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Study objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied. Design/setting/participants/interventions/outcome measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19. Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20–3/24/21) and 26,459 patients were admitted in the year prior (2/16/19–2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p

Background: Low-dose colchicine has been shown to lower major adverse cardiovascular events (MACE) among those with cardiovascular disease (CVD). It remains unclear how long a CVD patient needs to live to potentially benefit from colchicine. Our study aimed to determine the time to benefit (TTB) of colchicine in individuals with CVD. Methods: Literature searches were performed in PubMed for the cardiovascular outcome trial of colchicine in patients with CVD until October 12, 2023. The primary outcome measured was MACE. Reconstructed individual participant data (IPD) and the stratified Cox proportional hazards model were used to calculate the hazard ratio (HR) and 95 % confidence interval (CI) to estimate the efficacy of colchicine, and Weibull survival curves were fitted to estimate TTB for specific absolute risk reduction (ARR) thresholds (0.002, 0.005, and 0.01). Results: Four trials randomizing 11,594 adults aged between 59.8 and 66.5 years were included (follow-up duration: 12–28.6 months). Compared with placebo, colchicine reduced the risk of MACE (HR 0.68, 95 % CI: 0.60 to 0.78) but had no impact on cardiovascular and all-cause mortality. A TTB of 11.0 months (95 % CI: 0.59 to 21.3) was estimated to be needed to prevent 1 MACE in 100-colchicine-treated patients. The TTB for acute coronary syndrome was similar compared to stable coronary artery disease (10.7 vs. 11.2 months for ARR = 0.010). Conclusions: By using reconstructed IPD, this pooled analysis demonstrated that colchicine was associated with reduced nonfatal MACE, and the TTB was approximately 11.0 months to prevent 1 MACE per 100 patients.

Objective: To evaluate the impact of age and COVID-19 variant time period on morbidity and mortality among those hospitalized with COVID-19. Patients and Methods: Patients from the American Heart Association’s Get With The Guidelines COVID-19 cardiovascular disease registry (January 20, 2020-February 14, 2022) were divided into groups based on whether they presented during periods of wild type/alpha, delta, or omicron predominance. They were further subdivided by age (young: 18-40 years; older: more than 40 years), and characteristics and outcomes were compared. Results: The cohort consisted of 45,421 hospitalized COVID-19 patients (wild type/alpha period: 41,426, delta period: 3349, and omicron period: 646). Among young patients (18-40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.6; 95% CI, 1.3-2.1), major adverse cardiovascular events (MACE) (OR, 1.8; 95% CI, 1.3-2.5), and in-hospital mortality (OR, 2.2; 95% CI, 1.5-3.3) when compared with presentation during wild type/alpha. Among older patients (more than 40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.2; 95% CI, 1.1-1.3), MACE (OR, 1.5; 95% CI, 1.4-1.7), and in-hospital mortality (OR, 1.4; 95% CI, 1.3-1.6) when compared with wild type/alpha. Among older patients (more than 40 years), presentation during omicron associated with decreased odds of severe COVID-19 (OR, 0.7; 95% CI, 0.5-0.9) and in-hospital mortality (OR, 0.6; 95% CI, 0.5-0.9) when compared with wild type/alpha. Conclusion: Among hospitalized adults with COVID-19, presentation during a time of delta predominance was associated with increased odds of severe COVID-19, MACE, and in-hospital mortality compared with presentation during wild type/alpha. Among older patients (aged more than 40 years), presentation during omicron was associated with decreased odds of severe COVID-19 and in-hospital mortality compared with wild type/alpha.

