William J McKenna

University College London Hospitals NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (257)2773.4 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction. Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30% ± 12.97 from 32.93% ± 16.46 P = 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups. This is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.
    European Heart Journal 09/2015; DOI:10.1093/eurheartj/ehv390 · 15.20 Impact Factor
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    ABSTRACT: Contribuyente adicional: Constantinos O’Mahony (Reino Unido) Comité de la ESC para las Guías de Práctica Clínica (GPC): Jose Luis Zamorano (presidente) (España), Stephan Achenbach (Alemania), Helmut Baumgartner (Alemania), Jeroen J. Bax (Países Bajos), Héctor Bueno (España), Veronica Dean (Francia), Christi Deaton (Reino Unido), Çetin Erol (Turquía), Robert Fagard (Bélgica), Roberto Ferrari (Italia), David Hasdai (Israel), Arno W. Hoes (Países Bajos), Paulus Kirchhof (Alemania/Reino Unido), Juhani Knuuti (Finlandia), Philippe Kolh (Bélgica), Patrizio Lancellotti (Bélgica), Ales Linhart (República Checa), Petros Nihoyannopoulos (Reino Unido), Massimo F. Piepoli (Italia), Piotr Ponikowski (Polonia), Per Anton Sirnes (Noruega), Juan Luis Tamargo (España), Michal Tendera (Polonia), Adam Torbicki (Polonia), William Wijns (Bélgica) y Stephan Windecker (Suiza).
    Revista Espa de Cardiologia 01/2015; 68(1). DOI:10.1016/j.recesp.2014.12.001 · 3.79 Impact Factor
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    ABSTRACT: Background: Recent studies have demonstrated that longitudinal septal deformation in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) predict LV remodeling after CRT. However, the importance of septal deformation patterns for prediction of long-term survival is unknown. Methods: From 2 centers a total of 193 CRT candidates with LBBB (NYHA II-IV, EF≤35, and QRS≥120ms) underwent echocardiography before CRT. Longitudinal 2-D strain analysis in the apical four-chamber view identified four patterns based on previously defined criteria: double-peaked systolic pattern (type 1), early pre-ejection shortening peak followed by prominent systolic stretch (type 2), shortening with one systolic peak inside 70% of ejection phase (type 3) and normal septal peak timing outside early 70% (type 4) . Outcome was pre-defined as freedom from death, left ventricular assist device or heart transplantation over 4 years. Results: Thirty-six patients (19%) had early septal deformation pattern type 1, 49(25%) type 2, 44(23%) type 3 and 64(33%) pseudonormal septal contraction type 4. There were 35 deaths, 4 transplantations, and 6 left ventricular assist device implantations over 4 years. The event rate was 0.05% (2/36) for type 1, 14% (7/49) for type 2, 25% (11/44) for type 3, 39% (25/64) for type 4. Patients with type 1 and 2 patterns had a more favourable event-free survival HR 0.26, CI 0.09-0.81 (P=0.005) than type 3 HR 1.17, CI 0.06-2.2 (P=0.65). Patients with type 4 septal contraction showed poor event-free survival HR 2.8, CI 1.6-5.1 (<0.001). (Figure 1) Conclusions: In LBBB-patients, septal deformation strain patterns predict long-term survival after CRT. Pattern 1 and 2 are highly associated with long-term survival while patients with pattern 4 have a poor prognosis.
