Andrew T Cox

Quantification of Myocardial Extracellular Volume Fraction in Systemic AL Amyloidosis An Equilibrium Contrast Cardiovascular Magnetic Resonance Study

Background— Cardiac involvement predicts outcome in systemic AL amyloidosis and influences therapeutic options. Current methods of cardiac assessment do not quantify myocardial amyloid burden. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) to quantify the cardiac interstitial compartment, measured as myocardial extracellular volume (ECV) fraction, hypothesizing it would reflect amyloid burden. Methods and Results— Sixty patients with systemic AL amyloidosis (65% men, median age 65 years) underwent conventional clinical cardiovascular magnetic resonance, including late enhancement, equilibrium contrast cardiovascular magnetic resonance, and clinical cardiac evaluation, including ECG, echocardiography, assays of N-terminal pro-brain natriuretic peptide and Troponin T, and functional assessment comprising the 6-minute walk test in ambulant individuals. Cardiac involvement in the amyloidosis patients was categorized as definite, probable, or none, suspected by conventional criteria. Findings were compared with 82 healthy controls. Mean ECV was significantly greater in patients than healthy controls (0.25 versus 0.40, P <0.001) and correlated with conventional criteria for characterizing the presence of cardiac involvement, the categories of none, probable, definite corresponding to ECV of 0.276 versus 0.342 versus 0.488, respectively ( P <0.001). ECV was correlated with cardiac parameters by echocardiography (eg, Tissue Doppler Imaging [TDI] S-wave R=0.52, P<0.001) and conventional cardiovascular magnetic resonance (eg, indexed left ventricular mass R =0.56, P <0.001). There were also significant correlations with N-terminal pro-brain natriuretic peptide ( R =0.69, P <0.001) and Troponin T ( R =0.53, P =0.006). ECV was associated with smaller QRS voltages ( R =0.57, P <0.001) and correlated with poorer performance in the 6-minute walk test ( R =0.36, P =0.03). Conclusions— Myocardial ECV measurement has potential to become the first noninvasive test to quantify cardiac amyloid burden.

Should axis deviation or atrial enlargement be categorised as abnormal in young athletes? The athlete's electrocardiogram: time for re-appraisal of markers of pathology

AIMS The 2010 European Society of Cardiology (ESC) guidelines for electrocardiogram (ECG) interpretation in athletes are associated with a relatively high false positive rate and warrant modification to improve the specificity without compromising sensitivity. The aim of this study was to investigate whether non-specific anomalies such as axis deviation and atrial enlargement in isolation require further assessment in highly trained young athletes. METHOD AND RESULTS Between 2003 and 2011, 2533 athletes aged 14-35 years were investigated with 12-lead ECG and echocardiography. Electrocardiograms were analysed for non-training-related (Group 2) changes according to the 2010 ESC guidelines. Results were compared with 9997 asymptomatic controls. Of the 2533 athletes, 329 (13%) showed Group 2 ECG changes. Isolated axis deviation and isolated atrial enlargement comprised 42.6% of all Group 2 changes. Athletes revealed a slightly higher prevalence of these anomalies compared with controls (5.5 vs. 4.4%; P = 0.023). Echocardiographic evaluation of athletes and controls with isolated axis deviation or atrial enlargement (n = 579) failed to identify any major structural or functional abnormalities. Exclusion of axis deviation or atrial enlargement reduced the false positive rate from 13 to 7.5% and improved specificity from 90 to 94% with a minimal reduction in sensitivity (91-89.5%). CONCLUSION Isolated axis deviation and atrial enlargement comprise a high burden of Group 2 changes in athletes and do not predict underlying structural cardiac disease. Exclusion of these anomalies from current ESC guidelines would improve specificity and cost-effectiveness of pre-participation screening with ECG.

Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile

Background: Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. Methods: We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. Results: Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P=0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01–1.15; P=0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. Conclusions: Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC score >300 Agatston units or coronary plaques compared with sedentary males with a similar risk profile. The significance of these observations is uncertain, but the predominantly calcific morphology of the plaques in athletes indicates potentially different pathophysiological mechanisms for plaque formation in athletic versus sedentary men. Coronary plaques are more abundant in athletes, whereas their stable nature could mitigate the risk of plaque rupture and acute myocardial infarction.

