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Outcomes Following Continuous-Flow Left Ventricular Assist Device at Transplant Versus Non-Transplant Centers
S8 Journal of Cardiac Failure Vol. 22 No. 8S August 2016
Rapid-Fire Abstracts 017 Pulmonary Artery Pressures Decrease Over Time during Heart Failure Management Guided by Ambulatory Hemodynamic Monitoring in Real World Setting William T. Abraham1, Rita Jermyn2, David Shavelle3, Arvind Bimaraj4, Kunjat Bhatt5, Fareed Sheikh6, Eric Eichorn7, J. Thomas Heywood8, Sumant Lamba9, Rupinder Bharmi10, Rahul Agarwal10, Philip B. Adamson11, Lynne W. Stevenson12; 1The Ohio State University, Columbus, OH; 2Northwell Health, Manhasset, NY; 3University of Southern California, Los Angles, CA; 4Houston Methodist Hospital, Houston, TX; 5 Austin Heart Hospital, Austin, TX; 6St. Rose Dominican Hospital, Henderson, NV; 7 Medical City of Dallas, Dallas, TX; 8Scripps Health, La Jolla, CA; 9First Coast Cardiovascular Institute, Jacksonville, FL; 10St. Jude Medical, Sylmar, CA; 11St. Jude Medical, Austin, TX; 12Brigham and Women’s Hospital, Boston, MA Introduction: Elevated filling pressures in heart failure (HF) patients are associated with high risk for hospitalization and mortality. Implantable hemodynamic monitoring of pulmonary artery pressure (PAP) (CardioMEMS™ HF system, St. Jude Medical) in the CHAMPION Trial demonstrated that pressure guided HF management in previously hospitalized NYHA Class III patients was superior to using signs and symptoms in preventing HF hospitalizations. This effect was directly associated with a reduction in PA pressures over time. This study examines PA pressure changes in patients implanted with CardioMEMS sensor in clinical practice. Methods: PAP trends from the first consecutive 1400 patients implanted with the CardioMEMS™ HF system with at least 6 months of follow-up were analyzed. The mean PAP was evaluated using an area under the curve (AUC) methodology to estimate the total sum increase or decrease in mean PAP in mmHg-day during the 6 month follow up period relative to the first week baseline pressure. As a reference, the PAP trends are compared with the historical CHAMPION Trial. The AUC results are presented as Mean ± 2SE and P-values comparing the AUC are computed by t-test with equal variance. Results: Patients averaged 70 ± 12 years, 60% male, 35% with preserved EF and were followed for an average of 319 ± 91 days. At implant, the mean PAP for the post-market patients was 34.9 ± 9.8 mmHg (compared with 31.5 ± 10.7 mmHg for CHAMPION treatment and 32.2 ± 10.3 mmHg for CHAMPION control). The post-market patients had an AUC of −28.0 mmHg days at the 1 month time mark, −149.1 mmHg days at the 3month time mark and −427.0 mmHg days after 6 months of hemodynamic guided care (see Table and Figure). Conclusions: The first 1400 post-approval patients managed with hemodynamic guided HF care had higher PAP at baseline and experienced greater reduction in PAP over time compared to the CHAMPION Trial. “Real-world” utilization of implantable hemodynamic technology leads to significant lowering of cardiac filling pressures.
Fig. Relationship between serum chloride and odds of low diuretic efficiency. Red line represents the odds for low DE as a function of serum chloride relative to a reference value of 99 mmol/L (the median value in the population). Blue dashed line indicates a serum chloride value of 96, the cutoff value for hypochloremia. Blue bars at the bottom are the frequency of serum chloride levels in the population DE: diuretic efficiency.
