Imperial College London

Professor Stuart D Rosen

Faculty of MedicineNational Heart & Lung Institute

Professor of Practice (Cardiology)
 
 
 
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Contact

 

+44 (0)20 8967 5359stuart.rosen Website

 
 
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Location

 

Ealing HospitalEaling Hospital

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Summary

 

Publications

Publication Type
Year
to

227 results found

Nazir MS, Okafor J, Murphy T, Andres MS, Ramalingham S, Rosen SD, Chiribiri A, Plein S, Prasad S, Mohiaddin R, Pennell DJ, Baksi AJ, Khattar R, Lyon ARet al., 2024, Echocardiography versus Cardiac MRI for Measurement of Left Ventricular Ejection Fraction in Individuals with Cancer and Suspected Cardiotoxicity., Radiol Cardiothorac Imaging, Vol: 6

Purpose To compare left ventricular ejection fraction (LVEF) measured with echocardiography and cardiac MRI in individuals with cancer and suspected cardiotoxicity and assess the potential effect on downstream clinical decision-making. Materials and Methods In this prospective, single-center observational cohort study, participants underwent same-day two-dimensional (2D) echocardiography and cardiac MRI between 2011 and 2021. Participants with suboptimal image quality were excluded. A subset of 74 participants also underwent three-dimensional (3D) echocardiography. The agreement of LVEF derived from each modality was assessed using Bland-Altman analysis and at relevant thresholds for cardiotoxicity. Results A total of 745 participants (mean age, 60 years ± 5 [SD]; 460 [61.7%] female participants) underwent same-day echocardiography and cardiac MRI. According to Bland-Altman analysis, the mean bias was -3.7% ± 7.6 (95% limits of agreement [LOA]: -18.5% to 11.1%) for 2D echocardiography versus cardiac MRI. In 74 participants who underwent cardiac MRI, 3D echocardiography, and 2D echocardiography, the mean LVEFs were 60.0% ± 10.4, 58.4% ± 9.4, and 57.2% ± 8.9, respectively (P < .001). At the 50% LVEF threshold for detection of cardiotoxicity, there was disagreement for 9.3% of participants with 2D echocardiography and cardiac MRI. Agreement was better with 3D echocardiography and cardiac MRI (mean bias, -1.6% ± 6.3 [95% LOA: -13.9% to 10.7%]) compared with 2D echocardiography and cardiac MRI (mean bias, -2.8% ± 6.3 [95% LOA: -15.2% to 9.6%]; P = .016). Conclusion Two-dimensional echocardiography had variations of ±15% for LVEF measurement compared with cardiac MRI in participants with cancer and led to misclassification of approximately 10% of participants for cardiotoxicity detection. Three-dimensional echocardiography had better agreement with cardiac MRI and should be used as first-line imaging. Keywords: Ec

Journal article

Nazir MS, Okafor J, Murphy T, Andres MS, Ramalingham S, Rosen SD, Chiribiri A, Plein S, Prasad S, Mohiaddin R, Pennell DJ, Baksi AJ, Khattar R, Lyon ARet al., 2024, Erratum for: Echocardiography versus Cardiac MRI for Measurement of Left Ventricular Ejection Fraction in Individuals with Cancer and Suspected Cardiotoxicity., Radiol Cardiothorac Imaging, Vol: 6

Journal article

Gilbert DC, Nankivell M, Rush H, Clarke NW, Mangar S, Al-Hasso A, Rosen S, Kockelbergh R, Sundaram SK, Dixit S, Laniado M, McPhail N, Shaheen A, Brown S, Gale J, Deighan J, Marshall J, Duong T, Macnair A, Griffiths A, Amos CL, Sydes MR, James ND, Parmar MKB, Langley REet al., 2024, A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design., Clin Oncol (R Coll Radiol), Vol: 36, Pages: e11-e19

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort

Journal article

Talukder S, Ghose A, Chakraborty T, Olsson-Brown A, Ramalingam S, Rosen SD, Young K, Lyon AR, Ghosh AKet al., 2023, Evolving cardiac biomarkers for immune checkpoint inhibitor related myocarditis in cancer patients., Int J Cardiol Heart Vasc, Vol: 49, ISSN: 2352-9067

