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.

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.

Is There Any Interaction Between Sex and Renal Function Change During Hospital Stay in Patients Hospitalized With Acute Heart Failure?

BACKGROUND: Renal dysfunction is a strong predictor of outcomes in patients with acute heart failure (AHF). However, less is known about how sex may influence the prognostic import of renal function in AHF. METHODS AND RESULTS: In a post hoc analysis of the ASCEND-HF trial including 5377 patients with AHF (33% female), patients were categorized into 3 groups based on the changes in renal function during their hospital stay. Worsening, stable, and improving renal functions were defined as a ≥20% decrease, a <20% change, and a ≥20% increase in the estimated glomerular filtration rate, respectively. The primary outcome was the composite of 30-day all-cause mortality or HF rehospitalization. The median baseline and discharge estimated glomerular filtration rate were 58.4 and 56.9 mL/min/1.73 m2, respectively. Worsening, stable, and improving renal function was observed in 31.9%, 63.2, and 4.9% of patients, respectively. Worsening renal function was associated with adverse outcomes at 30 days (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.22-1.76). This association existed in both males and females (aHR 1.42 and aHR 1.56, respectively, both P < .01). There was an interaction between renal function changes and sex (P = .025), because improving renal function was associated with better outcomes in men (aHR 0.29, 95% CI 0.13-0.66) as compared with women (aHR 1.18, 95% CI 0.59-2.35). There was no interaction between the ejection fraction and renal function in association with subsequent outcomes. CONCLUSIONS: Irrespective of sex, worsening renal function was associated with poorer outcomes at 30 days in patients with AHF. More studies are warranted to further delineate the possible sex differences in this setting.

A novel computerised quantification of thyroid vascularity in the differentiation of malignant and benign thyroid nodules.

PURPOSE: Only five percent of thyroid nodules are malignant. It is important to find reliable and at the same time non-invasive methods to identify high-risk nodules. The aim of this study was to determine the diagnostic validity of a morphologic feature-oriented approach of ultrasound study for the identification of malignant thyroid nodules. MATERIAL AND METHODS: Seventy-one thyroid nodules in 71 consecutive patients were evaluated with both ultrasonography (US) and US-assisted fine needle aspiration biopsy (FNAB). Thyroid grey-scale and power Doppler US were performed, and a Windows-based software was designed to process power Doppler US (PDUS) images that were recorded directly by the US device. We provided a histogram graph of coloured pixels and calculated the Malignancy Index to identify the probability of malignancy for each thyroid nodule. RESULTS: Thirty-six nodules (50.7%) were determined to be malignant in FNAB. Area under the receiver operating curve was 0.91 (95% CI: 0.85-0.98) for PDUS-based malignancy index in differentiating malignant thyroid nodules from benign ones. The best cut-off point for malignancy index was determined to be 0.092, with a sensitivity of 86.1% and specificity of 80% in identifying malignant nodules. CONCLUSIONS: This PDUS-driven malignancy index using a contour-finding algorithm approach could accurately and reliably differentiate malignant and benign thyroid nodules. As a pre-FNAB assessment, the malignancy index may be able to reduce the number of patients with nodular thyroid disease undergoing this invasive procedure.

Alignment of site versus adjudication committee-based diagnosis with patient outcomes: Insights from the Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3 trial.

