Increased frequency and mortality in persons with neurological disorders during COVID-19.

Determining the frequency and outcomes of neurological disorders associated with coronavirus disease 2019 (COVID-19) is imperative for understanding risks and for recognition of emerging neurological disorders. We investigated the susceptibility and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among persons with premorbid neurological disorders, in addition to the post-infection incidence of neurological sequelae, in a case-control population-based cohort. Using health service data collected between 1 March 2020 and 30 June 2021, we constructed a cohort of SARS-CoV-2 RNA-positive (n = 177 892) and -negative (n = 177 800) adults who were age, sex and comorbidity matched and underwent RT-PCR testing at similar times. COVID-19-associated mortality rates were examined within the cohort. Neurological sequelae were analysed during the acute (<3 months) and the post-acute (3-9 months) phases post-infection. The risk of death was significantly greater in the SARS-CoV-2 RNA-positive (2140 per 100 000 person years) compared with RNA-negative (922 per 100 000 person years) over a follow-up of 9 months, particularly amongst those with premorbid neurological disorders: adjusted odds ratios (95% confidence interval) in persons with a prior history of parkinsonism, 1.65 (1.15-2.37); dementia, 1.30 (1.11-1.52); seizures, 1.91 (1.26-2.87); encephalopathy, 1.82 (1.02-3.23); and stroke, 1.74 (1.05-2.86). There was also a significantly increased risk for diagnosis of new neurological sequelae during the acute time phase after COVID-19, including encephalopathy, 2.0 (1.10-3.64); dementia, 1.36 (1.07-1.73); seizure, 1.77 (1.22-2.56); and brain fog, 1.96 (1.20-3.20). These risks persisted into the post-acute phase after COVID-19, during which inflammatory myopathy (2.57, 1.07-6.15) and coma (1.87, 1.22-2.87) also became significantly increased. Thus, persons with SARS-CoV-2 infection and premorbid neurological disorders are at greater risk of death, and SARS-CoV-2 infection was complicated by increased risk of new-onset neurological disorders in both the acute and post-acute phases of COVID-19.

Ambulatory Cardiology or General Internal Medicine Assessment Prior to Scheduled Major Vascular Surgery is Associated with Improved Outcomes.

OBJECTIVE: To characterize the association between ambulatory cardiology or general internal medicine (GIM) assessment prior to surgery and outcomes following scheduled major vascular surgery. BACKGROUND: Cardiovascular risk assessment and management prior to high-risk surgery remains an evolving area of care. METHODS: This is population-based retrospective cohort study of all adults who underwent scheduled major vascular surgery in Ontario, Canada, April 1, 2004-March 31, 2019. Patients who had an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included: composite of 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; composite of 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication. RESULTS: Among 50,228 patients, 20,484 (40.8%) underwent an ambulatory assessment prior to surgery: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Compared to patients who did not, those who underwent an assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989[24.4%] vs. 4,587[15.4%], P<0.001) and more frequent pre-operative cardiac testing (N=7,772[37.9%] vs. 6,113[20.6%], P<0.001) but, lower 30-day mortality (N=551[2.7%] vs. 970[3.3%], P<0.001). After application of IPTW, cardiology or GIM assessment prior to surgery remained associated with a lower 30-day mortality (weighted Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes. CONCLUSIONS: Major vascular surgery patients assessed by a cardiology or GIM physician prior to surgery have better outcomes than those who are not. Further research is needed to better understand potential mechanisms of benefit.

Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2 inhibitor uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart function clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2 inhibitors. Utilization of SGLT2 inhibitors increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95%CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95%CI 0.54-0.77). However, SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2 inhibitors in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2 inhibitors and improve implementation.

Dietary Sodium Intake and Outcomes: a Secondary Analysis From Sodium-HF.

