A clinical score to obviate the need for cardiac stress testing in patients with acute chest pain and negative troponins.

INTRODUCTION: Although cardiac stress testing may help establish the safety of early discharge in patients with suspected acute coronary syndromes and negative troponins, more cost-effective strategies are necessary. We aimed to develop a clinical prediction rule to safely obviate the need for cardiac stress testing in this setting. METHODS: A decision rule was derived in a prospective cohort of 3001 patients with acute chest pain and negative troponins, and validated in a set of 1473 subjects. The primary end point was a composite of positive cardiac stress testing (in the absence of a subsequent negative coronary angiogram), positive coronary angiography, or any major coronary events within 3 months. RESULTS: A score chart was built based on 7 variables: male sex (+2), age (+1 per decade from the fifth decade), diabetes mellitus (+2), hypercholesterolemia (+1), prior coronary revascularization (+2), type of chest pain (typical angina, +5; non-specific chest pain, -3), and non-diagnostic repolarization abnormalities (+2). In the validation set, the model showed good discrimination (c statistic = 0.84; 95% confidence interval, 0.82-0.87) and calibration (Hosmer-Lemeshow goodness-of-fit test, P= .34). If stress tests were avoided in patients in the validation sample with a sum score of 0 or lower, the number of referrals would be reduced by 23.4%, yielding a negative predictive value of 98.8% (95% confidence interval, 97.0%-99.7%). CONCLUSION: This novel prediction rule based on a combination of readily available clinical characteristics may be a valuable tool to decide whether stress testing can be reliably avoided in patients with acute chest pain and negative troponins.

Impact of electrocardiographic interpretability on outcome in patients referred for stress testing.

BACKGROUND: There is limited insight into the association of electrocardiographic interpretability with outcome in patients referred for stress testing. METHODS: Exercise echocardiography was performed in 8226 patients with known or suspected coronary artery disease. Electrocardiograms were considered uninterpretable in the presence of left bundle-branch block (LBBB), left ventricular hypertrophy (LVH) with strain, repolarization abnormalities because of digitalis therapy, ventricular paced rhythm, preexcitation or ST depression ≥ 0.1 mV because of other causes. End points were all-cause mortality, cardiac death and hard cardiac events (i.e. cardiac death or nonfatal myocardial infarction). RESULTS: A total of 2450 patients had uninterpretable electrocardiograms. During a follow-up period of 4.1 ± 3.5 years, there were 1011 deaths (of which 478 were cardiac deaths) and 1069 patients experienced a hard cardiac event. The 5-year rates of death, cardiac death and hard cardiac events were, respectively, 18.7%, 10.9% and 18.8% in patients with uninterpretable ECGs, compared with 9.5%, 4.1% and 10.9% in those with interpretable ECGs (P < 0.001). After covariate adjustment, lack of ECG interpretability remained an independent predictor of all-cause mortality (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.08-1.44, P = 0.002), cardiac death (HR 1.63, 95% CI 1.32-2.01, P < 0.001) and hard cardiac events (HR 1.28, 95% CI 1.11-1.47, P < 0.001). When the specific ECG abnormalities were included as covariates, LBBB, LVH and digitalis therapy remained predictors of cardiac death; LBBB and LVH were predictors of hard cardiac events, and LVH remained predictive of all-cause mortality. CONCLUSION: Uninterpretable ECGs portend a worse prognosis in patients referred for stress testing.

Left atrial size and risk for all-cause mortality and ischemic stroke.

BACKGROUND: Limited data are available on the relation between left atrial size and outcome among patients referred for clinically indicated echocardiograms. Our aim was to assess the association of left atrial size with all-cause mortality and ischemic stroke in a large cohort of patients referred for echocardiography. METHODS: Left atrial diameter was measured in 52 639 patients aged 18 years or older (mean age 61.8 [standard deviation (SD) 16.3] years; 52.9% men) who underwent a first transthoracic echocardiogram for clinical reasons at our institution between April 1990 and March 2008. The outcomes were all-cause mortality and nonfatal ischemic stroke. RESULTS: Based on the criteria of the American Society of Echocardiography, 50.4% of the patients had no left atrial enlargement, whereas 24.5% had mild, 13.3% had moderate and 11.7% had severe left atrial enlargement. Over a mean follow-up period of 5.5 (SD 4.1) years, 12 527 patients died, and 2314 patients had a nonfatal ischemic stroke. Cumulative 10-year survival was 73.7% among patients with normal left atrial size, 62.5% among those with mild enlargement, 54.8% among those with moderate enlargement and 45% among those with severe enlargement (p < 0.001). After adjustment in multivariable Cox proportional hazard analysis, left atrial diameter remained a predictor of all-cause mortality in both sexes (hazard ratio [HR] per 1-cm increment in left atrial size 1.17, 95% confidence interval [CI] 1.12-1.22, p < 0.001 in women, and HR 1.09, 95% CI 1.05-1.13, p < 0.001 in men) and of ischemic stroke in women (HR 1.25, 95% CI 1.14-1.37, p < 0.001). INTERPRETATION: Left atrial diameter has a graded and independent association with all-cause mortality in both sexes and with ischemic stroke in women.