BACKGROUND: Adjudication by an adjudication committee in clinical trials plays an important role in the assessment of outcomes. Controversy exists regarding the utility of adjudication committee versus site-based assessments and their relationship to subsequent clinical events. METHODS: This study is a secondary analysis of the Providing Rapid Out of Hospital Acute Cardiovascular Treatment-3 trial, which randomized patients with chest pain or shortness of breath for biomarker testing in the ambulance. The emergency department physician diagnosis at the time of emergency department disposition was compared with an adjudicated diagnosis assigned by an adjudication committee. The level of agreement between emergency department and adjudication committee diagnosis was evaluated using kappa coefficient and compared to clinical outcomes (30-day re-hospitalization, 30-day and 1-year mortality). RESULTS: Of the 477 patients, 49.3% were male with a median age of 70 years; hospital admission rate was 31.2%. The emergency department physicians and the adjudication committee disagreed in 55 cases (11.5%) with a kappa of 0.71 (95% confidence interval: 0.64, 0.78). The 30-day re-hospitalization, 30-day mortality, and 1-year mortality were 22%, 1.9%, and 9.4%, respectively. Although there were similar rates of re-hospitalization irrespective of adjudication, in cases of disagreement compared to agreement between adjudication committee and emergency department diagnosis, there was a higher 30-day (7.3% vs 1.2%, p = 0.002) and 1-year mortality (27.3% vs 7.1%, p < 0.001). CONCLUSION: Despite substantial agreement between the diagnosis of emergency department physicians and adjudication committee, in the subgroup of patients where there was disagreement, there was significantly worse short-term and long-term mortality.

Serum and tissue endothelin-1 are independent from intima-media thickness of peripheral arteries in patients with chronic kidney disease.

AIM: We aimed to study the relationship of peripheral arteries' atherosclerosis with serum and tissue endothelin-1 in chronic kidney disease patients. METHODS: Ninety patients were enrolled, including 35 patients with chronic kidney disease (case group), 31 patients with coronary artery diseases who were candidates for coronary artery bypass grafting (positive control group), and 24 living kidney donors (negative control group). Intima-media thickness of the common carotid and femoral arteries was determined by ultrasonography. Serum and tissue endothelin-1 were measured by ELISA method. RESULTS: The mean serum and tissue endothelin-1 levels in the donor group were significantly lower than other groups (p < 0.001 for both). The coronary artery bypass grafting group had higher carotid and femoral intima-media thickness than other groups (p < 0.001), and the chronic kidney disease group had higher carotid and femoral intima-media thickness than the donor group (p < 0.001). Regression analysis in all groups did not reveal any correlation between the carotid intima-media thickness/femoral intima-media thickness and the serum/tissue endothelin-1. There was a direct linear correlation between the carotid and femoral intima-media thickness (p < 0.001) in all groups. CONCLUSIONS: Endothelin-1 level and intima-media thickness were higher in the chronic kidney disease patients and coronary artery bypass grafting candidates, without any correlation between endothelin-1 and peripheral arteries' intima-media thickness of both groups. Perhaps endothelin-1 rises and remains high upon endothelial damage and initiation of atherosclerosis.

Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

BACKGROUND: Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. METHODS: All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 µg/L, or ferritin concentration between 100 and 300 µg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. RESULTS: Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. CONCLUSIONS: Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

Development and validation of machine learning algorithms based on electrocardiograms for cardiovascular diagnoses at the population level.

Artificial intelligence-enabled electrocardiogram (ECG) algorithms are gaining prominence for the early detection of cardiovascular (CV) conditions, including those not traditionally associated with conventional ECG measures or expert interpretation. This study develops and validates such models for simultaneous prediction of 15 different common CV diagnoses at the population level. We conducted a retrospective study that included 1,605,268 ECGs of 244,077 adult patients presenting to 84 emergency departments or hospitals, who underwent at least one 12-lead ECG from February 2007 to April 2020 in Alberta, Canada, and considered 15 CV diagnoses, as identified by International Classification of Diseases, 10th revision (ICD-10) codes: atrial fibrillation (AF), supraventricular tachycardia (SVT), ventricular tachycardia (VT), cardiac arrest (CA), atrioventricular block (AVB), unstable angina (UA), ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), pulmonary embolism (PE), hypertrophic cardiomyopathy (HCM), aortic stenosis (AS), mitral valve prolapse (MVP), mitral valve stenosis (MS), pulmonary hypertension (PHTN), and heart failure (HF). We employed ResNet-based deep learning (DL) using ECG tracings and extreme gradient boosting (XGB) using ECG measurements. When evaluated on the first ECGs per episode of 97,631 holdout patients, the DL models had an area under the receiver operating characteristic curve (AUROC) of <80% for 3 CV conditions (PTE, SVT, UA), 80-90% for 8 CV conditions (CA, NSTEMI, VT, MVP, PHTN, AS, AF, HF) and an AUROC > 90% for 4 diagnoses (AVB, HCM, MS, STEMI). DL models outperformed XGB models with about 5% higher AUROC on average. Overall, ECG-based prediction models demonstrated good-to-excellent prediction performance in diagnosing common CV conditions.