OBJECTIVES: This post hoc analysis of SODIUM-HF (Study of Dietary Intervention under 100 mmol in Heart Failure) assessed the association between baseline dietary sodium intake and change at 6 months with a composite of cardiovascular (CV) hospitalizations, emergency department visits and all-cause death at 12 and 24 months. BACKGROUND: Dietary sodium restriction is common advice for patients with heart failure (HF). Randomized clinical trials have not shown a beneficial effect of dietary sodium restriction on clinical outcomes. METHODS: A multivariable Cox proportional hazard regression model was used to assess the association of dietary sodium intake measured at randomization with primary and secondary endpoints. RESULTS: The study included 792 participants. Baseline sodium intake was ≤ 1500 mg/day in 19.9% (n = 158), 1501-3000 mg/day in 56.5% (n = 448) and > 3000 mg/day in 23.4% (n = 186) of participants. The factors associated with higher baseline sodium intake were higher calorie consumption, higher body mass index and recruitment from Canada. Multivariable analyses showed no association between baseline sodium intake nor magnitude of 6-month change or 12- or 24-month outcomes. In a responder analysis, participants achieving a sodium intake < 1500 mg at 6 months showed an association with a decreased risk for the composite outcome (adjusted HR 0.52 [95% CI 0.25, 1.07] P = 0.08) and CV hospitalization (adjusted HR 0.51 [95% CI 0.24, 1.09] P = 0.08) at 12 months. CONCLUSION: There was no association between dietary sodium intake and clinical outcomes over 24 months in patients with HF. Responder analyses suggest the need for further investigation of the effects of sodium reduction in those who achieve the targeted dietary sodium-reduction level.

Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial.

BACKGROUND: Dietary restriction of sodium has been suggested to prevent fluid overload and adverse outcomes for patients with heart failure. We designed the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) to test whether or not a reduction in dietary sodium reduces the incidence of future clinical events. METHODS: SODIUM-HF is an international, open-label, randomised, controlled trial that enrolled patients at 26 sites in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand). Eligible patients were aged 18 years or older, with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned (1:1), using a standard number generator and varying block sizes of two, four, or six, stratified by site, to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT02012179, and is closed to accrual. FINDINGS: Between March 24, 2014, and Dec 9, 2020, 806 patients were randomly assigned to a low sodium diet (n=397) or usual care (n=409). Median age was 67 years (IQR 58-74) and 268 (33%) were women and 538 (66%) were men. Between baseline and 12 months, the median sodium intake decreased from 2286 mg/day (IQR 1653-3005) to 1658 mg/day (1301-2189) in the low sodium group and from 2119 mg/day (1673-2804) to 2073 mg/day (1541-2900) in the usual care group. By 12 months, events comprising the primary outcome had occurred in 60 (15%) of 397 patients in the low sodium diet group and 70 (17%) of 409 in the usual care group (hazard ratio [HR] 0·89 [95% CI 0·63-1·26]; p=0·53). All-cause death occurred in 22 (6%) patients in the low sodium diet group and 17 (4%) in the usual care group (HR 1·38 [0·73-2·60]; p=0·32), cardiovascular-related hospitalisation occurred in 40 (10%) patients in the low sodium diet group and 51 (12%) patients in the usual care group (HR 0·82 [0·54-1·24]; p=0·36), and cardiovascular-related emergency department visits occurred in 17 (4%) patients in the low sodium diet group and 15 (4%) patients in the usual care group (HR 1·21 [0·60-2·41]; p=0·60). No safety events related to the study treatment were reported in either group. INTERPRETATION: In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events. FUNDING: Canadian Institutes of Health Research and the University Hospital Foundation, Edmonton, Alberta, Canada, and Health Research Council of New Zealand.

Association Between Vaccination Status and Outcomes in Patients Admitted to the ICU With COVID-19.

OBJECTIVES: Although COVID-19 vaccines can reduce the need for intensive care unit admission in COVID-19, their effect on outcomes in critical illness remains unclear. We evaluated outcomes in vaccinated patients admitted to the ICU with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the association between vaccination and booster status on clinical outcomes. DESIGN: Retrospective cohort. SETTING AND PATIENTS: All patients were admitted to an ICU between January 2021 (after vaccination was available) and July 2022 with a diagnosis of COVID-19 based on a SARS-CoV-2 polymerase chain reaction test in Alberta, Canada. INTERVENTIONS: None. MEASUREMENT: The propensity-matched primary outcome of all-cause in-hospital mortality was compared between vaccinated and unvaccinated patients, and vaccinated patients were stratified by booster dosing. Secondary outcomes were mechanical ventilation (MV) duration ICU length of stay (LOS). MAIN RESULTS: The study included 3,293 patients: 743 (22.6%) were fully vaccinated (54.6% with booster), 166 (5.0%) were partially vaccinated, and 2,384 (72.4%) were unvaccinated. Unvaccinated patients were more likely to require invasive MV (78.4% vs 68.2%), vasopressor use (71.1% vs 66.6%), and extracorporeal membrane oxygenation (2.1% vs 0.5%). In a propensity-matched analysis, in-hospital mortality was similar (31.8% vs 34.0%, adjusted odds ratio [OR], 1.25; 95% CI, 0.97-1.61), but median duration MV (7.6 vs 4.7 d; p < 0.001) and ICU LOS (6.6 vs 5.2 d; p < 0.001) were longer in unvaccinated compared to fully vaccinated patients. Among vaccinated patients, greater than or equal to 1 booster had lower in-hospital mortality (25.5% vs 40.9%; adjusted OR, 0.50; 95% CI, 0.0.36-0.68) and duration of MV (3.8 vs 5.6 d; p = 0.025). CONCLUSIONS: Nearly one in four patients admitted to the ICU with COVID-19 after widespread COVID-19 vaccine availability represented a vaccine-breakthrough case. Mortality risk remains substantial in vaccinated patients and similar between vaccinated and unvaccinated patients after the onset of critical illness. However, COVID-19 vaccination is associated with reduced ICU resource utilization and booster dosing may increase survivability from COVID-19-related critical illness.

