Atrial fibrillation and ischemic heart disease: (un)solved therapeutic dilemma?

Concomitant presence of atrial fibrillation and coronary artery disease requiring percutaneous coronary intervention is a frequent occurrence. The choice of optimal antithrombotic therapy, in this context, is still challenging. To offer the best protection both in terms of stroke and stent thrombosis, triple therapy with oral anticoagulation and dual antiplatelet therapy would be required. Several drug combinations have been tested in recent years, including direct oral anticoagulants, with the aim of balancing ischemic and bleeding risk. Both pharmacokinetic aspects of the molecules and patient's characteristics should be analyzed in choosing oral anticoagulation. Then, as suggested by guidelines, triple therapy should start with a seven-day duration and the aim to prolong to thirty days in high thrombotic risk patients. Dual therapy should follow to reach twelve months after coronary intervention. Even not fully discussed by the guidelines, in order to balance ischemic and bleeding risk it should also be considered: 1) integrated assessment of coronary artery disease and procedural complexity of coronary intervention; 2) appropriateness to maintain the anticoagulant drug dosage indicated in technical data sheet; the lack of data on the suspension of antiplatelet drugs one year after percutaneous intervention; 3) the possibility of combination therapy with ticagrelor; and 4) the need to treat the occurrence of paroxysmal atrial fibrillation during acute coronary syndrome. With data provided clinician should pursue a therapy as personalized as possible, both in terms of drug choice and treatment duration, in order to balance ischemic and bleeding risk.

Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology.

Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF.

Hemodynamic effects of heart rate lowering in patients admitted for acute heart failure: the RedRate-HF Study (Reduction of heart Rate in Heart Failure).

BACKGROUND: In patients admitted for acute heart failure (HF) indication for drugs which reduce the heart rate (HR) is debated. The multicentre prospective study Reduction of heart Rate in Heart Failure (RedRate-HF) was designed to analyse the hemodynamic effects of an early reduction of HR in acute HF. METHODS: Hemodynamic parameters were recorded by using the bioimpedance technique, which was shown to be accurate, highly reproducible and sensitive to intra-observer changes. Lowering HR was obtained by ivabradine 5 mg bd, given 48-72 h after admission on the top of optimized treatment. Patients were followed at 24, 48, 72 h after drug assumption and at hospital discharge. RESULTS: Twenty patients of a mean age of 67 ±â€Š15 years, BNP at entry 1348 ±â€Š1198 pg/ml were enrolled. Despite a clinical stabilization, after 48-72 h from admission, HR was persistently >70 bpm. Ivabradine was well tolerated in all patients with a significant increase in RR interval from 747 ±â€Š69 ms at baseline to 948 ±â€Š121 ms at discharge, P < 0.0001. Change in HR was associated with a significant increase in stroke volume (baseline 73 ±â€Š22 vs. 84 ±â€Š19 ml at discharge, P = 0.03), and reduction in left cardiac work index (baseline 3.6 ±â€Š1.2 vs. 3.1 ±â€Š1.1 kg/m2 at discharge, P = 0.04). Other measures of heart work were also significantly affected while cardiac output remained unchanged. CONCLUSION: The strategy of an early lowering of HR in patients admitted for acute HF on top of usual care is feasible and safe. The HR reduction causes a positive increase in stroke volume and may contribute to saving energy without affecting cardiac output.

NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population.

BACKGROUND: Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. METHODS: Serum NT-ProBNP levels were measured in 5502 people aged 45-79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. RESULTS: After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100-300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12-2.32, p = 0.012 and HR 2.96, 95% CI 1.75-5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17-2.10, p = 0.011 and HR 2.08, 95% CI 1.47-2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex. CONCLUSIONS: Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.

Right and left ventricular structures and functions in acute HFpEF: comparing the hypertensive pulmonary edema and worsening heart failure phenotypes.

