- Email: [email protected]
Cardiac resynchronization therapy is effective in patients with atrial fibrillation: interim results from the RESTORE-U.S. study
The 8th Annual Scientific Meeting baseline (248 vs. 220 %, p ⫽ 0.06,) and after one or two years of treatment. Plasma median levels of PAI-1 decreased from 32.6 to 32.0 and 31.1 µg/l, respectively (p ⬍ 0.05) in the C group while there was a non-significant increase in the M group, 32.2 to 36.4 and 36.8 µg/l, respectively. Also median levels of vWF decreased significantly in the C group from baseline to one year (248.6 vs. 223.3%, p ⬍ 0.05) without any decrease in the metoprolol group. Plasma tPA increased significantly in both treatment groups (p ⬍ 0.05). Conclusion: In patients with chronic heart failure, carvedilol was associated with beneficial effects on plasma levels of PAI-1 and vWF while no such effects were seen with metoprolol. These effects might have clinical implications in reducing the risk for atherothrombotic events.
224 Oxygen Saturation by Pulse Oximetry Is Not Predictive of Changes in Patient’s Self-Assessment of Dyspnea: A Sub-Study of the Randomized Interventions with TeZosentan (RITZ-1) Trial John R. Teerlink,1 Barry M. Massie,1 Uri Elkayam,2 Jalal K. Ghali,3 Guillermo TorreAmione,4 Christopher M. O’Connor,5 Maurizio Rainisio6; 1Cardiology, San Francisco VAMC/ UCSF, San Francisco, CA; 2Cardiology, USC Medical Center, Los Angeles, CA; 3Cardiology, Cardiac Centers of Louisiana, Shreveport, LA; 4Cardiology, Baylor College of Medicine, Houston, TX; 5Cardiology, Duke University Medical Center, Durham, NC; 6Actelion Pharmaceuticals LTD, Allschwill, Switzerland Background: Acute heart failure (AHF) is a major cause of morbidity and mortality, emphasizing the need for effective new therapies. The clinical development of new drugs has been challenging, as instruments with which to evaluate improvements in symptoms have not been generally validated, and may be unreliable or biased. A potential, readily available, and objective, though untested, marker of symptom improvement is a change in the patient’s oxygen saturation (O2 Sat). Methods: RITZ-1 was the largest AHF trial evaluating the efficacy of the dual receptor endothelin antagonist, tezosentan (Tezo), enrolling 669 patients admitted for AHF with dyspnea at rest or minimal exertion, requiring intravenous therapy. The primary endpoint was the patient’s change in dyspnea from baseline to 24 hr (Markedly improved to Worst; 8-level scale), and in a sub-group of 259 patients, room air O2 Sat was measured at 1, 2, 3, 4, 5, 6, 12, 18 and 24 hr on randomized placebo or Tezo. The relationship between the O2 Sat and 24 hr dyspnea assessment was assessed. Results: The baseline O2 Sat was 95 ⫾ 3%. Overall, there was no significant correlation between the 24 hr dyspnea assessment and either the 24-hr change from baseline O2 Sat or the 24 hr area under the curve (AUC) of the change from baseline O2 Sat. The 24 hr AUC O2 Sat change was statistically different (Student’s t-test, p ⫽ 0.007) between the placebo group (n ⫽ 112; Mean: ⫹0.5 ⫾ 2.4%) and the Tezo group (n ⫽ 111; ⫺0.5 ⫾ 2.8%). In the placebo group alone, there was a loose correlation between the 24 hr dyspnea assessment and the 24 hr AUC O2 Sat change (Spearmann correlation coefficient ⫽ 0.21, p ⫽ 0.027), while in the Tezo group this coefficient was not significantly different from zero. Correlations between the 24 hr dyspnea assessment and the 24 hr (non-AUC) change from baseline O2 Sat were not statistically significant in either of the treatment groups. Conclusions: The absence of a relationship between dyspnea and O2 Sat in the Tezosentan group might be explained by its potent pulmonary vasodilatory action and possible resulting V/Q mismatch, but the absence of a strong correlation in the placebo group indicates that O2 Sat is not a clinically useful surrogate for the symptom of dyspnea.