Summary: Background: Whether the accuracy of the phenotype ascribed to patients in electronic health records (EHRs) is associated with variation in prognosis and care provision is unknown. We investigated this for heart failure (HF, characterised as HF with preserved ejection fraction [HFpEF], HF with reduced ejection fraction [HFrEF] and unspecified HF). Methods: We included individuals aged 16 years and older with a new diagnosis of HF between January 2, 1998 and February 28, 2022 from linked primary and secondary care records in the Clinical Practice Research Datalink in England. We investigated the provision of guideline-recommended diagnostic investigations and pharmacological treatments. The primary outcome was a composite of HF hospitalisation or all-cause death, and secondary outcomes were time to HF hospitalisation, all-cause death and death from cardiovascular causes. We used Kaplan–Meier curves and log rank tests to compare survival across HF phenotypes and adjusted for potential confounders in Cox proportional hazards regression analyses. Findings: Of a cohort of 95,262 individuals, 1271 (1.3%) were recorded as having HFpEF, 10,793 (11.3%) as HFrEF and 83,198 (87.3%) as unspecified HF. Individuals recorded as unspecified HF were older with a higher prevalence of dementia. Unspecified HF, compared to patients with a recorded HF phenotype, were less likely to receive specialist assessment, echocardiography or natriuretic peptide testing in the peri-diagnostic period, or receive angiotensin-converting enzyme inhibitors, beta blockers or mineralocorticoid receptor antagonists up to 12 months after diagnosis (risk ratios compared to HFrEF, 0.64, 95% CI 0.63–0.64; 0.59, 0.58–0.60; 0.57, 0.55–0.59; respectively) and had significantly worse outcomes (adjusted hazard ratios compared to HFrEF, HF hospitalisation and death 1.66, 95% CI 1.59–1.74; all-cause mortality 2.00, 1.90–2.10; cardiovascular death 1.77, 1.65–1.90). Interpretation: Our findings suggested that absence of specification of HF phenotype in routine EHRs is inversely associated with clinical investigations, treatments and survival, representing an actionable target to mitigate prognostic and health resource burden. Funding: Japan Research Foundation for Healthy Aging and British Heart Foundation.

Background: Guideline-directed device therapies (GDDT) improve outcomes for eligible patients with heart failure (HF) with reduced ejection fraction (HFrEF). Utilization rates of device therapies in HFrEF after the 2012 ACCF/AHA/HRS Focused Update for Device-based Therapies of Cardiac Rhythm Abnormalities have not been well studied. Objective: Characterize the use of GDDT in newly indicated HFrEF patients from 2012 to 2019 using aggregated electronic health record (EHR) data. Methods: Computable phenotyping algorithms for implantable cardioverter defibrillator/cardiac resynchronization therapy-defibrillator (ICD/CRT-D) indications from the GuideLine Indications Detected in EHR for Heart Failure program (GLIDE-HF) used diagnoses, procedures, measures, prescriptions, and the output of natural language processed provider notes from de-identified Optum® EHR data. Patients had a diagnosis of HF, dilated cardiomyopathy, or prior infarct, and were included if they had HFrEF with >1 year of records prior to a new Class 1 or Class 2a indication for an ICD or cardiac resynchronization therapy with defibrillator (CRT-D) from 2012 to 2019. Results: Records showed 137,476 HFrEF patients were newly indicated for an ICD or CRT-D. GDDT was used in 14,892 of 36,358 (41.0%) CRT-D indicated patients and in 14,904 of 101,118 (14.7%) ICD-indicated patients. While GDDT use was low, 95.7% had echocardiography and 92.1% had prescriptions for beta-blockers or angiotensin-converting enzyme/angiotensin-receptor blockers medications. Conclusions: In this modern cohort of HF patients, a large proportion of eligible patients did not receive ICDs or CRT-Ds, while frequently receiving other indicated cardiovascular interventions and treatments.

Objectives: The relationship between prior glycemic status and outcomes in intracerebral hemorrhage (ICH) is not established. We hypothesized that higher hemoglobin (Hb) A1c is associated with worse outcomes in ICH. Patients and methods: Using the GWTG-Stroke registry, data on patients with ICH between April 1, 2003 and September 30, 2015 were harvested. Patients were divided into four ordinal groups based on HbA1c values of 8.0%. Outcomes (mortality, modified Rankin Scale (mRS), home discharge and independent ambulatory status) were analyzed for patients overall and separately for patients with or without history of diabetes using multivariable regression models. Results: Among 75,455 patients with ICH (with available HbA1c data), patients with lower HbA1c (8.0%), (15.0%; 205/1364) were associated with higher in-hospital mortality. Lower HbA1c was also associated with higher mRS, less chance of going home, and lower likelihood of having independent ambulatory status in patients with prior history of diabetes. Conclusions: Among patients with no reported history of diabetes, both very low and very high HbA1c were directly associated with higher in-hospital mortality. Only very low HbA1c was associated with higher mortality in known diabetic patients. Further studies are needed to better define the relationship between HbA1c and outcomes, for it may have important implications for care of ICH patients.

