Myocardial Injury by COVID-19 Infection Assessed by Cardiovascular Magnetic Resonance Imaging　- A Prospective Multicenter Study.

BACKGROUND: This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR).Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis. CONCLUSIONS: This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

Timing of prescription of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in patients hospitalized for acute heart failure with reduced/mildly reduced ejection fraction: a retrospective analysis.

Although angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) play critical roles in the treatment of heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF; left-ventricular ejection fraction ≤ 50%), the ideal timing for initiation in patients with acute heart failure (AHF) is unclear. We sought to clarify the timing and safety of ACEi/ARB prescription relative to hemodynamic stabilization (pre or post) in patients hospitalized with acute HFrEF/HFmrEF. This was a retrospective, observational analysis of electronic data of patients hospitalized for AHF at 17 Japanese hospitals. Among 9107 patients hospitalized with AHF, 2648 had HFrEF/HFmrEF, and 83.0% met the hemodynamic stabilization criteria within 10 days of admission. During hospitalization, 63.5% of patients with HFrEF/HFmrEF were prescribed an ACEi/ARB, 79.4% of which were prescribed pre-stabilization. In a multivariable analysis, patients treated with an ACEi/ARB pre-stabilization were more likely to have comorbid hypertension, diabetes mellitus, or ischemic heart disease. ACEi/ARB prescription timing was not associated with adverse events, including hypotension and renal impairment, and early prescription was associated with a lower incidence of subsequent worsening of HF. In clinical practice, more hospitalized patients with AHF received an ACEi/ARB before compared with after hemodynamic stabilization, and no safety concerns were observed. Moreover, early prescription may be associated with a lower incidence of worsening HF.

Nutrition Assessment and Education of Patients with Heart Failure by Cardiologists.

Although nutritional assessment and education are important for hospitalized patients with heart failure, the extent of their implementation in real-world clinical practice is unknown. Therefore, this study aimed to investigate the evaluation and management of nutrition during hospitalization for heart failure using a questionnaire survey for cardiologists.In this cross-sectional multicenter survey, 147 cardiologists from 32 institutions completed a web-based questionnaire (response rate, 95%).The survey showed that 78.2% of the respondents performed a nutritional assessment for hospitalized patients, whereas 38.3% used objective tools. In contrast, only 9.5% of the respondents evaluated the presence or absence of cardiac cachexia. Most respondents (89.8%) reported providing nutritional education to their patients before hospital discharge. However, compared with the number of respondents who provided information on sodium (97.0%) and water (63.6%) restrictions, a limited number of respondents provided guidance on optimal protein (20.5%) and micronutrient (9.1%) intake as part of the nutritional education. Less than 50% of the respondents provided guidance on optimal calorie intake (43.2%) and ideal body weight (34.8%) as a part of the nutritional education for patients identified as malnourished.Although nutritional assessment is widely performed for hospitalized patients with heart failure, most assessments are subjective rather than objective. Nutritional education, frequently provided before hospital discharge, is limited to information on water or salt intake restrictions. Therefore, more comprehensive and individualized nutritional assessments and counselling with a scientific basis are required.

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure: Rationale for and design of the EMPA-AHF trial.

AIMS: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. METHODS: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate <60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of <300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. CONCLUSION: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.

Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society.

Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptides-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions.

External Validation of the HELT-E2S2 Score in Japanese Patients With Nonvalvular Atrial Fibrillation　- A Pooled Analysis of the RAFFINE and SAKURA Registries.

