Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded. Participants were split into a predisposed HFpEF group, defined as HFpEF with normal natriuretic peptide levels based on an HFA-PEFF (Heart Failure Association Pretest Assessment, Echocardiography and Natriuretic Peptide, Functional Testing, and Final Etiology) score of 4 from the latest European Society of Cardiology guidelines, and an HFpEF group (HFA-PEFF score of ≥ 5). An asymptomatic control group without heart failure was also included. Clinical and cardiac MRI-based characteristics and outcomes were compared between groups. The primary end points were death, heart failure hospitalization, or stroke. Results A total of 213 participants with HFpEF, 151 participants with predisposed HFpEF, and 100 participants in the control group were analyzed. Compared with the control group, participants with predisposed HFpEF had worse left ventricular remodeling and function and higher systemic inflammation. Compared with participants with HFpEF, those with predisposed HFpEF, whether obese or not, were younger and had higher plasma volume, lower prevalence of atrial fibrillation, lower left atrial volume index, and less impaired left ventricular global longitudinal strain (-12.2% ± 2.8 vs -13.9% ± 3.1; P < .001) and early-diastolic global longitudinal strain rate (eGLSR, 0.52/sec ± 0.20 vs 0.57/sec ± 0.15; P = .03) but similar prognosis. Atrial fibrillation occurrence (hazard ratio [HR] = 3.90; P = .009), hemoglobin level (HR = 0.94; P = .001), and eGLSR (per 0.2-per-second increase, HR = 0.28; P = .002) were independently associated with occurrence of primary end points in participants with predisposed HFpEF. Conclusion Participants with predisposed HFpEF showed relatively unique clinical and cardiac MRI features, warranting greater clinical attention. eGLSR should be considered as a prognostic factor in participants with predisposed HFpEF. Keywords: Heart Failure with Preserved Ejection Fraction, Normal Natriuretic Peptide Levels, Cardiovascular Magnetic Resonance, Myocardial Strain, Prognosis Clinical trial registration no. NCT04603404 Supplemental material is available for this article. © RSNA, 2024.

Clinical features, myocardial strain and tissue characteristics of heart failure with preserved ejection fraction in patients with obesity: A prospective cohort study.

Background: The pathophysiology and subsequent myocardial dysfunction of heart failure with preserved ejection fraction (HFpEF) with comorbid obesity has not been extensively described. This study aimed to investigate the clinical features and cardiovascular magnetic resonance (CMR) derived myocardial strain and tissue characteristics in patients with HFpEF and comorbid obesity phenotype. Methods: In this prospective cohort study, we included consecutive patients admitted to Fuwai hospital in China who underwent CMR. Patients with HFpEF or obesity were diagnosed with demographic data, clinical presentation, laboratory test, and echocardiography or CMR imaging. The key exclusion criteria were cardiomyopathy, primary valvular heart disease, and significant coronary artery disease. Participant data were obtained from the electronic medical records database or inquiry. Comparisons of clinical features and CMR derived structural and functional parameters amongst different groups were made using one-way analysis of variance, or χ2 tests, and post hoc Bonferroni analysis where appropriate. Findings: Between January 1, 2019 and July 31, 2021, 280 participants (108 patients with HFpEF and obesity, 50 patients with HFpEF and normal weight, 72 patients with obesity, and 50 healthy controls) were enrolled. Compared with patients with HFpEF and normal weight, patients with HFpEF and obesity were younger males, and had higher plasma volume, uric acid and hemoglobin levels, yet less often atrial fibrillation, and lower NT-proBNP levels, and had higher left ventricular mass index, end-diastole/systole volume index, lower left atrial volume index, and worse myocardial strains (all p ≤ 0.05), but no remarkable difference in late gadolinium enhancement (LGE) presence and extracellular volume fraction (ECV). After adjusting for age, atrial fibrillation, and coronary artery disease, only global longitudinal strain (GLS, p = 0.031) and early-diastolic global longitudinal strain rate (eGLSR, p = 0.043) were considerably worse in patients with HFpEF and obesity versus patients with HFpEF and normal weight. Furthermore, early-diastolic strain rates showed no linear association with ECV in patients with HFpEF and obesity. Moreover, GLS demonstrated the highest diagnostic ability when compared with traditional CMR structural parameters and ECV to diagnose patients with HFpEF and obesity in the setting of obesity. Interpretation: Higher systemic inflammation, and worse GLS and eGLSR may be the distinct features of obesity-related HFpEF phenotype; strains and ECV may represent different mechanisms of HFpEF with obesity, deserving further study. Funding: The Construction Research Project of Key Laboratory (Cultivation) of Chinese Academy of Medical Sciences (2019PT310025); National Natural Science Foundation of China (81971588); Capital's Funds for Health Improvement and Research (CFH 2020-2-4034); Youth Key Program of High-level Hospital Clinical Research (2022-GSP-QZ-5).

