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Can Supplemental Oxygen Blunt Declines in Peripheral and Cerebral Oxygen Saturation in Heart Failure Patients?
S30 Journal of Cardiac Failure Vol. 22 No. 8S August 2016 079 The Albumin Globulin Ratio in Chronic Heart Failure—Implications for Mortality Beni R. Verma, Brent Williams, Ashley Honushefsky, Sunjeet Kaur, Sanjay Doddamani; Geisinger Health System, Danville, PA
078 Relation Between Therapy-Induced Changes in Natriuretic Peptide Levels and Long-term Therapeutic Effects on Morbidity/Mortality in Patients with Heart Failure and Reduced Ejection Fraction Michael McCauley1, Benjamin S. Wessler2, Kevin Morine2, Marvin A. Konstam2, James E. Udelson2; 1New York Medical College, Valhalla, NY; 2Tufts Medical Center, Boston, MA Introduction: Although brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels correlate with mortality for patients with heart failure and reduced ejection fraction (HFrEF), it is uncertain whether therapyinduced changes in natriuretic peptides (NPs) correlate with therapeutic effect on longterm mortality, as previous studies had limited NP data. Methods: We systematically identified HF drug and device interventions with at least 1 randomized, controlled trial (RCT) assessing mortality over ≥ 6 months in at least 500 patients with HFrEF. This search guided a search for biomarker trials assessing therapy-induced changes in NPs. We assessed the correlation between the short-term drug or device effect on NPs and the longer-term therapeutic effect on a) mortality, and b) the composite of all-cause mortality or HF hospitalization (ACM/HHF). Correlations were assessed using unweighted Spearman’s rho. Results: Of 38 distinct therapies with an identifiable mortality result (median follow-up of 26.5 months), 21 therapies (n = 59,129) had corresponding NP data. We identified 34 trials assessing the effect of those therapies on NP levels (n = 21,650), median follow-up of 24 weeks. No correlation was observed between therapy-induced placebo-corrected percent change in BNP or NT-proBNP and therapeutic effect on mortality (Spearman r = −0.291, P = .112) in patients with HFrEF (Figure). In addition, there was no correlation between therapeutic effect on mortality and placebocorrected absolute change in BNP (r = −0.323, P = .176) or NT-proBNP (r = −0.186, P = .506) when analyzed individually. We also observed no correlation between therapeutic effect on the placebo corrected percent change in NPs and intervention induced effect on the composite of ACM/HHF (r = 0.098, P = .751). Conclusions: Trial-level average drug or device induced changes in NP levels are not reliable predictors or surrogates for a therapeutic long-term effect on outcomes for patients with HFrEF.
Introduction: Heart failure (HF) is associated with low serum albumin and has a linear relationship with mortality. Globulin, the other major serum protein group, is a marker of inflammation that is altered in heart failure state. Yet its association with stable heart failure patients has not been well understood. We sought to determine whether alterations in the albumin globulin (AG) ratio were associated with mortality in stable heart failure patients. Methods: We studied a retrospective cohort of 13,117 unique patients within our clinical database at Geisinger Health System between January 1, 2001 and Dec 31, 2013. Kaplan-Meier survival estimates were calculated at every tenth of a year and plotted over five years by AG group. An early divergence of the survival curves was observed within approximately 12 months from baseline with little additional divergence thereafter. Thus, subsequent analyses were restricted to 6- and 12-month mortality. Cox proportional hazards models were developed to estimate the association between AG ratio and mortality endpoints. For mortality data source, we linked our cohort from electronic medical records with updated mortality data. Results: See table. We divided patients in to two groups as outlined below based on AG ratio of less or greater than 1.1. Mortality in the group 1 was higher. Calculated adjusted hazard ratio for 6 and 12 months were 1.7 (95% CI: 1.4, 2.0), P < .001; 1.6 (95% CI: 1.4, 1.9), P < .001. Furthermore, group 1 had higher concentrations of globulin and total proteins and lower albumin concentration. A low AG ratio was observed in higher BMI, advanced age and elevated transaminases. Conclusions: A low AG ratio in chronic heart failure patients is associated with high 6 and 12 month mortality. Since total protein and globulin concentrations were elevated, they may be a marker of chronic systemic inflammation and may serve to be a powerful predictor of mortality. Whether testing AG ratio is cost effective to predict failure mortality warrants further investigation.