BACKGROUND: The HELT-E2S2score, which assigns 1 point to Hypertension, Elderly aged 75-84 years, Low body mass index <18.5 kg/m2, and Type of atrial fibrillation (AF: persistent/permanent), and 2 points to Extreme Elderly aged ≥85 years and previous Stroke, has been proposed as a new risk stratification for strokes in Japanese AF patients, but has not yet undergone external validation.Methods and Results: We evaluated the prognostic performance of the HELT-E2S2score for stroke risk stratification using 2 large-scale registries in Japanese AF patients (n=7,020). During 23,241 person-years of follow-up (mean follow-up 1,208±450 days), 287 ischemic stroke events occurred. The C-statistic using the HELT-E2S2score was 0.661 (95% confidence interval [CI], 0.629-0.692), which was numerically higher than with the CHADS2score (0.644, 95% CI 0.613-0.675; P=0.15 vs. HELT-E2S2) or CHA2DS2-VASc score (0.650, 95% CI, 0.619-0.680; P=0.37 vs. HELT-E2S2). In the SAKURA AF Registry, the C-statistic of the HELT-E2S2score was consistently higher than the CHADS2and CHA2DS2-VASc scores across all 3 types of facilities comprising university hospitals, general hospitals, and clinics. However, in the RAFFINE Study, its superiority was only observed in general hospitals. CONCLUSIONS: The HELT-E2S2score demonstrated potential value for risk stratification, particularly in a super-aged society such as Japan. However, its superiority over the CHADS2or CHA2DS2-VASc scores may vary across different hospital settings.

Prognostic value of estimating appendicular muscle mass in heart failure using creatinine/cystatin C.

BACKGROUND AND AIMS: Heart failure with concomitant sarcopenia has a poor prognosis; therefore, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index (i.e., serum creatinine-to-cystatin C ratio [Cre/CysC]), was developed to estimate the ASMI. We hypothesized that this model was superior to the traditional model, which uses only anthropometric data to predict prognosis. This retrospective cohort study compared the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure. METHODS AND RESULTS: Among 847 patients, we estimated ASMI using an anthropometric model (incorporating age, body weight, and height) in 791 patients and a biomarker model (incorporating age, body weight, hemoglobin, and Cre/CysC) in 562 patients. The primary outcome was all-cause mortality. Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI (using the Asian Working Group for Sarcopenia cut-off) by the anthropometric and biomarker models, respectively. The two models showed a poor agreement in the diagnosis of low ASMI (kappa: 0.57, 95% confidence interval: 0.50-0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.32, p = 0.001) but not in the anthropometric model (hazard ratio: 0.79, p = 0.360). CONCLUSION: Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, and not the anthropometric model, was significantly associated with all-cause mortality.

Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure.

We investigated the clinical and prognostic implications of hyaluronic acid, a liver fibrosis marker, in patients with heart failure. We measured hyaluronic acid levels on admission in 655 hospitalized patients with heart failure between January 2015 and December 2019. Patients were stratified into three groups according to hyaluronic acid level: low (< 84.3 ng/mL, n = 219), middle (84.3-188.2 ng/mL, n = 218), and high (≥ 188.2 ng/mL, n = 218). The primary endpoint was all-cause death. The high hyaluronic acid group had higher N-terminal pro-brain-type natriuretic peptide levels, larger inferior vena cava, and shorter tricuspid annular plane systolic excursion than the other two groups. During the follow-up period (median 485 days), 132 all-cause deaths were observed: 27 (12.3%) in the low, 37 (17.0%) in the middle, and 68 (31.2%) in the high hyaluronic acid (P < 0.001) groups. Cox proportional hazards analysis revealed that higher log-transformed hyaluronic acid levels were significantly associated with all-cause death (hazard ratio, 1.38; 95% confidence interval, 1.15-1.66; P < 0.001). No significant interaction was observed between hyaluronic acid level and reduced/preserved left ventricular ejection fraction on all-cause death (P = 0.409). Hyaluronic acid provided additional prognostic predictability to pre-existing prognostic factors, including the fibrosis-4 index (continuous net reclassification improvement, 0.232; 95% confidence interval, 0.022-0.441; P = 0.030). In hospitalized patients with heart failure, hyaluronic acid was associated with right ventricular dysfunction and congestion and was independently associated with prognosis regardless of left ventricular ejection fraction.

Risk stratification of patients with cardiac sarcoidosis: the ILLUMINATE-CS registry.

