Table 2.

Overview of key clinical trials in CIED-based RM.

Device	Study	Patient Population	Data Collection and Storage	Frequency of Data Monitoring and Data Management	Outcome
Cardiovascular Implantable Electronic Device (CIED) Monitoring
CIEDs	FAST (2003–2008)	156 patients with NYHA class III–IV HF and a Medtronic CIED	-Software was downloaded onto the device to measure and store impedance measurements	-Recorded daily changes in intrathoracic impedance -Both clinicians and patients did not have access to data during the trial	-Increased sensitivity and lower unexplained detection rate in detecting HF events compared to weight monitoring
	OptiLINK HF (2008–2014)	1002 patients with NYHA class II–III HF, a Medtronic CIED, prior HFH within 12 months, recent diuretic treatment, or elevated BNP across 1 site in Europe	-Devices set to automatically transmit fluid index alerts in treatment arm	-Continuous data monitoring -A protocol-specified intervention algorithm was followed if alert triggered	-No difference in primary composite endpoint of all-cause death and cardiovascular hospitalization
	PARTNERS-HF (2004–2008)	694 patients with NYHA class III–IV HF and Medtronic CIED across 93 sites in the U.S.	-Collection of standard CIED-measured parameters	-Continuous data monitoring, but device interrogations occurred monthly	-Diagnostic algorithm successfully determined predictors of HFH
	REM-HF (2011–2014)	1650 patients with NYHA class II–IV HF with a CIED	-Collection of standard CIED-measured parameters -Data stored on electronic record	-Continuous data monitoring, but device interrogations occurred weekly -Formalized procedural handbook guided clinical management	-No difference in primary composite outcome of all-cause death or unplanned cardiovascular hospitalization
	MULTISENSE (2010–2014)	900 patients with NYHA class II–III HF with a CIED across 99 sites in Europe, Asia, and the U.S.	-Software was downloaded onto device that allowed data collection of HeartLogic algorithm parameters -Data downloaded at in-person visits or remotely using LATITUDE (computer platform) transmissions	-Continuous data monitoring used to give a daily HeartLogic index value	-Met prespecified, coprimary endpoint thresholds for sensitivity of detecting HF exacerbations and unexplained alert rate
	SELENE HF (2012–2017)	918 patients with NYHA class II–III HF across 34 sites in Europe	-Collection of standard CIED measured parameters	-Continuous data monitoring used to give a Seattle Heart Failure Model score	-Predictive algorithm successfully determined predictors of HFH
	TRUST (2005–2009), ECOST (2007–2010), IN-TIME (2007–2012)	2405 patients with HF and varying inclusion criteria across 171 sites in Europe and the U.S.	-Small, portable patient device receives data and transmits them automatically over a mobile phone, which links to the Home Monitoring Service Center on a secure site for review by clinical teams	-Daily transmissions of cumulative and last-saved diagnostic data	-Meta-analysis of three trials -Pooled effect demonstrated reduction in all-cause mortality and composite outcome of all-cause mortality or HFH

CIED, cardiovascular implantable electronic device; HF, heart failure; HFH, heart failure hospitalization; NYHA, New York Heart Association; U.S., United States.