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

162 results found

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withdrawal in a single arm crossover phase.Results: The mean heart rate (standard deviation) for those who had therapy withdrawn and did not relapse was 64.6bpm (10.7) at baseline and 74.7bpm (10.4) at follow-up compared to 68.3bpm (11.3) and 86.1bpm (11.8) for those who relapsed. After adjusting for baseline heart rate, patients who had therapy withdrawn and relapsed had a 10.4bpm (95% confidence intervals [CIs] 4.0-16.8) greater rise in heart rate compared to patients who had therapy withdrawn and did not relapse (p=0.002).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

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

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

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

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

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

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

Halliday BP, Wassall R, Lota A, Khalique Z, Gregson J, Newsome S, Jackson R, Rahneva T, Wage R, Smith G, Venneri L, Tayal U, Auger D, Midwinter W, Whiffin N, Rajani R, Dungu J, Cook S, Ware J, Baksi J, Pennell D, Rosen S, Cowie M, Cleland J, Prasad Set al., 2019, Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial, The Lancet, Vol: 393, Pages: 61-73, ISSN: 0140-6736

BackgroundPatients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown.MethodsWe did an open-label, pilot, randomised trial to examine the effect of phased withdrawal of heart failure medications in patients with previous dilated cardiomyopathy who were now asymptomatic, whose left ventricular ejection fraction (LVEF) had improved from less than 40% to 50% or greater, whose left ventricular end-diastolic volume (LVEDV) had normalised, and who had an N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentration less than 250 ng/L. Patients were recruited from a network of hospitals in the UK, assessed at one centre (Royal Brompton and Harefield NHS Foundation Trust, London, UK), and randomly assigned (1:1) to phased withdrawal or continuation of treatment. After 6 months, patients in the continued treatment group had treatment withdrawn by the same method. The primary endpoint was a relapse of dilated cardiomyopathy within 6 months, defined by a reduction in LVEF of more than 10% and to less than 50%, an increase in LVEDV by more than 10% and to higher than the normal range, a two-fold rise in NT-pro-BNP concentration and to more than 400 ng/L, or clinical evidence of heart failure, at which point treatments were re-established. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02859311.FindingsBetween April 21, 2016, and Aug 22, 2017, 51 patients were enrolled. 25 were randomly assigned to the treatment withdrawal group and 26 to continue treatment. Over the first 6 months, 11 (44%) patients randomly assigned to treatment withdrawal met the primary endpoint of relapse compared with none of those assigned to continue treatment (Kaplan-Meier estimate of event rate 45·7% [95% CI 28·5–67·2]; p=0·0001). After 6 months, 25 (96%) of 2

Journal article

Halliday BP, Wassail R, Lota AS, Khalique Z, Gregson J, Newsome S, Jackson R, Tayal T, Wage R, Smith G, Venneri L, Tayal U, Auger D, Midwinter W, Whiffin N, Rajani R, Dungu JN, Pantazis A, Cook SA, Ware JS, Baksi AJ, Pennell DJ, Rosen SD, Cowie MR, Cleland JGF, Prasad SKet al., 2019, Brief Comment Video to the Recommended Article of the Month, REVISTA PORTUGUESA DE CARDIOLOGIA, Vol: 38, Pages: 71-71, ISSN: 0870-2551

Journal article

Halliday BP, Wassall R, Lota A, Khalique Z, Gregson J, Pennell DJ, Rosen SD, Cowie MR, Cleland JG, Prasad SKet al., 2018, Withdrawal of Pharmacological Heart Failure Therapy in Recovered Dilated Cardiomyopathy - A Randomised Controlled Trial (TRED-HF), Scientific Sessions of the American-Heart-Association (AHA) / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E761-E761, ISSN: 0009-7322

Conference paper

Pareek N, Cevallos J, Moliner P, Shah M, Tan LL, Chambers V, Baksi AJ, Khattar RS, Sharma R, Rosen SD, Lyon ARet al., 2018, Activity and outcomes of a cardio-oncology service in the United Kingdom - a five-year experience, European Journal of Heart Failure, Vol: 20, Pages: 1721-1731, ISSN: 1388-9842