Saucerization: a modified uncapitonnage method of surgery for pulmonary hydatidosis.

BACKGROUND: There are contrary opinions regarding the surgical treatment of pulmonary hydatid cysts. We report our experience performing a modified version of uncapitonnage surgery, called "saucerization," for treating pulmonary hydatid cysts. METHODS: A total of 78 patients with pulmonary hydatid cysts were studied regarding their surgery outcome and the complication rate. The procedure used for cyst evacuation depended on whether the cyst had ruptured. If ruptured, cystotomy was done; otherwise, enucleation was preferred. To deal with the residual cavity in an uncapitonnage manner, we removed the thin margins of the pericyst and closed the bronchial openings at the cavity floor. All patients were followed up at least for 6 months. RESULTS: The intensive care unit stay ranged from 1 to 9 days. Incomplete lung expansion (six patients) was the main postoperative complication followed by wound infection (four patients) and persistent air leak (≥7 days) (one patient). There was one death. Dependence on mechanical ventilation and subsequent septic shock were also observed. The other patients exhibited no complications during the follow-up period. CONCLUSIONS: Our experience demonstrated a low complication rate associated with removing the thin margins of the residual cavity and changing the shape of it into a "saucer." The results were satisfactory and comparable to the results of other studies on pulmonary hydatid cysts.

Sodium Restriction in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Sodium restriction is a nonpharmacologic treatment suggested by practice guidelines for the management of patients with heart failure (HF). In this study, we synthesized the data from randomized controlled trials (RCTs) evaluating the effects of sodium restriction on clinical outcomes in patients with HF. METHODS: In this aggregate data meta-analysis, Cochrane Central, MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase Ovid, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus databases were searched up to April 2, 2022. RCTs were included if they investigated the effects of sodium/salt restriction as compared to no restriction on clinical outcomes in patients with HF. Outcomes of interest included mortality, hospitalization, change in New York Heart Association functional class, and quality of life (QoL). RESULTS: Seventeen RCTs were identified (834 and 871 patients in intervention and control groups, respectively). Sodium restriction did not reduce the risk of all-cause death (odds ratio, 0.95 [95% CI, 0.58-1.58]), hospitalization (odds ratio, 0.84 [95% CI, 0.62-1.13]), or the composite of death/hospitalization (odds ratio, 0.88 [95% CI, 0.63-1.23]). The results were similar in different subgroups, except for the numerically lower risk of death with reduced sodium intake reported in RCTs with dietary sodium at the 2000 to 3000 mg/d range as opposed to <2000 mg/d (and in RCTs with versus without fluid restriction as a co-intervention). Among RCTs reporting New York Heart Association change, 2 RCTs (which accounted for two-thirds of the data) showed improvement in New York Heart Association class with sodium restriction. Substantial heterogeneity existed for QoL: 6 RCTs showed improvement of QoL and 4 RCTs showed no improvement of sodium restriction on QoL. CONCLUSIONS: In a meta-analysis of RCTs, sodium restriction was not associated with fewer deaths or hospitalizations in patients with HF. Dietary sodium restriction may be associated with improvements in symptoms and QoL.

Towards artificial intelligence-based learning health system for population-level mortality prediction using electrocardiograms.