    European Heart Journal – Cardiovascular Imaging 12/2014; 15(suppl 2):ii161-ii164. DOI:10.1093/ehjci/jeu264 · 2.65 Impact Factor
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    ABSTRACT: Background—Sarcomere protein mutations in hypertrophic cardiomyopathy (HCM) induce subtle cardiac structural changes prior to the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic HCM pre-LVH (G+LVH−). Methods and Results—A multi-centre case-control study investigated crypts and 22 other cardiovascular magnetic resonance (CMR) parameters in subclinical HCM to determine their strength of association with sarcomere gene mutation carriage. The G+LVH− sample (n=73) was 29±13 years old and 51% male. Crypts were related to the presence of sarcomere mutations (for ≥1 crypt, β=2.5, 95% confidence interval [CI] 0.5-4.4, p=0.014; for ≥2 crypts, β=3.0, 95%CI 0.8-7.9, p=0.004). In combination with 3 other parameters: anterior mitral valve leaflet (AMVL) elongation (β=2.1, 95%CI 1.7-3.1, p<0.001), abnormal LV apical trabeculae (β=1.6, 95%CI 0.8-2.5, p<0.001), and smaller LV end-systolic volumes (β=1.4, 95%CI 0.5-2.3, p=0.001), multiple crypts indicated the presence of sarcomere gene mutations with 80% accuracy and an area under the curve of 0.85 (95%CI 0.8-0.9). In this G+LVH− population cardiac myosin-binding protein C mutation carriers had twice the prevalence of crypts when compared to the other combined mutations (47 vs. 23%; odds ratio, 2.9; 95%CI 1.1-7.9; p=0.045). Conclusions—The subclinical HCM phenotype measured by CMR in a multi-center environment and consisting of crypts (particularly multiple), AMVL elongation, abnormal trabeculae and smaller LV systolic cavity, is indicative of the presence of sarcomere gene mutations and highlights the need for further study.
    Circulation Cardiovascular Imaging 09/2014; 7(6). DOI:10.1161/CIRCIMAGING.114.002411 · 5.32 Impact Factor
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    ABSTRACT: Aims: We determined the contribution of the desmosomal cadherin desmoglein-2 to cell-cell cohesion in cardiomyocytes. In the intercalated disc, providing mechanical strength and electrical communication between adjacent cardiomyocytes, desmoglein-2 is closely associated with N-cadherin and gap junctions. Methods and results: We studied intercalated discs of HL-1 cardiomyocytes by immunostaining of desmoglein-2 and N-cadherin. Cohesion was measured using a liberase-based dissociation-assay and compared with cell-free single-molecule atomic force microscopy measurements. L-tryptophan caused irregular desmoglein-2 condensation, weakened cell-cell cohesion and impaired both homophilic desmoglein-2 and N-cadherin trans-interaction, whereas l-phenylalanine had no effect. L-tryptophan did not affect N-cadherin localization and its inhibitory effect on cell-cohesion and desmoglein-2 binding, but not on N-cadherin interaction, was blocked by a desmoglein-specific tandem peptide. Moreover, Ca(2+)-depletion, desmoglein-2 knockdown, a desmoglein-specific single peptide and certain desmoglein-2 mutations associated with arrhythmogenic cardiomyopathy reduced cell-cell cohesion, whereas cell adhesion was strengthened by desmoglein-2 overexpression. Since single peptide did not interfere with N-cadherin trans-interaction, these data indicate that (i) desmoglein-2 binding is crucial for cardiomyocyte cohesion and (ii) L-tryptophan reduced both desmoglein-2 and N-cadherin binding, whereas single and tandem peptide can be used to specifically target desmoglein-2-mediated adhesion. L-tryptophan and single peptide also induced ultrastructural alterations of areae compositae. Functional analyses at the organ level revealed reduced cardiomyocyte function and inefficient response to adrenergic stimulation in both L-tryptophan- and single peptide-challenged murine Langendorff hearts paralleled by redistribution of connexin 43 in L-tryptophan-treated heart slices. Conclusion: Our data demonstrate that desmoglein-2 plays a critical role in cardiomyocyte cohesion and function.
