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.

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.

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.

Exercise testing in heart failure: a contemporary discussion in an era of novel diagnostic techniques and biomarkers.

PURPOSE OF REVIEW: The purpose of this review is to highlight recent advances in the field of exercise testing for patients with heart failure. RECENT FINDINGS: The importance of assessment of cardiorespiratory fitness (CRF) and exercise testing in heart failure is highlighted in the consensus recommendation of the American Heart Association. Contemporary studies have validated the independent and incremental strength of CRF metrics in patients with heart failure and coronary artery disease. The use of respiratory gas analysis and imaging or hemodynamics during physical exercise is feasible and results in high prognostic utility across the continuum of heart failure. Understanding how CRF metrics complement existing and novel biomarkers and risk scores is an emerging subject of scientific inquiry. SUMMARY: In the current era of personalized medicine, integrating CRF, imaging and circulating biomarkers will allow us to further develop individualized strategies for improving outcome in patients with heart failure.

Contractile reserve and cardiopulmonary exercise parameters in patients with dilated cardiomyopathy, the two dimensions of exercise testing.

BACKGROUND: Left ventricular (LV) contractile reserve assessed using imaging and cardiopulmonary exercise testing (CPX) has been shown to predict outcome in patients with dilated cardiomyopathy (DCM). Few clinical studies have, however, analyzed the relationship between them. METHODS: A cohort of 75 ambulatory patients with DCM underwent stress treadmill echocardiography with CPX. LV contractile reserve was calculated as absolute change (ΔLVEF=LVEFpeak -LVEFrest ) and percent change (%LVEF=[(LVEFpeak -LVEFrest )/LVEFpeak) ]×100) in LVEF, circumferential and longitudinal strain (LS). Exercise capacity was measured as peak oxygen uptake (peak VO2 ) and ventilatory efficiency as the slope of minute ventilation to CO2 production (VE/VCO2 slope). Values of contractile reserve were compared to matched controls. We also explored which metric of ventricular response (absolute or percent change) was less dependent on baseline LV function. RESULTS: Patients with DCM had a mean age, rest and peak LVEF of 44±10 years, 42±10% and 50±12%, respectively. Among parameters of contractile reserve, peak cardiac output was the strongest parameter associated with peak VO2 (r=.63, P<.001). Along with age, sex, and BMI, it explained more than 70% of the variance in peak VO2 . In contrast, LVEF and LS were only weakly related to peak VO2 . With regard to ventilatory efficiency, the strongest parameter that emerged was right atrial volume index (r=.36, P<.001). Percent change in LVEF was more independent of baseline function than absolute change. CONCLUSION: Echocardiographic contractile reserve and CPX provide complementary information. Percent change in contractile reserve was most independent of baseline function, therefore may be preferred when analyzing the ventricular response to exercise.

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.

Asystole following complex partial seizures.

A case is presented of a patient with a long history of epilepsy who presents with recurrent seizures and develops a period of asystole. The case highlights the need to consider the potential arrhythmic complications of seizures and the clinical characteristics that may be present in those with epilepsy that may warrant evaluation for arrhythmias.

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.

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.

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.

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.

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.

Blood pressure in athletic preparticipation evaluation and the implication for cardiac remodelling.

OBJECTIVES: To explore blood pressure (BP) in athletes at preparticipation evaluation (PPE) in the context of recently updated US and European hypertension guidelines, and to determine the relationship between BP and left ventricular (LV) remodelling. METHODS: In this retrospective study, athletes aged 13-35 years who underwent PPE facilitated by the Stanford Sports Cardiology programme were considered. Resting BP was measured in both arms; repeated once if ≥140/90 mm Hg. Athletes with abnormal ECGs or known hypertension were excluded. BP was categorised per US/European hypertension guidelines. In a separate cohort of athletes undergoing routine PPE echocardiography, we explored the relationship between BP and LV remodelling (LV mass, mass/volume ratio, sphericity index) and LV function. RESULTS: In cohort 1 (n=2733, 65.5% male), 34.3% of athletes exceeded US hypertension thresholds. Male sex (B=3.17, p<0.001), body mass index (BMI) (B=0.80, p<0.001) and height (B=0.25, p<0.001) were the strongest independent correlates of systolic BP. In the second cohort (n=304, ages 17-26), systolic BP was an independent correlate of LV mass/volume ratio (B=0.002, p=0.001). LV longitudinal strain was similar across BP categories, while higher BP was associated with slower early diastolic relaxation. CONCLUSION: In a large contemporary cohort of athletes, one-third presented with BP levels above the current US guidelines' thresholds for hypertension, highlighting that lowering the BP thresholds at PPE warrants careful consideration as well as efforts to standardise measurements. Higher systolic BP was associated with male sex, BMI and height and with LV remodelling and diastolic function, suggesting elevated BP in athletes during PPE may signify a clinically relevant condition.

Time based versus strain based myocardial performance indices in hypertrophic cardiomyopathy, the merging role of left atrial strain.

