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Background: Early diagnosis of cardiac amyloidosis (CA) is crucial due to the promising effect of disease-modifying treatment. This calls for screening strategies to identify CA patients with so-called "red flags", such as carpal tunnel syndrome (CTS)., Objectives: This study aims to assess Troponin-T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as predictors for CA in patients with a history of surgery for bilateral carpal tunnel syndrome, a population suitable for systematic screening., Methods: Subjects with a history of surgery for bilateral CTS 5-15 years prior, identified using national registries were investigated for CA as per international recommendations. Sensitivity, specificity, positive and negative predictive values were assessed, and receiver operating curves were generated using logistic regression., Results: Among the 250 participants, 12 were diagnosed with CA, all with wild-type transthyretin amyloidosis. Elevated TnT levels (≥13 ng/L) were found in all CA patients and 25.6% (±2.8) of non-CA patients. The negative predictive value (NPV) of TnT <13 ng/L was 100%. For NT-ProBNP the NPV was 99.1% when age dependent cutoff levels were used. A combination of both biomarkers yielded an NPV of 99.1% and sensitivity of 99.7%. Early disease (Mayo or NAC stage 1) was found in 83% of identified patients with CA., Conclusion: This study demonstrates the utility of TnT and NT-ProBNP as negative predictors to exclude CA in a screening population with a history of surgery for CTS., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle., Objectives: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests)., Methods: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients., Results: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02)., Conclusions: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction., Competing Interests: Funding Support and Author Disclosures This project was supported, in part, by the American College of Cardiology and Merck Research Fellowship Award. Dr Brener has received consulting fees from Artract Medical and Osprey Medical. Dr Kanwar has served on the Medical Advisory Boards of Abiomed, CareDx, and CorWave. Dr Lander has served on the Medical Advisory Board of Abiomed. Dr Raina has received research support from United Therapeutics and Merck. Dr Sethi has received honoraria from Janssen and Chiessi; and has received institutional grant support from the American Heart Association’s COVID-19 Rapid Response Award. Dr Maurer has received funding from the National Institutes of Health (HL139671-01AL1 and AG K24AG036778); AD consulting income from Ionis, Alnylam, Eidos Therapeutics, Pfizer, Intellia, and Prothena; and his institution has also received funding for clinical trials for Ionis, Alnylam, Eidos Therapeutics, Pfizer, and Attralus. Dr Sayer has received consulting fees from Abbott. Dr Burkhoff has received an unrestricted institutional educational grant from Abiomed. Dr Uriel has received grant support from Abbott, Abiomed, and Fire1; and has served on the Medical Advisory Boards of Leviticus and Revamp. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Backgrounds and Aims: Hypertrophic cardiomyopathy (HCM) causes cardiac death through both sudden cardiac death (SCD) and death due to heart failure (HF). Although adipokines lead to adverse cardiac remodeling in HCM, the prognostic value of plasma adipokines in HCM remains unknown. We aimed to predict cardiac death in patients with HCM using plasma adipokines., Methods and Results: We performed a multicenter prospective cohort study of patients with HCM. The outcome was cardiac death including heart transplant, death due to HF, and SCD. With data from 1 institution (training set), a prediction model was developed using random forest classification algorithm based on 10 plasma adipokines. The performance of the prediction model adjusted for 8 clinical parameters was examined in samples from another institution (test set). Time-to-event analysis was performed in the test set to compare the rate of outcome events between the low-risk and high-risk groups determined by the prediction model. In total, 389 (267 in the training set; 122 in the test set) patients with HCM were included. During the median follow-up of 2.7 years, 21 patients experienced the outcome event. The area under the covariates-adjusted receiver-operating characteristics curve was 0.89 (95 % confidence interval [CI] 0.71-0.99) in the test set. revealed the high-risk group had a significantly higher risk of cardiac death (hazard ratio 17.8, 95 % CI 2.1-148.3, P = 0.008)., Conclusion: The present multicenter prospective study demonstrated that a panel of plasma adipokines predicts cardiac death in patients with HCM., Competing Interests: Declaration of competing interest This work was supported by the National Institutes of Health [R01 HL157216 and R01 HL168382 to Y.J.S., UL1 TR001873 to M.P.R., K24 HL107643 to M.P.R., and K24 AG036778 to M.S.M.], the American Heart Association [2 National Clinical and Population Research Awards and Career Development Award to Y.J.S.], Korea Institute of Oriental Medicine [W22005 to Y.J.S.], Feldstein Medical Foundation to Y.J.S., Columbia University Irving Medical Center Irving Institute for Clinical & Translational Research Precision Medicine Pilot Award to Y.J.S., and Columbia University Irving Medical Center Marjorie and Lewis Katz Cardiovascular Research Prize to Y.J.S. Y.J.S. has also received funding from Bristol-Myers Squibb, and consulting income from Bristol-Myers Squibb and Moderna Japan. M.S.M. has also received consulting income from Akcea, Alnylam, Eidos Therapeutics, Pfizer, Prothena, Novo Nordisk, and Intellia. The funding organizations did not have any role in the study design, collection, analysis, or interpretation of data, in writing of the manuscript, or in the decision to submit the article for publication. The researchers were independent from the funding organizations., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Age is among the most potent risk factors for developing heart failure and is