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Mortality and outcome differences between survivors and nonsurvivors in the insync cardiac resynchronization trial
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Journal of Cardiac Failure Vol. 5 No. 3 Suppl. 1 1999
196
197
Assessment of Left Ventricular Ejection Fraction in Heart Failure: Interchangeable Use of Three-Dimensional Echocardiography and Radionuclide Ventriculography Donald L. King, Lyna EI-Khoury Coffin, Jonathan Sankner-Bernstein; Medicine, Columbia University, New York, NY
Bioimpedance Monitoring for the Detection of Pulmonary Fluid in Heart Failure Patients: Equal Efficacy to Chest Radiography? William F. Peacock, 1 Nancy M. Albert, 2 Phillipine Kies, 1 Richard D. White, 3 Charles L. Emermanl; ~Emergency Medicine, The Cleveland Clinic, Cleveland, OH, 2Cardiology, The Cleveland Clinic, Cleveland, OH, 3Radiology, The Cleveland Clinic, Cleveland, OH
Background: Patients with congestive heart failure undergo repeated assessment of left ventricular ejection fraction to evaluate response to therapy and monitor disease progression, generally by either radionuclide ventriculography or echocardiography. Although ejection fraction measured in cross-sectional studies by three-dimensional echocardiography correlates well with that of radionuclide scans, no study has compared these techniques longitudinally. We tested the hypothesis that these techniques are interchangeable in their ability to detect changes in left ventricular performance produced by long-term anti-adrenergic therapy in patients with chronic heart failure. Methods: Thirty-six patients with mild to moderate symptoms (54% NYHA Class II, 46% NYHA Class III) despite therapy with digoxin, diuretics and angiotensin converting enzyme inhibitors underwent assessment of ventricular function by both radionuclide ventriculography and freehand three-dimensional echocardiography. Carvedilol was initiated at 3.125 mg BID and titrated to maximum tolerated dose (target of 25-50 mg BID). Ventricular function was reassessed by both techniques after 4-6 months. Results: Baseline mean ejection fraction was 22% for radionuclide ventriculography and 25% for three-dimensional echocardiography. After long-term therapy the mean ejection fractions were 27% and 31% respectively. The change measured by each method was statistically significant but the difference between the methods was not. Ejection fraction by radionuclide ventriculography showed an underestimation bias of 3-4% compared to three-dimensional echocardiography. Conclusions: Freehand three-dimensional echocardiography and radionuclide ventriculography are comparable when measuring change in ejection fraction during medical therapy in patients with advanced heart failure. Either of these methods may be used for measurement of left ventricular ejection fraction in longitudinal evaluation of heart failure patients.
The use of non-invasive thoracic bioimpedance monitoring may be of benefit in the diagnosis and management of heart failure (I-iF) patients suspected of having abnormal quantities of intrathoracic fluid. Increasing thoracic fluid volume corresponds to proportionally lower thoracic electrical impedance. This is measured and displayed numerically as "mean Zo". A lower Zo reflects increased thoracic water; a higher Zo implies a drier pulmonary state. The quantification of intrathoracic fluid by chest radiography is subjective. Theoretically, bioimpedance may offer greater reproducibility and sensitivity for detemfining the presence of abnormal thoracic fluid. There are no published works comparing the current subjective standard of chest radiography to bioimpedance measurement for quantifying thoracic water in heart failure patients. OBJECTIVE: To compare the detection of pulmonary fluid excess, by bioimpedance measurement, to a radiologisfs interpretation of the chest x-ray. METHODS: Prospective convenience sample. PARTICIPANTS: Any emergency department patient undergoing bioimpedance monitoring for suspected HF or shortness of breath. The mean Zo was measured prior to initiation of any therapy expected to result in thoracic fluid changes. A single radiologist, blinded to the clinical state of the patient and the bioimpedance data, interpreted all chest x-rays as "normal", having "evidence of cephalization", or demonstrating "abnormal pulmonary fluid". Radiographic evidence of abnormal pulmonary fluid was defined as the presence of Kerley B fines or pulmonary edema. This study is an amplification of a database previously reported in preliminary form as an abstract at the Society for Academic Emergency Medicine Annual meeting. STATISTICS: General Linear Model comparing CXR findings and initial mean Zo with post-hoc Bon Ferroni palrwise comparisons to determine significant variables. SETTING: 1,000 bed urban teaching hospital, 40,000 visit ED. RESULTS: 132 patients, mean age 66.8 y (31-94, SD= 13), 64.3% male, with an initial mean Zo-18.9 ohms (8.6-38.0, SD=5.2). There was a significant difference (P<0.0001) between patients with cephalization (Zo = 18.9 -+ 4.7 ohms) or abnormal pulmonary fluid on CXR (Zo-17.6 -+ 4.1 ohms) compared to normals (Zo=23.6 -+ 5.7 ohms, p<0.05). There was no difference between patients with cephalization and abnormal pulmonary fluid. Conclusions: Non-invasive bioimpedance measurement may detect puhnonary fluid not apparent on chest radiograph.