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226 Cardiac Resynchronization Therapy Is Effective in Patients with Atrial Fibrillation: Interim Results from the RESTORE-U.S. Study William T. Abraham,1 Howard J. Eisen,2 Jay N. Cohn3; 1Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH; 2Heart Failure and Transplant Center, Temple University School of Medicine, Philadelphia, PA; 3Department of Medicine, University of Minnesota Medical School, Minneapolis, MN Introduction: Cardiac resynchronization therapy (CRT) has been shown to improve symptoms, exercise tolerance, and ventricular function in patients with advanced HF (NYHA III, IV), LV dysfunction and prolonged QRS duration in sinus rhythm (SR). There are little data demonstrating the effectiveness of CRT in atrial fibrillation (AF) patients. Small studies, including MUSTIC AF, studied less than 100 AF patients. Also, most controlled clinical trials excluded chronic AF patients in order to avoid confounding results. The Registry of Cardiac Resynchronization Therapy-U.S. (RESTORE-U.S.) provides an opportunity to assess the largest subgroup of AF patients receiving CRT to date. Methods: RESTORE-U.S. is a prospective, observational study to assess the responses of patients to CRT in a standard care setting with followup of 12 months. Enrollment criteria are the same as the current clinical indications for CRT. The primary endpoints are changes in NYHA class, QOL as measured by the Minnesota Living with Heart Failure Questionnaire, physician and patient global assessments, and echocardiographic indices of cardiac function and dimension. Approximately 2000 patients will be enrolled at 200 sites. All patients are implanted with a Medtronic CRT or CRT⫹D system. Patients are evaluated at 1, 3, 6, and 12 months postimplantation. Echocardiographic evaluations are only performed at 12 months. Results: To date, 185 AF patients (paroxysmal, chronic or ablated) have received CRT. Baseline characteristics of AF patients are similar to the study population, although AF patients were more commonly in class IV (24% vs. 20%). At 1 month, 54% (N ⫽ 155) of the AF patients improved from a NYHA class III/IV to a class I/II, and 68% (N ⫽ 89) at 3 months. AF patients also experienced a 40% (N ⫽ 158) reduction in QOL score at 1 month, and 44% (N ⫽ 92) reduction at 3 months, indicating improvements in QOL. These data are consistent with the results of the physician and patient global assessments. The results seen in the AF subgroup are similar to the improvements seen in patients in SR. To date, the rate of adverse events was similar in the AF subgroup compared with the study population as a whole. Conclusions: CRT resulted in a significant improvement in functional status and QOL in HF patients with ventricular dyssynchrony and AF.
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Early Recognition of Diastolic Dysfunction in Primary Care Setting Ann Glasman,1 Yuanyi Song2; 1Internal Medicine, Truesdale Clinic, Fall River, MA; 2Premier Diagnostic Services, Inc, Avon, MA
Predictors of Hospital Length of Stay in a Surgical Approach to the Failing Heart: The ACORN Cardiac Support Device Randomized Trial Experience Juan M. Aranda, Jr.,1 Thomas M. Beaver,2 Richard S. Schofield,1 Dana D. Leach,1 Edward D. Staples,2 Spencer H. Kubo,3 on behalf of the ACORN Investigators; 1 Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL; 2Division of Thoracic and Cardiovascular Surgery, University of Florida Department of Surgery, Gainesville, FL; 3Acorn Cardiovascular, Inc, St Paul, MN
Introduction: Diastolic dysfunction, often not accompanied by recognized symptoms of congestive heart failure, is known to be associated with marked increase in all cause mortality. Isolated clinical symptoms of dyspnea on exertion (DOE) and peripheral edema (PE) described as minor Framingham criteria and not considered to be validated for the clinical diagnosis of CHF represent significant proportion of patients referred for echocardiography examination in our institution by primary care physicians. Considerable percentage of those patients have normal ejection fraction. Study hypothesis: using Doppler tissue imaging (TDI) of mitral annulus velocities combined with pulsed wave (PW) Doppler examination of mitral inflow and pulmonary vein (PV) flow may provide additional diagnostic information in patients with isolated symptoms of heart failure and normal systolic function. Methods: total of thirty-one patients were referred to our Echocardiography Laboratory by primary care physicians for evaluation of DOE or/and PE; twenty-seven of them had normal ejection fraction ⬎50%. All patients underwent the standardized protocol including PW examination of mitral inflow, PV flow and TDI. Group of thirty-eight asymptomatic patients with normal ejection fraction was used as a control group. Ratio of E (mitral early inflow peak velocity) to Ea (TDI early diastolic velocity) was calculated in all patients according to the protocol. Results: E to Ea ratio in the group of symptomatic patients with normal ejection fraction was noted to be significantly elevated (11.5 ⫾ 5.9 cm/s) as compare to control group (8.4 ⫾ 2.5 cm/s, P ⫽ 0.024). Conclusion: using TDI indices in patients with isolated symptoms of heart failure may be a powerful tool for early recognition of diastolic dysfunction. Awareness of the presence of diastolic heart failure by primary care physicians is an important step in prevention of CHF.
