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Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial

Smilowitz, Nathaniel R; Hade, Erinn M; Kornblith, Lucy Z; Castellucci, Lana A; Cushman, Mary; Farkouh, Michael; Gong, Michelle N; Heath, Anna; Hunt, Beverly J; Kim, Keri S; Kindzelski, Andrei; Lawler, Patrick; Leaf, David E; Goligher, Ewan; Leifer, Eric S; McVerry, Bryan J; Reynolds, Harmony R; Zarychanski, Ryan; Hochman, Judith S; Neal, Matthew D; Berger, Jeffrey S
BACKGROUND/UNASSIGNED:Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. OBJECTIVES/UNASSIGNED:We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. METHODS/UNASSIGNED:We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. RESULTS/UNASSIGNED:Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. CONCLUSION/UNASSIGNED:Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.
PMCID:10506136
PMID: 37727846
ISSN: 2475-0379
CID: 5603262

Age or Functional Debility to Predict Death After Percutaneous Coronary Intervention: Age Is More Than a Number [Comment]

Smilowitz, Nathaniel R; Rao, Sunil V
PMID: 37536797
ISSN: 1942-5546
CID: 5594632

The Reply [Letter]

Smilowitz, Nathaniel R; Rubinfeld, Gregory D
PMID: 37230599
ISSN: 1555-7162
CID: 5508602

Coronary Microvascular Disease in Contemporary Clinical Practice

Smilowitz, Nathaniel R; Toleva, Olga; Chieffo, Alaide; Perera, Divaka; Berry, Colin
Coronary microvascular disease (CMD) causes myocardial ischemia in a variety of clinical scenarios. Clinical practice guidelines support routine testing for CMD in patients with ischemia with nonobstructive coronary artery disease. Invasive testing to identify CMD requires Doppler or thermodilution measures of flow to determine the coronary flow reserve and measures of microvascular resistance. Acetylcholine coronary reactivity testing identifies concomitant endothelial dysfunction, microvascular spasm, or epicardial coronary spasm. Comprehensive testing may improve symptoms, quality of life, and patient satisfaction by establishing a diagnosis and guiding-targeted medical therapy and lifestyle measures. Beyond ischemia with nonobstructive coronary artery disease, testing for CMD may play a role in patients with acute myocardial infarction, angina following coronary revascularization, heart failure with preserved ejection fraction, Takotsubo syndrome, and after heart transplantation. Additional education and provider awareness of CMD and its role in cardiovascular disease is needed to improve patient-centered outcomes of ischemic heart disease.
PMID: 37259860
ISSN: 1941-7632
CID: 5522592

Cancer and Myocardial Infarction in Women

Panday, Priya; Hausvater, Anaïs; Pleasure, Mitchell; Smilowitz, Nathaniel R; Reynolds, Harmony R
Women who present with myocardial infarction (MI) are more likely to be diagnosed with nonobstructive coronary arteries (MINOCAs), spontaneous coronary artery dissection (SCAD), and takotsubo syndrome (TS) than men. Malignancy may predispose to MI and TS through shared risk factors and inflammatory mediators. This study aimed to determine the prevalence of cancer in women presenting with clinical syndrome of MI and the association between cancer and mechanism of MI presentation. Among 520 women with MI who underwent coronary angiography at NYU Langone Health from March 2016 to March 2020 or September 2020 to September 2021, 122 (23%) had a previous diagnosis of cancer. Patients with cancer were older at MI presentation but had similar co-morbidity to those without a cancer history. The most common cancers were breast (39%), gynecologic (15%), and gastrointestinal (13%). Women with cancer history were more likely to have TS (17% vs 11% without cancer history p = 0.049). Among women with a final diagnosis of MI, the type of MI (MINOCA, MI-coronary artery disease, or SCAD) was not significantly different between groups (p = 0.374). History of cancer was present in nearly a quarter of women presenting with MI and was associated with a greater likelihood of TS than MI. MINOCA and SCAD were not more common among women with a cancer history.
PMID: 36931164
ISSN: 1879-1913
CID: 5466542

Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association

Rajagopal, Sudarshan; Ruetzler, Kurt; Ghadimi, Kamrouz; Horn, Evelyn M; Kelava, Marta; Kudelko, Kristina T; Moreno-Duarte, Ingrid; Preston, Ioana; Rose Bovino, Leonie L; Smilowitz, Nathaniel R; Vaidya, Anjali
Pulmonary hypertension, defined as an elevation in blood pressure in the pulmonary arteries, is associated with an increased risk of death. The prevalence of pulmonary hypertension is increasing, with an aging population, a rising prevalence of heart and lung disease, and improved pulmonary hypertension survival with targeted therapies. Patients with pulmonary hypertension frequently require noncardiac surgery, although pulmonary hypertension is associated with excess perioperative morbidity and death. This scientific statement provides guidance on the evaluation and management of pulmonary hypertension in patients undergoing noncardiac surgery. We advocate for a multistep process focused on (1) classification of pulmonary hypertension group to define the underlying pathology; (2) preoperative risk assessment that will guide surgical decision-making; (3) pulmonary hypertension optimization before surgery to reduce perioperative risk; (4) intraoperative management of pulmonary hypertension to avoid right ventricular dysfunction and to maintain cardiac output; and (5) postoperative management of pulmonary hypertension to ensure recovery from surgery. Last, this scientific statement highlights the paucity of evidence to support perioperative pulmonary hypertension management and identifies areas of uncertainty and opportunities for future investigation.
PMID: 36924225
ISSN: 1524-4539
CID: 5522582

