Genetic cardiomyopathies commonly cause end-stage heart failure, yet genetic testing is inconsistently applied in heart transplant recipients. Identifying pathogenic/likely pathogenic (P/LP) variants clarifies etiology and informs familial risk, but data on diagnostic yield are limited. We performed a meta-analysis to quantify genetic testing yield in heart transplant recipients and implications for cascade testing. MEDLINE and Embase were searched for studies examining cardiomyopathy-focused genetic testing in heart transplant recipients. Pooled P/LP cardiomyopathy variant yields were estimated using random-effects models, stratified by cardiomyopathy phenotype. Cascade testing outcomes were summarized. Eleven studies met inclusion criteria. Overall, 32% (95% CI: 21-46%) of heart transplant recipients carried a P/LP variant. Yield was highest in non-ischemic cardiomyopathy (34%, 95% CI: 24-47%) and non-ischemic dilated cardiomyopathy cohorts (29%, 95% CI: 12-54%), and lowest in ischemic cardiomyopathy cohorts (8%, 95% CI: 4-18%). Heterogeneity ranged from I2 35% to 92%. Among studies reporting cascade testing outcomes, 52-92% of families underwent testing; 30-40% of relatives had P/LP variants, 15-69% of which demonstrated a phenotypic CM. While exact estimates should be interpreted cautiously given heterogeneity across cohorts, the consistency of findings suggests meaningful clinical relevance. Cardiomyopathy-focused genetic testing identifies P/LP variants in many heart transplant recipients, with important implications for cascade testing, supporting integration of cardiomyopathy-related genetic evaluation into heart transplant programs.

Background: Cancer and cardiovascular disease are the two leading causes of death in Canada. Although treatments have improved tremendously across the years, interventions such as radiotherapy and chemotherapies are known to have negative impacts on cardiovascular health and can lead to death if not treated in time. Using a retrospective approach, we determined factors associated with cancer therapy-related cardiac dysfunction (CTRCD). Methods: Patients followed through a dedicated Cardio-Oncology clinic with comprehensive screening for CTRCD were identified. CTRCD was defined as a drop in left ventricular ejection fraction of at least 10% to a value lower than 53%. We performed multivariable logistic regression to determine factors associated with CTRCD. Results: In total, 2460 patients with cancer were identified from clinical records—919 had breast cancer, 758 had hematologic malignancies, and 783 had other cancer types. Patients with breast cancer and hematologic malignancies were more likely to experience CTRCD, with odds ratios (ORs) of 2.10 (p = 0.059) and 1.96 (p = 0.047), respectively. Anthracycline and trastuzumab use were independently associated with CTRCD, with ORs of 1.98 (p = 0.002) and 3.19 (p < 0.001), respectively. In hematologic malignancy patients, hypertension (OR = 2.18, p = 0.047) and diabetes (OR = 2.31, p = 0.036) were also significant predictors of CTRCD. Conclusions: We confirmed the importance of anthracycline, trastuzumab, and radiation in the development of CTRCD. However, among patients with hematologic malignancies, traditional cardiovascular risk factors are also associated with CTRCD. This information could help physicians personalize CTRCD surveillance strategies.

Background:Tafamidis is an oral transthyretin stabilizer that improves survival in transthyretin amyloidosis cardiomyopathy (ATTR-CM), but only limited real-world data describe serial cardiac biomarker changes following treatment initiation. The primary objective of this study was to characterize longitudinal changes across multiple cardiac biomarker domains in tafamidis-treated ATTR-CM patients, to describe how these parameters evolve over time in routine clinical practice. We also report the same outcomes in untreated patients to reflect the natural disease history in a modern real-world cohort. Methods:Clinical, biochemical, and cardiac imaging parameters were serially assessed at baseline and 1-year follow-up for 145 ATTR-CM patients, both those treated and those untreated with tafamidis. Results:The median age was 80 years (range: 73-86), and 80 patients (55%) received tafamidis. At baseline, the treated group was younger and exhibited less advanced disease, relative to the untreated group. Treatment with tafamadis was associated with stabilization in N-terminal pro-B-type natriuretic peptide (NTproBNP) level, troponin-T level, and New York Heart Association functional class at 1-year follow-up, whereas the untreated group demonstrated worsening (all comparisons P < 0.05). Tafamidis treatment status was not significantly associated with National Amyloidosis Center or Mayo Clinic disease stage. Conclusions:NTproBNP level, troponin-T level, and New York Heart Association functional class remain stable over 1 year in a real-world cohort of tafamidis-treated ATTR-CM patients. These results may help inform therapeutic monitoring strategies in clinical practice.

