Recommendations for Statistical Reporting in Cardiovascular Medicine: A Special Report From the American Heart Association.

Statistical analyses are a crucial component of the biomedical research process and are necessary to draw inferences from biomedical research data. The application of sound statistical methodology is a prerequisite for publication in the American Heart Association (AHA) journal portfolio. The objective of this document is to summarize key aspects of statistical reporting that might be most relevant to the authors, reviewers, and readership of AHA journals. The AHA Scientific Publication Committee convened a task force to inventory existing statistical standards for publication in biomedical journals and to identify approaches suitable for the AHA journal portfolio. The experts on the task force were selected by the AHA Scientific Publication Committee, who identified 12 key topics that serve as the section headers for this document. For each topic, the members of the writing group identified relevant references and evaluated them as a resource to make the standards summarized herein. Each section was independently reviewed by an expert reviewer who was not part of the task force. Expert reviewers were also permitted to comment on other sections if they chose. Differences of opinion were adjudicated by consensus. The standards presented in this report are intended to serve as a guide for high-quality reporting of statistical analyses methods and results.

Performance of diagnostic criteria in patients clinically judged to have cardiac sarcoidosis: Is it time to regroup?

BACKGROUND: The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria to diagnose CS. AIMS: To compare the 3 main available diagnostic criteria in patients clinically judged to have CS. METHODS: We prospectively included patients clinically judged to have CS by a multidisciplinary sarcoidosis team from November 2016 to October 2017. We included only incident cases (diagnosis of CS within 1 year of inclusion). We applied retrospectively the following diagnostic criteria: the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), the Heart Rhythm Society (HRS), and the Japanese Circulation Society (JCS) 2016 criteria. RESULTS: We identified 69 patients. Diagnostic criteria classified patients as follows: WASOG as highly probable (1.4%), probable (52.2%), possible (0%), some criteria (40.6%), and no criteria (5.8%); HRS as histological diagnosis (1.4%), probable (52.2%), some criteria (40.6%), and no criteria (5.8%); JCS as histological diagnosis (1.4%), clinical diagnosis (58%), some criteria (39.1%), and no criteria (1.4%). Concordance was high between WASOG and HRS (κ = 1) but low between JCS and the others (κ = 0.326). CONCLUSIONS: A high proportion of patients clinically judged to have CS are unable to be classified according to the 3 main diagnostic criteria. There is low concordance between JCS criteria and the other 2 criteria (WASOG and HRS).

Technetium pyrophosphate uptake in transthyretin cardiac amyloidosis: Associations with echocardiographic disease severity and outcomes.

BACKGROUND: Quantitative uptake of Technetium 99 m-pyrophosphate (TcPYP) is sensitive and specific for diagnosing transthyretin cardiac amyloidosis (ATTR). We sought to examine the association between TcPYP uptake intensity and echocardiographic measures of disease severity and clinical outcomes. METHODS AND RESULTS: A retrospective analysis was performed of 75 patients who underwent TcPYP scintigraphy. Planar images were evaluated semiquantitatively and using heart-to-contralateral lung (H/CL) ratio. The associations between H/CL ratio and echocardiographic parameters and outcomes were evaluated using linear regression and Cox models, respectively. There were 48 patients diagnosed with ATTR with mean H/CL ratio 1.58 ± 0.22 (vs 1.08 ± 0.09 if semiquantitative score = 0). The H/CL ratio was not associated with any measured echocardiographic parameter. Both semiquantitative uptake grade and H/CL ratio were associated with all-cause mortality (P = 0.009 and 0.007, respectively) and all-cause mortality or heart failure hospitalization (P = 0.001 and 0.020, respectively); however, neither were associated with outcomes when limited to patients with confirmed ATTR (P = 0.18 and 0.465, respectively). CONCLUSION: In patients with suspected ATTR, quantitative and semiquantitative uptake intensity of TcPYP is associated with all-cause mortality as well as all-cause mortality or heart failure hospitalization. However, in those with confirmed ATTR, there is no association with echocardiographic disease severity or outcomes.

