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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.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.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.In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events.Canadian Institutes of Health Research and the University Hospital Foundation, Edmonton, Alberta, Canada, and Health Research Council of New Zealand.

Heart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Patients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P 0.001).Amongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.

The GUIDE-IT trial was, a multicenter, randomized, parallel group, unblinded study that randomized patients to having heart failure therapy titrated to achieve an NT-proBNP1000 pg/mL or to usual clinical care.We performed pre-specified subgroup analysis to look for the race and ethnicity-based differences in clinical outcomes of patients who were able to achieve GDMT or target NT-proBNP concentration of ≤1000 pg/mL at 90 days of follow-up. There were 894 patients enrolled in GUIDE-IT study. Of these, 733 participants had available data on 90-day guideline directed triple therapy and 616 on NT-proBNP. 35% of the patients were Black and 6% were Hispanic. Black patients were younger, had more comorbidities, lower EF, and higher NYHA class compared with non-Black. Adjusting for 90-day NT-proBNP and important baseline covariates, Black patients were at a higher risk than non-Black patients for HF hospitalization [HR, 2.19; 95% CI, 1.51-3.17; p0.0001], but at a similar risk for mortality [HR, 0.85.; 95% CI, 0.44-1.66; p = 0.64]. Similar results were seen adjusting for 90-day GDMT [HF hospitalization: Black vs non-Black, HR: 1.97; 1.41-2.77, P0.0001; mortality: HR: 0.70; 0.39-1.26, p = 0.23]. There were no significant differences between Hispanic and non-Hispanic patients with respect to heart failure hospitalization, cardiovascular or all-cause mortality. Over the study period, Black and Hispanic patients experienced smaller changes in physical function and quality of life as measured by the Kansas City Cardiomyopathy Questionnaire overall score.Compared to non-Black patients, Black patients in GUIDE-IT study had a higher risk of heart failure hospitalization, but a comparable risk of mortality, despite improved use of GDMT and achievement of similar biomarker targets.

Background Acute myocardial infarction (AMI) research is challenging as it requires enrollment of acutely ill patients. Patients are generally in a suboptimal state for providing informed consent. Patients’ understanding to verbal assents have not been previously examined in AMI research. Patients Acceptance and Comprehension to Written and Verbal Consent (PAC–VC) compared patients’ understanding and attitudes to verbal and written consents in AMI RCTs. Methods PAC–VC recruited patients from 3 AMI trials using both verbal N = 12 and written N = 6 consents. We compared patients’ understanding using two survey questionnaires. The first questionnaire used open-ended questions with multiple choice answers. The second questionnaire used a 5-point Likert scale to measure patients understanding and attitudes to the consent process. Overall answers average scores were categorized into three groups: Adequate understanding (71–100) %, Partial understanding (41–70)% and Inadequate understanding (0–40)%. Results Responses showed patients with verbal assent had adequate understanding to most components of informed consent, close to those of written consent. Most patients did not read written information entirely and believed that it is not important to make a final decision. Patients favoured to have written information be part of the consent but not necessarily presented during the initial consent process. Patients felt less pressured in the verbal assent arm than those of written consent. Conclusion Patients had adequate understanding to most components of verbal assent and comparable to those of written consent. Utilizing verbal assents in the acute care setting should be further assessed in larger trials.

Background Oral anticoagulation (OAC) therapy prevents morbidity and mortality in nonvalvular atrial fibrillation; whether location of diagnosis influences OAC uptake or adherence is unknown. Methods and Results Retrospective cohort study (2008–2019), identifying adults with incident nonvalvular atrial fibrillation across health care settings (emergency department, hospital, outpatient) at high risk of stroke. OAC uptake and adherence via proportion of days covered for direct OACs and time in therapeutic range for warfarin were measured. Proportion of days covered was categorized as low (0–39%), intermediate (40–79%), and high (80–100%). Warfarin control was defined as time in therapeutic range ≥65%. All‐cause mortality was examined at a 3‐year landmark. Among 75 389 patients with nonvalvular atrial fibrillation (47.0% women, mean 77.4 years), 19.7% were diagnosed in the emergency department, 59.1% in the hospital, and 21.2% in the outpatient setting. Ninety‐day OAC uptake was 51.6% in the emergency department, 50.9% in the hospital, and 67.9% in the outpatient setting ( P P values for trend Conclusions Locale of nonvalvular atrial fibrillation diagnosis is associated with varying OAC uptake and adherence. Interventions specific to health care settings are needed to improve stroke prevention.

