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AimsPatients visiting the emergency department (ED) or hospitalized for heart failure (HF) are at increased risk for subsequent adverse outcomes, however effective risk stratification remains challenging. We utilized a machine-learning (ML)-based approach to identify HF patients at risk of adverse outcomes after an ED visit or hospitalization using a large regional administrative healthcare data system.Methods and resultsPatients visiting the ED or hospitalized with HF between 2002-2016 in Alberta, Canada were included. Outcomes of interest were 30-day and 1-year HF-related ED visits, HF hospital readmission or all-cause mortality. We applied a feature extraction method using deep feature synthesis from multiple sources of health data and compared performance of a gradient boosting algorithm (CatBoost) with logistic regression modelling. The area under receiver operating characteristic curve (AUC-ROC) was used to assess model performance. We included 50,630 patients with 93,552 HF ED visits/hospitalizations. At 30-day follow-up in the holdout validation cohort, the AUC-ROC for the combined endpoint of HF ED visit, HF hospital readmission or death for the Catboost and logistic regression models was 74.16 (73.18-75.11) versus 62.25 (61.25-63.18), respectively. At 1-year follow-up corresponding values were 76.80 (76.1-77.47) versus 69.52 (68.77-70.26), respectively. AUC-ROC values for the endpoint of all-cause death alone at 30-days and 1-year follow-up were 83.21 (81.83-84.41) versus 69.53 (67.98-71.18), and 85.73 (85.14-86.29) versus 69.40 (68.57-70.26), for the CatBoost and logistic regression models, respectively.ConclusionsML-based modelling with deep feature synthesis provided superior risk stratification for HF patients at 30-days and 1-year follow-up after an ED visit or hospitalization using data from a large administrative regional healthcare system.

Background: Pulmonary hypertension is common among patients with heart failure (HF). Right ventricular systolic pressure (RVSP) is frequently used to assess its presence and severity. Although RVSP has been associated with adverse outcomes, the importance of serial measurements has not been studied. We evaluated associations between serial RVSP measurements and cardiovascular events in patients with HF. Methods: Patients with HF and 2 echocardiograms performed ≥ 6 months apart were included. RVSP was categorized, using the second echocardiogram, as follows: normal (< 40 mm Hg); severely elevated (≥ 60 mm Hg); moderately elevated (50-59 mm Hg); or mildly elevated (40-49 mm Hg). Patients also were classified according to change in RVSP categories between echocardiograms. The primary outcome was time to HF hospitalization (HFH) or all-cause mortality (ACM) after the second echocardiogram. Results: In total, 4319 patients were included (median age: 78 years; 52.1% female). During a median follow-up period of 19.4 months, HFH/ACM occurred in 2714 patients (62.8%). In multivariable analysis, baseline RSVP that was mildly elevated (1069 patients, hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.12-1.54), moderately elevated (797 patients, HR 1.54, 95% CI 1.30-1.82), or severely elevated (837 patients, HR 1.92, 95% CI 1.60-2.31) was independently associated with HFH/ACM. Additionally, improving RVSP was associated with increased HFH/ACM in both categorical (HR 1.16, 95% CI 1.01-1.33) and continuous analyses. Conclusions: RVSP measurements identify patients at increased risk who may require more-aggressive monitoring and medical therapy. Our study raises the hypothesis that, in addition to the absolute value of RVSP, improving RVSP category may identify higher-risk patients, but further study is needed to elucidate the underlying reasons. Résumé: Contexte: L’hypertension pulmonaire est fréquente chez les patients atteints d’insuffisance cardiaque. La pression systolique ventriculaire droite (PSVD) est souvent utilisée pour évaluer la présence et la gravité de l’hypertension pulmonaire. Bien que la PSVD ait été associée à des complications, l’importance de mesures répétitives n’a pas été étudiée. Nous avons évalué les liens entre des mesures répétitives de la PSVD et des événements cardiovasculaires chez des patients atteints d’insuffisance cardiaque. Méthodologie: Ont été inclus des patients atteints d’insuffisance cardiaque pour lesquels on disposait de deux échocardiogrammes réalisés dans un intervalle ≥ 6 mois. La PSVD a été catégorisée comme suit, au moyen du deuxième échocardiogramme : normale (

A 43-year-old man presented with severe heart failure secondary to high-risk light chain cardiac amyloidosis. He underwent chemotherapy and autologous stem cell transplantation with complete hematologic response. Serial cardiac magnetic resonance imaging post-transplant demonstrated gradual normalization of biventricular function and myocardial T1, a surrogate measure of disease burden.

