Imperial College London

ProfessorSanjayPrasad

Faculty of MedicineNational Heart & Lung Institute

Professor of Cardiomyopathy
 
 
 
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Contact

 

+44 (0)20 7352 8121s.prasad

 
 
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Location

 

CMR UnitRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

411 results found

Elming MB, Boas R, Hammer-Hansen S, Voges I, Nyktari E, Svendsen JH, Pehrson S, Dixen U, Philbert BT, Prasad SK, Kober L, Thune JJet al., 2022, Myocardial fibrosis and ventricular ectopy in patients with non-ischemic systolic heart failure: results from the DANISH trial, INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, ISSN: 1569-5794

Journal article

Hatipoglu S, Mohiaddin RH, Gatehouse P, Alpendurada F, Baksi AJ, Izgi C, Prasad SK, Pennell DJ, Krupickova Set al., 2022, Performance of artificial intelligence for biventricular cardiovascular magnetic resonance volumetric analysis in the clinical setting, INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, ISSN: 1569-5794

Journal article

Anthony C, Imran M, Pouliopoulos J, Emmanuel S, Iliff J, Liu Z, Moffat K, Qiu MR, McLean CA, Stehning C, Puntmann V, Vassiliou V, Ismail TF, Gulati A, Prasad S, Graham RM, McCrohon J, Holloway C, Kotlyar E, Muthiah K, Keogh AM, Hayward CS, Macdonald PS, Jabbour Aet al., 2022, Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation, CIRCULATION, Vol: 145, Pages: 1811-1824, ISSN: 0009-7322

Journal article

Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, Gregson J, Newsome S, Gulati A, Pua CJ, Halliday BP, Lota AS, Buchan RJ, Whiffin N, Kanapeckaite L, Baruah R, Jarman JWE, O'Regan DP, Barton PJR, Ware JS, Pennell DJ, Adriaans BP, Bekkers SCAM, Donovan J, Frenneaux M, Cooper LT, Januzzi JL, Cleland JGF, Cook SA, Deo RC, Heymans SRB, Prasad SKet al., 2022, Precision phenotyping of dilated cardiomyopathy using multidimensional data., Journal of the American College of Cardiology, Vol: 79, Pages: 2219-2232, ISSN: 0735-1097

BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to trad

Journal article

Tayal U, 2022, Exposure to elevated nitrogen dioxide concentrations and cardiac remodelling in patients with dilated cardiomyopathy, Journal of Cardiac Failure, Vol: 28, Pages: 924-934, ISSN: 1071-9164

Rationale: Empirical evidence suggests a strong link between exposure to air pollution and heart failure incidence, hospitalisations and mortality, but the biological basis of this remains unclear. Objective: To determine the relationship between differential air pollution levels and changes in cardiac structure and function in patients with dilated cardiomyopathy. Methods and Results: We undertook a prospective longitudinal observational cohort study of patients in England with dilated cardiomyopathy (enrollment 2009-2015; n=716, 66% male, 85% Caucasian) and conducted cross sectional analysis at the time of study enrollment. Annual average air pollution exposure estimates for nitrogen dioxide (NO2) and particulate matter with diameter ≤ 2.5µm (PM2.5) at enrolment were assigned to each residential postcode (on average 12 households). The relationship between air pollution and cardiac morphology was assessed using linear regression modelling. Greater ambient exposure to NO2 was associated with higher indexed left ventricular mass (4.3 g/m2 increase per interquartile range (IQR) increase in NO2, 95% CI 1.9 to 7.0 g/m2) and lower left ventricular ejection fraction (-1.5% decrease per IQR increase in NO2, 95% CI -2.7 to -0.2%), independent of age, sex, socio-economic status and clinical covariates. The associations were robust to adjustment for smoking status and geographical clustering by postcode area. The effect of air pollution on left ventricular mass was greatest in women. These effects were specific to NO2 exposure. Conclusion: Exposure to air pollution is associated with raised left ventricular mass and lower left ventricular ejection fraction, with the strongest effect in women. Whilst epidemiological associations between air pollution and heart failure have been established and supported by pre-clinical studies, our findings provide novel empirical evidence of cardiac remodelling and exposure to air pollution with important clinical and public health