Result
Variables Age (years) Males (%) BMI (kg/m2) Chronic liver disease (%) Chronic kidney disease (%) Systolic blood pressure (mm Hg) Myocardial Infarction (%)
Group 1 (AG < 1.1)
Group 2 (AG > 1.1)
P-value
75 52 30 6 34 128 22
74 50 30 3 26 128 21
<.001 <.001 <.001 <.001 <.001 .01 .51
080 Can Supplemental Oxygen Blunt Declines in Peripheral and Cerebral Oxygen Saturation in Heart Failure Patients? Jalal Vargha, Jeff Ziffra, Tariq Yousuf, Hesam Keshmiri, Marc Silver; University of Illinois-Chicago/Advocate Christ Medical Center, Oak Lawn, IL Objectives: 1) Additional study of peripheral (SpO2) and cerebral (SctO2) oxygenation as important non invasive and economical biomarkers in HF patients. 2) Further study of abnormal SctO2, despite normal SpO2, in heart failure patients and their decline at anaerobic threshold. 3) Describe the changes in oxygenation in the 6MW or exertion by observing the changes in SpO2 and SctO2. Background: Congestive heart failure (HF) includes global and cerebral hypoperfusion and hypoxia. Cerebral oximetry is a noninvasive technology using near-infrared spectroscopy (NIRS) to monitor regional cerebral tissue oxygen saturation (SctO2). NIRS has been widely used for assessing cerebral tissue oxygenation in a variety of populations. Previous studies have shown SctO2 may be used as a biomarker to help assess HF progression and to help guide HF treatment. Previous studies reported that HF patients have low resting cerebral oxygen saturation (SctO2) and have a decline in SctO2 approaching the anaerobic threshold (AT). This approach was applied to study peripheral (SpO2) and cerebral (SctO2) changes in oxygenation at rest and during 6 minute walk test (6MW) in order to study the impact of oxygen supplementation with exertion. Methods: We conducted a prospective cohort study in 31 patients with HF. 22 patients were male, 9 female, aged 33–90 years of age (66), had HF for an average of 50 months. LVEF ranged from 12–60% (32.8%) with only 4 patients > 55%. Average BNP was 515 pg/ml. During a non-urgent visit to our HF clinic, the patients performed a 6MW without additional oxygen followed by a second 6MW with oxygen (3L/min nasal cannula) 60 min later or starting the 6MW with oxygen followed by a second 6MW 60 min later without oxygen. SctO2 and SpO2 were continuously monitored. Results: 30 patients safely completed both 6MW. Walk distances with or without supplemental oxygen (773 vs 822 feet, respectively) were not significantly different. Similarly, SpO2-rest (97.8% vs 96.7%), SpO2-6 min (95.2%
The 20th Annual Scientific Meeting vs 95.5%), SctO2-rest (64.5% vs 62.7%) or SctO2-6 min (62.3 vs 61.3) did not significantly differ either with or without supplemental O2, respectively. During 6MW in HF patients, oxygen supplementation did not alter walk distances, baseline or post walk SpO2 or SctO2, nor modest exercise declines observed in SpO2 and SctO2. Discussion: This study shows the complexity of peripheral /cerebral oxygen delivery in HF patients. It also suggests that 6MW, even in symptomatic HF patients, may not approximate AT in most patients. Given concern that repetitive episodes of cerebral hypoxia may contribute to cognitive dysfunction, a better understanding of this physiology is needed. In addition, SctO2 monitoring continues to show the potential to investigate organ perfusion and provide non-invasive, economical HF monitoring and management of disease progression, co-morbidity and guide management.
