Benoy N. Shah

Clinical features of radiation-induced carotid atherosclerosis.

Carotid arteries frequently receive significant incidental doses of radiation during the treatment of malignant diseases, including head and neck cancer, breast cancer and lymphoma. Vascular injury after treatment may result in carotid artery stenosis and increased risk of neurological sequelae, such as stroke and transient ischaemic attack. The long latent interval from treatment to the development of clinical complications makes investigation of this process difficult, particularly in regard to the design of interventional clinical studies. Nevertheless, there is compelling clinical evidence that radiation contributes to carotid atherosclerosis. This overview examines the effect of radiotherapy on the carotid arteries, the underlying pathological processes and their clinical manifestations. The use of serum biomarkers in risk-prediction models and the potential value of new imaging techniques as tools for defining earlier surrogate end points will also be discussed.

Incremental Diagnostic and Prognostic Value of Contemporary Stress Echocardiography in a Chest Pain Unit Mortality and Morbidity Outcomes From a Real-World Setting

Background— Clinical assessment often cannot reliably or rapidly risk stratify patients hospitalized with suspected acute coronary syndrome. The real-world clinical value of stress echocardiography (SE) in these patients is unknown. Thus, we undertook this study to assess the feasibility, safety, ability for early triaging, and prediction of hard events of SE incorporated into a chest pain unit for patients admitted with acute chest pain, nondiagnostic ECG, and negative 12-hour troponin. Methods and Results— Accordingly, 839 consecutive patients who underwent clinical, ECG, and SE assessments within 24 hours of admission were assessed for feasibility, safety, impact on triaging and discharge, and 30-day readmission rate and were followed up for hard events (all-cause mortality and acute myocardial infarction). Of the 839 patients, 811 (96.7%) had diagnostic SE results. Median time to SE and median length of stay for normal SE patients (77%) were both 1 day. The 30-day readmission rate was 0.5%. During long-term follow-up of 27±11 months, 39 hard events (30 deaths and 9 acute myocardial infarctions) occurred. Kaplan-Meier estimates of hard events were 0.5% versus 6.6% in the normal versus abnormal SE groups, respectively, in the first year of follow-up (15 events in the first year). Among all prognostic variables, only abnormal SE (hazard ratio, 4.08; 95% confidence interval, 2.15–7.72; P<0.001) and advancing age (hazard ratio, 1.78; 95% confidence interval, 1.39–2.37; P<0.001) predicted hard events in multivariable regression analysis. Conclusions— SE incorporated into a chest pain unit has excellent feasibility and provides rapid assessment and discharge with accurate risk stratification of patients with suspected acute coronary syndrome but nondiagnostic ECG and negative 12-hour troponin.

Takotsubo (apical ballooning) syndrome in the recovery period following dobutamine stress echocardiography: a first report

We report a case of Takotsubo syndrome occurring in the recovery phase after a dobutamine stress echocardiogram. Takotsubo syndrome is a widely acknowledged cause of reversible left ventricular systolic dysfunction. It has garnered much attention from the cardiological community since its presentation frequently mimics that of ST-segment elevation myocardial infarction. The exact aetiology remains incompletely defined, although stress is recognized frequently as a precipitating factor. In recent years it has emerged that stress testing, as part of a patients investigative assessment, can also induce Takotsubos syndrome. All prior reports of dobutamine-induced Takotsubos syndrome have described apical ballooning at peak stress. We describe the case of an 85-year-old lady who developed apical ballooning in the recovery period after a dobutamine stress echocardiogram, despite having normal left ventricular wall motion at rest and at peak stress. We believe this to be the first such case reported in the literature. Dobutamine stress testing can precipitate Takotsubos syndrome not just at peak stress but also during the recovery period. All those performing dobutamine stress tests should be aware of this rare but potentially important complication.

The Feasibility and Clinical Utility of Myocardial Contrast Echocardiography in Clinical Practice: Results from the Incorporation of Myocardial Perfusion Assessment into Clinical Testing with Stress Echocardiography Study

BACKGROUND This prospective study investigated whether the incorporation of myocardial contrast echocardiography (MCE) into a clinical stress echocardiography service reproduces the benefits of assessing myocardial perfusion proved previously in research studies. METHODS MCE was performed during physiologic and pharmacologic clinical stress echocardiographic studies, and the value of myocardial perfusion to the reporting echocardiologists was categorized as of benefit (subclassified as incremental benefit over wall motion [WM] or greater confidence with WM) or of no added benefit. The presence and extent of inducible ischemia by WM and myocardial perfusion were documented and correlated with angiographic results in patients who underwent cardiac catheterization. RESULTS In total, 220 patients underwent simultaneous MCE during stress echocardiography by eight different operators. Overall, MCE was of benefit in 193 patients (88%), providing incremental benefit over WM in 25% and greater confidence with WM evaluation in 62%. MCE provided no added benefit in 27 patients (12%). MCE detected significantly more cases of ischemia than WM in the left anterior descending coronary artery territory (65% vs 53%, P = .02) and detected a greater ischemic burden than WM on a per patient basis (median, 5 [interquartile range, 3-8] vs 4 [interquartile range, 2-7] segments; P < .001) and across all coronary territories. MCE correctly identified a greater proportion of patients with multivessel disease than WM (76% vs 56%, P = .02) and a greater ischemic burden in patients with multivessel disease (median, 7 [interquartile range, 4-9] vs 5 [interquartile range, 1-8] segments; P < .001). CONCLUSIONS This prospective study is the first to demonstrate that the excellent feasibility and diagnostic utility of MCE, which have been documented in the research arena, are reproducible in the clinical arena.

