Quantifying assumptions underlying peak oxygen consumption equations across the body mass spectrum.

The goal of this study is to quantify the assumptions associated with the Wasserman-Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO2 ) equations across body mass index (BMI). Assumptions in pVO2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent-predicted VO2 (ppVO2 ) values for both equations and compared them using the Bland-Altman method. Assumptions associated with pVO2 across BMI categories were quantified by comparing the slopes of age-adjusted VO2 ratios (pVO2 /pre-exercise VO2 ) and ppVO2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m2 , pVO2 26.8 mlO2 /kg/min). The Bland-Altman plot revealed an average relative difference of -1.7% (95% CI: -2.1 to -1.2%) between WH and FRIEND ppVO2 values with greater differences among those with obesity. Analysis of the VO2 ratio to ppVO2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO2 may better inform the clinical interpretation of ppVO2 values during cardiopulmonary exercise test evaluations.

Improving Reporting of Exercise Capacity Across Age Ranges Using Novel Workload Reference Equations.

Exercise capacity (EC) is an important predictor of survival in the general population and in subjects with cardiopulmonary disease. Despite its relevance, considering the percent-predicted workload (%pWL) given by current equations may overestimate EC in older adults. Therefore, to improve the reporting of EC in clinical practice, our main objective was to develop workload reference equations (pWL) that better reflect the relation between workload and age. Using the Fitness Registry and the Importance of Exercise National Database (FRIEND), we analyzed a reference group of 6,966 apparently healthy participants and 1,060 participants with heart failure who underwent graded treadmill cardiopulmonary exercise testing. For the first group, the mean age was 44 years (18 to 79); 56.5% of participants were males and 15.4% had obesity. Peak oxygen consumption was 11.6 ± 3.0 METs in males and 8.5 ± 2.4 METs in females. After partition analysis, we first developed sex-specific pWL equations to allow comparisons to a healthy weight reference. For males, pWL (METs) = 14.1-0.9×10-3×age2 and 11.5-0.87×10-3×age2 for females. We used those equations as denominators of %pWL, and based on their distribution, we determined thresholds for EC classification, with average EC defined by the range corresponding to 85% to 115%pWL. Compared with %pWL using current equations, the new equations yielded better-calibrated %pWL across different age ranges. We also derived body mass index-adjusted pWL equations that better assessed EC in subjects with heart failure. In conclusion, the novel pWL equations have the potential to impact the report of EC in practice.

Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise.

BACKGROUND: Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF. METHODS: Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2. RESULTS: Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 ± 3.8 vs. 32.5 ± 9.8 mL/Kg*min-1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 ± 9.8% for patients with CHF compared to 61.1 ± 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 ± 51.0, 132.0 ± 38.8 and 155.6 ± 45.5s) than in controls (58.08 ± 13.2, 74.3 ± 21.1, 96.7 ± 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 ± 3.3, 41.9 ± 29.1 and 25.0 ± 13.6%) than in controls (10.1 ± 4.6, 62.1 ± 17.7 and 38.7 ± 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF. CONCLUSIONS: Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.

Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise

Abstract Background Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF. Methods Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2. Results Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 ± 3.8 vs. 32.5 ± 9.8 mL/Kg*min−1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 ± 9.8% for patients with CHF compared to 61.1 ± 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 ± 51.0, 132.0 ± 38.8 and 155.6 ± 45.5s) than in controls (58.08 ± 13.2, 74.3 ± 21.1, 96.7 ± 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 ± 3.3, 41.9 ± 29.1 and 25.0 ± 13.6%) than in controls (10.1 ± 4.6, 62.1 ± 17.7 and 38.7 ± 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF. Conclusions Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.

Association of left ventricular diastolic function with coronary artery calcium score: A Project Baseline Health Study.

