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Influence of Age on the Efficacy and Safety of Spironolactone in Heart Failure with Preserved Ejection Fraction
S12 Journal of Cardiac Failure Vol. 25 No. 8S August 2019
Moderated Poster Session I 027 Influence of Age on the Efficacy and Safety of Spironolactone in Heart Failure with Preserved Ejection Fraction Orly Vardeny1, Muthiah Vaduganathan2, Brian Claggett2, Akshay S. Desai2, Inder S. Anand1, Sanjiv J. Shah3, Eileen O’Meara4, Eldrin F. Lewis2, Jean Rouleau4, Bertram Pitt5, Marc A. Pfeffer2, Scott D. Solomon2; 1Minneapolis VA Health Care System, Minneapolis, MN; 2Brigham and Women’s Hospital, Boston, MA; 3Northwestern University, Chicago, IL; 4Montreal Heart Institute and University of Montreal, Montreal, QC, Canada; 5University of Michigan, Ann Arbor, MI Introduction: Heart failure with preserved ejection fraction (HFpEF) disproportionately affects older adults. Age-related changes in physiology and variable pharmacokinetics may affect drug efficacy and safety among older individuals. We examined efficacy and safety of spironolactone by age in the Americas region (N=1767) of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Methods: TOPCAT was an international, multicenter, prospective, randomized trial that enrolled patients with HF and left ventricular ejection fraction 45%, age 50 or older with eGFR 30ml/min/1.73 m2 and prior HF hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo over a mean follow up of 3.3 years. We assessed treatment effect (primary study composite of CV death, aborted cardiac arrest, and hospitalization for HF) and safety (permanent study medication discontinuation due to hyperkalemia, rise in serum creatinine to 3.0 mg/dL, gynecomastia, or allergic reaction or intolerance) by age categories (< 65, 65-74, and 75 years). Results: Number of participants were 492, 555, and 720 in the < 65, 65-74, and 75 age categories. Participants in the older age category were more commonly female, Caucasian, and had lower body mass index and eGFR compared to younger age categories. After multivariable adjustment for these differences, the efficacy of spironolactone on the primary outcome relative to placebo was similar across age categories (overall HR 0.83, 95% CI 0.70 - 0.99, p=0.038, pinteraction = 0.38, figure). However, there was an increased risk of the composite safety endpoint among those taking spironolactone compared to placebo (HR 2.55, 95% CI 1.91, 3.39, p<0.001), which was more pronounced among older age groups (p-interaction = 0.01). Conclusions: In patients with HFpEF, the efficacy of spironolactone was consistent across age categories, but treatment-related adverse events were more common in participants age 65 or older. These data support guideline recommendations for use of spironolactone in appropriately selected HFpEF regardless of age, but underscore that closer laboratory surveillance is critical in older individuals.
and outflow cannula positions were assessed by various MDCT parameters outlined in table 1. The incidence of stroke from time of implantation to one year post-LVAD implantation was obtained. Results: A total of 311 continuous-flow LVADs were implanted at our hospital from 2011-2016, of which 75 patients met inclusion criteria for the study. The study population was predominantly HM II with only 3 HVAD and 1 HM 3 patients. 11 patients had stroke within 1 year of LVAD implantation. There were no significant differences in baseline demographic or clinical characteristics between patients that had stroke versus those that did not. Patients with stroke had more acute angulation of outflow cannula relative to the aorta compared to patients without stroke (42⁰ versus 65⁰ respectively, p= 0.026). In addition, patients with stroke had a smaller diameter of anastomosis of the outflow cannula compared to those without stroke (1.3 cm versus 1.5 cm respectively, p= 0.013). The inflow cannula position did not impact incidence of stroke. Conclusions: Our study shows that LVAD outflow cannula orientation and size of anastomosis portend a higher risk of subsequent stroke. Therefore, it is imperative to optimize LVAD surgical implant techniques and device manufacturing to allow larger anastomosis site and less acute angulation of the outflow cannula.