AIMS: Cardio-oncology clinics optimise the cardiovascular status of cancer patients but there is a limited description of their structure, case mix, activity and results. The purpose of this paper is to describe the activity and outcomes of a cardio-oncology service, particularly with respect to supporting optimal cancer treatment and survival. METHODS AND RESULTS: We prospectively studied patients referred to our service from February 2011 to February 2016. New York Heart Association (NYHA) class and parameters of cardiac function were measured at baseline and after optimisation by our service. Up-titration of cardiac treatment, continuation of cancer therapy and mortality were used as outcome measures. Of the 535 patients (55.8% females) referred, rates of cardiotoxicity for anthracyclines, anti-HER2 agents and tyrosine kinase inhibitors were 75.8%, 69.8% and 62.1%, respectively. Patients with left ventricular systolic dysfunction (LVSD) (n =128) were younger, had higher rates of hypertension and previous exposure to chemotherapy/radiotherapy (P < 0.001). At a median follow-up of 360 days, 93.8% of the patients with LVSD showed improvement in left ventricular ejection fraction (45% pre vs. 53% post; P < 0.001) and NYHA class (NYHA III-IV in 22% pre vs. 10% post; P = 0.01). All patients with normal left ventricular ejection fraction and biochemical or functional myocardial toxicity and 88% of patients with LVSD were deemed fit for continuation of cancer therapy after cardiovascular optimisation. CONCLUSIONS: Through the establishment of a cardio-oncology service, it is feasible to achieve high rates of cardiac optimisation and cancer treatment continuation.

Journal article

Ferreira-Martins J, Tan L, Venneri L, Cevallos J, Pareek N, Ciburiene E, Moliner-Borja P, Chambers V, Khattar RS, Baksi AJ, Rosen SD, Lyon ARet al., 2018, Cardiovascular risk profiles in cardio-oncology - time matters, Heart Failure Association of ESC, Publisher: WILEY, Pages: 38-39, ISSN: 1388-9842

Conference paper

Patel HC, Hayward C, Wardle AJ, Middleton L, Lyon AR, Di Mario C, Salukhe TV, Sutton R, Rosen SDet al., 2018, The effect of head-up tilt upon markers of heart rate variability in patients with atrial fibrillation, Annals of Noninvasive Electrocardiology, Vol: 23, ISSN: 1082-720X

BACKGROUND: Heart rate variability (HRV) analysis is uncommonly undertaken in patients with atrial fibrillation (AF) due to an assumption that ventricular response is random. We sought to determine the effects of head-up tilt (HUT), a stimulus known to elicit an autonomic response, on HRV in patients with AF; we contrasted the findings with those of patients in sinus rhythm (SR). METHODS: Consecutive, clinically indicated tilt tests were examined for 207 patients: 176 in SR, 31 in AF. Patients in AF were compared to an age-matched SR cohort (n = 69). Five minute windows immediately before and after tilting were analyzed using time-domain, frequency-domain and nonlinear HRV parameters. Continuous, noninvasive assessment of blood pressure, heart rate and stroke volume were available in the majority of patients. RESULTS: There were significant differences at baseline in all HRV parameters between AF and age matched SR. HUT produced significant hemodynamic changes, regardless of cardiac rhythm. Coincident with these hemodynamic changes, patients in AF had a significant increase in median [quartile 1, 2] DFA-α2 (+0.14 [-0.03, 0.32], p < .005) and a decrease in sample entropy (-0.17 [-0.50, -0.01], p < .005). CONCLUSION: In the SR cohort, increasing age was associated with fewer HRV changes on tilting. Patients with AF had blunted HRV responses to tilting, mirroring those seen in an age matched SR group. It is feasible to measure HRV in patients with AF and the changes observed on HUT are comparable to those seen in patients in sinus rhythm.

Journal article

Doehner W, Ural D, Haeusler KG, Čelutkienė J, Bestetti R, Cavusoglu Y, Peña-Duque MA, Glavas D, Iacoviello M, Laufs U, Alvear RM, Mbakwem A, Piepoli MF, Rosen SD, Tsivgoulis G, Vitale C, Yilmaz MB, Anker SD, Filippatos G, Seferovic P, Coats AJS, Ruschitzka Fet al., 2017, Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association., European Journal of Heart Failure, ISSN: 1388-9842

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture.