BACKGROUND: Coronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear. METHODS: In the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography. The association between left ventricular (LV) diastolic function and CAC was assessed using multidimensional network and multivariable-adjusted regression analyses. Multivariable analysis was conducted on continuous LV diastolic parameters and categorical classification of LVDD and adjusted for traditional cardiometabolic risk factors. LVDD was defined using reference limits from a low-risk reference group without established cardiovascular disease, cardiovascular risk factors or evidence of CAC, (n â€‹= â€‹560). We also classified LVDD using the American Society of Echocardiography recommendations. RESULTS: The mean age of the participants was 51 â€‹± â€‹17 years with 56.6% female and 62.6% non-Hispanic White. Overall, 38.1% had hypertension; 13.7% had diabetes; and 39.9% had CAC >0. An intertwined network was observed between diastolic parameters, CAC score, age, LV mass index, and pulse pressure. In the multivariable-adjusted analysis, e', E/e', and LV mass index were independently associated with CAC after adjustment for traditional risk factors. For both e' and E/e', the effect size and statistical significance were higher across increasing CAC tertiles. Other independent correlates of e' and E/e' included age, female sex, Black race, height, weight, pulse pressure, hemoglobin A1C, and HDL cholesterol. The independent association with CAC was confirmed using categorical analysis of LVDD, which occurred in 554 participants (26.6%) using population-derived thresholds. CONCLUSION: In the PBHS study, the subclinical coronary atherosclerotic disease burden detected using CAC scoring was independently associated with diastolic function. GOV IDENTIFIER: NCT03154346.

Findings From Cardiovascular Evaluation of National Collegiate Athletic Association Division I Collegiate Student-Athletes After Asymptomatic or Mildly Symptomatic SARS-CoV-2 Infection.

OBJECTIVE: The risk of myocardial damage after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been controversial. The purpose of this study is to report the incidence of abnormal cardiovascular findings in National Collegiate Athletic Association (NCAA) Division I student-athletes with a history of SARS-CoV-2 infection. DESIGN: This is a case series of student-athletes with SARS-CoV-2 infection and their subsequent cardiac work-up, including troponin level, electrocardiogram, and echocardiogram. Additional testing was ordered as clinically indicated. SETTING: This study was conducted at a single NCAA Division I institution. PARTICIPANTS: Student-athletes were included if they tested positive for SARS-CoV-2 by PCR or antibody testing [immunoglobulin G (IgG)] from April 15, 2020 to October 31, 2020. INTERVENTION: Cardiac testing was conducted as part of postinfection screening. MAIN OUTCOME MEASURES: This study was designed to quantify abnormal cardiovascular screening results and cardiac diagnoses after SARS-CoV-2 infection in Division I collegiate athletes. RESULTS: Fifty-five student-athletes tested positive for SARS-CoV-2. Of these, 14 (26%) had a positive IgG and 41 (74%) had a positive PCR test. Eight abnormal cardiovascular screening evaluations necessitated further testing including cardiac magnetic resonance imaging (cMRI). Two athletes received new cardiac diagnoses, one probable early cardiomyopathy and one pericarditis, whereas the remaining 6 had normal cMRIs. CONCLUSIONS: These data support recent publications which recommend the de-escalation of cardiovascular testing such as cardiac MRI or echocardiogram for athletes who have recovered from asymptomatic or mildly symptomatic SARS-CoV-2 infection. Continued follow-up of these athletes for sequelae of SARS-CoV-2 is critical.

Comparison of the FRIEND and Wasserman-Hansen Equations in Predicting Outcomes in Heart Failure.

