High-frequency QRS analysis to supplement ST evaluation in exercise stress electrocardiography: Incremental diagnostic accuracy and net reclassification.

BACKGROUND: Exercise stress electrocardiography (ECG) alone is underutilized in part due to poor diagnostic accuracy. High-frequency QRS analysis (HF-QRS) is a novel tool to supplement ST evaluation during stress ECG. We compared the diagnostic accuracy and net reclassification of HF-QRS analysis compared with ST evaluation for substantial myocardial ischemia by exercise SPECT myocardial perfusion imaging (MPI). METHODS AND RESULTS: Exercise SPECT MPI was performed in 257 consecutive eligible patients (mean age 59 ± 12, 67% male). An ischemic HF-QRS pattern was defined as a ≥ 1 µV absolute reduction and a ≥ 50% relative reduction of the root-mean-square of the 150-250 Hz band signal in ≥ 3 leads. Left ventricular ischemia of ≥ 10% on SPECT MPI was the diagnostic standard for substantial myocardial ischemia. HF-QRS analysis demonstrated incremental diagnostic value to ST evaluation plus clinical risk factors (AUC 0.804 vs 0.749, P < .0001). A HF-QRS + ST -analysis strategy identified 92.3% of subjects with substantial ischemia and no abnormality in 59.9% of the cohort. No cardiac events occurred in patients without substantial ischemia identified by HF-QRS analysis. CONCLUSIONS: In this prospective analysis, exercise stress ECG with HF-QRS analysis identified any and substantial ischemia with high diagnostic accuracy and may allow more than half of referred patients to safely avoid imaging.

Quantitative cardiovascular magnetic resonance perfusion imaging identifies reduced flow reserve in microvascular coronary artery disease.

BACKGROUND: Preliminary semi-quantitative cardiovascular magnetic resonance (CMR) perfusion studies have demonstrated reduced myocardial perfusion reserve (MPR) in patients with angina and risk factors for microvascular disease (MVD), however fully quantitative CMR has not been studied. The purpose of this study is to evaluate whether fully quantitative CMR identifies reduced MPR in this population, and to investigate the relationship between epicardial atherosclerosis, left ventricular hypertrophy (LVH), extracellular volume (ECV), and perfusion. METHODS: Forty-six patients with typical angina and risk factors for MVD (females, or males with diabetes or metabolic syndrome) who had no obstructive coronary artery disease by coronary angiography and 20 healthy control subjects underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse sequence to quantify MPR. Subjects also underwent T1 mapping to quantify ECV, and computed tomographic (CT) coronary calcium scoring to assess atherosclerosis burden. RESULTS: In patients with risk factors for MVD, both MPR (2.21 [1.95,2.69] vs. 2.93 [2.763.19], p < 0.001) and stress myocardial perfusion (2.65 ± 0.62 ml/min/g, vs. 3.17 ± 0.49 ml/min/g p < 0.002) were reduced as compared to controls. These differences remained after adjusting for age, left ventricular (LV) mass, body mass index (BMI), and gender. There were no differences in native T1 or ECV between subjects and controls. CONCLUSIONS: Stress myocardial perfusion and MPR as measured by fully quantitative CMR perfusion imaging are reduced in subjects with risk factors for MVD with no obstructive CAD as compared to healthy controls. Neither myocardial hypertrophy nor fibrosis accounts for these differences.

Blood pressure and cardiovascular effects of new and emerging antidiabetic agents.

Despite remarkable declines in US cardiovascular disease morbidity and mortality over the last several decades, the prevalence of risk factors such as type 2 diabetes and hypertension remains high, associated with increasing obesity rates. Although optimal glycemic control remains a primary focus to decrease the disease burden, the FDA has issued guidance recommendations for documenting cardiovascular disease-related safety with research trials on new antidiabetic agents with more demanding requirements compared to past approval of existing therapies. This review will discuss the public health impact of type 2 diabetes, specifically with comorbid hypertension; mechanisms of action of the newest antidiabetic drug classes; and preliminary findings and potential clinical significance of the favorable blood pressure and body weight effects of the sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists; and additionally discuss two recent large cardiovascular outcome trials with dipeptidyl peptidase-4 inhibitors.

