Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association.

Cardiovascular disease remains the leading cause of death in patients with diabetes. Cardiovascular disease in diabetes is multifactorial, and control of the cardiovascular risk factors leads to substantial reductions in cardiovascular events. The 2015 American Heart Association and American Diabetes Association scientific statement, "Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence," highlighted the importance of modifying various risk factors responsible for cardiovascular disease in diabetes. At the time, there was limited evidence to suggest that glucose-lowering medications reduce the risk of cardiovascular events. At present, several large randomized controlled trials with newer antihyperglycemic agents have been completed, demonstrating cardiovascular safety and reduction in cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and heart failure. This AHA scientific statement update focuses on (1) the evidence and clinical utility of newer antihyperglycemic agents in improving glycemic control and reducing cardiovascular events in diabetes; (2) the impact of blood pressure control on cardiovascular events in diabetes; and (3) the role of newer lipid-lowering therapies in comprehensive cardiovascular risk management in adults with diabetes. This scientific statement addresses the continued importance of lifestyle interventions, pharmacological therapy, and surgical interventions to curb the epidemic of obesity and metabolic syndrome, important precursors of prediabetes, diabetes, and comorbid cardiovascular disease. Last, this scientific statement explores the critical importance of the social determinants of health and health equity in the continuum of care in diabetes and cardiovascular disease.

Imaging in heart failure with preserved ejection fraction: insights into echocardiography and cardiac magnetic resonance imaging.

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and represents more than half of all heart failure cases. It is defined by the presence of heart failure signs and symptoms, identification of cardiac structural abnormalities leading to high left ventricular filling pressures, and an EF > 50%. Common imaging findings in HFpEF include left ventricular hypertrophy, diastolic dysfunction, left atrial enlargement, and elevated pulmonary artery pressure (> 35 mm Hg). Echocardiography is the primary imaging modality for diagnosing HFpEF. It can be complemented by cardiac magnetic resonance (CMR) when further characterization is needed. Advances like real-time 3-dimensional echocardiography and speckle-tracking derived strain, as well as tissue characterization by CMR, have furthered our understanding of the mechanisms and aided in making the diagnosis of a diverse group of conditions that can present as HFpEF. This review aims to touch upon the imaging methods of characterizing HFpEF and discuss their role in specific disease entities.

Fibrosis as measured by the biomarker, tissue inhibitor metalloproteinase-1, predicts mortality in Age Gene Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study.

BACKGROUND: Fibrosis is a key pathological process in many chronic inflammatory disease states. AIMS: We hypothesized that tissue inhibitor metalloproteinase-1 and matrix metalloproteinase-9 (TIMP-1 and MMP-9), biomarkers of fibrosis, would predict all-cause mortality and we assessed the incremental value of these biomarkers when adjusting for clinical and other biomarkers. METHODS: The cohort included 5511 community-dwelling participants in the AGES-Reykjavik Study. The baseline Cox proportional hazards regression model was based on the Framingham Risk Score variables; we added TIMP-1, MMP-9, serum high-sensitivity C-reactive protein (hsCRP), and estimated glomerular filtration rate (eGFR). The primary outcome was all-cause 10-year mortality. Cause of death was categorized as cardiovascular death (CVD), cancer death, and other causes. RESULTS: Participants averaged 76 years and 43% were male. Ten-year mortality was 41% (2263 deaths). Of these, 915 (16.6%) died of cardiovascular disease (CVD), 543 (9.9%) with cancer, and 805 (14.6%) from other causes. For 10-year mortality, age was the strongest predictor (log likelihood χ2 = 798.7, P < 0.0001), followed by TIMP-1 (χ2 = 125.2, P < 0.0001), female gender, current smoker, diabetes mellitus, total cholesterol, eGFR (χ2 16.7, P < 0.0001), body mass index, and hsCRP (χ2 11.3, P = 0.0008) in that order. TIMP-1 and hsCRP had the highest continuous net reclassification improvement over the baseline model for 5-year survival [net reclassification index (NRI) 0.28 and 0.19, respectively, both P < 0.0001] and for 10-year survival (NRI 0.19 and 0.11, respectively, both statistically significant). CONCLUSION: TIMP-1 is the strongest predictor of all-cause mortality after age. The metabolic pathways regulating extracellular matrix homeostasis and fibrogenic processes appear pathologically relevant and are prognostically important.