The feasibility and value of linking electrocardiogram (ECG) data to longitudinal population-level administrative health data to facilitate the development of a learning healthcare system has not been fully explored. We developed ECG-based machine learning models to predict risk of mortality among patients presenting to an emergency department or hospital for any reason. Using the 12-lead ECG traces and measurements from 1,605,268 ECGs from 748,773 healthcare episodes of 244,077 patients (2007-2020) in Alberta, Canada, we developed and validated ResNet-based Deep Learning (DL) and gradient boosting-based XGBoost (XGB) models to predict 30-day, 1-year, and 5-year mortality. The models for 30-day, 1-year, and 5-year mortality were trained on 146,173, 141,072, and 111,020 patients and evaluated on 97,144, 89,379, and 55,650 patients, respectively. In the evaluation cohort, 7.6%, 17.3%, and 32.9% patients died by 30-days, 1-year, and 5-years, respectively. ResNet models based on ECG traces alone had good-to-excellent performance with area under receiver operating characteristic curve (AUROC) of 0.843 (95% CI: 0.838-0.848), 0.812 (0.808-0.816), and 0.798 (0.792-0.803) for 30-day, 1-year and 5-year prediction, respectively; and were superior to XGB models based on ECG measurements with AUROC of 0.782 (0.776-0.789), 0.784 (0.780-0.788), and 0.746 (0.740-0.751). This study demonstrates the validity of ECG-based DL mortality prediction models at the population-level that can be leveraged for prognostication at point of care.

Development and validation of echocardiography-based machine-learning models to predict mortality.

BACKGROUND: Echocardiography (echo) based machine learning (ML) models may be useful in identifying patients at high-risk of all-cause mortality. METHODS: We developed ML models (ResNet deep learning using echo videos and CatBoost gradient boosting using echo measurements) to predict 1-year, 3-year, and 5-year mortality. Models were trained on the Mackay dataset, Taiwan (6083 echos, 3626 patients) and validated in the Alberta HEART dataset, Canada (997 echos, 595 patients). We examined the performance of the models overall, and in subgroups (healthy controls, at risk of heart failure (HF), HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)). We compared the models' performance to the MAGGIC risk score, and examined the correlation between the models' predicted probability of death and baseline quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). FINDINGS: Mortality rates at 1-, 3- and 5-years were 14.9%, 28.6%, and 42.5% in the Mackay cohort, and 3.0%, 10.3%, and 18.7%, in the Alberta HEART cohort. The ResNet and CatBoost models achieved area under the receiver-operating curve (AUROC) between 85% and 92% in internal validation. In external validation, the AUROCs for the ResNet (82%, 82%, and 78%) were significantly better than CatBoost (78%, 73%, and 75%), for 1-, 3- and 5-year mortality prediction respectively, with better or comparable performance to the MAGGIC score. ResNet models predicted higher probability of death in the HFpEF and HFrEF (30%-50%) subgroups than in controls and at risk patients (5%-20%). The predicted probabilities of death correlated with KCCQ scores (all p < 0.05). INTERPRETATION: Echo-based ML models to predict mortality had good internal and external validity, were generalizable, correlated with patients' quality of life, and are comparable to an established HF risk score. These models can be leveraged for automated risk stratification at point-of-care. FUNDING: Funding for Alberta HEART was provided by an Alberta Innovates - Health Solutions Interdisciplinary Team Grant no. AHFMRITG 200801018. P.K. holds a Canadian Institutes of Health Research (CIHR) Sex and Gender Science Chair and a Heart & Stroke Foundation Chair in Cardiovascular Research. A.V. and V.S. received funding from the Mitacs Globalink Research Internship.

Use of Guideline-Directed Medical Therapy in Patients Aged ≥ 65 Years After the Diagnosis of Heart Failure: A Canadian Population-Based Study.