in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiologic literature. Hypothesis: Hypochloremia would be significantly associated with diuretic response and other cardiorenal metrics, and chloride supplementation would result in changes in these parameters. Methods: Two HF cohorts were included: (1) Observational: Patients receiving loop diuretics at the Yale Transitional Care Center (YTCC; N = 162); (2) Interventional Pilot: Stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after three days of 115 mmol/d supplemental lysine chloride (N = 10). Results: In YTCC, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46, P < .001) with no incremental contribution from serum sodium (r = −0.06, P = .49). Hypochloremic vs. non-hypochloremic patients exhibited renal wasting of chloride (P = .04) and of chloride relative to sodium (P = .01), despite better renal free water excretion (urine osmolality 372 ± 94 mOsm/kg vs. 507 ± 118, P < .001). Hypochloremia was associated with poor diuretic response (OR = 7.3, 95% CI 3.3–16.1, P < .001; Figure). In the interventional pilot, lysine chloride supplementation increased serum chloride levels by 2.2 ± 2.3 mmol/L and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in NTproBNP, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio. Conclusions: Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation improved serum chloride and provoked changes in several cardio-renal parameters.
019 Outcomes Following Continuous-Flow Left Ventricular Assist Device at Transplant Versus Non-Transplant Centers D. Marshall Brinkley1, David DeNofrio2, Robin Ruthazer2, Amanda R. Vest2, Gregory S. Couper2, Navin K. Kapur2, Michael S. Kiernan2; 1Brigham and Women’s Hospital, Boston, MA; 2Tufts Medical Center, Boston, MA
018 Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights J. Samuel Broughton1, Jennifer S. Hanberg1, Veena S. Rao1, Jozine M. ter Maaten2, Mahlet Assefa1, Justin Grodin3, W.H. Wilson Tang3, Jeffrey M. Testani1; 1Yale University, New Haven, CT; 2University of Groningen, Groningen, Netherlands; 3Cleveland Clinic, Cleveland, OH Introduction: Recent epidemiologic studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure (HF). Accumulating basic science evidence has identified chloride as a critical factor
Background: Since FDA approval of the HeartMate II Left Ventricular Assist Device (LVAD) as destination therapy (DT), the number of hospitals offering LVAD therapy has grown rapidly. An increasing number of LVAD implants are performed at centers without internal cardiac transplant programs. We sought to determine if outcomes following DT LVAD are similar for patients undergoing surgery at transplant versus nontransplant centers. Methods: Adult recipients of a primary, continuous-flow (CF) LVAD as DT between January 2009 and March 2014 from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) were included. Subjects were classified by implanting center as transplant (n = 3323) or non-transplant (n = 260). Center volume prior to 2012 was categorized as <15 or ≥15 implants. Baseline characteristics were compared between groups. Outcomes included 12 month survival censored at explant for recovery or transplantation, freedom from death or major adverse event, individual adverse event rates, hospitalization, and EQ5D quality of life. Results: Patients treated at transplant centers were generally sicker than those at non-transplant centers: 11.3% of patients at transplant were classified as INTERMACS patient profile 1 versus 6.2% at non-transplant centers (P = .04). Transplant center LVAD survival at 1- and 12-mo
The 20th Annual Scientific Meeting
•
HFSA
S9
was 94.2% (95% CI: 95.0-93.4) and 76.4% (77.9-74.8) compared to 94.2% (97.191.4) and 71.3% (77.4-65.2) at non-transplant centers (log-rank P = .30) (Figure). Center type was not associated with survival in univariable [HR 0.88 (0.70–1.12)] or multivariable [HR 0.86 (0.67–1.09)] analyses. Freedom from death or major adverse event was 29.0% (30.6-27.3) versus 29.8% (36.0-23.6) at transplant and nontransplant centers respectively (P = .47). Individual rates of infection, device malfunction or exchange, bleeding, stroke, right heart failure, and hospitalization were similar between groups. Improvement in 6-mo EQ5D visual analog scores was also similar (P = .45). Conclusion: In a modern, large cohort of patients undergoing CF-LVAD implantation, non-transplant centers have comparable survival and adverse event rates to transplant centers.