Journal article

Nazir MS, Murphy T, Poku N, Wheen P, Nowbar AN, Andres MS, Ramalingam S, Rosen SD, Nicol E, Lyon ARet al., 2023, Clinical Utility and Prognostic Value of Coronary Computed Tomography Angiography in Patients With Cancer., Am J Cardiol, Vol: 207, Pages: 448-454

There is growing interest in the role of coronary computed tomography angiography (CTA) in cardio-oncology. However, there is a paucity of real-world experience and outcome data for patients with cancer. This study sought to determine the clinical utility and prognostic value of coronary CTA in patients with cancer. In this prospective, single-center study, we recruited patients with cancer who underwent coronary CTA. Coronary artery disease (CAD) extent was classified as normal, nonobstructive (1% to 49% stenosis), and potentially obstructive (≥50% stenosis). Patients were followed up for a median of 9 months (interquartile range 3 to 30 months) for cancer-related deaths and major adverse cardiovascular events (MACEs) defined as nonfatal myocardial infarction, urgent unplanned revascularization, or cardiovascular death. The mean age of patients (n = 113) was 61 ± 12 years, and 68 were female (60%). The most common underlying cancers were breast (29%) and lymphoma (13%). A total of 25 patients had potentially obstructive CAD, most commonly of the left anterior descending artery. After coronary CTA, 88% statin-naive patients with potentially obstructive CAD were initiated on statin therapy. A total of 28/32 patients who were taking fluoropyrimidine chemotherapy (5-fluorouracil or capecitabine) continued therapy, of whom none had MACEs. Overall, there were no episodes of MACEs in this cohort and 11% had cancer-related deaths. Coronary CTA has an important role in the clinical decision-making in patients with cancer to detect CAD, initiate primary preventative therapy, and guide coronary revascularization. No MACEs occurred. Using this coronary CTA-guided approach, preventative therapy was initiated, and most patients continued prognostically important cancer therapy.

Journal article

Critchley HD, Yarovova E, Howell S, Rosen SDet al., 2023, Appreciating the links between heart failure and depression, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, ISSN: 1460-2725

Journal article

Anker MS, Potthoff SK, Lena A, Porthun J, Hadzibegovic S, Evertz R, Denecke C, Froehlich A-K, Sonntag F, Regitz-Zagrosek V, Rosen SD, Lyon AR, Luescher TF, Spertus JA, Anker SD, Karakas M, Bullinger L, Keller U, Landmesser U, Butler J, von Haehling Set al., 2023, Cardiovascular health-related quality of life in cancer: a prospective study comparing the ESC HeartQoL and EORTC QLQ-C30 questionnaire, EUROPEAN JOURNAL OF HEART FAILURE, ISSN: 1388-9842

Journal article

Rosen SD, 2023, The heart has its reasons that reason does not know - Neurocardiology continues to advance, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, ISSN: 1460-2725

Journal article

Macnair A, Nankivell M, Murray ML, Rosen SD, Appleyard S, Sydes MR, Forcat S, Welland A, Clarke NW, Mangar S, Kynaston H, Kockelbergh R, Al-Hasso A, Deighan J, Marshall J, Parmar M, Langley RE, Gilbert DCet al., 2023, Healthcare systems data in the context of clinical trials-A comparison of cardiovascular data from a clinical trial dataset with routinely collected data, CONTEMPORARY CLINICAL TRIALS, Vol: 128, ISSN: 1551-7144

Journal article

Lena A, Wilkenshoff U, Hadzibegovic S, Porthun J, Roesnick L, Froehlich A-K, Zeller T, Karakas M, Keller U, Ahn J, Bullinger L, Riess H, Rosen SD, Lyon AR, Luescher TF, Totzeck M, Rassaf T, Burkhoff D, Mehra MR, Bax JJ, Butler J, Edelmann F, Haverkamp W, Anker SD, Packer M, Coats AJS, von Haehling S, Landmesser U, Anker MSet al., 2023, Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 81, Pages: 1569-1586, ISSN: 0735-1097