Journal article

Bruengger AAS, Wechalekar K, Khattar R, Rosen SD, Robertus JL, Chau I, Morganstein D, Rosendahl U, Lyon A, Mohiaddin Ret al., 2017, Histologically proven myocardial carcinoid metastases: the value of multimodality imaging, Canadian Journal of Cardiology, Vol: 33, Pages: 1336.e9-1336.e12, ISSN: 1916-7075

We present a case of a patient with intramyocardial metastases from a carcinoid tumor. These findings were detected using cardiovascular magnetic resonance imaging, with functional metabolic activity analyzed using nuclear imaging and confirmed by histologic findings at surgical biopsy. This case highlights the value of cardiovascular magnetic resonance imaging and the importance of multimodality imaging.

Journal article

Venneri L, Danylenko O, Calicchio F, Manivarmane R, Tadic M, Baksi J, Rosen SD, Senior R, Lyon AR, Khattar RSet al., 2017, Cancer and myocardial dysfunction: observations from myocardial strain imaging in a dedicated cardio-oncology clinic, European Society of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 1292-1293, ISSN: 0195-668X

Conference paper

Halliday BP, Gulati A, Ali A, Guha K, Newsome S, Arzanauskaite M, Vassiliou VS, Lota A, izgi C, Tayal U, Khalique Z, stirrat C, auger D, pareek N, ismail TF, rosen SD, vazir A, alpendurada F, gregson J, frenneaux MP, cowie MR, cleland JG, cook SA, pennell DJ, Pennell DJ, prasad SKet al., 2017, Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction, Circulation, Vol: 135, Pages: 2106-2115, ISSN: 0009-7322

Background—Current guidelines only recommend the use of an implantable cardioverter defibrillator (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF)<35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70-80% of such patients have a LVEF>35%. Patients with a LVEF>35% also have low competing risks of death from non-sudden causes. Therefore, those at high-risk of SCD may gain longevity from successful ICD therapy. We investigated whether late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) identified patients with DCM without severe LV systolic dysfunction at high-risk of SCD.Methods—We prospectively investigated the association between mid-wall late gadolinium enhancement (LGE) and the pre-specified primary composite outcome of SCD or aborted SCD amongst consecutive referrals with DCM and a LVEF≥40% to our center between January 2000 and December 2011, who did not have a pre-existing indication for ICD implantation.Results—Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9-21.8; p<0.0001). Nine patients (8.9%) with LGE compared to 6 (2.0%) without (HR 4.9; 95% CI 1.8-13.5; p=0.002) died suddenly, whilst 10 patients (9.9%) with LGE compared to 1 patient (0.3%) without (HR 34.8; 95% CI 4.6-266.6; p<0.001) had aborted SCD. Following adjustment, LGE predicted the composite end-point (HR 9.3; 95% CI 3.9-22.3; p<0.0001), SCD (HR 4.8; 95% CI 1.7-13.8; p=0.003) and aborted SCD (HR 35.9; 95% CI 4.8-271.4; p<0.001). Estimated hazard ratios for the primary end-point for patients with a LGE extent of 0-2.5%, 2.5-5% and >5% compared to those without LGE were 10.6 (95%CI 3.9-29.4), 4.9 (9

Journal article

Chambers VJ, Pryse-Hawkins H, Fallon L, Sharma RK, Rosen SD, Lyon ARet al., 2017, An end of year review of patients with left ventricular systolic dysfunction secondary to cardiotoxic cancer therapy in a cardiac tertiary centre, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 19, Pages: 308-309, ISSN: 1388-9842

Journal article

Vivekanandan S, Landau DB, Counsell N, Warren DR, Khwanda A, Rosen SD, Parsons E, Ngai Y, Farrelly L, Hughes L, Hawkins MA, Fenwick JDet al., 2017, The Impact of Cardiac Radiation Dosimetry on Survival After Radiation Therapy for Non-Small Cell Lung Cancer, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, Vol: 99, Pages: 51-60, ISSN: 0360-3016