Journal article

Tsampasian V, Grafton-Clarke C, Ramos AEG, Asimakopoulos G, Garg P, Prasad S, Ring L, McCann GP, Rudd J, Dweck MR, Vassiliou VSet al., 2022, Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis, OPEN HEART, Vol: 9, ISSN: 2053-3624

Journal article

Thornton GD, Musa TA, Rigolli M, Loudon M, Chin C, Pica S, Malley T, Foley JRJ, Vassiliou VS, Davies RH, Captur G, Dobson LE, Moon JC, Dweck MR, Myerson SG, Prasad SK, Greenwood JP, McCann GP, Singh A, Treibel TAet al., 2022, Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement The British Society of Cardiovascular Magnetic Resonance AS700 Study, JAMA CARDIOLOGY, Vol: 7, Pages: 513-520, ISSN: 2380-6583

Journal article

Tayal U, gregson J, Buchan R, Whiffin N, Halliday B, Lota A, Roberts A, Baksi A, Voges I, Jarman J, Baruah R, Frenneaux M, Cleland J, Barton P, Pennell D, Ware J, Cook S, Prasad Set al., 2022, Moderate excess alcohol consumption and adverse cardiac remodelling in dilated cardiomyopathy, Heart, Vol: 108, Pages: 619-625, ISSN: 1355-6037

Objective The effect of moderate excess alcohol consumption is widely debated and has not been well defined in dilated cardiomyopathy (DCM). There is need for a greater evidence base to help advise patients. We sought to evaluate the effect of moderate excess alcohol consumption on cardiovascular structure, function and outcomes in DCM. Methods Prospective longitudinal observational cohort study. Patients with DCM (n=604) were evaluated for a history of moderate excess alcohol consumption (UK government guidelines; >14 units/week for women, >21 units/week for men) at cohort enrollment, had cardiovascular magnetic resonance and were followed up for the composite endpoint of cardiovascular death, heart failure and arrhythmic events. Patients meeting criteria for alcoholic cardiomyopathy were not recruited. ResultsDCM patients with a history of moderate excess alcohol consumption (n=98, 16%) had lower biventricular function and increased chamber dilatation of the left ventricle, right ventricle and left atrium, as well as increased left ventricular hypertrophy compared to patients without moderate alcohol consumption. They were more likely to be male (alcohol excess group– n =92, 94% vs n =306, 61%, p=<0.001). After adjustment for biological sex, moderate excess alcohol was not associated with adverse cardiac structure. There was no difference in mid-wall myocardial fibrosis between groups. Prior moderate excess alcohol consumption did not affect prognosis (HR 1.29, 0.73 to 2.26, p=0.38) during median follow up of 3.9 years. ConclusionDilated cardiomyopathy patients with moderate excess alcohol consumption have adverse cardiac structure and function at presentation but this is largely due to biological sex. Alcohol may contribute to sex-specific phenotypic differences in DCM. These findings help to inform lifestyle discussions for patients with dilated cardiomyopathy.

Journal article

Halliday B, Owen R, Gregson J, Vazir A, Wassall R, Khalique Z, Lota A, Tayal U, Hammersley D, Jones R, Pennell D, Cowie M, Cleland J, Prasad Set al., 2022, Changes in clinical and imaging variables during withdrawal of heart failure therapy in recovered dilated cardiomyopathy, ESC Heart Failure, Vol: 9, ISSN: 2055-5822

