COLE BAILEY - Academia.edu (original) (raw)
Papers by COLE BAILEY
Circulation, Jan 9, 2018
More than 50% of Americans with heart failure have preserved ejection fraction (HFpEF). Exercise ... more More than 50% of Americans with heart failure have preserved ejection fraction (HFpEF). Exercise intolerance is a hallmark of HFpEF, but the pathophysiology is not well understood. Diverse etiologies and incomplete mechanistic understanding have resulted in ineffective management strategies to improve the outcomes of HFpEF. Traditional therapies that have been beneficial in the treatment of heart failure with reduced ejection fraction (HFrEF), neurohormonal blockade in particular, have not been effective in treating HFpEF. In this review, we address underlying mechanisms of HFpEF and present the rationale supporting exercise as a component of comprehensive management.
Jacc-Heart Failure, Apr 1, 2018
Objectives-To characterize the functional and prognostic significance of oxygen uptake (VO 2) kin... more Objectives-To characterize the functional and prognostic significance of oxygen uptake (VO 2) kinetics following peak exercise in individuals with heart failure (HF). Background-It is unknown to what extent patterns of VO 2 recovery following exercise reflect circulatory response during exercise in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Methods-We investigated patients (30 HFpEF, 20 HFrEF, and 22 controls) who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring and a second distinct HF cohort (n=106) who underwent non-invasive CPET with assessment of long-term outcomes. Fick cardiac output (CO) and cardiac filling pressures were measured at rest and throughout exercise in the initial cohort. A novel metric, VO 2 recovery delay (VO 2 RD), defined as time until post-exercise VO 2 falls permanently below peak VO 2 , was measured to characterize VO 2 recovery kinetics. Results-VO 2 RD in patients with HFpEF (median (IQR), 25 (9,39) seconds) and HFrEF (28 (2,52) seconds) was in excess of controls (5 (0,7) seconds, p<0.0001 and p=0.003 respectively). VO 2 RD was inversely related to CO augmentation during exercise in HFpEF (ρ=−0.70) and HFrEF (ρ=−0.73, both p<0.001). In the second cohort, VO 2 RD predicted transplant-free survival
Journal of the American College of Cardiology, 2020
BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described i... more BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear. OBJECTIVES This study sought to investigate the association of exPH with clinical determinants and outcomes. METHODS The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality. RESULTS Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 AE 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n ¼ 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p ¼ 0.003). Both pre-and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both). CONCLUSIONS Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.
Journal of the American College of Cardiology, Apr 1, 2016
Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (... more Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (HFpEF). Mechanisms contributing to exercise intolerance in HFpEF remain incompletely understood. Methods: We performed cycle ergometry cardiopulmonary exercise testing in 31 HFpEF patients and 33 controls. Aerobic efficiency, defined as VO2/work slope during incremental ramp exercise, was used to impute the "internal work" (Watts, W) associated with leg movement during 3 min unloaded exercise (Figure, Panel A). Results: Compared to controls, HFpEF patients were older, with higher BMI and more likely to have HTN and DM (p<0.01 for all). VO2 excursion during unloaded exercise was significantly greater in HFpEF vs. controls (322[182] vs. 255[110] ml/min, p=0.03) despite lower aerobic efficiency (7.4±2.8 vs. 9.1±1.1 ml/min/W, p=0.004) during incremental ramp exercise. Imputed internal work was higher in HFpEF (37[29] vs. 27[15] W, p=0.005) as was the proportion of work performed during unloaded vs. ramp exercise (0.60[0.69] vs. 0.24[0.20], p<0.001) (Figure, Panel B). After adjusting for BMI, unloaded work was inversely related to pVO2 in HFpEF (-3.2 ml/min per W; p=0.005) but not in controls (p=0.38). Conclusions: HFpEF patients incur high metabolic cost with initiation of physical activity that is associated with reduced peak VO2. Accounting for the highly variable metabolic cost of low-level activity in HFpEF may aid in subphenotyping HFpEF patients according to mechanisms of activity intolerance.