031 SGLT-2 Inhibition Does Not Improve Left Ventricular Reverse Remodeling in Patients with Diabetes Mellitus Type 2 Swathi Roy, Andrisael G. Lacoste, Bushra Zaidi, Nolberto Hernandez, Lava R. Timsina, Muhammad Saad, Manoj Bhandari, Jonathan N. Bella, Timothy J. Vittorio; Bronx Care Hospital Centre, Bronx, NY
029 Association of LVAD Outflow Cannula Position with Stroke Risk Tanushree Agrawal1, Hernan G. Marcos-Abdala1, Raquel Araujo-Gutierrez1, Rishi Thaker2, Nadia Fida1, Mahwash Kassi1; 1Houston Methodist Hospital, Houston, TX; 2 Touro College of Osteopathic Medicine, New York City, NY Background: Stroke remains a major cause of morbidity and mortality in patients with left ventricular assist devices (LVAD). Although several studies have delineated clinical risk factors for development of stroke, it is not entirely clear whether changes in position/orientation of the LVAD cannula impact incidence of subsequent stroke. Hypothesis: We hypothesized that variations in surgical implant techniques for LVAD inflow and outflow cannula positions impact the subsequent risk of stroke. Methods: We conducted a retrospective review of all patients that underwent LVAD implantation at our institute between 2011 and 2016. All patients that underwent multi detector cardiac computed tomography (MDCT) were included in the analysis. Patients with non-contrast CT scans and poor imaging quality were excluded. Baseline demographic as well as clinical parameters were obtained for all patients. Inflow
Background: SGLT-2 inhibition reduces preload as well as afterload, arterial stiffness and systemic blood pressure thereby improving subendocardial blood flow in patients with heart failure (HF). These beneficial cardiovascular (CV) effects likely lower the risk of death and HF hospitalization. There is no known association between diastolic function parameters as determined by transthoracic echocardiography (TTE) and SGLT-2 inhibitor therapy. We hypothesized that in patients with diabetes mellitus type 2 (DMT2) the use of SGLT-2 inhibitors might improve TTE diastolic function parameters including left ventricular (LV) mass and LV mass index. We aimed to investigate the association between LV mass and LV mass index in patients with DMT2 before and after treatment with SGLT-2 inhibitors beyond 1 year. Methods: A retrospective chart review analysis of 141 patients who were prescribed SGLT-2 inhibitors either in the inpatient or outpatient settings at BronxCare Hospital Center between March 1, 2013 through March 31, 2018, was conducted. TTE variables including left atrial volume index (LAVI), LV mass, LV mass index (LVMI) and tricuspid regurgitant (TR) velocity were evaluated before and after prescribing SGLT-2 inhibition. These parameters were compared at baseline and beyond 1 year after treatment. Paired-t testing was used to examine the effect of SGLT-2 inhibition on changes in TTE parameters after 1-year post-treatment. The primary outcome was to detect the change in LV mass and LV mass index. The secondary outcome measures included all-cause and HF admissions. Results: Of the 1096 patients on SGLT-2 inhibitors, 361 patients had both pre and post treatment TTE done out of which 141 had TTE beyond1 year of treatment. The mean age of our population was 62 (§10.0) years out of which 61% were female. 60.8% of our populations were Hispanic. In the analysis, we observed that there was an increase in LV mass from 185.9 g to 201.3 g (p=0.002) and LV mass index from 94.5 to 101.7 (p=0.007) in subjects treated with SGLT-2 inhibitors beyond 1 year. We did not observe improvement in any other diastolic TTE parameters such as E/A ratio, RVSP and LAVI with the use of SGLT-2 inhibitors. However, there was no association between all-cause and HF admission as well as total mortality in subjects on SGLT-2 inhibitors (p>0.0999) Conclusion: Although SGLT-2 inhibitors have shown in the metabolic model to improve heart failure in diabetic patients, they did not show a potential role in the improvement of LV reverse remodeling. On the contrary, our data suggests a modest increase in LV mass and LVMI in patients with T2DM taking SGLT-2 inhibitors. Future studies with larger population size over an extended period of time are warranted to validate our results.
