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Atrial myopathy-characterized by changes in left atrial function and size-may precede and promote atrial fibrillation (AF) and cardiac thromboembolism. In people without prior AF or stroke, whether analysis of left atrial function and size can improve ischemic stroke prediction is unknown.To evaluate the association of echocardiographic left atrial function (reservoir, conduit, and contractile strain) and left atrial size (left atrial volume index) with ischemic stroke and determine whether these measures can improve the stroke prediction achieved by CHAProspective cohort study.ARIC (Atherosclerosis Risk in Communities) study.4917 ARIC participants without prevalent stroke or AF.Ischemic stroke events (2011 to 2019) were adjudicated by physicians. Left atrial strain was measured using speckle-tracking echocardiography.Over 5 years, the cumulative incidences of ischemic stroke in the lowest quintiles of left atrial reservoir, conduit, and contractile strain were 2.99% (95% CI, 1.89% to 4.09%), 3.18% (CI, 2.14% to 4.22%), and 2.15% (CI, 1.09% to 3.21%), respectively, and that of severe left atrial enlargement was 1.99% (CI, 0.23% to 3.75%). On the basis of the Akaike information criterion, left atrial reservoir strain plus CHAUnderascertainment of subclinical AF.In people without prior AF or stroke, when added to CHANational Heart, Lung, and Blood Institute of the National Institutes of Health.

Background Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-recommended medical therapy (GRMT) in heart failure (HF). Our aim was to evaluate the evolution and impact of MR after GRMT in the Biology study to Tailored treatment in chronic heart failure (BIOSTAT-CHF). Methods A retrospective post-hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Results Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate-severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate-severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint (unadjusted hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.57–2.63; p p Conclusions Among patients with HF undergoing GRMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate-severe MR after GRMT was associated with worse outcome. Graphical abstract

ImportanceHereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I (V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk.ObjectiveTo estimate age-dependent risks for cardiovascular events with the variant.Design, Settings, and ParticipantsThis cohort study analyzed Black participants from the Atherosclerosis Risk in Communities (ARIC) study attending visit 1 (1987-1989) (followed up until 2019; median follow-up, 27.6 years). Data analyses were completed from June 2022 to April 2023.ExposurepV142I carrier status.Main outcomesThe association between the variant and AF, HF hospitalization, mortality, and a composite of HF hospitalization or mortality was modeled by generating 10-year absolute risk differences for each year between ages 53 (the median age at visit 1) and 80 years, adjusting for the first 5 principal components of ancestry and sex. As an example, 5- and 10-year risk differences were specifically estimated for the composite outcome among participants surviving to age 80 years.ResultsAmong 3856 Black participants (including 124 carriers) at visit 1, 2403 (62%) were women, 2140 (56%) had hypertension, and 740 (20%) had diabetes, with no differences between groups. The 10-year absolute risk difference between ages 53 and 80 years increased over time for each outcome. Statistical significance for increased 10-year risk difference emerged near ages 65 years for AF, 70 years for HF hospitalization, and 75 years for mortality. Among participants surviving to age 80 years, carriers had a 20% (95% CI, 2%-37%) and 24% (95% CI, 1%-47%) absolute increased risk for HF hospitalization or death at 5 and 10 years, respectively. Thus, at age 80 years, only 4 carriers would need to be identified to attribute 1 HF hospitalization or death over the following decade to the variant.Conclusions and RelevanceIn this study, age-specific risks were provided for relevant outcomes with the pV142I variant. Despite a relatively benign course during earlier years, Black individuals who carry the pV142I variant surviving into later life may be particularly vulnerable. These data may inform timing for screening, risk counseling to patients, and potential strategies for early targeted therapy.