Journal article

Andres MS, Ramalingam S, Rosen SD, Baksi J, Khattar R, Kirichenko Y, Young K, Yousaf N, Okines A, Huddart R, Harrington K, Furness AJS, Turajlic S, Pickering L, Popat S, Larkin J, Lyon ARet al., 2022, The spectrum of cardiovascular complications related to immune-checkpoint inhibitor treatment Including myocarditis and the new entity of non inflammatory left ventricular dysfunction, CARDIO-ONCOLOGY, Vol: 8

Journal article

Andres M, Murphy TM, Poku N, Nazir S, Ramalingam S, Chambers V, Rosen SD, Lyon ARet al., 2022, Cardio-Oncology: a medical specialty in constant growth and evolution. the 10-year experience of the first cardio-oncology service in the United Kingdom, Publisher: OXFORD UNIV PRESS, Pages: 2564-2564, ISSN: 0195-668X

Conference paper

Stansfeld A, Radia U, Goggin C, Mahalingam P, Benson C, Napolitano A, Jones RL, Rosen SD, Karavasilis Vet al., 2022, Pharmacological strategies to reduce anthracycline-associated cardiotoxicity in cancer patients, EXPERT OPINION ON PHARMACOTHERAPY, Vol: 23, Pages: 1641-1650, ISSN: 1465-6566

Journal article

Nazir MS, Okafor J, Murphy T, Andres MS, Ramalingham S, Rosen SD, Chiribiri A, Plein S, Prasad S, Mohiaddin R, Pennell DJ, Khattar R, Baksi AJ, Lyon ARet al., 2022, LVEF MEASURED WITH SAME DAY ECHOCARDIOGRAPHY AND CMR IN PATIENTS WITH SUSPECTED CARDIOTOXICITY, BSCI/BSCCT Annual Meeting, Publisher: BMJ PUBLISHING GROUP, Pages: A11-A11, ISSN: 1355-6037

Conference paper

Rosen SD, 2022, The Flight of Yonah Swift or Abraham's Pendant, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, ISSN: 1460-2725

Journal article

Battisti NML, Andres MS, Lee KA, Ramalingam S, Nash T, Mappouridou S, Senthivel N, Asavisanu K, Obeid M, Tripodaki E-S, Angelis V, Fleming E, Goode EF, John S, Rosen SD, Allen M, Stanway S, Lyon AR, Ring Aet al., 2021, Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer, BREAST CANCER RESEARCH AND TREATMENT, Vol: 188, Pages: 149-163, ISSN: 0167-6806

Journal article

Halliday B, Vazir A, Owen R, Gregson J, Wassall R, Lota A, Khalique Z, Tayal U, Jones R, Hammersley D, Pantazis A, Baksi A, Rosen S, Pennell D, Cowie M, Cleland J, Prasad Set al., 2021, Heart rate as a marker of relapse during withdrawal of therapy in recovered dilated cardiomyopathy, JACC: Heart Failure, Vol: 9, Pages: 509-517, ISSN: 2213-1779

Objective: To determine the relationship between heart rate and relapse amongst patients in the TRED-HF trial. Background: Understanding markers and mechanisms of relapse amongst patients with recovered dilated cardiomyopathy (DCM) might enable personalised management.Methods: The relationship between serial heart rate measurements and relapse was examined amongst patients TRED-HF, a randomised trial which examined the safety and feasibility of withdrawing heart failure therapy amongst 51 patients with recovered DCM over 6 months. In total, 25 patients were randomised to therapy withdrawal and 26 to continue therapy, of whom 25 subsequently began therapy withdrawal in a single arm crossover phase.Results: The mean heart rate (standard deviation) for those who had therapy withdrawn and did not relapse was 64.6bpm (10.7) at baseline and 74.7bpm (10.4) at follow-up compared to 68.3bpm (11.3) and 86.1bpm (11.8) for those who relapsed. After adjusting for baseline heart rate, patients who had therapy withdrawn and relapsed had a 10.4bpm (95% confidence intervals [CIs] 4.0-16.8) greater rise in heart rate compared to patients who had therapy withdrawn and did not relapse (p=0.002). After adjusting for age, log NT-pro-BNP and LVEF, heart rate (per 10bpm - hazard ratio: 1.65, 95%CI 1.10-2.57, p=0.01) and change in heart rate from baseline (per 10bpm - hazard ratio: 1.70, 95%CI 1.12-2.57, p=0.01) were associated with relapse. The results remained qualitatively the same after adjusting for beta-blocker dose.Conclusion: For patients with DCM and improved LVEF, the rise in heart rate after withdrawing treatment identifies patients who are more likely to relapse. Whether the increase in heart rate is a marker or mediator of relapse requires investigation.

