- Email: [email protected]
Acute and Chronic Reduction in Functional Mitral Regurgitation with a Novel Percutaneous Mitral Annuloplasty Device in Experimental Heart Failure
The 8th Annual Scientific Meeting Index (CI) was 1.97 ⫾ 0.46 and 2.06 ⫾ 0.39 l/min/m2 at baseline and 24 hrs, and increased to 2.24 ⫾ 0.45 l/min/m2 72 hrs post implant (p ⬍ 0.05). 24 hrs post-removal, hemodynamic benefit was sustained: PCWP 21 ⫾ 7 mmHg; CI 2.32 ⫾ 0.47 l/min/ m2 (both p ⬍ 0.0001 vs. baseline) representing marked, sustained favorable shift in the Starling relation. (See Figure.) By day 4 post-implant cumulative input-output averaged -3.5L and weight loss averaged 2.2 (0–7.5) Kg. Conclusion: The Cancion쑓 CRS, a novel form of cardiac assist, acting through a low-flow, continuous aortic flow loop, induced progressive improvement in hemodyanamics, with both improved cardiac performance (shift in Starling relation) and negative fluid balance, in patients with exacerbated CHF. CRS, undergoing prospective, randomized, long-term investigation, represents a promising therapy for patients refractory to, or dependent on, IV inotropes.
019 Acute and Chronic Reduction in Functional Mitral Regurgitation with a Novel Percutaneous Mitral Annuloplasty Device in Experimental Heart Failure Jeetendra B. Patel,1 Calin V. Maniu,3 Charanjit S. Rihal,1 David G. Reuter,2 Margaret M. Redfield1; 1Cardiorenal Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN; 2Cardiac Dimensons Inc, Kirkland, WA; 3Cardiology, University of South Carolina, Charleston, SC Background: Functional mitral regurgitation (FMR) can exacerbate hemodynamic strain, LV remodeling, symptoms and potentially mortality in patients with heart failure (HF). Surgical mitral annuloplasty is often not an option in advanced HF, particularly in the elderly. Objective: To determine acute and chronic efficacy and safety of a novel percutaneous mitral annuloplasty (PMA) device placed in the coronary sinus (CS) to reduce FMR in experimental HF. Methods and Results: Fluoroscopic guided PMA was attempted in 12 anesthetized dogs with rapid pacing induced HF. After sizing the CS, the device was placed in the CS and the distal anchor deployed in the distal CS. Tension was placed on the device, reducing the mitral annular dimension while assessing the effect on FMR. Once annular dimension and severity of FMR were optimally reduced, the proximal anchor was deployed in the proximal CS. Coronary flow and CS integrity were assessed during and after placement. After final assessment, the device was uncoupled from the delivery system. No device was placed in 5 dogs due to early prototype size availability limitations (n ⫽ 2) or circumflex coronary flow impairment (n ⫽ 3). In the 7 remaining dogs, PMA acutely reduced annular dimension and FMR severity as assessed by MR jet area/LA area (43 ⫾ 4 % to 8 ⫾ 5%, p ⬍ 0.0001), regurgitant volume (14.7 ⫾ 2.1 ml to 3.1 ⫾ 0.5 ml, p ⬍ 0.05), effective regurgitant orifice (0.13 ⫾ 0.01 cm2 to 0.04 ⫾ 0.00 cm2, p ⬍ 0.05) and angiographic
•
HFSA
S23