Aims: To profile the changes in non-invasive clinical, biochemical and imaging markers during withdrawal of therapy in patients with recovered dilated cardiomyopathy, providing insights into the pathophysiology of relapse.Methods: Clinical, biochemical and imaging data from patients during phased withdrawal of therapy in the randomised or single-arm cross-over phases of TRED-HF were profiled. Clinical variables were measured at each study visit and imaging variables were measured at baseline, 16 weeks and 6 months. Results: Amongst the 49 patients (35% women, mean age 53.6 years [standard deviation 11.6]) who withdrew therapy, 20 relapsed. Increases in mean heart rate (7.6 beats per minute [95% CIs 4.5,10.7]), systolic blood pressure (6.6mmHg [95% CI 2.7,10.5]) and diastolic blood pressure (5.8mmHg [95% CI 3.1,8.5]) were observed within 4-8 weeks of starting to withdraw therapy. A rise in mean LV mass (5.1g/m2 [95%CI 2.8,7.3]) and LV end-diastolic volume (3.9ml/m2 [95% CI 1.1,6.7]) and a reduction in mean LV ejection fraction (-4.2 [95% CI -6.6, -1.8]) were seen by 16 weeks, the earliest imaging follow-up. Plasma NT-pro-BNP fell immediately after withdrawing beta-blockers and only tended to increase 6 months after beginning therapy withdrawal (mean change in log NT-pro-BNP at 6 months: 0.2, 95% CI -0.1,0.4). Conclusion: Changes in plasma NT-pro-BNP are a late feature of relapse, often months after a reduction in LV function. A rise in heart rate and blood pressure are observed soon after withdrawing therapy in recovered dilated cardiomyopathy, typically accompanied or closely followed by early changes in LV structure and function.

Journal article

Leyva F, Zegard A, Okafor O, Foley P, Umar F, Taylor RJ, Marshall H, Stegemann B, Moody W, Steeds RP, Halliday BP, Hammersley DJ, Jones RE, Prasad SK, Qiu Tet al., 2022, Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 79, Pages: 665-678, ISSN: 0735-1097

Journal article

Hammersley D, Buchan R, Lota A, Mach L, Jones R, Halliday B, Tayal U, Meena D, Dehghan A, Tzoulaki I, Baksi A, Pantazis A, Roberts A, Prasad S, Ware Jet al., 2022, Direct and indirect effect of the COVID-19 pandemic on patients with cardiomyopathy, Open Heart, Vol: 9, Pages: 1-9, ISSN: 2053-3624

Objectives: (i) To evaluate the prevalence and hospitalisation rate of COVID-19 infections amongst patients with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) in the Royal Brompton & Harefield Hospital Cardiovascular Research Centre (RBHH CRC) Biobank. (ii) To evaluate the indirect impact of the pandemic on patients with cardiomyopathy through the Heart Hive COVID-19 study. (iii) To assess the impact of the pandemic on national cardiomyopathy-related hospital admissions.Methods: (i) 1,236 patients (703 DCM, 533 HCM) in the RBHH CRC Biobank were assessed for COVID-19 infections and hospitalisations; ii) 207 subjects (131 cardiomyopathy, 76 without heart disease) in the Heart Hive COVID-19 study completed online surveys evaluating physical health, psychological wellbeing, and behavioural adaptations during the pandemic; (iii) 11,447 cardiomyopathy-related hospital admissions across NHS England were studied from NHS Digital Hospital Episode Statistics over 2019-2020. Results: A comparable proportion of patients with cardiomyopathy in the RBHH CRC Biobank had tested positive for COVID-19 compared with the UK population (1.1% vs 1.6%, p=0.14), but a higher proportion of those infected were hospitalised (53.8% vs 16.5%, p=0.002). In the Heart Hive COVID-19 study, more patients with cardiomyopathy felt their physical health had deteriorated due to the pandemic than subjects without heart disease (32.3% vs 13.2%, p=0.004) despite only 4.6% of the cardiomyopathy cohort reporting COVID-19 symptoms. A 17.9% year-on-year reduction in national cardiomyopathy-related hospital admissions was observed in 2020.Conclusion: Patients with cardiomyopathy had similar reported rates of testing positive for COVID-19 to the background population, but those with test-proven infection were hospitalised more frequently. Deterioration in physical health amongst patients could not be explained by COVID-19 symptoms, inferring a significant contribution of the indirect con

Journal article

Jones RE, Karamasis G, Dungu JN, Mohdnazri SR, Al-Janabi F, Hammersley DJ, Prasad SK, Tang KH, Kelly PA, Gedela S, Davies JR, Keeble TRet al., 2022, Stress perfusion cardiovascular magnetic resonance and serial fractional flow reserve assessment of the left anterior descending artery in patients undergoing right coronary artery chronic total occlusion revascularization, CARDIOLOGY JOURNAL, Vol: 29, Pages: 80-87, ISSN: 1897-5593

Journal article

Castiello T, Georgiopoulos G, Finocchiaro G, Claudia M, Gianatti A, Delialis D, Aimo A, Prasad Set al., 2022, COVID-19 and myocarditis: a systematic review and overview of current challenges., Heart Fail Rev, Vol: 27, Pages: 251-261

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19-30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.