Cardiometabolic biomarker patterns associated with cardiac MRI defined fibrosis and microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex disease process influenced by metabolic disorders, systemic inflammation, myocardial fibrosis, and microvascular dysfunction. The goal of our study is to identify potential relationships between plasma biomarkers and cardiac magnetic resonance (CMR) imaging markers in patients with HFpEF. Methods: Nineteen subjects with HFpEF and 15 age-matched healthy controls were enrolled and underwent multiparametric CMR and plasma biomarker analysis using the Olink® Cardiometabolic Panel (Olink Proteomics, Uppsala, Sweden). Partial least squares discriminant analysis (PLS-DA) was used to characterize CMR and biomarker variables that differentiate the subject groups into two principal components. Orthogonal projection to latent structures by partial least squares (OPLS) analysis was used to identify biomarker patterns that correlate with myocardial perfusion reserve (MPR) and extracellular volume (ECV) mapping. Results: A PLS-DA could differentiate between HFpEF and normal controls with two significant components explaining 79% (Q2 = 0.47) of the differences. For OPLS, there were 7 biomarkers that significantly correlated with ECV (R2 = 0.85, Q = 0.53) and 6 biomarkers that significantly correlated with MPR (R2 = 0.92, Q2 = 0.32). Only 1 biomarker significantly correlated with both ECV and MPR. Discussion: Patients with HFpEF have unique imaging and biomarker patterns that suggest mechanisms associated with metabolic disease, inflammation, fibrosis and microvascular dysfunction.

Functional and Economic Impact of INOCA and Influence of Coronary Microvascular Dysfunction.

OBJECTIVES: This study sought to better characterize the quality of life and economic impact in patients with symptoms of ischemia and no obstructive coronary disease (INOCA) and to identify the influence of coronary microvascular dysfunction (CMD). BACKGROUND: Patients with INOCA have a high symptom burden and an increased incidence of major adverse cardiac events. CMD is a frequent cause of INOCA. The morbidity associated with INOCA and CMD has not been well-characterized. METHODS: Sixty-six patients with INOCA underwent stress cardiac magnetic resonance with calculation of myocardial perfusion reserve (MPR); MPR 2.0 to 2.4 was considered borderline-reduced (possible CMD) and MPR <2.0 was defined as reduced (definite CMD). Subjects completed quality of life questionnaires to assess the morbidity and economic impact of INOCA. Questionnaire results were compared between INOCA patients with and without CMD. In addition, logistic regression was used to determine the predictors of CMD within the INOCA population. RESULTS: The prevalence of definite CMD was 24%. Definite or borderline CMD was present in 59% (MPR ≤2.4). Patients with INOCA reported greater physical limitation, angina frequency, and reduced quality of life compared to referent stable coronary artery disease and acute myocardial infarction populations. In addition, Patients with INOCA reported frequent time missed from work and work limitations, suggesting a substantial economic impact. No difference was observed in reported symptoms between INOCA patients with and without CMD. Glomerular filtration rate and body-mass index were significant predictors of CMD in multivariable regression analysis. CONCLUSIONS: INOCA is associated with high morbidity similar to other high-risk cardiac populations, and work limitations reported by Patients with INOCA suggest a substantial economic impact. CMD is a common cause of INOCA but is not associated with increased morbidity. These results suggest that there is significant symptom burden in the INOCA population regardless of etiology.

Frequency of Coronary Microvascular Dysfunction and Diffuse Myocardial Fibrosis (Measured by Cardiovascular Magnetic Resonance) in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is frequently accompanied by co-morbidities and a systemic proinflammatory state, resulting in coronary microvascular dysfunction (CMD), as well as myocardial fibrosis. The purpose of this study is to examine the relation between myocardial perfusion reserve (MPR) and diffuse myocardial fibrosis in patients with HFpEF using cardiovascular magnetic resonance. A single center study was performed in 19 patients with clinical HFpEF and 15 healthy control subjects who underwent quantitative first-pass perfusion imaging to calculate global MPR. T1 mapping was used to assess fibrosis and to calculate extracellular volume. Spiral cine displacement encoded stimulated echo was used to calculate myocardial strain. Comprehensive 2D echocardiograms with speckle tracking, cardiopulmonary exercise testing, and brain natriuretic peptide levels were also obtained. In patients with HFpEF, mean left ventricular EF was 61% ± 9% and left ventricular mass index 45 ± 12 g/m2. Compared with controls, HFpEF patients had reduced global MPR (2.29 ± 0.64 vs 3.38 ± 0.76, p = 0.002) and VO2 max (16.5 ± 6.8 vs 30.9 ± 7.7 ml/kg min, p <0.001) whereas extracellular volume (0.29 ± 0.04 vs 0.25 ± 0.04, p = 0.02), pulmonary artery systolic pressure (35.4 ± 13.7 vs 22.3 ± 5.4 mm Hg, p = 0.004), and average E/e' (15.0 ± 7.6 vs 8.6 ± 2.0, p = 0.005) were increased. Displacement encoded stimulated echo peak systolic circumferential strain (p = 0.60) as well as echocardiographic derived global longitudinal strain (p = 0.07) were similar between both groups. The prevalence of CMD, defined as global MPR <2.5, in the HFpEF group was 69%. In conclusion, HFpEF patients have a high prevalence of CMD and diffuse fibrosis. These parameters may be useful clinical end points for future therapeutic trials.

