Limb Outcomes With Ticagrelor Plus Aspirin in Patients With Diabetes Mellitus and Atherosclerosis.

BACKGROUND: Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. OBJECTIVES: This study sought to determine the effect of ticagrelor on limb events. METHODS: Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. RESULTS: Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; Pinteraction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (Pinteraction = 0.40) or TIMI major bleeding (Pinteraction = 0.3239). CONCLUSIONS: Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795).

Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is associated with polyneuropathy, cardiomyopathy, or both. The effects of eplontersen on cardiac structure and function were assessed. METHODS AND RESULTS: NEURO-TTRansform was an open-label trial involving 144 adults with ATTRv polyneuropathy (49 patients [34%] with cardiomyopathy) receiving eplontersen throughout and compared with a historical placebo group (n = 60; 30 patients [50%] with cardiomyopathy) from the NEURO-TTR trial at week 65. Treatment effect (eplontersen vs placebo), presented as mean difference (95% confidence interval) was analyzed after adjusting for age, sex, region, baseline value, ATTRv disease stage, previous ATTRv treatment, and V30M transthyretin variant. There were notable differences at baseline between the eplontersen group and historical placebo. In the cardiomyopathy subgroup, 65 weeks of eplontersen treatment was associated with improvement from baseline relative to placebo in left ventricular ejection fraction of 4.3% (95% confidence interval 1.40-21.01; P = .049) and stroke volume 10.64 mL (95% confidence interval 3.99-17.29; P = .002) while the remainder of echocardiographic parameters remained stable. CONCLUSIONS: Eplontersen was associated with stable or improved measures of cardiac structure and function vs historical placebo in patients with ATTRv polyneuropathy and cardiomyopathy. Further investigation into eplontersen's effect on transthyretin amyloid cardiomyopathy is being conducted in the CARDIO-TTRansform trial.

Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy.

Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P < .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P < .001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P < .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.

Living with heart failure: patient experiences and implications for physical activity and daily living.

AIMS: Heart failure (HF) substantially limits the ability of patients to engage in physical activities. A detailed understanding of how patients experience these limitations is required to develop valid and sensitive measures for use in clinical research. This qualitative study was designed to provide a thorough description of how HF patients experience physical activity limitations in their daily lives. METHODS AND RESULTS: Semi-structured interviews were conducted with 40 HF patients. Interview transcripts were coded with the aim of identifying key aspects of physical activity. Patients were divided between HF with preserved ejection fraction (n = 21, 52.5%) and HF with reduced ejection fraction (n = 19, 47.5%); the majority of patients were New York Heart Association Class II (n = 22, 52.5%) or Class III (n = 16, 40.0%). Relevant physical activity themes, including mobility and broader daily function areas, were identified. The most frequently reported mobility limitations involved difficulty walking (up a steep incline, up steps, and long distances), limited walking speed, difficulty standing for long periods of time, and difficulty carrying and lifting objects. These limitations were principally related to three HF symptoms: dyspnoea, tiredness/fatigue, and peripheral oedema. Patients adapted to their symptoms and related mobility limitations in several ways, including taking rests during an activity, doing an activity more slowly, and avoiding/refraining from an activity altogether. The broader daily function areas most commonly impacted by the mobility limitations were housework, exercising or playing sports, and going shopping. CONCLUSIONS: Heart failure patients report numerous physical activity limitations. These specific mobility and daily function areas can be measured using clinical outcome assessments (e.g. patient-reported outcomes and performance outcomes) in clinical trials and observational research. Accelerometry can be used to contribute to a holistic picture of patient functioning by passively collecting this type of data.

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial.

BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. INTERPRETATION: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. FUNDING: AstraZeneca.

Changes in premiums of cancelled nongroup plans under the Affordable Care Act.