Circulation-heart Failure, 2017
Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with asso... more Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with associated reversal of cardiomyocyte hypertrophy, restoration of adrenergic receptor density, and improvement in calcium handling. Unfortunately, translation of these changes into definitive functional recovery at the organ level is infrequent. Reports of LVAD explant rates due to cardiac recovery are highly variable depending on heart failure (HF) etiology and weaning criteria used, with reported rates ranging from 4.5 to 45%. 1 Institution specific LVAD explantion evaluation protocols exist that utilize isolated hemodynamic, imaging, and/or gas exchange measurements. However, protocols that provide comprehensive assessment of myocardial performance under dynamic loading conditions and in response to the highly relevant physiologic stress of exercise are lacking. The high reported rates of HF recurrence post-LVAD explantation provide further motivation to carefully assess cardiac reserve capacity prior to explantation. This case series describes the use of a novel protocol in two patients that integrates assessments of hemodynamic, imaging, and gas exchange measures during the state of rest, LVAD speed reduction, and exercise to uniquely characterize cardiac reserve capacity and guide LVAD explantation decision making.
Journal of Cardiac Failure
Circulation, 2016
Introduction: Sleep disordered breathing (SDB) is common among patients with cardiovascular disea... more Introduction: Sleep disordered breathing (SDB) is common among patients with cardiovascular disease, but its impact on physiologic responses to exercise remains unclear. Hypothesis: We sought to determine the functional significance of SDB and low nocturnal oxygen saturation (SaO2) on hemodynamic responses to exercise. Methods: We investigated subjects who underwent invasive cardiopulmonary exercise tests (iCPET) to evaluate dyspnea of unclear etiology who had evidence of SDB defined as an apnea hypopnea index (AHI) > 5 events/hour during a formal sleep study done within 3 years of the iCPET. Mean pulmonary artery pressure (mPAP) and mean wedge pressure (mPW) were indexed to cardiac output (CO) during exercise, with a mPAP-CO slope > 3 mmHg·min·L(-1) and a mPW-CO slope > 2 mmHg·min·L(-1) indicating an abnormal pulmonary vascular (PV) response to exercise. Results: A total of 120 patients (mean±SD age 58.2 ± 12.6 years, body mass index 31.6 ± 7.5) with SDB (mean AHI 18.9 ± 2...
Circulation, 2018
Introduction: Hepcidin is a master regulator of iron homeostasis that reduces iron absorption whe... more Introduction: Hepcidin is a master regulator of iron homeostasis that reduces iron absorption when circulating levels are elevated. In preclinical models, iron deficiency and inappropriately elevat...
Circulation, 2016
Introduction: Exercise intolerance, as quantified by degree of impairment in peak oxygen uptake (... more Introduction: Exercise intolerance, as quantified by degree of impairment in peak oxygen uptake (VO 2 ), is a cardinal manifestation of heart failure (HF). HF patients are known to have delayed VO 2 kinetics during recovery. However, it is unknown to what extent easily-discernible patterns of VO 2 recovery kinetics reflect circulatory response during exercise. Hypothesis: Delayed VO 2 kinetics, as indicated by the duration of recovery VO 2 plateau (RecVO 2 P), will indicate severity of impairment in cardiac output (CO) augmentation during exercise. Methods: Recovery O 2 kinetics were measured in 52 patients referred for cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring (n=16 normal controls, n=18 HFpEF with resting pulmonary arterial wedge pressure, PAWP≥15, and n=18 HFrEF with LVEF 2 recovery kinetics was calculated as time until O 2 uptake fell permanently below peak VO 2 (highest 30s median within final min of exercise, see Figure) as well as the time t...
Journal of the American College of Cardiology, 2020
BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described i... more BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear. OBJECTIVES This study sought to investigate the association of exPH with clinical determinants and outcomes. METHODS The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality. RESULTS Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 AE 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n ¼ 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p ¼ 0.003). Both pre-and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both). CONCLUSIONS Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.
Circulation, 2019
Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is curren... more Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF. Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes. Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met ...
American Journal of Physiology-Heart and Circulatory Physiology, 2017
Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. ... more Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work ...