Compliance with guideline-directed therapy in diabetic patients admitted with acute coronary syndrome: Findings from the American Heart Association's Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) program.

BACKGROUND: To evaluate and compare baseline characteristics, outcomes and compliance with guideline based therapy at discharge among diabetic and non-diabetic patients admitted with acute coronary syndromes (ACS). METHODS AND RESULTS: Study population consisted of 151,270 patients admitted with ACS from 2002 through 2008 at 411 sites participating in the American Heart Association's Get with the Guidelines (GWTG) program. Demographic variables, physical exam findings, laboratory data, left ventricular ejection fraction, length of stay, in-hospital mortality and discharge medications were compared between diabetic and non-diabetic patients. Temporal trends in compliance with guidelines directed therapy were evaluated. Of 151,270 patients, 48,938 (32%) had diabetes. Overall, diabetic patients were significantly older and more likely non-white. They had significantly more hypertension, atherosclerotic disease, CKD, and LV dysfunction and were more likely to present as NSTEMI. They had longer hospital stay and higher hospital mortality than non-diabetic patients. Diabetic patients were less likely to get LDL checks (65% vs 70%) and less frequently prescribed statins (85% vs 89%), RAAS blockers for LV dysfunction (80% vs 84%) and dual-antiplatelet therapy (69% vs 74%). Diabetic patients were less likely to achieve BP goals before discharge (75% vs 82%). Fewer diabetic patients met first medical contact to PCI time for STEMI (44% vs 52%). Temporal trends, however, showed continued progressive improvement in most performance measures from 2002 to 2008 (all P<.001). CONCLUSIONS: These data from a large cohort of ACS patients demonstrate gaps in compliance with guidelines directed therapy in diabetic patients but also indicate significant and continued improvement in most performance measures over time. Concerted efforts are needed to continue this positive trend.

CMR provides comparable measurements of diastolic function as echocardiography.

Clinical application of cardiac magnetic resonance (CMR) is expanding but CMR assessment of LV diastolic function is still being validated. The purpose of this study was to validate assessments of left ventricular (LV) diastolic dysfunction (DD) using CMR by comparing with transthoracic echocardiography (TTE) performed on the same day. Patients with suspected or diagnosed cardiomyopathy (n = 63) and healthy volunteers (n = 24) were prospectively recruited and included in the study. CMR diastolic parameters were measured on cine images and velocity-encoded phase contrast cine images and compared with corresponding parameters measured on TTE. A contextual correlation feature tracking method was developed to calculate the mitral annular velocity curve. LV DD was classified by CMR and TTE following 2016 guidelines. Overall DD classification was 78.1% concordant between CMR and TTE (p < 0.0001). The trans-mitral inflow parameters correlated well between the two modalities (E, r = 0.78; A, r = 0.90; E/A, r = 0.82; all p < 0.0001) while the remaining diastolic parameters showed moderate correlation (e', r = 0.64; E/e', r = 0.54; left atrial volume index (LAVi), r = 0.61; all p < 0.0001). Classification of LV diastolic function by CMR showed good concordance with standardized grades established for TTE. CMR-based LV diastolic function may be integrated in routine clinical practice.Name of the registry: Technical Development of Cardiovascular Magnetic Resonance Imaging. Trial registration number: NCT00027170. Date of registration: November 26, 2001. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT00027170.

Aortic valve disorders and left ventricular assist devices.