Journal article

Balaban G, Halliday BP, Hammersley D, Rinaldi CA, Prasad SK, Bishop MJ, Lamata Pet al., 2021, Left ventricular shape predicts arrhythmic risk in fibrotic dilated cardiomyopathy, EUROPACE, ISSN: 1099-5129

Journal article

Lota AS, Tsao A, Owen R, Halliday BP, Auger D, Vassiliou VS, Tayal U, Almogheer B, Vilches S, Al-Balah A, Patel A, Mouy F, Buchan R, Newsome S, Gregson J, Ware JS, Cook SA, Cleland JGF, Pennell DJ, Prasad SKet al., 2021, Prognostic significance of non-ischaemic patterns of myocardial fibrosis in patients with normal left ventricular volumes and ejection fraction – the FINALIZE study, JACC: Cardiovascular Imaging, Vol: 14, Pages: 2353-2365, ISSN: 1876-7591

Background: Non-ischaemic patterns of late gadolinium enhancement (LGE) with normal left ventricular volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance (CMR) but their prognostic significance, and consequently management, is uncertain. Objectives: To investigate the prognostic significance of LGE in patients without coronary artery disease and with normal range LV volumes and ejection fraction. Methods: Patients with mid-wall/subepicardial LGE and normal LV volumes, wall thickness and ejection fraction on CMR were enrolled and compared to a control group without LGE.57 The primary outcome was actual or aborted sudden cardiac death (SCD). Results: Of 748 patients enrolled, 401 had LGE and 347 did not. Median age was 50 years (IQR 38-61), LV ejection fraction 66% (IQR 62-70) and 287 (38%) were women. Scan indications included chest pain (40%), palpitation (33%) and breathlessness (13%). Nopatient experienced SCD and only one LGE+ patient (0.13%) had an aborted SCD in the 11th follow-up year. Over a median of 4.3years, thirty patients (4.0%) died. All-cause mortality was similar for LGE+/- patients (3.7% vs 4.3%; p=0.71) and was associated with age (H 2.04 per 10-years; 95%CI 1.46-2.79; p<0.001). Twenty-one LGE+ and 4 LGE- patients had an unplanned CV hospitalisation (HR 7.22; 95%CI 4.26-21.17; p<0.0001). Conclusion: There was a low SCD risk during long-term follow-up in patients with LGE but otherwise normal LV volumes and ejection fraction. Mortality was driven by age and not LGE presence, location or extent, although the latter was associated with greater CV hospitalisation for suspected myocarditis and symptomatic ventricular tachycardia.

Journal article

Vassiliou V, Pavlou M, Malley T, Halliday B, Tsampasian V, Raphael C, Tse G, Vieira M, Auger D, Everett R, Chin C, Alpendurada F, Pepper J, Pennell D, Newby D, Jabbour A, Dweck M, Prasad Set al., 2021, A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement, Scientific Reports, Vol: 11, ISSN: 2045-2322

The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care.

Journal article

Papageorgiou V, Jones K, Halliday B, Mindham R, Bruton J, Wassall R, Cleland J, Prasad S, Ward Het al., 2021, A qualitative exploration of participant and investigator perspectives from the TRED-HF trial, ESC Heart Failure, Vol: 8, Pages: 3760-3768, ISSN: 2055-5822