A 2-year review of the general internal medicine admissions to the British Role 3 Hospital in Camp Bastion, Afghanistan

Background Detailed knowledge of the likely volume and nature of the diseases presenting to deployed secondary care facilities aids operational planning. Now the British operation in Afghanistan has ended and a record of the experience is useful to preserve the lessons learned. Methods Over a 2-year period from April 2011, prospective demographic and clinical data were collected on consecutive general internal medicine admissions to the Role 3 Hospital in Camp Bastion, Afghanistan. Up to four different symptoms and diagnoses were coded using the WHO International Classification of Disease, V.10 for each patient. Results A total of 1368 medical patients were admitted. Of 1131 military admissions, 612 were from the UK (54.1%) and the remainder from 13 allied countries; 237 civilians came from 23 countries. Civilians were older than the military patients (p<0.001) but included five children. The 20 most frequent presenting symptoms were identified and there were 1626 diagnoses made. The 10 most frequent diagnoses were infectious gastroenteritis (12.6%), heat illness (4.3%), pneumonia (3.6%), epilepsy (2.6%), cellulitis (2.7%), migraine (1.8%), peptic ulcer disease (1.2%), myocardial infarction (1.2%), venous thromboembolism (1.2%) and pericarditis (0.7%). In 252 cases (18.4%) a firm diagnosis was not reached and a symptom was recorded. The five most frequent of these were undifferentiated febrile illnesses (4.6%), syncope (3.7%), chest pain (2.8%), headache (0.8%) and palpitations (0.7%). The mean hospital length of stay was 1.59 days and 72.2% of UK military patients were ‘returned to unit’. Three civilian patients died in hospital or following aeromedical evacuation and there were no deaths of any military patients. Discussion This study demonstrates the wide variety of presentations seen by physicians at an established military field hospital. This information informs the core syllabus of military physician training and will help facilitate planning for future medical support to similar military operations. Trial registration number RCDM/Res/Audit/1036/ 12/0305.

Late gadolinium enhancement in Brugada syndrome: A marker for subtle underlying cardiomyopathy?

BACKGROUND There is increasing evidence that the Brugada ECG pattern is a marker of subtle structural heart disease. OBJECTIVE The purpose of this study was to characterize patients with Brugada syndrome (BrS) using cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). METHODS BrS was diagnosed according to international guidelines. Twenty-six percent of patients with BrS carried SCN5A mutations. CMR data from 78 patients with BrS were compared with 78 healthy controls (44 ± 15 vs 42 ± 14 years; P = .434; and 64% vs 64% male; P = 1). RESULTS Right ventricular (RV) ejection fraction was slightly lower (61 ± 8% vs 64 ± 5%; P = .004) and RV end-systolic volume slightly greater (31 ± 10 mL/m2 vs 28 ± 6 mL/m2; P = .038) in BrS compared with controls. These values remained within the normal range. LGE was demonstrated in 8% of patients with BrS (left ventricular midwall LGE in 5%) but not in controls (P = .028). In patients with BrS with midwall LGE there were no other features of cardiomyopathy at the time of CMR, but genetic testing and follow-up revealed a desmoplakin mutation in 1 patient and evolution of T-wave inversion throughout all precordial ECG leads in another. Neither patient fulfils diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy. CONCLUSION Some patients with BrS have left ventricular midwall LGE consistent with an underlying cardiomyopathic process. Even cases without LGE show greater RV volumes and reduced RV function. These findings lend further support to the presence of subtle structural abnormalities in BrS. The BrS pattern with LGE may serve as early markers for evolution of a cardiomyopathic phenotype over time. CMR is a potentially useful adjunct investigation in the clinical evaluation of BrS.

A case of an avoidable admission to an Ebola treatment unit with malaria and an associated heat illness

We present a 27-year old British nurse admitted to the Kerry Town Ebola Treatment Unit, Sierra Leone, with symptoms fitting suspect-Ebola virus disease (EVD) case criteria. A diagnosis of Plasmodium falciparum malaria and heat illness was ultimately made, both of which could have been prevented through employing simple measures not utilised in this case. The dual pathology of her presentation was atypical for either disease meaning EVD could not be immediately excluded. She remained isolated in the red zone until 72 h from symptom onset. This case highlights why force protection measures are important to reduce the incidence of both malaria and heat illness in deployed military and civilian populations. These prevention measures are particularly pertinent during the current EVD epidemic where presenting with these pathologies requires clinical assessment in the ‘red zone’ of an Ebola treatment unit.

