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Featured researches published by John-Paul Carpenter.


Circulation | 2011

On T2* Magnetic Resonance and Cardiac Iron

John-Paul Carpenter; Taigang He; Paul Kirk; Michael Roughton; Lisa J. Anderson; Sofia V. De Noronha; Mary N. Sheppard; John B. Porter; J. Malcolm Walker; John C. Wood; Renzo Galanello; Gianluca Forni; Gualtiero Catani; Gildo Matta; Suthat Fucharoen; Adam Fleming; Michael J. House; Greg Black; David N. Firmin; Timothy G. St. Pierre; Dudley J. Pennell

Background— Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically via its reciprocal, T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans are limited. Methods and Results— Twelve human hearts were studied from transfusion-dependent patients after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure (n=4). After cardiovascular magnetic resonance R2* measurement, tissue iron concentration was measured in multiple samples of each heart with inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean±SD global myocardial iron causing severe heart failure in 10 patients was 5.98±2.42 mg/g dry weight (range, 3.19 to 9.50 mg/g), but in 1 outlier case of heart failure was 25.9 mg/g dry weight. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] (R2=0.910, P<0.001), leading to [Fe]=45.0×(T2*)−1.22 for the clinical calibration equation with [Fe] in milligrams per gram dry weight and T2* in milliseconds. Midventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron. Conclusions— These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration. The iron values are of considerable interest in terms of the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in vivo by cardiovascular magnetic resonance of the midseptum.


Circulation | 2013

The Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Nonischemic Dilated Cardiomyopathy

Ankur Gulati; Tevfik F Ismail; Andrew Jabbour; Francisco Alpendurada; Kaushik Guha; Nizar A. Ismail; Sadaf Raza; Jahanzaib Khwaja; Tristan D.H. Brown; Kishen Morarji; Emmanouil Liodakis; Michael Roughton; Ricardo Wage; Tapesh Pakrashi; Rakesh Sharma; John-Paul Carpenter; Stuart A. Cook; Martin R. Cowie; Ravi G. Assomull; Dudley J. Pennell; Sanjay Prasad

Background— Cardiovascular magnetic resonance is the gold-standard technique for the assessment of ventricular function. Although left ventricular volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether cardiovascular magnetic resonance assessment of RV function has prognostic value in DCM. Methods and Results— We prospectively studied 250 consecutive DCM patients with the use of cardiovascular magnetic resonance. RVSD, defined by RV ejection fraction ⩽45%, was present in 86 (34%) patients. During a median follow-up period of 6.8 years, there were 52 deaths, and 7 patients underwent cardiac transplantation. The primary end point of all-cause mortality or cardiac transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients without RVSD (49% versus 10%; hazard ratio, 5.90; 95% confidence interval [CI], 3.35–10.37; P<0.001). On multivariable analysis, RVSD remained a significant independent predictor of the primary end point (hazard ratio, 3.90; 95% CI, 2.16–7.04; P<0.001), as well as secondary outcomes of cardiovascular mortality or cardiac transplantation (hazard ratio, 3.35; 95% CI, 1.76–6.39; P<0.001), and heart failure death, heart failure hospitalization, or cardiac transplantation (hazard ratio, 2.70; 95% CI, 1.32–5.51; P=0.006). Assessment of RVSD improved risk stratification for all-cause mortality or cardiac transplantation (net reclassification improvement, 0.31; 95% CI 0.10–0.53; P=0.001). Conclusions— RVSD is a powerful, independent predictor of transplant-free survival and adverse heart failure outcomes in DCM. Cardiovascular magnetic resonance assessment of RV function is important in the evaluation and risk stratification of DCM patients.


Journal of Magnetic Resonance Imaging | 2013

In vivo comparison of myocardial T1 with T2 and T2* in thalassaemia major

Yanqiu Feng; Taigang He; John-Paul Carpenter; Andrew Jabbour; Mohammed H Alam; Peter D. Gatehouse; Andreas Greiser; Daniel Messroghli; David N. Firmin; Dudley J. Pennell

To compare myocardial T1 against T2 and T2* in patients with thalassemia major (TM) for myocardial iron characterization.