BACKGROUND: Limited data are available on right (RV) and left (LV) ventricular structures and functions in acute heart failure with preserved ejection fraction (AHF-pEF) presenting with hypertensive pulmonary edema (APE) versus predominant peripheral edema (peHF). METHODS AND RESULTS: In a prospective study of consecutive patients with AHF-pEF, 80 patients met inclusion and not exclusion criteria, and underwent echocardiographic and laboratory examination in the emergency ward. The survived (94%) were re-evaluated at the discharge. At admission, systolic, diastolic, pulse blood pressure (BP), and high sensitivity troponin I were higher (all P < 0.05) with APE than with peHF while brain-type natriuretic peptide (BNP), hemoglobin and estimated glomerular filtration rate (eGFR) did not differ between the two phenotypes. LV volumes and EF were comparable between APE and peHF, but APE showed lower relative wall thickness (RWT), smaller left atrial (LA) volume, higher pulse pressure/stroke volume (PP/SV), and higher ratio between the peak velocities of the early diastolic waves sampled by traditional and tissue Doppler modality (mitral E/e', all P < 0.05). Right ventricular and atrial (RA) areas were smaller, tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery peak systolic pressure (sPAP) were higher with APE than with peHF (all P < 0.05) while averaged degree of severity of tricuspid insufficiency was greater with peHF than with APE. At discharge, PP/SV, mitral E/e', sPAP, RV sizes were reduced from admission in both phenotypes (all P < 0.05) and did not differ anymore between phenotypes, whereas LV EF and TAPSE did not show significant changes over time and treatments. CONCLUSION: In AHF-pEF, at comparable BNP and LV EF, hypertensive APE showed eccentric LV geometry but smaller RV and RA sizes, and higher RV systolic function, increased LV ventricular filling and systemic arterial loads. AHF resolution abolished the differences in PP/SV and LV diastolic load between APE and peHF whereas APE remained associated with more eccentric RV and higher TAPSE.

BLITZ-HF: a nationwide initiative to evaluate and improve adherence to acute and chronic heart failure guidelines.

AIMS: To assess adherence to guideline recommendations among a large network of Italian cardiology sites in the management of acute and chronic heart failure (HF) and to evaluate if an ad-hoc educational intervention can improve their performance on several pharmacological and non-pharmacological indicators. METHODS AND RESULTS: BLITZ-HF was a cross-sectional study based on a web-based recording system with pop-up reminders on guideline recommendations used during two 3-month enrolment periods carried out 3 months apart (Phase 1 and 3), interspersed by face-to-face macro-regional benchmark analyses and educational meetings (Phase 2). Overall, 7218 patients with acute and chronic HF were enrolled at 106 cardiology sites. During the enrolment phases, 3920 and 3298 patients were included, respectively, 84% with chronic HF and 16% with acute HF in Phase 1, and 74% with chronic HF and 26% with acute HF in Phase 3. At baseline, adherence to guideline recommendations was already overall high for most indicators. Among acute HF patients, an improvement was obtained in three out of eight indicators, with a significant rise in echocardiographic evaluation. Among chronic HF patients with HF and preserved or mid-range ejection fraction, performance increased in two out of three indicators: creatinine and echocardiographic evaluations. An overall performance improvement was observed in six out of nine indicators in ambulatory HF with reduced ejection fraction patients with a significant increase in angiotensin receptor-neprilysin inhibitor prescription rates. CONCLUSIONS: Within a context of an already elevated level of adherence to HF guideline recommendations, a structured multifaceted educational intervention could be useful to improve performance on specific indicators. Extending this approach to other non-cardiology healthcare professionals, who usually manage patients with HF, should be considered.

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.

[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Twenty-year trends in heart failure among U.S. adults, 1999-2018: The growing impact of obesity and diabetes.

