAD) carriers, who underwent both CPET and 6MWT with oxygen consumption measurement. RESULTS: We enrolled 186 subjects (16 athletes, 40 healthy, 115 non-LVAD HF patients, and 15 LVAD carriers). CPET-peakV̇O2 was 41.0 [35.0-45.8], 26.2 [23.1-31.0], 12.8 [11.1-15.3], and 15.2 [13.6-15.6] ml/Kg/min in athletes, healthy, HF patients, and LVAD carriers, respectively (P < 0.001). During 6MWT they used 63.5 [56.3-76.8], 72.0 [57.8-81.0], 95.5 [80.3-109], and 95.0 [92.0-99.0] % of their peakV̇O2, respectively. None of the athletes, 1 healthy (2.5%), 30 HF patients (26.1%), and 1 LVAD carrier (6.7%), reached a 6MWT-V̇O2 higher than their CPET-peakV̇O2. Both 6MWT-V̇O2 and walked distance were significantly associated with CPET-peakV̇O2 in the whole population (R2 = 0.637 and R2 = 0.533, P ≤ 0.001) but not in the sub-groups. This was confirmed after adjustment for groups. CONCLUSIONS: The 6MWT can be a maximal effort especially in most severe HF patients and suggest that, in absence of prognostic studies related to 6MWT metabolic values, CPET should remain the first method of choice in the functional assessment of patients with HF as well as in sport medicine.

Effect of lateral position on rostral fluid shift and relationship to severity of Cheyne-Stokes respiration in heart failure patients.

PURPOSE: Lateral sleep position has a significant beneficial effect on the severity of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure (HF). We hypothesized that a reduction in rostral fluid shift from the legs in this position compared with the supine position may contribute to this effect. METHODS: In patients with CSR-CSA and an apnea-hypopnea index (AHI) ≥ 15/h (by standard polysomnography), uncalibrated leg fluid volume was measured in the supine, left lateral decubitus, and right lateral decubitus positions (in-laboratory assessment). The correlation between postural changes in fluid volume and corresponding changes in AHI was evaluated. Since there was no difference in both leg fluid volume and AHI between the right and left positions, measurements in these two conditions were combined into a single lateral position. RESULTS: In 18 patients with CSR-CSA, leg fluid volume increased by 2.7 ± 3.1% (p = 0.002) in the lateral position compared to the supine position, while AHI decreased by 46 ± 20% (p < 0.0001) with the same postural change. The correlation between postural changes in AHI and leg fluid volume was 0.22 (p = 0.42). Changes in leg fluid volume were a slow phenomenon, whereas changes in CSR-CSA severity were almost synchronous with changes in posture. CONCLUSION: Lateral position causes a reduction in rostral fluid shift compared to the supine position, but this change does not correlate with the corresponding change in CSR-CSA severity. The two changes occur on different time scales. These findings question the role of postural changes in rostral fluid shift as a determinant of corresponding changes in CSR-CSA severity.

[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.

Patients' Clinical and Psychological Status in Different COVID-19 Waves in Italy: A Quanti-Qualitative Study.

BACKGROUND: COVID-19 waves have been characterized by different clinical manifestations, a decrease of functional abilities, and the presence of psychological symptoms. The aims of this study were to investigate differences in physical and psychological symptoms during the three Italian waves of the coronavirus pandemic. METHODS: Patients undergoing a functional, cardiological and pneumological check-up follow-up at ICS Maugeri Institutes, 2-3 months after recovery from COVID-19 were consecutively recruited to participate in the study, completing a quanti-qualitative questionnaire about anxiety, depression, PTSD symptoms, and personal resources. RESULTS: 104 patients were recruited: 44 and 60 during the first and second/third pandemic waves, respectively. Physical comorbidities were more present in the second/third waves compared to the first one, while no significant differences were found in anxious and depressive symptoms, which were significantly higher than normal during the three waves; PTSD symptoms were reported by 56.3% of patients. Family, social support, and a positive mindset were described as resources to cope with the COVID-19 burden. Negative affects arose during outbreaks (panic) and the disease (fear), while positive affect (joy) characterized only the follow-up period. CONCLUSION: This study shows how psychophysical symptoms might change during the pandemic waves and highlights the importance of protective factors to balance the subjective distress.

COVID-19 teleassistance and teleconsultation: a matched case-control study (MIRATO project, Lombardy, Italy).