Background: Guideline-directed medical therapy (GDMT) improves clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Despite its proven efficacy, GDMT is underutilized in clinical practice. The current study examines GDMT utilization after incident hospitalization for HF to promote medication initiation, and titration to target dosing within a reasonable time period. Methods: This observational study identified 66,372 patients with HFrEF who were aged ≥ 65 years and had an incident HF hospitalization, using administrative health data (2013-2018). GDMT (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, ß-blockers (BB), and mineralocorticoid receptor antagonists ) received within the 6 months after hospitalization was evaluated by monitoring therapy combinations, optimal dosing (proportion receiving ≥ 50% of the target dose for these inhibitors and blockers, and any dose of MRA), and maximal and last dose assessed, and by use of a GDMT intensity score. Results: Among patients with HFrEF, 4768 (7.2%) were on no therapy, 17,184 (25.9%), were on monotherapy, 30,912 (46.6%) were on dual therapy, and 13,508 (20.4%) were on triple therapy. Only 8747 (13.2%) and 5484 (8.3%) achieved optimal GDMT based on the maximum dose and the last dispensed dose, respectively, within 6 months postdischarge. Finally, 38,869 (58.6%) achieved < 50% of the maximum intensity score, 23,006 (34.7%) achieved between 50% and 74% of the maximum intensity score, and 4497 (6.8%) achieved a score that was ≥ 75% of the maximum intensity score. Conclusions: Current pharmacologic management for patients with HFrEF does not align with the Canadian guidelines. Given this gap in care, innovative strategies to optimize care in patients with HFrEF are needed.

Introduction: Les traitements médicamenteux préconisés dans les lignes directrices (TMPLD) permettent d'améliorer les résultats cliniques des patients atteints d'insuffisance cardiaque à fraction d'éjection réduite (ICFER). En dépit des preuves de leur efficacité, les TMPLD sont sous-utilisés dans la pratique clinique. La présente étude porte sur l'utilisation des TMPLD après une hospitalisation incidente en raison d'une IC afin de favoriser l'amorce de la médication, et l'ajustement de la posologie en vue d'atteindre la dose cible dans un délai raisonnable. Méthodes: Cette étude observationnelle portait sur 66 372 patients atteints d'ICFER qui avaient ≥ 65 ans et une hospitalisation incidente en raison d'une IC, et reposait sur les données administratives sur la santé (2013-2018). Nous avons évalué les TMPLD (inhibiteurs de l'enzyme de conversion de l'angiotensine, bloqueurs des récepteurs de l'angiotensine, ß-bloquants [BB] et antagonistes des récepteurs des minéralocorticoïdes [ARM]) reçus dans les six mois après l'hospitalisation par la surveillance des combinaisons de traitement, la posologie optimale (proportion recevant ≥ 50 % de la dose cible pour ces inhibiteurs et ces bloquants, et toute dose d'ARM), la dose maximale et la dernière dose évaluées, et par l'utilisation d'un score d'intensité des TMPLD. Résultats: Parmi les patients atteints d'ICFER, 4 768 (7,2 %) n'avaient reçu aucun traitement, 17 184 (25,9 %), avaient reçu une monothérapie, 30 912 (46,6 %) avaient reçu une bithérapie et 13 508 (20,4 %) avaient reçu une trithérapie. Seuls 8 747 (13,2 %) et 5 484 (8,3 %) avaient obtenu les TMPLD optimaux en fonction de la dose maximale et de la dernière dose administrée, et ce, respectivement, dans les six mois après la sortie de l'hôpital. Enfin, 38 869 (58,6 %) avaient obtenu < 50 % du score d'intensité maximale, 23 006 (34,7 %) avaient obtenu entre 50 % et 74 % du score d'intensité maximale, et 4 497 (6,8 %) avaient obtenu un score qui était ≥ 75 % du score d'intensité maximale. Conclusions: La prise en charge pharmacologique actuelle des patients atteints d'ICFER va à l'encontre des lignes directrices canadiennes. Compte tenu de cette lacune dans les soins, des stratégies novatrices pour optimiser les soins aux patients atteints d'ICFER sont nécessaires.

Prevalence of Cardiovascular Disease in a Population-Based Cohort of High-Cost Healthcare Services Users.