Early Diastolic Longitudinal Strain Rate at MRI and Outcomes in Heart Failure with Preserved Ejection Fraction.

Background Assessment of subclinical myocardial dysfunction by using feature tracking has shown promise in prognosis evaluation of heart failure with preserved ejection fraction (HFpEF). Global early diastolic longitudinal strain rate (eGLSR) can identify earlier diastolic dysfunction; however, limited data are available on its prognostic value in HFpEF. Purpose To evaluate the association between left ventricular (LV) eGLSR and primary composite outcomes (all-cause death or heart failure hospitalization) in patients with HFpEF. Materials and Methods In this retrospective study, consecutive patients with HFpEF (included from January 2010 to March 2013) underwent cardiovascular MRI. The correlation between eGLSR and variables was assessed by using linear regression. The association between eGLSR (obtained with use of feature tracking) and outcomes was analyzed by using Cox proportional regression. Results A total of 186 patients with HFpEF (mean age ± standard deviation, 59 years ± 12; 77 women) were included. The eGLSR was weakly correlated with LV end-diastole volume index (Pearson correlation coefficient [r] = -0.35; P < .001), heart rate (r = 0.35; P < .001), and LV ejection fraction (r = 0.30; P < .001) and moderately correlated with LV end-systole volume index (r = -0.41; P < .001). At a median follow-up of 9.2 years (interquartile range, 8.7-10.0 years), 72 patients experienced primary composite outcomes. Impaired eGLSR, defined as an eGLSR of less than 0.57 per second, was associated with a greater rate of heart failure hospitalization or all-cause death (hazard ratio, 2.0 [95% CI: 1.1, 3.7]; P = .02) after adjusting for multiple clinical and imaging-based variables. Conclusion Left ventricular global early diastolic longitudinal strain rate obtained from cardiovascular MRI feature tracking was independently associated with adverse outcomes in patients with heart failure with preserved ejection fraction. © RSNA, 2021 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on October 22, 2021.

Ischemic Heart Disease: Noninvasive Imaging Techniques and Findings.

Ischemic heart disease is a leading cause of death worldwide and comprises a large proportion of annual health care expenditure. Management of ischemic heart disease is now best guided by the physiologic significance of coronary artery stenosis. Invasive coronary angiography is the standard for diagnosing coronary artery stenosis. However, it is expensive and has risks including vascular access site complications and contrast material-induced nephropathy. Invasive coronary angiography requires fractional flow reserve (FFR) measurement to determine the physiologic significance of a coronary artery stenosis. Multiple noninvasive cardiac imaging modalities can also anatomically delineate or functionally assess for significant coronary artery stenosis, as well as detect the presence of myocardial infarction (MI). While coronary CT angiography can help assess the degree of anatomic stenosis, its inability to assess the physiologic significance of lesions limits its specificity. Physiologic significance of coronary artery stenosis can be determined by cardiac MR vasodilator or dobutamine stress imaging, CT stress perfusion imaging, FFR CT, PET myocardial perfusion imaging (MPI), SPECT MPI, and stress echocardiography. Clinically unrecognized MI, another clear indicator of physiologically significant coronary artery disease, is relatively common and is best evaluated with cardiac MRI. The authors illustrate the spectrum of imaging findings of ischemic heart disease (coronary artery disease, myocardial ischemia, and MI); highlight the advantages and disadvantages of the various noninvasive imaging methods used to assess ischemic heart disease, as illustrated by recent clinical trials; and summarize current indications and contraindications for noninvasive imaging techniques for detection of ischemic heart disease. Online supplemental material is available for this article. Published under a CC BY 4.0 license.

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.

Individualizing Revascularization Strategy for Diabetic Patients With Multivessel Coronary Disease.