strongly associated with adverse outcomes. As the global population continues to age and the prevalence of heart failure rises, understanding the role of aging in the development and progression of this chronic disease is essential. Although chronologic age is on a fixed course, biological aging is more variable and potentially modifiable in patients with heart failure. This review describes the current knowledge on mechanisms of biological aging that contribute to the pathogenesis of heart failure. The discussion focuses on 3 hallmarks of aging-impaired proteostasis, mitochondrial dysfunction, and deregulated nutrient sensing-that are currently being targeted in therapeutic development for older adults with heart failure. In assessing existing and emerging therapeutic strategies, the review also enumerates the importance of incorporating geriatric conditions into the management of older adults with heart failure and in ongoing clinical trials., Competing Interests: Funding Support and Author Disclosures Dr Goyal has received grant support from National Institutes of Health (NIH) grants K76AG064428 and R21AG077092; and has received personal fees from Sensorum Health, Agepha Pharma, and Axon Therapies. Dr Maurer has received grant support from NIH grants R01HL139671 and R01AG081582-01; has received grants and personal fees from Alnylam, Pfizer, Eidos, Prothena, and Ionis; and has received personal fees from AstraZeneca, Akcea, Intellia, and Novo Nordisk. Dr Roh has received grant support from NIH grants K76AG064328 and R01HL170058, Hassenfeld Scholars Award, MGH Transformative Scholars Award, and the Fred and Ines Yeatts Fund for Innovative Research; and has received research support from Genentech, Amgen, and Keros Therapeutics., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is most commonly associated with obstructive symptoms and sudden cardiac death; however, predominantly nonobstructive advanced heart failure in HCM, marked by medically refractory disease with severe functional impairment, occurs in 5% to 7% of patients with HCM. The diagnosis relies on the integration of imaging (echocardiography/cardiac magnetic resonance), hemodynamic data, and cardiopulmonary exercise testing to identify the patients who will benefit from advanced heart failure therapies. Most advanced heart failure therapies focus on systolic dysfunction and are not always applicable to this patient population. Left ventricular assist devices may be an option in a highly selected population with left ventricular dilation. Heart transplantation is often the best option for patients with advanced heart failure in HCM with excellent post-transplantation survival., Competing Interests: Funding Support and Author Disclosures Dr Shimada was supported by the National Institutes of Health (R01 HL157216). Dr Maurer was supported by funding from the National Institutes of Health (HL139671-01, AG R21AG058348, and AG K24AG036778). Dr Clerkin was supported by the National Institutes of Health (K23 HL148528). Dr Shimada has received research support from the American Heart Association National Clinical and Population Research Awards, an American Heart Association Career Development Award, the Korea Institute of Oriental Medicine, a Columbia University Irving Medical Center Irving Institute for Clinical and Translational Research Precision Medicine Pilot Award, and Bristol Myers Squibb; and consulting income from Bristol Myers Squibb; and his institution has also received funding for clinical trials for Bristol Myers Squibb. Dr Maurer has received consulting income from Akcea, Alnylam, Eidos Therapeutics, Pfizer, Prothena, Novo Nordisk, and Intellia; and his institution has also received funding for clinical trials for Alnylam, Eidos Therapeutics, Pfizer, and Prothena. Dr Sayer has received consulting fees from Abbott. Dr Uriel has received grants from Abbott, Abiomed, and Fire 1; and served on the medical advisory board for Livemetric, Leviticus, and Revamp outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Spinal stenosis is one of the most common neurosurgical diseases and a leading cause of pain and disability. Wild-type transthyretin amyloid (ATTRwt) has been found in the ligamentum flavum (LF) of a significant subset of patients with spinal stenosis who undergo decompression surgery. Histologic and biochemical analyses of LF specimens from spinal stenosis patients, normally discarded as waste, have the potential to help elucidate the underlying pathophysiology of spinal stenosis and possibly allow for medical treatment of stenosis and screening for other systemic diseases. In the present review, we discuss the utility of analyzing LF specimens after spinal stenosis surgery for ATTRwt deposits. Screening for ATTRwt amyloidosis cardiomyopathy through LF specimens has led to the early diagnosis and treatment of cardiac amyloidosis in several patients, with more expected to benefit from this process. Emerging evidence in the literature also point to ATTRwt as a contributor to a previously unrecognized subtype of spinal stenosis in patients who might, in the future, benefit from medical therapy. In the present report, we review the current literature regarding the early detection of ATTRwt cardiomyopathy via LF screening and the possible contribution of ATTRwt deposits in the LF to spinal stenosis development., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, and cardiac amyloidosis (CA) is one of the causes of HFpEF, that has established and emerging treatment options. However, it remains an underdiagnosed and often overlooked cause of HFpEF. The importance of early diagnosis cannot be emphasized enough, as emerging therapies are more effective early in the course of the disease. Further, because of the unique physiologic and hemodynamic features of CA, patients poorly tolerate traditional heart failure medications and experience worse outcomes compared with other causes of HFpEF. With the aging of the population, transthyretin (ATTR) CA, once thought to be a rare disease, will become the most common type of systemic amyloidosis. ATTR-CA is increasingly recognized due to enhanced clinical