OBJECTIVES: To examine the effect of the Affordable Care Act (ACA) on changes in premiums for subscribers of nongrandfathered, nongroup insurance plans that were "cancelled." STUDY DESIGN: Retrospective multivariate analyses. METHODS: Changes in annual premiums post ACA were evaluated across subgroups of subscriber and health plan characteristics. Data was derived from databases containing information on premiums, plan benefit, and demographics for subscribers aged 18 to 64 years within Kaiser Permanente of the Mid-Atlantic States. A linear regression model was used to examine the independent association between subscriber and health plan characteristics on the relative change in premiums. RESULTS: In 2013, 4169 nongroup subscribers were enrolled in plans that were cancelled as a result of the ACA. The median pre-ACA premium was $3240 (range = $780-$39,492), which increased by a median of 21.3% (range = -77.4% to 193.6%), or $685 (range = -$27,464 to $8676), post ACA in 2014. Premiums increased more for high-deductible plans (median = 63.7%) than standard-deductible plans (median = 8.4%). Due to shifts in the age curve, premiums decreased for more than half of women aged 18 to 44 years, but increased by 35.2% for women aged 55 to 64 years. Premiums fell by 15.5% for subscribers who did not pass standard medical underwriting due to preexisting conditions. CONCLUSIONS: Changes in premiums in the nongroup market post ACA, varied substantially across subgroups, primarily due to differences in the amount of coverage, changes in rating criteria, shifts in the age curve, and anticipated differences in risk selection and composition of the risk pool. Given the extent of this variation, it would be incorrect to conclude the ACA as being uniformly beneficial or detrimental to subscribers of these cancelled plans.

Risk of Vascular Toxicity with Platinum Based Chemotherapy in Elderly Patients with Bladder Cancer.

PURPOSE: Platinum based chemotherapy is widely used for bladder cancer but is associated with vascular toxicity, especially thromboembolism. We evaluated the short-term (less than 1 year) and intermediate-term (2 to 5 years) vascular toxicity of platinum agents in older patients with bladder cancer. MATERIALS AND METHODS: We identified Medicare beneficiaries 66 to 94 years old diagnosed with stage II-III bladder cancer from 1998 to 2007 in the SEER-Medicare database. We measured the association between platinum based chemotherapy and vascular events (thromboembolic and nonthromboembolic) using Cox proportional hazard regression models. RESULTS: The sample included 5,057 patients, of whom 21.3% received platinum based chemotherapy. Patients receiving platinum based chemotherapy were more likely to be younger and male with less comorbidity than those not receiving any chemotherapy. During the first year after diagnosis the patients who received platinum based chemotherapy had a higher risk of a thromboembolic event (19.8% vs 11.6%, AHR 1.43, 95% CI 1.17-1.75) compared to those who did not receive chemotherapy. The likelihood of having a thromboembolic outcome was similar whether platinum chemotherapy was cisplatin based (21.1%, AHR 1.56, 95% CI 1.22-2.00) or carboplatin based (18.9%, AHR 1.35, 95% CI 1.07-1.71). During years 2 to 5 after diagnosis there was no significant association between platinum chemotherapy and the risk of thromboembolic events. The risk of nonthromboembolic vascular events was not increased with platinum chemotherapy in either period. CONCLUSIONS: Patients receiving platinum based chemotherapy were at higher risk for thromboembolism but not other vascular events, particularly in the first year after diagnosis. This risk of thromboembolism is similar for cisplatin and carboplatin.

National trends in stroke after acute myocardial infarction among Medicare patients in the United States: 1999 to 2010.

BACKGROUND: Stroke is a common and important adverse event after acute myocardial infarction (AMI) in the elderly. It is unclear whether the risk of stroke after AMI has changed with improvements in treatments and outcomes for AMI in the last decade. METHODS: To assess trends in risk of stroke after AMI, we used a national sample of Medicare data to identify Fee-for-Service patients (n = 2,305,441) aged ≥65 years who were discharged alive after hospitalization for AMI from 1999 to 2010. RESULTS: We identified 57,848 subsequent hospitalizations for ischemic stroke and 4,412 hospitalizations for hemorrhagic stroke within 1 year after AMI. The 1-year rate of ischemic stroke decreased from 3.4% (95% CI 3.3%-3.4%) to 2.6% (2.5%-2.7%; P < .001). The risk-adjusted annual decline was 3% (hazard ratio, 0.97; [0.97-0.98]) and was similar across all age and sex-race groups. The rate of hemorrhagic stroke remained stable at 0.2% and did not differ by subgroups. The 30-day mortality for patients admitted with ischemic stroke after AMI decreased from 19.9% (18.8%-20.9%) to 18.3% (17.1%-19.6%) and from 48.3% (43.0%-53.6%) to 45.7% (40.3%-51.2%) for those admitted with hemorrhagic stroke. We observed a decrease in 1-year mortality from 37.8% (36.5%-39.1%) to 35.3% (33.8%-36.8%) for ischemic stroke and from 66.6% (61.4%-71.5%) to 60.6% (55.1%-65.9%) for hemorrhagic stroke. CONCLUSIONS: From 1999 to 2010, the 1-year risk for ischemic stroke after AMI declined, whereas the risk of hemorrhagic stroke remained unchanged. However, 30-day and 1-year mortality continued to be high.