AIMS: This study evaluated the prognosis and prognostic factors of patients with cardiac sarcoidosis (CS), an underdiagnosed disease. METHODS AND RESULTS: Patients from a retrospective multicentre registry, diagnosed with CS between 2001 and 2017 based on the 2016 Japanese Circulation Society or 2014 Heart Rhythm Society criteria, were included. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and documented fatal ventricular arrhythmia events (FVAE), each constituting exploratory endpoints. Among 512 registered patients, 148 combined events (56 heart failure hospitalizations, 99 documented FVAE, and 49 all-cause deaths) were observed during a median follow-up of 1042 (interquartile range: 518-1917) days. The 10-year estimated event rates for the primary endpoint, all-cause death, heart failure hospitalizations, and FVAE were 48.1, 18.0, 21.1, and 31.9%, respectively. On multivariable Cox regression, a history of ventricular tachycardia (VT) or fibrillation [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.59-4.00, P < 0.001], log-transformed brain natriuretic peptide (BNP) levels (HR 1.28, 95% CI 1.07-1.53, P = 0.008), left ventricular ejection fraction (LVEF) (HR 0.94 per 5% increase, 95% CI 0.88-1.00, P = 0.046), and post-diagnosis radiofrequency ablation for VT (HR 2.65, 95% CI 1.02-6.86, P = 0.045) independently predicted the primary endpoint. CONCLUSION: Although mortality is relatively low in CS, adverse events are common, mainly due to FVAE. Patients with low LVEF, with high BNP levels, with VT/fibrillation history, and requiring ablation to treat VT are at high risk.

Clinical significance of 123I-BMIPP washout rate in patients with uncertain chronic heart failure.

BACKGROUND: Recently, triglyceride deposit cardiomyovasculopathy (TGCV) with defective intracellular lipolysis was found to be a disease that causes heart failure. As a diagnostic criterion for TGCV, an Iodaine-123-ß-methyl iodophenyl-pentadecanoic acid washout rate (BMIPP WOR) of < 10% is used, but its clinical significance in patients with heart failure remains to be clarified. METHODS: In 62 hospitalized patients with chronic heart failure, 123I-BMIPP myocardial single-photon emission computed tomography (SPECT) was performed predischarge state. The prevalence of TGCV was investigated. Subsequently, follow-up was conducted for ≥ 90 days (mean: 724.6 ± 392.7 days), and the association between the BMIPP WOR and cardiac events was examined, establishing all-cause mortality and admission due to heart failure as endpoints. RESULTS: Of the 62 patients, the WOR was < 10% in 41 (66.1%). Of these, 26 (41.9%) were diagnosed with definite TGCV. Furthermore, cardiac events were noted in 12 patients (19.4%). Analysis with Cox proportional hazards models showed that the BMIPP WOR < 4.5% was a significant event-predicting factor [HR 4.29, 95% CI: 1.20-16.87; p = 0.0245]. On a Kaplan-Meier curve, the WOR was 4.5%; there was a significant difference in the incidence of events (p = 0.0298). CONCLUSION: In the predischarge state of heart failure, 123I-BMIPP myocardial SPECT was performed. In approximately 40% of the patients, a diagnosis of TGCV was made. The results suggested that the BMIPP WOR is useful for predicting the prognosis of chronic heart failure patients regardless of TGCV.

New-Onset Atrial Fibrillation in Patients With Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease　- Insights From the CLAVIS-COVID Registry.

BACKGROUND: Both pre-existing atrial fibrillation (AF) and new-onset AF (NOAF) are observed in patients with coronavirus disease 2019 (COVID-19); however, the effect of AF on clinical outcomes is unclear. This study aimed to investigate the effect of AF, especially NOAF, on the outcomes of hospitalized patients with COVID-19.Methods and Results: This study analyzed 673 COVID-19 patients with cardiovascular diseases and risk factors (CVDRF). Patients were divided into 3 groups; pre-existing AF (n=55), NOAF (n=28), and sinus rhythm (SR) (n=590). The baseline characteristics and in-hospital outcomes were evaluated. The mean age of the patients was 68 years, 65.4% were male, and the in-hospital mortality rate was 15.6%. The NOAF group demonstrated a higher in-hospital mortality rate (42.9%) than the pre-existing AF (30.9%) and SR (11.2%) groups (P<0.001). Patients with NOAF had a higher incidence of acute respiratory syndrome, multiple organ disease, hemorrhage, and stroke than those with pre-existing AF and NOAF. NOAF was independently associated with in-hospital mortality after adjusting for pre-existing AF and 4C mortality score (odds ratio [95% confidence interval]: 4.71 [1.63-13.6], P<0.001). CONCLUSIONS: Patients with NOAF had significantly worse outcomes as compared to patients with pre-existing AF and SR. The incidence of NOAF would be a useful predictor of clinical outcomes during hospitalization.