Non-invasive assessment of low- and intermediate-risk patients with chest pain.

Coronary artery disease (CAD) remains a significant global public health burden despite advancements in prevention and therapeutic strategies. Common non-invasive imaging modalities, anatomic and functional, are available for the assessment of patients with stable chest pain. Exercise electrocardiography is a long-standing method for evaluation for CAD and remains the initial test for the majority of patients who can exercise adequately with a baseline interpretable electrocardiogram. The addition of cardiac imaging to exercise testing provides incremental benefit for accurate diagnosis for CAD and is particularly useful in patients who are unable to exercise adequately and/or have uninterpretable electrocardiograms. Radionuclide myocardial perfusion imaging and echocardiography with exercise or pharmacological stress provide high sensitivity and specificity in the detection and further risk stratification of patients with CAD. Recently, coronary computed tomography angiography has demonstrated its growing role to rule out significant CAD given its high negative predictive value. Although less available, stress cardiac magnetic resonance provides a comprehensive assessment of cardiac structure and function and provides a high diagnostic accuracy in the detection of CAD. The utilization of non-invasive testing is complex due to various advantages and limitations, particularly in the assessment of low- and intermediate-risk patients with chest pain, where no single study is suitable for all patients. This review will describe currently available non-invasive modalities, along with current evidence-based guidelines and appropriate use criteria in the assessment of low- and intermediate-risk patients with suspected, stable CAD.

Prognostic Value of Myocardial Scarring on CMR in Patients With Cardiac Sarcoidosis.

OBJECTIVES: This study sought to perform a systematic review and meta-analysis to understand the prognostic value of myocardial scarring as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging in patients with known or suspected cardiac sarcoidosis. BACKGROUND: Although CMR is increasingly used for the diagnosis of cardiac sarcoidosis, the prognostic value of CMR has been less well described in this population. METHODS: PubMed, Cochrane CENTRAL, and metaRegister of Controlled Trials were searched for CMR studies with ≥1 year of prognostic data. Primary endpoints were all-cause mortality and a composite outcome of arrhythmogenic events (ventricular arrhythmia, implantable cardioverter-defibrillator shock, sudden cardiac death) plus all-cause mortality during follow-up. Summary effect estimates were generated with random-effects modeling. RESULTS: Ten studies were included, involving a total of 760 patients with a mean follow-up of 3.0 ± 1.1 years. Patients had a mean age of 53 years, 41% were male, 95.3% had known extracardiac sarcoidosis, and 21.6% had known cardiac sarcoidosis. The average ejection fraction was 57.8 ± 9.1%. Patients with LGE had higher odds for all-cause mortality (odds ratio [OR]: 3.06; p < 0.03) and higher odds of the composite outcome (OR: 10.74; p < 0.00001) than those without LGE. Patients with LGE had an increased annualized event rate of the composite outcome (11.9% vs. 1.1%; p < 0.0001). CONCLUSIONS: In patients with known or suspected cardiac sarcoidosis, the presence of LGE on CMR imaging is associated with increased odds of both all-cause mortality and arrhythmogenic events.

Cardiovascular Disease in Hispanics/Latinos in the United States.

