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  • 1
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    Prognostic Significance of Nonischemic Myocardial Fibrosis in Patients With Normal LV Volumes and Ejection-Fraction
    Elsevier BV ; 2021
    In:  JACC: Cardiovascular Imaging Vol. 14, No. 12 ( 2021-12), p. 2353-2365
    Details
    In: JACC: Cardiovascular Imaging, Elsevier BV, Vol. 14, No. 12 ( 2021-12), p. 2353-2365
    Type of Medium: Online Resource
    ISSN: 1936-878X
    URL: Article
    DOI: 10.1016/j.jcmg.2021.05.016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 2
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    Abstract 11639: Effect of Diabetes Mellitus on Clinical Phenotype and Cardiovascular Mortality in Non-Ischaemic Dilated Cardiomyopathy
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. Suppl_1 ( 2022-11-08)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
    Abstract: Introduction: Diabetes mellitus (DM) is common amongst patients with heart failure (HF) and associated with adverse outcomes. Historically this has been attributed to the association with atherosclerotic disease. We assessed the effect of DM on phenotype and outcomes in patients with non-ischaemic dilated cardiomyopathy (DCM). Methods: Prospective observational cohort study of 727 patients with DCM. All underwent a cardiac MRI and long-term follow up. The primary endpoint was CV death. Results: Of 727 patients with DCM (472 men, mean age 55 years, median LVEF 40%), 88 (12.1%) had DM at enrolment, of whom 19 (21.6%) were managed with insulin, 52 (59.0%) with oral hypoglycaemic agents (OHA) alone and 17 (19.3%) by diet alone. Enrolment predated guideline recommendations for SGLT2 inhibitors for HF. Patients with DM were older, had higher BMI, higher NYHA class, more were hypertensive and treated with loop diuretics (all p 〈 0.001), ACEi/ARB (p=0.02) and mineralocorticoid receptor antagonists (p=0.002). Compared to patients without DM, those with DM had lower LVEF (mean difference -4% [95%CI -7 to -1], p=0.007) and more had myocardial fibrosis (OR 1.81 [1.13 to 2.91] adjusted for age and sex). After median follow up 7.7 years, 71 patients died from CV causes. DM was associated with higher cumulative incidence of CV death on univariate analysis (log rank p 〈 0.001, Figure), but not after adjusting for age, sex, LVEF, NYHA, fibrosis, LAVi and RVEF (HR 1.66, 0.91 to 3.02, p=0.10). Patients with DM treated with insulin or OHA were at greater risk of CV death even after adjusting for the above variables (HR 2.02, 1.11 to 3.67, p=0.04). DM managed by diet alone was not associated with excess risk. Conclusions: DM is associated with adverse LV remodelling and fibrosis in patients with DCM; the subset requiring OHA or insulin had worse CV prognosis. Risk factor and lifestyle management may improve outcomes. Further studies are needed to assess whether added risk is attenuated by SGLT2 inhibitors.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.146.suppl_1.11639
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 3
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    Phenotype, outcomes and natural history of early‐stage non‐ischaemic cardiomyopathy
    Wiley ; 2023
    In:  European Journal of Heart Failure
    Details
    In: European Journal of Heart Failure, Wiley
    Abstract: To characterise the phenotype, clinical outcomes and rate of disease progression in patients with early‐stage non‐ischaemic cardiomyopathy (early‐NICM). Methods and results We conducted a prospective observational cohort study of patients with early‐NICM assessed by late‐gadolinium‐enhancement cardiovascular magnetic resonance. Cases were classified into the following subgroups: isolated left ventricular dilation (early‐NICM H‐/D+ ), non‐dilated left ventricular cardiomyopathy (early‐NICM H+/D‐ ) or early dilated cardiomyopathy (early‐NICM H+/D+ ). Clinical follow‐up for major adverse cardiovascular events (MACE) included non‐fatal life‐threatening arrhythmia, unplanned cardiovascular hospitalisation or cardiovascular death. A subset of patients (n=119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early‐NICM (median age 46 years [interquartile range 36‐58], 94 [37%] women, median LVEF 55% [52‐59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p=0.90), however fibrosis mass was lowest in early‐NICM H‐/D+ , higher in early‐NICM H+/D‐ and highest in early‐NICM H+/D+ (p=0.03). Over a median follow‐up of 7.9 (5.5‐10.0) years, 28 patients (11%) experienced MACE. Non‐sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36‐11.00, p 〈 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73‐8.20, p 〈 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73‐15.18, p=0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early‐NICM to DCM with LVEF 〈 50% over a median of 16 (11‐34) months. Conclusion Early‐NICM is not benign. Fibrosis develops early in the phenotypic course. In‐depth characterisation enhances risk stratification and might aid clinical management. This article is protected by copyright. All rights reserved.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Article
    DOI: 10.1002/ejhf.3037
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 4
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    Predictors of left ventricular remodelling in patients with dilated cardiomyopathy – a cardiovascular magnetic resonance study
    Wiley ; 2020
    In:  European Journal of Heart Failure Vol. 22, No. 7 ( 2020-07), p. 1160-1170
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 22, No. 7 ( 2020-07), p. 1160-1170