Aim We explored the experiences and motivations of participants and staff who took part in the TRED-HF trial (Therapy withdrawal in REcovered Dilated cardiomyopathy). MethodsWe conducted a qualitative study, using semi-structured interviews, with participants (n=12) and the research team (n=4) from the TRED-HF trial. Interviews were carried out in 2019 and were audio-recorded and transcribed. Data were managed using NVivo and analysed using framework analysis. A patient representative provided guidance on the interpretation of findings and presentation of themes to ensure these remained meaningful, and an accurate representation, to those living with dilated cardiomyopathy.ResultsThree key themes emerged from the data: (1) perception of health; (2) experiences and relationships with healthcare services and researchers; and (3) perception of risk. Study participants held differing perceptions of their health; some did not consider themselves to have a heart condition or disagreed with the medical term ‘heart failure’. Relationships between participants, research staff and clinical management teams influenced participants’ experiences and decision-making during the trial, including following clinical advice. There were differences in participants’ perceptions of risk and their decisions to take heart failure medication after the trial was completed. Although the original TRED-HF trial did not provide the results many had hoped for, a strong motivator for taking part was the opportunity to withdraw medication in a safely monitored environment which had been previously considered by some participants before. Investigators acknowledged that the insights gained from the study can now be used to support evidence-based conversations with patients.Conclusion For people whose dilated cardiomyopathy is in remission, decisions to continue, reduce or stop their medication are influenced by perceptions of personal health, perceive risk and the important o

Journal article

Simoes Monteiro de Marvao A, McGurk K, Zheng S, Thanaj M, Bai W, Duan J, Biffi C, Mazzarotto F, Statton B, Dawes T, Savioli N, Halliday B, Xu X, Buchan R, Baksi A, Quinlan M, Tokarczuk P, Tayal U, Francis C, Whiffin N, Theotokis A, Zhang X, Jang M, Berry A, Pantazis A, Barton P, Rueckert D, Prasad S, Walsh R, Ho C, Cook S, Ware J, O'Regan Det al., 2021, Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy, Journal of the American College of Cardiology, Vol: 78, Pages: 1097-1110, ISSN: 0735-1097

Background: Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomereencoding genes, but little is known about the clinical significance of these variants in thegeneral population.Objectives: To compare lifetime outcomes and cardiovascular phenotypes according to thepresence of rare variants in sarcomere-encoding genes amongst middle-aged adults.Methods: We analysed whole exome sequencing and cardiac magnetic resonance (CMR)imaging in UK Biobank participants stratified by sarcomere-encoding variant status.Results: The prevalence of rare variants (allele frequency <0.00004) in HCM-associatedsarcomere-encoding genes in 200,584 participants was 2.9% (n=5,712; 1 in 35), and theprevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was0.25% (n=493, 1 in 407). SARC-HCM-P/LP variants were associated with increased risk ofdeath or major adverse cardiac events compared to controls (HR 1.69, 95% CI 1.38 to 2.07,p<0.001), mainly due to heart failure endpoints (HR 4.23, 95% CI 3.07 to 5.83, p<0.001). In21,322 participants with CMR, SARC-HCM-P/LP were associated with asymmetric increasein left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) buthypertrophy (≥13mm) was only present in 18.4% (n=9/49, 95% CI 9 to 32%). SARC-HCMP/LP were still associated with heart failure after adjustment for wall thickness (HR 6.74,95% CI 2.43 to 18.7, p<0.001).Conclusions: In this population of middle-aged adults, SARC-HCM-P/LP variants have lowaggregate penetrance for overt HCM but are associated with increased risk of adversecardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absoluteevent rates are low, identification of these variants may enhance risk stratification beyondfamilial disease.

Journal article

Le TT, Huang B, Pua CJ, Tornekar V, Schumacher-Maurer A, Toh DF, Bryant J, Ang B, Corden B, Prasad SK, Tang HC, Cook SA, Chin CWLet al., 2021, Lowering the Recommended Maximal Wall Thickness Threshold Improves Diagnostic Sensitivity in Asians With Hypertrophic Cardiomyopathy, JACC: Asia, Vol: 1, Pages: 218-226