081 Increasing NT-ProBNP Levels Are Associated With Heart Failure Hospitalizations In Patients With Continuous Flow Left Ventricular Assist Devices Tania Vora, Ahmed Sara, Farooq H. Sheikh, Samer S. Najjar, David T. Majure; MedStar Washington Hospital Center, Washington, DC Background: Natriuretic peptides (NP) are both diagnostic and prognostic markers in patients with heart failure. Following LVAD implant, NP levels have been shown to decrease from pre-implant levels. Whether NP levels predict acute heart failure (AHF) hospitalizations post-LVAD implantation is unknown. Methods: All patients implanted with an LVAD between 1/2010 and 10/2015 were reviewed. Outpatient NT-ProBNP levels were collected. All hospitalizations for AHF post-LVAD implant were identified. We compared change in NT-ProBNP levels over time in patients who were and were not hospitalized for AHF using mixed effects linear regression model. Results: During the study, 278 patients received an LVAD. 201 patients had NTProBNP values available for analysis. Of these, 56 (33.5%) were hospitalized with AHF. An average of 15.7 ± 10.0 NT-ProBNP values were measured in the AHF group as compared to 14.4 ± 11.0 in those not hospitalized for AHF (P = .46). As compared to patients not hospitalized, AHF group patients were more often men (85.7% vs. 64.9%, P = .005), had higher BMI (29.6 ± 5.7 vs. 28.0 ± 6.4, P = .03) and were more often hypertensive pre-implant (78.6% vs. 58.6% P = .01). Average NTproBNP level of the AHF group was 3948 ± 4362 pmol/L (range 62.2–47704), while average level for non-AHF was 2279 ± 1903 pmol/L (range 32.6–22708) (P < .001). The slope of change in NT-ProBNP for the AHF group was 1.8 ± 1.8 pmol/L/day as compared to -2.1 ± 0.57 pmol/L/day for non AHF group (Figure). The change in NT-ProBNP was significantly different between the groups (P < .01). Conclusion: Patients hospitalized for AHF following LVAD had higher average NT-ProBNP levels and greater increases in NT-ProBNP levels over time than patients not hospitalized with AHF. Whether biomarker guided therapy could attenuate frequency of AHF hospitalizations should be further explored.
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HFSA
S31
082 Plasma Renin Activity in Distinct Patient Populations with Heart Failure and Reduced Ejection Fraction Petra Nijst1, Frederik H. Verbrugge1, Pieter Martens1, Philippe B. Bertrand1, Matthias Dupont1, Gary S. Francis2, W.H. Wilson Tang3, Wilfried Mullens1; 1Ziekenhuis Oost Limburg/ UHasselt, Genk, Belgium; 2University of Minnesota Health Heart Care, Minneapolis, MN; 3Cleveland Clinic, Cleveland, OH Background: Renin-angiotensin-aldosterone system (RAAS) activation in heart failure with reduced ejection fraction (HFREF) is detrimental through cardiac remodeling and water/salt retention. Aims: This study aims to describe RAAS activity in distinct HFREF populations—acute decompensation, chronic HFREF and HFREF with normalized ejection fraction after cardiac resynchronization therapy (CRT)—and to assess its prognostic impact. Methods and Results: In 72 acute decompensated HFREF patients (ADHF), 78 chronic HFREF patients without clinical signs of congestion and 53 patients with HF with normalized ejection fraction (HFNEF), venous blood samples and hemodynamic parameters were obtained. Subjects were prospectively followed up to 30 months. Plasma renin activity (PRA) is significantly lower in ADHF (1.5 ng/ml/h [0.8;5.7]) compared to stable HFREF (7.6 ng/ml/h [2.2;18.1] and HFNEF patients (3.9 ng/ml/h [1.0;13.0]) (all P < .05) (Fig. 1). PRA was significantly associated with arterial blood pressure, renin-angiotensin system blocker dose, beta-blocker dose, and mineralocorticoid receptor antagonist use (all P < .05) but not with age, left ventricular ejection fraction, heart rate, loop diuretic dose, creatinine or NT-pro BNP (all P > .05). High PRA levels are associated with increased cardiovascular mortality or HF admission in acute ADHF, but not in stable HFREF or HFNEF (Fig. 2). Conclusion: PRA is significantly elevated in ambulatory chronic HFREF patients, even when ejection fraction has normalized after CRT which is associated with blood pressure and medication use. Yet, in contrast to ADHF where PRA levels predict cardiovascular mortality and rehospitalizations, PRA levels are not associated with outcome in chronic HFREF and HFNEF.