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme alpha-galactosidase. While AFD is recognized as a progressive multi-system disorder, infiltrative cardiomyopathy causing a number of cardiovascular manifestations is recognized as an important complication of this disease. AFD affects both men and women, although the clinical presentation typically varies by sex, with men presenting at a younger age with more neurologic and renal phenotype and women developing a later onset variant with more cardiovascular manifestations. AFD is an important cause of increased myocardial wall thickness, and advances in imaging, in particular cardiac magnetic resonance imaging and T1 mapping techniques, have improved the ability to identify this disease non-invasively. Diagnosis is confirmed by the presence of low alpha-galactosidase activity and identification of a mutation in the GLA gene. Enzyme replacement therapy remains the mainstay of disease modifying therapy, with two formulations currently approved. In addition, newer treatments such as oral chaperone therapy are now available for select patients, with a number of other investigational therapies in development. The availability of these therapies has significantly improved outcomes for AFD patients. Improved survival and the availability of multiple agents has presented new clinical dilemmas regarding disease monitoring and surveillance using clinical, imaging and laboratory biomarkers, in addition to improved approaches to managing cardiovascular risk factors and AFD complications. This review will provide an update on clinical recognition and diagnostic approaches including differentiation from other causes of increased ventricular wall thickness, in addition to modern strategies for management and follow-up.

Abstract Aims 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. Methods and results 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

Abstract Background Hereditary transthyretin amyloidosis is an uncommon multisystem disorder caused by mutation of the transthyretin protein, leading to peripheral neuropathy often with autonomic features, cardiomyopathy, or a mixed phenotype. Multiple other organ systems can be involved with ophthalmologic, renal, hematologic, gastrointestinal, and/or genitourinary symptoms and signs. This often results in assessments by multiple specialists and significant delays before the diagnosis is recognized. With the recent advent of potentially lifesaving therapies, early diagnosis has become even more important. Our case highlights the protean aspects of this disease as well as the difficulty of making this diagnosis, especially in the absence of a clear family history. Case presentation We report the case of a 64-year-old man of East-Asian descent who presented with diarrhea, mild anemia, and symptoms of peripheral neuropathy. Numerous investigations and specialist evaluations did not identify a cause. Progression of neurologic symptoms and the development of new hematologic abnormalities ultimately led to consideration of hereditary transthyretin amyloidosis. The diagnosis was confirmed after re-examining previously acquired gastrointestinal biopsies and pursuing genetic testing, which confirmed a pathogenic mutation in the transthyretin gene. He was subsequently started on a novel gene-silencing therapy. On clinical follow-up 8 months after initiation of therapy, the patient described stabilization of previously progressive numbness, weakness, and weight loss with an unchanged neurologic examination and stable repeat electrophysiologic testing. Conclusions Hereditary transthyretin amyloidosis is a challenging disease to recognize in early stages owing to its multisystem and nonspecific manifestations. Recent approval of novel therapies highlights the importance of early diagnosis before irreversible organ damage occurs.

Background:. Carpal tunnel syndrome (CTS) is common in patients with transthyretin amyloidosis (ATTR), and many experience residual symptoms and/or develop recurrent disease following routine carpal tunnel release (CTR). An extended CTR with median nerve neurolysis is recommended for thorough nerve decompression. Tissue confirmation of amyloidosis can be performed at the time of CTR with biopsies of the transverse carpal ligament and/or tenosynovium. Methods:. We describe a retrospective, single-center experience performing an extended CTR technique including unilateral and bilateral cases for 13 consecutive patients (18 wrists) with ATTR and symptomatic median neuropathy at the wrist. Results:. The mean patient age was 83 (range 67–90) years and 11 (85%) were men. Notable intraoperative findings in all cases included thickened tenosynovium and median nerve epineurium, and adherence of the median nerve to the deep surface of transverse carpal ligament. Pathology findings were positive for amyloidosis from both the transverse carpal ligament and the tenosynovium biopsies in all patients. Conclusions:. Extended CTR with simultaneous wrist tissue biopsy can be safely performed for ATTR patients with CTS. Characteristic intraoperative findings should increase clinical suspicion for undiagnosed ATTR and prompt performance of biopsy for diagnostic confirmation. Volar wrist tenosynovial biopsy is our preferred tissue for confirmation of ATTR, for patients with and without CTS, given its safety profile and 100% pathological yield in our series.

BackgroundAtrial fibrillation (AF) is a commonly encountered cardiac arrhythmia associated with morbidity and substantial healthcare costs. While patients with cardiovascular disease experience the greatest risk of new-onset AF, no risk model has been developed to predict AF occurrence in this population. We hypothesized that a patient-specific model could be delivered using cardiovascular magnetic resonance (CMR) disease phenotyping, contextual patient health information, and machine learning.MethodsNine thousand four hundred forty-eight patients referred for CMR imaging were enrolled and followed over a 5-year period. Seven thousand, six hundred thirty-nine had no prior history of AF and were eligible to train and validate machine learning algorithms. Random survival forests (RSFs) were used to predict new-onset AF and compared to Cox proportional-hazard (CPH) models. The best performing features were identified from 115 variables sourced from three data domains: (i) CMR-based disease phenotype, (ii) patient health questionnaire, and (iii) electronic health records. We evaluated discriminative performance of optimized models using C-index and time-dependent AUC (tAUC).ResultsA RSF-based model of 20 variables (CIROC-AF-20) delivered an overall C-index of 0.78 for the prediction of new-onset AF with respective tAUCs of 0.80, 0.79, and 0.78 at 1-, 2- and 3-years. This outperformed a novel CPH-based model and historic AF risk scores. At 1-year of follow-up, validation cohort patients classified as high-risk of future AF by CIROC-AF-20 went on to experience a 17.3% incidence of new-onset AF, being 24.7-fold higher risk than low risk patients.ConclusionsUsing phenotypic data available at time of CMR imaging we developed and validated the first described risk model for the prediction of new-onset AF in patients with cardiovascular disease. Complementary value was provided by variables from patient-reported measures of health and the electronic health record, illustrating the value of multi-domain phenotypic data for the prediction of AF.