Evolving, innovating, and revolutionary changes in cardiovascular imaging: We've only just begun!

In this review, we highlight the need for innovation and creativity to reinvent the field of nuclear cardiology. Revolutionary ideas brought forth today are needed to create greater value in patient care and highlight the need for more contemporary evidence supporting the use of nuclear cardiology practices. We put forth discussions on the need for disruptive innovation in imaging-guided care that places the imager as a central force in care coordination. Value-based nuclear cardiology is defined as care that is both efficient and effective. Novel testing strategies that defer testing in lower risk patients are examples of the kind of innovation needed in today's healthcare environment. A major focus of current research is the evolution of the importance of ischemia and the prognostic significance of non-obstructive atherosclerotic plaque and coronary microvascular dysfunction. Embracing novel paradigms, such as this, can aid in the development of optimal strategies for coronary disease management. We hope that our article will spurn the field toward greater innovation and focus on transformative imaging leading the way for new generations of novel cardiovascular care.

The elusive role of myocardial perfusion imaging in stable ischemic heart disease: Is ISCHEMIA the answer?

The assessment of ischemia through myocardial perfusion imaging (MPI) is widely accepted as an index step in the diagnostic evaluation of stable ischemic heart disease (SIHD). Numerous observational studies have characterized the prognostic significance of ischemia extent and severity. However, the role of ischemia in directing downstream SIHD care including coronary revascularization has remained elusive as reductions in ischemic burden have not translated to improved clinical outcomes in randomized trials. Importantly, selection bias leading to the inclusion of many low risk patients with minimal ischemia have narrowed the generalizability of prior studies along with other limitations. Accordingly, an ongoing randomized controlled trial entitled ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) will compare an invasive coronary revascularization strategy vs a conservative medical therapy approach among stable patients with moderate to severe ischemia. The results of ISCHEMIA may have a substantial impact on the management of SIHD and better define the role of MPI in current SIHD pathways of care.

Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization.

BACKGROUND: Coronary flow reserve (CFR), an integrated measure of focal, diffuse, and small-vessel coronary artery disease (CAD), identifies patients at risk for cardiac death. We sought to determine the association between CFR, angiographic CAD, and cardiovascular outcomes. METHODS AND RESULTS: Consecutive patients (n=329) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography were followed (median 3.1 years) for cardiovascular death and heart failure admission. The extent and severity of angiographic disease were estimated with the use of the CAD prognostic index, and CFR was measured noninvasively by positron emission tomography. A modest inverse correlation was seen between CFR and CAD prognostic index (r=-0.26; P<0.0001). After adjustment for clinical risk score, ejection fraction, global ischemia, and early revascularization, CFR and CAD prognostic index were independently associated with events (hazard ratio for unit decrease in CFR, 2.02; 95% confidence interval, 1.20-3.40; P=0.008; hazard ratio for 10-U increase in CAD prognostic index, 1.17; 95% confidence interval, 1.01-1.34; P=0.032). Subjects with low CFR experienced rates of events similar to those of subjects with high angiographic scores, and those with low CFR or high CAD prognostic index showed the highest risk of events (P=0.001). There was a significant interaction (P=0.039) between CFR and early revascularization by coronary artery bypass grafting, such that patients with low CFR who underwent coronary artery bypass grafting, but not percutaneous coronary intervention, experienced event rates comparable to those with preserved CFR, independently of revascularization. CONCLUSIONS: CFR was associated with outcomes independently of angiographic CAD and modified the effect of early revascularization. Diffuse atherosclerosis and associated microvascular dysfunction may contribute to the pathophysiology of cardiovascular death and heart failure, and impact the outcomes of revascularization.

Outcomes for Patients With Diabetes After Continuous-Flow Left Ventricular Assist Device Implantation.