BACKGROUND: The aim of this study is to evaluate trends in heart failure (HF) prevalence, impact of accompanying risk factors and use of effective therapeutic regimens during the last two decades in the general adult US population. METHODS: We analyzed data obtained from the 1999-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Among a total of 34,403 participants 40 years or older who attended the mobile examination center visit, 1690 reported a diagnosis of HF. Trends in participant features across calendar periods were assessed by linear regression for continuous variables and logistic regression for binary variables. RESULTS: Prevalence of self-reported HF did not change significantly from 1999 to 2002 to 2015-2018 (~3.5%), while obesity and diabetes showed a progressive increase in prevalence, affecting ~65% and ~ 45% of patients with HF in the most recent calendar period, respectively. In parallel, use of glucose lowering drugs (especially metformin and insulin) as well as statins increased from 1999 to 2010, with significant improvement of the lipid control. A modest improvement in blood pressure control was achieved in association with a significant increase in the use of angiotensin receptor blockers and beta-blockers. CONCLUSIONS: In the last 20 years, the prevalence of HF in US adults remained stable, while both obesity and diabetes increased, with the two conditions affecting half of patients with HF. Improvements in the control of dyslipidemia and, to a lesser extent, blood pressure, was detected; nonetheless, a significant gap remains in guideline-directed use of HF and diabetes medications.

Sex-related differences in patients with coronavirus disease 2019: results of the Cardio-COVID-Italy multicentre study.

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.

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.

Ventricular arrhythmias and ARNI: is it time to reappraise their management in the light of new evidence?

The remarkable scientific progress in the treatment of patients with heart failure (HF) and reduced ejection fraction (HFrEF) has more than halved the risk of sudden cardiac death (SCD) in this setting. However, SCD remains one of the major causes of death in this patient population. Beyond the acknowledged role of beta blockers and inhibitors of the renin-angiotensin-aldosterone system (RAAS), a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNI), proved to reduce the overall cardiovascular mortality and, more specifically, the risk of SCD in HFrEF patients. The mechanism by which ARNI may reduce the mortality connected with harmful ventricular arrhythmias is not utterly clear. A variety of direct and indirect mechanisms have been suggested, but a favorable left ventricular reverse remodeling seems to play a key role in this setting. Furthermore, the well-known protective effect of implantable cardioverter-defibrillator (ICD) has been debated in HFrEF patients with non-ischemic cardiomyopathy (NICM) arguing against the role of primary prevention ICD in this setting, particularly when ARNI therapy is considered. The purpose of this review was to provide insights into the SCD mechanisms involved in HFrEF patients together with the current role of electrical therapies and new drug agents in this setting. Graphical abstract.

Epidemiology of cardiomyopathies: essential context knowledge for a tailored clinical work-up.

Cardiomyopathies (CMPs) are primary disorders of myocardial structure and function in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease. Knowledge of the incidence and prevalence of CMPs may help clinicians to compare their observations in clinical practice with expected cases per person-year and to avoid under-reporting in clinical context. Currently, available estimates of prevalence and incidence of CMPs are based on clinical data, collected with a wide variability in population-source, and before the genetic testing evolved as a standard diagnostic tool. This review focuses on the epidemiology of CMPs in subjects aged between 18 and 55 years. A structured up-to-date diagnostic flow-chart for CMPs diagnosis and assessment is proposed to avoid misdiagnosis of CMPs in the young population and in subjects with unexplained cardiac disorders.

Nonalcoholic Fatty Liver Disease, Liver Fibrosis and Cardiovascular Disease in the Adult US Population.

Background: Cardiovascular disease (CVD) risk is higher in patients with nonalcoholic fatty liver disease (NAFLD). Aim: To evaluate whether this can be attributed to the link between NAFLD and known CVD risk factors or to an independent contribution of liver steatosis and fibrosis. Methods: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included participants older than 40 years with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. History of CVD was self-reported and defined as a composite of coronary artery disease and stroke/transient ischemic attacks. Results: Among the 2734 included participants, prevalence of NAFLD was 48.6% (95% CI 45.1-51.4), 316 participants (9.7%, 95% CI 8.1-11.6) had evidence of significant liver fibrosis and 371 (11.5%, 95% CI 9.5-13.9) had a history of CVD. In univariate analysis, patients with CVD had a higher prevalence of steatosis (59.6% vs 47.1%, p=0.013), but not fibrosis (12.9% vs 9.3%, p=0.123). After adjustment for potential confounders in a multivariable logistic regression model, neither steatosis nor significant fibrosis were independently associated with CVD and heart failure. Conclusions: In this population-based study, we did not identify an independent association between steatosis and fibrosis and CVD. Large prospective cohort studies are needed to provide a more definitive evidence on this topic.