Journal article

Rosen S, Dhillon E, Singh H, 2021, ROLE OF THE DAY CARE UNIT IN THE OPTIMAL MANAGEMENT OF HEART FAILURE PATIENTS, Publisher: BMJ PUBLISHING GROUP, Pages: A114-A114, ISSN: 1355-6037

Conference paper

Sutton R, Fedorowski A, Olshansky B, Gert van Dijk J, Abe H, Brignole M, de Lange F, Kenny RA, Lim PB, Moya A, Rosen SD, Russo V, Stewart JM, Thijs RD, Benditt DGet al., 2021, Tilt testing remains a valuable asset, European Heart Journal, Vol: 42, Pages: 1654-1660, ISSN: 0195-668X

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.

Journal article

Dobson R, Ghosh AK, Ky B, Marwick T, Stout M, Harkness A, Steeds R, Robinson S, Oxborough D, Adlam D, Stanway S, Rana B, Ingram T, Ring L, Rosen S, Plummer C, Manisty C, Harbinson M, Sharma V, Pearce K, Lyon AR, Augustine DXet al., 2021, BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving Anthracyclines and/or Trastuzumab, JACC: CARDIOONCOLOGY, Vol: 3, Pages: 1-16, ISSN: 2666-0873

Journal article

Dobson R, Ghosh AK, Ky B, Marwick T, Stout M, Harkness A, Steeds R, Robinson S, Oxborough D, Adlam D, Stanway S, Rana B, Ingram T, Ring L, Rosen S, Plummer C, Manisty C, Harbinson M, Sharma V, Pearce K, Lyon AR, Augustine DXet al., 2021, British Society for Echocardiography and British Cardio-Oncology Society guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab, ECHO RESEARCH AND PRACTICE, Vol: 8, Pages: G1-G18, ISSN: 2055-0464

Journal article

Langley RE, Gilbert DC, Duong T, Clarke NW, Nankivell M, Rosen SD, Mangar S, Macnair A, Sundaram SK, Laniado ME, Dixit S, Madaan S, Manetta C, Pope A, Scrase CD, Mckay S, Muazzam IA, Collins GN, Worlding J, Williams ST, Paez E, Robinson A, McFarlane J, Deighan J, Marshall J, Forcat S, Weiss M, Kockelbergh R, Alhasso A, Kynaston H, Parmar Met al., 2021, Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme, LANCET, Vol: 397, Pages: 581-591, ISSN: 0140-6736

Journal article

Lyon AR, Dent S, Stanway S, Earl H, Brezden-Masley C, Cohen-Solal A, Tocchetti CG, Moslehi JJ, Groarke JD, Bergler-Klein J, Khoo V, Tan LL, Anker MS, von Haehling S, Maack C, Pudil R, Barac A, Thavendiranathan P, Ky B, Neilan TG, Belenkov Y, Rosen SD, Iakobishvili Z, Sverdlov AL, Hajjar LA, Macedo AVS, Manisty C, Ciardiello F, Farmakis D, de Boer RA, Skouri H, Suter TM, Cardinale D, Witteles RM, Fradley MG, Herrmann J, Cornell RF, Wechelaker A, Mauro MJ, Milojkovic D, de Lavallade H, Ruschitzka F, Coats AJS, Seferovic PM, Chioncel O, Thum T, Bauersachs J, Andres MS, Wright DJ, Lopez-Fernandez T, Plummer C, Lenihan Det al., 2020, Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from theCardio-OncologyStudyGroup of theHeartFailureAssociation of theEuropeanSociety ofCardiology in collaboration with theInternationalCardio-OncologySociety, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 22, Pages: 1945-1960, ISSN: 1388-9842