Background Percentage of age-predicted peak oxygen uptake (VO2) achieved (ppVO2) has been widely used to stratify risk in patients with heart failure. However, there are limitations to traditional normal standards. We compared the recently derived FRIEND (Fitness Registry and the Importance of Exercise: A National Data Base) equation to the widely used Wasserman-Hansen (WH) ppVO2 equation to predict outcomes in patients with heart failure. Methods and Results A subgroup of 4055 heart failure patients from the FRIEND registry (mean age 53±15 years) was followed for a mean of 28±16 months. The FRIEND and WH equations along with measured peak VO2 expressed in mL/kg-1 per min-1 were compared for mortality and composite cardiovascular events. ppVO2 was higher for the FRIEND versus the WH equation (66±30% versus 58±25%; P<0.001). The areas under the receiver operating characteristic curves were slightly but significantly higher for the FRIEND equation for mortality (0.74 versus 0.72; P=0.03) and cardiac events (0.70 versus 0.68; P=0.008). Area under the receiver operating characteristic curve for measured peak VO2 was 0.70 (P<0.001) for mortality and 0.73 (P<0.001) for cardiovascular events. For each 1-SD higher ppVO2 for the FRIEND equation, mortality was reduced by 18% (hazard ratio, 0.82; 95% CI, 0.69-0.97; P<0.02); for each 1-SD higher ppVO2 for the WH equation, the mortality was reduced by 17% (hazard ratio, 0.83; 95% CI, 0.71-0.97; P=0.02). The corresponding reductions in risk per 1 SD for cardiovascular events for the FRIEND and WH equations were 23 and 21%, respectively (both P<0.001). Conclusions Peak VO2 expressed as percentage of an age-predicted standard strongly predicts mortality and major cardiovascular events in patients with heart failure. The FRIEND registry equation exhibited test characteristics slightly superior to the commonly used WH equation.

Cardiopulmonary Exercise Testing With Echocardiography to Assess Recovery in Patients With Ventricular Assist Devices.

The left ventricular assist device (LVAD) is an established treatment for select patients with end-stage heart failure. Some patients recovered and are considered for explantation. Assessing recovery involves exercise testing and echo ramping on full and minimal LVAD support. Combined cardiopulmonary exercise testing with simultaneous echo ramping (CPET-R) has not been well studied. Patients were included if they had CPET within the previous 6 months, were clinically stable, and had an INR >2.0 on the day of examination. Patients had CPET-R on two occasions within 14 days: (a) with LVAD at therapeutic speed and (b) with LVAD at the lowest speed possible. Six patients were between 29 and 75 years (two female). One patient did not complete a turn-down test due to evidence of ischemia on initial CPET-R subsequently confirmed as a significant coronary artery stenosis on angiography. There were no significant differences in CPET or echo metrics between LVAD speeds. Two patients were explanted due to presumed LV recovery and remained event free for 30 and 47 months, respectively. Serial CPET-R seems safe and feasible for the evaluation of LV and global function and may result in improved clinical decision making for LVAD explantation.

CTA pulmonary artery enlargement in patients with severe aortic stenosis: Prognostic impact after TAVR.

BACKGROUND: Identifying high-risk patients who will not derive substantial survival benefit from TAVR remains challenging. Pulmonary hypertension is a known predictor of poor outcome in patients undergoing TAVR and correlates strongly with pulmonary artery (PA) enlargement on CTA. We sought to evaluate whether PA enlargement, measured on pre-procedural computed tomography angiography (CTA), is associated with 1-year mortality in patients undergoing TAVR. METHODS: We retrospectively included 402 patients undergoing TAVR between July 2012 and March 2016. Clinical parameters, including Society of Thoracic Surgeons (STS) score and right ventricular systolic pressure (RVSP) estimated by transthoracic echocardiography were reviewed. PA dimensions were measured on pre-procedural CTAs. Association between PA enlargement and 1-year mortality was analyzed. Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS: The median follow-up time was 433 (interquartiles 339-797) days. A total of 56/402 (14%) patients died within 1 year after TAVR. Main PA area (area-MPA) was independently associated with 1-year mortality (hazard ratio per standard deviation equal to 2.04 [95%-confidence interval (CI) 1.48-2.76], p â€‹< â€‹0.001). Area under the curve (95%-CI) of the clinical multivariable model including STS-score and RVSP increased slightly from 0.67 (0.59-0.75) to 0.72 (0.72-0.89), p â€‹= â€‹0.346 by adding area-MPA. Although the AUC increased, differences were not significant (p â€‹= â€‹0.346). Kaplan-Meier analysis showed that mortality was significantly higher in patients with a pre-procedural non-indexed area-MPA of ≥7.40 â€‹cm2 compared to patients with a smaller area-MPA (mortality 23% vs. 9%; p â€‹< â€‹0.001). CONCLUSIONS: Enlargement of MPA on pre-procedural CTA is independently associated with 1-year mortality after TAVR.