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.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, β-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.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%) achieved50% 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.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.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.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, β-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.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 obtenu50 % 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.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.

Aim We assessed a subset of the 5040 patients in VICTORIA receiving sacubitril/valsartan, either at randomization (n = 731) or post-randomization drop-in use (n = 425), to evaluate the relationship between the efficacy and safety of combination therapy with vericiguat. Methods and results The efficacy of vericiguat on the primary composite endpoint, heart failure (HF) hospitalization, and all-cause mortality was assessed. Safety outcomes included symptomatic hypotension, syncope, worsening renal function, and hyperkalaemia. At randomization, 731 patients received sacubitril/valsartan; they were more frequently from Western Europe or North America, had lower ejection fraction and systolic blood pressure, and more use of triple background HF therapy (65.9% vs. 58.6%), biventricular pacemakers (17.9% vs. 14.1%), or implantable cardioverter defibrillators (42.3% vs. 25.3%). For patients on versus not on sacubitril/valsartan at randomization, adjusted hazard ratios (95% confidence intervals) for vericiguat's treatment effect on the primary composite outcome, cardiovascular death, and HF hospitalization were 0.92 (0.71-1.19) versus 0.89 (0.80-0.98), 0.71 (0.45-1.12) versus 0.95 (0.82-1.11), and 0.98 (0.74-1.29) versus 0.87 (0.78-0.98), respectively. No significant interaction existed between sacubitril/valsartan and vericiguat's treatment effect (p-values for interaction: 0.81, 0.23 and 0.47, respectively). Post-randomization, more drop-in sacubitril/valsartan use occurred in those assigned to placebo (n = 238) versus vericiguat (n = 187) (p = 0.007). Symptomatic hypotension (21.0% vs. 23.1%; p = 0.41), renal dysfunction (29.9% vs. 31.9%; p = 0.50), and hyperkalaemia (10.3% vs. 7.9%; p = 0.20) in patients receiving sacubitril/valsartan (n = 992) for >= 3 months were not different by treatment arm. Conclusions Concomitant use of sacubitril/valsartan for at least 3 months did not alter the efficacy of vericiguat and was similarly safe and tolerated in both study arms. Sacubitril/valsartan was initiated more frequently after randomization in patients assigned to placebo versus vericiguat. Clinical Trial Registration: NCT02861534.

Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such as hypotension, acute kidney injury (AKI), or hypoglycemia. We sought to achieve consensus among clinical experts on recommendations for SDMG that could be studied in future intervention studies.A modified Delphi process following the Conducting and Reporting Delphi Studies reporting guidelines.An international group of clinicians with expertise relevant to SDMG was recruited through purposive and snowball sampling. A scoping review of the literature was presented, followed by three sequential rounds of development, refinement, and voting on recommendations. Meetings were held virtually and structured to allow participants to provide their input and rapidly prioritize and refine ideas.Opinions of participants were measured as the percentage who agreed with each recommendation, whereas consensus was defined as75% agreement.Quantitative data were summarized using counts and percentages. A qualitative content analysis was performed to capture the context of the discussion around recommendations and any additional considerations brought forward by participants.The final panel included 26 clinician participants from four countries and 10 clinical disciplines. Participants reached a consensus on 42 specific recommendations: five regarding the signs and symptoms accompanying volume depletion that should trigger SDMG; six regarding signs that should prompt urgent contact with a health care provider including a reduced level of consciousness, severe vomiting, low blood pressure, presence of ketones, tachycardia, and fever; and 14 related to scenarios and strategies for patient self-management, including frequent glucose monitoring, checking ketones, fluid intake, and consumption of food to prevent low blood sugars. There was consensus that renin-angiotensin system inhibitors, diuretics, non-steroidal anti-inflammatory drugs, sodium-glucose cotransporter-2 inhibitors, and metformin should be temporarily stopped. Participants recommended that insulin, sulfonylureas, and meglitinides be held only if blood glucose was low and that basal and bolus insulin be increased by 10-20% if blood glucose was elevated. There was consensus on six recommendations related to the resumption of medications within 24-48 hours of the resolution of symptoms and the presence of normal patterns of eating and drinking.Participants were from high-income countries, predominantly Canada. Findings may not be generalizable to implementation in other settings.A multidisciplinary panel of clinicians reached a consensus on recommendations for SDMG in the presence of signs and symptoms of volume depletion, as well as self-management strategies and medication instructions in this setting. These recommendations may inform the design of future trials of SDMG strategies.