Limited data exist to characterize novel measures of left atrial (LA) structure and function in older adults without prevalent heart failure (HF).The aim was to assess reference range of LA measures, their associations with N-terminal pro-B-type natriuretic-peptide (NT-proBNP) and the related risk for incident HF or death.We analyzed LA structure (LA maximal [LAViMax] and minimal volume indexed by body surface area) and function (LA emptying fraction, LA reservoir, conduit, and contraction strain) in 4,901 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 75 ± 5 years, 40% male, and 19% Black) without prevalent HF. We assessed sex-specific 10th and 90th percentile ARIC-based reference limits in 301 participants free of prevalent cardiovascular disease, and related LA measures to NT-proBNP and incident HF or death (median follow-up of 5.5 years) in the whole ARIC cohort.Approximately 20% of the overall population had LA abnormalities according to the ARIC-based reference limit. Each LA measure was associated with NT-proBNP and, except for LAViMax, with incident HF or death after multivariable adjustment (including left ventricular function and NT-proBNP). Results were consistent in participants with normal LAViMax (P for interaction0.05). LA measures were prognostic for both incident HF with preserved ejection fraction or death and incident HF with reduced ejection fraction or death. When added to HF risk factors and NT-proBNP (baseline C-statistics = 0.74) all LA measures, except for LAViMax, significantly enhanced the prognostic accuracy.Novel measures of LA structure and function, but not standard assessment by LAViMax, are associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP.

Guidelines on heart failure (HF) define iron deficiency (ID) as a serum ferritin 100 ng/mL or, when 100-299 ng/mL, a transferrin saturation (TSAT) 20%. Inflammation (common in HF) may hinder interpretation of serum ferritin.This study sought to investigate how different definitions of ID affect its prevalence and relationship to prognosis in ambulatory patients with chronic HF.Prevalence, relationship with patients' characteristics, and outcomes of various ID definitions were evaluated among patients with HF referred to a regional clinic (Hull LifeLab) from 2001 to 2019.Of 4,422 patients with HF (median age 75 years [range: 68-82 years], 60% men, 32% with reduced left ventricular ejection fraction), 46% had TSAT 20%, 48% had serum iron ≤13 μmol/L, 57% had serum ferritin 100 ng/mL, and 68% fulfilled current guideline criteria for ID, of whom 35% had a TSAT20%. Irrespective of definition, ID was more common in women and those with more severe symptoms, anemia, or preserved ejection fraction. TSAT 20% and serum iron ≤13 μmol/L, but not guideline criteria, were associated with higher 5-year mortality (HR: 1.27; 95% CI: 1.14-1.43; P 0.001; and HR: 1.37; 95% CI: 1.22-1.54; P 0.001, respectively). Serum ferritin 100 ng/mL tended to be associated with lower mortality (HR: 0.91; 95% CI: 0.81-1.01; P = 0.09).Different definitions of ID provide discordant results for prevalence and prognosis. Definitions lacking specificity may attenuate the benefits of intravenous iron observed in trials while definitions lacking sensitivity may exclude patients who should receive intravenous iron. Prespecified subgroup analyses of ongoing randomized trials should address this issue.

Heart failure (HF) is characterized by frequent hospital admissions due to acute decompensation and shortened life span with a progressive clinical course leading to an advanced stage where traditional therapies become ineffective. Due to aging of the population and improved therapies, only a small of proportion of patients with advanced HF are candidates for surgical treatments, such as mechanical circulatory support or heart transplantation. In most cases, prompt identification and management of congestion is paramount to improving symptoms and quality of life and avoiding progression to severe multiorgan dysfunction and death.

Background: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. Methods: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. Results: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26–0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (100 mg/L). Conclusions: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.

Aims To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. Methods and results The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08–5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). Conclusions Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

The left atrium is a dynamic chamber with peculiar characteristics. Stressors and disease mechanisms may deeply modify its structure and function, leading to left atrial remodelling and disease. Left atrial disease is a predictor of poor outcomes. It may be a consequence of left ventricular systolic and diastolic dysfunction and neurohormonal and inflammatory activation and/or actively contribute to the progression and clinical course of heart failure through multiple mechanisms such as left ventricular filling and development of atrial fibrillation and subsequent embolic events. There is growing evidence that therapy may improve left atrial function and reverse left atrial remodelling. Whether this translates into changes in patient's prognosis is still unknown. In this review we report current data about changes in left atrial size and function across different stages of development and progression of heart failure. At each stage, drug therapies, lifestyle interventions and procedures have been associated with improvement in left atrial structure and function, namely a reduction in left atrial volume and/or an improvement in left atrial strain function, a process that can be defined as left atrial reverse remodelling and, in some cases, this has been associated with improvement in clinical outcomes. Further evidence is still needed mainly with respect of the possible role of left atrial reverse remodelling as an independent mechanism affecting the patient's clinical course and as regards better standardization of clinically meaningful changes in left atrial measurements. Summarizing current evidence, this review may be the basis for further studies.