Cardiovascular diseases (CVD) are the leading cause of mortality in the United States and Western world for all groups with one exception: CVDs are the number 2 cause of death for Hispanics/Latinos behind cancer with overall cancer rates lower for Latinos relative to non-Hispanic Whites (NHWs). Despite a significantly worse risk factor profile marked by higher rates of traditional and non-traditional determinants, some CVD prevalence and mortality rates are significantly lower among Latinos relative NHWs. These findings support a need for greater understanding of CVDs specifically among Latinos in order to better document prevalence, appropriately model risk and resilience, and improve targeting of intervention efforts. The current aim is to provide a state-of-the-science review of CVDs amongst Latinos including a review of the epidemiological evidence, risk factor prevalence, and evaluation of the breadth and quality of the data. Questions concerning the generalizability of current risk models, the Hispanic paradox as it relates to CVDs, contributing psychosocial and sociocultural factors, and future directions are discussed.

Development and Validation of Risk Prediction Models for Cardiovascular Events in Black Adults: The Jackson Heart Study Cohort.

IMPORTANCE: Cardiovascular risk assessment is a fundamental component of prevention of cardiovascular disease (CVD). However, commonly used prediction models have been formulated in primarily or exclusively white populations. Whether risk assessment in black adults is dissimilar to that in white adults is uncertain. OBJECTIVES: To develop and validate risk prediction models for CVD incidence in black adults, incorporating standard risk factors, biomarkers, and subclinical disease. DESIGN, SETTING, AND PARTICIPANTS: The Jackson Heart Study (JHS), a longitudinal community-based study of 5301 black adults in Jackson, Mississippi. Inclusive study dates were the date of a participant's first visit (September 2000 to March 2004) to December 31, 2011. The median (75th percentile) follow-up was 9.1 (9.7) years. The dates of the analysis were August 2013 to May 2015. Measurements included standard risk factors, including age, sex, body mass index, systolic and diastolic blood pressure, ratio of fasting total cholesterol to high-density lipoprotein cholesterol, estimated glomerular filtration rate, antihypertensive therapy, diabetes mellitus, and smoking; blood biomarkers; and subclinical disease measures, including ankle-brachial index, carotid intimal-medial thickness, and echocardiographic left ventricular hypertrophy and systolic dysfunction. MAIN OUTCOMES AND MEASURES: Incident CVD event was defined as the first occurrence of myocardial infarction, coronary heart disease death, congestive heart failure, stroke, incident angina, or intermittent claudication. Model performance was compared with the American College of Cardiology/American Heart Association (ACC/AHA) CVD risk algorithm and the Framingham Risk Score (FHS) refitted to the JHS data and evaluated in the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis cohorts. RESULTS: The study cohort comprised 3689 participants with mean (SD) age at baseline was 53 (11) years, and 64.8% (n = 2390) were female. Over a median of 9.1 years, 270 participants (166 women) experienced a first CVD event. A simple combination of standard CVD risk factors, B-type natriuretic peptide, and ankle-brachial index (model 6) yielded modest improvement over a model without B-type natriuretic peptide and ankle-brachial index (C statistic, 0.79; 95% CI, 0.75-0.83 [relative integrated discrimination improvement, 0.22; 95% CI, 0.15-0.30]). However, the reclassification improvement was not substantially different between model 6 and the ACC/AHA CVD Pooled Cohort risk equations or between model 6 and the FHS. The models discriminated reasonably well in the ARIC and Multi-Ethnic Study of Atherosclerosis data (C statistic range, 0.70-0.77). CONCLUSIONS AND RELEVANCE: Our findings using the JHS data in the present study are valuable because they confirm that current FHS and ACC/AHA risk algorithms work well in black individuals and are not easily improved on. A unique risk calculator for black adults may not be necessary.

The Role of Hypertension in Race-Ethnic Disparities in Cardiovascular Disease.

Race-ethnic disparities in cardiovascular disease (CVD) have persisted in the USA over the past few decades. Hypertension (HTN) is a significant contributor to CVD, including coronary heart disease, stroke, end-stage kidney disease and overall mortality and race-ethnic disparities in longevity. Additionally, both non-Hispanic blacks (NHBs) and Hispanic adults have been known to have higher prevalence of poorly controlled blood pressure compared to non-Hispanic whites (NHWs). Addressing these disparities has been a focus of programs such as the Million Hearts initiative. This review will provide an update of available data on HTN in various race-ethnic groups, including awareness, treatment, and control and note the recent progress in HTN control across all race/ethnic groups. We will also discuss the recent 2014 U.S. HTN guideline that has led to debate regarding the potential impact of BP goals in older persons on worsening CVD disparities, with disproportionate effects on women and NHBs.