The suboptimal implementation of guideline-directed medical therapy (GDMT) for heart failure (HF) patients has been linked with poor clinical outcomes. Little is known about the potential role of cardiology residency training programs in improving trainees' (ie, future cardiologists') ability to utilize GDMT.In this survey-based study, we examined the degree of exposure to ambulatory HF patient management among cardiology trainees in Canada. All cardiology residency program directors (n = 15; 100% response rate) completed our survey.Although 9 programs (60%) mandated ≥ 3 ambulatory cardiology rotations, only 3 (20%) required ≥ 2 ambulatory HF rotations. When HF rotations were provided, only 7 programs (47%) offered moderate or higher exposure to ambulatory nontransplant HF patients (defined as ≥ 5 clinics/rotations). This element was independent of program- and institution-specific characteristics. All institutions had a multidisciplinary HF clinic, and the majority (13 [87%]) had access to an inpatient HF service, a consultative HF service, and/or a specialist pharmacist. Furthermore, 13 program directors (87%) agreed on the importance of adopting HF training curriculum and their program's readiness to implement such a module.The current state of HF training among cardiology residencies is suboptimal and in need of improvement. Most programs have access to a HF clinic, a specialist pharmacist, or an inpatient consultative service, which would facilitate adoption of a HF management curriculum that focuses on practical and experiential aspects of GDMT optimization. This program, which is under development, will be offered to training programs nationwide, to enable trainees to manage this growing and increasingly complex patient population.Une mise en application sous-optimale des traitements médicaux recommandés dans les lignes directrices (TMRLD) dans les cas de patients atteints d’insuffisance cardiaque (IC) a été associée à des issues cliniques défavorables. On en sait peu sur le rôle éventuel des programmes de résidence en cardiologie sur l’amélioration des capacités des stagiaires (c.-à-d. des futurs cardiologues) à mettre en œuvre les TMRLD.Notre étude s’appuyant sur un sondage a permis d’examiner le niveau d’exposition des stagiaires en cardiologie au Canada à la prise en charge des patients ambulatoires atteints d’IC. La direction de tous les programmes de résidence en cardiologie (n = 15; taux de réponse de 100 %) a participé à notre sondage.Alors que neuf programmes (60 %) exigeaient ≥ trois stages en cardiologie ambulatoire, seulement trois d’entre eux (20 %) exigeaient ≥ deux stages en IC ambulatoire. Parmi les programmes offrant des stages en IC, seulement sept (47 %) offraient une exposition modérée à élevée à des patients ambulatoires atteints d’IC et n’ayant pas reçu de greffe (cette exposition était établie à cinq cliniques par stage ou plus); le niveau d’exposition à ces patients ne dépendait pas des caractéristiques du programme ou de l’établissement. Dans tous les établissements, une clinique multidisciplinaire spécialisée en IC était présente, et la majorité d’entre eux (13 [87 %]) bénéficiaient également d’un service pour les patients hospitalisés atteints d’IC, d’un service de consultation en IC et/ou de la présence d’un pharmacien spécialisé. De plus, la direction de 13 programmes (87 %) se disait en accord avec l’importance d’adopter un curriculum de formation portant sur l’IC et considérait que leur programme était prêt à intégrer un tel module.L’état actuel de la formation en IC dans les programmes de résidence en cardiologie n’est pas optimal, et des améliorations sont nécessaires. La plupart des programmes ont accès à une clinique en IC, un pharmacien spécialisé ou un service de consultation pour les patients hospitalisés, ce qui pourrait faciliter l’adoption d’un curriculum de prise en charge de l’IC portant sur l’expérience concrète de l’optimisation des TMRLD. Ce module, qui est en cours d’élaboration, sera offert à tous les programmes de formation à travers le Canada, pour permettre aux stagiaires de mieux prendre en charge cette population de patients qui gagne en nombre et en complexité.