021 Effects Of Nesiritide On Pulmonary Hypertension In Heart Transplant Candidates Reynolds M. Delgado,1 Branislav Radovancevic,1 Cynthia D. Thomas,1 Lisa A. Nemeth,1 Biswajit Kar,1 Rajko Radovancevic,1 Guillermo Torre-Amione,2 O.H. Frazier1; 1Transplant Service, Texas Heart Institute, Houston, TX; 2Baylor College of Medicine, Houston, TX Background: Nesiritide infusion has been proven an effective therapy for heart failure to decrease pulmonary capillary wedge pressure, increase cardiac index and induce diuresis. However, the effects on reversibility of pulmonary hypertension (PHTN) are not well studied. We evaluated the effects of infusion of nesiritide in heart failure patients awaiting heart transplantation. Methods: We prospectively enrolled 19 heart transplant candidates with PHTN. PHTN was defined as one of the following: systolic pulmonary artery pressure (sPAP) ⱖ55 mmHg, peripheral vascular resistance (PVR) ⱖ 4.0 wood units and/or transpulmonary gradient (TPG) defined as difference between the mean pulmonary artery pressure and mean pulmonary capillary wedge pressure (PCWP) ⱖ12 mmHg. Each patient served as his own control. Reversibility of PHTN was defined as: a 30% decrease in the qualifying parameter. Nesiritide infusion was started with a 2 mcg/kg bolus over 60 seconds with immediate initiation of maintenance infusion of 0.01 mcg/kg/min. Hemodynamic parameters were obtained hourly via pulmonary artery catheter utilizing thermodilution technique. An increase of 0.005 mcg/kg/min was initiated hourly until endpoint or a total of 3 increases (maximum dose of 0.025 mcg/kg/min). Results: Fifteen men and 4 women, mean age 56 ⫾ 12 years, NYHA class IV had mean sPAP at baseline 66 ⫾ 10 mmHg and TPG 17.9 ⫾ 3.9 mmHg. Only one patient did not meet target endpoint. Mean PVR decreased from 5.1 ⫾ 1.8 mmHg to 3.2 ⫾ 1.7 mmHg, P ⬍ 0.0001. Mean TPG decreased from 17.9 ⫾ 3.9 mmHg to 12.0 ⫾ 3.7 mmHg, P ⬍ 0.0001. PCWP did not change significantly 26.2 ⫾ 5.3 to 25.7 ⫾ 9.3 P ⫽ 0.822. None of the patients required withdrawal/down-titration of drug due to hypotension. Conclusions: Based on these data nesiritide may be useful in assessment of reversibility of PHTN and in preventing right heart failure or dysfunction in patients undergoing heart transplantation or left ventricular assist device implantation.
MR grade (2.8 ⫾ 0.3 to 1.0 ⫾ 0.3, p ⬍ 0.001). Dogs were then followed for four weeks following device placement while rapid pacing was continued. FMR severity assessed in the conscious state was reduced as compared to pre-device levels (MR jet area/LA area 33 ⫾ 3% prior to device versus 11 ⫾ 4% 4 weeks after device, p ⬍ 0.05). At the conclusion of the study, hearts were perfusion fixed and the relationship of the distal CS, the device and the circumflex artery was assessed. Extremely close proximity of the circumflex artery and distal CS appeared to be a risk factor for compromise of coronary flow. Conclusion: PMA results in significant decrease in severity of FMR both acutely and chronically. Circumflex coronary flow impingement is a potential side effect in patients with left dominant coronary anatomy and a patent native circumflex. Clinical application will need to address this potential limitation with monitoring of circumflex coronary flow during implantation.