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199
Are Observation Periods Necessary during Initiation and Uptitration of Carvedilol in Heart Failure Patients? James E. Udelson, 1 Diane Miller, 2 Nell Shnsterman, 2 Marvin A. Konstaml; 1Cardiology, Tufts, N.E. Medical Center, Boston, MA, 2SKB, Philadelphia, PA
Mortality and Outcome Differences between Survivors and Nonsurvivors in the InSync Cardiac Resynchronization Trial A. Tang, D. Gras, P. Mabo, C. Buclmall, H. Oude-Luttikhuis, A. KirsteinPedersen, InSync Group;
Current recommendations call for a 2 hour observation period in a clinic or office setting during initiation and uptitration of carvedilol for outpatients with stable mild-to-moderate heart failure. To examine the strength of the data supporting that reconamendation, we reviewed information on 1869 patients enrolled in carvedilol heart failure trials. Among patients initiated at a dose of 3.125 mg, there were no reported instances of investigator-defined symptomatic adverse events, while 4 such events (0.2%) occurred in patients initiated at 6.25 rag, including symptomatic hypotension, worsening CHF and dizziness, from which all patients recovered. Other reported adverse events considered non-serious were infrequent at initiation of either 3.125 mg or 6.25 mg: mild dizziness (2.3 and 3.1% respectively), low blood pressure (2.3 and 1.4%), and cardiac failure (0 and 0.7%). Among the 1196 pts enrolled in the US Carvedilol Heart Failure Trials, the 6.25 mg dose initiated during the challenge phase resulted in a 2.7% incidence of new systolic BP< 80 mm Hg, and an incidence of only 0.2% new HR< 50 bpm seen during the office or clinic observation period. Hence, important adverse events or changes in vital signs requiring intervention are very infrequent during initiation and initial uptitration of cm'vedilol in stable outpatients with heart failure. These data call into question the time- and expense-consuming need to observe and monitor all such patients in the office or clinic setting when starting this therapy.
The InSync clinical study is a prospective, multicenter, longitudinal trial evaluating cardiac resynchronization therapy in patients with advanced heart failure (NYHA class III/IV), dilated cardiomyopathy (EF<35%, LVEDD>60mm) and ventricular conduction abnormalities (QRS>150ms). Patients were followed in the trial with respect to measured clinical endpoints. METHODS: One hundred and one patients implanted with the InSync system, including a transvenous left ventricular lead via the coronary venous vasculatore, were included in this analysis. RESULTS: Patient survival was 81.6% (16 deaths) at 6 months (follow-up, FU, of 255 days). There were two additional late deaths at 261 and 491 days post-implant for a total of 18. Ten of the deaths were classified as sudden. All outcomes showed significant improvements in the survivors between baseline and last FU visit (mean FU: 193-+ 115,*p<0.05). No significance was observed in the nonsurvivors (mean FU: 97-+ 117 days). Comparison of improvements in outcomes between the survivors and nonsurvivors showed a significant difference only for NYHA class (**p<0.05).
Survivors
NYHA class** Quality of Life 6 rain walk,m LVEF,% QRS duration,ms
Baseline 3.3-+0.5 56 + 17 291+-116 22+8 180-+29
Non-survivors LastFU 2.2+-0.8 * 35+21 * 353-+130" 30-+11 * 156+22 *
Baseline 3.4+-0.5 5 2+- 18 314-+98 25-+6 178_+34
LastFU 3.1+-0.8 38-+24 345-+88 26-+9 164-+31
CONCLUSIONS: The InSync Trial had an 18% six month mortality rate. The improvement in NYHA class was significantly greater in the survivors compared to the nonsurvivors. Cardiac resynchronization therapy may provide improved outcomes in symptomatic heart failure patients with ventricular conduction abnormalities. Randomized controlled studies may provide additional information regarding predictors of mortality and outcomes of responders to cardiac resynchronization therapy.