Heart failure (HF) is a leading complication of nonvalvular atrial fibrillation (NVAF), and the presence of both conditions worsens prognosis. Sex-specific associations between NVAF and outcomes focus on stroke; less is known about HF. We evaluated sex differences in incident HF in NVAF.We identified adults age ≥ 65 years hospitalized for incident NVAF without prior HF from April 2010 to March 2018 in Canada. The primary outcome was incident HF hospitalization, with a secondary composite outcome of incident HF hospitalization or all-cause mortality at 1 year. Cox proportional hazard regression models were constructed for the association between sex and outcomes, adjusting for age, comorbidities, socioeconomic status, cardioversion, and medications.Of 68,909 NVAF patients, 53.8% were women. Women had a higher rate of the primary outcome (30.0% vs 25.6%,In this nationwide study of incident NVAF without HF, women age ≥ 75 years were more likely to develop HF or die than men. Strategies to prevent HF in older women with NVAF are needed.L’insuffisance cardiaque (IC) est une complication majeure de la fibrillation auriculaire non valvulaire (FANV), et la présence des deux affections assombrit le pronostic. Les associations entre la FANV et ses complications en fonction du sexe ont surtout porté sur l’AVC; on en connaît moins sur l’IC. Nous avons évalué les différences entre les sexes pour l’IC fortuite dans la FANV.Nous avons identifié des adultes de ≥ 65 ans, sans antécédents d’IC, hospitalisés pour une FANV fortuite entre avril 2010 et mars 2018 au Canada. L’hospitalisation à la suite d’une IC fortuite constituait le critère d’évaluation principal, le critère d’évaluation secondaire composé comprenait les hospitalisations pour un épisode d’IC fortuite ou le décès toutes causes confondues à un an. Des modèles de régression à risques proportionnels de Cox ont servi à évaluer l’association entre le sexe et les résultats, après correction en fonction de l’âge, des comorbidités, de la situation socio-économique, de la cardioversion et de la médication.Le groupe étudié comptait 68 909 patients atteints de FANV dont 53,8 % étaient des femmes. Les femmes étaient plus nombreuses à répondre au critère d’évaluation principal (30,0 % vs 25,6 %,Dans cette étude nationale sur la FANV fortuite sans IC, les femmes de ≥ 75 ans étaient plus susceptibles de développer une IC ou de décéder que les hommes d’où la nécessité de mettre en place des stratégies de prévention de l’IC chez les femmes plus âgées atteintes de FANV.

The use of electronic medical records has rapidly been adopted world-wide, which has resulted in multiple new opportunities for cardiovascular research. These include the following: (1) the development and assessment of clinical decision tools, meant to increase quality of care; (2) harnessing data linkages to examine genetic, epidemiological, and pharmacological associations on an unprecedented scale; and (3) harnessing electronic medical records to facilitate the conduct of cardiovascular clinical trials. While these opportunities promise to revolutionize cardiovascular care and research, enthusiasm should be tempered while further assessment of true clinical utility has been undertaken.

Introduction: Heart failure and mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared heart failure with reduced EF. However, HFmrEF may be a transitory state and serial imaging might clarify if these patients demonstrate an increasing, decreasing or stable EF. Hypothesis: LVEF trajectory can identify sub-groups of patients with HFmrEF with different prognosis. Materials and Methods: Patients with a diagnosis of HF and at least two echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. They were classified based on change from their first echocardiogram as: a) HFmrEF-Incr if LVEF had increased ≥ 10% (n=450), b) HFmrEF-Dec if LVEF had decreased ≥10% (n=512), or c) HFmrEF-stable if they did not meet the other criteria (n=389). The primary outcome was a composite of all-cause mortality or cardiovascular hospitalization (ACM/CVH). Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, medical history, and medications. Results: In total, 1351 patients with HFmrEF were included (median age 74, 35.8% women). During a median follow-up of 15.3 months, ACM/CVH occurred in 811 patients (324 ACM, 487 CVH). HFmrEF-Incr was associated with a lower incidence of ACM/CVH compared to patients with HFmrEF-Stable (adjusted HR 0.72, 95% CI 0.59 - 0.87, p Conclusions: Patients with HFmrEF and positive trajectory of LVEF were less likely to experience adverse outcomes, while those with a negative LVEF trajectory demonstrated a trend to higher risk. Categories based on LVEF trajectory provide clinically meaningful information and may help physicians make decisions regarding the need to pursue more aggressive medical therapy and surveillance.