Value of exercise echocardiography for predicting mortality in elderly patients.

BACKGROUND: Elderly patients with suspected or known coronary artery disease are often referred for pharmacological stress testing. Data on the value of exercise echocardiography (ExEcho) for predicting outcome (particularly all-cause mortality) in these patients are scarce. METHODS: Peak treadmill ExEcho was performed in 2159 patients ≥ 70 years of age with known or suspected coronary artery disease. Left ventricular wall motion was evaluated at baseline and with exercise, and the increase in wall motion score index from rest to peak exercise (ΔWMSI) was calculated. Ischaemia was diagnosed when new or worsening wall motion abnormalities developed with exercise. The end points were all-cause mortality and major cardiac events (cardiac death or myocardial infarction). RESULTS: Ischaemia developed in 844 patients (38·6%) during exercise. Over a mean follow-up of 3·5 ± 3·1 years, 439 deaths occurred. The cumulative 5-year mortality rate was 29·3% in patients with ischaemia versus 16·8% in those without ischaemia (P < 0·001). After covariate adjustment, ΔWMSI remained an independent predictor of mortality [hazard ratio (HR) 2·37, 95% confidence interval (CI) 1·66-3·39, P < 0·001] and major cardiac events (HR 3·48, 95% CI 2·11-5·74, P < 0·001). These results remained significant even in patients with chronotropic incompetence. When added to a model with clinical, resting echocardiographic and exercise electrocardiogram variables, ExEcho results provided incremental value for the prediction of both end points (P < 0·001). CONCLUSIONS: ExEcho is feasible in elderly patients with suspected or known coronary artery disease and provides useful information for risk stratification in these patients.

Prognostic value of exercise echocardiography in patients with atrial fibrillation.

AIMS: Non-invasive imaging techniques for the detection of coronary artery disease (CAD) may have technical problems in patients with atrial fibrillation (AF). Although the prognostic value of exercise echocardiography (ExEcho) has been well established in several subgroups of patients, it has not yet been specifically evaluated in these patients. METHODS AND RESULTS: From a population of 8095 patients with known or suspected CAD referred for ExEcho, 419 had AF at the time of the tests. Ischaemia was defined as the development of new or worsening wall motion abnormalities with exercise. Endpoints were hard cardiac events (i.e. cardiac death or non-fatal myocardial infarction). Mean age was 68.4 +/- 8.5 years, and 256 patients (61.1%) were men. Ischaemia was detected in 92 patients (22%). Over a mean follow-up of 3.10 +/- 2.98 years, 59 hard cardiac events occurred. The 5-year hard cardiac event rate was 37.3% in patients with ischaemia, when compared with 14.5% in patients without ischaemia (P < 0.001). In multivariate analysis, ischaemia on ExEcho remained an independent predictor of hard cardiac events (hazard ratio 1.99, 95% confidence interval 1.06-3.74, P = 0.03), and also provided incremental value over clinical, resting echocardiographic and treadmill exercise data for the prediction of hard cardiac events (P = 0.04). CONCLUSION: ExEcho provides significant prognostic information for predicting hard cardiac events in patients with AF.

Oral contrast echocardiography for the diagnosis of left atrial encroachment.

The differential diagnosis of masses encroaching on the left atrium may be challenging. We describe a case in which contrast echocardiography using a carbonated drink provided a rapid and simple way to clarify the diagnosis of an incidental mass causing extrinsic compression of the left atrium. Given its simplicity and availability, we believe that it should be considered as a first line tool for clarifying the diagnosis in cases of echocardiographic evidence of left atrial encroachment of unknown origin.

Extrinsic compression of the left atrium by a mediastinal hematoma secondary to inadvertent carotid puncture.