Aortic valve disorders are important considerations in advanced heart failure patients being evaluated for left ventricular assist devices (LVAD) and those on LVAD support. Aortic insufficiency (AI) can be present prior to LVAD implantation or develop de novo during LVAD support. It is usually a progressive disorder and can lead to impaired LVAD effectiveness and heart failure symptoms. Severe AI is associated with worsening hemodynamics, increased hospitalizations, and decreased survival in LVAD patients. Diagnosis is made with echocardiographic, device assessment, and/or catheterization studies. Standard echocardiographic criteria for AI are insufficient for accurate diagnosis of AI severity. Management of pre-existing AI includes aortic repair or replacement at the time of LVAD implant. Management of de novo AI on LVAD support is challenging with increased risks of repeat surgical intervention, and percutaneous techniques including transcatheter aortic valve replacement are assuming greater importance. In this manuscript, we provide a comprehensive approach to contemporary diagnosis and management of aortic valve disorders in the setting of LVAD therapy.

Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension.

Background: Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RVFnRec). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition. Methods: We evaluated 63 incident patients with PAH by right heart catheterization and cardiac MRI (CMR) at diagnosis and CMR and invasive cardiopulmonary exercise (CPET) following treatment (∻11 months). Sex, age, race/ethnicity matched healthy control subjects (n=62) with one-time CMR and non-invasive CPET were recruited from the PVDOMICS project. We examined therapeutic CMR changes relative to the evidence-based peak oxygen consumption (VO2 peak )>15mL/kg/min to define RVFnRec by receiver operating curve analysis. Afterload was measured in the as mean pulmonary artery pressure, resistance, compliance, and elastance. Results: A drop in RV end-diastolic volume of -15 mL best defined RVFnRec (AUC 0.87, P=0.0001) and neared upper 95% CI RVEDV of controls. 22/63 (35%) of subjects met this cutoff which was reinforced by freedom from clinical worsening, RVFnRec 1/21 (5%) versus no RVFnRec 17/42, 40%, (log rank P=0.006). A therapy-associated increase of 0.8 mL/mmHg in compliance had the best predictive value of RVFnRec (AUC 0.76, CI 0.64-0.88, P=0.001). RVFnRec subjects had greater increases in stroke volume, and cardiac output at exercise. Conclusions: RVFnRec defined by RVEDV therapeutic decrease of -15mL predicts exercise capacity, freedom from clinical worsening, and nears normalization. A therapeutic improvement of compliance is superior to other measures of afterload in predicting RVFnRec. RVFnRec is also associated with increased RV output reserve at exercise. Clinical Perspective: What is new?: Right ventricular functional recovery (RVFnRec) represents a novel endpoint of therapeutic success in PAH. We define RVFnRec as treatment associated normative RV changes related to function (peak oxygen consumption). Normative RV imaging changes are compared to a well phenotyped age, sex, and race/ethnicity matched healthy control cohort from the PVDOMICS project. Previous studies have focused on RV ejection fraction improvements. However, we show that changes in RVEDV are perhaps more important in that improvements in LV function also occur. Lastly, RVFnRec is best predicted by improvements in pulmonary artery compliance versus pulmonary vascular resistance, a more often cited metric of RV afterload.What are the clinical implications?: RVFnRec represents a potential non-invasive assessment of clinical improvement and therapeutic response. Clinicians with access to cardiac MRI can obtain a limited scan (i.e., ventricular volumes) before and after treatment. Future study should examine echocardiographic correlates of RVFnRec.

Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension.

BACKGROUND: Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RV functional recovery [RVFnRec]). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition. METHODS: We evaluated 63 incident patients with pulmonary arterial hypertension by right heart catheterization and cardiac magnetic resonance imaging at diagnosis and cardiac magnetic resonance imaging and invasive cardiopulmonary exercise testing following treatment (≈11 months). Sex, age, ethnicity matched healthy control subjects (n=62) with 1-time cardiac magnetic resonance imaging and noninvasive cardiopulmonary exercise testing were recruited from the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) project. We examined therapeutic cardiac magnetic resonance imaging changes relative to the evidence-based peak oxygen consumption (VO2peak)>15 mL/(kg·min) to define RVFnRec by receiver operating curve analysis. Afterload was measured as mean pulmonary artery pressure, resistance, compliance, and elastance. RESULTS: A drop in RV end-diastolic volume of -15 mL best defined RVFnRec (area under the curve, 0.87; P=0.0001) and neared upper 95% CI RV end-diastolic volume of controls. This cutoff was met by 22 out of 63 (35%) patients which was reinforced by freedom from clinical worsening, RVFnRec 1 out of 21 (5%) versus no RVFnRec 17 out of 42, 40% (log-rank P=0.006). A therapy-associated increase of 0.8 mL/mm Hg in compliance had the best predictive value of RVFnRec (area under the curve, 0.76; [95% CI, 0.64-0.88]; P=0.001). RVFnRec patients had greater increases in stroke volume, and cardiac output at exercise. CONCLUSIONS: RVFnRec defined by RV end-diastolic volume therapeutic decrease of -15 mL predicts exercise capacity, freedom from clinical worsening, and nears normalization. A therapeutic improvement of compliance is superior to other measures of afterload in predicting RVFnRec. RVFnRec is also associated with increased RV output reserve at exercise.