Circulation. Heart failure, 2017
Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with asso... more Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with associated reversal of cardiomyocyte hypertrophy, restoration of adrenergic receptor density, and improvement in calcium handling. Unfortunately, translation of these changes into definitive functional recovery at the organ level is infrequent. Reports of LVAD explant rates due to cardiac recovery are highly variable depending on heart failure (HF) etiology and weaning criteria used, with reported rates ranging from 4.5 to 45%. 1 Institution specific LVAD explantion evaluation protocols exist that utilize isolated hemodynamic, imaging, and/or gas exchange measurements. However, protocols that provide comprehensive assessment of myocardial performance under dynamic loading conditions and in response to the highly relevant physiologic stress of exercise are lacking. The high reported rates of HF recurrence post-LVAD explantation provide further motivation to carefully assess cardiac reserve capacity prior to explantation. This case series describes the use of a novel protocol in two patients that integrates assessments of hemodynamic, imaging, and gas exchange measures during the state of rest, LVAD speed reduction, and exercise to uniquely characterize cardiac reserve capacity and guide LVAD explantation decision making.
Journal of the American College of Cardiology, 2016
Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (... more Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (HFpEF). Mechanisms contributing to exercise intolerance in HFpEF remain incompletely understood. Methods: We performed cycle ergometry cardiopulmonary exercise testing in 31 HFpEF patients and 33 controls. Aerobic efficiency, defined as VO2/work slope during incremental ramp exercise, was used to impute the "internal work" (Watts, W) associated with leg movement during 3 min unloaded exercise (Figure, Panel A). Results: Compared to controls, HFpEF patients were older, with higher BMI and more likely to have HTN and DM (p<0.01 for all). VO2 excursion during unloaded exercise was significantly greater in HFpEF vs. controls (322[182] vs. 255[110] ml/min, p=0.03) despite lower aerobic efficiency (7.4±2.8 vs. 9.1±1.1 ml/min/W, p=0.004) during incremental ramp exercise. Imputed internal work was higher in HFpEF (37[29] vs. 27[15] W, p=0.005) as was the proportion of work performed during unloaded vs. ramp exercise (0.60[0.69] vs. 0.24[0.20], p<0.001) (Figure, Panel B). After adjusting for BMI, unloaded work was inversely related to pVO2 in HFpEF (-3.2 ml/min per W; p=0.005) but not in controls (p=0.38). Conclusions: HFpEF patients incur high metabolic cost with initiation of physical activity that is associated with reduced peak VO2. Accounting for the highly variable metabolic cost of low-level activity in HFpEF may aid in subphenotyping HFpEF patients according to mechanisms of activity intolerance.
Circulation, Jan 9, 2018
More than 50% of Americans with heart failure have preserved ejection fraction (HFpEF). Exercise ... more More than 50% of Americans with heart failure have preserved ejection fraction (HFpEF). Exercise intolerance is a hallmark of HFpEF, but the pathophysiology is not well understood. Diverse etiologies and incomplete mechanistic understanding have resulted in ineffective management strategies to improve the outcomes of HFpEF. Traditional therapies that have been beneficial in the treatment of heart failure with reduced ejection fraction (HFrEF), neurohormonal blockade in particular, have not been effective in treating HFpEF. In this review, we address underlying mechanisms of HFpEF and present the rationale supporting exercise as a component of comprehensive management.
Jacc-Heart Failure, Apr 1, 2018
Objectives-To characterize the functional and prognostic significance of oxygen uptake (VO 2) kin... more Objectives-To characterize the functional and prognostic significance of oxygen uptake (VO 2) kinetics following peak exercise in individuals with heart failure (HF). Background-It is unknown to what extent patterns of VO 2 recovery following exercise reflect circulatory response during exercise in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Methods-We investigated patients (30 HFpEF, 20 HFrEF, and 22 controls) who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring and a second distinct HF cohort (n=106) who underwent non-invasive CPET with assessment of long-term outcomes. Fick cardiac output (CO) and cardiac filling pressures were measured at rest and throughout exercise in the initial cohort. A novel metric, VO 2 recovery delay (VO 2 RD), defined as time until post-exercise VO 2 falls permanently below peak VO 2 , was measured to characterize VO 2 recovery kinetics. Results-VO 2 RD in patients with HFpEF (median (IQR), 25 (9,39) seconds) and HFrEF (28 (2,52) seconds) was in excess of controls (5 (0,7) seconds, p<0.0001 and p=0.003 respectively). VO 2 RD was inversely related to CO augmentation during exercise in HFpEF (ρ=−0.70) and HFrEF (ρ=−0.73, both p<0.001). In the second cohort, VO 2 RD predicted transplant-free survival
Journal of the American College of Cardiology, 2020
BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described i... more BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear. OBJECTIVES This study sought to investigate the association of exPH with clinical determinants and outcomes. METHODS The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality. RESULTS Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 AE 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n ¼ 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p ¼ 0.003). Both pre-and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both). CONCLUSIONS Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.