awareness; advances in diagnostic imaging that have led to a diagnostic approach that does not require a biopsy, as well as the recent introduction of novel disease-modifying treatments. ATTR-CA causes restrictive and infiltrative cardiomyopathy that results in heart failure, atrial and ventricular arrhythmias, and conduction disease, and is associated with significant morbidity and mortality. Our goal in this review is to provide an overview of the historical, epidemiologic, diagnostic, and therapeutic evolution of ATTR-CA, and to emphasize the importance of early suspicion and detection of HFpEF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition., Methods: All patients who were followed post-HT for ATTR-CA at our center were included. Baseline demographics and post-HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31 quantifies autonomic symptoms, with a higher score [0-100] indicating more severe autonomic dysfunction) and Polyneuropathy Disability Score (PND, range from 0 [asymptomatic] to IV [confined to wheelchair/bed]) questionnaires., Results: Twelve patients (5 wild-type, 7 variant [6 p.Val142Ile, 1 p.Thr80Ala]) were included. Mean age at HT was 64.6 (SD: 4.8) years, 83.3% male, and 50% Black. At a median of 4.0 years (IQR 2.4, 5.9) post-HT, 8 patients had symptoms of ATTR deposition (5 with gastrointestinal involvement, 4 orthopedic and 4 neurologic), with 4 patients having ≥2 body systems involved. There were no patients with recurrent cardiac involvement. Median COMPASS-31 score was 17.3 (IQR 11.3, 23.5) at 3.9 years (IQR 2.4, 5.9) post-HT. Four patients had a PND score of stage 1 (sensory disturbance), 1 patient was stage 2 (impaired walking) and 1 patient stage 3b (required a walking aid)., Conclusions: More than 50% of patients had evidence of progressive or de novo ATTR deposition post-HT, impairing quality of life despite a well-functioning cardiac allograft. These observations highlight an unmet need to establish the role of formal surveillance and treatment of TTR using TTR disease-modifying therapies, which may maintain or improve quality of life post-HT for ATTR-CA., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Systemic immunoglobulin light-chain amyloidosis is characterized by pathologic deposition of immunoglobulin light chains as amyloid fibrils in vital organs, leading to organ impairment and eventual death. That the process is reversible was evidenced in an in vivo experimental model in which fibril-reactive chimeric monoclonal antibody (mAb) 11-1F4 directly targeted human light-chain amyloid deposits and affected their removal via a phagocyte-mediated response. To determine the tolerability and potential amyloidolytic effect of this agent (now designated mAb CAEL-101), we conducted a phase 1a/b study involving 27 patients, most of whom had manifestations of organ involvement. This was an open-label study in which phase 1a patients received mAb CAEL-101 as a single intravenous infusion with escalating dose levels from 0.5 mg/m2 to 500 mg/m2 to establish the maximum tolerated dose (MTD). In phase 1b, the antibody was administered as a graded series of 4 weekly infusions. For both phases, there were no drug-related serious adverse events or dose-limiting toxicities among recipients, and the MTD was not reached. The majority of patients had deep hematologic responses but persistent organ disease prior to treatment. Fifteen of 24 patients (63%) who manifested cardiac, renal, hepatic, gastrointestinal, or soft tissue involvement had a therapeutic response to mAb CAEL-101 as evidenced by serum biomarkers or objective imaging modalities with a median time to response of 3 weeks. Infusions of mAb CAEL-101 were well tolerated and, for the majority, resulted in improved organ function, notably for those with cardiac impairment. This trial was registered at www.clinicaltrials.gov as #NCT02245867., (© 2021 by The American Society of Hematology.)

Objectives: Because patients with ATTRv cardiomyopathy are more likely to be male, this analysis aimed to increase information on associations between sex and genotype, phenotype, and degree of myocardial involvement in ATTRv amyloidosis., Background: Transthyretin amyloid cardiomyopathy is a progressive, fatal disease that occurs due to accumulation of wild-type or variant (ATTRv) transthyretin amyloid fibrils in the myocardium., Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy., Results: There were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro-B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height)., Conclusions: In this analysis, myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males., Competing Interests: Funding Support and Author Disclosures The THAOS registry and this analysis were sponsored by Pfizer. Medical writing support was provided by Joshua Fink, PhD, of Engage Scientific Solutions and funded by Pfizer. Dr Rapezzi has received research grants from Pfizer and consultancy fees from Pfizer; Alnylam, and Prothena. Dr Milandri has received consultancy fees from Alnylam. Dr. Dispenzieri has received research grants from Celgene, Millennium, Pfizer, Janssen, and Alnylam; funding from Pfizer for meeting expenses (travel); and attended advisory boards for Akcea and Intellia. Dr Kristen has received research support from and advisory board attendance for Pfizer. Dr Wixner has received consulting fees, travel support for lectures, and advisory boards from Pfizer, Akcea, and Alnylam. Dr Maurer has received grants and/or personal fees from Akcea, Alnylam, Eidos, GlaxoSmithKline, Ionis, Pfizer, and Prothena. Dr Garcia-Pavia has received speaker and/or consulting fees from Pfizer, Eidos, Alnylam, Prothena, Neurimmune, and Akcea; and research funding from Alnylam and Pfizer. Dr Tournev has received sponsorship from Pfizer for participation in advisory boards, congresses, and conferences. Dr Planté-Bordeneuve is serving as a medical advisor for Pfizer, Alnylam, Eidos, and Ionis. Drs Chapman and Amass are full-time employees of Pfizer and hold stock and/or stock options with Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac involvement and dysfunction are common in patients