Moderated Poster Session I 027 Influence of Age on the Efficacy and Safety of Spironolactone in Heart Failure with Preserved Ejection Fraction Orly Vardeny1, Muthiah Vaduganathan2, Brian Claggett2, Akshay S. Desai2, Inder S. Anand1, Sanjiv J. Shah3, Eileen O’Meara4, Eldrin F. Lewis2, Jean Rouleau4, Bertram Pitt5, Marc A. Pfeffer2, Scott D. Solomon2; 1Minneapolis VA Health Care System, Minneapolis, MN; 2Brigham and Women’s Hospital, Boston, MA; 3Northwestern University, Chicago, IL; 4Montreal Heart Institute and University of Montreal, Montreal, QC, Canada; 5University of Michigan, Ann Arbor, MI Introduction: Heart failure with preserved ejection fraction (HFpEF) disproportionately affects older adults. Age-related changes in physiology and variable pharmacokinetics may affect drug efficacy and safety among older individuals. We examined efficacy and safety of spironolactone by age in the Americas region (N=1767) of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Methods: TOPCAT was an international, multicenter, prospective, randomized trial that enrolled patients with HF and left ventricular ejection fraction 45%, age 50 or older with eGFR 30ml/min/1.73 m2 and prior HF hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo over a mean follow up of 3.3 years. We assessed treatment effect (primary study composite of CV death, aborted cardiac arrest, and hospitalization for HF) and safety (permanent study medication discontinuation due to hyperkalemia, rise in serum creatinine to 3.0 mg/dL, gynecomastia, or allergic reaction or intolerance) by age categories (< 65, 65-74, and 75 years). Results: Number of participants were 492, 555, and 720 in the < 65, 65-74, and 75 age categories. Participants in the older age category were more commonly female, Caucasian, and had lower body mass index and eGFR compared to younger age categories. After multivariable adjustment for these differences, the efficacy of spironolactone on the primary outcome relative to placebo was similar across age categories (overall HR 0.83, 95% CI 0.70 - 0.99, p=0.038, pinteraction = 0.38, figure). However, there was an increased risk of the composite safety endpoint among those taking spironolactone compared to placebo (HR 2.55, 95% CI 1.91, 3.39, p<0.001), which was more pronounced among older age groups (p-interaction = 0.01). Conclusions: In patients with HFpEF, the efficacy of spironolactone was consistent across age categories, but treatment-related adverse events were more common in participants age 65 or older. These data support guideline recommendations for use of spironolactone in appropriately selected HFpEF regardless of age, but underscore that closer laboratory surveillance is critical in older individuals.
and outflow cannula positions were assessed by various MDCT parameters outlined in table 1. The incidence of stroke from time of implantation to one year post-LVAD implantation was obtained. Results: A total of 311 continuous-flow LVADs were implanted at our hospital from 2011-2016, of which 75 patients met inclusion criteria for the study. The study population was predominantly HM II with only 3 HVAD and 1 HM 3 patients. 11 patients had stroke within 1 year of LVAD implantation. There were no significant differences in baseline demographic or clinical characteristics between patients that had stroke versus those that did not. Patients with stroke had more acute angulation of outflow cannula relative to the aorta compared to patients without stroke (42⁰ versus 65⁰ respectively, p= 0.026). In addition, patients with stroke had a smaller diameter of anastomosis of the outflow cannula compared to those without stroke (1.3 cm versus 1.5 cm respectively, p= 0.013). The inflow cannula position did not impact incidence of stroke. Conclusions: Our study shows that LVAD outflow cannula orientation and size of anastomosis portend a higher risk of subsequent stroke. Therefore, it is imperative to optimize LVAD surgical implant techniques and device manufacturing to allow larger anastomosis site and less acute angulation of the outflow cannula.