Journal of Cardiac Failure Vol. 5 No. 3 Suppl. 1 1999
196
197
Assessment of Left Ventricular Ejection Fraction in Heart Failure: Interchangeable Use of Three-Dimensional Echocardiography and Radionuclide Ventriculography Donald L. King, Lyna EI-Khoury Coffin, Jonathan Sankner-Bernstein; Medicine, Columbia University, New York, NY
Bioimpedance Monitoring for the Detection of Pulmonary Fluid in Heart Failure Patients: Equal Efficacy to Chest Radiography? William F. Peacock, 1 Nancy M. Albert, 2 Phillipine Kies, 1 Richard D. White, 3 Charles L. Emermanl; ~Emergency Medicine, The Cleveland Clinic, Cleveland, OH, 2Cardiology, The Cleveland Clinic, Cleveland, OH, 3Radiology, The Cleveland Clinic, Cleveland, OH
Background: Patients with congestive heart failure undergo repeated assessment of left ventricular ejection fraction to evaluate response to therapy and monitor disease progression, generally by either radionuclide ventriculography or echocardiography. Although ejection fraction measured in cross-sectional studies by three-dimensional echocardiography correlates well with that of radionuclide scans, no study has compared these techniques longitudinally. We tested the hypothesis that these techniques are interchangeable in their ability to detect changes in left ventricular performance produced by long-term anti-adrenergic therapy in patients with chronic heart failure. Methods: Thirty-six patients with mild to moderate symptoms (54% NYHA Class II, 46% NYHA Class III) despite therapy with digoxin, diuretics and angiotensin converting enzyme inhibitors underwent assessment of ventricular function by both radionuclide ventriculography and freehand three-dimensional echocardiography. Carvedilol was initiated at 3.125 mg BID and titrated to maximum tolerated dose (target of 25-50 mg BID). Ventricular function was reassessed by both techniques after 4-6 months. Results: Baseline mean ejection fraction was 22% for radionuclide ventriculography and 25% for three-dimensional echocardiography. After long-term therapy the mean ejection fractions were 27% and 31% respectively. The change measured by each method was statistically significant but the difference between the methods was not. Ejection fraction by radionuclide ventriculography showed an underestimation bias of 3-4% compared to three-dimensional echocardiography. Conclusions: Freehand three-dimensional echocardiography and radionuclide ventriculography are comparable when measuring change in ejection fraction during medical therapy in patients with advanced heart failure. Either of these methods may be used for measurement of left ventricular ejection fraction in longitudinal evaluation of heart failure patients.
The use of non-invasive thoracic bioimpedance monitoring may be of benefit in the diagnosis and management of heart failure (I-iF) patients suspected of having abnormal quantities of intrathoracic fluid. Increasing thoracic fluid volume corresponds to proportionally lower thoracic electrical impedance. This is measured and displayed numerically as "mean Zo". A lower Zo reflects increased thoracic water; a higher Zo implies a drier pulmonary state. The quantification of intrathoracic fluid by chest radiography is subjective. Theoretically, bioimpedance may offer greater reproducibility and sensitivity for detemfining the presence of abnormal thoracic fluid. There are no published works comparing the current subjective standard of chest radiography to bioimpedance measurement for quantifying thoracic water in heart failure patients. OBJECTIVE: To compare the detection of pulmonary fluid excess, by bioimpedance measurement, to a radiologisfs interpretation of the chest x-ray. METHODS: Prospective convenience sample. PARTICIPANTS: Any emergency department patient undergoing bioimpedance monitoring for suspected HF or shortness of breath. The mean Zo was measured prior to initiation of any therapy expected to result in thoracic fluid changes. A single radiologist, blinded to the clinical state of the patient and the bioimpedance data, interpreted all chest x-rays as "normal", having "evidence of cephalization", or demonstrating "abnormal pulmonary fluid". Radiographic evidence of abnormal pulmonary fluid was defined as the presence of Kerley B fines or pulmonary edema. This study is an amplification of a database previously reported in preliminary form as an abstract at the Society for Academic Emergency Medicine Annual meeting. STATISTICS: General Linear Model comparing CXR findings and initial mean Zo with post-hoc Bon Ferroni palrwise comparisons to determine significant variables. SETTING: 1,000 bed urban teaching hospital, 40,000 visit ED. RESULTS: 132 patients, mean age 66.8 y (31-94, SD= 13), 64.3% male, with an initial mean Zo-18.9 ohms (8.6-38.0, SD=5.2). There was a significant difference (P<0.0001) between patients with cephalization (Zo = 18.9 -+ 4.7 ohms) or abnormal pulmonary fluid on CXR (Zo-17.6 -+ 4.1 ohms) compared to normals (Zo=23.6 -+ 5.7 ohms, p<0.05). There was no difference between patients with cephalization and abnormal pulmonary fluid. Conclusions: Non-invasive bioimpedance measurement may detect puhnonary fluid not apparent on chest radiograph.