AIMS: The myocardial performance index (MPI) is a time-based index of global myocardial performance. In this study, we sought to compare the prognostic value of the MPI with other strain and remodelling indices in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We enrolled 126 patients with HCM and 50 age- and sex-matched controls. Along with traditional echocardiographic assessment, MPI, left ventricular global longitudinal strain (LVGLS), E/e' ratio, and total left atrial (LA) global strain (LAS) were also measured. Time-based MPI was calculated from flow or tissue-based pulse wave Doppler (PWD and TDI) as the (isovolumic-relaxation and contraction time)/systolic-time. We used hierarchical clustering and network analysis to better visualize the relationship between parameters. The primary endpoint was the composite of all-cause death, heart transplantation, left ventricular assist device implantation, and clinical worsening. Left ventricular outflow tract (LVOT) obstruction was present in 56% of patients. Compared with controls, patients with HCM had worse LVGLS (-14.0 ± 3.4% vs. -19.6 ± 1.5%), higher E/e' (12.9 ± 7.2 vs. 6.1 ± 1.5), LA volume index (LAVI) (36.4 ± 13.8 ml/m2 vs. 25.6 ± 6.7 ml/m2), and MPI (0.55 ± 0.17 vs. 0.40 ± 0.11 for PWD and 0.59 ± 0.22 vs. 0.46 ± 0.09 for TDI) (all P < 0.001). During a median follow-up of 55 months, 47 endpoints occurred. PWD or TDI-based MPI was not associated with outcome, while LAVI, LAS, LVGLS, and E/e' were (all P < 0.01). On multivariable analysis, LVOT obstruction (P < 0.001), LAS (P < 0.001), and E/e' (P = 0.02) were retained as independent associates. They were in different clusters suggesting complemental relationship between them. CONCLUSION: Time-based index is less predictive of outcome than strain or tissue Doppler indices. LAS may be a promising prognostic marker in HCM.

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.

Improving risk stratification in heart failure with preserved ejection fraction by combining two validated risk scores.

Introduction: The Intermountain Risk Score (IMRS) was developed and validated to predict short-term and long-term mortality in hospitalised patients using demographics and commonly available laboratory data. In this study, we sought to determine whether the IMRS also predicts all-cause mortality in patients hospitalised with heart failure with preserved ejection fraction (HFpEF) and whether it is complementary to the Get with the Guidelines Heart Failure (GWTG-HF) risk score or N-terminal pro-B-type natriuretic peptide (NT-proBNP). Methods and results: We used the Stanford Translational Research Integrated Database Environment to identify 3847 adult patients with a diagnosis of HFpEF between January 1998 and December 2016. Of these, 580 were hospitalised with a primary diagnosis of acute HFpEF. Mean age was 76±16 years, the majority being female (58%), with a high prevalence of diabetes mellitus (36%) and a history of coronary artery disease (60%). Over a median follow-up of 2.0 years, 140 (24%) patients died. On multivariable analysis, the IMRS and GWTG-HF risk score were independently associated with all-cause mortality (standardised HRs IMRS (1.55 (95% CI 1.27 to 1.93)); GWTG-HF (1.60 (95% CI 1.27 to 2.01))). Combining the two scores, improved the net reclassification over GWTG-HF alone by 36.2%. In patients with available NT-proBNP (n=341), NT-proBNP improved the net reclassification of each score by 46.2% (IMRS) and 36.3% (GWTG-HF). Conclusion: IMRS and GWTG-HF risk scores, along with NT-proBNP, play a complementary role in predicting outcome in patients hospitalised with HFpEF.

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.

Incremental Value of Aortomitral Continuity Calcification for Risk Assessment after Transcatheter Aortic Valve Replacement.

PURPOSE: To investigate the association of aortomitral continuity calcification (AMCC) with all-cause mortality, postprocedural paravalvular leak (PVL), and prolonged hospital stay in patients undergoing transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: The authors retrospectively evaluated 329 patients who underwent TAVR between March 2013 and March 2016. AMCC, aortic valve calcification (AVC), and coronary artery calcification (CAC) were quantified by using preprocedural CT. Pre-procedural Society of Thoracic Surgeons (STS) score was recorded. Associations between baseline AMCC, AVC, and CAC and 1-year mortality, PVL, and hospital stay longer than 7 days were analyzed. RESULTS: The median follow-up was 415 days (interquartiles, 344-727 days). After 1 year, 46 of the 329 patients (14%) died and 52 (16%) were hospitalized for more than 7 days. Of the 326 patients who underwent postprocedural echocardiography, 147 (45%) had postprocedural PVL. The CAC score (hazard ratio: 1.11 per 500 points) and AMCC mass (hazard ratio: 1.13 per 500 mg) were associated with 1-year mortality. AVC mass (odds ratio: 1.93 per 100 mg) was associated with postprocedural PVL. Only the STS score was associated with prolonged hospital stay (odds ratio: 1.19 per point). CONCLUSION: AMCC is associated with mortality within 1 year after TAVR and substantially improves individual risk classification when added to a model consisting of STS score and AVC mass only.Supplemental material is available for this article.© RSNA, 2019See also the commentary by Brown and Leipsic in this issue.

A longitudinal big data approach for precision health.

Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus. The cohort underwent integrative personalized omics profiling from samples collected quarterly for up to 8 years (median, 2.8 years) using clinical measures and emerging technologies including genome, immunome, transcriptome, proteome, metabolome, microbiome and wearable monitoring. We discovered more than 67 clinically actionable health discoveries and identified multiple molecular pathways associated with metabolic, cardiovascular and oncologic pathophysiology. We developed prediction models for insulin resistance by using omics measurements, illustrating their potential to replace burdensome tests. Finally, study participation led the majority of participants to implement diet and exercise changes. Altogether, we conclude that deep longitudinal profiling can lead to actionable health discoveries and provide relevant information for precision health.