BACKGROUND: Diabetes mellitus (DM) is a risk factor for mortality among patients with heart failure as well as for patients who undergo cardiothoracic surgery. However it is unknown whether DM is associated with increased mortality or major complications during continuous-flow left ventricular assist device (CF-LVAD) support. METHODS AND RESULTS: We retrospectively reviewed 300 consecutive adults who received CF-LVADs at a single center in the years 2006-2013; 129 patients had DM before LVAD, as defined by American Diabetes Association criteria (HbA1c ≥6.5% and/or taking DM medications). Compared with the non-DM group, DM patients were older, with a higher pre-LVAD body mass index, more ischemic heart failure etiology, and higher pre-LVAD creatinine. Ninety-three patients died on LVAD support, 43 with DM and 50 without DM (P = .4526). After control for 9 covariates in a Cox proportional hazards model, DM was unassociated with all-cause mortality (hazard ratio 0.883, 95% confidence interval 0.571-1.366; P = .5768). Diabetes was also unassociated with the adverse event end points of stroke/transient ischemic attack, intracerebral hemorrhage, pump thrombosis, and device-related infections. CONCLUSIONS: Diabetes is common in LVAD recipients (43% of the present cohort) but does not increase mortality or rates of major adverse events during CF-LVAD support.

Impact of aortic valve replacement on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction.

BACKGROUND: The optimal management of low-gradient "severe" aortic stenosis (mean gradient <40 mm Hg, indexed aortic valve area ≤0.6 cm2/m2) with preserved left ventricular ejection fraction remains controversial because gradients may be similar after aortic valve replacement (AVR). We compared outcomes of low-gradient severe aortic stenosis with AVR or medical therapy. METHODS AND RESULTS: Comprehensive echocardiographic measurements including hemodynamic calculations were completed in 260 prospectively identified patients with symptomatic low-gradient severe aortic stenosis. Patients were followed up for mortality over 28±24 months. AVR was performed in 123 patients (47%). Compared with AVR patients, medically treated patients had a higher prevalence of diabetes mellitus (25% versus 41%, P=0.009), lower stroke volume index (36.4±8.4 versus 34.4±8.7 mL/m2, P=0.02), higher pulmonary artery pressure (38±11 versus 48±21 mm Hg, P=0.001), and higher creatinine level (1.1±0.4 versus 1.22±0.5 mg/dL, P=0.02). These and other clinically relevant variables were entered into a propensity model that reflected likelihood of referral to AVR. This score and other variables were entered into a Cox model to explore the independent effect of AVR on outcome. During follow-up, 105 patients died (40%): 32 (30%) in the AVR group and 73 (70%) in the medical treatment group. AVR (hazard ratio, 0.54; 95% confidence interval, 0.32-0.94; P<0.001) was independently associated with outcome and remained a strong predictor of survival after adjustment for propensity score. Medical therapy was associated with 2-fold greater all-cause mortality than AVR. The protective effect of AVR was similar in 125 patients with normal flow (stroke volume index >35 mL/m2; P=0.22). CONCLUSIONS: AVR is associated with better survival than medical therapy in patients with symptomatic low-gradient severe AS and preserved left ventricular ejection fraction.

Is there a role for diastolic function assessment in era of delayed enhancement cardiac magnetic resonance imaging?: a multimodality imaging study in patients with advanced ischemic cardiomyopathy.

UNLABELLED: Cardiac magnetic resonance (CMR) identifies important prognostic variables in ischemic cardiomyopathy (ICM) patients such as left ventricular (LV) volumes, LV ejection fraction (LVEF), peri-infarct zone, and myocardial scar burden (MSB). It is unknown whether Doppler-based diastolic dysfunction (DDF) retains its prognostic value in ICM patients, in the context of current imaging, medical, and device therapies. METHODS: Diastolic function was evaluated in ICM patients (LVEF ≤ 40% and ≥ 70% stenosis in ≥ 1 coronary artery) who underwent transthoracic echocardiogram and delayed hyperenhancement CMR studies within 7 days. The association of DDF with the combined end point was assessed after risk-adjustment using Cox proportional hazards models. RESULTS: A total of 360 patients with severe LV dysfunction (LVEF = 24 ± 9%) and extensive MSB (31 ± 17%) were evaluated; DDF was present in all patients (stage 1%-44%, stage 2%-25%, stage 3%-31%). There were 130 events (124 deaths and 6 heart transplants) over a median follow-up of 5.8 years (IQR, 3.7-7.4 years). On multivariable analysis, DDF > stage 1 (HR, 1.37; P = .007) was associated with the combined end-point, independent of clinical risk score (HR, 2.40; P < .0001), implantable cardioverter defibrillator implantation (HR, 0.60; P = .009), incomplete revascularization (HR, 1.32; P = .003), mitral regurgitation (HR, 3.37; P = .01), peri-infarct zone area (HR, 1.04; P = 0.02), and MSB (HR, 1.02; P = .01). DDF had incremental prognostic value for the combined end-point (model χ(2) increased from 89 to 95, P = .02). CONCLUSION: DDF is a powerful predictor of mortality in ICM patients with significant LV dysfunction, independent of clinical and CMR data. DDF assessment provides incremental value, improving risk stratification.

