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1.
J Card Fail ; 2022 Jun 09.
Article in English | MEDLINE | ID: covidwho-1944396

ABSTRACT

BACKGROUND: Patients with heart failure (HF) are at high risk for adverse outcomes when they have COVID-19. Reports of COVID-19 vaccine-related cardiac complications may contribute to vaccine hesitancy in patients with HF. METHODS: To analyze the impact of COVID-19 vaccine status on clinical outcomes in patients with HF, we conducted a retrospective cohort study of the association of COVID-19 vaccination status with hospitalizations, intensive care unit admission and mortality after adjustment for covariates. Inverse probability treatment-weighted models were used to adjust for potential confounding. RESULTS: Of 7094 patients with HF, 645 (9.1%) were partially vaccinated, 2200 (31.0%) were fully vaccinated, 1053 were vaccine-boosted (14.8%), and 3196 remained unvaccinated (45.1%) by January 2022. The mean age was 73.3 ± 14.5 years, and 48% were female. Lower mortality rates were observed in patients who were vaccine-boosted, followed by those who were fully vaccinated; they experienced lower mortality rates (HR 0.33; CI 0.23, 0.48) and 0.36 (CI 0.30, 0.43), respectively, compared to unvaccinated individuals (P< 0.001) over the mean follow-up time of 276.5 ± 104.9 days, whereas no difference was observed between those who were unvaccinated or only partially vaccinated. CONCLUSION: COVID-19 vaccination was associated with significant reduction in all-cause hospitalization rates and mortality rates, lending further evidence to support the importance of vaccination implementation in the high-risk population of patients living with HF.

2.
J Card Fail ; 2022 Jun 16.
Article in English | MEDLINE | ID: covidwho-1894841

ABSTRACT

INTRODUCTION: There are varied opinions in the United States regarding many aspects of care related to COVID-19. The purpose of this study was to examine the opinions of health care personnel and the policies of heart transplant centers concerning practices for the prevention and treatment of COVID-19 in donors and recipients of heart transplants. METHODS: Two anonymous, electronic web-based surveys were developed: 1 was administered to health care personnel through a mailing list maintained by the Heart Failure Society of America (HFSA); another was administered to U.S. medical adult and pediatric heart transplant (HT) program directors. Individual and group e-mails were sent with an embedded link to the respective surveys in February 2022. RESULTS: A total of 176 individuals (8.6%) responded to the survey administered through the HFSA. Of medical directors of transplant programs, 78 (54% response rate) completed a separate survey on their centers' policies. Although 95% (n = 167) of individuals indicated vaccination against COVID-19 should be required prior to HT, only 67% (n = 52) of centers mandated that practice. Similarly, 61% of individuals thought vaccination should be required prior to HT for caregivers, but only 13% of transplant centers mandated caregiver vaccination. Of the centers, 63% reported considering donors despite histories of recent COVID-19 infection (within 3 months), and 47% considered donors with current positive polymerase chain reaction tests. Regarding post-transplant care, only 22% of programs routinely measured antibodies to COVID-19, and 71% used tixagevimab/cilgavimab (Evusheld) for pre-exposure prophylaxis. CONCLUSIONS: There were significant differences between individual preferences and centers' practices with respect to COVID-19 management of candidates for and recipients of HT. Additionally, there was wide variation in policies among centers, reflecting the need for further study to inform consistent guidance and recommendations across centers to optimize equitable care for this high-risk patient population.

3.
J Card Fail ; 28(3): 351-352, 2022 03.
Article in English | MEDLINE | ID: covidwho-1750974
5.
J Am Coll Cardiol ; 79(9): 917-928, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1706820

ABSTRACT

Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Thromboembolism/prevention & control , Thrombosis/prevention & control , COVID-19/therapy , Critical Care , Enoxaparin/therapeutic use , Hospitalization , Humans , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thromboembolism/virology , Thrombosis/virology
6.
Clin Infect Dis ; 73(11): e4090-e4099, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561046

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.