Prevalence and Prognostic Relevance of Isolated Tubular Dysfunction in Patients With Acute Heart Failure.

BACKGROUND: Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF).Methods and Results:This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and TD (urinary ß-2-microglobulin ≥300 µg/gCr). Patients were grouped according to the presence/absence of GD and TD as having neither condition (n=116), isolated TD (n=101), isolated GD (n=83), or coexisting GD plus TD (n=189). During a median follow up of 466 days (interquartile range: 170-871 days), 107 deaths were observed. Kaplan-Meier curve analysis revealed that, relative to the absence of a GD and TD group, higher mortality rates were observed in the groups with isolated TD, isolated GD, and coexisting GD plus TD (log-rank P<0.001). Similarly, the adjusted Cox regression analyses revealed that significantly higher risks of mortality were associated with isolated TD, isolated GD, and coexisting GD plus TD. Moreover, isolated GD and isolated TD were both independently associated with increased risks of all-cause mortality. CONCLUSIONS: As a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

Sex differences in the prevalence and prognostic impact of physical frailty and sarcopenia among older patients with heart failure.

BACKGROUND AND AIMS: Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear. METHODS AND RESULTS: We included 1332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19-3.16; P = 0.008 for men; HR, 1.63; 95% CI, 0.84-3.13; P = 0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13-3.31; P = 0.017 for men; HR, 3.18; 95% CI, 1.59-5.64; P = 0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P = 0.806 for frailty; P = 0.254 for sarcopenia). CONCLUSIONS: Frailty and sarcopenia negatively affect older patients with heart failure from both sexes. CLINICAL TRIALS: This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled.

Sarcopenic obesity is associated with impaired physical function and mortality in older patients with heart failure: insight from FRAGILE-HF.

BACKGROUND: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. METHODS: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). RESULTS: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012). CONCLUSION: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure. TRIAL REGISTRATION: University Hospital Information Network (UMIN-CTR: UMIN000023929 ).

Multidomain Frailty as a Therapeutic Target in Elderly Patients with Heart Failure.

Heart failure and frailty share aging as a strong risk factor. The prevalence of frailty has been shown to be particularly high in elderly patients with heart failure. Moreover, it is important not to confine frailty to physical aspects. Rather, it should be considered to consist of multiple domains, including physical disability, psychiatric disorders, cognitive impairment, depression, and social disconnection. Development of interventions that can improve frailty domains are not well established, although observational studies have evaluated the association of various frailty domains and their prognostic impact. Some interventions, including resistance exercise, functional exercise, and respiratory muscle training have been demonstrated to hold potential for improving physical frailty. In terms of cognitive dysfunction, previous studies have demonstrated that exercise therapy is also effective for cognitive dysfunction. The social domain of frailty is one of the least investigated domains, particularly in patients with heart failure. However, heart failure is also strongly associated with physical frailty and cognitive impairment and has a poor prognosis in old patients. The prevalence of social frailty in elderly patients who need hospitalization due to heart failure is higher than previously thought. Very few studies have tested interventions targeting social frailty. Frailty and heart failure affect each other, and both are becoming increasingly important in society. In this article, we review the physical, cognitive, and social domains of frailty and the possible interventions to improve them in patients with heart failure.

Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure.

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.