020 Ventricular Arrhythmias before LVAD Do Not Increase Risk of Mortality or Rehospitalization Praveen Rao, David Raymer, Christopher Sparrow, Michael Nassif, Eric Novak, Daniel Cooper, Shane LaRue, Gregory Ewald, Justin Vader; Washington University in St. Louis/Barnes-Jewish Hospital, St. Louis, MO Introduction: Ventricular arrhythmias (VA) are common in patients with heart failure and can be predictive of VA after left ventricular assist device (LVAD) placement. As a result, presence of VA is often considered as part of an LVAD evaluation. However, it is uncertain if a history of VA results in worse outcomes after LVAD. Methods: We retrospectively analyzed data from patients who underwent continuous flow-LVAD implant at Barnes-Jewish Hospital from 2005–2013. Patients were assigned to one of three groups: those without a history of VA prior to LVAD, those with a history of pre-LVAD VA but whose primary reason for LVAD was not VA, and those with a history of pre-LVAD VA whose primary reason for LVAD was heart failure with refractory VA. Outcomes were ICD shock occurrence, VA occurrence, mortality, and time to first rehospitalization. For ICD shock and ventricular arrhythmia, patients were followed for 1-year post LVAD. For death and rehospitalization, patients were followed on average 1.44 ± 1.20 years. Results: There were 281 patients included for analysis. Significant differences were noted in the rate of post -LVAD ICD shocks (P = .037) and VA (P = .003), but no differences in rates of mortality (logrank P = .77) or time to first rehospitalization (logrank P = .65). Conclusion: In LVAD patients, a history of VA was associated with significantly more ICD shocks and VA after LVAD, but was not associated with a higher rate of mortality or rehospitalization. Even in those patients whose LVAD was implanted primarily for heart failure with refractory VA, rates of death and rehospitalization were similar. This suggests that LVADs potentially mitigate deleterious effects of VA. However, further programming, medication, and procedural strategies are needed to reduce post-LVAD ICD shocks and ventricular arrhythmias.
021 Racial Differences, Outcomes and Response to Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction: PARADIGM-HF Eldrin F. Lewis1, Brian Claggett1, Scott D. Solomon1, John J.V. McMurray1, Karl Swedberg1, Akshay S. Desai1, Jean L. Rouleau1, Michael Zile1, Victor C. Shi2, Martin P. Lefkowitz2, Milton Packer3; 1Brigham and Women’s Hospital, Boston, MA; 2Novartis, East Hanover, NJ; 3Baylor Heart and Vascular Institute, Dallas, TX Introduction: Self-described black patients tend to develop heart failure (HF) at an earlier age and have worse outcomes. Recent studies demonstrate higher hospitalization rate. We examined the association between race and baseline characteristics, outcomes, and efficacy of sacubitril/valsartan in PARADIGM-HF. Methods: PARADIGM-HF randomized 8399 patients with HF, reduced ejection fraction, mild elevation in natriuretic peptides to sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Baseline characteristics of self-described black and white patients (other racial groups were excluded for this analysis) enrolled in PARADIGM-HF were compared. The incidence of the primary composite outcome of cardiovascular mortality or HF hospitalization and its components were calculated for each racial group. The interaction between race and the effects of sacubitril/valsartan vs. enalapril was examined. Results: Black patients represented 26% of the patients enrolled in the United States. Black patients (n = 428) were younger, more likely female, and had better renal function and NYHA class than white patients (n = 5544); however, black patients had lower LVEF and more prior HF hospitalization (Table). Black patients had a higher incidence rate of CV mortality, HF hospitalization, or combination than white patients (Table). Among black patients, angioedema occurred in 2 patients during run-in and 5 patients post-randomization with sacubitril/valsartan and 2 patients during run-in and 1 patients post-randomization with enalapril. Among white patients, angioedema occurred in 6 patients during run-in and 10 patients post-randomization with sacubitril/ valsartan and 9 patients during run-in and 5 patients post-randomization with enalapril. The relative risk reduction for the primary outcome with sacubitril/valsartan compared with enalapril was similar in black (HR 0.81, 95% CI 0.57–1.15, P = .24) and