Journal of Cardiovascular Magnetic Resonance | 2011

On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

Dudley J. Pennell; John-Paul Carpenter; Michael Roughton; Zi Cabantchik

BackgroundTrials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM) patients. Treatment effects with improved left ventricular (LV) ejection fraction (EF) have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful.MethodsThis retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR) to the relative risk (RR) of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM) and 63-70% (lower half of the normal range for TM).ResultsA total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p < 0.001) and the higher EF stratum (EF 63-70%, RR 0.893 p = 0.001).ConclusionThese data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.


European Heart Journal | 2010

Relation of myocardial T2* to right ventricular function in thalassaemia major

Francisco Alpendurada; John-Paul Carpenter; Monica Deac; Paul Kirk; J. Malcolm Walker; John B. Porter; Winston Banya; Taigang He; Gill Smith; Dudley J. Pennell

AIMS Myocardial T2* cardiovascular magnetic resonance (CMR) provides a rapid and reproducible measure of cardiac iron loading and is being increasingly used worldwide for monitoring of transfusion-dependent thalassaemia patients. Although myocardial siderosis (T2* <20 ms) is associated with impaired left ventricular (LV) function, little is known of its relation with right ventricular (RV) function. The aim of this study was to investigate the relationship between cardiac T2* and RV function. METHODS AND RESULTS A retrospective analysis of 319 patients with beta-thalassaemia major presenting for their first CMR scan was performed (45.1% male, mean age 25.6 years). In patients with normal myocardial T2* (>20 ms), the RV ejection fraction (EF) was within the normal range in 98% of patients. When myocardial T2* was <20 ms, there was a progressive and significant decline in RV EF. There was a linear relationship between RV and LV EF. CONCLUSION Myocardial iron deposition is strongly associated with RV dysfunction, which mirrors the decrease in LV function seen with worsening cardiac iron loading. Right ventricular dysfunction may play a significant role in heart failure associated with myocardial siderosis.


Journal of Cardiovascular Magnetic Resonance | 2012

Effects of combined deferiprone with deferoxamine on right ventricular function in thalassaemia major

Francisco Alpendurada; Gill Smith; John-Paul Carpenter; Sunil V. Nair; Mark A. Tanner; Winston Banya; Carlo Dessì; Renzo Galanello; John Malcolm Walker; Dudley J. Pennell

BackgroundCombination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR).MethodsWe retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading.ResultsIn the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01).ConclusionsIn the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis.


International Journal of Cardiology | 2013

Prognostic value of cardiovascular magnetic resonance in patients with suspected arrhythmogenic right ventricular cardiomyopathy

Monica O. Deac; Francisco Alpendurada; Fariba Fanaie; Raj Vimal; John-Paul Carpenter; Adelle Dawson; Christopher A Miller; Isabelle Roussin; Elisa Di Pietro; Tevfik F Ismail; Michael Roughton; Joyce Wong; Dana Dawson; Janice A. Till; Mary N. Sheppard; Raad H. Mohiaddin; Philip J. Kilner; Dudley J. Pennell; Sanjay Prasad

BACKGROUND Early recognition and accurate risk stratification are important in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Identification of predictors of outcome by cardiovascular magnetic resonance (CMR) in patients undergoing evaluation for ARVC is limited. We investigated the predictive value of morphological abnormalities detected by CMR for major clinical events in patients with suspected ARVC. METHODS We performed a longitudinal study on 369 consecutive patients with at least one criterion for ARVC. Abnormal CMR was defined by the presence of one of the following: increased right ventricular (RV) volumes, reduced RV ejection fraction, RV regional wall motion abnormalities, myocardial fatty infiltration, and myocardial fibrosis. The end-point was a composite of cardiac death, sustained ventricular tachycardia, ventricular fibrillation, and appropriate ICD discharge. RESULTS Twenty patients met the composite end-point over a mean follow-up of 4.3±1.5 years. An abnormal CMR was an independent predictor of outcomes (p<0.001). The presence of multiple abnormalities heralded a particular high risk of events (HR 23.0, 95% CI 5.7-93.2, p<0.001 for 2 abnormalities; HR 35.8, 95% CI 9.7-132.6, p<0.001 for 3 or more abnormalities). The positive predictive value of an abnormal CMR study was 21.0% for an adverse event, whilst the negative predictive value of a normal CMR study was 98.8% over the follow-up period. CONCLUSIONS CMR provides important prognostic information in patients under evaluation for ARVC. A normal study portends a good prognosis. Conversely, the presence of multiple abnormalities identifies a high risk group of patients who may benefit from ICD implantation.