Prognostic Implications of Reductions in Heart Rates in Patients With Acute Heart Failure and Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with acute heart failure (AHF). Heart rate (HR) also changes significantly over time. However, the association between changes in HR in AF patients and prognosis is uncertain.Methods and Results:We investigated the association between HR reduction in AF achieved within 48 h of admission and 60-day mortality in patients with AHF from the REALITY-AHF study. The percentage HR (%HR) reduction was calculated as (baseline HR-HR at 48 h) / baseline HR × 100. The primary endpoint was 60-day all-cause mortality. In 468 patients with confirmed AF at both admission and 48 h after admission, the median HR at these time points was 105±31 and 84±18 beats/min, respectively. The median %HR reduction was 15.4% (interquartile range 2.2-31.4%). During the 60 days of admission, 39 deaths (8.3%) were recorded, and the %HR reduction within 48 h was significantly associated with 60-day mortality in the unadjusted model (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.77-0.95; P=0.005) and after adjusting for other covariates (HR 0.81; 95% CI 0.68-0.96; P=0.016).Furthermore, the %HR reduction was associated with a significant reduction in 60-day mortality in patients with higher baseline HR. CONCLUSIONS: %HR reduction is associated with a better short-term prognosis in patients with AHF presenting with AF, particularly in those with a rapid ventricular response.

Multiple Cardiovascular Diseases or Risk Factors Increase the Severity of Coronavirus Disease 2019.

BACKGROUND: This study aimed to determine whether disease severity varied according to whether coronavirus disease 2019 (COVID-19) patients had multiple or single cardiovascular diseases and risk factors (CVDRFs).Methods and Results:COVID-19 patients with single (n=281) or multiple (n=412) CVDRFs were included retrospectively. Multivariable logistic regression showed no significant difference in the risk of in-hospital death between groups, but patients with multiple CVDRFs had a significantly higher risk of acute respiratory distress syndrome (odds ratio: 1.75, 95% confidence interval: 1.09-2.81). CONCLUSIONS: COVID-19 patients with multiple CVDRFs have a higher risk of complications than those with a single CDVRF.

Association Between Statin Use Prior to Admission and Lower Coronavirus Disease 2019 (COVID-19) Severity in Patients With Cardiovascular Disease or Risk Factors.

BACKGROUND: Cardiovascular diseases and/or risk factors (CVDRF) have been reported as risk factors for severe coronavirus disease 2019 (COVID-19).Methods and Results:In total, we selected 693 patients with CVDRF from the CLAVIS-COVID database of 1,518 cases in Japan. The mean age was 68 years (35% females). Statin use was reported by 31% patients at admission. Statin users exhibited lower incidence of extracorporeal membrane oxygenation (ECMO) insertion (1.4% vs. 4.6%, odds ratio [OR]: 0.295, P=0.037) and septic shock (1.4% vs. 6.5%, OR: 0.205, P=0.004) despite having more comorbidities such as diabetes mellitus. CONCLUSIONS: This study suggests the potential benefits of statins use against COVID-19.

Clinical and Biomarker Profiles and Prognosis of Elderly Patients With Coronavirus Disease 2019 (COVID-19) With Cardiovascular Diseases and/or Risk Factors.

BACKGROUND: This study investigated the effects of age on the outcomes of coronavirus disease 2019 (COVID-19) and on cardiac biomarker profiles, especially in patients with cardiovascular diseases and/or risk factors (CVDRF).Methods and Results:A nationwide multicenter retrospective study included 1,518 patients with COVID-19. Of these patients, 693 with underlying CVDRF were analyzed; patients were divided into age groups (<55, 55-64, 65-79, and ≥80 years) and in-hospital mortality and age-specific clinical and cardiac biomarker profiles on admission evaluated. Overall, the mean age of patients was 68 years, 449 (64.8%) were male, and 693 (45.7%) had underlying CVDRF. Elderly (≥80 years) patients had a significantly higher risk of in-hospital mortality regardless of concomitant CVDRF than younger patients (P<0.001). Typical characteristics related to COVID-19, including symptoms and abnormal findings on baseline chest X-ray and computed tomography scans, were significantly less prevalent in the elderly group than in the younger groups. However, a significantly (P<0.001) higher proportion of elderly patients were positive for cardiac troponin (cTn), and B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP) levels on admission were significantly higher among elderly than younger patients (P<0.001 and P=0.001, respectively). CONCLUSIONS: Elderly patients with COVID-19 had a higher risk of mortality during the hospital course, regardless of their history of CVDRF, were more likely to be cTn positive, and had significantly higher BNP/NT-proBNP levels than younger patients.