Introduction: \ud Limited data exist regarding the prognostic relevance of changes in left atrial (LA) dimensions in patients with heart failure (HF). We assessed changes in LA dimension and their relation with outcomes after optimization of guideline-directed medical therapy (GDMT) in patients with worsening HF.\ud \ud Methods and Results: \ud LA diameter was assessed at baseline and 9 months after GDMT optimization in 632 patients (mean age 65.8±12.1 years, 22.3% female) enrolled in BIOSTAT-CHF. LA adverse remodelling (LAAR) was defined as an increase in LA diameter on transthoracic echocardiography between baseline and 9 months. After the 9-month visit, patients were followed for a median of 13 further months. LAAR was observed in 247 patients (39%). Larger baseline LA diameter (odds ratio (OR) 0.90; 95% confidence interval (95% CI) 0.87 – 0.93; p

The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial.Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean differencesThese findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).

Aims Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-directed medical therapy (GDMT) in heart failure (HF). We evaluated the evolution and impact of MR after GDMT in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Methods and results A retrospective post hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate–severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate–severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint [unadjusted hazard ratio (HR), 2.03; 95% confidence interval (CI): 1.57–2.63; P Conclusions Among patients with HF undergoing GDMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate–severe MR after GRMT was associated with worse outcome.

Aims An increasing number of patients with heart failure (HF) progresses to an advanced stage, characterized by persistent and sever symptoms and worse prognosis. A detailed characterization of patients with advanced HF is needed to optimize clinical management and timely refer for heart transplant or left ventricular assist device implantation. Methods and results A retrospective analysis was performed on patients with HF who were admitted to hospital or performed an outpatient visit at our centre (Spedali Civili di Brescia, Brescia, Italy) from 1 January 2020 to 31 December 2020, and who had at least one of the following high-risk characteristics: (1) previous or ongoing requirement for inotropes; (2) persisting New York Heart Association (NYHA) class III or IV and/or persistently high natriuretic peptides (BNP or NT-proBNP); (3) end-organ dysfunction, defined as worsening renal or liver dysfunction in the setting of HF; (4) ejection fraction (EF) Conclusions In our contemporary, real-world cohort of HF patients with high-risk characteristics, mid-term prognosis was poor, and the use of updated HFA-ESC criteria defining advanced HF identified a subset at increased risk of mortality.

Introduction: Atrial cardiomyopathy, characterized by abnormalities in left atrial (LA) size and function, is a risk factor for atrial fibrillation (AF) and ischemic stroke. We aimed to determine if 2D-echocardiographic (2DE) LA strain and volumetric parameters are independently associated with ischemic stroke and the extent to which AF mediates this risk in the ARIC study, a community-based cohort study. Methods: We included 4817 ARIC participants (mean age 75; 59% women; 22% Black) and who had 2DE in 2011-13. We evaluated LA volume index (maximum, minimum), LA emptying fraction (total, passive, active), LA strain (reservoir, conduit, contractile). Incident ischemic strokes (2013-2019) were physician adjudicated after review of medical records. AF was ascertained from hospitalization discharge codes and 2-week ambulatory rhythm monitoring in 2016-17. We used multivariable Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals (CI) of LA parameters for stroke and performed mediation analyses to quantify the indirect effect of AF in these associations. Results: After a median follow-up of 5.9 years, each SD increment in LA reservoir stain, LA conduit strain, LA contractile strain, total LA emptying fraction, and active LA emptying fraction was associated with a percent (95% CI) decrease in stroke risk of 27 (14-38), 19 (4-32), 17 (4-29), 19 (6-31), and 14 (1-26), respectively. Greater left atrial minimum, but not maximum volume index was associated with higher stroke risk. The proportion of these associations which was mediated by AF ranged from 3-36%. Our findings remained unchanged in sensitivity analysis excluding participants with AF and on anticoagulants. Conclusions: The associations of LA strain and volumetric parameters with stroke are minimally mediated by AF. Future research should determine whether LA strain and volumetric analysis can guide anticoagulation for stroke prevention in people independent of AF status.