Rapid-Fire Abstracts 017 Pulmonary Artery Pressures Decrease Over Time during Heart Failure Management Guided by Ambulatory Hemodynamic Monitoring in Real World Setting William T. Abraham1, Rita Jermyn2, David Shavelle3, Arvind Bimaraj4, Kunjat Bhatt5, Fareed Sheikh6, Eric Eichorn7, J. Thomas Heywood8, Sumant Lamba9, Rupinder Bharmi10, Rahul Agarwal10, Philip B. Adamson11, Lynne W. Stevenson12; 1The Ohio State University, Columbus, OH; 2Northwell Health, Manhasset, NY; 3University of Southern California, Los Angles, CA; 4Houston Methodist Hospital, Houston, TX; 5 Austin Heart Hospital, Austin, TX; 6St. Rose Dominican Hospital, Henderson, NV; 7 Medical City of Dallas, Dallas, TX; 8Scripps Health, La Jolla, CA; 9First Coast Cardiovascular Institute, Jacksonville, FL; 10St. Jude Medical, Sylmar, CA; 11St. Jude Medical, Austin, TX; 12Brigham and Women’s Hospital, Boston, MA Introduction: Elevated filling pressures in heart failure (HF) patients are associated with high risk for hospitalization and mortality. Implantable hemodynamic monitoring of pulmonary artery pressure (PAP) (CardioMEMS™ HF system, St. Jude Medical) in the CHAMPION Trial demonstrated that pressure guided HF management in previously hospitalized NYHA Class III patients was superior to using signs and symptoms in preventing HF hospitalizations. This effect was directly associated with a reduction in PA pressures over time. This study examines PA pressure changes in patients implanted with CardioMEMS sensor in clinical practice. Methods: PAP trends from the first consecutive 1400 patients implanted with the CardioMEMS™ HF system with at least 6 months of follow-up were analyzed. The mean PAP was evaluated using an area under the curve (AUC) methodology to estimate the total sum increase or decrease in mean PAP in mmHg-day during the 6 month follow up period relative to the first week baseline pressure. As a reference, the PAP trends are compared with the historical CHAMPION Trial. The AUC results are presented as Mean ± 2SE and P-values comparing the AUC are computed by t-test with equal variance. Results: Patients averaged 70 ± 12 years, 60% male, 35% with preserved EF and were followed for an average of 319 ± 91 days. At implant, the mean PAP for the post-market patients was 34.9 ± 9.8 mmHg (compared with 31.5 ± 10.7 mmHg for CHAMPION treatment and 32.2 ± 10.3 mmHg for CHAMPION control). The post-market patients had an AUC of −28.0 mmHg days at the 1 month time mark, −149.1 mmHg days at the 3month time mark and −427.0 mmHg days after 6 months of hemodynamic guided care (see Table and Figure). Conclusions: The first 1400 post-approval patients managed with hemodynamic guided HF care had higher PAP at baseline and experienced greater reduction in PAP over time compared to the CHAMPION Trial. “Real-world” utilization of implantable hemodynamic technology leads to significant lowering of cardiac filling pressures.
Fig. Relationship between serum chloride and odds of low diuretic efficiency. Red line represents the odds for low DE as a function of serum chloride relative to a reference value of 99 mmol/L (the median value in the population). Blue dashed line indicates a serum chloride value of 96, the cutoff value for hypochloremia. Blue bars at the bottom are the frequency of serum chloride levels in the population DE: diuretic efficiency.