Journal article

Andres MS, Baksi J, Khattar R, Rosen SD, Lyon ARet al., 2020, The broad spectrum of cardiovascular adverse events related to immune check point inhibitors, European-Society-of-Cardiology (ESC) Congress, Publisher: OXFORD UNIV PRESS, Pages: 3286-3286, ISSN: 0195-668X

Conference paper

Dayer M, MacIver DH, Rosen SD, 2020, The central nervous system and heart failure, FUTURE CARDIOLOGY, Vol: 17, Pages: 363-382, ISSN: 1479-6678

Journal article

Vaishampayan UN, Muzaffar J, Velcheti V, Winer I, Hoimes CJ, Rosen SD, Spreafico A, McDermott DF, Chu QS-C, Dumas O, Gilbert L, Hirte H, Curtis KK, Du Y, Bidollari I, Sun L, Putiri E, Losey HC, Dezube B, Ernstoff MSet al., 2020, ALKS 4230 monotherapy and in combination with pembrolizumab (pembro) in patients (pts) with refractory solid tumours (ARTISTRY-1), ESMO Virtual Congress, Publisher: ELSEVIER, Pages: S708-S709, ISSN: 0923-7534

Conference paper

Hendry BM, Stafford N, Arnold AD, Sangwaiya A, Manglam V, Rosen SD, Arnold Jet al., 2020, Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID-19 patients, PHARMACOLOGY RESEARCH & PERSPECTIVES, Vol: 8, ISSN: 2052-1707

Journal article

Howell S, Yarovova E, Khwanda A, Rosen SDet al., 2019, Cardiovascular effects of psychotic illnesses and antipsychotic therapy, HEART, Vol: 105, Pages: 1852-1859, ISSN: 1355-6037

Journal article

Liew F, Gargoum F, Potter R, Rosen SD, Ward S, Hind M, Polkey MIet al., 2019, Platypnoea-orthodeoxia syndrome: beware of investigations undertaken supine, Thorax, Vol: 74, Pages: 917-919, ISSN: 1468-3296

Platypnoea-orthodeoxia syndrome (POS) is a rare disorder, manifesting as deoxygenation occurring when the patient is in the upright position. Four broad mechanisms for the condition have been described: intracardiac shunts, intrapulmonary shunts, hepatopulmonary syndrome and pulmonary ventilation-perfusion mismatch. Here, we present the first case of POS in a patient with a proven right to left intracardiac shunt occurring in the context of postural hypotension and normal right heart pressures. We highlight the need to carry out investigations in the upright position before discounting intracardiac shunting as a cause for the syndrome. Short-term improvement of the syndrome was obtained with medical management of the patient's orthostatic hypotension and as such suggests a conservative management strategy for similar patients, which may delay the need for invasive procedures to close the anatomical defect.

Journal article

Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nuñez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, Seidman CEet al., 2019, Genetic variants associated with cancer therapy-induced cardiomyopathy, Circulation, Vol: 140, Pages: 31-41, ISSN: 0009-7322

BackgroundCancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and pre-existing cardiovascular disorders. These parametersincompletely account for substantial inter-individual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM.MethodsWe studied 213 CCM patients from three cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped breast cancer adults (n=73) and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including nine pre-specified genes were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas (TCGA) participants(n=2053), healthy volunteers(n=445), and ancestry-matchedreference population. Clinical characteristics and outcomes were assessed, stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice.ResultsCCM was diagnosed 0.4-9 years after chemotherapy; 90% of these patients received anthracyclines. Adult CCM patients had cardiovascular risk factors similar to the U.S. population. Among nine prioritized genes CCM patients had more rare protein-altering variants than comparative cohorts (p≤1.98e-04). Titin-truncating variants (TTNtv) predominated, occurring in 7.5% CCM patients versus 1.1% TCGA participants (p=7.36e-08), 0.7% healthy volunteers (p=3.42e-06), and 0.6% reference population (p=5.87e-14). Adult CCM patients with TTNtv experienced more heart failure and atrial fibrillation (p=0.003)and impaired myocardial recovery (p=0.03) than those without.Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wildtype (p=0.0004 and p<0.002, respectively).ConclusionsUnrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtv, increased the risk for CCM in children and adults, and adverse cardiac events

Journal article

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