presenting with AL and ATTR Amyloidosis. Cardiopulmonary exercise testing (CPET) performance is the gold standard to quantify functional capacity., Patients and Methods: In this study, we evaluated CPET measurements in 41 patients with cardiac Amyloidosis and their correlation with current amyloid specific staging criteria., Results: In both AL and ATTR cardiac Amyloidosis, percent predicted peak VO2 is significantly reduced and correlates with biomarker abnormalities. The association of cardiac biomarkers with peak VO2 is stronger for AL Amyloidosis (NT-proBNP (r = -0.57, P=0.006), Troponin (r = -0.70, p < 0.001) than ATTR (NT-proBNP (r = -0.4, P = 0.04) and Troponin (r = -0.57, P = 0.002) despite lower left ventricular mass in the former, suggesting that this may be further evidence for light chain toxicity in AL amyloidosis., Conclusion: Our findings suggest further evidence for AL toxicity., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: This study aimed to characterize trends in technetium Tc 99m pyrophosphate ( 99m Tc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA., Background: 99m Tc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of 99m Tc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics., Methods: Patients undergoing 99m Tc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed., Results: Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p < 0.001). Among 753 patients (516 men, mean age 77 years), 307 (41%) had a visual score of 0, 177 (23%) of 1, and 269 (36%) of 2 or 3. Of 751 patients with analyzable heart to contralateral chest ratios, 249 (33%) had a ratio ≥1.5. Monoclonal protein testing status was assessed in 550 patients, of these, 174 (32%) did not undergo both serum immunofixation and serum free light chain analysis tests, and 331 (60%) did not undergo all 3 tests-serum immunofixation, serum free light chain analysis, and urine protein electrophoresis. Of 196 patients with confirmed ATTR-CA, 143 (73%) had genetic testing for transthyretin mutations. In 103 patients undergoing cardiac biopsy, grades 2 and 3 99mTc-PYP had sensitivity of 94% and specificity of 89% for ATTR-CA with 100% specificity for grade 3 scans. With respect to SPECT as a reference standard, planar imaging had false positive results in 16 of 25 (64%) grade 2 scans., Conclusions: Use of noninvasive testing with 99m Tc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling., Competing Interests: FUNDING SUPPORT AND AUTHOR DISCLOSURES Dr. Poterucha has reported stock ownership in Abbott Laboratories, AbbVie, Inc, Baxter International, and Edwards Lifesciences. Dr. Einstein serves as a consultant to W. L. Gore and Associates; and has received funding paid to his institution from the NIH, Canon Medical Systems, USA, Roche Medical Systems, and W.L. Gore and Associates. Dr. Bokhari serves on advisory board of Pfizer, Inc., EIDOS Therapeutics, Inc.; and serves as a speaker for Pfizer, Inc. and Astellas, Inc. Dr. Maurer has received research funding paid to his institution funding from NIH/NIA, Pfizer, Inc., Novartis, Ionis Pharmaceuticals, Prothena Biosciences Limited, and EIDOS Therapeutics, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Only a subset of patients with hypertrophic cardiomyopathy (HCM) develop adverse cardiac events - e.g., end-stage heart failure, cardiovascular death. Current risk stratification methods are imperfect, limiting identification of high-risk patients with HCM. Our aim was to improve the prediction of adverse cardiac events in patients with HCM using machine learning methods., Methods: We applied modern machine learning methods to a prospective cohort of adults with HCM. The outcome was a composite of death due to heart failure, heart transplant, and sudden death. As the reference model, we constructed logistic regression model using known predictors. We determined 20 predictive characteristics based on random forest classification and a priori knowledge, and developed 4 machine learning models. Results Of 183 patients in the cohort, the mean age was 53 (SD = 17) years and 45% were female. During the median follow-up of 2.2 years (interquartile range, 0.6-3.8), 33 subjects (18%) developed an outcome event, the majority of which (85%) was heart transplant. The predictive accuracy of the reference model was 73% (sensitivity 76%, specificity 72%) while that of the machine learning model was 85% (e.g., sensitivity 88%, specificity 84% with elastic net regression). All 4 machine learning models significantly outperformed the reference model - e.g., area under the receiver-operating-characteristic curve 0.79 with the reference model vs. 0.93 with elastic net regression (p < 0.001)., Conclusions: Compared with conventional risk stratification, the machine learning models demonstrated a superior ability to predict adverse cardiac events. These modern machine learning methods may enhance identification of high-risk HCM subpopulations., Competing Interests: Declaration of competing interest No author has a relationship with industry to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis (ATTRv) and wild-type transthyretin (ATTRwt)., Background: ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt., Methods: In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv., Results: There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 [95% confidence interval (CI): 0.474 to 1.052]; p = 0.0875) and ATTRv (hazard ratio: 0.690 [95% CI: 0.408 to 1.167]; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p < 0.0001) and ATTRv (79.61 ± 29.83 m; p = 0.008); and Kansas City Cardiomyopathy Questionnaire Overall Summary score in ATTRwt (12.72 ± 2.10; p < 0.0001) and ATTRv (18.18 ± 7.75; p = 0.019)., Conclusions: Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889)., Competing Interests: Funding Support and Author Disclosures Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual anonymized participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information. This study was sponsored by Pfizer. Dr. Rapezzi has received unrestricted research grants and fees for advisory board meetings from Pfizer. Dr. Elliott has received consultancy