Background: Surgical correction of mitral regurgitation and passive cardiac restraint device placement have been shown to promote reverse remodeling of the ventricles. However, these procedures currently require sternotomy and may result in prolonged recovery. Because there is little reported experience in open chest surgery in patients with heart failure other than left ventricular assist device implantation and heart transplantation, we sought to determine predictors of hospital length of stay in patients enrolled in the ACORN Cardiac Support Device (CSD) randomized trial. Methods: Baseline characteristics of patients receiving CSD, CSD and mitral valve surgery, or mitral valve surgery alone were analyzed by quartile hospital length of stay. Predictors of length of stay were assessed using multivariate analysis. Results: Of 235 patients considered for this analysis, 52 received CSD, 87 received mitral valve replacement and CSD, and 96 received mitral valve surgery only. Multivariate analysis revealed that nonwhite race (p ⫽ 0.009), MVO2 (p ⫽ 0.007), and brain natriuretic peptide (BNP) level (p ⫽ 0.002) were the strongest predictors of hospital length of stay. BNP levels ⬎100 pg/ml were associated with length of stay ⬎9 days. (See figure.) We also examined the predictive value of a simple baseline heart rate and blood pressure measurement for operative risk and length of stay. Patients with baseline heart rates ⬎90 bpm and systolic blood pressure ⬍100 mmHg at the time of surgery had greater length of stay (p ⫽ 0.01) adjusted for race, peak MVO2, and BNP levels. Conclusion: In patients with stable but progressive heart failure with or without severe mitral regurgitation undergoing CSD implant, mitral valve surgery, or both, the factors associated with increased length of hospital stay include nonwhite race, peak MVO2, elevated BNP levels, higher heart rates, and lower blood pressure. These results suggest that postoperative length of stay for and advanced heart failure population may be relatively easy to predict with some simple clinical measures.
224 Oxygen Saturation by Pulse Oximetry Is Not Predictive of Changes in Patient’s Self-Assessment of Dyspnea: A Sub-Study of the Randomized Interventions with TeZosentan (RITZ-1) Trial John R. Teerlink,1 Barry M. Massie,1 Uri Elkayam,2 Jalal K. Ghali,3 Guillermo TorreAmione,4 Christopher M. O’Connor,5 Maurizio Rainisio6; 1Cardiology, San Francisco VAMC/ UCSF, San Francisco, CA; 2Cardiology, USC Medical Center, Los Angeles, CA; 3Cardiology, Cardiac Centers of Louisiana, Shreveport, LA; 4Cardiology, Baylor College of Medicine, Houston, TX; 5Cardiology, Duke University Medical Center, Durham, NC; 6Actelion Pharmaceuticals LTD, Allschwill, Switzerland Background: Acute heart failure (AHF) is a major cause of morbidity and mortality, emphasizing the need for effective new therapies. The clinical development of new drugs has been challenging, as instruments with which to evaluate improvements in symptoms have not been generally validated, and may be unreliable or biased. A potential, readily available, and objective, though untested, marker of symptom improvement is a change in the patient’s oxygen saturation (O2 Sat). Methods: RITZ-1 was the largest AHF trial evaluating the efficacy of the dual receptor endothelin antagonist, tezosentan (Tezo), enrolling 669 patients admitted for AHF with dyspnea at rest or minimal exertion, requiring intravenous therapy. The primary endpoint was the patient’s change in dyspnea from baseline to 24 hr (Markedly improved to Worst; 8-level scale), and in a sub-group of 259 patients, room air O2 Sat was measured at 1, 2, 3, 4, 5, 6, 12, 18 and 24 hr on randomized placebo or Tezo. The relationship between the O2 Sat and 24 hr dyspnea assessment was assessed. Results: The baseline O2 Sat was 95 ⫾ 3%. Overall, there was no significant correlation between the 24 hr dyspnea