Journal of the American College of Cardiology, Apr 1, 2016
Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (... more Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (HFpEF). Mechanisms contributing to exercise intolerance in HFpEF remain incompletely understood. Methods: We performed cycle ergometry cardiopulmonary exercise testing in 31 HFpEF patients and 33 controls. Aerobic efficiency, defined as VO2/work slope during incremental ramp exercise, was used to impute the "internal work" (Watts, W) associated with leg movement during 3 min unloaded exercise (Figure, Panel A). Results: Compared to controls, HFpEF patients were older, with higher BMI and more likely to have HTN and DM (p<0.01 for all). VO2 excursion during unloaded exercise was significantly greater in HFpEF vs. controls (322[182] vs. 255[110] ml/min, p=0.03) despite lower aerobic efficiency (7.4±2.8 vs. 9.1±1.1 ml/min/W, p=0.004) during incremental ramp exercise. Imputed internal work was higher in HFpEF (37[29] vs. 27[15] W, p=0.005) as was the proportion of work performed during unloaded vs. ramp exercise (0.60[0.69] vs. 0.24[0.20], p<0.001) (Figure, Panel B). After adjusting for BMI, unloaded work was inversely related to pVO2 in HFpEF (-3.2 ml/min per W; p=0.005) but not in controls (p=0.38). Conclusions: HFpEF patients incur high metabolic cost with initiation of physical activity that is associated with reduced peak VO2. Accounting for the highly variable metabolic cost of low-level activity in HFpEF may aid in subphenotyping HFpEF patients according to mechanisms of activity intolerance.
Circulation-heart Failure, 2017
Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with asso... more Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with associated reversal of cardiomyocyte hypertrophy, restoration of adrenergic receptor density, and improvement in calcium handling. Unfortunately, translation of these changes into definitive functional recovery at the organ level is infrequent. Reports of LVAD explant rates due to cardiac recovery are highly variable depending on heart failure (HF) etiology and weaning criteria used, with reported rates ranging from 4.5 to 45%. 1 Institution specific LVAD explantion evaluation protocols exist that utilize isolated hemodynamic, imaging, and/or gas exchange measurements. However, protocols that provide comprehensive assessment of myocardial performance under dynamic loading conditions and in response to the highly relevant physiologic stress of exercise are lacking. The high reported rates of HF recurrence post-LVAD explantation provide further motivation to carefully assess cardiac reserve capacity prior to explantation. This case series describes the use of a novel protocol in two patients that integrates assessments of hemodynamic, imaging, and gas exchange measures during the state of rest, LVAD speed reduction, and exercise to uniquely characterize cardiac reserve capacity and guide LVAD explantation decision making.
Journal of Cardiac Failure
Circulation, 2016
Introduction: Sleep disordered breathing (SDB) is common among patients with cardiovascular disea... more Introduction: Sleep disordered breathing (SDB) is common among patients with cardiovascular disease, but its impact on physiologic responses to exercise remains unclear. Hypothesis: We sought to determine the functional significance of SDB and low nocturnal oxygen saturation (SaO2) on hemodynamic responses to exercise. Methods: We investigated subjects who underwent invasive cardiopulmonary exercise tests (iCPET) to evaluate dyspnea of unclear etiology who had evidence of SDB defined as an apnea hypopnea index (AHI) > 5 events/hour during a formal sleep study done within 3 years of the iCPET. Mean pulmonary artery pressure (mPAP) and mean wedge pressure (mPW) were indexed to cardiac output (CO) during exercise, with a mPAP-CO slope > 3 mmHg·min·L(-1) and a mPW-CO slope > 2 mmHg·min·L(-1) indicating an abnormal pulmonary vascular (PV) response to exercise. Results: A total of 120 patients (mean±SD age 58.2 ± 12.6 years, body mass index 31.6 ± 7.5) with SDB (mean AHI 18.9 ± 2...
Circulation, 2018
Introduction: Hepcidin is a master regulator of iron homeostasis that reduces iron absorption whe... more Introduction: Hepcidin is a master regulator of iron homeostasis that reduces iron absorption when circulating levels are elevated. In preclinical models, iron deficiency and inappropriately elevat...