    Abstract: There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling. Methods and results Prospective study of patients with recent‐onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P  = 0.02). Baseline myocardial strain ( P  = 0.39 global longitudinal strain), interstitial myocardial fibrosis ( P  = 0.41), replacement myocardial fibrosis ( P  = 0.25), and right ventricular contractile reserve ( P  = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = −0.22, P  = 0.23) or baseline LVEF (r = 0.07, P  = 0.62). Men were more likely to experience adverse LV remodelling ( P  = 0.01) but age ( P  = 0.88) and disease‐modifying heart failure medication (beta‐blocker, P  = 0.28; angiotensin‐converting enzyme inhibitor, P  = 0.92) did not predict follow‐up LVEF. Conclusions Substantial recovery of LV function occurs within 12 months in most patients with recent‐onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.v22.7
    DOI: 10.1002/ejhf.1734
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 5
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    Iatrogenic myocarditis—biomarkers, cardiovascular MRI and the need for early diagnosis
    Oxford University Press (OUP) ; 2018
    In:  Oxford Medical Case Reports Vol. 2018, No. 1 ( 2018-01-01)
    Details
    In: Oxford Medical Case Reports, Oxford University Press (OUP), Vol. 2018, No. 1 ( 2018-01-01)
    Type of Medium: Online Resource
    ISSN: 2053-8855
    URL: Article
    DOI: 10.1093/omcr/omx096
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2766251-2
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  • 6
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    Direct and indirect effect of the COVID-19 pandemic on patients with cardiomyopathy
    BMJ ; 2022
    In:  Open Heart Vol. 9, No. 1 ( 2022-01), p. e001918-
    Details
    In: Open Heart, BMJ, Vol. 9, No. 1 ( 2022-01), p. e001918-
    Abstract: (1) To evaluate the prevalence and hospitalisation rate of COVID-19 infections among patients with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) in the Royal Brompton and Harefield Hospital Cardiovascular Research Centre (RBHH CRC) Biobank. (2) To evaluate the indirect impact of the pandemic on patients with cardiomyopathy through the Heart Hive COVID-19 study. (3) To assess the impact of the pandemic on national cardiomyopathy-related hospital admissions. Methods (1) 1236 patients (703 DCM, 533 HCM) in the RBHH CRC Biobank were assessed for COVID-19 infections and hospitalisations; (2) 207 subjects (131 cardiomyopathy, 76 without heart disease) in the Heart Hive COVID-19 study completed online surveys evaluating physical health, psychological well-being, and behavioural adaptations during the pandemic and (3) 11 447 cardiomyopathy-related hospital admissions across National Health Service (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 consequences of the pandemic. Trial registration number NCT04468256
    Type of Medium: Online Resource
    ISSN: 2053-3624
    URL: Article
    DOI: 10.1136/openhrt-2021-001918
    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 7
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    Abstract 10960: Genetic Overlap of Acute Myocarditis and Inherited Cardiomyopathy
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Background: Myocarditis may predispose to dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Familial data indicate a potential genetic susceptibility shared with arrhythmogenic cardiomyopathy (ACM). We present the first large-scale genotype-phenotype study of adults with acute myocarditis. Methods: A cohort comprising 336 consecutive patients with acute myocarditis was enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterised cardiomyopathy-associated genes. The burden of rare protein altering variants (PAV) in ACM genes, DCM genes, and TTN specifically, were compared with local healthy controls sequenced on the same platform (n=1053). Case ascertainment was assessed against national hospital admission data. Results: We identified rare protein-altering variants in 23% of cases compared to 16% in controls (Δ+6.8%; p=0.021), with rare truncating variants (tv) in 6% of cases compared to 〈 1% of controls ((Δ+5%; p=0.0097). In London (n=230; median left ventricular ejection fraction (LVEF) 63%), which was representative of national myocarditis admissions, 4.8% of cases carried rare tv, particularly within ACM genes (3% cases vs 0% controls; odds ratio 8.2; p=0.001). This was predominantly driven by desmoplakin (DSP)-tv in patients with normal LVEF. In Maastricht (n=106; median LVEF 30%), rare tv in DCM genes were enriched, particularly TTN-tv found in 7% (all with LVEF 〈 50%) compared to 1% in controls (OR 3.6; p=0.0116). During a median follow-up of 1.9 years, all-cause mortality was greatest in those with a DCM variant (18% vs 4% with no variant; OR 5.0; p=0.004). Conclusion: We identified enrichment of cardiomyopathy gene variants in acute myocarditis patients, dominated by DSP-tv in those with normal LVEF and TTN-tv in those with reduced LVEF. Incorporation of genetic testing may be beneficial to identify such high-risk individuals and guide family screening in acute myocarditis patients.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.10960
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 8
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    Genetic Architecture of Acute Myocarditis and the Overlap With Inherited Cardiomyopathy
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. 15 ( 2022-10-11), p. 1123-1134
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. 15 ( 2022-10-11), p. 1123-1134
