Study of Autologous Bone Marrow Derived Mononuclear Cells for Treatment of Ebstein Anomaly

Number of adverse events from time of index procedure

Safety assessment of adverse events from time of index procedure will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Analysis of cardiac adverse events is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: 24 months post index procedure

Severity of adverse events from time of index procedure

Safety assessment of severity of adverse events from time of index procedure will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: 24 months post index procedure

Number of subjects who died

Safety assessment of all-cause mortality will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: 24 months post index procedure

Number of subjects with sustained symptomatic cardiac arrhythmias

Safety assessment of sustained symptomatic cardiac arrhythmias will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: 24 months post index procedure

Number of subjects with myocardial infarction

Safety assessment of myocardial infarctions will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: 24 months post index procedure

Number of subjects with unexpected, invasive cardiovascular procedures

Safety assessment of unexpected, invasive cardiovascular procedures will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: 24 months post index procedure

Number of serious adverse events

Safety assessment of serious adverse events will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: 24 months post index procedure

Percentage of subjects in the treatment group that have cells delivered

Feasibility of the BM-MNC cell therapy will be evaluated comparing number of subjects enrolled in the treatment group to subjects in the treatment group who are accrued and have cells delivered by percentage using the binomial distribution and exact confidence limits given.

Time frame: 24 months post index procedure

Percentage of subjects in the treatment group completing the 24 month follow-up

Feasibility of the BM-MNC cell therapy will be evaluated comparing number of subjects enrolled in the treatment group to subjects in the treatment group who are accrued and have cells delivered, who complete the 24 month follow-up visit by percentage.

Time frame: 24 months post index procedure

Incidence of cardiac related hospitalizations from time of Ebstein repair

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 1, 6, and 24 months post index procedure

Incidence of cardiac arrhythmias from time of index procedure

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 1, 6, and 24 months post index procedure

Change in CT derived right ventricular dimensions from time of pre-operative evaluation

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. End volume measurements recorded using mL and indexed to body surface area (BSA) using mL/m\^2.A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will be used to distinguish common rates from very rare rates. Analysis is in terms of yes/no information at 24 months.If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 6 and 24 months post index procedure

Change in echocardiography derived cardiac output from time of pre-operative evaluation

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group.Volume is measured in L/min and Volume Index is L/min/m\^2.Using t-test will have 80% power to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group to distinguish common rates from very rare rates. Analysis in terms of yes/no information at 24 months. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 1, 6, and 24 months post index procedure

Change in NT-Pro-BNP derived cardiac function trend from time of pre-operative evaluation

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: During hospitalization up to 29 days, 1, 6 and 24 months post index procedure

Incidence of cardiac related hospitalizations in the treatment group from time of pre-operative evaluation compared to the control group

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 1, 6, and 24 months post index procedure

Incidence of cardiac arrhythmias in the treatment group from time of pre-operative evaluation compared to the control group

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 1, 6, and 24 months post index procedure

Change in MRI derived cardiac output in the treatment group from time of pre-operative evaluation compared to the control group

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group.Volume is measured in L/min and Volume Index is L/min/m\^2.Using t-test will have 80% power to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group to distinguish common rates from very rare rates. Analysis in terms of yes/no information at 24 months.If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 6 and 24 months post index procedure

Change in echocardiography derived right ventricular dimensions from time of pre-operative evaluation

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. End volume measurements recorded using mL and indexed to body surface area (BSA) using mL/m\^2,diameter as cm.A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will be used to distinguish common rates from very rare rates. Analysis is in terms of yes/no information at 24 months.If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 1, 6, and 24 months post index procedure

Change in NT-Pro-BNP derived cardiac function trend in the treatment group from time of pre-operative evaluation compared to the control group

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: During hospitalization up to 29 days, 1, 6, and 24 month post index procedure

Number of serious adverse events from time of enrollment

Safety assessment of the number of serious adverse events from time of enrollment will be analyzed by counts and percents using the chi-square test and Cochran-Armitage test for trends, and the two groups compared using the Fisher exact test. A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect a difference in a sample size of 10 in each group. Thus having reasonable power to distinguish common rates for adverse events from very rare rates. Subjects will be censored upon lost to follow up. If some subjects are lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method and comparison between the two groups using the log-rank test. A confidence interval for the difference between groups will be given.

Time frame: index procedure

Percentage of subjects in the treatment group whose cells meet all release criteria

Feasibility of the BM-MNC cell therapy will be evaluated comparing number of subjects enrolled in the treatment group to subjects in the treatment group with collected bone marrow and the bone marrow cells have met all product release criteria to any products that did not meet release criteria by percentage.

Time frame: 24 months post index procedure

Change in CT derived cardiac output from time of pre-operative evaluation

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group.Volume is measured in L/min and Volume Index is L/min/m\^2.Using t-test will have 80% power to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group to distinguish common rates from very rare rates. Analysis in terms of yes/no information at 24 months. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 6 and 24 months post index procedure

Change in MRI derived right ventricle ejection fraction in the treatment group from time of pre-operative evaluation compared to the control group

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group measured in %.Using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 6 and 24 months post index procedure

Change in MRI derived right ventricular dimensions in the treatment group from time of pre-operative evaluation compared to the control group

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group. End volume measurements recorded using mL and indexed to body surface area (BSA) using mL/m\^2.A sample size of 10 in each group using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will be used to distinguish common rates from very rare rates. Analysis is in terms of yes/no information at 24 months.If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 6 and 24 months post index procedure

Change in CT derived right ventricle ejection fraction from time of pre-operative evaluation

Efficacy will be evaluated using analysis of covariance (ANCOVA) from baseline to 24 months post-index procedure comparing outcomes between the treatment group to the control group measured in %.Using t-test will have 80% power to detect an effect size of 1.325 with a 0.050 two-sided significance level to identify a difference between means from the two groups. Descriptive statistics such as mean, median, SD, min, max, and 95% confidence intervals of the mean, and frequency distributions will be calculated for all variables by group. Fisher exact test will have 80% power to detect a difference in a sample size of 10 in each group having reasonable power to distinguish common rates from very rare rates. Analysis is in terms of the yes/no information at 24 months. Subjects will be censored upon lost to follow up. If a subject is lost to follow-up then fractions at 24 months will be described using the Kaplan-Meier method.

Time frame: 6 and 24 months post index procedure