fees from Pfizer and Alnylam. Dr. Damy has served on a scientific advisory board for Pfizer; has received funding from Pfizer for scientific meeting expenses; and his institution has received grant support from Pfizer. Dr. Nativi-Nicolau’s institution has received funding for clinical trials from Pfizer, Akcea, and Eidos; and has received educational grants from Pfizer. Dr. Nativi-Nicolau has been a consultant for Pfizer, Eidos, Akcea, and Alnylam. Dr. Berk has received consultancy fees from Alnylam Pharmaceutical, Akcea Therapeutics, Intellia Therapeutics, and Corino Therapeutics. Dr. Boman has served on scientific advisory boards for Pfizer; and has received funding for scientific meetings. Mr. Gundapaneni, Drs. Patterson and Sultan are employees of and hold stock options with Pfizer. At the time of this analysis, Dr. Schwartz was an employee of Pfizer; holds stock and stock options with Pfizer, and is now retired. Dr. Maurer has received grant support from the National Institutes of Health (HL HL139671-01, AG R21AG058348, and AG K24AG036778); his institution has received funding for clinical trials from Pfizer, Prothena, Eidos, and Alnylam; and he has received consulting income from Pfizer, GlaxoSmithKline, Eidos, Prothena, Akcea, and Alnylam. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic amyloidosis of the immunoglobulin light-chain (AL) or transthyretin type (ATTR) is a multisystem protein deposition disease that often involves the heart. Delays in diagnosis are very common and can have detrimental consequences on patient outcomes. Because both major types can now be distinguished quickly and treated effectively, clear approaches are required. There have been advances in radioisotope scintigraphy, monoclonal protein testing and mass spectrometry for typing that need coordinated application. We have entered an era in which rapid diagnosis and ready therapy will save lives, therefore we must develop coherent approaches to this multisystem disease. The prognosis for AL has improved significantly with the incorporation of novel agents such as proteasome inhibitors, immunomodulators and monoclonal antibodies against plasma cells. Multiple independent studies have demonstrated the efficacy of these agents in AL, though tolerability can become an issue with dose reductions required in many cases. Median overall survival for patients achieving complete responses after stem cell transplant and consolidation exceeds a decade. The prognosis for ATTR, both age-related wild-type (ATTRwt) and hereditary due to variants of transthyretin (ATTRv), has improved as well due to the availability of the stabilizer tafamidis and the RNA-interference agents patisiran and inotersen. In both AL and ATTR, with elimination or suppression of the pathologic amyloid-forming protein, symptomatic involvement of the heart, kidneys and peripheral nervous system can improve as well. In this review, we present the current state of diagnosing and treating the two major types of systemic amyloidosis, emphasizing the coherent clinical application of the new tools and treatments. Implementation of the approaches we provide will enable rapid identification of amyloid type and rational selection of therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this study was to evaluate the relationship between calorie intake and post-discharge outcomes in hospitalized patients with heart failure (HF)., Background: Malnutrition increases adverse outcomes in HF, and dietary sodium restriction may inadvertently worsen nutritional intake., Methods: In a dietary intervention trial, baseline nutritional intake in HF inpatients was estimated using the Block Food Frequency Questionnaire (FFQ), and the Nutritional Risk Index (NRI) was calculated. Insufficient calorie intake was defined as <90% of metabolic needs, and a 15-point micronutrient deficiency score was created. Adjusted linear, logistic, and negative binomial regression were used to evaluate associations between insufficient calorie intake and quality of life (using the Kansas City Cardiomyopathy Questionnaire Clinical Summary [KCCQ-CS]), readmission risk, and days rehospitalized over 12 weeks., Results: Among 57 participants (70 ± 8 years of age; 31% female; mean body mass index 32 ± 8 kg/m 2 ); median sodium and calorie intake amounts were 2,987 mg/day (interquartile range [IQR]: 2,160 to 3,540 mg/day) and 1,602 kcal/day (IQR: 1,201 to 2,142 kcal/day), respectively; 11% of these patients were screened as malnourished by the NRI. All patients consuming <2,000 mg/day sodium had insufficient calorie intake; this group also more frequently had dietary micronutrient and protein deficiencies. At 12 weeks, patients with insufficient calorie intake had less improvement in the KCCQ-CS score (β = -14.6; 95% confidence interval [CI]: -27.3 to -1.9), higher odds of readmission (odds ratio: 14.5; 95% CI: 2.2 to 94.4), and more days rehospitalized (incident rate ratio: 31.3; 95% CI: 4.3 to 229.3)., Conclusions: Despite a high prevalence for obesity and rare overt malnutrition, insufficient calorie intake was associated with poorer post-discharge quality of life and increased burden of readmission in patients with HF. Inpatient dietary assessment could improve readmission risk stratification and identify patients for nutritional intervention. (Geriatric Out of Hospital Randomized Meal Trial in Heart Failure [GOURMET-HF] NCT02148679)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Although no therapies are approved for light chain (AL) amyloidosis, cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is considered standard of care. Based on outcomes of daratumumab in multiple myeloma (MM), the phase 3 ANDROMEDA study (NCT03201965) is evaluating daratumumab-CyBorD vs CyBorD in newly diagnosed AL amyloidosis. We report results of the 28-patient safety run-in. Patients received subcutaneous daratumumab (DARA SC) weekly in cycles 1 to 2, every 2 weeks in cycles 3 to 6, and every 4 weeks thereafter for up to 2 years. CyBorD was given weekly for 6 cycles. Patients had a median of 2 involved organs (kidney, 68%; cardiac, 61%). Patients received a median of 16 (range, 