Peripheral Oxygen Extraction and Exercise Limitation in Asymptomatic Patients with Diabetes Mellitus.

Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59 ± 11 years and 56% male sex), and compared with 31 age, sex and body mass index-matched normoglycemic controls. Cardiopulmonary exercise testing with resting followed by stress echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO2) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO2). Peripheral extraction was calculated as the ratio of VO2 to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain, E/e', and relative wall thickness. Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO2(<80%) and 18 (18%) presented abnormal VE/VCO2slope (>34). There was no significant difference in peak cardiac output; however, peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e' (beta = -0.24, p = 0.004) was associated with lower peak VO2 along with age, sex and body mass index (R2 = 0.53). A cluster analysis found left ventricular longitudinal strain, E/e', relative wall thickness and peak VO2 in different clusters. In conclusion, impaired peripheral extraction may contribute to reduced peak VO2in asymptomatic patients with DM. Furthermore, a cluster analysis suggests that cardiopulmonary exercise testing and echocardiography may be complementary for defining subclinical heart failure in patients with DM.

Incremental value of diastolic stress test in identifying subclinical heart failure in patients with diabetes mellitus.

AIMS: Resting echocardiography is a valuable method for detecting subclinical heart failure (HF) in patients with diabetes mellitus (DM). However, few studies have assessed the incremental value of diastolic stress for detecting subclinical HF in this population. METHODS AND RESULTS: Asymptomatic patients with Type 2 DM were prospectively enrolled. Subclinical HF was assessed using systolic dysfunction (left ventricular longitudinal strain <16% at rest and <19% after exercise in absolute value), abnormal cardiac morphology, or diastolic dysfunction (E/e' > 10). Metabolic equivalents (METs) were calculated using treadmill speed and grade, and functional capacity was assessed by percent-predicted METs (ppMETs). Among 161 patients studied (mean age of 59 ± 11 years and 57% male sex), subclinical HF was observed in 68% at rest and in 79% with exercise. Among characteristics, diastolic stress had the highest yield in improving detection of HF with 57% of abnormal cases after exercise and 45% at rest. Patients with revealed diastolic dysfunction during stress had significantly lower exercise capacity than patients with normal diastolic stress (7.3 ± 2.1 vs. 8.8 ± 2.5, P < 0.001 for peak METs and 91 ± 30% vs. 105 ± 30%, P = 0.04 for ppMETs). On multivariable modelling found that age (beta = -0.33), male sex (beta = 0.21), body mass index (beta = -0.49), and exercise E/e' >10 (beta = -0.17) were independently associated with peak METs (combined R2 = 0.46). A network correlation map revealed the connectivity of peak METs and diastolic properties as central features in patients with DM. CONCLUSION: Diastolic stress test improves the detection of subclinical HF in patients with diabetes mellitus.

Molecular Choreography of Acute Exercise.

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

Impact of the distance from the chest wall to the heart on surface ECG voltage in athletes.

OBJECTIVE: Available ECG criteria for detection of left ventricular (LV) hypertrophy have been reported to have limited diagnostic capability. Our goal was to describe how the distance between the chest wall and the left ventricle determined by echocardiography affected the relationship between ECG voltage and LV mass (LVM) in athletes. METHODS: We retrospectively evaluated digitised ECG data from college athletes undergoing routine echocardiography as part of their preparticipation evaluation. Along with LV mass and volume, we determined the chest wall-LV distance in the parasternal short-axis and long-axis views from two-dimensional transthoracic echocardiographic images and explored the relation with ECG QRS voltages in all leads, as well as summed voltages as included in six major ECG-LVH criteria. RESULTS: 239 athletes (43 women) were included (age 19±1 years). In men, greater LV-chest wall distance was associated with higher R-wave amplitudes in leads aVL and I (R=0.20 and R=0.25, both p<0.01), while in women greater distance was associated with higher R-amplitudes in V5 and V6 (R=0.42 and R=0.34, both p<0.01). In women, the chest wall-LV distance was the only variable independently (and positively) associated with R V5 voltage, while LVM, height and weight contributed to the relationship in men. CONCLUSIONS: The chest wall-LV distance was weakly associated with ECG voltage in athletes. Inconsistent associations in men and women imply different intrathoracic factors affecting impedance and conductance between sexes. This may help explain the poor relationship between QRS voltage and LVM in athletes.