022
020 Randomized Controlled Trial of Ultrafiltration Versus Usual Care for Hospitalized Patients with Heart Failure: Preliminary Report of the Rapid Trial Bradley A. Bart,1 Andrew Boyle,1 Alan J. Bank,1 Inder Anand,1 Maria Teresa Olivari,1 Mark Kraemer,1 Shari Mackedanz,1 Mike Schollmeyer,2 Steven R. Goldsmith1; 1 Cardiology, Minnesota Heart Failure Consortium, Minneapolis, MN; 2CHF Solutions, Inc., Brooklyn Park, MN
Relationship of Serum Digoxin Concentration to Mortality and Morbidity in Women in the Digitalis Investigation Group (DIG) Trial: A Retrospective Analysis Kirkwood F. Adams,1 J. Herbert Patterson,1 Wendy A. Gattis,2 Christopher M. O’Connor,2 Craig R. Lee,1 Todd A. Schwartz,1 Mihai Gheorghiade3; 1Medicine; Pharmacy; Biostatistics, University of North Carolina - Chapel Hill, Chapel Hill, NC; 2Medicine, Duke University, Durham, NC; 3Medicine, Northwestern University, Chicago, IL
Introduction: Ultrafiltration (UF) effectively and safely removes excess fluid in patients (pts) with CHF. It is not widely used for CHF because of the need for central IV access, ICU monitoring, and skilled personnel. The system 100 (CHF Solutions, Inc.) is a new UF device the does not required central IV access, ICU monitoring or skilled dialysis personnel. The role of UF for CHF using this less invasive device has yet to be defined. Hypothesis: Pts hospitalized for CHF treated with a single, 8 hour UF session in addition to best medical therapy will achieve greater weight loss 24 hours after enrollment compared to pts receiving best medical therapy alone. Methods: Pts admitted for CHF with evidence of volume overload at 6 local hospitals were randomized to a single, 8 hour UF session in addition to best medical care or best medical care alone. Major exclusion criteria included: hemodynamic instability requiring pressors, severe stenotic valvular disease and acute coronary syndromes. For pts assigned to the UF treatment arm, UF therapy was initiated as soon after enrollment as logistically possible. The primary endpoint of the trial is weight loss 24 hours after the time of enrollment and the enrollment target is 40. Results: This preliminary report includes the first 33 pts enrolled. All continuous and categorical variables are expressed as medians and percentages, respectively. Sixteen pts were assigned to the UF group and UF was successfully delivered to 14 (2 pts failed to complete UF due to vascular access issues). The clinical features of the study group are: age 67, male sex 66%, prior MI 27%, HTN 55%, DM 34%, NYHA III/IV 25%/75%, EF 25%. Total fluid removal, weight loss and symptom results at the 24 hour endpoint are reported in the table below; results represent group assignments according to the intention to treat principle. Conclusions: Our preliminary results show that a treatment strategy including UF in addition to medical therapy is associated with greater fluid removal, weight loss and symptom relief compared to medical therapy alone in pts hospitalized with CHF and volume overload. Final results of the RAPID trial will be available soon.
Background: Controversy continues concerning the clinical utility of digoxin in women with heart failure. Detailed characterization of the relationship between serum digoxin concentration and outcomes in both genders is needed to better determine the risk benefit ratio of this drug for heart failure in women. Methods: We performed a retrospective analysis of data from the Digitalis Investigation Group trial to further investigate the relationship between clinical outcomes and serum digoxin concentration in women and men. The principal study analysis reviewed a total of 4944 patients with heart failure due to left ventricular systolic dysfunction who survived for at least four weeks (all 3366 patients randomized to placebo and 1578 of 3372 patients randomized to digoxin who had a serum concentration measured between 6 and 30 hours (inclusive) after the last dose of study drug at 4 weeks. Multivariable modeling was performed to determine the association between serum digoxin concentration and mortality and morbidity and to evaluate the possibility of gender differences in response to digoxin therapy. Results: For women with a serum concentration from 0.5 to 0.7 ng/ml, the hazard ratio for mortality was 0.80 (95% confidence interval 0.58 to 1.10, p ⫽ 0.166) and for serum concentrations from 0.5 to 0.9 ng/ml, the hazard ratio was 0.84 (95% confidence interval 0.62 to 1.13, p ⫽ 0.246). The test for an interaction between gender and the relationship of serum digoxin concentration to mortality was nonsignificant (p ⫽ 0.783). For women with a serum concentration from 0.5 to 0.9 ng/ml, the hazard ratio for the risk of death or hospitalization for worsening heart failure was 0.74 (95% confidence interval 0.58 to 0.93, p ⫽ 0.011); p for interaction ⫽ 0.685. Conclusions: Retrospective analysis of patients from the Digitalis Investigation Group trial indicates that digoxin is an effective treatment for heart failure in women when this drug is used at low serum concentrations. A beneficial effection morbidity and no excess mortality was observed at serum concentrations ⬍ 1.0 ng/ml.