Subject(s)
COVID-19 , Organ Transplantation , Cohort Studies , Humans , Male , Middle Aged , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients
7.
JACC Heart Fail ; 9(12): 927-937, 2021 12.
Article in English | MEDLINE | ID: covidwho-1527732

ABSTRACT

OBJECTIVES: The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). BACKGROUND: Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom. METHODS: The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO2), slope of minute ventilation to CO2 production (VE/VCO2 slope), and end tidal pressure of CO2 (PetCO2) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing. RESULTS: Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO2 averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO2). VE/VCO2 slope was 30 ± 7. PetCO2 at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO2 <80% predicted. All patients with peak VO2 <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO2 had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO2 (n = 17), and/or hypocapnia PetCO2 <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS. CONCLUSIONS: Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.


Subject(s)
COVID-19 , Heart Failure , Adult , Dyspnea/diagnosis , Dyspnea/etiology , Exercise Test , Female , Humans , Male , Middle Aged , Oxygen Consumption , SARS-CoV-2 , Stroke Volume , Ventricular Function, Left
8.
JAMA Cardiol ; 7(1): 17-25, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1499191

ABSTRACT

Importance: The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. Objective: To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. Design, Setting, and Participants: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Intervention: Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. Main Outcomes and Measures: The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Results: Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. Conclusions and Relevance: The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. Trial Registration: ClinicalTrials.gov Identifier: NCT02816736.


Subject(s)
Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Biphenyl Compounds/therapeutic use , Heart Failure/drug therapy , Valsartan/therapeutic use , Biomarkers/blood , Double-Blind Method , Drug Combinations , Female , Heart Failure/blood , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Stroke Volume
11.
J Am Soc Nephrol ; 32(1): 151-160, 2021 01.
Article in English | MEDLINE | ID: covidwho-1080996

ABSTRACT

BACKGROUND: Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described. METHODS: This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality. RESULTS: Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up. CONCLUSIONS: AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , SARS-CoV-2 , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Acute Kidney Injury/urine , Aged , Aged, 80 and over , COVID-19/mortality , Female , Hematuria/etiology , Hospital Mortality , Hospitals, Private/statistics & numerical data , Hospitals, Urban/statistics & numerical data , Humans , Incidence , Inpatients , Leukocytes , Male , Middle Aged , New York City/epidemiology , Proteinuria/etiology , Renal Dialysis , Retrospective Studies , Treatment Outcome , Urine/cytology
13.
J Med Internet Res ; 22(11): e24018, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-979821

ABSTRACT

BACKGROUND: COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking. OBJECTIVE: The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points. METHODS: We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions. RESULTS: Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction. CONCLUSIONS: We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Machine Learning/standards , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Acute Kidney Injury/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cohort Studies , Electronic Health Records , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Hospitals , Humans , Male , Middle Aged , New York City/epidemiology , Pandemics , Prognosis , ROC Curve , Risk Assessment/methods , Risk Assessment/standards , SARS-CoV-2 , Young Adult
16.
BMJ Open ; 10(11): e040736, 2020 11 27.
Article in English | MEDLINE | ID: covidwho-947830

ABSTRACT

OBJECTIVE: The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive. DESIGN: Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive. SETTING: All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system. PARTICIPANTS: Participants over the age of 18 years were included. PRIMARY OUTCOMES: We investigated in-hospital mortality during the study period. RESULTS: A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 µg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 µg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL. CONCLUSIONS: In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged.


Subject(s)
COVID-19/blood , Critical Care , Hospital Mortality , Hospitalization , Pandemics , Adolescent , Adult , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/mortality , Comorbidity , Critical Care/statistics & numerical data , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hospitals , Humans , Lymphocytes/metabolism , Male , Middle Aged , New York City/epidemiology , Procalcitonin/blood , Retrospective Studies , Risk Factors , SARS-CoV-2 , Young Adult
17.
J Am Coll Cardiol ; 76(20): 2334-2348, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-899039