BACKGROUND: Data are limited data on the prevalence of cardiovascular disease (CVD) and multimorbidity in contemporary cohorts of high-cost users (HCUs) in Canada.We examined the following: (i) the prevalence of CVD, with a comparison of total healthcare costs among HCUs with vs without CVD; (ii) the contribution of other comorbidities to costs among HCUs with CVD; and (iii) the trajectory of healthcare costs in the years before and after becoming an HCU. METHODS: The study included adult Alberta patients in the Canadian Institutes of Health Research/Canadian Institute for Health Information Dynamic Cohort of Complex, High System Users from 2011-2012 through 2014-2015. We examined total healthcare costs, including hospital, ambulatory care, physician services, and drugs. RESULTS: Among 88,536 HCUs, 23.4% had no CVD, 28.9% were hospitalized with a primary diagnosis of CVD, and 47.7% were hospitalized with a secondary diagnosis of CVD. Total healthcare costs were $2.0 billion (20.4% non-hospital costs), $2.8 billion (24.1% non-hospital costs), and $4.9 billion (19.8% non-hospital costs), respectively, in the 3 groups. Many HCUs with CVD were frail (74.2%) and many had diabetes (33.8%) or chronic obstructive pulmonary disease (27.9%), which contributed to higher costs and mortality. Healthcare expenditures in HCUs with CVD were several times higher than per capita health expenditures in the years prior to, and following, their inclusion in the dynamic HCU cohort. CONCLUSIONS: CVD is very common in HCUs of healthcare. HCUs with CVD have high rates of frailty and multimorbidity. Further research is needed to identify and intervene earlier, in order to flatten the cost curve in these complex patients.

INTRODUCTION: Les données sur la prévalence des maladies cardiovasculaires (MCV) et de la multimorbidité au sein des cohortes contemporaines de grands utilisateurs (GU) du Canada sont limitées. Nous avons examiné ce qui suit : (i) la prévalence des MCV en comparant les coûts totaux des soins de santé entre les GU atteints de MCV et les GU non atteints de MCV; (ii) la contribution des autres comorbidités aux coûts liés aux GU atteints de MCV; (iii) la trajectoire des coûts des soins de santé dans les années avant et après avoir été considérés comme un GU. MÉTHODES: L'étude portait sur des patients adultes de l'Alberta de la Cohorte dynamique de grands utilisateurs du système de santé aux besoins complexes de 2011-2012 à 2014-2015 des Instituts de recherche en santé du Canada et de l'Institut canadien d'information sur la santé. Nous avons examiné les coûts totaux des soins de santé, notamment les coûts hospitaliers, les coûts des soins ambulatoires, des services médicaux et des médicaments. RÉSULTATS: Parmi les 88 536 GU, 23,4 % n'avaient pas de MCV, 28,9 % étaient hospitalisés et avaient un diagnostic principal de MCV, et 47,7 % étaient hospitalisés et avaient un diagnostic secondaire de MCV. Les coûts totaux des soins de santé des 3 groupes étaient respectivement de 2,0 G$ (20,4 % de coûts non hospitaliers), 2,8 G$ (24,1 % de coûts non hospitaliers) et 4,9 G$ (19,8 % de coûts non hospitaliers). Plusieurs GU atteints de MCV étaient fragiles (74,2 %) et beaucoup avaient le diabète (33,8 %) ou une maladie pulmonaire obstructive chronique (27,9 %), qui contribuaient à des coûts et à une mortalité plus élevés. Les dépenses de santé par personne liées aux GU atteints de MCV étaient beaucoup plus élevées que les dépenses de santé par personne dans les années qui précédaient ou suivaient leur inclusion dans la cohorte dynamique de GU atteints de MCV. CONCLUSIONS: Les GU de soins de santé sont très fréquemment atteints de MCV. Les GU atteints de MCV présentent des taux de fragilité et de multimorbidité élevés. D'autres recherches sont nécessaires pour cerner et intervenir plus tôt afin d'aplatir la courbe des coûts chez ces patients aux besoins complexes.

Practice guidelines and clinical risk assessment models: is it time to reform?