Transcatheter Closure of Complex Left Circumflex to Coronary Sinus Fistula.

Coronary artery fistulae connecting the left circumflex to the coronary sinus are rare. Surgical closure of coronary sinus connections is technically challenging because of the location, especially in high-risk surgical patients. We used multimodality imaging to delineate the drainage site and successfully closed a left circumflex to coronary sinus fistula using a transcatheter closure technique. (Level of Difficulty: Advanced.).

Statin-Induced Triad of Autoimmune Myocarditis, Myositis, and Transaminitis.

Despite well-established cardiovascular benefits, statins have been associated with myopathic side effects ranging from myalgias to rhabdomyolysis and autoimmune necrotizing myositis. Statins have not been previously shown to cause myocarditis. Our case highlights this rare entity.

Cardiovascular Impact of Race and Ethnicity in Patients With Diabetes and Obesity: JACC Focus Seminar 2/9.

Obesity and type 2 diabetes mellitus are highly prevalent and increasing in the United States among racial/ethnic minority groups. Type 2 diabetes mellitus, which is driven by many factors including elevated levels of adiposity, is an exemplar health disparities disease. Pervasive disparities exist at every level from risk factors through outcomes for U.S. racial/ethnic minority groups, including African American, Hispanic/LatinX American, and Asian American populations. Disparities in clinical care exist including hemoglobin A1c control, lower prescription rates of newer antihyperglycemic medications, along with greater rates of complications postbariatric surgery. Underpinning these disparities are the social determinants of health affecting provider-patient interactions, access to resources, and healthy built environments. We review the best practices to address cardiometabolic disparities in the current cardiovascular guidelines and describe recommendations for cross-cutting strategies to advance equity in obesity and type 2 diabetes across U.S. racial/ethnic groups.

Comparison of professional medical society guidelines for appropriate use of coronary computed tomography angiography.

BACKGROUND: Multiple appropriate use criteria (AUC) exist for the evaluation of coronary artery disease (CAD), but there is little data on the agreement between AUC from different professional medical societies. The aim of this study is to compare the appropriateness of coronary computed tomography angiography (CCTA) exams assessed using multimodality AUC from the American College of Cardiology Foundation (ACCF) versus the American College of Radiology (ACR). METHODS: In a single-center prospective cohort study from June 2014 to 2016, 1005 consecutive subjects referred for evaluation of known or suspected CAD received a contrast-enhanced CCTA. The primary outcome was the agreement of appropriateness ratings using ACCF and ACR guidelines, measured by the kappa statistic. A secondary outcome was the rate of obstructive CAD by appropriateness rating. RESULTS: Among 1005 subjects, the median (5-95th percentile) age was 59 (37-76) years with 59.0% male. The ACCF criteria classified 39.6% (n = 398) appropriate, 24.2% (n = 243) maybe appropriate, and 36.2% (n = 364) rarely appropriate. The ACR guidelines classified 72.3% (n = 727) appropriate, 2.6% (n = 26) maybe appropriate, and 25.1% (n = 252) rarely appropriate. ACCF and ACR appropriateness ratings were in agreement for 55.0% (n = 553). Overall, there was poor agreement (kappa 0.27 [95% confidence interval 0.23-0.31]). By both AUC methods, a low rate of obstructive CAD was observed in the rarely appropriate exams (ACCF 7.1% [n = 26 of 364] and ACR 13.5% [n = 34 of 252]). CONCLUSIONS: Compared to ACCF criteria, the ACR guidelines of appropriateness were broader and classified significantly more CCTA exams as appropriate. The poor agreement between appropriateness ratings from the ACCF and ACR AUC guidelines evokes implications for reimbursement and future test utilization.