Heart failure (HF), and especially HF with preserved ejection fraction (HFpEF), remains a challenging condition to define. The heterogenous nature of this population may be related to a variety of underlying etiologies interacting myocardial dysfunction.Alberta HEART study was a prospective, observational cohort that enrolled participants along the spectrum of heart failure including: healthy controls, people at risk of HF, and patients with HF and preserved (HFpEF) or reduced ejection fraction (HFrEF). We aimed to explore phenotypes of patients with HF and at-risk of developing HF. Utilising 27 detailed clinical, echocardiographic and biomarker variables, latent class analysis with and without multiple imputation was undertaken to identify distinct clinical phenotypes.Of 621 participants, 191 (30.8%) and 169 (27.2%) were adjudicated by cardiologists to have HFpEF and HFrEF respectively. In the overall cohort, latent class analysis identified four distinct phenotypes. Phenotype A (n=152, 24.5%) was a healthy and low risk group. Phenotype B (n=129, 20.8%) demonstrated increased left ventricular mass and end-diastolic volumes, with elevated natriuretic peptides and clinical features of congestion. Phenotype C (n=128, 20.6%) was primarily characterised by obesity (80%) and normal indexed cardiac chamber sizes, low natriuretic peptide levels and minimal features of congestion. Phenotype D (n=212, 34.1%) consisted of elderly patients with clinical features of congestions. Phenotypes B and D demonstrated the highest risk of mortality and hospitalization over a median follow-up of 3.7 years.Phenotypes with congestive features demonstrated increased risk profiles. Heart failure is a heterogenous classification which requires further work to appropriately categorise patients based on the underlying etiology or mechanism of impairment.

With recent advances in the pharmacological management of type 2 diabetes mellitus (T2DM), there is a growing need to understand which patients optimally benefit from these novel therapies. Various clinical clustering methodologies have emerged that utilise data-agnostic strategies to categorise patients that have similar clinical characteristics and outcomes; broadly, this characterisation is termed phenotyping. In patients with T2DM, we aimed to describe patient characteristics from phenotype studies, their cardiovascular risk profiles and the impact of antihyperglycemic treatment.Numerous phenotypic studies have been undertaken that have utilised a combination of clinical, biochemical, imaging and genetic variables. Each of these has produced phenotypes that display a spectrum of cardiovascular risk. Studies that aimed to describe pathophysiological phenotypes generally identified five phenotypes: autoimmune phenotype, insulin-related phenotypes (including permutations of insulin deficiency and resistance), obesity phenotype, ageing phenotype, and a sex-related phenotype. Studies examining risk profiles have demonstrated that across such phenotypes there is a spectrum of risk for diabetic complications. Few studies have examined treatment effects across these phenotypes, and thus provide little insights towards making phenotype-guided treatment decisions Clustering analyses in patients with T2DM have identified distinct phenotypes with unique risk profiles. Further studies are needed that harness the use of clinical, biochemical, imaging and genetic data to explore therapeutic heterogeneity and response to antihyperglycemic treatment across the spectrum of patient phenotypes.

Background: Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF); however, there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Our primary hypothesis was that routine use of CMR will yield more specific diagnoses in nonischemic HF. Our secondary hypothesis was that routine use of CMR will improve patient outcomes. Methods: Patients with nonischemic HF were randomized to routine versus selective CMR. Patients in the routine strategy underwent echocardiography and CMR, whereas those assigned to selective use underwent echocardiography with or without CMR according to the clinical presentation. HF causes was classified from the imaging data as well as by the treating physician at 3 months (primary outcome). Clinical events were collected for 12 months. Results: A total of 500 patients (344 male) with mean age 59±13 years were randomized. The routine and selective CMR strategies had similar rates of specific HF causes at 3 months clinical follow-up (44% versus 50%, respectively; P =0.22). At image interpretation, rates of specific HF causes were also not different between routine and selective CMR (34% versus 30%, respectively; P =0.34). However, 24% of patients in the selective group underwent a nonprotocol CMR. Patients with specific HF causes had more clinical events than those with nonspecific caused on the basis of imaging classification (19% versus 12%, respectively; P =0.02), but not on clinical assessment (15% versus 14%, respectively; P =0.49). Conclusions: In patients with nonischemic HF, routine CMR does not yield more specific HF causes on clinical assessment. Patients with specific HF causes from imaging had worse outcomes, whereas HF causes defined clinically did not. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01281384.