BACKGROUND: In patients with diabetes and multivessel coronary artery disease (CAD), the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial demonstrated that, on average, coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) for major acute cardiovascular events (MACE) and angina reduction. Nonetheless, multivessel PCI remains a common revascularization strategy in the real world. OBJECTIVES: To translate the results of FREEDOM to individual patients in clinical practice, risk models of the heterogeneity of treatment benefit were built. METHODS: Using patient-level data from 1,900 FREEDOM patients, the authors developed models to predict 5-year MACE (all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke) and 1-year angina after CABG and PCI using baseline covariates and treatment interactions. Parsimonious models were created to support clinical use. The models were internally validated using bootstrap resampling, and the MACE model was externally validated in a large real-world registry. RESULTS: The 5-year MACE occurred in 346 (18.2%) patients, and 310 (16.3%) had angina at 1 year. The MACE model included 8 variables and treatment interactions with smoking status (c = 0.67). External validation in stable CAD (c = 0.65) and ACS (c = 0.68) demonstrated comparable performance. The 6-variable angina model included a treatment interaction with SYNTAX score (c = 0.67). PCI was never superior to CABG, and CABG was superior to PCI for MACE in 54.5% of patients and in 100% of patients with history of smoking. CONCLUSIONS: To help disseminate the results of FREEDOM, the authors created a personalized risk prediction tool for patients with diabetes and multivessel CAD that could be used in shared decision-making for CABG versus PCI by estimating each patient's personal outcomes with both treatments.

The prevalence and management of angina among patients with chronic coronary artery disease across US outpatient cardiology practices: insights from the Angina Prevalence and Provider Evaluation of Angina Relief (APPEAR) study.

Although eliminating angina is a primary goal in treating patients with chronic coronary artery disease (CAD), few contemporary data quantify prevalence and severity of angina across US cardiology practices. The authors hypothesized that angina among outpatients with CAD managed by US cardiologists is low and its prevalence varies by site. Among 25 US outpatient cardiology clinics enrolled in the American College of Cardiology Practice Innovation and Clinical Excellence (PINNACLE) registry, we prospectively recruited a consecutive sample of patients with chronic CAD over a 1- to 2-week period at each site between April 2013 and July 2015, irrespective of the reason for their appointment. Eligible patients had documented history of CAD (prior acute coronary syndrome, prior coronary revascularization procedure, or diagnosis of stable angina) and ≥1 prior office visit at the practice site. Angina was assessed directly from patients using the Seattle Angina Questionnaire Angina Frequency score. Among 1257 patients from 25 sites, 7.6% (n = 96) reported daily/weekly, 25.1% (n = 315) monthly, and 67.3% (n = 846) no angina. The proportion of patients with daily/weekly angina at each site ranged from 2.0% to 24.0%, but just over half (56.3%) were on ≥2 antianginal medications, with wide variability across sites (0%-100%). One-third of outpatients with chronic CAD managed by cardiologists report having angina in the prior month, and 7.6% have frequent symptoms. Among those with frequent angina, just over half were on ≥2 antianginal medications, with wide variability across sites. These findings suggest an opportunity to improve symptom control.

Association Between Cardiac Rehabilitation Participation and Health Status Outcomes After Acute Myocardial Infarction.

