Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)

The primary efficacy endpoint will evaluate the effect of CRT=ON versus CRT=OFF in time to event of a combined endpoint of all-cause mortality or first hospitalization for worsening heart failure.

Time frame: From date of randomization until date of death from any cause or date of first hospitalization for worsening heart failure, whichever came first, assessed up to date of study exit, with a mean treatment duration of 1.6 years

Population: This analysis was carried out according to the intention-to-treat principle. Follow-up was censored at study closure, date of death, LVAD, heart transplant, withdrawal from the study, or loss to follow-up, whichever came first. 4 deaths in CRT OFF group and 1 death in CRT ON group were after LVAD/transplant and are not included in this analysis.

The primary safety endpoint will evaluate the complication-free rate of the Lumax HF-T CRT-D devices in the narrow QRS subject population.

Time frame: 6 months

Population: The primary safety endpoint included all subjects undergoing an implant procedure.

Quality of Life was evaluated using the Minnesota Living with Heart Failure (MLHF) Quality of Life (QOL) Questionnaire.The questionnaire consists of 21 questions to measure the subjects' perception of how their HF and its treatment affected their ability to live as they wanted during the last month. The questions describe different ways in which some people are affected (i.e. physical, socioeconomic, and psychological impairments). If a question does not apply to a subject or is not related to their HF, then they can answer with a 0. If it does apply to them, then they can rate (from 1 to 5) how much it has affected them. From the 21 questions, the lowest possible total score is 0, and the highest possible total score is 105. A lower score is desirable. Therefore, a negative change in QOL score from baseline to 6 months represents an improvement in quality of life, while a positive change in QOL score from baseline to 6 months represents a worsening in quality of life.

Time frame: Changes between baseline and 6 months

Population: Subjects with Baseline \& 6-month QOL scores. 25 subjects (15 CRT ON, 10 CRT OFF) that were in the study at least 6 months and that did not have 6-month QOL data, had 3-month data inputted using the LOCF principle.

Evaluate the effects of CRT=ON compared to CRT=OFF in relation to a composite endpoint of all-cause mortality, hospitalization for worsening heart failure and change in the MLHF Quality of Life Questionnaire. This composite endpoint used a weighted scoring scale based on the African-American Heart Failure Trial (A-HeFT) study Endpoint Score. (Taylor, AL, Ziesche, S, Yancy, C, et al. Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure. N Engl J Med 2004; 351:2049-57.) Composite Endpoint Scoring: Vital Status: Death (-3), Survival to end of trial (0), Hospitalization: 1st hospitalization for HF (-1), No hospitalization (0), QOL score:\* Improvement by ≥ 10 units (+2), Improvement by 5-9 units (+1), Change by \< 5 units (0), Worsening by 5-9 units (-1), Worsening by ≥ 10 (-2). Possible total score -6 to +2. \*QOL score details are provided in Secondary Outcome Measure 5.

Time frame: Composite of death, worsening heart failure hospitalization (up to 24 months), and change in QOL (at 6 months)

Population: Subjects with a potential of 24 months of follow-up.

Evaluate the effects of CRT=ON compared to CRT=OFF in relation to the change in NYHA classification. NYHA classes: Class I - Subjects with cardiac disease, but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation,dyspnea, or anginal pain. Class II - Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III - Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV - Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

Time frame: 6 months

Population: Subjects with Baseline \& 6-month NYHA classification. 18 subjects (9 CRT ON, 9 CRT OFF) that were in the study at least 6 months and that did not have 6-month NYHA data, had the most recent post-randomization NYHA inputted using the Last Observation Carried Forward (LOCF) principle.

Evaluate the all-cause mortality rate between the CRT=ON compared to CRT=OFF group.

Time frame: From date of randomization up to date of study exit, with a mean treatment duration of 1.6 years

Evaluate the effects of CRT=ON compared to CRT=OFF on the rate of hospitalization for worsening heart failure (WHF).

Time frame: Study duration from randomization to study exit