assessment and either the 24-hr change from baseline O2 Sat or the 24 hr area under the curve (AUC) of the change from baseline O2 Sat. The 24 hr AUC O2 Sat change was statistically different (Student’s t-test, p ⫽ 0.007) between the placebo group (n ⫽ 112; Mean: ⫹0.5 ⫾ 2.4%) and the Tezo group (n ⫽ 111; ⫺0.5 ⫾ 2.8%). In the placebo group alone, there was a loose correlation between the 24 hr dyspnea assessment and the 24 hr AUC O2 Sat change (Spearmann correlation coefficient ⫽ 0.21, p ⫽ 0.027), while in the Tezo group this coefficient was not significantly different from zero. Correlations between the 24 hr dyspnea assessment and the 24 hr (non-AUC) change from baseline O2 Sat were not statistically significant in either of the treatment groups. Conclusions: The absence of a relationship between dyspnea and O2 Sat in the Tezosentan group might be explained by its potent pulmonary vasodilatory action and possible resulting V/Q mismatch, but the absence of a strong correlation in the placebo group indicates that O2 Sat is not a clinically useful surrogate for the symptom of dyspnea.
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226 Cardiac Resynchronization Therapy Is Effective in Patients with Atrial Fibrillation: Interim Results from the RESTORE-U.S. Study William T. Abraham,1 Howard J. Eisen,2 Jay N. Cohn3; 1Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH; 2Heart Failure and Transplant Center, Temple University School of Medicine, Philadelphia, PA; 3Department of Medicine, University of Minnesota Medical School, Minneapolis, MN Introduction: Cardiac resynchronization therapy (CRT) has been shown to improve symptoms, exercise tolerance, and ventricular function in patients with advanced HF (NYHA III, IV), LV dysfunction and prolonged QRS duration in sinus rhythm (SR). There are little data demonstrating the effectiveness of CRT in atrial fibrillation (AF) patients. Small studies, including MUSTIC AF, studied less than 100 AF patients. Also, most controlled clinical trials excluded chronic AF patients in order to avoid confounding results. The Registry of Cardiac Resynchronization Therapy-U.S. (RESTORE-U.S.) provides an opportunity to assess the largest subgroup of AF patients receiving CRT to date. Methods: RESTORE-U.S. is a prospective, observational study to assess the responses of patients to CRT in a standard care setting with followup of 12 months. Enrollment criteria are the same as the current clinical indications for CRT. The primary endpoints are changes in NYHA class, QOL as measured by the Minnesota Living with Heart Failure Questionnaire, physician and patient global assessments, and echocardiographic indices of cardiac function and dimension. Approximately 2000 patients will be enrolled at 200 sites. All patients are implanted with a Medtronic CRT or CRT⫹D system. Patients are evaluated at 1, 3, 6, and 12 months postimplantation. Echocardiographic evaluations are only performed at 12 months. Results: To date, 185 AF patients (paroxysmal, chronic or ablated) have received CRT. Baseline characteristics of AF patients are similar to the study population, although AF patients were more commonly in class IV (24% vs. 20%). At 1 month, 54% (N ⫽ 155) of the AF patients improved from a NYHA class III/IV to a class I/II, and 68% (N ⫽ 89) at 3 months. AF patients also experienced a 40% (N ⫽ 158) reduction in QOL score at 1 month, and 44% (N ⫽ 92) reduction at 3 months, indicating improvements in QOL. These data are consistent with the results of the physician and patient global assessments. The results seen in the AF subgroup are similar to the improvements seen in patients in SR. To date, the rate of adverse events was similar in the AF subgroup compared with the study population as a whole. Conclusions: CRT resulted in a significant improvement in functional status and QOL in HF patients with ventricular dyssynchrony and AF.
