A Chronicle ICD system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death or serious injury of subject, (3) results in the explant of any Chronicle ICD component,and/or (4) causes permanent loss of significant function of the implanted system.

All 406 subjects with an attempted implant of the Chronicle ICD system.

A Chronicle IHM system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death or serious injury of subject, (3) results in the explant of any Chronicle IHM component,and/or (4) causes permanent loss of significant function of the implanted system.

All subjects with an attempted implant of the Chronicle IHM system were included in this analysis. At the time the study stopped, there was only one subject with an attempted Chronicle IHM implant. Thus this objective was not analyzed.

The rate of HF-related events (hospitalizations >24h, hospitalizations <24h with IV therapy, ED visits with IV therapy, and urgent clinic visits with IV therapy) during the 12-month randomized follow-up period was compared between the Chronicle and Control groups.

All randomized subjects

The endpoint for this objective was defined as the cumulative days in hospital for heart failure (HF) expressed as a percentage of hospital free follow-up days during the 12-month randomized period. The relatedness of the events was based on the primary reason for which the subject was originally admitted to the hospital or seen in the emergency department or at an urgent visit, not on the development of new events that occur during hospitalization.

All follow-up from all randomized subjects were included in this analysis.

The rate of CV-related events (hospitalizations >24h, hospitalizations <24h with IV therapy, ED visits with IV therapy, and urgent clinic visits with IV therapy) during the 12-month randomized follow-up period was compared between the Chronicle and Control groups.

All randomized follow-up for all randomized subjects.

Death from any cause or heart failure related hospitalization greater than 24 hours during the 12-month randomized period

All randomized subjects

All-cause events were defined as hospitalizations, hospitalizations <24 hours necessitating intravenous therapy, emergency department visits necessitating intravenous therapy or urgent visits necessitating intravenous therapy.

All randomized follow-up from all randomized subjects

The definitions of worsened, improved, and unchanged are as follows:

Worsened: Subject dies, is hospitalized for worsening heart failure, permanently discontinues blinded randomized assignment and has worsening heart failure at time of study discontinuation, demonstrates worsening NYHA Class at LOCF, or moderate-marked worsening of global assessment score at LOCF.

Improved: Subject has not worsened, and demonstrates improvement in NYHA class and/or moderate-marked improvement in subject global assessment score.

Unchanged: Subject is neither worsened nor improved.

All randomized follow-up from all randomized subjects were included.

Percentage of randomized days spent in the intensive care unit for heart failure. Reason for hospitalization was determined by the adverse event adjudication committee.

All randomized subjects.

Randomized days alive outside of the hospital was computed for each subject as the total number of randomized days minus the number of randomized days spent in the hospital for any cause.

All randomized subjects.

Death from any cause during the 12-month randomization period

All randomized subjects.

The rate of change of cardiovascular medications in changes per subject month were computed and compared between treatment groups.

All randomized subjects.

The average daily median estimated pulmonary arterial diastolic pressure (ePAD) was computed for each subject with at least 90 days of ePAD data available and compared between the Treatment and Control arms.

At least 90 days of ePAD data were required for each subject during the 12-month randomized period to be included in the analysis.

The average daily median estimated pulmonary arterial diastolic pressure (ePAD) was computed for each subject with at least 90 days of ePAD data available and compared between the Control Arm subjects with and without a heart failure related event during the 12-month randomized period.

All Control Arm subjects with at least 90 days of pressure data available during the 12-month randomized follow-up period.

The outcome is the change in NYHA functional class between the baseline visit and the 12-month follow-up visit. At baseline subjects were required to be NYHA functional class II or III. The outcome will show the percentage of subjects that were functional class II and III at baseline and functional class I, II, III, or IV at the 12-month visit. The percent improvement from baseline is calculated as the percentage of subjects with a lower NYHA functional class at the 12-month visit compared to their NHYA functional class at baseline.

Subjects were required to have an NYHA functional class assessment at the baseline and 12-month follow-up visit to be included in this analysis.

The outcome is the change in distance walked in 6-minutes in meters between the baseline visit and the 12-month follow-up visit. The change in distance walked was calculated within each subject as the distance walked in 6-minutes at the 12-month visit minus the distance walked in 6-minutes at the baseline visit. Positive values indicate an increase in the distance walked in 6-minutes from baseline.

Subjects were required to complete the 6-minute hall walk test at both the baseline and 12-month visit to be included in the analysis of this objective.

Change in estimated glomerular filtration rate (eGFR) from baseline to the 12-month follow-up visit. eGFR was estimated using the MDRD forumula from the National Kidney Foundation (American Journal of Kidney Diseases 39: S1-299). Change in eGFR was computed as the 12-month eGFR value minus the baseline eGFR value. Positive values indicate an increase in eGFR from baseline and negative values indicate a decrease in eGFR from baseline.

Subjects were required to have creatinine values available at the baseline and 12-month visit to be included in the analysis of this objective.

Intracardiac pressure monitoring was deemed successful following defibrillation testing if physiological pressure waveforms were present following defibrillation testing.

Of the 406 subjects with an attempted implant of the Chronicle ICD system, 366 completed defibrillation testing as part of their ICD implant procedure.

The outcome measure is the percentage of subjects implanted with the Chronicle ICD who completed defibrillation testing and had a 10 Joule safety margin

Of the 406 subjects with an attempted implant of the Chronicle ICD system, 366 completed defibrillation testing.

The outcome is the change in the Minnesota Living with Heart Failure® (MNLWHF) questionnaire response from baseline to the 12-month follow-up visit. The MNLWHF questionnaire is a 21 question questionnaire scored from zero (no impact of heart failure) to 5 (severe impact of heart failure). The composite MNLWHF score ranges from 0 (no impact of heart failure) to 105 (severe impact of heart failure). Change in MNLWHF score was computed as the 12-month minus the baseline score.

Subjects were required to respond to the baseline and 12-month follow-up visit to be included in the analysis.

The rate of spontaneous VT (ventricular tachycardia)/VF (ventricular fibrillation) episodes during the 12-month follow-up period in episodes per subject month was compared between the Treatment Arm and the Control Arm

All 399 subjects successfully implanted with the Chronicle ICD were included in the analysis.