Background: Hypertrophic cardiomyopathy (HCM) is defined as left ventricular end-diastolic maximal wall thickness (WTMax) ≥15.0 mm, without accounting for ethnicity, sex, and body size. It is well-established that Asians have smaller hearts than do Caucasians. Objectives: This study aims to examine the implications of this single absolute WTMax threshold on the diagnosis of HCM in Asians. Methods: The study consisted of 360 healthy volunteers (male: n = 174; age: 50 ± 12 years) and 114 genetically characterized patients with HCM (male: n = 83; age: 52 ± 13 years; genotype-positive, n = 39). All participants underwent cardiovascular magnetic resonance. WTMax was measured semiautomatically at end-diastole according to the standard 16 myocardial segments. Results: Healthy male volunteers had increased WTMax compared with that of female volunteers (8.4 ± 1.2 mm vs 6.6 ± 1.1 mm, respectively; P < 0.001). Conversely, WTMax was similar between male and female patients with HCM (15.2 ± 3.4 mm vs 14.7 ± 3.0 mm, respectively; P = 0.484) and between those with and without a pathogenic gene variant (P = 0.828). Using the recommended diagnostic threshold of 15.0 mm, 56 patients with HCM had WTMax <15.0 mm and no healthy volunteers had WTMax >15.0 mm (specificity of 100% and sensitivity of 51%). Lowering WTMax thresholds to 10.0 mm in female patients and 12.0 mm in male patients did not affect specificity (100%) but significantly improved sensitivity (84%). Despite lower left ventricular mass, female patients with HCM demonstrated more features of adverse cardiac remodeling than did male patients: increased myocardial fibrosis, higher asymmetric ratio, and disproportionately worse myocardial strain. Conclusions: The study highlights cautious application of guideline-recommended WTMax to diagnose HCM in Asians. Lowering WTMax to account for ethnicity and sex improves diagnostic sensitivity without compromising specificity.

Journal article

Bermejo IA, Bautista-Rodriguez C, Fraisse A, Voges I, Gatehouse P, Kang H, Piccinelli E, Rowlinson G, Lane M, Semple T, Moscatelli S, Dwornik M, Lota A, Di Salvo G, Wage R, Prasad SK, Mohiaddin R, Pennell DJ, Thavendiranathan P, Krupickova Set al., 2021, Short-Term sequelae of Multisystem Inflammatory Syndrome in Children Assessed by CMR, JACC-CARDIOVASCULAR IMAGING, Vol: 14, Pages: 1666-1667, ISSN: 1936-878X

Journal article

Hatipoglu S, Almogheer B, Mahon C, Houshmand G, Uygur B, Giblin GT, Krupickova S, Baksi AJ, Alpendurada F, Prasad SK, Babu-Narayan SV, Gatzoulis MA, Mohiaddin RH, Pennell DJ, Izgi Cet al., 2021, Clinical Significance of Partial Anomalous Pulmonary Venous Connections (Isolated and Atrial Septal Defect Associated) Determined by Cardiovascular Magnetic Resonance, CIRCULATION-CARDIOVASCULAR IMAGING, Vol: 14, ISSN: 1941-9651

Journal article

Krupickova S, Hatipoglu S, DiSalvo G, Voges I, Redfearn D, Foldvari S, Eichhorn C, Chivers S, Puricelli F, Delle-Donne G, Barth C, Pennell DJ, Prasad SK, Daubeney PEFet al., 2021, Left ventricular noncompaction in pediatric population: could cardiovascular magnetic resonance derived fractal analysis aid diagnosis?, JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, Vol: 23, ISSN: 1097-6647

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

Tayal U, Ware JS, Lakdawala NK, Heymans S, Prasad SKet al., 2021, Understanding the genetics of adult-onset dilated cardiomyopathy: what a clinician needs to know., European Heart Journal, Vol: 42, Pages: 2384-2396, ISSN: 0195-668X

There is increasing understanding of the genetic basis to dilated cardiomyopathy and in this review, we offer a practical primer for the practising clinician. We aim to help all clinicians involved in the care of patients with dilated cardiomyopathy to understand the clinical relevance of the genetic basis of dilated cardiomyopathy, introduce key genetic concepts, explain which patients and families may benefit from genetic testing, which genetic tests are commonly performed, how to interpret genetic results, and the clinical applications of results. We conclude by reviewing areas for future research in this dynamic field.