JAK Inhibition with Ruxolitinib in Patients with COVID-19 and Severe Pneumonia: Multicenter Clinical Experience from a Compassionate Use Program in Italy.

Jak inhibitors are potent anti-inflammatory drugs that have the potential to dampen the hyperactive inflammatory response associated with severe COVID-19. We reviewed the clinical outcomes of 218 patients with COVID-19 hospitalized for severe pneumonia and treated with ruxolitinib through a compassionate use program. Data on the duration of treatment; outcomes at 4, 7, 14, and 28 days; oxygen support requirements; clinical status; and laboratory parameters were retrospectively collected. Overall, according to the physician evaluation, 66.5% of patients showed improvement at follow-up; of these, 83.5% showed improvement by day 7. Oxygen support status also showed improvement, and by day 7, 21.6% of patients were on ambient air, compared with 1.4% at baseline, which increased to 48.2% by day 28. Significant decreases in C-reactive protein and increases in the lymphocyte total count were already observed by day 4, which seemed to correlate with a positive outcome. At the end of the observation period, 87.2% of patients were alive. No unexpected safety findings were observed, and grade 3/4 adverse events were reported in 6.9% of patients.

The prognostic value of serial troponin measurements in patients admitted for COVID-19.

AIMS: Myocardial injury (MI) in coronavirus disease-19 (COVID-19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in-hospital evolution of MI and its prognostic impact. METHODS AND RESULTS: We performed an analysis from an Italian multicentre study enrolling COVID-19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in-hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10-13.09, P = 0.035). CONCLUSIONS: In patients admitted for COVID-19, re-test MI on Day 2 provides a prognostic value. A non-negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement.

Comparing the Prognostic Impact of Prediabetes with Diabetes in a Nationwide Cohort of Patients with Chronic Coronary Syndromes: An Analysis of the START Registry.

AIMS: Using data from the nationwide prospective START registry that enrolled a large cohort of patients with chronic coronary syndromes (CCS), we aimed to investigate whether the presence of diabetes mellitus (DM) and pre-DM independently affected the risk of cardiovascular events at 1-year follow-up. METHODS: We assessed the impact of DM and pre-DM on all-cause mortality and a composite of all-cause mortality and hospitalization for cardiovascular causes at 1-year follow-up. RESULTS: Among the 3,778 patients with available fasting plasma glucose data at study entry, 37% were classified as DM, 25% as pre-DM, and 38% as no DM. At 1 year, patients with DM had higher rates of all-cause death (p = 0.004) and death/cardiovascular hospitalization (p = 0.003) than those with pre-DM or without DM. Conversely, no significant differences in the adverse event rate were found between patients with pre-DM and those without DM. At unadjusted Cox analysis, DM resulted as a predictor of both death for any cause (hazard ratio [HR]: 2.41; 95% confidence intervals [CI]: 1.34-4.34; p = 0.003) and all-cause death/hospitalization for cardiovascular causes (HR: 1.29; 95% CI: 1.02-1.62; p = 0.03). However, DM did not result as an independent predictor of either endpoint at multivariate analysis. CONCLUSIONS: The risk of 1-year major events among patients with CCS and pre-DM is comparable to that of patients with CCS and normoglycemic status and is lower than that of patients with DM.

Implications of atrial fibrillation on the clinical course and outcomes of hospitalized COVID-19 patients: results of the Cardio-COVID-Italy multicentre study.

AIMS: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events. CONCLUSION: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.