Poorly controlled type 2 diabetes mellitus is associated with the development of cardiovascular and renal complications, resulting in significant morbidity and mortality. Intensive glycemic control has been a major focus for clinical trials and novel drug development. However, narrow treatment strategies developed strictly for glycemic control did not confer a large risk reduction in cardiovascular events. There were also only modest effects in reducing the progression of diabetic kidney disease. Recent cardiovascular safety trials and the dedicated renal protection trial CREDENCE (Canagliflozin on Renal and Cardiovascular Outcomes in Participants with Diabetic Nephropathy) have shown that the sodium-glucose cotransporter-2 (SGLT2) inhibitors, a newer generation of antihyperglycemic agents, improve both cardiovascular and renal outcomes when added to guideline-recommended treatment. This review examines the current evidence on the mechanism underlying the cardiorenal effects of SGLT2 inhibitors and summarizes clinical trial evidence and safety data related to the use of SGLT2 inhibitors for cardiovascular and renal protection.

Understanding cardiac MR TTo evaluate the effects of gender, age, and presence of heart failure risk factors on myocardial native TRetrospective, cross-sectional, observational study.Secondary analysis of cardiac MR data, separated by gender and health status, based on the presence of at least one heart failure risk factor.Cardiac MR imaging at 1.5T, including TInterventricular septal region-of-interest analysis for assessment of native T1 and ECV.Group comparisons performed using Student t-test, or nonparametric equivalent. Linear regression was used to assess relationships between age and TNative TNative T3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1307-1317.

Aim: To investigate the relationship between heart rate and survival in patients with heart failure (HF) and coexisting atrial fibrillation (AF). Methods and Results: Patients with AF included in the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) meta-analysis were the main focus of this analysis (3259 patients from 17 studies). The outcome was all-cause mortality at 3 years. Heart rate was analysed as a categorical (tertiles; T1 ≤77 b.p.m., T2 78–98 b.p.m., T3 ≥98 b.p.m.) and continuous variable. Cox proportional hazard models were used to compare the risk of all-cause death between tertiles of baseline heart rate. Patients in the highest tertile were more often female, less likely to have an ischaemic aetiology or diabetes, had a lower ejection fraction but higher blood pressure and New York Heart Association (NYHA) class. Higher heart rate was associated with higher mortality in patients with sinus rhythm (SR) but not in those in AF. In patients with heart failure and reduced ejection fraction (HF-REF) and AF, death rates per 100 patient years were lowest in the highest heart rate tertile (T1 18.9 vs. T3 15.9) but this difference was not statistically significant (P = 0.10). In patients with heart failure and preserved ejection fraction (HF-PEF), death rates per 100 patient years were highest in the highest heart rate tertile (T1 14.6 vs. T3 16.0, P = 0.014). However, after adjustment for other important prognostic variables, higher heart rate was no longer associated with higher mortality in HF-PEF (or HF-REF). Conclusions: In this meta-analysis of patients with HF, heart rate does not have the same prognostic significance in patients in AF as it does in those in SR, irrespective of ejection fraction or treatment with beta-blocker.