IMPORTANCE: Cardiac rehabilitation (CR) improves survival after acute myocardial infarction (AMI), and referral to CR has been introduced as a performance measure of high-quality care. The association of participation in CR with patients' health status (eg, quality of life, symptoms, and functional status) is poorly defined. OBJECTIVE: To examine the association of participation in CR with health status outcomes after AMI. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted of patients enrolled in 2 AMI registries: PREMIER, from January 1, 2003, to June 28, 2004, and TRIUMPH, from April 11, 2005, to December 31, 2008. The analytic cohort was restricted to 4929 patients with data available on baseline health status, 6- or 12- month follow-up health status, and participation in CR. Data analysis was performed from 2014 to 2015. EXPOSURES: Participation in at least 1 CR session within 6 months of hospital discharge. MAIN OUTCOMES AND MEASURES: Patient health status was quantified using the Seattle Angina Questionnaire (SAQ) and the 12-Item Short-Form Health Survey (SF-12). The primary outcomes of interest were the mean differences in SAQ domain scores during the 12 months after AMI between patients who did and did not participate in CR. Secondary outcomes were the mean differences in the SF-12 summary scores and all-cause mortality. RESULTS: After successfully matching the cohorts of the 4929 patients (3328 men and 1601 women; mean [SD] age, 60.0 [12.2] years) for the propensity to participate in CR and comparing the groups using linear, mixed-effects models, mean differences in the SAQ and SF-12 domain scores were similar at 6 and 12 months between the 2012 patients participating in CR (3 were unable to be matched) and the 2894 who did not participate (20 were unable to be matched). At 6 months, the mean difference was -0.76 (95% CI, -2.05 to 0.52) for the SAQ quality of life score, -1.53 (95% CI, -2.57 to -0.49) for the SAQ angina frequency score, 0.38 (95% CI, -0.51 to 1.27) for the SAQ treatment satisfaction score, -0.42 (95% CI, -1.65 to 0.79) for the SAQ physical limitation score, 0.50 (95% CI, -0.22 to 1.22) for the SF-12 physical component score, and 0.13 (95% CI, -0.53 to 0.79) for the SF-12 mental component score. At 12 months, the mean difference was -0.89 (95% CI, -2.20 to 0.43) for the SAQ quality of life score, -1.05 (95% CI, -2.12 to 0.02) for the SAQ angina frequency score, 0.38 (95% CI, -0.54 to 1.29) for the SAQ treatment satisfaction score, -0.14 (95% CI, -1.41 to 1.14) for the SAQ physical limitation score, 0.17 (95% CI, -0.57 to 0.92) for the SF-12 physical component score, and 0.12 (95% CI, -0.56 to 0.80) for the SF-12 mental component score. In contrast, the hazard rate of all-cause mortality (up to 7 years) associated with participating in CR was 0.59 (95% CI, 0.46-0.75). CONCLUSIONS AND RELEVANCE: In a cohort of 4929 patients with AMI, we found that those who did and did not participate in CR had similar reported health status during the year following AMI; however, participation in CR did confer a significant survival benefit. These findings underscore the need for increased use of validated patient-reported outcome measures to further examine if and how health status can be maximized for patients who participate in CR.

Predicting Likelihood for Coronary Artery Bypass Grafting After Non-ST-Elevation Myocardial Infarction: Finding the Best Prediction Model.

BACKGROUND: Up to half of patients with non-ST-elevation myocardial infarction (NSTEMI) do not receive dual antiplatelet therapy before angiography "pretreatment" because of the risk of increased bleeding if coronary artery bypass grafting (CABG) operation is needed. Several models have been published that predict the likelihood of CABG after NSTEMI, but they have not been independently validated. The purpose of this study was to validate these models and improve the best one. METHODS: We studied patients with NSTEMI who were enrolled in the 24-center Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registry between 2005 and 2008. Previous CABG prediction models were assessed using c-statistics and calibration assessments to determine the best model. Variables from TRIUMPH likely to be associated with CABG were tested to see whether they could improve the best model's performance. RESULTS: Among 2,473 patients with NSTEMI, 11.8% underwent in-hospital CABG. C-statistics for the Modified Thrombolysis in Myocardial Infarction, Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18, Poppe, and Global Risk of Acute Coronary Events (GRACE) models were 0.54, 0.61, 0.61, and 0.62, respectively. The GRACE model showed the best discrimination and calibration. From the TRIUMPH registry, preselected variables were added to the GRACE model but did not significantly improve model discrimination. A GRACE model risk score of less than 9 had high sensitivity (96%), thus making it useful for predicting patients with NSTEMI who were at low risk for requiring CABG, which included approximately 21% of patients with NSTEMI. CONCLUSIONS: This study could not improve on the GRACE model, which had the best predictive value for identifying a need for CABG after NSTEMI with a broader range of predicted risk levels and high sensitivity, especially in patients with scores lower than 9.

Patient and physician discordance in reporting symptoms of angina among stable coronary artery disease patients: Insights from the Angina Prevalence and Provider Evaluation of Angina Relief (APPEAR) study.