PurposeThe heart receives high radiation doses during radiation therapy of advanced-stage lung cancer. We have explored associations between overall survival, cardiac radiation doses, and electrocardiographic (ECG) changes in patients treated in IDEAL-CRT, a trial of isotoxically escalated concurrent chemoradiation delivering tumor doses of 63 to 73 Gy.Methods and MaterialsDosimetric and survival data were analyzed for 78 patients. The whole heart, pericardium, AV node, and walls of left and right atria (LA/RA-Wall) and ventricles (LV/RV-Wall) were outlined on radiation therapy planning scans, and differential dose-volume histograms (dDVHs) were calculated. For each structure, dDVHs were approximated using the average dDVH and the 10 highest-ranked structure-specific principal components (PCs). ECGs at baseline and 6 months after radiation therapy were analyzed for 53 patients, dichotomizing patients according to presence or absence of “any ECG change” (conduction or ischemic/pericarditis-like change). All-cause death rate (DR) was analyzed from the start of treatment using Cox regression.Results38% of patients had ECG changes at 6 months. On univariable analysis, higher scores for LA-Wall-PC6, Heart-PC6, “any ECG change,” and larger planning target volume (PTV) were significantly associated with higher DR (P=.003, .009, .029, and .037, respectively). Heart-PC6 and LA-Wall-PC6 represent larger volumes of whole heart and left atrial wall receiving 63 to 69 Gy. Cardiac doses ≥63 Gy were concentrated in the LA-Wall, and consequently Heart-PC6 was highly correlated with LA-Wall-PC6. “Any ECG change,” LA-Wall-PC6 scores, and PTV size were retained in the multivariable model.ConclusionsWe found associations between higher DR and conduction or ischemic/pericarditis-like changes on ECG at 6 months, and between higher DR and higher Heart-PC6 or LA-Wall-PC6 scores, which are closely related to heart or left atrial wall volumes receiving

Journal article

Patel HC, Hayward C, Keegan J, Gatehouse PD, Rajani R, Khattar RS, Mohiaddin RH, Rosen SD, Lyon AR, Di Mario Cet al., 2017, Effects of renal denervation on vascular remodelling in patients with heart failure and preserved ejection fraction: A randomised control trial, JRSM Cardiovascular Disease, Vol: 6, ISSN: 2048-0040

Objective:To assess the effect of renal denervation (RDT) on micro- and macro-vascular function in patients with heartfailure with preserved ejection fraction (HFpEF).Design:A prospective, randomised, open-controlled trial with blinded end-point analysis.Setting:A single-centre London teaching hospital.Participants:Twenty-five patients with HFpEF who were recruited into the RDT-PEF trial.Main outcome measures:Macro-vascular: 24-h ambulatory pulse pressure, aorta distensibilty (from cardiac magneticresonance imaging (CMR), aorta pulse wave velocity (CMR), augmentation index (peripheral tonometry) and renal arteryblood flow indices (renal MR). Micro-vascular: endothelial function (peripheral tonometry) and urine microalbuminuria.Results:At baseline, 15 patients were normotensive, 9 were hypertensive and 1 was hypotensive. RDT did not lowerany of the blood pressure indices. Though there was evidence of abnormal vascular function at rest, RDT did not affectthese at 3 or 12 months follow-up.Conclusions:RDT did not improve markers of macro- and micro-vascular function.

Journal article

Rosen SD, 2017, Iatrogenic heart failure, Oxford Textbook of Heart Failure, Editors: Clark, McDonagh, Publisher: Oxford University Press

Book chapter

Gilbert DC, Duong T, Kynaston HG, Alhasso AA, Cafferty FH, Rosen SD, Kanaga-Sundaram S, Dixit S, Laniado M, Madaan S, Collins G, Pope A, Welland A, Nankivell M, Wassersug R, Parmar MK, Langley RE, Abel PDet al., 2016, Quality of life outcomes from the PATCH trial evaluating LHRH agonists versus transdermal oestradiol for androgen suppression in advanced prostate cancer, BJU International, Vol: 119, Pages: 667-675, ISSN: 1464-4096