We present the case of a 63-year-old man who underwent surgical closure of a paravalvular mitral leak. Immediately after surgery, transesophageal echocardiography revealed the appearance of a mediastinal hematoma encroaching on the left atrium and separating the esophageal probe from the posterior left atrial wall. The cause was an inadvertent puncture of the carotid artery, presumably during central venous line insertion prior to surgery.

Value of the coronary artery disease consortium rule in patients with acute chest pain and negative troponins referred for exercise stress testing.

OBJECTIVE: To assess the value of the pretest probability (PTP) of coronary artery disease (CAD) for predicting stress testing results and coronary events in patients with acute chest pain and negative troponins. PATIENTS AND METHODS: A total of 3527 patients without a history of CAD referred to our chest pain unit with suspected acute coronary syndromes, nondiagnostic ECGs, and negative troponin levels underwent exercise stress testing. PTP was estimated with the CAD consortium prediction rule, and was categorized as low (<15%), low-intermediate (15-65%), intermediate-high (66-85%), and high (>85%). The endpoints were the presence of signs of inducible myocardial ischemia on stress testing and the occurrence of coronary events within 6 months. RESULTS: The probability of exercise-induced myocardial ischemia was 2.6, 12.6, 42.9, and 82.1% in patients with low, low-intermediate, intermediate-high, and high PTP, respectively (Ptrend<0.001). The cumulative rate of coronary events within 6 months was also significantly lower in patients with low PTP of CAD (0.8%) than in those with low-intermediate (6.9%), intermediate-high (32.5%), or high PTP (66.7%) (Ptrend<0.001). Per 10% increment in PTP of CAD, the adjusted odds ratios for inducible myocardial ischemia and coronary events within 6 months were, respectively, 1.71 (95% confidence interval: 1.61-1.85) and 1.87 (95% confidence interval: 1.74-2.01). CONCLUSION: PTP was associated strongly with the likelihood of exercise-induced myocardial ischemia and coronary events in patients with suspected acute coronary syndromes and negative troponins. The yield of stress testing in the subset of patients with low PTP was very low.

Indexed left atrial size predicts all-cause and cardiovascular mortality in patients undergoing aortic valve surgery.

OBJECTIVES: The enlargement of the left atrium has been identified as a marker of chronically increased left ventricular filling pressure and left ventricular diastolic dysfunction. This study aims to evaluate the association of indexed left atrial diameter with stroke, cardiovascular mortality, the combined event, and all-cause mortality in patients who underwent aortic valve surgery. METHODS: Indexed left atrial diameter was measured in 2011 adult patients (mean age, 70.9 ± 10.8 years; 58.7% were men) who underwent aortic valve surgery between January 2008 and March 2016. RESULTS: On the basis of the criteria of the American Society of Echocardiography, indexed left atrial diameter was normal in 64% of patients, mildly enlarged in 12.4% of patients, moderately enlarged in 9.2% of patients, and severely enlarged in 14.3% of patients. Over a mean follow-up period of 3.2 ± 2.1 years, there were 334 deaths and 97 strokes. Cardiovascular mortality survival at 5 years among patients with normal, mild, moderate, and severe left atrial enlargement was 91.6%, 86.8%, 77.9%, and 77.4%, respectively (P < .001). After covariable adjustment, Cox regression analysis showed indexed left atrial diameter as an independent predictor of all-cause mortality (hazard ratio per 1-cm/m2 increment, 1.545; 95% confidence interval, 1.252-1.906, P < .001), cardiovascular death (hazard ratio per 1-cm/m2 increment, 1.971; 95% confidence interval, 1.541-2.520; P < .001), and the combined event (hazard ratio per 1-cm/m2 increment, 1.673; 95% confidence interval, 1.321-2.119; P < .001). CONCLUSIONS: Indexed left atrial diameter is a strong predictor of long-term outcomes in patients with aortic valve diseases who undergo surgery.

[Diagnostic and prognostic efficiency of 24-hour Holter monitoring in patients with syncope]. / Rendimiento diagnóstico y pronóstico del registro Holter de 24horas en pacientes con síncope.