Performance of single-energy metal artifact reduction in cardiac computed tomography: A clinical and phantom study.

BACKGROUND: To investigate the performance of a reconstruction algorithm, single-energy metal artifact reduction (SEMAR), against standard reconstruction in cardiac computed tomography (CT) studies of patients with implanted metal and in a defibrillator lead phantom. METHODS: From a retrospective, cross-sectional clinical study with institutional review board approval of 118 patients with implanted metal, 122 cardiac CT studies from November 2009 to August 2016 performed on a 320-detector row scanner with standard and SEMAR reconstructions were included. The maximum beam hardening artifact radius, artifact attenuation variation surrounding the implanted metal, and image quality on a 4-point scale (1-no/minimal artifact to 4-severe artifact) were assessed for each reconstruction. A defibrillator lead phantom study was performed at different tube potentials and currents with both reconstruction methods. Maximum beam hardening artifact radius and average artifact attenuation variation were measured. RESULTS: In the clinical study, SEMAR markedly reduced the maximum beam hardening artifact radius by 77% (standard: 14.8 mm [IQR 9.7-22.2] vs. SEMAR: 3.4 mm [IQR 2.2-7.1], p < 0.0001) and artifact attenuation variation by 51% (standard: 130.0 HU [IQR 75.9-184.4] vs. SEMAR: 64.3 HU [IQR 48.2-89.2], p < 0.0001). Image quality improved with SEMAR (standard: 3 [IQR 2-3.5] vs. SEMAR: 2 [IQR 1-2.5], p < 0.0001). The defibrillator lead phantom study confirmed these results across varying tube potentials and currents. CONCLUSIONS: SEMAR reconstruction achieved superior image quality and markedly reduced maximum beam hardening artifact radius and artifact attenuation variation compared to standard reconstruction in 122 clinical cardiac CT studies of patients with implanted metal and in a defibrillator lead phantom study.

Cardiovascular outcome trials of the newer anti-diabetic medications.

Concerns of elevated cardiovascular disease (CVD) risk with some anti-diabetic medications warranted phase 4 clinical trials to demonstrate CVD safety of newly marketed anti-diabetic drugs. Although initially designed to evaluate safety, some of these CVD outcome trials (CVOTs) have in fact shown CVD benefits. New medication classes, like glucagon-like peptide 1 (GLP-1) analogues and sodium-glucose co-transporter 2 (SGLT2) inhibitors, have shown reductions in the risk of major adverse cardiovascular events (MACE) including, myocardial infarction, stroke, CV death, and heart failure (HF). Perhaps more importantly, SGLT2 inhibitors demonstrated reduction in the risk of HF hospitalizations, being the first class of anti-diabetic drugs to do so. Conversely, dipeptidyl peptidase 4 (DPP-4) inhibitors did not significantly affect atherosclerotic CVD end-points and some actually increased the risk of HF hospitalizations. Further, the adverse/beneficial CVD effects of these medications may not be class specific. This review focuses on the main results of these CVOTs while highlighting the heterogeneity of CVD end-points within each class and discusses important mechanistic insights and adverse effect profiles.

Cardiovascular Protection with Anti-hyperglycemic Agents.