ABSTRACT

BACKGROUND: Patients with pre-existing heart failure (HF) are likely at higher risk for adverse outcomes in coronavirus disease-2019 (COVID-19), but data on this population are sparse. OBJECTIVES: This study described the clinical profile and associated outcomes among patients with HF hospitalized with COVID-19. METHODS: This study conducted a retrospective analysis of 6,439 patients admitted for COVID-19 at 1 of 5 Mount Sinai Health System hospitals in New York City between February 27 and June 26, 2020. Clinical characteristics and outcomes (length of stay, need for intensive care unit, mechanical ventilation, and in-hospital mortality) were captured from electronic health records. For patients identified as having a history of HF by International Classification of Diseases-9th and/or 10th Revisions codes, manual chart abstraction informed etiology, functional class, and left ventricular ejection fraction (LVEF). RESULTS: Mean age was 63.5 years, and 45% were women. Compared with patients without HF, those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%; adjusted odds ratio: 3.64; 95% confidence interval: 2.56 to 5.16; p < 0.001), and mortality (40.0% vs. 24.9%; adjusted odds ratio: 1.88; 95% confidence interval: 1.27 to 2.78; p = 0.002). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use. CONCLUSIONS: History of HF was associated with higher risk of mechanical ventilation and mortality among patients hospitalized for COVID-19, regardless of LVEF.


Subject(s)
COVID-19/mortality , Heart Failure , Hospitalization , Aged , Aged, 80 and over , COVID-19/diagnosis , Cohort Studies , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors
18.
J Am Coll Cardiol ; 76(17): 2011-2023, 2020 Oct 27.
Article in English | MEDLINE | ID: covidwho-872170

ABSTRACT

The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection. Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019. What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities. Myocardial injury occurs in approximately one-quarter of hospitalized patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality. The central pathophysiology underlying cardiovascular injury is the interplay between virus binding to the angiotensin-converting enzyme 2 receptor and the impact this action has on the renin-angiotensin system, the body's innate immune response, and the vascular response to cytokine production. The purpose of this review was to describe the mechanisms underlying cardiovascular injury, including that of thromboembolic disease and arrhythmia, and to discuss their clinical sequelae.


Subject(s)
Cardiovascular Diseases/virology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Humans , Pandemics , SARS-CoV-2
19.
J Am Coll Cardiol ; 76(16): 1815-1826, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-849705

ABSTRACT

BACKGROUND: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. OBJECTIVES: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. METHODS: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. RESULTS: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. CONCLUSIONS: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.


Subject(s)
Anticoagulants , Autopsy/statistics & numerical data , Coronavirus Infections , Hospitalization/statistics & numerical data , Pandemics , Pneumonia, Viral , Post-Exposure Prophylaxis , Thromboembolism , Aged , Anticoagulants/classification , Anticoagulants/therapeutic use , Betacoronavirus/isolation & purification , Blood Coagulation , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Hospital Mortality , Humans , Male , New York City/epidemiology , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Post-Exposure Prophylaxis/methods , Post-Exposure Prophylaxis/statistics & numerical data , Risk Adjustment/methods , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/mortality , Thromboembolism/prevention & control , Thromboembolism/virology
20.
JACC Heart Fail ; 8(10): 789-799, 2020 10.
Article in English | MEDLINE | ID: covidwho-816609

ABSTRACT

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).


Subject(s)
Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Heart Failure/drug therapy , Tetrazoles/therapeutic use , Betacoronavirus , Biphenyl Compounds , COVID-19 , Cardiotonic Agents/therapeutic use , Coronavirus Infections , Dose-Response Relationship, Drug , Double-Blind Method , Drug Combinations , Early Termination of Clinical Trials , Glomerular Filtration Rate , Heart Failure/metabolism , Heart Failure/physiopathology , Heart Transplantation , Heart-Assist Devices , Hospitalization/statistics & numerical data , Humans , Hypotension/chemically induced , Natriuretic Peptide, Brain/metabolism , Pandemics , Peptide Fragments/metabolism , Pneumonia, Viral , SARS-CoV-2 , Stroke Volume , Valsartan
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