Time to Triple Therapy in Patients With de Novo Heart Failure With Reduced Ejection Fraction: a Population-Based Study.

BACKGROUND: Quadruple therapy is recommended for the management of patients with heart failure (HF) and reduced ejection fraction (HFrEF). In order to provide background and identify barriers to quadruple therapy, in this study, the aim was to explore the time to initiation of triple therapy in a population-based cohort of patients with de novo HF. METHODS: Adult patients with de novo hospital or emergency department (ED) diagnosis of HF between April 1, 2008, and March 31, 2018, in Alberta, Canada, were included and were linked to echocardiography data to identify patients with HFrEF (EF ≤ 40%). Any treatment with angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers/ angiotensin receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was captured if prescribed for ≥ 28 days and filled at least once during the 12 months after the index episode. RESULTS: Among 14,092 patients with de novo HF and available echocardiography data, 54.9% had HFrEF. By 1 year after diagnosis, of those in the HFrEF cohort, 9.5% had received no therapy, 27.5% monotherapy, 41.6% dual therapy, and 21.4% triple therapy. The median (interquartile range) of time to mono-, dual- and triple therapy in patients with HFrEF were 1 (0, 26), 8 (0, 44), and 14 (0, 52) days, respectively. Patients who received triple therapy were younger, more likely to be male and to have higher frequencies of coronary artery disease, higher glomerular filtration rates and lower left ventricular ejection fraction levels compared to their counterparts. Patients with triple therapy had lower rates of clinical outcomes compared to those on no, mono or dual therapy (adjusted hazard ratio 0.15, 95% confidence interval 0.13, 0.17 for the composite outcome of death, hospitalization due to HF, or ED visit due to HF). CONCLUSION: Despite guideline recommendations, triple therapy is underused and is slowly deployed in patients with HFrEF, even after hospitalization and ED presentation.

Kidney function monitoring and trajectories in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently co-exist. The frequency of kidney monitoring and range of kidney function in patients with AF in clinical practice are uncertain. METHODS: All adult Albertans with AF between 2008 and 2017 were identified using ICD-9 and -10 codes 427.3 and I48. Kidney Disease Improving Global Outcomes (KDIGO) risk categories were defined using eGFR by the Chronic Kidney Disease Epidemiology Collaborative equation and albuminuria results within 6 months of eGFR measurement. eGFR trajectories were compared from baseline to maximum value within the following year. RESULTS: Among 105,946 patients with AF, 16.0% were KDIGO category G1 (eGFR ≥ 90), 49.0% G2 (60-89.9), 19.8% G3a (45-59.9), 11.4% G3b (30-44.9), and G4 3.8% (15-29.9). Albuminuria was normal/mild 83.4%, moderate 11.7%, and severe 4.9%. Kidney monitoring was more common among people with lower eGFR and worse albuminuria, from approximately twice annually for G1-2/A1-2 to 8 times annually in stage G4A3. Approximately 60-80% of patients received guideline-recommended monitoring, consistent across KDIGO stages. With lower baseline eGFR, annual change in eGFR decreased while the relative proportion of patients who worsened compared to improved increased: for baseline eGFR 60-89.9, 16.7% worsened vs 6.7% improved, but for eGFR 30-44.9, 8.8% worsened but only 1.0% improved. CONCLUSION: The frequency of kidney function monitoring in patients with AF increased with worsening KDIGO risk category and adhered to KDIGO guidelines in approximately three quarters of patients. A minority of patients had moderate to severe eGFR impairment, of whom most remained stable over 1 year.