Background: During the COVID-19 pandemic, telemedicine has been recognised as a powerful modality to shorten the length of hospital stay and to free up beds for the sicker patients. Lombardy, and in particular the areas of Bergamo, Brescia, and Milan, was one of the regions in Europe most hit by the COVID-19 pandemic. The primary aim of the MIRATO project was to compare the incidence of severe events (hospital readmissions and mortality) in the first three months after discharge between COVID-19 patients followed by a Home-Based Teleassistance and Teleconsultation (HBTT group) program and those discharged home without Telemedicine support (non-HBTT group). Methods: The study was designed as a matched case-control study. The non-HBTT patients were matched with the HBTT patients for sex, age, presence of COVID-19 pneumonia and number of comorbidities. After discharge, the HBTT group underwent a telecare nursing and specialist teleconsultation program at home for three months, including monitoring of vital signs and symptoms. Further, in this group we analysed clinical data, patients' satisfaction with the program, and quality of life. Results: Four hundred twenty-two patients per group were identified for comparison. The median age in both groups was 70 ± 11 years (62% males). One or more comorbidities were present in 86% of the HBTT patients and 89% in the non-HBTT group (p = ns). The total number of severe events was 17 (14 hospitalizations and 3 deaths) in the HBTT group and 40 (26 hospitalizations and 16 deaths) in the non-HBTT group (p = 0.0007). The risk of hospital readmission or death after hospital discharge was significantly lower in HBTT patients (Log-rank Test p = 0.0002). In the HBTT group, during the 3-month follow-up, 5,355 teleassistance contacts (13 ± 4 per patient) were performed. The number of patients with one or more symptoms declined significantly: from 338 (78%) to 183 (45%) (p < 0.00001). Both the physical (ΔPCS12: 5.9 ± 11.4) component and the mental (ΔMCS12: 4.4 ± 12.7) component of SF-12 improved significantly (p < 0.0001). Patient satisfaction with the program was very high in all participants. Conclusions: Compared to usual care, an HBTT program can reduce severe events (hospital admissions/mortality) at 3-months from discharge and improve symptoms and quality of life. Clinical trial registration: www.ClinicalTrials.gov, NCT04898179.

Day and night heart rate variability using 24-h ECG recordings: a systematic review with meta-analysis using a gender lens.

PURPOSE: Increasing evidence demonstrates that gender-related factors, and not only biological sex, are relevant in the physiological and pathophysiological mechanisms of the cardiovascular system, including the cardiac autonomic regulation. Sex and gender may also affect daytime and night-time cardiac autonomic control. This meta-analysis aimed to provide a comparison between healthy women and men on heart rate variability using 24-h ECG recordings pointing out sex- and gender-related factors. METHODS: A systematic search was conducted to include studies focusing on both sex and gender differences related to heart rate variability indices in the time and frequency domains. Descriptive data were extracted by two independent reviewers. For each index, standardized mean differences with 95% confidence intervals were computed and a pooled estimate using a fixed- or random-effects model was applied. RESULTS: Twenty-seven studies were included in the meta-analysis. The results showed that only seven studies reported some information about gender-related factors. Concerning sex-related differences, women had a shorter mean RR interval and lower variability of the time domain indices than men. Sex-related differences concerning frequency domain indices were more evident during night-time compared to daytime. CONCLUSION: The characterization of gender-related factors in the study of heart rate variability using 24-h ECG recordings is still sporadic and underexplored. The meta-analysis results could not conclusively support a significant increase of high frequency power in women, although women showed a reduced total power and low frequency to high frequency ratio. There is a strong need for considering heart rate variability in relation to gender-related variables.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Functional outcome after cardiac rehabilitation and its association with survival in heart failure across the spectrum of ejection fraction.