Journal article

Gorecka M, McCann GP, Berry C, Ferreira VM, Moon JC, Miller CA, Chiribiri A, Prasad S, Dweck MR, Bucciarelli-Ducci C, Dawson D, Fontana M, Macfarlane PW, McConnachie A, Neubauer S, Greenwood JPet al., 2021, Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19: protocol design of COVID-HEART-a UK, multicentre, observational study, JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, Vol: 23, ISSN: 1097-6647

Journal article

Halliday B, Owen R, Gregson J, Vassiliou V, Chen X, Wage R, Lota A, Khalique Z, Tayal U, Hammersley D, Jones R, Baksi A, Cowie M, Cleland J, Pennell D, Prasad Set al., 2021, Myocardial remodelling after withdrawing therapy for heart failure in patients with recovered dilated cardiomyopathy: insights from TRED-HF, European Journal of Heart Failure, Vol: 23, Pages: 293-301, ISSN: 1388-9842

Aims: To characterize adverse ventricular remodelling after withdrawing therapy in recovered dilated cardiomyopathy (DCM). Methods and results: TRED-HF was a randomized controlled trial with a follow-on single-arm cross-over phase that examined the safety and feasibility of therapy withdrawal in patients with recovered DCM over 6 months. The primary endpoint was relapse of heart failure defined by (i) a reduction in left ventricular (LV) ejection fraction >10% and to <50%, (ii) >10% increase in LV end-diastolic volume and to above the normal range, (iii) a twofold rise in N-terminal pro-B-type natriuretic peptide and to >400 ng/L, or (iv) evidence of heart failure. LV mass, LV and right ventricular (RV) global longitudinal strain (GLS) and extracellular volume were measured using cardiovascular magnetic resonance at baseline and follow-up (6 months or relapse) for 48 patients. LV cell and extracellular matrix masses were derived. The effect of withdrawing therapy, stratified by relapse and genotype, was investigated in the randomized and follow-on phases. In the randomized comparison, withdrawing therapy led to an increase in mean LV mass [5.4 g/m2; 95% confidence interval (CI) 1.3–9.5] and cell mass (4.2 g/m2; 95% CI 0.5–8.0) and a reduction in LV (3.5; 95% CI 1.6–5.5) and RV (2.4; 95% CI 0.1–4.7) GLS. In a non-randomized comparison of all patients (n = 47) who had therapy withdrawn in either phase, there was an increase in LV mass (6.2 g/m2; 95% CI 3.6–8.9; P = 0.0001), cell mass (4.0 g/m2; 95% CI 1.8–6.2; P = 0.0007) and matrix mass (1.7 g/m2; 95% CI 0.7–2.6; P = 0.001) and a reduction in LV GLS (2.7; 95% CI 1.5–4.0; P = 0.0001). Amongst those who had therapy withdrawn and did not relapse, similar changes were observed (n = 28; LV mass: 5.1 g/m2, 95% CI 1.5–8.8, P = 0.007; cell mass: 3.7 g/m2, 95% CI 0.3–7.0, P = 0.03; matrix mass: 1.7 g/m2, 95% CI 0.4–3.0, P = 0.02; LV GLS: 1.7, 95% CI

Journal article

Zhang Q, Werys K, Popescu IA, Biasiolli L, Ntusi NAB, Desai M, Zimmerman SL, Shah DJ, Autry K, Kim B, Kim HW, Jenista ER, Huber S, White JA, McCann GP, Mohiddin SA, Boubertakh R, Chiribiri A, Newby D, Prasad S, Radjenovic A, Dawson D, Schulz-Menger J, Mahrholdt H, Carbone I, Rimoldi O, Colagrande S, Calistri L, Michels M, Hofman MBM, Anderson L, Broberg C, Andrew F, Sanz J, Bucciarelli-Ducci C, Chow K, Higgins D, Broadbent DA, Semple S, Hafyane T, Wormleighton J, Salerno M, He T, Plein S, Kwong RY, Jerosch-Herold M, Kramer CM, Neubauer S, Ferreira VM, Piechnik SKet al., 2021, Quality assurance of quantitative cardiac T1-mapping in multicenter clinical trials - A T1 phantom program from the hypertrophic cardiomyopathy registry (HCMR) study, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 330, Pages: 251-258, ISSN: 0167-5273

Journal article

Prasad S, Halliday B, 2021, Myocardial fibrosis in dilated cardiomyopathy – moving from stratifying risk to improving outcomes, JACC: Cardiovascular Imaging, ISSN: 1876-7591