    Cardiovascular Research 09/2014; 104(2). DOI:10.1093/cvr/cvu206 · 5.94 Impact Factor
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    ABSTRACT: Aims The concealed phase of arrhythmogenic right ventricular cardiomyopathy (ARVC) may initially manifest electrophysiologically. No studies have examined dynamic conduction/repolarization kinetics to distinguish benign right ventricular outflow tract ectopy (RVOT ectopy) from ARVC's early phase. We investigated dynamic endocardial electrophysiological changes that differentiate early ARVC disease expression from RVOT ectopy. Methods 22 ARVC (12 definite based upon family history and mutation carrier status, 10 probable) patients without right ventricular structural anomalies underwent high-density non-contact mapping of the right ventricle. These were compared to data from 14 RVOT ectopy and 12 patients with supraventricular tachycardias and normal hearts. Endocardial & surface ECG conduction and repolarization parameters were assessed during a standard S1-S2 restitution protocol. Results Definite ARVC without RV structural disease could not be clearly distinguished from RVOT ectopy during sinus rhythm or during steady state pacing. Delay in Activation Times at coupling intervals just above the ventricular effective refractory period (VERP) increased in definite ARVC (43±20 ms) more than RVOT ectopy patients (36±14 ms, p = 0.03) or Normals (25±16 ms, p = 0.008) and a progressive separation of the repolarisation time curves between groups existed. Repolarization time increases in the RVOT were also greatest in ARVC (definite ARVC: 18±20 ms; RVOT ectopy: 5±14, Normal: 1±18, p<0.05). Surface ECG correlates of these intracardiac measurements demonstrated an increase of greater than 48 ms in stimulus to surface ECG J-point pre-ERP versus steady state, with an 88% specificity and 68% sensitivity in distinguishing definite ARVC from the other groups. This technique could not distinguish patients with genetic predisposition to ARVC only (probable ARVC) from controls. Conclusions Significant changes in dynamic conduction and repolarization are apparent in early ARVC before detectable RV structural abnormalities, and were present to a lesser degree in probable ARVC patients. Investigation of dynamic electrophysiological parameters may be useful to identify concealed ARVC in patients without disease pedigrees by using endocardial electrogram or paced ECG parameters.
    PLoS ONE 07/2014; 9(7):e99125. DOI:10.1371/journal.pone.0099125 · 3.23 Impact Factor
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    ABSTRACT: Objective Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM. Methods We conducted a prospective cohort study in a tertiary referral centre. Consecutive patients with HCM (n=711, median age 56.3 years, IQR 46.7–66.6; 70.0% male) underwent LGE-CMR and were followed for a median 3.5 years. The primary end point was SCD or aborted SCD. Results Overall, 471 patients (66.2%) had myocardial fibrosis (median 5.9% of left ventricular mass, IQR: 2.2–13.3). Twenty-two (3.1%) reached the primary end point. The extent but not the presence of fibrosis was a significant univariable predictor of the primary end point (HR per 5% LGE: 1.24, 95% CI 1.06 to 1.45; p=0.007 and HR for LGE: 2.69, 95% CI 0.91 to 7.97; p=0.073, respectively). However, on multivariable analysis, only LV-EF remained statistically significant (HR: 0.92, 95% CI 0.89 to 0.95; p<0.001). For the secondary outcome of cardiovascular mortality/aborted SCD, the presence and the amount of fibrosis were significant predictors on univariable but not multivariable analysis after adjusting for LV-EF and non-sustained ventricular tachycardia. Conclusions The amount of myocardial fibrosis was a strong univariable predictor of SCD risk. However, this effect was not maintained after adjusting for LV-EF. Further work is required to elucidate the interrelationship between fibrosis and traditional predictors of outcome in HCM.
    Heart (British Cardiac Society) 06/2014; 100(23). DOI:10.1136/heartjnl-2013-305471 · 5.60 Impact Factor
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    ABSTRACT: The KCNQ1 gene encodes the Kv7.1 potassium channel which complexes with KCNE1 in the human heart to produce the repolarising IKs current. Mutations in KCNQ1 can perturb IKs function and cause long QT syndrome type 1 (LQT1). In LQT1, compound mutations are relatively common and are associated with increased disease severity. LQT1 compound mutations have been shown to increase channel dysfunction but whether other disease mechanisms, such as defective channel trafficking, contribute to the increase in arrhythmic risk has not been determined. Using an imaging-based assay we investigated the effects of four compound heterozygous mutations (V310I/R594Q, A341V/P127T, T391I/Q530X, A525T/R518X), one homozygous mutation (W248F) and one novel compound heterozygous mutation (A178T/K422fs39X) on channel trafficking. By analysing the effects in the equivalent of a homozygous, heterozygous and compound heterozygous condition we identify three different types of behaviour. A341V/P127T and W248F/W248F had no effect, whilst V310I/R594Q had a moderate, but not compound, effect on channel trafficking. In contrast, T391I/Q530X, A525T/R518X and A178T/K422fs39X severely disrupted channel trafficking when expressed in compound form. In conclusion, we have characterised the disease mechanisms for six LQT1 compound mutations and report that for four of these defective channel trafficking underlies the severe clinical phenotype.