Clinical outcomes in fulminant myocarditis requiring extracorporeal membrane oxygenation: a weighted meta-analysis of 170 patients.

BACKGROUND: Fulminant myocarditis (FM) is often a self-resolving entity if the patient survives the acute illness. Venoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for treatment of cardiogenic shock or cardiac arrest due to FM. However, clinical outcomes are not well understood, in part because of small study sizes. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining survival rates for ECMO. METHODS: A systematic Medline search was conducted on ECMO for the treatment of FM, updated up to November 2012. Studies with n ≥10 published in the year 2000 or later that reported survival to hospital discharge for FM requiring ECMO were included. Studies that reported only on pediatric patients were excluded. The smaller of studies with overlapping patients were excluded. Cochran Q and I(2) were calculated and reported. RESULTS: Six studies were included in the analysis, encompassing 170 patients. The minimum and maximum reported rates of survival to hospital discharge were 60.0% and 87.5%, respectively. The cumulative rate was 115/170. The calculated Cochran Q value was 3.63, which was not significant for heterogeneity. The I(2) value was 0%. The pooled estimate rate was 66.9% with a 95% confidence interval of 59.4%-73.7%. CONCLUSION: More than two-thirds of patients with FM and either cardiogenic shock and/or cardiac arrest survive to hospital discharge with ECMO. These findings could be used in the risk-benefit analysis when initiation of a cardiopulmonary bypass system is being considered for FM.

Assessing the prognostic implications of myocardial perfusion studies: identification of patients at risk vs patients who may benefit from intervention?

Stress myocardial perfusion imaging (MPI) has a well-established role in improving risk stratification. Recent analyses, compared with older data, suggest that the yield of stress MPI has decreased. In part, this trend relates to testing patients with heterogeneous, but improved, risk factor modification. In this setting, positron emission tomography with myocardial flow reserve enhances risk stratification as it reflects the end result of atherosclerosis. Recent studies have also emphasized the clinical impact of incremental risk stratification by assessing net reclassification improvement (NRI). Previous retrospective studies have favored an ischemic threshold to select patients that benefit from revascularization, but this finding has not been corroborated in randomized trials. However, no large randomized trial has directly tested a strategy of revascularization for patients with at least a moderate amount of ischemia at risk. Unfortunately, even when faced with a significantly abnormal MPI result, subsequent action is too often absent.

Race, Genotype, and Prognosis in Black Patients With Transthyretin Cardiac Amyloidosis.