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Early Recognition of Diastolic Dysfunction in Primary Care Setting Ann Glasman,1 Yuanyi Song2; 1Internal Medicine, Truesdale Clinic, Fall River, MA; 2Premier Diagnostic Services, Inc, Avon, MA
Predictors of Hospital Length of Stay in a Surgical Approach to the Failing Heart: The ACORN Cardiac Support Device Randomized Trial Experience Juan M. Aranda, Jr.,1 Thomas M. Beaver,2 Richard S. Schofield,1 Dana D. Leach,1 Edward D. Staples,2 Spencer H. Kubo,3 on behalf of the ACORN Investigators; 1 Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL; 2Division of Thoracic and Cardiovascular Surgery, University of Florida Department of Surgery, Gainesville, FL; 3Acorn Cardiovascular, Inc, St Paul, MN
Introduction: Diastolic dysfunction, often not accompanied by recognized symptoms of congestive heart failure, is known to be associated with marked increase in all cause mortality. Isolated clinical symptoms of dyspnea on exertion (DOE) and peripheral edema (PE) described as minor Framingham criteria and not considered to be validated for the clinical diagnosis of CHF represent significant proportion of patients referred for echocardiography examination in our institution by primary care physicians. Considerable percentage of those patients have normal ejection fraction. Study hypothesis: using Doppler tissue imaging (TDI) of mitral annulus velocities combined with pulsed wave (PW) Doppler examination of mitral inflow and pulmonary vein (PV) flow may provide additional diagnostic information in patients with isolated symptoms of heart failure and normal systolic function. Methods: total of thirty-one patients were referred to our Echocardiography Laboratory by primary care physicians for evaluation of DOE or/and PE; twenty-seven of them had normal ejection fraction ⬎50%. All patients underwent the standardized protocol including PW examination of mitral inflow, PV flow and TDI. Group of thirty-eight asymptomatic patients with normal ejection fraction was used as a control group. Ratio of E (mitral early inflow peak velocity) to Ea (TDI early diastolic velocity) was calculated in all patients according to the protocol. Results: E to Ea ratio in the group of symptomatic patients with normal ejection fraction was noted to be significantly elevated (11.5 ⫾ 5.9 cm/s) as compare to control group (8.4 ⫾ 2.5 cm/s, P ⫽ 0.024). Conclusion: using TDI indices in patients with isolated symptoms of heart failure may be a powerful tool for early recognition of diastolic dysfunction. Awareness of the presence of diastolic heart failure by primary care physicians is an important step in prevention of CHF.
Background: Surgical correction of mitral regurgitation and passive cardiac restraint device placement have been shown to promote reverse remodeling of the ventricles. However, these procedures currently require sternotomy and may result in prolonged recovery. Because there is little reported experience in open chest surgery in patients with heart failure other than left ventricular assist device implantation and heart transplantation, we sought to determine predictors of hospital length of stay in patients enrolled in the ACORN Cardiac Support Device (CSD) randomized trial. Methods: Baseline characteristics of patients receiving CSD, CSD and mitral valve surgery, or mitral valve surgery alone were analyzed by quartile hospital length of stay. Predictors of length of stay were assessed using multivariate analysis. Results: Of 235 patients considered for this analysis, 52 received CSD, 87 received mitral valve replacement and CSD, and 96 received mitral valve surgery only. Multivariate analysis revealed that nonwhite race (p ⫽ 0.009), MVO2 (p ⫽ 0.007), and brain natriuretic peptide (BNP) level (p ⫽ 0.002) were the strongest predictors of hospital length of stay. BNP levels ⬎100 pg/ml were associated with length of stay ⬎9 days. (See figure.) We also examined the predictive value of a simple baseline heart rate and blood pressure measurement for operative risk and length of stay. Patients with baseline heart rates ⬎90 bpm and systolic blood pressure ⬍100 mmHg at the time of surgery had greater length of stay (p ⫽ 0.01) adjusted for race, peak MVO2, and BNP levels. Conclusion: In patients with stable but progressive heart failure with or without severe mitral regurgitation undergoing CSD implant, mitral valve surgery, or both, the factors associated with increased length of hospital stay include nonwhite race, peak MVO2, elevated BNP levels, higher heart rates, and lower blood pressure. These results suggest that postoperative length of stay for and advanced heart failure population may be relatively easy to predict with some simple clinical measures.