Circulation, 2016
Introduction: Exercise intolerance, as quantified by degree of impairment in peak oxygen uptake (... more Introduction: Exercise intolerance, as quantified by degree of impairment in peak oxygen uptake (VO 2 ), is a cardinal manifestation of heart failure (HF). HF patients are known to have delayed VO 2 kinetics during recovery. However, it is unknown to what extent easily-discernible patterns of VO 2 recovery kinetics reflect circulatory response during exercise. Hypothesis: Delayed VO 2 kinetics, as indicated by the duration of recovery VO 2 plateau (RecVO 2 P), will indicate severity of impairment in cardiac output (CO) augmentation during exercise. Methods: Recovery O 2 kinetics were measured in 52 patients referred for cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring (n=16 normal controls, n=18 HFpEF with resting pulmonary arterial wedge pressure, PAWP≥15, and n=18 HFrEF with LVEF 2 recovery kinetics was calculated as time until O 2 uptake fell permanently below peak VO 2 (highest 30s median within final min of exercise, see Figure) as well as the time t...
Journal of the American College of Cardiology, 2020
BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described i... more BACKGROUND Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear. OBJECTIVES This study sought to investigate the association of exPH with clinical determinants and outcomes. METHODS The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality. RESULTS Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 AE 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n ¼ 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p ¼ 0.003). Both pre-and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both). CONCLUSIONS Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.
Circulation, 2019
Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is curren... more Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF. Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes. Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met ...
American Journal of Physiology-Heart and Circulatory Physiology, 2017
Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. ... more Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work ...
Circulation. Heart failure, 2017
Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with asso... more Left ventricular assist devices (LVADs) provide decongestion of the left ventricle (LV) with associated reversal of cardiomyocyte hypertrophy, restoration of adrenergic receptor density, and improvement in calcium handling. Unfortunately, translation of these changes into definitive functional recovery at the organ level is infrequent. Reports of LVAD explant rates due to cardiac recovery are highly variable depending on heart failure (HF) etiology and weaning criteria used, with reported rates ranging from 4.5 to 45%. 1 Institution specific LVAD explantion evaluation protocols exist that utilize isolated hemodynamic, imaging, and/or gas exchange measurements. However, protocols that provide comprehensive assessment of myocardial performance under dynamic loading conditions and in response to the highly relevant physiologic stress of exercise are lacking. The high reported rates of HF recurrence post-LVAD explantation provide further motivation to carefully assess cardiac reserve capacity prior to explantation. This case series describes the use of a novel protocol in two patients that integrates assessments of hemodynamic, imaging, and gas exchange measures during the state of rest, LVAD speed reduction, and exercise to uniquely characterize cardiac reserve capacity and guide LVAD explantation decision making.
Journal of the American College of Cardiology, 2016
Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (... more Background: Exercise intolerance is a cardinal symptom of heart failure with preserved ejection (HFpEF). Mechanisms contributing to exercise intolerance in HFpEF remain incompletely understood. Methods: We performed cycle ergometry cardiopulmonary exercise testing in 31 HFpEF patients and 33 controls. Aerobic efficiency, defined as VO2/work slope during incremental ramp exercise, was used to impute the "internal work" (Watts, W) associated with leg movement during 3 min unloaded exercise (Figure, Panel A). Results: Compared to controls, HFpEF patients were older, with higher BMI and more likely to have HTN and DM (p<0.01 for all). VO2 excursion during unloaded exercise was significantly greater in HFpEF vs. controls (322[182] vs. 255[110] ml/min, p=0.03) despite lower aerobic efficiency (7.4±2.8 vs. 9.1±1.1 ml/min/W, p=0.004) during incremental ramp exercise. Imputed internal work was higher in HFpEF (37[29] vs. 27[15] W, p=0.005) as was the proportion of work performed during unloaded vs. ramp exercise (0.60[0.69] vs. 0.24[0.20], p<0.001) (Figure, Panel B). After adjusting for BMI, unloaded work was inversely related to pVO2 in HFpEF (-3.2 ml/min per W; p=0.005) but not in controls (p=0.38). Conclusions: HFpEF patients incur high metabolic cost with initiation of physical activity that is associated with reduced peak VO2. Accounting for the highly variable metabolic cost of low-level activity in HFpEF may aid in subphenotyping HFpEF patients according to mechanisms of activity intolerance.