Background Black Americans have more atrial fibrillation risk factors but lower atrial fibrillation risk than White Americans. Left atrial (LA) enlargement and/or dysfunction, frequent atrial tachycardia (AT), and premature atrial contractions (PAC) are associated with increased atrial fibrillation risk. Racial differences in these factors may exist that could explain the difference in atrial fibrillation risk. Methods and Results We included 2133 ARIC (Atherosclerosis Risk in Communities) study participants (aged 74±4.5 years[mean±SD], 59% women, 27% Black participants) who had echocardiograms in 2011 to 2013 and wore the Zio XT Patch (a 2‐week continuous heart monitor) in 2016 to 2017. Linear regression was used to analyze (1) differences in AT/day or PAC/hour between Black and White participants, (2) differences in LA measures between Black and White participants, and (3) racial differences in the association of LA measures with AT or PAC frequency. Compared with White participants, Black participants had a higher prevalence of cardiovascular risk factors and disease, lower AT frequency, greater LA size, and lower LA function. After multivariable adjustments, Black participants had 37% (95% CI, 24%–47%) fewer AT runs/day than White participants. No difference in PAC between races was noted. Greater LA size and reduced LA function are associated with more AT and PAC runs; however, no race interaction was present. Conclusions Differences in LA measures are unlikely to explain the difference in atrial fibrillation risk between Black and White individuals. Despite more cardiovascular risk factors and greater atrial remodeling, Black participants have lower AT frequency than White participants. Future research is needed to elucidate the protective mechanisms that confer resilience to atrial arrhythmias in Black individuals.

The ongoing COVID-19 pandemic highlighted a significant interplay between cardiovascular disease (CVD), COVID-19 related inflammatory status, and depression. Cardiovascular (CV) injury is responsible for a substantial percentage of COVID-19 deaths while COVID-19 social restrictions emerged as a non-negligible risk factor for CVD as well as a variety of mental health issues, and in particular, depression. Inflammation seems to be a shared condition between these two disorders. Gender represents a potential modifying factor both in CVD and depression, as well as in COVID-19 short- and long-term outcomes, particularly in cases involving long-term COVID complications. Results from emerging studies indicate that COVID-19 pandemic affected male and female populations in different ways. Women seem to experience less severe short-term complications but suffer worse long-term COVID complications, including depression, reduced physical activity, and deteriorating lifestyle habits, all of which may impact CV risk. Here, we summarize the current state of knowledge about the interplay between COVID-19, depression, and CV risk in women.

Purpose of Review The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action. Recent Findings Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Summary Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.

Introduction: Prior research indicates that higher LTPA is associated with better left ventricular (LV) diastolic function, but not with left atrial volume index (LAVI). Left atrial (LA) strain is a more sensitive marker of LA pathology. Hence, we evaluated association of LTPA with LA strain in the ARIC study, a community-based cohort study. Hypothesis: Higher LTPA is associated with better LA reservoir, conduit and contractile function. Methods: We included 4005 participants (mean age 75 years, 63% female, 21% black) with 2D echocardiographic (2DE) LA % strain data, LTPA data, and without prevalent coronary heart disease, valvular heart disease, heart failure, atrial fibrillation, and stroke at Visit 5 (V5, 2011-13). We estimated LTPA as metabolic equivalent-minutes per week from validated Baecke questionnaire and categorized it as poor, intermediate, or ideal as per AHA recommendation. We categorized change in LTPA from V3 (1993-95) to V5 as persistently poor (referent), decreasing, increasing, or persistently active. LA reservoir, conduit, and contractile % strain were measured from speckle-tracking 2DE. Linear regression was used to evaluate association of LTPA with LA function. We modeled LTPA (1) cross-sectionally at V5 as a continuous variable and (2) change from V3 to V5, as continuous and categorical variables (referent- persistently poor). Results: Higher LTPA at V5 (Table) and persistently high (vs poor) LTPA from V3 to 5 (β estimate -0.89, 95% CI -1.40, -0.38) were significantly associated with better LA conduit function after adjusting for CV risk factors, LV function, and LAVI. The same associations with LA reservoir function were no longer significant after adjusting for CV risk factors. LTPA was not associated with LA contractile function (Table). Conclusions: Consistent with LTPA’s salutary effect on LV diastolic function, higher LTPA is associated with better LA conduit function. Maintaining high LTPA from midlife to late-life may be beneficial in mitigating age-related changes in cardiac function.