in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiologic literature. Hypothesis: Hypochloremia would be significantly associated with diuretic response and other cardiorenal metrics, and chloride supplementation would result in changes in these parameters. Methods: Two HF cohorts were included: (1) Observational: Patients receiving loop diuretics at the Yale Transitional Care Center (YTCC; N = 162); (2) Interventional Pilot: Stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after three days of 115 mmol/d supplemental lysine chloride (N = 10). Results: In YTCC, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46, P < .001) with no incremental contribution from serum sodium (r = −0.06, P = .49). Hypochloremic vs. non-hypochloremic patients exhibited renal wasting of chloride (P = .04) and of chloride relative to sodium (P = .01), despite better renal free water excretion (urine osmolality 372 ± 94 mOsm/kg vs. 507 ± 118, P < .001). Hypochloremia was associated with poor diuretic response (OR = 7.3, 95% CI 3.3–16.1, P < .001; Figure). In the interventional pilot, lysine chloride supplementation increased serum chloride levels by 2.2 ± 2.3 mmol/L and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in NTproBNP, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio. Conclusions: Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation improved serum chloride and provoked changes in several cardio-renal parameters.
019 Outcomes Following Continuous-Flow Left Ventricular Assist Device at Transplant Versus Non-Transplant Centers D. Marshall Brinkley1, David DeNofrio2, Robin Ruthazer2, Amanda R. Vest2, Gregory S. Couper2, Navin K. Kapur2, Michael S. Kiernan2; 1Brigham and Women’s Hospital, Boston, MA; 2Tufts Medical Center, Boston, MA
018 Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights J. Samuel Broughton1, Jennifer S. Hanberg1, Veena S. Rao1, Jozine M. ter Maaten2, Mahlet Assefa1, Justin Grodin3, W.H. Wilson Tang3, Jeffrey M. Testani1; 1Yale University, New Haven, CT; 2University of Groningen, Groningen, Netherlands; 3Cleveland Clinic, Cleveland, OH Introduction: Recent epidemiologic studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure (HF). Accumulating basic science evidence has identified chloride as a critical factor
Background: Since FDA approval of the HeartMate II Left Ventricular Assist Device (LVAD) as destination therapy (DT), the number of hospitals offering LVAD therapy has grown rapidly. An increasing number of LVAD implants are performed at centers without internal cardiac transplant programs. We sought to determine if outcomes following DT LVAD are similar for patients undergoing surgery at transplant versus nontransplant centers. Methods: Adult recipients of a primary, continuous-flow (CF) LVAD as DT between January 2009 and March 2014 from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) were included. Subjects were classified by implanting center as transplant (n = 3323) or non-transplant (n = 260). Center volume prior to 2012 was categorized as <15 or ≥15 implants. Baseline characteristics were compared between groups. Outcomes included 12 month survival censored at explant for recovery or transplantation, freedom from death or major adverse event, individual adverse event rates, hospitalization, and EQ5D quality of life. Results: Patients treated at transplant centers were generally sicker than those at non-transplant centers: 11.3% of patients at transplant were classified as INTERMACS patient profile 1 versus 6.2% at non-transplant centers (P = .04). Transplant center LVAD survival at 1- and 12-mo
The 20th Annual Scientific Meeting
•
HFSA
S9
was 94.2% (95% CI: 95.0-93.4) and 76.4% (77.9-74.8) compared to 94.2% (97.191.4) and 71.3% (77.4-65.2) at non-transplant centers (log-rank P = .30) (Figure). Center type was not associated with survival in univariable [HR 0.88 (0.70–1.12)] or multivariable [HR 0.86 (0.67–1.09)] analyses. Freedom from death or major adverse event was 29.0% (30.6-27.3) versus 29.8% (36.0-23.6) at transplant and nontransplant centers respectively (P = .47). Individual rates of infection, device malfunction or exchange, bleeding, stroke, right heart failure, and hospitalization were similar between groups. Improvement in 6-mo EQ5D visual analog scores was also similar (P = .45). Conclusion: In a modern, large cohort of patients undergoing CF-LVAD implantation, non-transplant centers have comparable survival and adverse event rates to transplant centers.