1-23) treatment cycles. Treatment-emergent adverse events were consistent with DARA SC in MM and CyBorD. Infusion-related reactions occurred in 1 patient (grade 1). No grade 5 treatment-emergent adverse events occurred; 5 patients died, including 3 after transplant. Overall hematologic response rate was 96%, with a complete hematologic response in 15 (54%) patients; at least partial response occurred in 20, 22, and 17 patients at 1, 3, and 6 months, respectively. Renal response occurred in 6 of 16, 7 of 15, and 10 of 15 patients, and cardiac response occurred in 6 of 16, 6 of 13, and 8 of 13 patients at 3, 6, and 12 months, respectively. Hepatic response occurred in 2 of 3 patients at 12 months. Daratumumab-CyBorD was well tolerated, with no new safety concerns versus the intravenous formulation, and demonstrated robust hematologic and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT03201965., (© 2020 by The American Society of Hematology.)

Objectives: This study sought to describe the patterns of heart failure (HF)-exacerbating medications used among older adults hospitalized for HF and to examine determinants of HF-exacerbating medication use., Background: HF-exacerbating medications can potentially contribute to adverse outcomes and could represent an important target for future strategies to improve post-hospitalization outcomes., Methods: Medicare beneficiaries ≥65 years of age with an adjudicated HF hospitalization between 2003 and 2014 were derived from the geographically diverse REGARDS (Reasons for Geographic and Racial Difference in Stroke) cohort study. Major HF-exacerbating medications, defined as those listed on the 2016 American Heart Association Scientific Statement listing medications that can precipitate or induce HF, were examined. Patterns of prescribing medications at hospital admission and at discharge were examined, as well as changes that occurred between admission and discharge; and a multivariable logistic regression analysis was conducted to identify determinants of harmful prescribing practices following HF hospitalization (defined as either the continuation of an HF-exacerbating medications or an increase in the number of HF-exacerbating medications between hospital admission and discharge)., Results: Among 558 unique individuals, 18% experienced a decrease in the number of HF-exacerbating medications between admission and discharge, 19% remained at the same number, and 12% experienced an increase. Multivariable logistic regression analysis revealed that diabetes (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.18 to 2.75]) and small hospital size (OR: 1.93; 95% CI: 1.18 to 3.16) were the strongest, independently associated determinants of harmful prescribing practices., Conclusions: HF-exacerbating medication regimens are often continued or started following an HF hospitalization. These findings highlight an ongoing need to develop strategies to improve safe prescribing practices in this vulnerable population., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to examine outcomes after left ventricular assist device (LVAD) implantation in older adults (>75 years of age)., Background: An aging heart failure population together with improvements in mechanical circulatory support (MCS) technology have led to increasing LVAD implantations in older adults. However, data presenting age-specific outcomes are limited., Methods: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) who required durable MCS between 2008 and 2017 were included. Patients were stratified by 4 age groups: <55 years of age, 55 to 64 years of age, and >75 years of age. Kaplan-Meier survival estimates were used to assess post-LVAD outcomes, with log-rank testing used to compare groups. Univariate and multivariate cox proportional hazard regression models were used to determine predictors of survival and complications., Results: A total of 20,939 individuals received an LVAD during the study period: 7,743 (37.0%) were <55 years of age, 6,755 (32.3%) were 55 to 64 years of age, 5,418 (25.9%) were 65 to 74 years of age, and 1,023 (4.9%) were ≥75 years of age or older. After multivariate adjustment, adults ≥75 years of age had increased mortality post-LVAD implantation. Elderly patients with LVADs had a higher incidence of gastrointestinal bleeding but lower rates of device thrombosis. Compared to 84.5% of patients <55 years of age who were discharged home, only 46.8% of adults ≥75 years of age were discharged home following implantation (p < 0.001). Use of a RVAD, serum albumin level, and 6-min walk test distances were identified as predictors of outcomes in the oldest cohort., Conclusions: Despite careful selection of older adults for LVAD implantation, age remains a significant predictor of mortality. Higher bleeding and lower clotting risk in elderly patients with LVADs support the use of a less intense antithrombotic regimen in this unique population., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a volumetric measure of left ventricular myocardial shortening. We examined the relationship of MCF, measured by cardiac magnetic resonance imaging (cMRI), to incident cardiovascular (CV) events within the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: Participants (n = 5000, aged 45-84 years) underwent cMRI., Primary Outcome: CVD events (myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease: CHD death, and stroke death)., Secondary Outcomes: CHD and heart failure (HF) events. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for outcomes., Results: There were 299 incident CVD, 188 CHD, and 151 HF events over 10.2 years. The lowest MCF quartile was associated with an increased risk for incident CVD [HR 2.42, CI: 1.58-3.72], CHD [HR 2.32, CI: 1.36-3.96] and HF events [HR 1.99, CI: 1.15-3.44]. In a model adjusted for demographics, CV risk factors, antihypertensive and lipid-lowering medication use, each standard deviation decrease in MCF was associated with incident CVD [HR 1.42, CI: 1.23-1.64], CHD [HR 1.40, CI: 1.17-1.67] and HF [HR 1.58, CI: 1.30-1.94]. In a subgroup analysis of participants with preserved ejection fraction and without left ventricular hypertrophy, the lowest MCF quartile and each standard deviation decrease in MCF was also associated with an increased risk for incident CVD in fully-adjusted analyses., Conclusions: MCF is a novel measure that can be measured using cMRI. In this multi-ethnic cohort, MCF is a measure that can be used to predict incident CVD events., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Amyloidosis is caused by extracellular deposition of abnormal protein fibrils, resulting in destruction of tissue architecture and impairment of organ function. The most common forms of systemic amyloidosis are light-chain and transthyretin-related (ATTR). ATTR can result from an autosomal dominant hereditary transmission of mutated genes in the transthyretin or from a wild-type form of disease (ATTRwt), previously known as senile cardiac amyloidosis. With the aging of the worldwide population, ATTRwt will emerge as the most common type of cardiac amyloidosis that clinicians encounter. Diagnosis of systemic amyloidosis is often delayed, either because of the false assumption that it is a rare disease, or because of misdiagnosis as a result of mistaking it with other conditions. Clinicians must integrate clinical clues from history, physical examination, and common diagnostic tests to raise suspicion for ATTRwt. The historical gold standard for diagnosis of cardiac amyloid is endomyocardial biopsy analysis with pathological distinction of precursor protein type, but this method often results in delayed diagnosis because of the limited availability of expertise to perform and interpret the endomyocardial biopsy specimen. Emerging noninvasive imaging modalities provide easier, accurate screening for ATTRwt. These modalities include advanced echocardiography, using strain imaging and the myocardial contraction fraction; nuclear scintigraphy, which can differentiate between ATTR and light-chain cardiac amyloid; and cardiac magnetic resonance imaging, using extracellular volume measurement, late gadolinium enhancement, and distinct T1 mapping. These novel approaches reveal insights into the prevalence, clinical course, morphological effects, and prognosis of ATTRwt., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The presence of multimorbidity is known to be related to adverse clinical outcomes. However, its association with mortality in patients undergoing cardiac valve replacement is not known., Methods: Multimorbidity (as a continuous variable) was characterized in adults receiving cardiac valve replacement surgery between 2008 and 2012 within Kaiser Permanente Northern California based on information from health plan electronic health records. Our primary outcome was 3-year all-cause mortality after surgery. We used Cox proportional hazards regression to evaluate the independent association of each additional comorbidity with mortality., Results: Among 3686 eligible patients, mean age was 67.9±13.5years and median comorbidity burden was 3 (IQR: 2). The presence of most individual comorbidities except hypertension and hyperlipidemia did not occur in isolation. The unadjusted annual incidence (per 100 person-years) of death increased with higher comorbidity burden: ≤1: 4.61 (95% CI: 3.29-6.45), 2-3: 13.7 (95% CI: 11.9-15.8), 4-5: 23.6 (95% CI: 20.6-26.9), and ≥6: 43.4(95% CI: 34.6-54.4). Advancing age, diabetes mellitus, cerebrovascular accident, heart failure, lung disease, urgent status and use of aldosterone-receptor antagonists were independently associated with an increased risk of mortality. In multivariable analyses, each additional comorbidity was significantly associated with an increased risk of long-term (adjusted hazard ratio (HR) 1.30, 95% CI: 1.22-1.39) but not short-term mortality (HR 0.92, 95% CI: 0.80-1.07)., Conclusions: Our study demonstrated that multimorbidity in patients undergoing cardiac valve replacement is significantly associated with long-term but not short-term mortality., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The purpose of this study was to provide insight into the potential for left atrium (LA) to aortic mechanical circulatory support as a treatment for patients with heart failure with preserved ejection fraction (HFpEF)., Background: Although HFpEF arises from different etiologies, 1 hallmark of all forms of this syndrome is a small or minimally-dilated left ventricle (LV). Consequently, the use of traditional mechanical circulatory support in end-stage patients has been difficult. In contrast, HFpEF is also characterized by a large LA., Methods: Hemodynamic characteristics of 4 distinct HFpEF phenotypes were characterized from the published data: 1) hypertrophic cardiomyopathies; 2) infiltrative diseases; 3) nonhypertrophic HFpEF; and 4) HFpEF with common cardiovascular comorbidities (e.g., hypertension). Employing a previously-described cardiovascular simulation, the effects of a low-flow, micropump-based LA decompression device were modeled. The effect of sourcing blood from the LV versus the LA was compared., Results: For all HFpEF phenotypes, mechanical circulatory support significantly increased cardiac output, provided a mild increase in blood pressure, and markedly reduced pulmonary and LA pressures. LV sourcing of blood reduced LV end-systolic volume into a range likely to induce suction. With LA sourcing, however, LV end-systolic volume increased compared with baseline. Due to pre-existing LA enlargement, LA volumes remained sufficiently elevated, thus minimizing the risk of suction., Conclusions: This theoretical analysis suggests that a strategy involving pumping blood from the LA to the arterial system may provide a viable option for end-stage HFpEF. Special considerations apply to each of the 4 types of HFpEF phenotypes described. Finally, an HFpEF-specific clinical profile scoring system (such as that of INTERMACS [Interagency Registry for Mechanically Assisted Circulatory Support]) would aid in the selection of patients with the appropriate risk-benefit ratio for implantation of an active pump., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although 1.4 million elderly Americans survive hospitalization involving