Background Heart failure (HF) readmission rates have been a significant concern for healthcare systems globally. Accurate predictive models are essential to identify patients at high readmission risk and implement timely interventions. Current models often lack comprehensive variables that reflect both clinical and patient and/or caregiver perspectives. We aimed to develop a consensus-driven approach to identify essential variables for inclusion in HF hospital readmission risk prediction algorithms. Methods A Delphi panel comprised of clinicians and patient and/or caregiver partners was assembled. The Delphi panelists were recruited from the province of Alberta, Canada. The panel consisted of 13 individuals, including 9 healthcare providers and 4 patients and/or caregivers. The review panel was provided with a list of variables from a previously completed systematic literature review. Three rounds were conducted. The panel also determined the directionality of the association. Results A total of 99 variables were identified through literature and physician input. Panelists reached a consensus on 61 variables, which were deemed to be associated with the risk of readmission for any cause within 30 days of discharge after HF hospitalization. Clinician ratings on consensus were consistently higher than those of nonclinicians. Conclusions This study successfully identified 61 variables associated with HF readmission risk through a modified Delphi process, incorporating both clinician and patient and/or caregiver perspectives. These findings provide a foundation for future research and the development of more comprehensive and accurate risk prediction models. Including diverse stakeholder input highlights the importance of integrating medical expertise and patient experiences in improving HF management and reducing readmission rates.

This environmental scan aims to identify and describe initiatives implemented in Alberta, one of the few Canadian provinces with a unified health delivery system, to reduce heart failure (HF)readmissions. It also acknowledges the challenges in attributing direct benefits to these interventions. Using snowball sampling, we identified and recruited 11 employees and clinicians from Alberta Health Services (AHS) who possessed significant historical institutional knowledge about HF. Academic and grey literature were reviewed related to Alberta's readmission reduction initiatives and reported outcomes. Unstructured, in-depth interviews were conducted to clarify timelines and provide detailed descriptions of these interventions. Our findings indicate substantial clinician efforts over 15 years to address all-cause readmissions post HF hospitalization in Alberta, encompassing a range of interventions from small-scale projects to large multi-city, multi-stakeholder initiatives. Assessing the impact of smaller interventions on provincial readmission rates proved challenging; however, five major initiatives collectively led to a 1.8% reduction in 30-day all-cause readmissions province-wide (from 22.2% to 20.4%, p=0.04). Key factors that appeared to support these efforts included utilization of the EMR system, stakeholder engagement in standardized care, effective communication practices, and appropriate resource allocation. Clinical teams are now integrating successful components from these initiatives into the province-wide clinical information system, Connect Care, to enhance care coordination and patient outcomes. This environmental scan highlights various comprehensive initiatives in Alberta aimed at improving patient care and reducing readmission after HF hospitalization. While an overall 1.8% reduction in readmission rates was observed over the 15 years, attributing this change directly to the interventions is challenging due to various implementation barriers and the complexity of healthcare delivery. Continued efforts towards personalized care and innovative EMR utilization hold promise for further improvement in HF readmission rates. Key Words: Heart failure, readmissions, environmental scan, clinical pathways, health outcomes, patient-centered care ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Informed consent was obtained prior to each interview. Ethics was obtained from the Conjoint Health Research Ethics Board REB20-0684 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data cannot be shared publicly because to respect the privacy of the participants. Data are available from the University of Calgary Institutional Data Access / Ethics Committee (contact via cfreb{at}ucalgary.ca) for researchers who meet the criteria for access to confidential data.

Background: Cardiovascular magnetic resonance (CMR)-derived left ventricle filling pressure (LVFPcmr) has shown strong correlation with invasively measured values and early promise as a prognostic marker in defined patient populations. Objectives: The authors sought to describe associations of LVFPcmr with future heart failure (HF) outcomes in a large, diverse CMR referral population with stratified analyses by left ventricular (LV) ejection fraction (LVEF) subgroups. Methods: We analyzed consecutively enrolled patients in the Cardiovascular Imaging Registry of Calgary registry between 2015 and 2021 followed for at least 3 years for the occurrence of HF hospitalization, cardiac transplantation, or LV assist device implantation. Subjects completed baseline patient-reported health questionnaires, followed by CMR imaging. Sex-specific LVFPcmr was calculated. Results: A total of 9,588 patients were analyzed (median age 57 years; 62% males). Over a median follow-up of 6.4 years, 1,142 patients (12%) experienced the primary outcome. LVFPcmr was significantly associated with the outcome after adjusting for clinically relevant variables (subdistribution HR: 1.988 for an LVFPcmr of 18.7 [Q3] vs 14.0 mm Hg [Q1]; 95% CI: 1.659-2.381; P < 0.001). Using a survival-based approach, an optimal cutpoint of 18 mm Hg for LVFPcmr was identified. LVFPcmr ≥18 mm Hg remained independently associated with the outcome in the overall cohort, as well as LVEF subgroups. Respective adjusted HR for patients with LVEF <40%, 40 to 50% and >50% were 1.510 (1.216-1.876), 1.582 (1.153-2.171), and 2.865 (2.307-3.559). The latter group demonstrated similar value in patients with vs without coronary disease. Conclusion: LVFPcmr is a powerful predictor of future HF outcomes in broad referral populations inclusive of patients with reduced, mildly reduced, and preserved LV function.