Diabetes mellitus is a major risk factor for cardiovascular (CV) disease. Conversely, CV disease is responsible for a majority of the deaths in patients with diabetes. Many drug trials have concentrated on blood glucose (hemoglobin A1c) reduction. This strategy, while reducing microvascular outcomes like nephropathy and neuropathy, has little or no effect on reducing macrovascular events like heart attack, stroke, and heart failure. It has been postulated that hypoglycemia may counterbalance some of the beneficial effects of anti-hyperglycemic agents, but this is not proven. Further, trial evidence for thiazolidinediones (rosiglitazone and pioglitazone) showed increased risk of heart failure and raised concerns about increased myocardial infarction. This heightened awareness of potentially harmful CV effects of otherwise effective hypoglycemic drugs resulted in regulatory mandates for CV outcome trials to ascertain the safety of newer anti-hypoglycemic agents appearing on the market. Three new classes of anti-hyperglycemic agents have been introduced in recent years. While dipeptidyl peptidase-4 (DPP-4) inhibitors exhibited increased heart failure hospitalization in the SAVOR-TIMI 53 trial evaluating saxagliptin and in the secondary analysis of the EXAMINE trial for alogliptin, the effects of glucagon-like peptide-1 (GLP-1) analogs and sodium-glucose co-transporter-2 (SGLT2) inhibitors on CV outcomes in diabetes have largely been positive. The LEADER and SUSTAIN-6 trials evaluating the safety and efficacy of the GLP-1 analogs liraglutide and semaglutide, respectively, showed a statistically significant reduction in the primary outcome (major adverse cardiac events [MACE]: CV death, myocardial infarction, and stroke) and the secondary combined outcome when compared to placebo. Results of the TECOS trial for sitagliptin were, however, neutral (no net CV benefit or harm), questioning the class effect of GLP-1 analogs. Results of the SGLT2 inhibitor trials were more uniform. While EMPA-REG (evaluating empagliflozin) and CANVAS (evaluating canagliflozin) showed a reduction in the MACE end point, dapagliflozin had a net neutral effect on MACE in DECLARE-TIMI 58. All three SGLT2 inhibitors, however, showed a significant reduction in heart failure hospitalizations. Although initially designed to keep potentially harmful anti-hyperglycemic agents off the market, the CV outcome trials have provided clinicians with a new set of anti-hyperglycemic drugs with proven CV benefit in patients with diabetes and CV disease, thus expanding the field of CV secondary prevention. There is a need to inculcate GLP-1 analogs and SGLT2 inhibitors that reduce major CV events and heart failure hospitalizations (alongside lifestyle management and metformin) in the treatment of patients with diabetes and CV disease.

Myocardial segmental thickness variability on echocardiography is a highly sensitive and specific marker to distinguish ischemic and non-ischemic dilated cardiomyopathy in new onset heart failure.

The aim of this study was to determine non-invasive diagnostic markers by echocardiography that differentiate ischemic dilated (ICM) from non-ischemic dilated cardiomyopathy (NICM) in patients with new onset heart failure. We identified 100 consecutive new heart failure patients with dilated cardiomyopathy (valvular etiology excluded). Clinical risk factors, medication history, serum biomarkers, ECG and echocardiographic variables were compared between the ICM and NICM groups (as confirmed by coronary angiography). Mean age, left ventricular size and ejection fraction were 56 years, 6.1 cm and 26% respectively. A total of 24% had ICM. Patients with ICM were older (65 vs. 53 years; P < 0.001). No significant difference was observed between ICM and NICM among 18 clinical variables, 7 laboratory tests, 6 EKG parameters and 10 of the 13 echocardiographic markers evaluated. Segmental wall thickness variability, regional wall motion abnormality and RV enlargement on echocardiogram (echo) differentiated ICM from NICM. Segmental thickness variability outperformed wall motion abnormality in diagnosing ICM with a sensitivity and specificity of 79.2 and 98.7% versus 62.5 and 84.2% respectively. RV enlargement was not sensitive but 90.6% specific for predicting NICM. Myocardial segmental thickness variability on echo, resulting from thinned infarcted or hibernating myocardium, is a highly sensitive and specific marker to differentiate ICM from NICM in new onset heart failure.

Association of Unrecognized Myocardial Infarction With Long-term Outcomes in Community-Dwelling Older Adults: The ICELAND MI Study.

