In this prospective pilot study, patients who were hospitalized for AHF, had an LVEF <40% but no immediate indication for device implant, and received an ILR before hospital discharge were enrolled.

Clinical follow-up visits were scheduled at 3 and 6 months and every 6 months thereafter. Device data were reviewed monthly through the Care-Link remote monitoring system or at any time the patients had symptoms (ClinicalTrials.gov; Identifier: NCT01216670). CARRYING-ON for HF Study design is reported in Figure 1.

Informed consent was obtained from each enrolled patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the local ethics committee.

The aim of the study was to assess the capability of loop recording to recognize early signs of prespecified clinical and arrhythmic events in this cohort of patients. Prespecified events were: (1) CV mortality or unplanned CV hospitalization and (2) any cardiac arrhythmic event detected by the implanted device (Sinus bradycardia: ≤ 30 beats per minutes (bpm), ≥ 8s; Sinus arrest: ≥ 5s; atrioventricular (AV) block (2°, 3°): ≤ 30 bpm, ≥ 8s; atrial fibrillation (AF): > 6 min; non-sustained ventricular tachycardia (VT): ≥ 125 bpm, ≥16 beats; sustained VT: > 30 sec). The main inclusion criteria were: (1) a history of at least 1 HF hospitalization, emergency department visit, or urgent office visit necessitating intravenous (IV) diuretic or augmentation of oral diuretic, IV inotropic, or IV vasodilator or other HF parenteral therapy within 15 days prior to device implant; (2) an implanted Medtronic Reveal XT ILR device (< 15 days post-implant); and (3) LVEF < 40%. Main exclusion criteria were: (1) New York Heart Association (NYHA) Class IV (chronic or ambulatory); (2) planned or previous implant of an implantable cardioverter defibrillator (ICD) or pacemaker device; (3) severe chronic obstructive pulmonary disease; (4) permanent AF at time of enrolment; and (5) ST segment elevation at electrocardiogram (ECG). A Reveal XT ILR was used for continuous cardiac monitoring. The ILR was implanted within 15 days the AHF event. All the patients enrolled received a remote monitoring system and were requested to transmit Reveal XT data on a monthly base or in case any symptoms occurred.

Continuous data were summarized as mean and standard deviation or median and 25th-75th percentiles in case of skewed distributions. Absolute and relative frequencies were reported for categorical variables. Kaplan-Meier method was used to display the time to first event. The mean cumulative function (MCF) plot for the number of recurrent events was used to display the overtime trend of the events rate. Statistical analyses were performed using SAS 9.3 for Windows (SAS Institute Inc, Cary, NC).

The patients on average were 73±10 years old, 12 (67%) were male, and 7 (39%) had ischemic cardiomyopathy. According to guidelines, all the patients at the time of enrollment had no immediate indication to receive a permanent implantable cardiac device: 8 (44%) patients had LVEF > 35%, 2patients were in NYHA functional class I, and 9 (50%) patients were not under optimized pharmacological treatment for HF at the time of the AHF event. Most patients (15/18, 83%) were on beta-blocker therapy (11 were on bisoprolol 2.5 mg twice a day and 4 were on carvedilol 12.5 mg twice a day). Further baseline characteristics are reported in Table 1.

Abbreviations: ACE, angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blocker; CAD, coronary artery disease; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; MI, myocardial infarction; NS-VT, non-sustained ventricular tachycardia; NYHA, New York Heart Association.

^aData are expressed as mean ± standard deviation or absolute (relative) frequencies.

During a median follow-up of 593 days (mean 509+260), major CV events occurred in 13 patients (72%, median time to first combined event 162 days (39-606)); 11 patients had at least 1 cardiac arrhythmic event, 2 had at least 1 clinical event (CV hospitalization or CV death), and 4 had both arrhythmic and clinical events. Figure 2 shows clinical and arrhythmic events incidence and distribution.

Six (33%) patients experienced 10 major clinical events; 5 (50%) of which were HF-related with 1 patient dying due to HF (terminal rhythm: asystole) and 1 patient dying due to an acute CV event (ruptured cerebral aneurysm). Distribution of detected major clinical and arrhythmic events is reported in Table 2.

Abbreviations: AF, atrial fibrillation; AT, atrial tachycardia; AV, atrioventricular; CV, cardiovascular; HF, heart failure; VT, ventricular tachycardia.

^aData are expressed as absolute (relative) frequencies.

^bThe 2 events of death also had previous hospitalizations.

During follow-up, 3 (16%) patients were implanted with a permanent cardiac device according to current guidelines (in 2 patients who developed sustained-VT, a cardiac resynchronization therapy with defibrillator backup device (CRT-D) was implanted; in the 1 patient with sinus arrest and LVEF < 35%, a single chamber ICD was implanted). Eight patients suffered paroxysmal AF that was often asymptomatic (62%); the mean CHADS₂ score in these 8 patients was 3.0+0.7, as all had a CHADS₂ score ≥2.

As per heart rate (HR), we computed its circadian behavior: the 2 patients who had a nocturnal HR > 70 bpm for > 85% of the night had major clinical events, while this occurred in only 3/16 (19%) of the patients with nocturnal HR < 70 bmp.

Figure 3 shows Kaplan-Meier analysis for clinical and arrhythmic events, both for time to first combined event (Figure 3a) and for cumulative combined events incidence (Figure 3b).

The main limitation of this pilot study is the small number of patients enrolled. Our study, planned as a feasibility and methodology study, was not powered to determine the overall prevalence of CV events after an AHF episode nor to test the effectiveness of ILR in reducing CV events in this population. The primary aim was descriptive as a preliminary fundamental information to design a larger comparative study.

The CARRYING ON for HF study provided meaningful information on the many (72%) patients hospitalized for an acute HF episode who are not eligible, according to current guidelines, to receive an implantable cardiac device and who later develop CV and arrhythmic events during the follow-up.

The present finding provides some background for future prospective studies aimed at the assessment of the risk stratification of continuous cardiac monitoring in HF patients who are not deemed eligible for immediate implantation of a permanent cardiac device.