Preliminary Results UF Versus Usual Care For CHF
Fluid removal 24 hrs (ml) Weight loss 24 hrs (Kg) CHF symptoms 24 hrs (% worse or no change)
UF (n ⫽ 16)
Usual Care (n ⫽ 17)
4800 ⫾ 1622 2.4 ⫾ 1.36 6.7
2050 ⫾ 1949 1.5 ⫾ 1.60 29.4
019 Acute and Chronic Reduction in Functional Mitral Regurgitation with a Novel Percutaneous Mitral Annuloplasty Device in Experimental Heart Failure Jeetendra B. Patel,1 Calin V. Maniu,3 Charanjit S. Rihal,1 David G. Reuter,2 Margaret M. Redfield1; 1Cardiorenal Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN; 2Cardiac Dimensons Inc, Kirkland, WA; 3Cardiology, University of South Carolina, Charleston, SC Background: Functional mitral regurgitation (FMR) can exacerbate hemodynamic strain, LV remodeling, symptoms and potentially mortality in patients with heart failure (HF). Surgical mitral annuloplasty is often not an option in advanced HF, particularly in the elderly. Objective: To determine acute and chronic efficacy and safety of a novel percutaneous mitral annuloplasty (PMA) device placed in the coronary sinus (CS) to reduce FMR in experimental HF. Methods and Results: Fluoroscopic guided PMA was attempted in 12 anesthetized dogs with rapid pacing induced HF. After sizing the CS, the device was placed in the CS and the distal anchor deployed in the distal CS. Tension was placed on the device, reducing the mitral annular dimension while assessing the effect on FMR. Once annular dimension and severity of FMR were optimally reduced, the proximal anchor was deployed in the proximal CS. Coronary flow and CS integrity were assessed during and after placement. After final assessment, the device was uncoupled from the delivery system. No device was placed in 5 dogs due to early prototype size availability limitations (n ⫽ 2) or circumflex coronary flow impairment (n ⫽ 3). In the 7 remaining dogs, PMA acutely reduced annular dimension and FMR severity as assessed by MR jet area/LA area (43 ⫾ 4 % to 8 ⫾ 5%, p ⬍ 0.0001), regurgitant volume (14.7 ⫾ 2.1 ml to 3.1 ⫾ 0.5 ml, p ⬍ 0.05), effective regurgitant orifice (0.13 ⫾ 0.01 cm2 to 0.04 ⫾ 0.00 cm2, p ⬍ 0.05) and angiographic
•
HFSA
S23
021 Effects Of Nesiritide On Pulmonary Hypertension In Heart Transplant Candidates Reynolds M. Delgado,1 Branislav Radovancevic,1 Cynthia D. Thomas,1 Lisa A. Nemeth,1 Biswajit Kar,1 Rajko Radovancevic,1 Guillermo Torre-Amione,2 O.H. Frazier1; 1Transplant Service, Texas Heart Institute, Houston, TX; 2Baylor College of Medicine, Houston, TX Background: Nesiritide infusion has been proven an effective therapy for heart failure to decrease pulmonary capillary wedge pressure, increase cardiac index and induce diuresis. However, the effects on reversibility of pulmonary hypertension (PHTN) are not well studied. We evaluated the effects of infusion of nesiritide in heart failure patients awaiting heart transplantation. Methods: We prospectively enrolled 19 heart transplant candidates with PHTN. PHTN was defined as one of the following: systolic pulmonary artery pressure (sPAP) ⱖ55 mmHg, peripheral vascular resistance (PVR) ⱖ 4.0 wood units and/or transpulmonary gradient (TPG) defined as difference between the mean pulmonary artery pressure and mean pulmonary capillary wedge pressure (PCWP) ⱖ12 mmHg. Each patient served as his own control. Reversibility of PHTN was defined as: a 30% decrease in the qualifying parameter. Nesiritide infusion was started with a 2 mcg/kg bolus over 60 seconds with immediate initiation of maintenance infusion of 0.01 mcg/kg/min. Hemodynamic parameters were obtained hourly via pulmonary artery catheter utilizing thermodilution technique. An