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

Value of Strain Imaging and Maximal Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy

Longitudinal strain (LS) has been shown to be predictive of outcome in hypertrophic cardiomyopathy (HC). Percent predicted peak oxygen uptake (ppVO2), among other cardiopulmonary exercise testing (CPX) metrics, is a strong predictor of prognosis in HC. However, there has been limited investigation into the combination of LS and CPX metrics. This study sought to determine how LS and parameters of exercise performance contribute to prognosis in HC. One hundred and thirty-one consecutive patients with HC who underwent CPX and stress echocardiography were included. Global, septal, and lateral LS were assessed at rest and stress. Eighty matched individuals were used as controls. Patients were followed for the composite end point of death and worsening heart failure. All absolute LS components were lower in patients with HC than in controls (global 14.3\u2009\ub1\u20094.0% vs 18.8\u2009\ub1\u20092.2%, p 52\u2009ml/m2, and ppVO2 <80%. The combination of lateral LS, LAVI, and ppVO2 presents a simple model for outcome prediction

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) &gt; 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.Funding Agencies|Fulbright Commission; Swedish Heart Foundation; Swedish Society of Medicine; County Council of Ostergotland, Sweden; Stanford Cardiovascular Institute</p

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 &gt;=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&amp;lt;0.001), body mass index (BMI) (B=0.80, p&amp;lt;0.001) and height (B=0.25, p&amp;lt;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

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

ObjectiveAvailable 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.MethodsWe 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.Results239 athletes (43 women) were included (age 191years). In men, greater LV-chest wall distance was associated with higher R-wave amplitudes in leads aVL and I (R=0.20and R=0.25, both p&amp;lt;0.01), while in women greater distance was associated with higher R-amplitudes in V5 and V6 (R=0.42and R=0.34, both p&amp;lt;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.ConclusionsThe 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.Funding Agencies|Fulbright Commission; Swedish Heart Foundation; Swedish Society of Medicine; County Council of Ostergotland, Sweden; Stanford Cardiovascular Institute</p

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.status: publishe

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 &amp; PLUSMN; 3.8 vs. 32.5 &amp; PLUSMN; 9.8 mL/Kg*min-1, p &amp;lt; 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 &amp; PLUSMN; 9.8% for patients with CHF compared to 61.1 &amp; PLUSMN; 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 &amp; PLUSMN; 51.0, 132.0 &amp; PLUSMN; 38.8 and 155.6 &amp; PLUSMN; 45.5s) than in controls (58.08 &amp; PLUSMN; 13.2, 74.3 &amp; PLUSMN; 21.1, 96.7 &amp; PLUSMN; 36.8s; p &amp;lt; 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 &amp; PLUSMN; 3.3, 41.9 &amp; PLUSMN; 29.1 and 25.0 &amp; PLUSMN; 13.6%) than in controls (10.1 &amp; PLUSMN; 4.6, 62.1 &amp; PLUSMN; 17.7 and 38.7 &amp; PLUSMN; 15.1%; all p &amp;lt; 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

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 ± 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.status: publishe

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.status: publishe