Cognitive abnormalities, including memory deficits, are common in heart failure (HF). Brain structures, including the hippocampus, fornix, and thalamus participate in memory processing, and most show structural injury and functional deficits in HF. The mammillary bodies and fornix play essential roles in spatial and working memory processing, interact with other structures, and may also be injured in HF. We assessed mammillary body volumes and cross-sectional fornix areas in 17 HF and 50 control subjects using high-resolution T1-weighted magnetic resonance images. Mammillary body volumes and fornix cross-sectional areas were significantly reduced bilaterally in HF, and these differences remained after controlling age, gender, and intracranial volume. Mammillary body and fornix injury may contribute to the compromised spatial and working memory deficits in HF. Pathological processes eliciting the damage may include injury accompanying hypoxic/ischemic processes in pathologic HF perfusion and breathing, and thiamine deficiency accompanying diuretic use and nutritional mal-absorption in the condition.

For more than two decades, there has been continuing evidence of lipid oxidation playing a central role in atherogenesis. The oxidation hypothesis of atherogenesis has evolved to focus on specific proinflammatory oxidized phospholipids that result from the oxidation of LDL phospholipids containing arachidonic acid and that are recognized by the innate immune system in animals and humans. These oxidized phospholipids are largely generated by potent oxidants produced by the lipoxygenase and myeloperoxidase pathways. The failure of antioxidant vitamins to influence clinical outcomes may have many explanations, including the inability of vitamin E to prevent the formation of these oxidized phospholipids and other lipid oxidation products of the myeloperoxidase pathway. Preliminary data suggest that the oxidation hypothesis of atherogenesis and the reverse cholesterol transport hypothesis of atherogenesis may have a common biological basis.The levels of specific oxidized lipids in plasma and lipoproteins, the levels of antibodies to these lipids, and the inflammatory/anti-inflammatory properties of HDL may be useful markers of susceptibility to atherogenesis. Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides may both promote a reduction in oxidized lipids and enhance reverse cholesterol transport and therefore may have therapeutic potential.

Treatment of human artery wall cells with apolipoprotein A-I (apoA-I), but not apoA-II, with an apoA-I peptide mimetic, or with high density lipoprotein (HDL), or paraoxonase, rendered the cells unable to oxidize low density lipoprotein (LDL). Human aortic wall cells were found to contain 12-lipoxygenase (12-LO) protein. Transfection of the cells with antisense to 12-LO (but not sense) eliminated the 12-LO protein and prevented LDL-induced monocyte chemotactic activity. Addition of 13(S)-hydroperoxyoctadecadienoic acid [13(S)-HPODE] and 15(S)-hydroperoxyeicosatetraenoic acid [15(S)-HPETE] dramatically enhanced the nonenzymatic oxidation of both 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and cholesteryl linoleate. On a molar basis 13(S)-HPODE and 15(S)-HPETE were approximately two orders of magnitude greater in potency than hydrogen peroxide in causing the formation of biologically active oxidized phospholipids (m/z 594, 610, and 828) from PAPC. Purified paraoxonase inhibited the biologic activity of these oxidized phospholipids. HDL from 10 of 10 normolipidemic patients with coronary artery disease, who were neither diabetic nor receiving hypolipidemic medications, failed to inhibit LDL oxidation by artery wall cells and failed to inhibit the biologic activity of oxidized PAPC, whereas HDL from 10 of 10 age- and sex-matched control subjects did. We conclude that a) mildly oxidized LDL is formed in three steps, one of which involves 12-LO and each of which can be inhibited by normal HDL, and b) HDL from at least some coronary artery disease patients with normal blood lipid levels is defective both in its ability to prevent LDL oxidation by artery wall cells and in its ability to inhibit the biologic activity of oxidized PAPC. —Navab, M., S. Y. Hama, G. M. Anantharamaiah, K. Hassan, G. P. Hough, A. D. Watson, S. T. Reddy, A. Sevanian, G. C. Fonarow, and A. M. Fogelman. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3. J. Lipid Res. 2000. 41: 1495–1508.