BACKGROUND: Clinical practice guidelines and Risk Assessment Models (RAMs) are some useful tools to bring medical evidences into our daily clinical practice. Despite the improvement over the time, they still have some shortcomings. DISCUSSION: One of these shortcomings is the arbitrary cutoffs used in these tools to facilitate the decision making process. This problem is to some extent due to the "Black or White" approach of modern medicine in making the decisions, whilst in the real world and our daily practice we used mostly an uncertain approach, which is called recently as "Fuzzy" thinking approach. SUMMARY: The authors of this article believe that the fuzzy type of thinking may resolve the above mentioned shortcomings of clinical practice guideline or risk assessment models and they tried to discuss about this using an example about Venous Thromboembolism related guidelines and RAMs.

Chloride in Heart Failure: The Neglected Electrolyte.

The increasing burden of heart failure (HF) and emerging knowledge regarding chloride as a prognostic marker in HF have increased the interest in the pathophysiology and interactions of chloride abnormalities with HF-related factors and treatments. Chloride is among the major electrolytes that play a unique role in fluid homeostasis and is associated with cardiorenal and neurohormonal systems. This review elucidates the role of chloride in the pathophysiology of HF, evaluates the effects of treatment on chloride (eg, diuretic agents cause higher urinary chloride excretion and consequently serum hypochloremia), and discusses recent evidence for the association between chloride levels and mortality.

Herpes Simplex Virus Type 2 Seroprevalence in Pregnant Women in Urmia, Northwest of Iran, during 2014-2015

Background: Herpes simplex virus type 2 (HSV-2) seroprevalence has been shown to be a potential sign of infection in pregnant women, and it could be applied to check HSV-2 transmission. This study evaluated the anti-HSV-2 IgG prevalence in pregnant women who were referred to health centers in Urmia, Northwest of Iran, during 2014-2015. Methods: Serum samples were collected from 86 pregnant women and tested for Anti-HSV-2-specific IgG using a commercial enzyme-linked immunosorbent assays kit. Results: Five (5.8%) pregnant women showed the presence of Anti-HSV-2-specific IgG antibodies. Previous abortion was reported in 16 (19.7%) and 2 subjects in the seronegative and seropositive groups, respectively. Conclusion: Data from the present study indicate a lower number of HSV-2 seropositives among the pregnant women in Urmia. This reduction would be a result of low number of studied subjects used in the present study; hence, assessing a large sample is recommended.

Ventricular Dysfunction in Patients with Coronary Slow-Flow Phenomenon: A Single-center Case-control Study.

BACKGROUND: Coronary slow-flow phenomenon (CSFP), characterized by delayed distal vessel opacification of contrast, in the absence of significant epicardial coronary stenosis, has effects on exercise capacity and clinical outcomes. The aim of this study was to explore the systolic and diastolic function of patients with CSFP and to compare it with a group of controls with normal coronary anatomy and flow. MATERIALS AND METHODS: In this case-control study, 45 consecutive CSFP patients and 45 age-, body mass index-, and presentation season-matched controls with normal coronary arteries and normal coronary flows were enrolled from Seyyedoshohada Heart Center from March 2015 to March 2016. A transthoracic echocardiography was done by a blinded echocardiographer using both conventional and tissue Doppler imaging techniques. RESULTS: Patients with CSFP were more likely to be male (P = 0.006) and smoker (P = 0.02) compared to controls. Other risk factors were not different between the two groups. There were no differences between groups in terms of the peak early (E) and late (A) diastolic velocities, deceleration time, early (E') and late (A') peak diastolic velocities at the mitral annulus, and the systolic mitral annular velocity (S'). Global longitudinal strain and peak systolic strain rates was lower in patients with CSFP compared to controls (-16.7% ±2.4% vs. -18.9% ±1.6%, P < 0.001 and 1.10 ± 0.1 vs. 1.24 ± 0.3, P = 0.008, respectively). CONCLUSION: Patients with CSFP showed signs of the left ventricular systolic dysfunction in tissue Doppler echocardiography, which underlines the importance of close follow-up in these patients. Patients with CSFP should be screened for ventricular function preferably by tissue Doppler echocardiography.