Previous studies suggest worse outcomes in patients with variant transthyretin cardiac amyloidosis (ATTR-CA) because of valine-to-isoleucine substitution at Position 122 (V122I) (ATTRv-CA) compared with patients with wild-type (WT) disease (ATTRwt-CA). Given V122I is almost exclusively found in Black patients, it is unclear if this is attributable to the biology of genotype or racial differences. Patients with ATTR-CA diagnosed between January 2001 and August 2021 were characterized into 3 categories: (1) White with ATTRwt-CA (White-WT); (2) Black with V122I ATTRv-CA (Black-V122I), and (3) Black with ATTRwt-CA (Black-WT). Event-free survival (composite of death, left ventricular assist device, or cardiac transplant) was evaluated using univariable and multivariable analyses over a median follow-up of 1.6 (0.7 to 2.90) years. Of 694 ATTR-CA patients, 502 (72%) were White-WT, 139 Black-V122I (20%), and 53 Black-WT (8%). Notably, 28% of Black patients with ATTR-CA had WT disease and not the V122I variant. Using multivariable modeling to adjust for several prognostic features, Black-V122I had higher risk of the composite adverse outcome compared with a grouped cohort of patients with WT disease (White-WT and Black-WT) (hazard ratio [HR] 1.82, confidence interval [CI] 1.30-2.56, p < 0.001). Furthermore, the Black cohort as a whole (Black-V122I and Black-WT) demonstrated greater risk of adverse outcomes compared with White-WT (HR 1.63, CI 1.19-2.24, p = 0.002). Black-V122I had greater risk of the primary end point compared with White-WT (HR 1.80, CI 1.27-2.56, p = 0.001). Black patients with ATTR-CA have worse event-free survival than White-WT despite risk adjustment. However, it remains unclear whether this is driven by differences in race or genotype given the smaller number of Black-WT patients. Approximately one-quarter of Black patients had WT, of which a greater proportion were female compared with White-WT.

Survival in patients with severe ischemic cardiomyopathy undergoing revascularization versus medical therapy: association with end-systolic volume and viability.

BACKGROUND: The value of assessment of viability as a predictor of surgical revascularization benefit in ischemic cardiomyopathy has recently been questioned in a large trial. We sought to determine whether the contribution of viability as myocardial scar burden (SB) to predict revascularization outcomes could be modulated by end-systolic volume index (ESVi). METHODS AND RESULTS: Delayed hyperenhancement-MRI was obtained in 450 patients with ≥70% stenosis in ≥1 epicardial coronary artery (75% men; median age, 62.8 ± 10.7 years; mean left ventricular ejection fraction, 23 ± 9%; mean ESVi, 115 ± 50 mL) from 2002 to 2006. SB was quantified as scar percentage (infarcted mass/total left ventricular mass). Subsequent surgical revascularization was performed in 245 (54%) patients and subsequent percutaneous coronary interventions were performed in 28 (6%) patients. A propensity score was developed for revascularization. Cox proportional hazards models of all-cause mortality were used for risk adjustment. Over a mean follow-up of 5.8 ± 2.7 years, 186 (41%) deaths occurred. After adjusting for prior revascularization, sex, diabetes, age, use of cardiac resynchronization therapy, implantable cardioverter defibrillator, mitral regurgitation, and mitral valve procedures; an interaction between scar percentage and ESVi (P=0.016) and an interaction between post-MRI revascularization and ESVi (P=0.0017) were independently associated with mortality. ESVi demonstrated a significant interaction with revascularization and female sex, such that enhanced survival was associated with ESVi. ESVi also showed an interaction with SB; better survival was associated with lower volumes and less scar. CONCLUSIONS: ESVi and SB provide independent, incremental prognostic value in patients with severe ischemic cardiomyopathy. The risk associated with SB should not be assessed in isolation.

Appropriate test selection for single-photon emission computed tomography imaging: association with clinical risk, posttest management, and outcomes.