This trial sought to evaluate whether vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator, was superior to placebo, on a background of standard of care, in increasing the time to the first occurrence of the composite endpoints of cardiovascular (CV) death and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction (HFrEF). Deficiency in sGC-derived cyclic guanosine monophosphate (cGMP) causes both myocardial dysfunction and impaired endothelium-dependent vasomotor regulation that includes the myocardial microcirculation. Experimental studies have suggested multiple potential benefits of sGC stimulators including prevention, or even reversal, of left ventricular hypertrophy and fibrosis, as well as reduction of ventricular afterload through both systemic and pulmonary vasodilation. Hence, restoration of sufficient nitric oxide (NO)-sGC-cGMP signaling has been proposed as an important treatment target in HF. Vericiguat has been shown to directly stimulate sGC and enhance sGC sensitivity to endogenous NO. Available phase IIb data in HFrEF patients indicate vericiguat is safe and well-tolerated, and exploratory analyses indicate that it results in a dose-dependent, clinically significant reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the highest tested dose. VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) is a randomized, placebo-controlled, parallel group, multicenter, double-blind, event-driven phase 3 trial of vericiguat in subjects with HFrEF. Approximately 4,872 subjects will be randomized to evaluate the efficacy and safety of vericiguat compared with placebo on a background of standard of care. After a screening phase of up to 30 days, eligible subjects will be treated until the required number of cardiovascular deaths is observed. The estimated median follow-up duration is approximately 18 months. All subjects will be followed until study completion to assess for the occurrence of endpoint events. VICTORIA will establish the efficacy and safety of vericiguat on cardiovascular death and HF hospitalization in patients with HFrEF. (A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction [HFrEF]-VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).

Background: The 2013 heart failure (HF) guidelines of the American College of Cardiology Foundation and American Heart Association (ACCF-AHA) restricted the indications for chronic resynchronization therapy (CRT). The impact of this guideline change has not been described. Methods: Using data from

This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4,1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984).

Background— Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. Methods and Results— We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146–155), 10 589 (51%) and 11 422 (55%) had an eGFR Conclusions— Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.

To determine the efficacy, effectiveness, and safety of cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillators (ICD) in patients with left ventricular systolic dysfunction (LVSD).A systematic and comprehensive literature search was conducted to identify randomized controlled trials (RCTs) evaluating efficacy and observational studies evaluating effectiveness or safety of CRT and/or ICD in patients with LVSD.Study selection, quality assessment, and data extraction were completed by several investigators in duplicate and independently. Random-effects models were used for analyses.From 11,340 citations, we identified 14 RCTs (4,420 patients) for the CRT efficacy review, 106 studies (9,209 patients) for the CRT effectiveness review, 89 studies (9,677 patients) for the CRT safety review, 12 RCTs (8,516 patients) for the ICD efficacy review, 48 studies (15,097 patients) for the ICD effectiveness review, and 49 studies (12,592 patients) for the ICD safety review-all studies enrolled only patients with LVSD. An additional 12 studies (68,848 patients) were included for an analysis of peri-implant outcomes for all patients with ICD (i.e., not only LVSD patients). All patients in the CRT studies had LVSD (mean LVEF from 21 to 30 percent) and prolonged QRS duration (mean from 155 to 209 msec), and 91 percent had New York Heart Association (NYHA) class III or IV symptoms. In patients with LVSD and heart failure symptoms, CRT improved ejection fraction (weighted mean difference 3.0 percent [95% CI, 0.9 to 5.1]), quality of life (weighted mean reduction in Minnesota Living with Heart Failure Questionnaire 8.0 points [95% CI, 5.6 to 10.4 points]), and function (59 percent of CRT recipients vs. 37 percent of controls improved by at least one NYHA class in the RCTs and between 63 percent and 82 percent of CRT recipients improved by at least one NYHA class in observational studies). The proportion of patients hospitalized for HF was reduced by 37 percent (95% CI, 7 to 57 percent) and all-cause mortality was reduced by 22 percent (95% CI, 9 to 33 percent; NNT=29 over 6 months). Implant success rate was 93 percent, 0.3 percent of patients with LVSD died during implantation. Over a median 11-month followup, 6.6 percent of CRT devices exhibited lead problems and 5 percent malfunctioned. In patients with LVSD, ICD reduced all-cause mortality by 20 percent (95% CI, 10 to 29 percent; NNT=20 over 35 months). ICD implant success rate was 99 percent and peri-implant deaths occurred in 1.2 percent of LVSD patients and 1.3 percent of all implantees. The frequency of post-implantation complications in LVSD patients per 100 patient years included 1.4 (95% CI, 1.2 to 1.6) device malfunctions, 1.5 (95% CI, 1.3 to 1.8) lead problems, 0.6 (95% CI, 0.5 to 0.8) implant site infections, and 19.1 (95% CI, 16.5 to 22.0) inappropriate discharges in RCT participants and 4.7 (95% CI, 4.3 to 5.1) inappropriate discharges in patients enrolled in observational studies.ICD and CRT reduce all-cause mortality in patients with LVSD meeting RCT entry criteria. The incremental benefit of CRT plus ICD over CRT alone in patients with LVSD remains uncertain. None of the trials reported differences in the efficacy of CRT or ICD across patient subgroups, nor did our meta-regression detect any subgroup effects; however, subgroup analyses and meta-regression using aggregate trial data are post-hoc analyses and were underpowered to detect such effects. Examination of individual patient trial data is urgently needed to define which clinical subgroups are most likely to benefit from these devices.