198
199
Are Observation Periods Necessary during Initiation and Uptitration of Carvedilol in Heart Failure Patients? James E. Udelson, 1 Diane Miller, 2 Nell Shnsterman, 2 Marvin A. Konstaml; 1Cardiology, Tufts, N.E. Medical Center, Boston, MA, 2SKB, Philadelphia, PA
Mortality and Outcome Differences between Survivors and Nonsurvivors in the InSync Cardiac Resynchronization Trial A. Tang, D. Gras, P. Mabo, C. Buclmall, H. Oude-Luttikhuis, A. KirsteinPedersen, InSync Group;
Current recommendations call for a 2 hour observation period in a clinic or office setting during initiation and uptitration of carvedilol for outpatients with stable mild-to-moderate heart failure. To examine the strength of the data supporting that reconamendation, we reviewed information on 1869 patients enrolled in carvedilol heart failure trials. Among patients initiated at a dose of 3.125 mg, there were no reported instances of investigator-defined symptomatic adverse events, while 4 such events (0.2%) occurred in patients initiated at 6.25 rag, including symptomatic hypotension, worsening CHF and dizziness, from which all patients recovered. Other reported adverse events considered non-serious were infrequent at initiation of either 3.125 mg or 6.25 mg: mild dizziness (2.3 and 3.1% respectively), low blood pressure (2.3 and 1.4%), and cardiac failure (0 and 0.7%). Among the 1196 pts enrolled in the US Carvedilol Heart Failure Trials, the 6.25 mg dose initiated during the challenge phase resulted in a 2.7% incidence of new systolic BP< 80 mm Hg, and an incidence of only 0.2% new HR< 50 bpm seen during the office or clinic observation period. Hence, important adverse events or changes in vital signs requiring intervention are very infrequent during initiation and initial uptitration of cm'vedilol in stable outpatients with heart failure. These data call into question the time- and expense-consuming need to observe and monitor all such patients in the office or clinic setting when starting this therapy.
The InSync clinical study is a prospective, multicenter, longitudinal trial evaluating cardiac resynchronization therapy in patients with advanced heart failure (NYHA class III/IV), dilated cardiomyopathy (EF<35%, LVEDD>60mm) and ventricular conduction abnormalities (QRS>150ms). Patients were followed in the trial with respect to measured clinical endpoints. METHODS: One hundred and one patients implanted with the InSync system, including a transvenous left ventricular lead via the coronary venous vasculatore, were included in this analysis. RESULTS: Patient survival was 81.6% (16 deaths) at 6 months (follow-up, FU, of 255 days). There were two additional late deaths at 261 and 491 days post-implant for a total of 18. Ten of the deaths were classified as sudden. All outcomes showed significant improvements in the survivors between baseline and last FU visit (mean FU: 193-+ 115,*p<0.05). No significance was observed in the nonsurvivors (mean FU: 97-+ 117 days). Comparison of improvements in outcomes between the survivors and nonsurvivors showed a significant difference only for NYHA class (**p<0.05).
Survivors
NYHA class** Quality of Life 6 rain walk,m LVEF,% QRS duration,ms
Baseline 3.3-+0.5 56 + 17 291+-116 22+8 180-+29
Non-survivors LastFU 2.2+-0.8 * 35+21 * 353-+130" 30-+11 * 156+22 *
Baseline 3.4+-0.5 5 2+- 18 314-+98 25-+6 178_+34
LastFU 3.1+-0.8 38-+24 345-+88 26-+9 164-+31
CONCLUSIONS: The InSync Trial had an 18% six month mortality rate. The improvement in NYHA class was significantly greater in the survivors compared to the nonsurvivors. Cardiac resynchronization therapy may provide improved outcomes in symptomatic heart failure patients with ventricular conduction abnormalities. Randomized controlled studies may provide additional information regarding predictors of mortality and outcomes of responders to cardiac resynchronization therapy.