Clinical and prognostic value of stress echocardiography appropriateness criteria for evaluation of coronary artery disease in a tertiary referral centre

Objective Appropriateness criteria for stress echocardiography (SE) have been published to reduce the rate of inappropriate testing. We sought to investigate the clinical impact and prognostic value of these criteria. Methods 250 consecutive patients undergoing SE for evaluation of coronary artery disease were classified into appropriate, uncertain and inappropriate categories according to appropriateness criteria. A positive SE was defined as the development of new wall motion abnormalities or a biphasic response. The primary end point was the composite of myocardial infarction and death. Results Of the 250 SE, 120 (48%) were dobutamine studies and 130 (52%) were exercise studies. 156 (62.4%), 71 (28.4%) and 23 (9.2%) were classified as appropriate, inappropriate and uncertain, respectively. A significantly greater proportion of studies classified as appropriate 71 (45.5%) demonstrated inducible ischaemia compared with inappropriate studies 9 (12.7%) or uncertain studies 4 (17.4%), p<0.0001. During a median follow-up of 12.4 months, events occurred in 18 (11.5%), 2 (2.8%) and 0 patients classified as appropriate, inappropriate and uncertain, respectively. Event-free survival was significantly reduced in patients with a SE demonstrating ischaemia compared with patients without inducible ischaemia, p<0.0001. Kaplan–Meier curves demonstrated reduced event-free survival in patients with whose studies were classified as appropriate compared to inappropriate (p=0.01) or uncertain (p=0.05). Conclusions Appropriateness criteria differentiate between patients at high risk of ischaemia, subsequent revascularisation/cardiac events (appropriate group) and those at low risk of events (inappropriate group). A large proportion of SE is currently performed in inappropriate patients. Implementation of the criteria in clinical practice would reduce unnecessary testing.

Myocardial Contrast Echocardiography for Simultaneous Assessment of Function and Perfusion in Real Time A Technique Comes of Age

Contrast agents are now widely used in stress echocardiography (SE) to improve visualization of the endocardial border, improve confidence in wall motion assessment, and reduce the number of uninterpretable images. The use of contrast agents in SE has also been shown to improve accuracy of wall motion assessment for the detection of coronary artery disease (CAD) compared with unenhanced SE images.1 Contrast stress echocardiography has been shown to impact positively on downstream costs.2 The ability of contrast agents, which contain microbubbles that mimic red blood cell rheology, to enable visualization of myocardial perfusion resulted in rapid development of both microbubble and equipment technology that allowed the use of contrast echocardiography for the detection of myocardial perfusion in clinical cardiology.3 Numerous single and multicenter studies have proved that myocardial contrast perfusion stress echocardiography is now a clinical tool for the detection of CAD.4 The ability of myocardial contrast SE to assess function and perfusion simultaneously makes it a unique technique for the assessment of CAD. Article see p 1217 The study by Gaibazzi et al5 in this issue of Circulation adds to the growing literature of the prognostic value of perfusion and function assessed simultaneously …

Clinical Utility and Prognostic Value of Appropriateness Criteria in Stress Echocardiography for the Evaluation of Valvular Heart Disease

We examined the prognostic value of stress echocardiography appropriateness criteria for evaluation of valvular heart disease in 100 consecutive patients. Of the studies, 49%, 36%, and 15% were classified as appropriate, uncertain, and inappropriate, respectively. Over a median of 12.6 months, 24 events (12 deaths and 12 heart failure admissions) occurred. The 12-month event-free survival was significantly reduced in patients with appropriate or uncertain studies compared with patients with inappropriate studies (p = 0.04 and p = 0.005, respectively). There was no survival difference between patients with an appropriate or uncertain indication (p = 0.1). The only independent predictors of events were a positive stress echocardiogram (hazard ratio: 15.5, p < 0.0001) and left ventricular ejection fraction (hazard ratio: 0.95, p = 0.02). The appropriateness criteria for evaluation of valvular heart disease provide the ability to differentiate between patients at high- (appropriate group) and low- (inappropriate group) risk of cardiac events. Reclassification of the uncertain group may improve the differential value of these criteria.