BACKGROUND: There is limited evidence regarding the effects of cardiac rehabilitation (CR) in patients with heart failure and preserved ejection fraction (HFpEF). METHODS: We studied 1784 patients admitted to inpatient CR. The patients were grouped into HFpEF (EF≥0.50), HF with mildly reduced EF (HFmrEF; EF 41-49), and HF with reduced EF (HFrEF; EF≤0.40). A standardized 6-min walking test was performed at admission and discharge. Measures of functional outcome were: (1) absolute increase in 6-min walking distance (6MWD) from admission to discharge >50 m and (2) increase in 6MWD to ≥300 among the patients who walked <300 m at admission. RESULTS: After adjustment, the patients with HFpEF or HFmrEF were as likely as those with HFrEF to achieve an increase in 6MWD >50 m (odds ratio 0.95 [95%CI 0.71-1.24; p=0.648] and 1.04 [95%CI 0.77-1.41; p=0.769], respectively) or an increase in 6MWD to ≥300 m (odds ratio 0.79 [95%CI 0.51-1.23; p=0.299] and 0.65 [95%CI 0.38-1.12; p=0.118], respectively). The adjusted hazard ratio of 5-year mortality for patients who achieved an increase in 6MWD >50 m was 0.60 (95%CI 0.51-0.71; p<0.001) and that for patients who achieved an increase in 6MWD at discharge to ≥300 m 0.61 (95%CI 0.48-0.79; p<0.001). In each EF group, both outcomes remained independently associated with improved survival. CONCLUSIONS: Our data suggest that patients with HFpEF or HFmrEF are as likely as those with HFrEF to benefit from CR in terms of functional improvement. Functional improvement was independently associated with improved long-term survival, regardless of EF.

Evidence of Carotid Atherosclerosis Vulnerability Regression in Real Life From Magnetic Resonance Imaging: Results of the MAGNETIC Prospective Study.

Background Atherosclerosis vulnerability regression has been evidenced mostly in randomized clinical trials with intensive lipid-lowering therapy. We aimed to demonstrate vulnerability regression in real life, with a comprehensive quantitative method, in patients with asymptomatic mild to moderate carotid atherosclerosis on a secondary prevention program. Methods and Results We conducted a single-center prospective observational study (MAGNETIC [Magnetic Resonance Imaging as a Gold Standard for Noninvasive Evaluation of Atherosclerotic Involvement of Carotid Arteries]): 260 patients enrolled at a cardiac rehabilitation center were followed for 3 years with serial magnetic resonance imaging. Per section cutoffs (95th/5th percentiles) were derived from a sample of 20 consecutive magnetic resonance imaging scans: (1) lipid-rich necrotic core: 26% of vessel wall area; (2) intraplaque hemorrhage: 12% of vessel wall area; and (3) fibrous cap: (a) minimum thickness: 0.06 mm, (b) mean thickness: 0.4 mm, (c) projection length: 11 mm. Patients with baseline magnetic resonance imaging of adequate quality (n=247) were classified as high (n=63, 26%), intermediate (n=65, 26%), or low risk (n=119, 48%), if vulnerability criteria were fulfilled in ≥2 contiguous sections, in 1 or multiple noncontiguous sections, or in any section, respectively. Among high-risk patients, a conversion to any lower-risk status was found in 11 (17%; P=0.614) at 6 months, in 16 (25%; P=0.197) at 1 year, and in 19 (30%; P=0.009) at 3 years. Among patients showing any degree of carotid plaque vulnerability, 21 (16%; P=0.014) were diagnosed at low risk at 3 years. Conclusions This study demonstrates with a quantitative approach that vulnerability regression is common in real life. A secondary prevention program can promote vulnerability regression in asymptomatic patients in the mid to long term.

Effect of Algorithmic Music Listening on Cardiac Autonomic Nervous System Activity: An Exploratory, Randomized Crossover Study.

It is proven that music listening can have a therapeutic impact in many clinical fields. However, to assume a curative value, musical stimuli should have a therapeutic logic. This study aimed at assessing short-term effects of algorithmic music on cardiac autonomic nervous system activity. Twenty-two healthy subjects underwent a crossover study including random listening to relaxing and activating algorithmic music. Electrocardiogram (ECG) and non-invasive arterial blood pressure were continuously recorded and were later analyzed to measure Heart Rate (HR) mean, HR variability and baroreflex sensitivity (BRS). Statistical analysis was performed using a general linear model, testing for carryover, period and treatment effects. Relaxing tracks decreased HR and increased root mean square of successive squared differences of normal-to-normal (NN) intervals, proportion of interval differences of successive NN intervals greater than 50 ms, low-frequency (LF) and high-frequency (HF) power and BRS. Activating tracks caused almost no change or an opposite effect in the same variables. The difference between the effects of the two stimuli was statistically significant in all these variables. No difference was found in the standard deviation of normal-to-normal RR intervals, LFpower in normalized units and LFpower/HFpower variables. The study suggests that algorithmic relaxing music increases cardiac vagal modulation and tone. These results open interesting perspectives in various clinical areas.

Prevalence of Psychopathological Symptoms and Their Determinants in Four Healthcare Workers' Categories during the Second Year of COVID-19 Pandemic.