Interval Endurance and Resistance Training as Part of a Community-Based Secondary Prevention Program for Patients With Diabetes Mellitus and Coronary Artery Disease.

PURPOSE: High-intensity interval training (HIIT) has been observed to improve health and fitness in patients with cardiovascular disease. High-intensity interval training may not be appropriate in community-based settings. Moderate-intensity interval training (MIIT) and resistance training (RT) are emerging as effective alternatives to HIIT. These have not been well investigated in a community-based cardiac maintenance program. METHODS: Patients with coronary artery disease and/or diabetes mellitus participated in clinical examinations and a 6-mo exercise program. Center-based MIIT and home-based moderate continuous intensity exercise were performed for 3-5 d/wk for 30-40 min/session. RT, nutritional counseling, coping, and behavioral change strategies were offered to all patients. Within-group changes in clinical metrics and exercise performance were assessed on a per-protocol basis after 6 mo. RESULTS: Two hundred ninety-two patients (74%) concluded the 6-mo program. There were no serious adverse events. The peak oxygen uptake and peak workload increased significantly, 21.8 ± 6.1 to 22.8 ± 6.3 mL/kg/min and 128 ± 39 to 138 ± 43 W, respectively (both P < .001). Submaximal exercise performance increased from 68 ± 19 to 73 ± 22 W (P < .001). Glycated hemoglobin decreased from 6.57 ± 0.93% to 6.43 ± 0.12%, (P = .023). Daily injected insulin dosage was reduced from 42 IU (interquartile range: 19.0, 60.0) to 26 IU (interquartile range: 0, 40.3, P < .001). CONCLUSIONS: MIIT and RT were feasible and effective in a community-based cardiac maintenance program for patients with cardiovascular disease, improving exercise performance, and blood glucose control.

Value of Neutrophil to Lymphocyte Ratio and Its Trajectory in Patients Hospitalized With Acute Heart Failure and Preserved Ejection Fraction.

The neutrophil to lymphocyte ratio (NLR) has been proposed as a simple and routinely obtained marker of inflammation. This study sought to determine whether the NLR on admission as well as NLR trajectory would be complementary to the Get with the Guidelines Heart Failure (GWTG-HF) risk score in patients hospitalized with acute heart failure with preserved ejection fraction (HFpEF).Using the Stanford Translational Research Database, we identified 443 patients between January 2002 and December 2013 hospitalized with acute HFpEF and with complete data of NLR both on admission and at discharge. The primary endpoint was all-cause mortality. Mean age was 77 ±â€¯16 years, 58% were female, with a high prevalence of diabetes mellitus (35.4%), coronary artery disease (58.2%), systemic hypertension (96.6%) and history of atrial fibrillation (57.5%). Over a median follow-up of 2.2 years, 121 (27.3%) patients died. The median NLR on admission was 6.5 (IQR 3.6 - 11.1); a majority of patients decreased their NLR during the course of hospitalization. On multivariable Cox modeling, both NLR on admission (HR 1.18 95% CI (1.00 - .38), p = 0.04) and absolute NLR trajectory (HR 1.26 95% CI (1.10 - 1.45), p = 0.001) were shown to be incremental to GWTG-HF risk score (p < 0.05) for outcome prediction. Adding the NLR or absolute NLR trajectory to the GWTG-HF risk score significantly improved the area under the operator-receiver curve and the reclassification up to 3 years after admission.This simple, readily available marker of inflammation may be useful when stratifying the risk of patients hospitalized with HFpEF.

Echocardiographic Assessment of Left Ventricular Remodeling in American Style Footballers.