An evaluation of the burden placed on the General Internal Medicine team at the Role 3 Hospital in Camp Bastion by UK Armed Forces personnel presenting with symptoms resulting from previously identified disease

Introduction During previous deployments of the British Armed Forces, a significant proportion of aeromedical evacuations were accounted for with recurrent symptoms from a known disease that had often triggered occupational medical downgrading. Many servicemen and women had deployed inappropriately, and by doing so became a burden on the deployed medical facilities. Commanders performing systematic medical risk assessments prior to departure might have prevented these individuals from deploying. This study was designed to assess the avoidable burden from recurrent disease during the current Afghanistan operation. Methods A cross-sectional study reviewing the hospital and computerised primary care medical records of consecutive patients admitted under the General Physicians to the Role 3 Hospital in Camp Bastion over 9 months from April 2011. The occupational medical grading, diagnosis, disposal and whether the disease was recurrent were recorded. Results Of 270 patients admitted, 14 (5.2%) were medically downgraded. The computerised records were unavailable for 31 (11.5%) patients. All those patients who were medically downgraded were graded ‘Medically Limited Deployable’. In the downgraded group, only one patient presented with recurrent symptoms from their pre-existing condition (Crohns disease). In the non-downgraded group, two patients presented with symptoms relating to their previous diagnoses. One presented with a second heat illness and should have been medically downgraded and not have been deployed, while the other patient had previously been investigated for recurrent syncope and was upgraded 6 months prior to deploying. All three patients underwent aeromedical evacuation but only two of these were considered to have been avoidable. Discussion The number of general medical admissions to the Role 3 Hospital due to a pre-existing disease is very low.

A review of the documentation in the British Armed Forces electronic patient record following discharge from the Role 3 Hospital in Camp Bastion

Introduction The British Role 3 Hospital in Camp Bastion, Afghanistan, uses a different electronic patient record (EPR) to Defence Primary Health Care and the two cannot directly communicate. Consequently, hospital discharge information is transferred by printed letter to primary care, introducing a step where information can be lost. This study was designed to test the hypothesis that the primary care EPR contained an accurate summary of the secondary care admission. Methods Cross-sectional information on consecutive General Internal Medicine patients at the hospital was collected and compared with the primary care EPR. Results From April 2011 the hospital records of 270 patients were reviewed. 239 primary care records were available for comparison. Of 185 patients discharged back to their unit the EPR of 43.8% contained a comprehensive summary, 23.2% contained the scanned discharge letter and 50.8% contained an account of their hospital admission but not necessarily a comprehensive summary. Of the 54 patients evacuated to the UK, the EPRs of 48.1% contained a summary, 68.1% contained the scanned discharge letter and 75.9% contained some account of their hospital admission. More of the evacuated group had their admission documented in the primary care EPR (p=0.001). Only 56.5% of all primary care records contained some account of the hospital admission. Discussion The primary care record is not a reliable record of operational hospital admission and presents an unrecognised potential patient safety issue. The systems responsible for the transfer of discharge summary data need to be appraised to prevent it continuing. Retrospective action should be considered to rectify this problem in former hospital patients.

Apical ballooning (takotsubo) syndrome with concurrent ST-segment elevation myocardial infarction

We present the case of a 61-year-old woman admitted with chest pain and an ECG demonstrating ST-segment elevation in the lateral leads. Emergency coronary angiography demonstrated an occluded obtuse marginal branch. Percutaneous intervention was unsuccessful as the lesion could not be crossed with a wire. Left ventriculography and transthoracic echocardiography demonstrated hypokinesis of the entire apex but preserved contractility of the basal segments, consistent with a diagnosis of apical ballooning syndrome (ABS). Cardiac MRI demonstrated myocardial oedema in all mid to apical segments, with a left ventricular ejection fraction (LVEF) of 38%. Repeat study at 5 months demonstrated an infarct in the distribution of the occluded artery with late gadolinium enhancement, consistent with a diagnosis of a lateral wall myocardial infarction and an improvement in the LVEF to 51%. The case illustrates the novel observation that ABS and acute myocardial infarction may rarely occur simultaneously.

The Hearts of Heroes: the epidemiology of cardiac disease in the UK Armed Forces

When the general public look from the outside at the armed services, their impression is often one of earnest young men and women who are the pinnacle of physical fitness and health, and put their lives on the line for their country. There is usually sadness and respect for those killed on active operations, having put themselves in harms way. Therefore, when the public discover that more than 1 in 10 deaths in the UK Armed Forces are due to cardiovascular disease, the air of sadness is invariably replaced with surprise and disbelief. These figures, while lower than those due to deaths in accidents, are approaching the numbers of those due to suicide in the armed services; yet deaths from cardiac disease are barely recognised by society, in spite of many of them being avoidable. This article reviews the epidemiology of cardiac disease in the UK Armed Forces, both in terms of morbidity and mortality. It outlines current understanding and gaps in the knowledge regarding the burden of cardiovascular disease in the military population. The particular demographics of the Armed Forces and its influence on cardiac disease burden are discussed. The role of inherited and congenital diseases in younger servicemen and women is highlighted, as is the trend that with increasing age, the burden of disease shifts to ischaemic heart disease, which becomes the dominant cause of both death and disability.