Approaches to enhancing radiation safety in cardiovascular imaging: a scientific statement from the American Heart Association.

Education, justification, and optimization are the cornerstones to enhancing the radiation safety of medical imaging. Education regarding the benefits and risks of imaging and the principles of radiation safety is required for all clinicians in order for them to be able to use imaging optimally. Empowering patients with knowledge of the benefits and risks of imaging will facilitate their meaningful participation in decisions related to their health care, which is necessary to achieve patient-centered care. Limiting the use of imaging to appropriate clinical indications can ensure that the benefits of imaging outweigh any potential risks. Finally, the continually expanding repertoire of techniques that allow high-quality imaging with lower radiation exposure should be used when available to achieve safer imaging. The implementation of these strategies in practice is necessary to achieve high-quality, patient-centered imaging and will require a shared effort and investment by all stakeholders, including physicians, patients, national scientific and educational organizations, politicians, and industry.

Contemporary use of dual antiplatelet therapy for preventing cardiovascular events.

OBJECTIVES: CHARISMA was a landmark randomized clinical trial that failed to demonstrate a benefit of dual antiplatelet therapy (DAPT) over aspirin alone for preventing cardiovascular events. However, subgroup analyses of the trial found fewer major adverse cardiovascular events (MACEs) for patients with established cardiovascular disease but more MACEs for patients with multiple risk factors without established cardiovascular disease. Our objective was to examine DAPT use in contemporary clinical practice after publication of CHARISMA results. STUDY DESIGN: Retrospective analysis of a large clinical registry of outpatient cardiovascular visits to over 1000 physicians that collected data on patient clinical history, symptoms, vital signs, and medications. METHODS: Clinical characteristics and prescription rates of aspirin and clopidogrel were compared for patients with established cardiovascular disease and for patients with only multiple cardiovascular risk factors. Prescription of DAPT by calendar quarter was evaluated from 2008 to 2011 using multivariable Poisson regression models. RESULTS: Of 167,839 patients with established cardiovascular disease, 20.5% were prescribed both aspirin and clopidogrel. Of 20,478 patients with multiple risk factors but no known cardiovascular disease, 3.5% were prescribed both aspirin and clopidogrel. Across 14 calendar quarters, prescription rates of DAPT did not change significantly for patients with established CVD but decreased for patients with multiple risk factors with an incidence rate ratio of 0.77. CONCLUSIONS: Use of DAPT is modest in patients with established cardiovascular disease, for whom the CHARISMA trial suggested decreased MACEs, and prescription rates have remained stable over time. Use of DAPT in patients with multiple risk factors only, for whom CHARISMA suggested that DAPT may lead to increased MACE, was low and decreased over time.

National trends in recurrent AMI hospitalizations 1 year after acute myocardial infarction in Medicare beneficiaries: 1999-2010.

BACKGROUND: There are few data characterizing temporal changes in hospitalization for recurrent acute myocardial infarction (AMI) after AMI. METHODS AND RESULTS: Using a national sample of 2 305 441 Medicare beneficiaries hospitalized for AMI from 1999 to 2010, we evaluated changes in the incidence of 1-year recurrent AMI hospitalization and mortality using Cox proportional hazards models. The observed recurrent AMI hospitalization rate declined from 12.1% (95% CI 11.9 to 12.2) in 1999 to 8.9% (95% CI 8.8 to 9.1) in 2010, a relative decline of 26.4%. The observed recurrent AMI hospitalization rate declined by a relative 27.7% in whites, from 11.9% (95% CI 11.8 to 12.1) to 8.6% (95% CI 8.5 to 8.8) versus a relative decline in blacks of 13.6% from 13.2% (95% CI 12.6 to 13.8) to 11.4% (95% CI 10.9 to 12.0). The risk-adjusted rate of annual decline in recurrent AMI hospitalizations was 4.1% (HR 0.959; 95% CI 0.958 to 0.961), and whites experienced a higher rate of decline (HR 0.957, 95% CI 0.956 to 0.959) than blacks (HR 0.974, 95% CI 0.970 to 0.979).The overall, observed 1-year mortality rate after hospitalization for recurrent AMI declined from 32.4% in 1999 to 29.7% in 2010, a relative decline of 8.3% (P<0.05). In adjusted analyses, 1-year mortality after recurrent AMI hospitalization declined 1.8% per year (HR, 0.982; 95% CI 0.980 to 0.985). CONCLUSIONS: In a national sample of Medicare beneficiaries hospitalized for AMI from 1999 to 2010, hospitalization for recurrent AMI decreased, as did subsequent mortality, albeit to a lesser extent. The risk of recurrent AMI hospitalization declined less in black patients than in whites, increasing observed racial disparities by the end of the study period.