Several athletic programs incorporate echocardiography during pre-participation screening of American Style Football (ASF) players with great variability in reported echocardiographic values. Pre-participation screening was performed in National Collegiate Athletic Association Division I ASF players from 2008 to 2016 at the Division of Sports Cardiology. The echocardiographic protocol focused on left ventricular (LV) mass, mass-to-volume ratio, sphericity, ejection fraction, and longitudinal Lagrangian strain. LV mass was calculated using the area-length method in end-diastole and end-systole. A total of two hundred and thirty players were included (18±1 years, 57% were Caucasian, body mass index 29±4 kg/m2) after four players (2%) were excluded for pathological findings. Although there was no difference in indexed LV mass by race (Caucasian 78±11 vs. African American 81±10 g/m2, p=0.089) or sphericity (Caucasian 1.81±0.13 vs. African American 1.78±0.14, p=0.130), the mass-to-volume ratio was higher in African Americans (0.91±0.09 vs. 0.83±0.08, p<0.001). No race-specific differences were noted in LV longitudinal Lagrangian strain. Player position appeared to have a limited role in defining LV remodeling. In conclusion, significant echocardiographic differences were observed in mass-to-volume ratio between African American and Caucasian players. These demographics should be considered as part of pre-participation screening.

Limitations of Electrocardiography for Detecting Left Ventricular Hypertrophy or Concentric Remodeling in Athletes.

BACKGROUND: Electrocardiography (ECG) is used to screen for left ventricular hypertrophy (LVH), but common ECG-LVH criteria have been found less effective in athletes. The purpose of this study was to comprehensively evaluate the value of ECG for identifying athletes with LVH or a concentric cardiac phenotype. METHODS: A retrospective analysis of 196 male Division I college athletes routinely screened with ECG and echocardiography within the Stanford Athletic Cardiovascular Screening Program was performed. Left-ventricular mass and volume were determined using echocardiography. LVH was defined as left ventricular mass (LVM) >102 g/m²; a concentric cardiac phenotype as LVM-to-volume (M/V) ≥1.05 g/mL. Twelve-lead electrocardiograms including high-resolution time intervals and QRS voltages were obtained. Thirty-seven previously published ECG-LVH criteria were applied, of which the majority have never been evaluated in athletes. C-statistics, including area under the receiver operating curve (AUC) and likelihood ratios were calculated. RESULTS: ECG lead voltages were poorly associated with LVM (r = 0.18-0.30) and M/V (r = 0.15-0.25). The proportion of athletes with ECG-LVH was 0%-74% across criteria, with sensitivity and specificity ranging between 0% and 91% and 27% and 99.5%, respectively. The average AUC of the criteria in identifying the 11 athletes with LVH was 0.57 (95% confidence interval [CI] 0.56-0.59), and the average AUC for identifying the 8 athletes with a concentric phenotype was 0.59 (95% CI 0.56-0.62). CONCLUSION: The diagnostic capacity of all ECG-LVH criteria were inadequate and, therefore, not clinically useful in screening for LVH or a concentric phenotype in athletes. This is probably due to the weak association between LVM and ECG voltage.

Utility of High-Sensitivity and Conventional Troponin in Patients Undergoing Transcatheter Aortic Valve Replacement: Incremental Prognostic Value to B-type Natriuretic Peptide.

High-sensitivity Troponin (hs-Tn) has emerged as a useful marker for patients with myocardial injury or heart failure. However, few studies have compared intermediate and hs-Tn in patients undergoing transcatheter aortic valve replacement (TAVR). Moreover, there remains uncertainty of which thresholds are the most useful for discriminating ventricular dysfunction or outcome. In this study we prospectively enrolled 105 patients with severe aortic stenosis (AS) who underwent TAVR as well as blood sampling for high-sensitivity (hs-TnI) and conventional troponin I (EXL-LOCI and RXL) assessment. Patients underwent comprehensive pre-procedure echocardiography. Ventricular dysfunction was defined using left ventricular mass index (LVMI), LV global longitudinal strain (LVGLS) and LV end-diastolic pressure. The mean age was 84.0 ± 8.7 years old and 60% were male sex with mean transaortic pressure gradient of 50.1 ± 16.0 mmHg and AVA of 0.63 ± 0.19 cm2. When using a threshold of 6 ng/L, 77% had positive hs-TnI while 27% had positive hs-TnI using recommended thresholds (16 ng/L for female and 34 ng/L for male). Troponin levels were higher in the presence of abnormal LV phenotypes. The strongest correlate of troponin was LVMI. During median follow-up of 375 days, 21 patients (20%) died. Lower threshold of hs-TnI and EXL-TnI was more discriminatory for overall mortality (Log-rank P = 0.03 for both), while higher threshold of hs-TnI (p = 0.75) and RXL-TnI were not (p = 0.30). Combining hs-TnI and BNP improved to predict long-term outcome (p = 0.004). In conclusion, hs-TnI levels correlated with the degree of LV dysfunction phenotypes. Furthermore, applying a lower threshold for hs-TnI performed better for outcome prediction than a recommended threshold in patients undergoing TAVR. Combining hs-TnI with BNP helped better risk stratification.