078 Relation Between Therapy-Induced Changes in Natriuretic Peptide Levels and Long-term Therapeutic Effects on Morbidity/Mortality in Patients with Heart Failure and Reduced Ejection Fraction Michael McCauley1, Benjamin S. Wessler2, Kevin Morine2, Marvin A. Konstam2, James E. Udelson2; 1New York Medical College, Valhalla, NY; 2Tufts Medical Center, Boston, MA Introduction: Although brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels correlate with mortality for patients with heart failure and reduced ejection fraction (HFrEF), it is uncertain whether therapyinduced changes in natriuretic peptides (NPs) correlate with therapeutic effect on longterm mortality, as previous studies had limited NP data. Methods: We systematically identified HF drug and device interventions with at least 1 randomized, controlled trial (RCT) assessing mortality over ≥ 6 months in at least 500 patients with HFrEF. This search guided a search for biomarker trials assessing therapy-induced changes in NPs. We assessed the correlation between the short-term drug or device effect on NPs and the longer-term therapeutic effect on a) mortality, and b) the composite of all-cause mortality or HF hospitalization (ACM/HHF). Correlations were assessed using unweighted Spearman’s rho. Results: Of 38 distinct therapies with an identifiable mortality result (median follow-up of 26.5 months), 21 therapies (n = 59,129) had corresponding NP data. We identified 34 trials assessing the effect of those therapies on NP levels (n = 21,650), median follow-up of 24 weeks. No correlation was observed between therapy-induced placebo-corrected percent change in BNP or NT-proBNP and therapeutic effect on mortality (Spearman r = −0.291, P = .112) in patients with HFrEF (Figure). In addition, there was no correlation between therapeutic effect on mortality and placebocorrected absolute change in BNP (r = −0.323, P = .176) or NT-proBNP (r = −0.186, P = .506) when analyzed individually. We also observed no correlation between therapeutic effect on the placebo corrected percent change in NPs and intervention induced effect on the composite of ACM/HHF (r = 0.098, P = .751). Conclusions: Trial-level average drug or device induced changes in NP levels are not reliable predictors or surrogates for a therapeutic long-term effect on outcomes for patients with HFrEF.
Introduction: Heart failure (HF) is associated with low serum albumin and has a linear relationship with mortality. Globulin, the other major serum protein group, is a marker of inflammation that is altered in heart failure state. Yet its association with stable heart failure patients has not been well understood. We sought to determine whether alterations in the albumin globulin (AG) ratio were associated with mortality in stable heart failure patients. Methods: We studied a retrospective cohort of 13,117 unique patients within our clinical database at Geisinger Health System between January 1, 2001 and Dec 31, 2013. Kaplan-Meier survival estimates were calculated at every tenth of a year and plotted over five years by AG group. An early divergence of the survival curves was observed within approximately 12 months from baseline with little additional divergence thereafter. Thus, subsequent analyses were restricted to 6- and 12-month mortality. Cox proportional hazards models were developed to estimate the association between AG ratio and mortality endpoints. For mortality data source, we linked our cohort from electronic medical records with updated mortality data. Results: See table. We divided patients in to two groups as outlined below based on AG ratio of less or greater than 1.1. Mortality in the group 1 was higher. Calculated adjusted hazard ratio for 6 and 12 months were 1.7 (95% CI: 1.4, 2.0), P < .001; 1.6 (95% CI: 1.4, 1.9), P < .001. Furthermore, group 1 had higher concentrations of globulin and total proteins and lower albumin concentration. A low AG ratio was observed in higher BMI, advanced age and elevated transaminases. Conclusions: A low AG ratio in chronic heart failure patients is associated with high 6 and 12 month mortality. Since total protein and globulin concentrations were elevated, they may be a marker of chronic systemic inflammation and may serve to be a powerful predictor of mortality. Whether testing AG ratio is cost effective to predict failure mortality warrants further investigation.