BACKGROUND: A principal goal of treating patients with coronary artery disease (CAD) is to minimize angina and optimize quality of life. For this, physicians must accurately assess presence and frequency of patients' angina. The accuracy with which cardiologists estimate their patients' angina in contemporary, busy outpatient clinics across the United States (US) is unknown. METHODS: We enrolled patients with CAD across 25 US cardiology outpatient practices. Patients completed the Seattle Angina Questionnaire before their visit, which assessed their angina and quality of life over the prior 4 weeks. The Seattle Angina Questionnaire angina frequency domain categorized patients' angina as none, daily/weekly, or monthly. After the visit, cardiologists estimated the frequency of their patients' angina using the same categories. Kappa statistic helped to assess agreement between patient-reported and cardiologist-estimated angina. RESULTS: Among 1,257 outpatients with CAD, 67% reported no angina, 25% reported monthly angina, and 8% reported daily/weekly angina. When patients reported no angina, cardiologists accurately estimated this 93% of the time, but when patients reported monthly or daily/weekly angina symptoms, cardiologists agreed 17% and 69% of the time, respectively. Among patients with daily/weekly angina, 26% were noted as having no angina by their physicians. Agreement between patients' and cardiologists' reports (assessed by the kappa statistic) was 0.48 (95% CI 0.44-0.53), indicating moderate agreement. CONCLUSIONS: Among outpatients with stable CAD, there is substantial discordance between patient-reported and cardiologist-estimated burden of angina. Inclusion of patient-reported health status measures in routine clinical care may support better recognition of patients' symptoms by physicians.

Effect of angina under-recognition on treatment in outpatients with stable ischaemic heart disease.

AIMS: Almost a third of outpatients with chronic coronary artery disease (CAD) report having angina in the prior month, which is frequently under-recognized by their cardiologists. Whether under-recognition is associated with less treatment escalation to control angina, and potential underuse of treatment, is unknown. METHODS AND RESULTS: Patients with CAD from 25 US cardiology outpatient practices completed the Seattle Angina Questionnaire (SAQ) prior to their clinic visit, and angina was categorized as daily, weekly, monthly and no angina. Cardiologists (n=155) independently quantified patients' angina, blinded to patients' SAQ scores. Under-recognition was defined as the physician reporting a lower category of angina frequency than the patient. Among 1257 patients with CAD, 411 reported angina in the past month, of whom 178 (43.3%) patients were under-recognized. Treatment escalation-defined as intensification (up-titration or addition) of antianginal medications, referral for diagnostic testing or revascularization, or hospital admission-occurred in 106 (25.8%) patients with angina. Patients with under-recognized angina were less likely to get treatment escalation than patients whose angina was appropriately recognized (8.4% vs 39.1%, P<0.001). In a hierarchical multivariable logistic regression model adjusting for demographic and clinical characteristics, as well as the burden of angina, under-recognition remained strongly associated with a lack of treatment escalation (adjusted OR 0.10, 95% CI 0.04-0.21, P<0.001). CONCLUSIONS: Under-recognition of angina in cardiology outpatient practices is associated with less aggressive treatment escalation and may lead to poorer angina control. Standardizing clinical recognition of angina using validated tools could reduce under-recognition of angina, facilitate treatment, and potentially improve outcomes.

Variation in patients' perceptions of elective percutaneous coronary intervention in stable coronary artery disease: cross sectional study.

OBJECTIVES: To assess the perceptions of patients with stable coronary artery disease of the urgency and benefits of elective percutaneous coronary intervention and to examine how they vary across centers and by providers. DESIGN: Cross sectional study. SETTING: 10 US academic and community hospitals performing percutaneous coronary interventions between 2009 and 2011. PARTICIPANTS: 991 patients with stable coronary artery disease undergoing elective percutaneous coronary intervention. MAIN OUTCOME MEASURES: Patients' perceptions of the urgency and benefits of percutaneous coronary intervention, assessed by interview. Multilevel hierarchical logistic regression models examined the variation in patients' understanding across centers and operators after adjusting for patient characteristics, using median odds ratios. RESULTS: The most common reported benefits from percutaneous coronary intervention were to extend life (90%, n=892; site range 80-97%) and to prevent future heart attacks (88%, n=872; site range 79-97%). Although nearly two thirds of patients (n=661) reported improvement of symptoms as a benefit of percutaneous coronary intervention (site range 52-87%), only 1% (n=9) identified this as the only benefit. Substantial variability was noted in the ways informed consent was obtained at each site. After adjusting for patient and operator characteristics, the median odds ratios showed significant variation in patients' perceptions of percutaneous coronary intervention across sites (range 1.4-3.1) but not across operators within a site. CONCLUSION: Patients have a poor understanding of the benefits of elective percutaneous coronary intervention, with significant variation across sites. No sites had a high proportion of patients accurately understanding the benefits. Coupled with the wide variability in the ways in which hospitals obtain informed consent, these findings suggest that hospital level interventions into the structure and processes of obtaining informed consent for percutaneous coronary intervention might improve patient comprehension and understanding.