    Abstract: Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. Methods: This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterized cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Results: Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared with 〈 1% of healthy controls ( P =0.0097). In the London cohort (n=230; median age, 33 years; 84% men), patients were representative of national myocarditis admissions (median age, 32 years; 71% men; 66% case ascertainment), and there was enrichment of rare truncating variants (tv) in ACM-associated genes (3.1% of cases versus 0.4% of controls; odds ratio, 8.2; P =0.001). This was driven predominantly by DSP -tv in patients with normal LV ejection fraction and ventricular arrhythmia. In Maastricht (n=106; median age, 54 years; 61% men), there was enrichment of rare truncating variants in DCM-associated genes, particularly TTN -tv, found in 7% (all with left ventricular ejection fraction 〈 50%) compared with 1% in controls (odds ratio, 3.6; P =0.0116). Across both cohorts over a median of 5.0 years (interquartile range, 3.9–7.8 years), all-cause mortality was 5.4%. Two-thirds of deaths were cardiovascular, attributable to worsening heart failure (92%) or sudden cardiac death (8%). The 5-year mortality risk was 3.3% in genotype-negative patients versus 11.1% for genotype-positive patients ( P adjusted =0.08). Conclusions: We identified DCM- or ACM-associated genetic variants in 8% of patients with acute myocarditis. This was dominated by the identification of DSP -tv in those with normal left ventricular ejection fraction and TTN -tv in those with reduced left ventricular ejection fraction. Despite differences between cohorts, these variants have clinical implications for treatment, risk stratification, and family screening. Genetic counseling and testing should be considered in patients with acute myocarditis to help reassure the majority while improving the management of those with an underlying genetic variant.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.058457
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 9
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    Abstract 11185: Impact of Covid-19 on Acute Myocarditis Hospital Admissions in the National Health Service of England, Uk (2019-2020)
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Introduction: Acute myocarditis has been reported in patients infected with COVID-19 in case series and imaging-based studies. We sought to assess this link by evaluating trends in hospital admissions due to acute myocarditis and COVID-19 on a national level during the pandemic. Methods: Data on all NHS England hospital admissions with a primary or secondary diagnosis of acute myocarditis were acquired and curated from the NHS Digital hospital episode statistics dataset from 2019-2020. COVID-19 data was obtained from the UK government daily statistics. Rolling averages over 28-day periods are presented. Results: Across all ages, there were 1,894 hospital admissions due to myocarditis in 2019 compared with 1,610 in 2020 (15% reduction). During the first national lockdown (23 rd Mar-19 th Jun 2020), myocarditis admissions were 32% lower than the same period in 2019. During the second lockdown (5 th Nov-2 nd Dec), myocarditis admissions were 9% greater than in 2019, although this increase was not sustained throughout December despite the subsequent surge in COVID-19 admissions. In general, patients admitted in 2020, compared to 2019, were older (median age 46 years, interquartile range 28-61 vs 41 years, IQR 26-58; p 〈 0.001), but sex (66% men), ethnicity (39% non-Caucasian, 9% unknown) and duration of hospital admission (median 2 days; IQR 1-4) were similar for both years. Discussion: As COVID-19 admissions peaked in early 2020, there was a sharp decline in myocarditis admissions, probably attributed to profound disruptions in healthcare provision, but possibly due to reduced transmission of other viruses during lockdown. Whilst myocarditis admissions increased during the second lockdown, there was no clear association between COVID-19 and myocarditis admission numbers. Further research may identify delayed presentations or sequelae of myocarditis, particularly following the larger COVID-19 peak in January 2021, as well as the impact of the vaccination programme.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.11185
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 10
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    Myocardial remodelling after withdrawing therapy for heart failure in patients with recovered dilated cardiomyopathy: insights from TRED‐HF
    Wiley ; 2021
    In:  European Journal of Heart Failure Vol. 23, No. 2 ( 2021-02), p. 293-301
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 23, No. 2 ( 2021-02), p. 293-301
    Abstract: 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/m 2 ; 95% confidence interval (CI) 1.3–9.5] and cell mass (4.2 g/m 2 ; 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/m 2 ; 95% CI 3.6–8.9; P  = 0.0001), cell mass (4.0 g/m 2 ; 95% CI 1.8–6.2; P  = 0.0007) and matrix mass (1.7 g/m 2 ; 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/m 2 , 95% CI 1.5–8.8, P  = 0.007; cell mass: 3.7 g/m 2 , 95% CI 0.3–7.0, P  = 0.03; matrix mass: 1.7 g/m 2 , 95% CI 0.4–3.0, P  = 0.02; LV GLS: 1.7, 95% CI 0.1–3.2, P  = 0.04). Patients with TTN variants ( n  = 10) who had therapy withdrawn had a greater increase in LV matrix mass (mean effect of TTN : 2.6 g/m 2 ; 95% CI 0.4–4.8; P  = 0.02). Conclusion In TRED‐HF, withdrawing therapy caused rapid remodelling, with early tissue and functional changes, even amongst patients who did not relapse.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.v23.2
    DOI: 10.1002/ejhf.2063
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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