Role of Resilience in the Psychological Recovery of Women With Acute Myocardial Infarction

Arabadjian, Milla; Duberstein, Zoe T; Sperber, Sarah H; Kaur, Kiranjot; Kalinowski, Jolaade; Xia, Yuhe; Hausvater, Anaïs; O'Hare, Olivia; Smilowitz, Nathaniel R; Dickson, Victoria Vaughan; Zhong, Hua; Berger, Jeffrey S; Hochman, Judith S; Reynolds, Harmony R; Spruill, Tanya M
Background Psychological well-being is important among individuals with myocardial infarction (MI) given the clear links between stress, depression, and adverse cardiovascular outcomes. Stress and depressive disorders are more prevalent in women than men after MI. Resilience may protect against stress and depressive disorders after a traumatic event. Longitudinal data are lacking in populations post MI. We examined the role of resilience in the psychological recovery of women post MI, over time. Methods and Results We analyzed a sample from a longitudinal observational multicenter study (United States, Canada) of women post MI, between 2016 and 2020. Perceived stress (Perceived Stress Scale-4 [PSS-4]) and depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]) were assessed at baseline (time of MI) and 2 months post MI. Demographics, clinical characteristics, and resilience (Brief Resilience Scale [BRS]) were collected at baseline. Low and normal/high resilience groups were established as per published cutoffs (BRS scores <3 or ≥3). Mixed-effects modeling was used to examine associations between resilience and psychological recovery over 2 months. The sample included 449 women, mean (SD) age, 62.2 (13.2) years, of whom 61.1% identified as non-Hispanic White, 18.5% as non-Hispanic Black, and 15.4% as Hispanic/Latina. Twenty-three percent had low resilience. The low resilience group had significantly higher PSS-4 and PHQ-2 scores than the normal/high resilience group at all time points. In adjusted models, both groups showed a decrease in PSS-4 scores over time. Conclusions In a diverse cohort of women post MI, higher resilience is associated with better psychological recovery over time. Future work should focus on developing strategies to strengthen resilience and improve psychological well-being for women with MI. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02905357; Unique identifier: NCT02905357.
PMID: 37026542
ISSN: 2047-9980
CID: 5463912

Frailty Assessment and Perioperative Major Adverse Cardiovascular Events After Non-Cardiac Surgery

Siddiqui, Emaad; Banco, Darcy; Berger, Jeffrey S; Smilowitz, Nathaniel R
OBJECTIVE:Frailty is an emerging risk factor for adverse outcomes. However, perioperative frailty assessments derived from electronic health records (EHR) have not been studied on a large scale. We aim to estimate the prevalence of frailty and the associated incidence of major adverse cardiovascular events (MACE) among adults hospitalized for non-cardiac surgery. METHODS:Adults aged ≥45 years hospitalized for non-cardiac surgery between 2004-2014 were identified from the National Inpatient Sample. The validated Hospital Frailty Risk Score (HFRS) derived from International Classification of Diseases codes was used to classify patients as low (HFRS <5), medium (5-10), or high (>10) frailty risk. The primary outcome was MACE, defined as myocardial infarction, cardiac arrest, and in-hospital mortality. Multivariable logistic regression was used to estimate the adjusted odds of MACE stratified by age and HFRS. RESULTS:A total of 55,349,978 hospitalizations were identified, of which 81.0%, 14.4%, and 4.6% had low, medium, and high HFRS, respectively. Patients with higher HFRS had more cardiovascular risk factors and comorbidities. MACE occurred during 2.5% of surgical hospitalizations and was common among patients with high frailty scores (high HFRS: 9.1%, medium: 6.9%, low: 1.3%, p<0.001). Medium (adjusted odds ratio [aOR] 2.05, 95% CI 2.02 to 2.08) and high (aOR 2.75, 95% CI 2.70 to 2.79) HFRS were associated with greater odds of MACE versus low HFRS, with the greatest odds of MACE observed in younger individuals 45-64 years (interaction p-value <0.001). CONCLUSIONS:The HFRS may identify frail surgical inpatients at risk for adverse perioperative cardiovascular outcomes.
PMID: 36657557
ISSN: 1555-7162
CID: 5419242

Can We Predict Who Will Have Angina Relief From Percutaneous Coronary Intervention? [Editorial]

Smilowitz, Nathaniel R; Seto, Arnold H
PMID: 36974679
ISSN: 1941-7632
CID: 5463152

Prevalence of anaemia subtypes among patients with hidradenitis suppurativa [Letter]

Obijiofor, Chinemelum; Smilowitz, Nathaniel; Garshick, Michael; Parameswaran, Anupama
PMID: 36914613
ISSN: 1468-3083
CID: 5462472