    Biochemical Journal 06/2014; 462(1). DOI:10.1042/BJ20140425 · 4.40 Impact Factor
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    ABSTRACT: Myocardial abnormalities have been identified in hypertrophic cardiomyopathy(HCM) gene mutation carriers without hypertrophy(G+LVH-). Some of these changes may be mutation-related but whether they can predict gene carriage in relatives of HCM probands is unknown. We developed a method for tracking trabecular and mitral valve(MV) development in embryonic mouse hearts using high-resolution episcopic microscopy(HREM). We used these insights to instruct on human cardiac morphology by cardiovascular magnetic resonance(CMR) hypothesising that a combination of cardiac abnormalities could predict gene carriage in HCM before the appearance of LVH.
    Heart (British Cardiac Society); 06/2014
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    ABSTRACT: Introduction Left ventricular noncompaction (LVNC) is characterised by prominent ventricular myocardial trabeculations, composed of sheets of cardiomyocytes. They form early during cardiogenesis but their development is complex. Measuring trabecular complexity in animal models of cardiac disease is important as abnormal trabecular patterns are increasingly been recognised to coexist with several other cardiac conditions, not just LVNC. We describe an innovative approach that utilises fractal algorithms and high-resolution episcopic microscopy (HREM) to study the developmental timing of myocardial trabeculation in mouse and we validate it using a recently described LVNC mouse model (NOTCH pathway regulator Mib1 mutant). Methods HREM (2–3 μm resolution) analysis was performed prospectively on 123 embryonic mouse hearts consisting of wild-type (WT) NIMR:Parkes, WT C57BL/6 and Mib1 flox; cTnT-cre mutant and WT littermates. HREM permits the 2D/3D imaging of tissue samples as they are physically sectioned. Datasets underwent fractal analysis using a box-counting approach (Figure 1). Results LV trabecular complexity showed a significant drop between E14.5 and E18.5 (Figure 2). Across all embryonic stages, the apical half of the LV retained the highest fractal dimensions (FD) when compared to the base. By E18.5 the myocardium was almost fully compacted registering the lowest FD. For the first time, we demonstrate that strain-specific differences in LV trabecular patterning exist in mouse because NIMR:Parkes compacts earlier than C57BL/6 (Figure 3). Reslicing experiments (Figure 4) and separate validation tests on Mib1 mutants and WT littermates (Fig.5) confirmed how the proposed methodology is a reliable and effective tool for the detection of mutagenesis-related differences in trabeculation. Conclusion Reported here is a method in which sequential, 2D sections of mouse embryo hearts may be analysed using a fractal algorithm to calculate ventricular trabecular complexity – a technique so sensitive, that small inter-strain differences in somitogenesis are detectable in mouse pups. Precise knowledge of the trabecular architecture as it presents itself in WT, is a prerequisite for the correct identification of pathological trabecular phenotypes in mouse models of cardiac disease, explaining the need for a quantitative fractal atlas of trabecular development. Fractal mathematics in combination with HREM has the potential to answer to many developmental biology questions in the heart, with future applicability to other organ systems and to other species.
    Heart (British Cardiac Society) 06/2014; 100(Suppl 3):A125-A128. DOI:10.1136/heartjnl-2014-306118.230 · 5.60 Impact Factor
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    ABSTRACT: Hypertrophic cardiomyopathy and anomalous origin of the coronary artery from the opposite sinus are common causes of sudden cardiac death. These entities have rarely been reported together. Here we present the case of a 48-year-old woman with hypertrophic cardiomyopathy and significant left ventricular outflow tract obstruction. She was referred for septal reduction therapy for symptomatic left ventricular outflow tract obstruction refractory to medical therapy. Cardiac catheterization and coronary artery computed tomography angiogram revealed a single coronary artery arising from the right sinus of Valsalva, coursing between the aorta and the right ventricular outflow tract. The patient underwent septal myectomy and placement of an implantable cardioverter defibrillator.
    The Annals of Thoracic Surgery 06/2014; 97(6):2190-3. DOI:10.1016/j.athoracsur.2013.07.122 · 3.85 Impact Factor
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    ABSTRACT: To describe our Centre's experience of percutaneous mitral repair in Hypertrophic Cardiomyopathy (HCM).