Valvular heart disease: a call for global collaborative research initiatives

The burden of valvular heart disease (VHD) is rising rapidly as life expectancy increases. The prevalence in the USA alone is 13% in those aged over 75 years,1 while the global prevalence of rheumatic heart disease is estimated at 15.6–19.6 million.2 Despite this, the treatment of VHD still lacks an adequate research base. None of the 64 recommendations in the 2012 European Society of Cardiology (ESC) VHD guidelines3 had Level A evidence and only 14% had Level B evidence. This compares with 28% at Level A and 42% at Level B among the 270 recommendations in the 2010 ESC myocardial revascularisation guidelines.4 Therefore, there is an urgent need to stimulate the investigation. In this article, we identify deficits in our knowledge which may be amenable to research and make a call for national and international collaborative efforts to address this evidence gap. The prevalence of VHD in industrialised countries has been extrapolated from studies predominantly conducted in the USA,1 while the prevalence of rheumatic disease in sub-Saharan Africa is extrapolated from studies in North Africa. True figures need to be established nationally, while for rare causes of VHD (eg, carcinoid or antiphospholipid syndrome), this might be better done using international registries with standardised protocols. Serial echocardiography within these projects will improve our understanding of the contemporary natural history of VHD, which was previously determined in small cohorts of patients and generally with fewer comorbidities compared with the present. The genetics and developmental biology of VHD are poorly understood. Collation of genetic analyses from established bio-banks and twin studies may identify new determinants of disease or its progression. Such techniques may also provide clues towards the development of treatments for challenging conditions such as endomyocardial fibrosis. Lipid-lowering therapy has not been successful in modifying the progression …

The clinical impact of contemporary stress echocardiography in morbid obesity for the assessment of coronary artery disease

Objective Non-invasive cardiac imaging may suffer from poor image quality in morbidly obese individuals. This study aimed to determine the clinical value of contemporary stress echocardiography (SE) in morbidly obese patients referred for assessment of suspected coronary artery disease (CAD). Methods This prospective, multicentre observational study was conducted in two district hospitals and one tertiary centre in London, UK. Individuals with body mass index ≥35 kg/m2 referred for SE were evaluated. The percentage of patients with obstructive CAD on coronary angiography, following abnormal SE, was assessed. Patient outcomes were determined with follow-up for the composite end-point of all-cause mortality, myocardial infarction and late revascularisation. Results Over a 13-month period, 209 morbidly obese patients underwent SE, and contrast agent was used in 96% of patients. A diagnostic result was obtained in 200/209 (96%) patients. Of 32 (15%) patients with inducible ischaemia, 25 underwent angiography, 22 (88%) had corresponding significant CAD and, of these, 16 (77%) underwent revascularisation. Conversely, only 2/157 patients (1.3%) with normal SE underwent angiography, and none underwent revascularisation. Over a mean follow-up period of 17.8±5.4 months, there were nine events. The annualised cardiac event rate after a normal SE was 0.95%. Events were more frequent in patients with inducible ischaemia versus those without ischaemia (5/32 (15.6%) vs 4/153 (2.6%); p=0.002). Ejection fraction <50% (HR 9.5; 95% CI 2.4 to 38.0; p=0.002) and inducible ischaemia (HR 9.4; 95% CI 2.5 to 35.8; p=0.001) were predictors of outcome on univariable Cox regression analysis. Conclusions Contemporary SE has excellent feasibility and positive predictive value and resulted in appropriate risk stratification of symptomatic patients with significant obesity. A normal SE portends an excellent outcome over the short–intermediate term in this high-risk patient population.

On the 50th anniversary of the first description of a multistage exercise treadmill test: re-visiting the birth of the ‘Bruce protocol’

This calendar year, 2013, marks the 50th anniversary of the publication of an article which, unbeknown to the authors, was the first report of what would become one of the most widely used and researched tests in clinical cardiology throughout the world during the 20th century—the Bruce protocol exercise treadmill test (ETT).1 This editorial describes the historical background to the introduction of the ETT, the rationale for a multistage protocol, the first account of the ‘Bruce protocol’ and provides a brief discussion on the late Professor Robert Bruce himself. Although it had long been known that evaluating a symptomatic patient during exertion might disclose evidence of coronary artery disease, before the advent of the Bruce treadmill test there was no safe, standardised and validated stress protocol that could be used to monitor cardiovascular haemodynamic changes in exercising patients. Masters two-step test,2 a submaximal exercise test for diagnosing ‘coronary insufficiency’ (in which ECGs were recorded during and after a patient repeatedly ascended and descended two steps) was often used, but it was too strenuous for some patients, inadequate for simultaneous assessment of cardiac and respiratory function during exercise and, measured by the energy expenditure per unit of weight, stressed the underweight patient considerably more than the overweight patient.1 Submaximal stress tests were the preferred stress technique; the concept of testing patients to their maximum exercise capacity was almost unthinkable, owing to the perceived risk of complications, a perception reinforced by reports of major complications even during submaximal stress testing.3 Nonetheless, Bruce recognised that many patients were not reliably or reproducibly stressed. Consequently, he tested initially a single-stage treadmill test in thousands of normal volunteers and subsequently, in cardiac patients, proving its feasibility, safety and reproducibility.4 This stress was only moderate for normal subjects and cardiac patients …