Cardiopulmonary Exercise Testing, Impedance Cardiography, and Reclassification of Risk in Patients Referred for Heart Failure Evaluation.

BACKGROUND: An impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which impedance cardiography (ICG) during exercise in combination with cardiopulmonary exercise test (CPX) responses reclassified risk for adverse events in patients with HF. METHODS AND RESULTS: CPX and ICG were performed in 1236 consecutive patients (48±15 years) evaluated for HF. Clinical, ICG and CPX variables were acquired at baseline and subjects were followed for the composite outcome of cardiac-related death, hospitalization for worsening HF, cardiac transplantation, and left ventricular assist device implantation. Cox proportional hazards analyses including clinical, noninvasive hemodynamic, and CPX variables were performed to determine their association with the composite endpoint. Net reclassification improvement (NRI) was calculated to quantify the impact of adding hemodynamic responses to a model including established CPX risk markers on reclassifying risk. There were 422 events. Among CPX variables, peak VO2 and indices of ventilatory inefficiency (VE/VCO2 slope, oxygen uptake efficiency slope) were significant predictors of risk for adverse events. Among hemodynamic variables, change in cardiac index, peak cardiac time interval, and peak left cardiac work index were the strongest predictors of risk. Having 5 impaired CPX and ICG responses to exercise yielded a sevenfold higher risk for adverse events compared with having no abnormal responses. Combining ICG responses to CPX resulted in NRIs ranging between 0.34 and 0.89, attributable to better reclassification of events. CONCLUSION: Cardiac hemodynamics determined by ICG complement established CPX measures in reclassifying risk among patients with HF.

Approaching Higher Dimension Imaging Data Using Cluster-Based Hierarchical Modeling in Patients with Heart Failure Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality, accounting for the majority of heart failure (HF) hospitalization. To identify the most complementary predictors of mortality among clinical, laboratory and echocardiographic data, we used cluster based hierarchical modeling. Using Stanford Translational Research Database, we identified patients hospitalized with HFpEF between 2005 and 2016 in whom echocardiogram and NT-proBNP were both available at the time of admission. Comprehensive echocardiographic assessment including left ventricular longitudinal strain (LVLS), right ventricular function and right ventricular systolic pressure (RVSP) was performed. The outcome was defined as all-cause mortality. Among patients identified, 186 patients with complete echocardiographic assessment were included in the analysis. The cohort included 58% female, with a mean age of 78.7 ± 13.5 years, LVLS of -13.3 ± 2.5%, an estimated RVSP of 38 ± 13 mmHg. Unsupervised cluster analyses identified six clusters including ventricular systolic-function cluster, diastolic-hemodynamic cluster, end-organ function cluster, vital-sign cluster, complete blood count and sodium clusters. Using a stepwise hierarchical selection from each cluster, we identified NT-proBNP (standard hazard ratio [95%CI] = 1.56 [1.17-2.08]) and RVSP (1.37 [1.09-1.78]) as independent correlates of outcome. When adding these parameters to the well validated Get with the Guideline Heart Failure risk score, the Chi-square was significantly improved (p = 0.01). In conclusion, NT-proBNP and RVSP were independently predictive in HFpEF among clinical, imaging, and biomarker parameters. Cluster-based hierarchical modeling may help identify the complementally predictive parameters in small cohorts with higher dimensional clinical data.