031 SGLT-2 Inhibition Does Not Improve Left Ventricular Reverse Remodeling in Patients with Diabetes Mellitus Type 2 Swathi Roy, Andrisael G. Lacoste, Bushra Zaidi, Nolberto Hernandez, Lava R. Timsina, Muhammad Saad, Manoj Bhandari, Jonathan N. Bella, Timothy J. Vittorio; Bronx Care Hospital Centre, Bronx, NY
029 Association of LVAD Outflow Cannula Position with Stroke Risk Tanushree Agrawal1, Hernan G. Marcos-Abdala1, Raquel Araujo-Gutierrez1, Rishi Thaker2, Nadia Fida1, Mahwash Kassi1; 1Houston Methodist Hospital, Houston, TX; 2 Touro College of Osteopathic Medicine, New York City, NY Background: Stroke remains a major cause of morbidity and mortality in patients with left ventricular assist devices (LVAD). Although several studies have delineated clinical risk factors for development of stroke, it is not entirely clear whether changes in position/orientation of the LVAD cannula impact incidence of subsequent stroke. Hypothesis: We hypothesized that variations in surgical implant techniques for LVAD inflow and outflow cannula positions impact the subsequent risk of stroke. Methods: We conducted a retrospective review of all patients that underwent LVAD implantation at our institute between 2011 and 2016. All patients that underwent multi detector cardiac computed tomography (MDCT) were included in the analysis. Patients with non-contrast CT scans and poor imaging quality were excluded. Baseline demographic as well as clinical parameters were obtained for all patients. Inflow
Background: SGLT-2 inhibition reduces preload as well as afterload, arterial stiffness and systemic blood pressure thereby improving subendocardial blood flow in patients with heart failure (HF). These beneficial cardiovascular (CV) effects likely lower the risk of death and HF hospitalization. There is no known association between diastolic function parameters as determined by transthoracic echocardiography (TTE) and SGLT-2 inhibitor therapy. We hypothesized that in patients with diabetes mellitus type 2 (DMT2) the use of SGLT-2 inhibitors might improve TTE diastolic function parameters including left ventricular (LV) mass and LV mass index. We aimed to investigate the association between LV mass and LV mass index in patients with DMT2 before and after treatment with SGLT-2 inhibitors beyond 1 year. Methods: A retrospective chart review analysis of 141 patients who were prescribed SGLT-2 inhibitors either in the inpatient or outpatient settings at BronxCare Hospital Center between March 1, 2013 through March 31, 2018, was conducted. TTE variables including left atrial volume index (LAVI), LV mass, LV mass index (LVMI) and tricuspid regurgitant (TR) velocity were evaluated before and after prescribing SGLT-2 inhibition. These parameters were compared at baseline and beyond 1 year after treatment. Paired-t testing was used to examine the effect of SGLT-2 inhibition on changes in TTE parameters after 1-year post-treatment. The primary outcome was to detect the change in LV mass and LV mass index. The secondary outcome measures included all-cause and HF admissions. Results: Of the 1096 patients on SGLT-2 inhibitors, 361 patients had both pre and post treatment TTE done out of which 141 had TTE beyond1 year of treatment. The mean age of our population was 62 (§10.0) years out of which 61% were female. 60.8% of our populations were Hispanic. In the analysis, we observed that there was an increase in LV mass from 185.9 g to 201.3 g (p=0.002) and LV mass index from 94.5 to 101.7 (p=0.007) in subjects treated with SGLT-2 inhibitors beyond 1 year. We did not observe improvement in any other diastolic TTE parameters such as E/A ratio, RVSP and LAVI with the use of SGLT-2 inhibitors. However, there was no association between all-cause and HF admission as well as total mortality in subjects on SGLT-2 inhibitors (p>0.0999) Conclusion: Although SGLT-2 inhibitors have shown in the metabolic model to improve heart failure in diabetic patients, they did not show a potential role in the improvement of LV reverse remodeling. On the contrary, our data suggests a modest increase in LV mass and LVMI in patients with T2DM taking SGLT-2 inhibitors. Future studies with larger population size over an extended period of time are warranted to validate our results.