Epidemiology of Worsening Heart Failure in a Population-based Cohort from Alberta, Canada: Evaluating Eligibility for Treatment With Vericiguat.

BACKGROUND: Patients with heart failure (HF) and a reduced ejection fraction (HFrEF) who experience worsening HF (WHF) events are at increased risk of adverse outcomes and experience significant morbidity and mortality. We herein describe the epidemiology of these patients and identify those potentially eligible for vericiguat therapy in this population-based study. METHODS AND RESULTS: This retrospective cohort study included hospitalized or emergency department patients with a primary diagnosis of HF and a left ventricular ejection fraction (LVEF) of less than 45% diagnosed between April 1, 2009, and March 31, 2019 in Alberta, Canada, with follow-up to March 31, 2020. Inclusion criteria from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection (VICTORIA) trial were applied to explore eligibility for vericiguat. Among 25,629 patients with HF and LVEF data, 9948 (38.8%) had HFrEF, of which 5259 (52.8%) experienced WHF at some point during a median 5.8 years of follow-up, and 38.3% of those met the vericiguat trial eligibility criteria. Compared with patients with HFrEF without WHF, those with WHF were older, with more comorbidities, worse renal function, and similar LVEF status, but greater use of HF medications at baseline. At the time of WHF, 27% of those with HFrEF and WHF were on triple therapy, 50.6% were on dual therapy, and 15.4% were on monotherapy. All-cause mortality and the composite outcome of all-cause mortality or cardiovascular hospitalization at 1-year of follow-up were higher in the HFrEF with WHF cohort compared with HFrEF without WHF (adjusted hazard ratios of 1.92 and 1.51, respectively, both P < .0001). CONCLUSIONS: Approximately one-half of patients with HFrEF experienced WHF over the long-term follow-up. Most were not on triple therapy, highlighting the underuse of the existing standard-of-care treatments and opportunities for application of newer therapies; more than one-third of patients with HFrEF may be eligible for vericiguat. LAY SUMMARY: Among patients with heart failure (HF), those who experience worsening HF (WHF) are at increased risk of adverse outcomes. A few new therapies, including vericiguat, have emerged recently for patients with HF and reduced ejection fraction. However, the epidemiology, treatment patterns, and outcomes of patients with WHF in large representative populations is unclear. In the current study, approximately one-half of the patients with HF and reduced ejection fraction experienced WHF and 38.3% were potentially eligible for vericiguat therapy. The guideline-recommended therapies were under-utilized among patients with WHF, which highlights the need for initiatives to address this care gap.

The Incidence and Prevalence of Cardiac Amyloidosis in a Large Community-Based Cohort in Alberta, Canada.

BACKGROUND: Despite the improved awareness of cardiac amyloidosis among clinicians, its incidence and prevalence is not well-described in a community setting. We sought to investigate the incidence and prevalence of cardiac amyloidosis in the community. METHODS AND RESULTS: In the adult population of Alberta, we examined 3 cohorts: (1) probable cases of cardiac amyloidosis: the presence of physician-assigned diagnosis of amyloidosis (International Classification of Diseases [ICD]-10 code E85; ICD-9 277.3) and 1 or more health care encounter for heart failure (HF) (ICD-10 I50; ICD-9 428); (2) possible cardiac amyloidosis: the presence of clinical phenotypes suggestive of amyloidosis; and (3) a comparator HF cohort without amyloidosis. Between 2004 and 2018, 982 of the 145,329 patients with HF were identified as probable cardiac amyloidosis. During the same period, the incidence rates of probable cardiac amyloidosis increased from 1.38 to 3.69 per 100,000 person-years and the prevalence rates increased from 3.42 to 14.85 per 100,000 person-years (Ptrend < .0001). Patients with probable cardiac amyloidosis were more likely to be male, have a higher comorbidity burden, greater health care use, and poorer outcomes as compared with patients with HF without amyloidosis. A much larger group of patients was identified as possible cardiac amyloidosis (n = 46,255), with similar increase in prevalence from 2004 to 2018 (from 416 to 850 per 100,000 person-years). CONCLUSIONS: The incidence and prevalence of cardiac amyloidosis has increased over the last decade. Given the advent of new therapies for cardiac amyloidosis and considering their high cost, it is imperative to devise strategies to screen, identify, and track patients with cardiac amyloidosis from administrative databases.