Background: Experience with sacubitril-valsartan in real-world patients with heart failure and reduced ejection fraction (HFrEF) is congruent with findings from clinical trials. Detailed assessment of safety and clinical outcomes in the Canadian context is less well explored. Methods: The PAtient RegisTry assessing effectiveness and safety of HEart failure treatment with LCZ696 acrOss CaNada (PARTHENON) was a prospective, observational, multicentre study. Patients with HFrEF who were prescribed sacubitril-valsartan were recruited from 32 sites across Canada and followed for at least 3 years. The primary outcome was the association between baseline natriuretic peptide levels and the combined endpoint of all-cause mortality or all-cause hospitalization. Secondary outcomes included incidence of hypotension, hyperkalemia, and renal impairment. Additionally, observed all-cause mortality was compared with risk-model predicted mortality. Results: A total of 996 patients were enrolled in the registry; 19.1% discontinued the study early, and 10.8% died. No statistically significant association occurred between baseline natriuretic peptide levels and all-cause mortality or all-cause hospitalization (adjusted hazard ratio 1.04; 95% confidence interval: 0.91-1.20). Clinically relevant hypotension, hyperkalemia, and an increased creatinine level were observed in 24%, 4%, and 24%, respectively. The mean absolute change in left ventricular ejection fraction over 18 months was +8.2% +/- 10.8%. The observed 3-year mortality rate was lower than the 3-year mortality rate predicted by the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (10.8%, vs 29% +/- 13.7%); observed survival was higher than the Seattle Heart Failure Model predicted survival (89.2%, vs 53.4% +/- 26.4%). Conclusions: The PARTHENON registry confirms the safety and tolerability of sacubitril-valsartan in patients with HFrEF in a real-world setting. The registry also demonstrated improvement in left ventricular ejection fraction, and a lower mortality rate, compared to the predicted mortality rate in this population.

Background: Hospital readmissions within 7 days after discharge are considered highly avoidable and undesirable for the patient and hospital. It is important to clarify gaps in the quality of inpatient care to identify strategies to address this problem. Aims: We aimed to describe the precipitating factors and determine the potential avoidability of 7-day readmissions after hospitalization for heart failure (HF). Methods: A health record audit was undertaken of patients discharged after hospitalization for HF from Calgary, Alberta hospitals. Content analysis was undertaken to identify factors precipitating readmission, and readmission's avoidability was qualitatively examined and scored based on descriptive categories. Results: Of 18,590 patients admitted to the hospital for HF during the study period, 191 HF patients were readmitted within 7 days (50% female; mean age 78 years). Potentially avoidable readmissions (57%) were due to unresolved symptoms, unaddressed social or self-care issues, adverse events from the index admission, high disability without added services, and discussions of palliative care without added services. Readmissions deemed less avoidable (43%) were due to new health issues, recurring symptoms post-stability at discharge, or refusal of care. Conclusion: Only half of hospital readmissions within 7 days after HF discharge were related to HF and more than half were scored as avoidable. We provide novel criteria for identifying the avoidability of 7-day readmissions that could be used for assessing HF patients' readiness for discharge and potentially reducing readmission rates. Keywords: Heart failure; Risk factors; Heart disease; Chronic disease; Readmission ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This doctoral study was supported by the Izaak Walton Killam Memorial Scholarship and Alberta Innovates - Health Solutions (AIHS) Clinician Researcher Fellowship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Conjoint Health Research Ethics Board of Alberta of the University of Calgary gave ethical approval for this work (REB-E-25279) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data cannot be shared publicly because to respect the privacy of the participants. Data are available from the University of Calgary Institutional Data Access / Ethics Committee (contact via cfreb{at}ucalgary.ca) for researchers who meet the criteria for access to confidential data.

Heart failure with preserved ejection fraction (HFpEF) refers to a clinical condition in which the signs of heart failure, such as pulmonary congestion, peripheral edema, and increased natriuretic peptide levels, are present despite normal ejection fractions and the absence of other causes (eg, pericardial disease). The ejection fraction cutoff for the definition of HFpEF has varied in the past, but recent society guidelines have settled on a consensus of 50%. HFpEF is particularly common in the elderly population. The aim of this narrative review is to summarize the available literature regarding HFpEF in elderly patients in terms of evidence for the age dependence, specific clinical features, and underlying mechanisms. In the clinical arena, we review the epidemiology, discuss distinct clinical phenotypes typically seen in elderly patients, the importance of frailty, the role of biomarkers, and the role of medical therapies (including sodium-glucose cotransport protein 2 inhibitors, renin-angiotensin-aldosterone system blockers, angiotensin receptor/neprilysin inhibitors, diuretics, and β-adrenergic receptor blockers). We then go on to discuss the basic mechanisms implicated in HFpEF, including cellular senescence, fibrosis, inflammation, mitochondrial dysfunction, enhanced production of reactive oxygen species, abnormal cellular calcium handling, changes in microRNA signalling, insulin resistance, and sex hormone changes. Finally, we review knowledge gaps and promising areas of future investigation. Improved understanding of the specific clinical manifestations of HFpEF in elderly individuals and of the fundamental mechanisms that contribute to the age-related risk of HFpEF promises to lead to novel diagnostic and treatment approaches that will improve outcomes for this common cardiac disorder in a vulnerable population.