Background: Tafamidis is a costly therapy that improves outcomes for patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM), although significant knowledge gaps exist for predicting longer-term response to treatment. The purpose of this study was to examine baseline predictors of adverse outcomes and their association with tafamidis treatment in comparison with those untreated in a clinical cohort from a Canadian ATTR-CM referral center. Methods: Patients with a confirmed diagnosis of ATTR-CM were included. Multivariable modeling was used to identify baseline variables associated with the primary outcome of all-cause mortality and secondary outcomes of cardiovascular mortality or hospitalization. Cox proportional hazard and competing risk analyses were used, with tafamidis modeled as a time-varying covariate. Results: In total, 139 ATTR-CM patients were included, with a median age of 80.9 years [74.3–86.6 years], from 2011 to 2022. The mean follow-up was 2.9 ± 1.8 years. Eighty (55%) patients were treated with tafamidis. All-cause mortality and cardiovascular mortality alone were associated with the following baseline variables: age, clinical frailty scale, systolic blood pressure, renal function, and right ventricular size and function (all p < 0.05), with no identified interactions with tafamidis treatment. Only baseline renal function was associated with cardiovascular hospitalization (p < 0.05). Conclusion: Important baseline variables associated with adverse ATTR-CM disease outcomes included renal function, systolic blood pressure, frailty, and right ventricular size and function. The risk factors were independent of treatment with tafamidis. These findings may help improve risk stratification for determining eligibility for ATTR-CM therapies. [ABSTRACT FROM AUTHOR]

Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is commonly diagnosed in older adults, in particular the wild-type (ATTRwt), which is regarded as an age-related disease. With an aging population and improved diagnostic techniques, the prevalence and incidence of ATTR-CM will continue to increase. With increased availability of mortality reducing ATTR-CM therapies, patients are living longer. The predominant clinical manifestation of ATTR-CM is heart failure, while other cardiovascular manifestations include arrhythmia and aortic stenosis. Given their older age at diagnosis, patients often present with multiple age-related comorbidities, some of which can be exacerbated by ATTR, including neurologic, musculoskeletal, and gastrointestinal problems. Considerations related to older patient care, such as frailty, cognitive decline, polypharmacy, falls/mobility, functional capacity, caregiver support, living environment, quality of life and establishing goals of care are particularly important for many patients with ATTR-CM. Furthermore, the high cost ATTR treatments has increased interest in establishing improved predictors of response to therapy, with assessment of frailty emerging as a potentially important determinant. Multidisciplinary care inclusive of collaboration with geriatric and elder care medicine specialists, and others such as neurology, orthopedic surgery, electrophysiology and transcatheter aortic valve replacement clinics, is now an important component of ATTR-CM management. This review will examine current aspects of the management of older ATTR-CM patients, including shared care with multiple medical specialists, the emerging importance of frailty assessment and other considerations for using ATTR therapies.

Patients with Tetralogy of Fallot (TOF) have multiple surgical sequelae altering the pulmonary flow hemodynamics. Repaired TOF (rTOF) adults frequently develop pulmonary regurgitation impacting the blood flow pressure, right ventricle load, and pulmonary hemodynamics. We aimed to evaluate the pulmonary flow hemodynamics using 4D-flow magnetic resonance imaging (MRI) for characterizing altered blood flow, viscous energy loss (EL), wall shear stress (WSS), pressure drop (PD), and ventricular flow analysis (VFA) in rTOF patients. We hypothesized that 4D-flow based parameters can identify pulmonary blood flow alterations. A total of 17 rTOF patients (age: 29 ± 10 years, 35% women) and 20 controls (age: 36 ± 12 years, 25% women) were scanned using a dedicated cardiac MRI protocol. Peak velocity and regurgitant fraction were significantly higher for rTOF patients (p < 0.001). WSS was consistently elevated along the PA in the rTOF (p ≤ 0.05). The rTOF average circumferential WSS was higher than axial WSS at the main pulmonary artery (p ≤ 0.001). PD and EL were consistently higher in the rTOF as compared with controls (p < 0.05). For VFA, delayed ejection increased and retained inflow decreased in rTOF patients (p < 0.001). To conclude, this study demonstrated that 4D-flow MRI pulmonary flow in the rTOF can exhibit altered peak velocity, valvular regurgitation, WSS, EL, PD, and VFA.