OBJECTIVES: To compare quality of life (QoL) outcomes at 6 months between men with advanced prostate cancer (PCa) receiving either transdermal oestradiol (tE2) or LHRH agonists (LHRHa) for androgen deprivation therapy (ADT). PATIENTS AND METHODS: Men with locally advanced or metastatic PCa participating in an ongoing randomised, multi-centre UK trial comparing tE2 versus LHRHa for ADT were enrolled into a QoL sub-study. tE2 was delivered via 3 or 4 transcutaneous patches containing 100mcg of oestradiol/24 hours. LHRHa was administered as per local practice. Patients completed questionnaires based on EORTC QLQ-C30 with prostate-specific module QLQ PR25. The primary outcome measure was global QoL score at 6 months, compared between randomised arms. RESULTS: 727 men were enrolled between August 2007 and 5 October 2015 (412 tE2, 315 LHRHa) with QoL questionnaires completed at both baseline and 6 months. Baseline clinical characteristics were similar between arms: median age 74 years (interquartile range [IQR] 68-79), median PSA 44 ng/ml (IQR 19-119), and 40% (294/727) had metastatic disease. At 6 months, patients on tE2 reported higher global QoL than LHRHa (mean difference +4.2, 95% CI 1.2 to 7.1, p=0.006), less fatigue and improved physical function. Men in the tE2 arm were less likely to experience hot flushes (8% vs 46%), and report a lack of sexual interest (59% vs 74%) and sexual activity, but had higher rates of significant gynecomastia (37% vs 5%). The higher incidence of hot flushes among LHRHa patients appear to account for both the reduced global QoL and increased fatigue in the LHRHa arm compared to tE2 arm. CONCLUSION: Patients receiving tE2 for ADT had better 6-month self-reported QoL outcomes compared to those on LHRHa, but increased likelihood of gynecomastia. The ongoing trial will evaluate clinical efficacy, and longer term QoL. These findings are also potentially relevant for short-term neoadjuvant ADT. This article is protected by copyright. All righ

Journal article

Patel HC, Rosen SD, Hayward C, Vassiliou V, Smith GC, Wage RR, Bailey J, Rajani R, Lindsay AC, Pennell DJ, Underwood SR, Prasad SK, Mohiaddin R, Gibbs JSR, Lyon AR, Di Mario Cet al., 2016, Renal denervation in heart failure with preserved ejection fraction (RDF-PEF): a randomised controlled trial, European Journal of Heart Failure, Vol: 18, Pages: 703-712, ISSN: 1879-0844

AimHeart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RD) might be helpful and there are no data currently in humans with HFpEF.Methods and ResultsIn this single-centre, randomised, open-controlled study we included 25 patients with HFpEF (preserved left ventricular (LV) ejection fraction, left atrial (LA) dilatation or LV hypertrophy and raised B-type natriuretic peptide (BNP) or echocardiographic assessment of filling pressures). Patients were randomised (2:1) to RD with the Symplicity™ catheter or continuing medical therapy. The primary success criterion was not met in that there were no differences between groups at 12 months for Minnesota Living with Heart Failure Questionnaire score, peak oxygen uptake (VO2) on exercise, BNP, E/e’, LA volume index or LV mass index. A greater proportion of patients improved at three months in the RD group with respect to VO2 peak (56% vs 13%, P=0.025) and E/e’ (31% vs 13%, P=0.04). Change in estimated glomerular filtration rate was comparable between groups. Two patients required plain balloon angioplasty during the RD procedure to treat renal artery wall oedema.ConclusionThis study was terminated early due to difficulties in recruitment and was underpowered to detect whether RD improved the endpoints of: quality of life, exercise function, biomarkers and left heart remodelling. The procedure was safe in patients with HFpEF though two patients did require intra-procedure renal artery dilatation.

Journal article

Vassiliou VS, Patel HC, Rosen SD, Auger D, Hayward C, Alpendurada F, Lyon AR, Pennell DJ, Di Mario C, Prasad SKet al., 2016, Left atrial dilation in patients with heart failure and preserved ejection fraction: Insights from cardiovascular magnetic resonance, International Journal of Cardiology, Vol: 210, Pages: 158-160, ISSN: 1874-1754

Journal article

Patel HC, Moser JB, Otero S, Hayward C, Rosen SD, Lyon AR, Mohiaddin R, Di Mario C, Padley Set al., 2015, The proximity of abdominal structures to the renal artery: a study to assess the potential risks of renal denervation, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 657-658, ISSN: 0195-668X

Conference paper

Patel HC, Hayward C, Patel K, Rosen SD, Lyon AR, Di Mario C, Ahsan SYet al., 2015, The changing landscape of oral anti-arrhythmic prescriptions for atrial fibrillation in England: 1998-2014, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1068-1068, ISSN: 0195-668X

Conference paper

Venneri L, Calicchio F, Manivarmane R, Baksi AJ, Rosen SD, Senior R, Lyon AR, Khattar RSet al., 2015, Impaired myocardial function despite normal ejection fraction in patients on current cancer drug therapies, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 150-150, ISSN: 0195-668X

Conference paper

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