Journal of Cardiovascular Magnetic Resonance | 2013

On myocardial siderosis and left ventricular dysfunction in hemochromatosis

John-Paul Carpenter; Agata Grasso; John B. Porter; Farrukh Shah; James Dooley; Dudley J. Pennell

BackgroundChronically increased intestinal iron uptake in genetic hemochromatosis (HC) may cause organ failure. Whilst iron loading from blood transfusions may cause dilated cardiomyopathy in conditions such as thalassemia, the in-vivo prevalence of myocardial siderosis in HC is unclear, and its relation to left ventricular (LV) dysfunction is controversial. Most previous data on myocardial siderosis in HC has come from post-mortem studies.MethodsCardiovascular magnetic resonance (CMR) was performed at first presentation of 41 HC patients (58.9 ±14.1 years) to measure myocardial iron and left ventricular (LV) ejection fraction (EF).ResultsIn 31 patients (genetically confirmed HFE-HC), the HFE genotype was C282Y/C282Y (n = 30) and C282Y/H63D (n = 1). Patients with other genotypes (n = 10) were labeled genetically unconfirmed HC. Of the genetically confirmed HFE-HC patients, 6 (19%) had myocardial siderosis (T2* <20 ms). Of these, 5 (83%) had heart failure and reduced LVEF which was correlated to the severity of siderosis (R2 0.57, p = 0.049). Two patients had follow-up scans and both had marked improvements in T2* and LVEF following venesection. Myocardial siderosis was present in 6/18 (33%) of patients with presenting ferritin ≥1000 μg/L at diagnosis but in 0/13 (0%) patients with ferritin <1000 μg/L (p = 0.028). Overall however, the relation between myocardial siderosis and ferritin was weak (R2 0.20, p = 0.011). In the 10 genetically unconfirmed HC patients, 1 patient had mild myocardial siderosis but normal EF. Of all 31 patients, 4 had low LVEF from other identifiable causes without myocardial siderosis.ConclusionMyocardial siderosis was present in 33% of newly presenting genetically confirmed HFE-HC patients with ferritin >1000 μg/L, and was the commonest cause of reduced LVEF. Heart failure due to myocardial siderosis was only found in these HFE-HC patients, and was reversible with venesection. Myocardial iron was normal in patients with other causes of LV dysfunction.


Journal of Magnetic Resonance Imaging | 2013

Automated truncation method for myocardial T2* measurement in thalassemia.

Taigang He; Jun Zhang; John-Paul Carpenter; Yanqiu Feng; Gillian C. Smith; Dudley J. Pennell; David N. Firmin

To propose an automated truncation method for myocardial T2* measurement and evaluate this method on a large population of patients with iron loading in the heart and scanned at multiple magnetic resonance imaging (MRI) centers.


Journal of Cardiovascular Magnetic Resonance | 2010

Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload

John-Paul Carpenter; Francisco Alpendurada; Monica Deac; Alicia M. Maceira; Maciej Garbowski; Paul Kirk; J. Malcolm Walker; John B. Porter; Farrukh Shah; Winston Banya; Taigang He; Gillian C. Smith; Dudley J. Pennell

AimWe aimed to define reference ranges for right ventricular (RV) volumes, ejection fraction (EF) in thalassemia major patients (TM) without myocardial iron overload.Methods and resultsRV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance). All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 ± 4.1% vs 61.6 ± 6%, p = 0.0009; females 66.3 ± 5.1% vs 62.6 ± 6.4%, p = 0.017), which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%). RV end-diastolic volume index was higher in male TM patients (mean 98.1 ± 17.3 mL vs 88.4 ± 11.2 mL/m2, p = 0.027), with a higher upper limit (132 vs 110 mL/m2) but this difference was of borderline significance for females (mean 86.5 ± 13.6 mL vs 80.3 ± 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2). The cardiac index was raised in TM patients (males 4.8 ± 1.0 L/min vs 3.4 ± 0.7 L/min, p < 0.0001; females 4.5 ± 0.8 L/min vs 3.2 ± 0.8 L/min, p < 0.0001). No differences in RV mass index were identified.ConclusionThe normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients.

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Dudley J. Pennell

National Institutes of Health

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John B. Porter

University College London

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David N. Firmin

National Institutes of Health

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Paul Kirk

Imperial College London

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Michael Roughton

Royal College of Physicians

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J. Malcolm Walker

University College Hospital

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