BACKGROUND AND OBJECTIVE: Syncope is a common condition and complex to diagnose. The yield of the 24h-Holter ECG in this context has not been clearly defined. The aim of this study was to evaluate its diagnostic and prognostic capacity in these patients. PATIENTS AND METHOD: Retrospective study of 6,006 consecutive patients sent to our unit for 24h-Holter ECG monitoring for syncope. We registered the diagnostic findings and abnormal findings potentially related to an arrhythmic cause of syncope. The prognostic endpoint was a combination of death or the need for device implantation (pacemaker or defibrillator) within one year. RESULTS: 242 patients (4%) presented diagnostic findings and 472 (7.9%) had some abnormal findings. In 328 cases device implantation was necessary within one year, but up to 66% of these patients did not have any relevant findings on the Holter monitoring. A total of 564 patients presented the combined event, including 36.8% of patients with diagnostic findings and 8.2% without them. CONCLUSIONS: 24h-Holter ECG monitoring presents a limited diagnostic and prognostic yield in unselected patients with syncope.

Troponin levels within the normal range and probability of inducible myocardial ischemia and coronary events in patients with acute chest pain.

BACKGROUND/OBJECTIVES: Patients with suspected acute coronary syndromes and negative cardiac troponin (cTn) levels are deemed at low risk. Our aim was to assess the effect of cTn levels on the frequency of inducible myocardial ischemia and subsequent coronary events in patients with acute chest pain and cTn levels within the normal range. METHODS: We evaluated 4474 patients with suspected acute coronary syndromes, nondiagnostic electrocardiograms and serial cTnI levels below the diagnostic threshold for myocardial necrosis using a conventional or a sensitive cTnI assay. The end points were the probability of inducible myocardial ischemia and coronary events (i.e., coronary death, myocardial infarction or coronary revascularization within 3 months). RESULTS: The probability of inducible myocardial ischemia was significantly higher in patients with detectable peak cTnI levels (25%) than in those with undetectable concentrations (14.6%, p<0.001). These results were consistent regardless of the type of cTnI assay, the type of stress testing modality, or the timing for cTnI measurement, and remained significant after multivariate adjustment (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.21-1.79, p<0.001). The rate of coronary events at 3 months was also significantly higher in patients with detectable cTnI levels (adjusted OR 2.08, 95% CI 1.64-2.64, p<0.001). CONCLUSIONS: Higher cTnI levels within the normal range were associated with a significantly increased probability of inducible myocardial ischemia and coronary events in patients with suspected acute coronary syndromes and seemingly negative cTnI.

[Prognostic value of treadmill exercise echocardiography]. / Valor pronóstico de la ecocardiografía de ejercicio en cinta rodante.

INTRODUCTION AND OBJECTIVES: Exercise echocardiography (EE) is useful for diagnosing coronary disease, but little is known about its value for risk stratification. We aimed to determine: a) whether data from EE supplemented clinical data and data from exercise testing and resting echocardiography in predicting cardiac events; and b)whether the number and location of abnormal regions and their responses to exercise influenced risk stratification. PATIENTS AND METHOD: The 2,436 patients referred for EE were followed up for 2.1+/-1.5 years. Some 120 serious cardiovascular events (i.e., non-fatal myocardial infarction or cardiovascular death) occurred before revascularization. RESULTS: In 1203 patients (49%), EE gave abnormal results. There were 89 events in patients with an abnormal result (7.3%) and 31 in those with a normal result (2.5%; P<.0001). Multivariate analysis of clinical data, and data from exercise testing, resting echocardiography, and EE showed that male sex (RR=1.7; 95% CI, 1.1-2.8; P=.02), metabolic equivalents or METs (RR=0.9; 95% CI, 0.86-0.98; P=.01), peak heart rate x blood pressure (RR= 0.9;95% CI, 0.9; P=.002), resting wall motion score index (RR=2.5; 95% CI, 1.5-4.1; P<.0001), and number of abnormal regions at peak exercise (RR=1.4; 95% CI, 1.2-1.7; P<.0001) were independently associated with the risk of a serious event (final model chi2, 170; incremental P<.0001). The same variables, excluding sex, were independently associated with cardiovascular death (final model chi2, 169; incremental P=.01). CONCLUSIONS: Exercise echocardiography supplements clinical data and data from exercise testing and resting echocardiography in patients with known or suspected coronary artery disease.

Trends in referral patterns, invasive management, and mortality in elderly patients referred for exercise stress testing.