Result
Variables Age (years) Males (%) BMI (kg/m2) Chronic liver disease (%) Chronic kidney disease (%) Systolic blood pressure (mm Hg) Myocardial Infarction (%)
Group 1 (AG < 1.1)
Group 2 (AG > 1.1)
P-value
75 52 30 6 34 128 22
74 50 30 3 26 128 21
<.001 <.001 <.001 <.001 <.001 .01 .51
080 Can Supplemental Oxygen Blunt Declines in Peripheral and Cerebral Oxygen Saturation in Heart Failure Patients? Jalal Vargha, Jeff Ziffra, Tariq Yousuf, Hesam Keshmiri, Marc Silver; University of Illinois-Chicago/Advocate Christ Medical Center, Oak Lawn, IL Objectives: 1) Additional study of peripheral (SpO2) and cerebral (SctO2) oxygenation as important non invasive and economical biomarkers in HF patients. 2) Further study of abnormal SctO2, despite normal SpO2, in heart failure patients and their decline at anaerobic threshold. 3) Describe the changes in oxygenation in the 6MW or exertion by observing the changes in SpO2 and SctO2. Background: Congestive heart failure (HF) includes global and cerebral hypoperfusion and hypoxia. Cerebral oximetry is a noninvasive technology using near-infrared spectroscopy (NIRS) to monitor regional cerebral tissue oxygen saturation (SctO2). NIRS has been widely used for assessing cerebral tissue oxygenation in a variety of populations. Previous studies have shown SctO2 may be used as a biomarker to help assess HF progression and to help guide HF treatment. Previous studies reported that HF patients have low resting cerebral oxygen saturation (SctO2) and have a decline in SctO2 approaching the anaerobic threshold (AT). This approach was applied to study peripheral (SpO2) and cerebral (SctO2) changes in oxygenation at rest and during 6 minute walk test (6MW) in order to study the impact of oxygen supplementation with exertion. Methods: We conducted a prospective cohort study in 31 patients with HF. 22 patients were male, 9 female, aged 33–90 years of age (66), had HF for an average of 50 months. LVEF ranged from 12–60% (32.8%) with only 4 patients > 55%. Average BNP was 515 pg/ml. During a non-urgent visit to our HF clinic, the patients performed a 6MW without additional oxygen followed by a second 6MW with oxygen (3L/min nasal cannula) 60 min later or starting the 6MW with oxygen followed by a second 6MW 60 min later without oxygen. SctO2 and SpO2 were continuously monitored. Results: 30 patients safely completed both 6MW. Walk distances with or without supplemental oxygen (773 vs 822 feet, respectively) were not significantly different. Similarly, SpO2-rest (97.8% vs 96.7%), SpO2-6 min (95.2%
The 20th Annual Scientific Meeting vs 95.5%), SctO2-rest (64.5% vs 62.7%) or SctO2-6 min (62.3 vs 61.3) did not significantly differ either with or without supplemental O2, respectively. During 6MW in HF patients, oxygen supplementation did not alter walk distances, baseline or post walk SpO2 or SctO2, nor modest exercise declines observed in SpO2 and SctO2. Discussion: This study shows the complexity of peripheral /cerebral oxygen delivery in HF patients. It also suggests that 6MW, even in symptomatic HF patients, may not approximate AT in most patients. Given concern that repetitive episodes of cerebral hypoxia may contribute to cognitive dysfunction, a better understanding of this physiology is needed. In addition, SctO2 monitoring continues to show the potential to investigate organ perfusion and provide non-invasive, economical HF monitoring and management of disease progression, co-morbidity and guide management.