increase of 0.005 mcg/kg/min was initiated hourly until endpoint or a total of 3 increases (maximum dose of 0.025 mcg/kg/min). Results: Fifteen men and 4 women, mean age 56 ⫾ 12 years, NYHA class IV had mean sPAP at baseline 66 ⫾ 10 mmHg and TPG 17.9 ⫾ 3.9 mmHg. Only one patient did not meet target endpoint. Mean PVR decreased from 5.1 ⫾ 1.8 mmHg to 3.2 ⫾ 1.7 mmHg, P ⬍ 0.0001. Mean TPG decreased from 17.9 ⫾ 3.9 mmHg to 12.0 ⫾ 3.7 mmHg, P ⬍ 0.0001. PCWP did not change significantly 26.2 ⫾ 5.3 to 25.7 ⫾ 9.3 P ⫽ 0.822. None of the patients required withdrawal/down-titration of drug due to hypotension. Conclusions: Based on these data nesiritide may be useful in assessment of reversibility of PHTN and in preventing right heart failure or dysfunction in patients undergoing heart transplantation or left ventricular assist device implantation.
MR grade (2.8 ⫾ 0.3 to 1.0 ⫾ 0.3, p ⬍ 0.001). Dogs were then followed for four weeks following device placement while rapid pacing was continued. FMR severity assessed in the conscious state was reduced as compared to pre-device levels (MR jet area/LA area 33 ⫾ 3% prior to device versus 11 ⫾ 4% 4 weeks after device, p ⬍ 0.05). At the conclusion of the study, hearts were perfusion fixed and the relationship of the distal CS, the device and the circumflex artery was assessed. Extremely close proximity of the circumflex artery and distal CS appeared to be a risk factor for compromise of coronary flow. Conclusion: PMA results in significant decrease in severity of FMR both acutely and chronically. Circumflex coronary flow impingement is a potential side effect in patients with left dominant coronary anatomy and a patent native circumflex. Clinical application will need to address this potential limitation with monitoring of circumflex coronary flow during implantation.
022
020 Randomized Controlled Trial of Ultrafiltration Versus Usual Care for Hospitalized Patients with Heart Failure: Preliminary Report of the Rapid Trial Bradley A. Bart,1 Andrew Boyle,1 Alan J. Bank,1 Inder Anand,1 Maria Teresa Olivari,1 Mark Kraemer,1 Shari Mackedanz,1 Mike Schollmeyer,2 Steven R. Goldsmith1; 1 Cardiology, Minnesota Heart Failure Consortium, Minneapolis, MN; 2CHF Solutions, Inc., Brooklyn Park, MN
Relationship of Serum Digoxin Concentration to Mortality and Morbidity in Women in the Digitalis Investigation Group (DIG) Trial: A Retrospective Analysis Kirkwood F. Adams,1 J. Herbert Patterson,1 Wendy A. Gattis,2 Christopher M. O’Connor,2 Craig R. Lee,1 Todd A. Schwartz,1 Mihai Gheorghiade3; 1Medicine; Pharmacy; Biostatistics, University of North Carolina - Chapel Hill, Chapel Hill, NC; 2Medicine, Duke University, Durham, NC; 3Medicine, Northwestern University, Chicago, IL
Introduction: Ultrafiltration (UF) effectively and safely removes excess fluid in patients (pts) with CHF. It is not widely used for CHF because of the need for central IV access, ICU monitoring, and skilled personnel. The system 100 (CHF Solutions, Inc.) is a new UF device the does not required central IV access, ICU monitoring or skilled dialysis personnel. The role of UF for CHF using this less invasive device has yet to be defined. Hypothesis: Pts hospitalized for CHF treated with a single, 8 hour UF session in addition to best medical therapy will achieve greater weight loss 24 hours after enrollment compared to pts receiving best medical therapy alone. Methods: Pts admitted for CHF with evidence of volume overload at 6 local hospitals were randomized to a single, 8 hour UF session in addition to best medical care or best medical care alone. Major exclusion criteria included: hemodynamic instability requiring pressors, severe stenotic valvular disease and acute coronary syndromes. For pts assigned to the UF treatment arm, UF therapy was initiated as soon after enrollment as logistically possible. The primary endpoint of the trial is weight loss 24 hours after the time of enrollment and the enrollment target is 40. Results: This preliminary report includes the first 33 pts enrolled. All continuous and categorical variables are expressed as medians and percentages, respectively. Sixteen pts were assigned to the UF group and UF was successfully delivered to 14 (2 pts failed to complete UF due to vascular access issues). The clinical features of the study group are: age 67, male sex 66%, prior MI 27%, HTN 55%, DM 34%, NYHA III/IV 25%/75%, EF 25%. Total fluid removal, weight loss and symptom results at the 24 hour endpoint are reported in the table below; results represent group assignments according to the intention to treat principle. Conclusions: Our preliminary results show that a treatment strategy including UF in addition to medical therapy is associated with greater fluid removal, weight loss and symptom relief compared to medical therapy alone in pts hospitalized with CHF and volume overload. Final results of the RAPID trial will be available soon.
Background: Controversy continues concerning the clinical utility of digoxin in women with heart failure. Detailed characterization of the relationship between serum digoxin concentration and outcomes in both genders is needed to better determine the risk benefit ratio of this drug for heart failure in women. Methods: We performed a retrospective analysis of data from the Digitalis Investigation Group trial to further investigate the relationship between clinical outcomes and serum digoxin concentration in women and men. The principal study analysis reviewed a total of 4944 patients with heart failure due to left ventricular systolic dysfunction who survived for at least four weeks (all 3366 patients randomized to placebo and 1578 of 3372 patients randomized to digoxin who had a serum concentration measured between 6 and 30 hours (inclusive) after the last dose of study drug at 4 weeks. Multivariable modeling was performed to determine the association between serum digoxin concentration and mortality and morbidity and to evaluate the possibility of gender differences in response to digoxin therapy. Results: For women with a serum concentration from 0.5 to 0.7 ng/ml, the hazard ratio for mortality was 0.80 (95% confidence interval 0.58 to 1.10, p ⫽ 0.166) and for serum concentrations from 0.5 to 0.9 ng/ml, the hazard ratio was 0.84 (95% confidence interval 0.62 to 1.13, p ⫽ 0.246). The test for an interaction between gender and the relationship of serum digoxin concentration to mortality was nonsignificant (p ⫽ 0.783). For women with a serum concentration from 0.5 to 0.9 ng/ml, the hazard ratio for the risk of death or hospitalization for worsening heart failure was 0.74 (95% confidence interval 0.58 to 0.93, p ⫽ 0.011); p for interaction ⫽ 0.685. Conclusions: Retrospective analysis of patients from the Digitalis Investigation Group trial indicates that digoxin is an effective treatment for heart failure in women when this drug is used at low serum concentrations. A beneficial effection morbidity and no excess mortality was observed at serum concentrations ⬍ 1.0 ng/ml.
Preliminary Results UF Versus Usual Care For CHF
Fluid removal 24 hrs (ml) Weight loss 24 hrs (Kg) CHF symptoms 24 hrs (% worse or no change)
UF (n ⫽ 16)
Usual Care (n ⫽ 17)
4800 ⫾ 1622 2.4 ⫾ 1.36 6.7
2050 ⫾ 1949 1.5 ⫾ 1.60 29.4