Importance: Cardiac magnetic resonance (CMR) imaging can identify unrecognized myocardial infarction (UMI) in the general population. Unrecognized myocardial infarction by CMR portends poor prognosis in the short term but, to our knowledge, long-term outcomes are not known. Objective: To determine the long-term outcomes of UMI by CMR compared with clinically recognized myocardial infarction (RMI) and no myocardial infarction (MI). Design, Setting, and Participants: Participants of the population-based, prospectively enrolled ICELAND MI cohort study (aged 67-93 years) were characterized with CMR at baseline (from January 2004-January 2007) and followed up for up to 13.3 years. Kaplan-Meier time-to-event analyses and a Cox regression were used to assess the association of UMI at baseline with death and future cardiovascular events. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were a composite of major adverse cardiac events (MACE: death, nonfatal MI, and heart failure). Results: Of 935 participants, 452 (48.3%) were men; the mean (SD) age of participants with no MI, UMI, and RMI was 75.6 (5.3) years, 76.8 (5.2) years, and 76.8 (4.7) years, respectively. At 3 years, UMI and no MI mortality rates were similar (3%) and lower than RMI rates (9%). At 5 years, UMI mortality rates (13%) increased and were higher than no MI rates (8%) but still lower than RMI rates (19%). By 10 years, UMI and RMI mortality rates (49% and 51%, respectively) were not statistically different; both were significantly higher than no MI (30%) (P < .001). After adjusting for age, sex, and diabetes, UMI by CMR had an increased risk of death (hazard ratio [HR], 1.61; 95% CI, 1.27-2.04), MACE (HR, 1.56; 95% CI, 1.26-1.93), MI (HR, 2.09; 95% CI, 1.45-3.03), and heart failure (HR, 1.52; 95% CI, 1.09-2.14) compared with no MI and statistically nondifferent risk of death (HR, 0.99; 95% CI, 0.71-1.38) and MACE (HR, 1.23; 95% CI, 0.91-1.66) vs RMI. Conclusions and Relevance: In this study, all-cause mortality of UMI was higher than no MI, but within 10 years from baseline evaluation was equivalent with RMI. Unrecognized MI was also associated with an elevated risk of nonfatal MI and heart failure. Whether secondary prevention can alter the prognosis of UMI will require prospective testing.

In-Hospital Outcomes of Percutaneous Coronary Intervention in America's Safety Net: Insights From the NCDR Cath-PCI Registry.

OBJECTIVES: This study compared risk-adjusted percutaneous coronary intervention (PCI) outcomes of safety-net hospitals (SNHs) and non-SNHs. BACKGROUND: Although risk adjustment is used to compare hospitals, SNHs treat a disproportionate share of uninsured and underinsured patients, who may have unmeasured risk factors, limited health care access, and poorer outcomes than patients treated at non-SNHs. METHODS: Using the National Cardiovascular Data Registry CathPCI Registry from 2009 to 2015, we analyzed 3,746,961 patients who underwent PCI at 282 SNHs (hospitals where ≥10% of PCI patients were uninsured) and 1,134 non-SNHs. The relationship between SNH status and risk-adjusted outcomes was assessed. RESULTS: SNHs were more likely to be lower volume, rural hospitals located in the southern states. Patients treated at SNHs were younger (63 vs. 65 years), more often nonwhite (17% vs. 12%), smokers (33% vs. 26%), and more likely to be admitted through the emergency department (48% vs. 38%) and to have an ST-segment elevation myocardial infarction (20% vs. 14%) than non-SNHs (all p < 0.001). Patients undergoing PCI at SNHs had higher risk-adjusted in-hospital mortality (odds ratio: 1.23; 95% confidence interval: 1.17 to 1.32; p < 0.001), although the absolute risk difference between groups was small (0.4%). Risk-adjusted bleeding (odds ratio: 1.05; 95% confidence interval: 1.00 to 1.12; p = 0.062) and acute kidney injury rates (odds ratio: 1.01; 95% confidence interval: 0.96 to 1.07; p = 0.51) were similar. CONCLUSIONS: Despite treating a higher proportion of uninsured patients with more acute presentations, risk-adjusted PCI-related in-hospital mortality of SNHs is only marginally higher (4 additional deaths per 1,000 PCI cases) than non-SNHs, whereas risk-adjusted bleeding and acute kidney injury rates are comparable.