081 Increasing NT-ProBNP Levels Are Associated With Heart Failure Hospitalizations In Patients With Continuous Flow Left Ventricular Assist Devices Tania Vora, Ahmed Sara, Farooq H. Sheikh, Samer S. Najjar, David T. Majure; MedStar Washington Hospital Center, Washington, DC Background: Natriuretic peptides (NP) are both diagnostic and prognostic markers in patients with heart failure. Following LVAD implant, NP levels have been shown to decrease from pre-implant levels. Whether NP levels predict acute heart failure (AHF) hospitalizations post-LVAD implantation is unknown. Methods: All patients implanted with an LVAD between 1/2010 and 10/2015 were reviewed. Outpatient NT-ProBNP levels were collected. All hospitalizations for AHF post-LVAD implant were identified. We compared change in NT-ProBNP levels over time in patients who were and were not hospitalized for AHF using mixed effects linear regression model. Results: During the study, 278 patients received an LVAD. 201 patients had NTProBNP values available for analysis. Of these, 56 (33.5%) were hospitalized with AHF. An average of 15.7 ± 10.0 NT-ProBNP values were measured in the AHF group as compared to 14.4 ± 11.0 in those not hospitalized for AHF (P = .46). As compared to patients not hospitalized, AHF group patients were more often men (85.7% vs. 64.9%, P = .005), had higher BMI (29.6 ± 5.7 vs. 28.0 ± 6.4, P = .03) and were more often hypertensive pre-implant (78.6% vs. 58.6% P = .01). Average NTproBNP level of the AHF group was 3948 ± 4362 pmol/L (range 62.2–47704), while average level for non-AHF was 2279 ± 1903 pmol/L (range 32.6–22708) (P < .001). The slope of change in NT-ProBNP for the AHF group was 1.8 ± 1.8 pmol/L/day as compared to -2.1 ± 0.57 pmol/L/day for non AHF group (Figure). The change in NT-ProBNP was significantly different between the groups (P < .01). Conclusion: Patients hospitalized for AHF following LVAD had higher average NT-ProBNP levels and greater increases in NT-ProBNP levels over time than patients not hospitalized with AHF. Whether biomarker guided therapy could attenuate frequency of AHF hospitalizations should be further explored.
•
HFSA
S31
082 Plasma Renin Activity in Distinct Patient Populations with Heart Failure and Reduced Ejection Fraction Petra Nijst1, Frederik H. Verbrugge1, Pieter Martens1, Philippe B. Bertrand1, Matthias Dupont1, Gary S. Francis2, W.H. Wilson Tang3, Wilfried Mullens1; 1Ziekenhuis Oost Limburg/ UHasselt, Genk, Belgium; 2University of Minnesota Health Heart Care, Minneapolis, MN; 3Cleveland Clinic, Cleveland, OH Background: Renin-angiotensin-aldosterone system (RAAS) activation in heart failure with reduced ejection fraction (HFREF) is detrimental through cardiac remodeling and water/salt retention. Aims: This study aims to describe RAAS activity in distinct HFREF populations—acute decompensation, chronic HFREF and HFREF with normalized ejection fraction after cardiac resynchronization therapy (CRT)—and to assess its prognostic impact. Methods and Results: In 72 acute decompensated HFREF patients (ADHF), 78 chronic HFREF patients without clinical signs of congestion and 53 patients with HF with normalized ejection fraction (HFNEF), venous blood samples and hemodynamic parameters were obtained. Subjects were prospectively followed up to 30 months. Plasma renin activity (PRA) is significantly lower in ADHF (1.5 ng/ml/h [0.8;5.7]) compared to stable HFREF (7.6 ng/ml/h [2.2;18.1] and HFNEF patients (3.9 ng/ml/h [1.0;13.0]) (all P < .05) (Fig. 1). PRA was significantly associated with arterial blood pressure, renin-angiotensin system blocker dose, beta-blocker dose, and mineralocorticoid receptor antagonist use (all P < .05) but not with age, left ventricular ejection fraction, heart rate, loop diuretic dose, creatinine or NT-pro BNP (all P > .05). High PRA levels are associated with increased cardiovascular mortality or HF admission in acute ADHF, but not in stable HFREF or HFNEF (Fig. 2). Conclusion: PRA is significantly elevated in ambulatory chronic HFREF patients, even when ejection fraction has normalized after CRT which is associated with blood pressure and medication use. Yet, in contrast to ADHF where PRA levels predict cardiovascular mortality and rehospitalizations, PRA levels are not associated with outcome in chronic HFREF and HFNEF.