020 Ventricular Arrhythmias before LVAD Do Not Increase Risk of Mortality or Rehospitalization Praveen Rao, David Raymer, Christopher Sparrow, Michael Nassif, Eric Novak, Daniel Cooper, Shane LaRue, Gregory Ewald, Justin Vader; Washington University in St. Louis/Barnes-Jewish Hospital, St. Louis, MO Introduction: Ventricular arrhythmias (VA) are common in patients with heart failure and can be predictive of VA after left ventricular assist device (LVAD) placement. As a result, presence of VA is often considered as part of an LVAD evaluation. However, it is uncertain if a history of VA results in worse outcomes after LVAD. Methods: We retrospectively analyzed data from patients who underwent continuous flow-LVAD implant at Barnes-Jewish Hospital from 2005–2013. Patients were assigned to one of three groups: those without a history of VA prior to LVAD, those with a history of pre-LVAD VA but whose primary reason for LVAD was not VA, and those with a history of pre-LVAD VA whose primary reason for LVAD was heart failure with refractory VA. Outcomes were ICD shock occurrence, VA occurrence, mortality, and time to first rehospitalization. For ICD shock and ventricular arrhythmia, patients were followed for 1-year post LVAD. For death and rehospitalization, patients were followed on average 1.44 ± 1.20 years. Results: There were 281 patients included for analysis. Significant differences were noted in the rate of post -LVAD ICD shocks (P = .037) and VA (P = .003), but no differences in rates of mortality (logrank P = .77) or time to first rehospitalization (logrank P = .65). Conclusion: In LVAD patients, a history of VA was associated with significantly more ICD shocks and VA after LVAD, but was not associated with a higher rate of mortality or rehospitalization. Even in those patients whose LVAD was implanted primarily for heart failure with refractory VA, rates of death and rehospitalization were similar. This suggests that LVADs potentially mitigate deleterious effects of VA. However, further programming, medication, and procedural strategies are needed to reduce post-LVAD ICD shocks and ventricular arrhythmias.
021 Racial Differences, Outcomes and Response to Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction: PARADIGM-HF Eldrin F. Lewis1, Brian Claggett1, Scott D. Solomon1, John J.V. McMurray1, Karl Swedberg1, Akshay S. Desai1, Jean L. Rouleau1, Michael Zile1, Victor C. Shi2, Martin P. Lefkowitz2, Milton Packer3; 1Brigham and Women’s Hospital, Boston, MA; 2Novartis, East Hanover, NJ; 3Baylor Heart and Vascular Institute, Dallas, TX Introduction: Self-described black patients tend to develop heart failure (HF) at an earlier age and have worse outcomes. Recent studies demonstrate higher hospitalization rate. We examined the association between race and baseline characteristics, outcomes, and efficacy of sacubitril/valsartan in PARADIGM-HF. Methods: PARADIGM-HF randomized 8399 patients with HF, reduced ejection fraction, mild elevation in natriuretic peptides to sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Baseline characteristics of self-described black and white patients (other racial groups were excluded for this analysis) enrolled in PARADIGM-HF were compared. The incidence of the primary composite outcome of cardiovascular mortality or HF hospitalization and its components were calculated for each racial group. The interaction between race and the effects of sacubitril/valsartan vs. enalapril was examined. Results: Black patients represented 26% of the patients enrolled in the United States. Black patients (n = 428) were younger, more likely female, and had better renal function and NYHA class than white patients (n = 5544); however, black patients had lower LVEF and more prior HF hospitalization (Table). Black patients had a higher incidence rate of CV mortality, HF hospitalization, or combination than white patients (Table). Among black patients, angioedema occurred in 2 patients during run-in and 5 patients post-randomization with sacubitril/valsartan and 2 patients during run-in and 1 patients post-randomization with enalapril. Among white patients, angioedema occurred in 6 patients during run-in and 10 patients post-randomization with sacubitril/ valsartan and 9 patients during run-in and 5 patients post-randomization with enalapril. The relative risk reduction for the primary outcome with sacubitril/valsartan compared with enalapril was similar in black (HR 0.81, 95% CI 0.57–1.15, P = .24) and