Highly stressful situations, such as the current COVID-19 pandemic, induce constant changes in the mental state of people who experience them. In the present study, we analyzed the prevalence of some psychological symptoms and their determinants in four different categories of healthcare workers during the second year of the pandemic. A total of 265 physicians, 176 nurses, 184 other healthcare professionals, and 48 administrative employees, working in different Italian healthcare contexts, answered a questionnaire including variables about their mental status and experience with the pandemic. The mean scores for anxiety and depressive symptoms measured more than one year after the onset of the pandemic did not reach the pathological threshold. In contrast, post-traumatic and burnout symptoms tended toward the critical threshold, especially in physicians. The main determinant of psychological distress was perceived stress, followed by job satisfaction, the impact of COVID-19 on daily work, and a lack of recreational activities. These results increase the knowledge of which determinants of mental distress would be important to act on when particularly stressful conditions exist in the workplace that persist over time. If well-implemented, specific interventions focused on these determinants could lead to an improvement in employee well-being and in the quality of care provided.

Cognitive impairment, frailty and rehabilitation outcome in older cardiorespiratory patients. DEC_FRAinRIAB: Study protocol.

BACKGROUND: Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are two clinical conditions often associated with functional worsening, cognitive dysfunctions, treatment non-adherence, psychological distress and poor quality of life (QoL). In addition, since patients suffering from these conditions are often older adults, the presence of frailty syndrome could worsen the clinical situation. METHODS AND DESIGN: This study protocol of a prospective multi-center clinical trial, will be conducted at two hospitals of the Istituti Clinici Scientifici Maugeri IRCCS group, from July 2020 until December 2022. CHF and COPD older patients (age ≥65) will undergo a multidisciplinary assessment at admission, discharge and at 6 months follow-up, from an inpatient rehabilitation program: disease-related clinical characteristics, functional variables, cognitive screening, treatment adherence, anxiety, depression, QoL and frailty. The estimated sample size will consist of 300 patients. DISCUSSION: The expected results are related to the possibility of an improvement in the areas of intervention after the rehabilitative program and the maintenance of these improvements over time. The assessment of clinical and functional status, cognitive impairment, treatment adherence, psychosocial characteristics, and frailty could provide more specific and useful information about the main features to be considered in the evaluation and treatment of older patients suffering from CHF and COPD undergoing a rehabilitative pathway. TRIAL REGISTRATION: The study has been registered on January 28, 2022 with the ClinicalTrials.gov NCT05230927 registration number (clinicaltrials.gov/ct2/show/NCT05230927).

When Outcomes Diverge: Age and Cardiovascular Risk as Determinants of Mortality and ICU Admission in COVID-19.

BACKGROUND: Hospital mortality and admission to the Intensive Care Unit (ICU) are markers of disease severity in COVID-19 patients. Cardiovascular co-morbidities are one of the main determinants of negative outcomes. In this study we investigated the impact of cardiovascular co-morbidities on mortality and admission to the ICU in first-wave COVID-19 patients. METHODS: A multicenter, retrospective, cohort study. A total of 1077 patients were analyzed for mortality and ICU admission. Cardiovascular risk factors were explored as determinants of the outcomes after correction for other confounders. RESULTS: In the multivariable model, after correction for age, only a history of heart failure remained independently associated (p = 0.0013) with mortality (hazard ratio 2.22, 95% confidence interval 1.37 to 3.62). Age showed a mortality risk increase of 8% per year (hazard ratio 1.08, 95% confidence interval 1.05 to 1.10, p = 0.001). The transition from ward to the ICU had, as a single determinant, the age, but in a reversed fashion (hazard ratio 0.96, 95% confidence interval 0.94 to 0.98, p = 0.0002). CONCLUSIONS: Once adjusted for the main determinant of mortality (age) heart failure only remained independently associated with mortality. Admission to the ICU was less likely for elderly patients. This may reflect the catastrophic impact of the first wave of COVID-19 pandemic in terms of ICU bed availability in Lombardy, leading to a selection process for ICU admission.

Machine learning for prediction of in-hospital mortality in coronavirus disease 2019 patients: results from an Italian multicenter study.

BACKGROUND: 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. METHODS AND RESULTS: 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 ±â€Š13.2 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). CONCLUSION: 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.

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry.

BACKGROUND: It is uncertain whether exposure to renin-angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. METHODS: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. RESULTS: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). CONCLUSIONS: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.

Combined Role of Troponin and Natriuretic Peptides Measurements in Patients With Covid-19 (from the Cardio-COVID-Italy Multicenter Study).

Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs' cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.