intensive care annually, many are at risk for early mortality following discharge. No models that predict the likelihood of death after discharge exist explicitly for this population. Therefore, we derived and externally validated a 6-month postdischarge mortality prediction model for elderly ICU survivors., Methods: We derived the model from medical record and claims data for 1,526 consecutive patients aged ≥ 65 years who had their first medical ICU admission in 2006 to 2009 at a tertiary-care hospital and survived to discharge (excluding those patients discharged to hospice). We then validated the model in 1,010 patients from a different tertiary-care hospital., Results: Six-month mortality was 27.3% and 30.2% in the derivation and validation cohorts, respectively. Independent predictors of mortality (in descending order of contribution to the model's predictive power) were a do-not-resuscitate order, older age, burden of comorbidity, admission from or discharge to a skilled-care facility, hospital length of stay, principal diagnoses of sepsis and hematologic malignancy, and male sex. For the derivation and external validation cohorts, the area under the receiver operating characteristic curve was 0.80 (SE, 0.01) and 0.71 (SE, 0.02), respectively, with good calibration for both (P = 0.31 and 0.43)., Conclusions: Clinical variables available at hospital discharge can help predict 6-month mortality for elderly ICU survivors. Variables that capture elements of frailty, disability, the burden of comorbidity, and patient preferences regarding resuscitation during the hospitalization contribute most to this model's predictive power. The model could aid providers in counseling elderly ICU survivors at high risk of death and their families.

Objectives: This study sought to evaluate the impact of frailty in older adults undergoing transcatheter aortic valve replacement (TAVR) for symptomatic aortic stenosis., Background: Frailty status impacts prognosis in older adults with heart disease; however, the impact of frailty on prognosis after TAVR is unknown., Methods: Gait speed, grip strength, serum albumin, and activities of daily living status were collected at baseline and used to derive a frailty score among patients who underwent TAVR procedures at a single large-volume institution. The cohort was dichotomized on the basis of median frailty score into frail and not frail groups. The impact of frailty on procedural outcomes (stroke, bleeding, vascular complications, acute kidney injury, and mortality at 30 days) and 1-year mortality was evaluated., Results: Frailty status was assessed in 159 subjects who underwent TAVR (age 86 ± 8 years, Society of Thoracic Surgery Risk Score 12 ± 4). Baseline frailty score was not associated with conventionally ascertained clinical variables or Society of Thoracic Surgery score. Although high frailty score was associated with a longer post-TAVR hospital stay when compared with lower frailty score (9 ± 6 days vs. 6 ± 5 days, respectively, p = 0.004), there were no significant crude associations between frailty status and procedural outcomes, suggesting adequacy of the standard selection process for identifying patients at risk for periprocedural complications after TAVR. Frailty status was independently associated with increased 1-year mortality (hazard ratio: 3.5, 95% confidence interval: 1.4 to 8.5, p = 0.007) after TAVR., Conclusions: Frailty was not associated with increased periprocedural complications in patients selected as candidates to undergo TAVR but was associated with increased 1-year mortality after TAVR. Further studies will evaluate the independent value of this frailty composite in older adults with aortic stenosis., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Orthostatic hypotension (OH) is traditionally defined as a decline in systolic or diastolic blood pressure of >20 or >10 mm Hg, respectively, after 1 or 3 minutes of upright posture. OH is common in the elderly, but has not been consistently demonstrated to be an independent risk factor for falls in nursing home residents. Previous studies have used the standard definition of OH in assessing fall risk. No study has sought to determine if the timing of postural changes in blood pressure adds prognostic value; if changes in systolic, diastolic, or mean blood pressure are equivalent in predicting subsequent falls; and what degree of decline in blood pressure has the best predictive value., Objective: We sought to define the timing and degree of orthostatic changes in blood pressure in a cohort of elderly nursing home residents during active standing and to explore the relationship to subsequent falls to test the hypothesis that orthostatic changes in blood pressure with noninvasive beat-to-beat technology would predict falls in nursing home residents better than the standard definition of OH., Methods: One hundred eleven elderly (88 +/- 7 years) residents of a long-term care facility had measurement of orthostatic blood pressure changes during active standing for up to 3 minutes with a real-time continuous, noninvasive beat-to-beat blood pressure device. Falls were determined prospectively over a median follow-up period of 270 days (range, 8-657 days). The degree and timing of declines in systolic, diastolic, or mean blood pressure and their association with subsequent falls was determined using a time-to-event analysis., Results: Forty-six subjects (41%) fell. The standard definition of OH was not predictive of subsequent falls (hazard ratio 1.03 at 1 minute and 1.32 at 3 minutes, P = not significant). Other measures of orthostatic blood pressure changes were also not associated with a significant increase in risk for subsequent falls, including declines in blood pressure within the first minute of standing., Conclusion: The standard definition of OH was not an independent predictor of falls in frail nursing home residents. A one-time measure for the presence of postural hypotension using beat-to-beat tonometry was not predictive of fall risk. The timing and degree of orthostatic changes in blood pressure does not significantly enhance risk prediction for falls.