Cardiovascular events, early discontinuation of trastuzumab, and their impact on survival.

To evaluate how often trastuzumab therapy is ended early (i.e., early discontinuation) and how cardiovascular events and early discontinuation affect survival among older women with breast cancer. A population-based cohort of female Medicare beneficiaries with stage I-III breast cancer in 2005-2009 who received trastuzumab was assembled and followed through 2011. Completed trastuzumab treatment was defined as ≥11 months of continuous trastuzumab treatments with no delay between trastuzumab treatments >45 days. We identified trastuzumab-associated cardiovascular events as those occurring within 45 days before or after the last trastuzumab treatment. Using Cox proportional hazard models, we examined the association between early discontinuation of trastuzumab and cardiovascular events on all-cause mortality. Our cohort consisted of 585 women (mean age: 71.6 years). Approximately 41 % of women discontinued trastuzumab therapy early. Patients with early discontinuation of trastuzumab were more likely to have heart failure /cardiomyopathy, atrial fibrillation, and other cardiovascular events than women who completed trastuzumab. Cardiovascular events were strongly associated with an increased risk of all-cause mortality [adjusted hazard ratio (AHR) 3.54; 95 % confidence interval (CI) 1.87 to 6.68]. Women with early discontinuation of trastuzumab had a non-significant increase in risk of all-cause mortality (AHR: 1.74; 95 % CI 0.94 to 3.23), compared to women who completed trastuzumab. Early trastuzumab discontinuation was common among older patients, and often associated with adverse cardiovascular events. Development of cardiovascular events was associated with a higher mortality risk than early trastuzumab discontinuation, implying that reducing cardiovascular complications from trastuzumab therapy could likely have a substantive impact on overall survival in this population.

Developing a data infrastructure for a learning health system: the PORTAL network.

The Kaiser Permanente & Strategic Partners Patient Outcomes Research To Advance Learning (PORTAL) network engages four healthcare delivery systems (Kaiser Permanente, Group Health Cooperative, HealthPartners, and Denver Health) and their affiliated research centers to create a new national network infrastructure that builds on existing relationships among these institutions. PORTAL is enhancing its current capabilities by expanding the scope of the common data model, paying particular attention to incorporating patient-reported data more systematically, implementing new multi-site data governance procedures, and integrating the PCORnet PopMedNet platform across our research centers. PORTAL is partnering with clinical research and patient experts to create cohorts of patients with a common diagnosis (colorectal cancer), a rare diagnosis (adolescents and adults with severe congenital heart disease), and adults who are overweight or obese, including those with pre-diabetes or diabetes, to conduct large-scale observational comparative effectiveness research and pragmatic clinical trials across diverse clinical care settings.

Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer.

BACKGROUND: Adjuvant trastuzumab improves survival for women with human epidermal growth factor receptor 2-positive breast cancer, but increases risk for heart failure (HF) and cardiomyopathy (CM). However, clinical trials may underestimate HF/CM risk because they enroll younger subjects with fewer cardiac risk factors. We sought to develop a clinical risk score that identifies older women with breast cancer who are at higher risk of HF or CM after trastuzumab. METHODS AND RESULTS: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified women with breast cancer who received adjuvant trastuzumab. Using a split-sample design, we used a proportional hazards model to identify candidate predictors of HF/CM in a derivation cohort. A risk score was constructed using regression coefficients, and HF/CM rates were calculated in the validation cohort. The sample consisted of 1664 older women (mean age 73.6 years) with 3-year HF/CM rate of 19.1%. A risk score consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was able to classify HF/CM risk into low (0 to 3 points), medium (4 to 5 points), and high (≥6 points) risk strata with 3-year rates of 16.2%, 26.0%, and 39.5%, respectively. CONCLUSIONS: A 7-factor risk score was able to stratify 3-year risk of HF/CM after trastuzumab between the lowest and highest risk groups by more than 2-fold in a Medicare population. These findings will inform future research aimed at further developing a clinical risk score for HF/CM for breast cancer patients of all ages.

ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

The American College of Cardiology Foundation along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical presentations for stable ischemic heart disease (SIHD) to consider use of stress testing and anatomic diagnostic procedures. This document reflects an updating of the prior Appropriate Use Criteria (AUC) published for radionuclide imaging (RNI), stress echocardiography (Echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for SIHD. This is in keeping with the commitment to revise and refine the AUC on a frequent basis. A major innovation in this document is the rating of tests side by side for the same indication. The side-by-side rating removes any concerns about differences in indication or interpretation stemming from prior use of separate documents for each test. However, the ratings were explicitly not competitive rankings due to the limited availability of comparative evidence, patient variability, and range of capabilities available in any given local setting. The indications for this review are limited to the detection and risk assessment of SIHD and were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Eighty clinical scenarios were developed by a writing committee and scored by a separate rating panel on a scale of 1-9, to designate Appropriate, May Be Appropriate, or Rarely Appropriate use following a modified Delphi process following the recently updated AUC development methodology. The use of some modalities of testing in the initial evaluation of patients with symptoms representing ischemic equivalents, newly diagnosed heart failure, arrhythmias, and syncope was generally found to be Appropriate or May Be Appropriate, except in cases where low pre-test probability or low risk limited the benefit of most testing except exercise electrocardiogram (ECG). Testing for the evaluation of new or worsening symptoms following a prior test or procedure was found to be Appropriate. In addition, testing was found to be Appropriate or May Be Appropriate for patients within 90 days of an abnormal or uncertain prior result. Pre-operative testing was rated Appropriate or May Be Appropriate only for patients who had poor functional capacity and were undergoing vascular or intermediate risk surgery with 1 or more clinical risk factors or an organ transplant. The exercise ECG was suggested as an Appropriate test for cardiac rehabilitation clearance or for exercise prescription purposes. Testing in asymptomatic patients was generally found to be Rarely Appropriate, except for calcium scoring and exercise testing in intermediate and high-risk individuals and either stress or anatomic imaging in higher-risk individuals, which were all rated as May Be Appropriate. All modalities of follow-up testing after a prior test or percutaneous coronary intervention (PCI) within 2 years and within 5 years after coronary artery bypass graft (CABG) in the absence of new symptoms were rated Rarely Appropriate. Pre-operative testing for patients with good functional capacity, prior normal testing within 1 year, or prior to low-risk surgery also were found to be Rarely Appropriate. Imaging for an exercise prescription or prior to the initiation of cardiac rehabilitation was Rarely Appropriate except for cardiac rehabilitation clearance for heart failure patients.

National trends in heart failure hospitalization after acute myocardial infarction for Medicare beneficiaries: 1998-2010.

BACKGROUND: Previous studies have reported conflicting findings regarding how the incidence of heart failure (HF) after acute myocardial infarction (AMI) has changed over time, and data on contemporary national trends are sparse. METHODS AND RESULTS: Using a complete national sample of 2 789 943 AMI hospitalizations of Medicare fee-for-service beneficiaries from 1998 through 2010, we evaluated annual changes in the incidence of subsequent HF hospitalization and mortality using Poisson and survival analysis models. The number of patients hospitalized for HF within 1 year after AMI declined modestly from 16.1 per 100 person-years in 1998 to 14.2 per 100 person years in 2010 (P<0.001). After adjusting for demographic factors, a relative 14.6% decline for HF hospitalizations after AMI was observed over the study period (incidence risk ratio, 0.854; 95% confidence interval, 0.809-0.901). Unadjusted 1-year mortality following HF hospitalization after AMI was 44.4% in 1998, which decreased to 43.2% in 2004 to 2005, but then increased to 45.5% by 2010. After adjusting for demographic factors and clinical comorbidities, this represented a 2.4% relative annual decline (hazard ratio, 0.976; 95% confidence interval, 0.974-0.978) from 1998 to 2007, but a 5.1% relative annual increase from 2007 to 2010 (hazard ratio, 1.051; 95% confidence interval, 1.039-1.064). CONCLUSIONS: In a national sample of Medicare beneficiaries, HF hospitalization after AMI decreased from 1998 to 2010, which may indicate improvements in the management of AMI. In contrast, survival after HF following AMI remains poor, and has worsened from 2007 to 2010, demonstrating that challenges still remain for the treatment of this high-risk condition after AMI.