INTRODUCTION: Scarce data are available on the temporal patterns in clinical characteristics and outcomes of elderly patients referred for exercise stress testing. We aimed to assess the trends in baseline characteristics, tests results, referrals for invasive management, and mortality in these patients. METHODS: We evaluated 11,192 patients aged ≥65years who were referred for exercise stress testing between January 1998 and December 2013. Calendar years were grouped into four quadrennia (1998-2001, 2002-2005, 2006-2009, and 2010-2013), and trends in clinical characteristics of the patients, type and results of the tests, referrals for invasive management, and mortality across the different periods were assessed. RESULTS: Despite a progressive decrease in the proportion of patients with non-interpretable baseline electrocardiograms or prior history of coronary artery disease, there was a gradual and marked increase in the use of cardiac imaging from 32.8% in 1998-2001 to 67.6% in 2010-2013 (p<0.001). In addition, despite a gradual decline in the probability of positive exercise stress testing both without imaging (from 18.9 to 13.6%, p<0.001) and with imaging assessment (from 40.2 to 29.7%, p<0.001), the cumulative rate of coronary revascularization at 1year increased (from 10.8 to 13.7%, p<0.001). One-year mortality also decreased progressively from 3% to 1.6% (p<0.001). CONCLUSIONS: Among older adults referred for exercise stress testing, we observed a decline over time in the probability of inducible myocardial ischemia, an increase in the use of cardiac imaging and in the rate of coronary revascularization, and an improvement in the survival rate at 1year.

Incremental value of exercise echocardiography over exercise electrocardiography in a chest pain unit.

BACKGROUND: Limited data are available on the added value of exercise echocardiography (ExEcho) over exercise electrocardiography (ExECG) in patients with suspected acute coronary syndromes (ACS) referred to a chest pain unit. We aimed to assess the incremental value of ExEcho over ExECG in this setting. METHODS: ExECG and ExEcho were performed in parallel in 1052 patients with suspected ACS, nondiagnostic but interpretable electrocardiograms, and negative serial troponin results. The primary outcome was a composite of coronary death, nonfatal myocardial infarction or unstable angina with angiographic documentation of significant coronary artery disease within 6 months. RESULTS: The primary outcome occurred in 2/614 patients (0.3%) with both negative ExECG and ExEcho, 3/60 (5%) with positive ExECG and negative ExEcho, 73/135 (54.1%) with negative ExECG and positive ExEcho, 106/136 (77.9%) with both positive ExECG and ExEcho, and 8/107 (7.5%) with inconclusive results. The addition of ExEcho data to a model based on clinical and ExECG data significantly increased the c statistic from 0.898 to 0.968 (change +0.070, 95% confidence interval 0.052-0.092), with a continuous net reclassification improvement of 1.56 and an integrated discrimination improvement of 22% (p<0.001). Decision curve analysis showed that a strategy of referral to coronary angiography based on ExEcho was associated with the highest net benefit and with the largest reduction in unnecessary coronary angiographies. CONCLUSION: ExEcho provides significant incremental prognostic information and higher net clinical benefit than a strategy based on ExECG in patients referred to a chest pain unit for suspected ACS and negative troponin levels.

Temporal changes in the use and results of exercise echocardiography.

AIMS: Limited data are available regarding changes over time in referral patterns and outcomes of non-invasive cardiac stress testing. Our aim was to evaluate the temporal changes in the use and results of exercise echocardiography in our area of reference. METHODS AND RESULTS: A total of 12 339 patients referred to our unit for exercise echocardiography between 1997 and 2012 were included. We divided the 16-year period into four quadrennia and evaluated the changes in clinical data, results of the tests, referrals for invasive management and outcomes. We observed a gradual decrease in the frequency of detection of myocardial ischaemia from 35.3% in1997-2000 to 25.4% in 2009-12 (P < 0.001). There was also a progressive increase in the prevalence of cardiovascular risk factors and in the frequency of non-ischaemic chest pain and dyspnoea, while the proportion of patients with prior myocardial infarction and non-interpretable electrocardiograms declined. The rate of referral to coronary angiography within 6 months decreased from 24.8% in 1997-2000 to 19.6% in 2009-12 (P < 0.001), but the rate of coronary revascularization remained almost unchanged (13.1 to 11.7%, P for the trend = 0.16). We also observed a progressive decrease in the 1-year mortality rate from 3.4 to 1% (P < 0.001). CONCLUSION: Over a 16-year period, there was a gradual decrease in the frequency of myocardial ischaemia among patients referred to our unit for exercise echocardiography, which was parallel to changes in their clinical profile. However, this was not accompanied by a significant reduction in the rate of coronary revascularization.