Journal article

Raphael C, Mitchell F, Kanaganayagam G, liew A, Di Pietro E, Vieira M, Kanapeckaite L, Newsome S, Gregson J, Owen R, Hsu L-Y, Vassiliou V, Cooper R, Ali A, Ismail T, Wong B, Sun K, Gatehouse P, Firmin D, Cook S, Frenneaux M, Arai A, O'Hanlon R, Pennell D, Prasad Set al., 2021, Cardiovascular magnetic resonance predictors of heart failure in hypertrophic cardiomyopathy: the role of myocardial replacement fibrosis and the microcirculation, Journal of Cardiovascular Magnetic Resonance, Vol: 26, ISSN: 1097-6647

IntroductionHeart failure (HF) in hypertrophic cardiomyopathy (HCM) is associated with high morbidity and mortality. Predictors of HF, in particular the role of myocardial fibrosis and microvascular ischemia remain unclear. We assessed the predictive value of cardiovascular magnetic resonance (CMR) for development of HF in HCM in an observational cohort study.MethodsSerial patients with HCM underwent CMR, including adenosine first-pass perfusion, left atrial (LA) and left ventricular (LV) volumes indexed to body surface area (i) and late gadolinium enhancement (%LGE- as a % of total myocardial mass). We used a composite endpoint of HF death, cardiac transplantation, and progression to NYHA class III/IV.ResultsA total of 543 patients with HCM underwent CMR, of whom 94 met the composite endpoint at baseline. The remaining 449 patients were followed for a median of 5.6 years. Thirty nine patients (8.7%) reached the composite endpoint of HF death (n = 7), cardiac transplantation (n = 2) and progression to NYHA class III/IV (n = 20). The annual incidence of HF was 2.0 per 100 person-years, 95% CI (1.6–2.6). Age, previous non-sustained ventricular tachycardia, LV end-systolic volume indexed to body surface area (LVESVI), LA volume index ; LV ejection fraction, %LGE and presence of mitral regurgitation were significant univariable predictors of HF, with LVESVI (Hazard ratio (HR) 1.44, 95% confidence interval (95% CI) 1.16–1.78, p = 0.001), %LGE per 10% (HR 1.44, 95%CI 1.14–1.82, p = 0.002) age (HR 1.37, 95% CI 1.06–1.77, p = 0.02) and mitral regurgitation (HR 2.6, p = 0.02) remaining independently predictive on multivariable analysis. The presence or extent of inducible perfusion defect assessed using a visual score did not predict outcome (p = 0.16, p = 0.27 respectively).DiscussionThe annual incidence of HF in a contemporary ambulatory HCM population undergoing CMR

Journal article

Garnier S, Harakalova M, Weiss S, Mokry M, Regitz-Zagrosek V, Hengstenberg C, Cappola TP, Isnard R, Arbustini E, Cook SA, van Setten J, Calis JJA, Hakonarson H, Morley MP, Stark K, Prasad SK, Li J, O'Regan DP, Grasso M, Mueller-Nurasyid M, Meitinger T, Empana J-P, Strauch K, Waldenberger M, Marguiles KB, Seidman CE, Kararigas G, Meder B, Haas J, Boutouyrie P, Lacolley P, Jouven X, Erdmann J, Blankenberg S, Wichter T, Ruppert V, Tavazzi L, Dubourg O, Roizes G, Dorent R, de Groote P, Fauchier L, Trochu J-N, Aupetit J-F, Bilinska ZT, Germain M, Voelker U, Hemerich D, Raji I, Bacq-Daian D, Proust C, Remior P, Gomez-Bueno M, Lehnert K, Maas R, Olaso R, Saripella GV, Felix SB, McGinn S, Duboscq-Bidot L, van Mil A, Besse C, Fontaine V, Blanche H, Ader F, Keating B, Curjol A, Boland A, Komajda M, Cambien F, Deleuze J-F, Doerr M, Asselbergs FW, Villard E, Tregoueet D-A, Charron Pet al., 2021, Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23, European Heart Journal, Vol: 42, Pages: 2000-2011, ISSN: 0195-668X

Aims Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure.Methods and results We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene.Conclusion This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.

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