AIMS African-American carriers of the transthyretin (TTR) valine-to-isoleucine substitution (V122I) are at increased risk of heart failure, yet many have relatively subtle abnormalities of left ventricular (LV) function. We sought to explore the influence of this mutation on left atrial (LA) structure and function in this population. METHODS AND RESULTS We assessed 1225 genotyped African-Americans (age range, 67-89 years) participating in the Atherosclerosis Risk in Communities study who underwent echocardiography and were in sinus rhythm at study Visit 5 (2011 to 2013). Six LA parameters [LA maximum/minimum volume index, ejection fraction, and LA reservoir, conduit, and contractile longitudinal strains (LS)] were compared between V122I TTR variant carriers (n = 46) and non-carriers (n = 1179). LA minimum volume index was significantly greater and LA contractile LS was worse in carriers than non-carriers (19.5 ± 10.6 mL/m2 vs. 16.3 ± 8.4 mL/m2 ; 15.0 ± 5.8% vs. 16.8 ± 5.7%, respectively, both P

Background Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited. Methods Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between d-dimer levels and PE incidence was evaluated using restricted cubic splines models. Results The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9–24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission d-dimer [4344 (1099–15,118) vs. 818.5 (417–1460) ng/mL, p p p = 0.06). In multivariate regression, only d-dimer was associated with PE (HR 1.72, 95% CI 1.13–2.62; p = 0.01). The relation between d-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline d-dimer Conclusions PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of d-dimer in this population need to be clarified. Graphic abstract

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

Aims: In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known. Methods and results: A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1). Conclusions: Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.

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 0.05 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.

Background Maximal left atrial (LA) volume is reported by most echocardiography laboratories and is associated with clinical outcomes in patients with heart failure (HF). Recent studies suggest that minimal LA volume may better reflect left ventricular filling pressure and may be more prognostic than maximal LA volume. This study assessed the prognostic value of indexed minimal LA volume (LAVImin) in patients with HF with preserved ejection fraction. Methods and Results We assessed the relationship of LAVImin with a primary composite end point of cardiovascular death, aborted cardiac death, or HF hospitalization in 347 patients with HF with preserved ejection fraction enrolled from the Americas region in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We compared LAVImin with indexed maximal LA volume with respect to their prognostic values. In addition, we assessed if LA functional parameters provide additional prognostic information over LAVImin. During a median follow‐up of 2.5 years, 107 patients (31%) experienced a primary composite end point. LAVImin was associated with increased risk of a primary composite outcome (hazard ratio [HR], 1.35; 95% CI, 1.12–1.61) and HF hospitalization alone (HR, 1.42; 95% CI, 1.17–1.71) after adjusting for clinical confounders and ejection fraction. In contrast, indexed maximal LA volume was not related to the primary composite outcome, but related to HF alone (HR, 1.25; 95% CI, 1.02–1.54). In comparison with indexed maximal LA volume, LAVImin was significantly more prognostic for primary composite outcome ( P for comparison=0.032). Both LA emptying fraction and LA strain were prognostic of primary outcome independent of LAVImin (all P Conclusions In patients with HF with preserved ejection fraction, LAVImin was more predictive of cardiovascular outcome than indexed maximal LA volume, suggesting this measure may be more physiologically relevant and might better identify patients at high risk for cardiovascular events. LA functional parameters provide prognostic information independent of LAVImin. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00094302.

To assess to what extent left atrial (LA) structure and function are associated with non-specific heart failure symptoms, so that patients were classified as HF stage A and B. Mechanisms underlying the transition to overt HF in patients with stage A and B HF are unclear. Consecutive outpatients undergoing echocardiography and clinical evaluation and classified as HF stage A and B with preserved left ventricular ejection fraction (LVEF) were included. The association between LA measures [volume (LAVi), peak longitudinal-(PALS), contraction-(PACS) and conduit-strain] and non-specific HF symptoms was assessed using adjusted logistic regression analyses. The incremental value of atrial myopathy in symptoms prediction on top of clinical or echocardiographic confounders was assessed through ROC curves analyses. The cohort comprehended 185 patients (63 ± 16 years, 47% women) of whom 133 (72%) were asymptomatic, and 52 (28%) reported non-specific HF symptoms. After adjustment for clinical and echocardiographic confounders for HF symptoms, LAVi, PALS and PACS were associated with symptoms (p