    Heart (British Cardiac Society) 06/2014; 100 Suppl 3(Suppl 3):A54-5. DOI:10.1136/heartjnl-2014-306118.94 · 5.60 Impact Factor
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    ABSTRACT: Background Cardiac sarcoidosis (CS) is associated with poor outcomes, but detection remains difficult.Few studies evaluate 18-fluorodeoxyglucose positron emission tomography (PET) and cardiac magnetic resonance imaging (MRI) for CS diagnosis. None examine a novel hybrid PET-MR approach. We sought to examine the diagnostic accuracy of hybrid PET-MR imaging for CS detection. Methods 51 consecutive patients with biopsy-proven or clinically suspected CS (age 48 ± 13 years, 32% males) underwent hybrid PET-MR imaging. 18-FDG tracer uptake and late gadolinium enhancement (LGE) were qualitatively assessed on a binary scale and quantitatively by measuring standardised uptake value (SUV) and % LGE detected in each myocardial segment. Sensitivity and specificity of PET-MR for CS diagnosis was calculated. Inter-modality agreement was performed by the Cohen κ method. Coefficient of variance (COV) was performed to determine whether SUV quantification analysis discriminated between CS presence and absence. Results 37 (73%) of the patients had confirmed sarcoidosis; 46% were histologically proven and 59% had cardiac involvement according to JMHW guidelines. FDG uptake on PET-MR was equivalent to PET-CT (p < 0.001), confirming that simultaneous hybrid PET-MR is feasible. When considered in isolation, sensitivity of PET and MR at detecting abnormalities was 0.65 and 0.6, respectively. In contrast, hybrid imaging had improved sensitivity of 0.89 in detecting probable cardiac sarcoidosis with specificity, positive and negative predictive values of 0.42, 0.8 and 0.6, respectively. Sensitivity for detecting confirmed CS using hybrid PET-MR was 100%. Notably, there was poor inter-modality agreement between the location of increased SUV and LGE (k = 0.021). This may reflect the natural history of CS with progression from inflammation to scar and also account for the sensitivity of hybrid imaging. Coefficient of variance analysis of SUV uptake suggested that a COV above 25% predicted CS. Conclusion This is the first study to describe the feasibility and improved diagnostic accuracy of novel hybrid cardiac PET-MR imaging in CS. This technique may allow for more accurate and earlier diagnoses and may also allow titration of therapy according to disease activity.
    Heart (British Cardiac Society) 06/2014; 100(Suppl 3):A80. DOI:10.1136/heartjnl-2014-306118.135 · 5.60 Impact Factor
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    ABSTRACT: Background: -Exercise testing is performed in patients with hypertrophic cardiomyopathy (HCM) to evaluate blood pressure response, a risk factor for sudden cardiac death. The prognostic role of exercise gas exchange variables is unknown. Methods and results: -Between 1998 and 2010, 1,898 patients (age 47 ± 15 years, range 16 to 86 years; 67% male) with HCM underwent cardiopulmonary exercise testing (CPX). A total of 178 (9.4%) patients reached the primary endpoint of all-cause mortality or heart transplant (death/transplant) during a median follow up of 5.6 years (IQR 2.6 to 8.9), giving an annual event rate of 1.6 % per person year. Peak oxygen consumption, V̇O2 (adjusted HR 0.82, 95% CI 0.77-0.88, p<0.001), ventilatory efficiency, V̇EV̇CO2 (adjusted HR 1.10, 95% CI 1.00-1.22, p=0.049) and ventilatory anaerobic threshold, VAT (adjusted HR 0.82, 95% CI 0.70-0.96, p=0.016) were predictors of the primary outcome after correction for age, sex, left atrial size, non-sustained VT and ejection fraction. The overall adjusted death/transplant estimates for patients in the lowest quartile with peak V̇O2 ≤ 15.3 ml/kg/min were 14% at 5-years and 31% at 10-years. Peak V̇O2 (HR 0.81, 95% CI 0.77-0.86, p<0.01) and V̇EV̇CO2 (HR 1.10, 95% CI 1.08-1.13, p<0.001) were predictors of death due to heart failure or transplantation but not sudden cardiac death or ICD shocks. Conclusions: -CPX testing provides prognostic information in patients with HCM. Sub-maximal exercise parameters, such as ventilatory efficiency and anaerobic threshold, measured alone or in combination with peak V̇O2 predict death from heart failure.