The effect that supervised or unsupervised exercise training has on aerobic capacity (peak oxygen consumption [VO2peak]), muscle strength and quality of life in older women with heart failure remains unknown.To examine the effect of six months (three months supervised followed by three months unsupervised) of aerobic training (AT) or combined aerobic and strength training (CAST) on VO2peak, muscle strength and quality of life in older women with heart failure.Twenty older women (mean age +/- SD, 72+/-8 years) with clinically stable heart failure were randomly assigned to AT (n=10) or CAST (n=10). Supervised AT was performed two days per week at 60% to 70% heart rate reserve, whereas unsupervised training was performed two days per week at a rate of perceived exertion of 12 to 14 on the Borg scale. The CAST group also performed one to two sets of low-to-moderate intensity strength training two days per week.Supervised AT or CAST resulted in an increase in VO2peak (12%; P0.05) and leg press strength (13%; P0.05) that returned to baseline after unsupervised training. Vertical row strength was greater (+23%; P0.05) after supervised CAST and remained unchanged after supervised or unsupervised AT. Supervised or unsupervised exercise training was not associated with a significant change in quality of life.Supervised AT or CAST are effective modes of exercise to improve VO2peak and muscle strength in older women with heart failure. However, the improvements in VO2peak and muscle strength are not maintained with unsupervised exercise training.

There is uncertainty about whether physician specialty influences the outcomes of outpatients with congestive heart failure after adjustment for differences in case mix. Our objective was to determine the impact of physician specialty on outcomes in outpatients with new-onset congestive heart failure.The study was a population-based retrospective cohort study involving patients with new-onset congestive heart failure discharged from 128 acute care hospitals in Alberta between Apr. 1, 1998, and July 1, 2000. Outcomes were resource utilization (clinic visits, emergency department visits and hospital admissions) and survival at 30 days and 1 year.A total of 3136 patients were discharged from hospital with a new diagnosis of congestive heart failure (median age 76 years, 50% men). Of these, 1062 (34%) received no follow-up visits for cardiovascular care, 738 (24%) were seen by a family physician (FP) alone, 29 (1%) by a specialist (cardiologist or general internist) alone and 1307 (42%) by both a specialist and an FP. Compared with patients who received no follow-up cardiovascular care, patients who received regular cardiovascular follow-up visits with a physician had fewer visits to the emergency department (38% v. 80%), fewer were admitted to hospital (13% v. 94%), and the adjusted 1-year mortality was lower (22% v. 37%) (all p0.001). Compared with patients who received combined specialist and FP care, patients cared for exclusively by FPs had fewer outpatient visits (median 9 v. 17 in the first year), fewer of these patients presented to the emergency department (24% v. 45% in the first year), and fewer were readmitted for cardiovascular care (7% v. 16%) (all p0.001). However, the adjusted mortality at 1 year was lower among patients treated with combined care (17% v. 28%, p0.001) despite a higher burden of comorbidities. In a multivariate model adjusting for comorbidities (with no cardiovascular follow-up visits as the reference category), the mortality was lower among patients followed on an outpatient basis by an FP alone (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.53-0.82) or by an FP and a specialist (OR 0.34, 95% CI 0.28-0.42). In a proportional hazards model with time-dependent covariates (with adjustment for frequency of follow-up visits), the risk of all-cause mortality was reduced significantly (hazard ratio 0.98, 95% CI 0.97- 0.99) with each specialist visit compared with FP care alone.Patients with congestive heart failure followed by both specialists and FPs had significantly better survival than those followed by FPs alone (or those who received no specific cardiovascular follow-up care). Methods to improve timely and appropriate access to specialists and to improve collaborative care structures are needed.