BACKGROUND: Appropriate use criteria (AUC) for stress single-photon emission computed tomography (SPECT) are only one step in appropriate use of imaging. Other steps include pretest clinical risk evaluation and optimal management responses. We sought to understand the link between AUC, risk evaluation, management, and outcome. METHODS: We used AUC to classify 1,199 consecutive patients (63.8 ± 12.5 years, 56% male) undergoing SPECT as inappropriate, uncertain, and appropriate. Framingham score for asymptomatic patients and Bethesda angina score for symptomatic patients were used to classify patients into high (≥5%/y), intermediate, and low (≤1%/y) risk. Subsequent patient management was defined as appropriate or inappropriate based on the concordance between management decisions and the SPECT result. Patients were followed up for a median of 4.8 years, and cause of death was obtained from the social security death registry. RESULTS: Overall, 62% of SPECTs were appropriate, 18% inappropriate, and 20% uncertain (only 5 were unclassified). Of 324 low-risk studies, 108 (33%) were inappropriate, compared with 94 (15%) of 621 intermediate-risk and 1 (1%) of 160 high-risk studies (P < .001). There were 79 events, with outcomes of inappropriate patients better than uncertain and appropriate patients. Management was appropriate in 986 (89%), and appropriateness of patient management was unrelated to AUC (P = .65). CONCLUSION: Pretest clinical risk evaluation may be helpful in appropriateness assessment because very few high-risk patients are inappropriate, but almost half of low-risk patients are inappropriate or uncertain. Appropriate patient management is independent of appropriateness of testing.

Gated SPECT in assessment of regional and global left ventricular function: an update.

Gated myocardial perfusion SPECT (GSPECT) is a major clinical tool, widely used for performing myocardial perfusion imaging procedures. In this review, we have presented the fundamentals of GSPECT and the ways in which the functional measurements it provides have contributed to the emergence of myocardial perfusion SPECT in its important role as a major tool of modern cardiac imaging. GSPECT imaging has shown unique capability to provide accurate, reproducible and operator-independent quantitative data regarding myocardial perfusion, global and regional systolic and diastolic function, stress-induced regional wall-motion abnormalities, ancillary markers of severe and extensive disease, left ventricular geometry and mass, as well as the presence and extent of myocardial scar and viability. Adding functional data to perfusion provides an effective means of increasing both diagnostic accuracy and reader's confidence in the interpretation of the results of perfusion scans. Assessment of global and regional LV function has improved the prognostic power of myocardial perfusion SPECT and has been shown in a large registry to add to the perfusion assessment in predicting benefit from revascularization.

Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA.

There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials.

Incremental prognostic significance of combined cardiac magnetic resonance imaging, adenosine stress perfusion, delayed enhancement, and left ventricular function over preimaging information for the prediction of adverse events.

BACKGROUND: Although cardiac magnetic resonance imaging (CMR) is capable of yielding extensive data in routine practice, the relative incremental prognostic value of adenosine stress perfusion, myocardial delayed enhancement (DE), and left ventricular volumes and function is unclear. METHODS AND RESULTS: We followed up 908 consecutive patients who underwent combined CMR for suspicion of coronary stenosis and/or ischemia at 2.6 ± 1.2 years, during which 101 total cardiac events occurred (all-cause death, myocardial infarction, or late revascularization). Increase in Cox proportional-hazards model global χ² (χ²) with the addition of CMR data after adjustment for clinical data defined incremental prognostic value. Cardiac magnetic resonance imaging without abnormalities had a 2.4% event rate per year (<1% cardiac death or myocardial infarction). Abnormal CMR was associated with event rates of 5.6% to 7.0% per year, varying with which and how many components were abnormal. After adjusting for the pre-CMR data (age, dyspnea, prior coronary artery disease, resting heart rate, renal disease, and diabetes mellitus, χ²:43.6, P<0.0001; C index 0.695), the addition of left ventricular ejection fraction, aortic flow, delayed enhancement, and stress perfusion data all incrementally increased χ² (55.2, 63.3, 68.0, and 68.9, respectively; all P<0.00001; C indices 0.717, 0.722, 0.747, and 0.736). The number of abnormal CMR domains both added incremental prognostic value and risk stratified patients with respect to risk of events. CONCLUSIONS: CMR analysis of ventricular volume, aortic flow, myocardial viability, and stress perfusion all add incremental value for prediction of adverse events over pre-CMR data and can be combined to further enhance prognostication. Normal combined CMR confers a low risk of subsequent cardiac events.

Comparative effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial.

BACKGROUND: There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. METHODS AND RESULTS: We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P=0.59). Compared with ETT, index testing costs were higher for exercise MPI (P<0.001), whereas downstream procedural costs were slightly lower (P=0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI (P<0.001). CONCLUSIONS: In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00282711.