    Heart (British Cardiac Society) 06/2014; 100(Suppl 3):A50-A51. DOI:10.1136/heartjnl-2014-306118.88 · 5.60 Impact Factor
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    ABSTRACT: Pre-participation cardiovascular evaluation is being recommended by a growing number of sporting bodies and scientific organisations in an attempt to identify athletes harbouring quiescent cardiac conditions which put them at risk of exercise-related sudden cardiac death (SCD). However cardiac adaptation to exercise may itself result in ECG patterns that overlap with those observed in several cardiac conditions, including hypertrophic cardiomyopathy (HCM), the leading cause of SCD in athletes worldwide. This raises significant challenges for physician's involved in ECG-based pre-participation cardiovascular evaluation of athletes with respect to distinguishing physiological from pathological ECG changes. Data demonstrates that cardiac conditions such as hypertension may modulate the HCM phenotype. However the effect of exercise on the HCM phenotype remains unknown. We compared the ECGs and echocardiographic parameters of athletes with HCM to sedentary HCM patients and healthy athletes to establish whether physical activity modifies the phenotype in HCM.
    Heart (British Cardiac Society) 06/2014; 100(Suppl 3):A51. DOI:10.1136/heartjnl-2014-306118.89 · 5.60 Impact Factor
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    ABSTRACT: -Mutations in genes coding for sarcomeric proteins cause hypertrophic cardiomyopathy (HCM). Subtle abnormalities of the myocardium may be present in mutation carriers without hypertrophy (G+LVH-) but are difficult to quantify. Fractal analysis has been used to define trabeculae in LV noncompaction and to identify normal racial variations. We hypothesized that trabeculae measured by fractal analysis of cardiovascular magnetic resonance (CMR) images are abnormal in G+LVH- patients providing a preclinical marker of disease in HCM. -CMR was performed on 40 G+LVH- patients (33±15yrs, 38% men), 67 patients with a clinical diagnosis of HCM (53±15yrs, 76% men; 31 with a pathogenic mutation (G+LVH+)) and 69 matched healthy volunteers (44±15yrs, 57% men). Trabeculae were quantified by fractal analysis of cine slices to calculate the fractal dimension (FD) - a unitless index of endocardial complexity calculated from endocardial contours after segmentation. In G+LVH- patients apical LV trabeculation was increased compared to controls (maximal apical FD, 1.249±0.07 vs 1.199±0.05, P=0.001). In G+LVH+ and G-LVH+ cohorts, maximal apical FD was greater than in controls (P<0.0001) irrespective of gene status (G+LVH+: 1.370±0.08; G-LVH+: 1.380±0.09). Compared to controls, G+LVH- patients also had a higher frequency of clefts (28 vs 8%, P=0.02), longer anterior mitral valve leaflets (23.5±3.0 vs 19.7±3.1mm, P<0.0001), greater septal systolic wall thickness (12.6±3.2 vs 11.2±2.1mm, P=0.03), higher ejection fraction (71±4 vs 69±4 %, P=0.03) and smaller end-systolic volumes (38±9 vs 43±12mls, P=0.03). -Increased myocardial trabecular complexity is one of several preclinical abnormalities in HCM sarcomere gene mutation carriers without LVH.
    Circulation Cardiovascular Genetics 04/2014; 7(3). DOI:10.1161/CIRCGENETICS.113.000362 · 4.60 Impact Factor
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    ABSTRACT: Recent efforts have focused on improving specificity of the European Society of Cardiology (ESC) criteria for ECG interpretation in athletes. These criteria are derived predominantly from white athletes (WAs) and do not account for the effect of Afro-Caribbean ethnicity or novel research questioning the relevance of several isolated ECG patterns. We assessed the impact of the ESC criteria, newly published Seattle criteria and a group of proposed refined criteria in a large cohort of black athletes (BAs) and WAs. Between 2000-2012, 1208 BAs were evaluated with history, examination, 12-lead ECG and further investigations as appropriate. Electrocardiograms were retrospectively analysed according to the ESC recommendations, Seattle criteria, and proposed refined criteria which exclude several specific ECG patterns when present in isolation. All 3 criteria were also applied to 4297 WAs and 103 young athletes with hypertrophic cardiomyopathy (HCM). The ESC recommendations raised suspicion of a cardiac abnormality in 40.4% of BAs and 16.2% of WAs. The Seattle criteria reduced abnormal ECGs to 18.4% in BAs and 7.1% in WAs. The refined criteria further reduced abnormal ECGs to 11.5% in BAs and 5.3% in WAs. All 3 criteria identified 98.1% of athletes with HCM. Compared to ESC recommendations, the refined criteria improved specificity from 40.3% to 84.2% in BAs and from 73.8% to 94.1% in WAs without compromising the sensitivity of the ECG in detecting pathology. Refinement of current ECG screening criteria has the potential to significantly reduce the burden of false-positive ECGs in athletes, particularly BAs.
    Circulation 03/2014; 129(16). DOI:10.1161/CIRCULATIONAHA.113.006179 · 14.43 Impact Factor
  • Srijita Sen-Chowdhry · William J McKenna
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    ABSTRACT: Abstract The classic cardiocutaneous syndromes of Naxos and Carvajal are rare. The myocardial disorder integral to their pathology - arrhythmogenic cardiomyopathy - is arguably not uncommon, with a prevalence of up to 1 in 1,000 despite almost certain under-recognition. Yet the study of cardiocutaneous syndromes has been integral to evolution of the contemporary perspective of arrhythmogenic cardiomyopathy - its clinical course, disease spectrum, genetics, and cellular and molecular mechanisms. Here we discuss how recognition of the association of hair and skin abnormalities with underlying heart disease transformed our conception of a little-understood but important cause of sudden cardiac death.
    Cell Communication & Adhesion 02/2014; 21(1):3-11. DOI:10.3109/15419061.2013.876415 · 1.52 Impact Factor
  • Srijita Sen-Chowdhry · William J McKenna
    Cardiology 01/2014; 127(4):265-274. DOI:10.1159/000357379 · 2.18 Impact Factor
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    Biophysical Journal 01/2014; 106(2):644a-645a. DOI:10.1016/j.bpj.2013.11.3568 · 3.97 Impact Factor

Publication Stats

18k Citations
2,773.40 Total Impact Points


  • 2006–2015
    • University College London Hospitals NHS Foundation Trust
      • Department of Medicine
      Londinium, England, United Kingdom
    • Imperial College London
      Londinium, England, United Kingdom
  • 2014
    • Yale University
      New Haven, Connecticut, United States
  • 2003–2014
    • Liverpool Heart And Chest Hospital
      Liverpool, England, United Kingdom
    • University of Pavia
      Ticinum, Lombardy, Italy
    • Tzaneio General Hospital of Piraeus
      Le Pirée, Attica, Greece
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 2004–2013
    • University College London
      • Institute of Cardiovascular Science
      Londinium, England, United Kingdom
    • Baylor College of Medicine
      Houston, Texas, United States
  • 2012
    • Statens Serum Institut
      København, Capital Region, Denmark
  • 2011
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
    • Beth Israel Deaconess Medical Center
      • Department of Pathology
      Boston, MA, United States
  • 2008
    • University of Oxford
      Oxford, England, United Kingdom
  • 2007
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • Imperial Valley College
      IPL, California, United States
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2005
    • National Sports Medicine Institute
      Leesburg, Virginia, United States
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 1997–2003
    • St George's, University of London
      • Cardiovascular Sciences Research Centre
      Londinium, England, United Kingdom
    • University of London
      Londinium, England, United Kingdom
  • 2002
    • Kagoshima University
      Kagosima, Kagoshima, Japan
  • 1996–2002
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • University Hospital Magdeburg
      Magdeburg, Saxony-Anhalt, Germany
  • 2000
    • University-Hospital of Padova
      Padua, Veneto, Italy
  • 1999
    • Karolinska University Hospital
      • Department of Cardiology
      Tukholma, Stockholm, Sweden
  • 1993–1995
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1994
    • Harvard Medical School
      • Department of Genetics
      Boston, MA, United States
  • 1990
    • Brigham and Women's Hospital
      Boston, Massachusetts, United States