RefCheck Maintenance Notice

On Monday, December 3, 2018, from 16:00-18:00 EST, RefCheck will be undergoing maintenance. RefCheck is the process where, during copyediting, all references are extracted from the manuscript file, parsed, matched against various databases (eg, PubMed and CrossRef), and automatically corrected. For more information on RefCheck, please visit our Knowledge Base.

Who will be affected?

Advertisement

Citing this Article

Right click to copy or hit: ctrl+c (cmd+c on mac)

Published on 26.04.16 in Vol 5, No 2 (2016): Apr-Jun

This paper is in the following e-collection/theme issue:

    Original Paper

    Cardiac Rhythm Monitoring After Acute Decompensation for Heart Failure: Results from the CARRYING ON for HF Pilot Study

    1Dept Molecular Medicine, University of Pavia, Italy, Sesto San Giovanni, Milano,, Italy

    2Policlinico di Monza, Cardiovascular Department, Monza, Italy

    3Clinica San Gaudenzio, Novara, Italy

    4Azienda Ospedaliera S.Anna, Como, Italy

    5IRCCS Multimedica, Sesto San Giovanni, Milano, Italy

    6Medtronic Regional Clinical Center, Roma, Italy

    7Medtronic Italia, Milano, Italy

    Corresponding Author:

    Emilio Vanoli, MD PhD

    Dept Molecular Medicine, University of Pavia, Italy

    IRCCS MultiMedica, Via Milanese 300,

    Sesto San Giovanni, Milano,, 20099

    Italy

    Phone: 39 3482638297

    Fax:39 0224209335

    Email:


    ABSTRACT

    Background: There’s scarce evidence about cardiovascular events (CV) in patients with hospitalization for acute heart failure (HF) and no indication for immediate device implant.

    Objective: The CARdiac RhYthm monitorING after acute decompensatiON for Heart Failure study was designed to assess the incidence of prespecified clinical and arrhythmic events in this patient population.

    Methods: In this pilot study, 18 patients (12 (67%) male; age 72±10; 16 (89%) NYHA II-III), who were hospitalized for HF with low left ventricular ejection fraction (LVEF) (<40%) and no immediate indication for device implant received an implantable loop recorder (ILR) before hospital discharge. Follow-up visits were scheduled at 3 and 6 months, and at every 6 months until study closure; device data were remotely reviewed monthly. CV mortality, unplanned CV hospitalization, and major arrhythmic events during follow-up were analyzed.

    Results: During a median follow-up of 593 days, major CV occurred in 13 patients (72%); of those, 7 patients had at least 1 cardiac arrhythmic event, 2 had at least a clinical event (CV hospitalization or CV death), and 4 had both an arrhythmic and a CV event. Six (33%) patients experienced 10 major clinical events, 5 of them (50%) were HF related. During follow-up, 2 (11%) patients died due to a CV cause and 3 (16%) patients received a permanent cardiac device.

    Conclusions: After an acute HF hospitalization, patients with LVEF<40% and who are not readily eligible for permanent cardiac device implant have a known high incidence of major CV event. In these patients, ILR allows early detection of major cardiac arrhythmias and the ability to react appropriately in a timely manner.

    Trial Registration: ClinicalTrials.gov NCT01216670; https://clinicaltrials.gov/ct2/show/NCT01216670

    JMIR Res Protoc 2016;5(2):e62

    doi:10.2196/resprot.4380

    KEYWORDS

    Crowdfunding campaign to support this specific research

    We help JMIR researchers to raise funds to pursue their research and development aimed at tackling important health and technology challenges. If you would like to show your support for this author, please donate using the button below. The funds raised will directly benefit the corresponding author of this article (minus 8% admin fees). Your donations will help this author to continue publishing open access papers in JMIR journals. Donations of over $100 may also be acknowledged in future publications.

    keyboard with crowdfunding key instead of enter key

    Suggested contribution levels: $20/$50/$100



    Introduction

    Acute heart failure (AHF) episodes that induce hospitalizations represent one of the largest causes of health status deterioration [1]. About 45% of patients hospitalized with AHF will be rehospitalized at least once (and 15% at least twice) within 12 months [2]. Estimates of the risk of death or rehospitalization within 60 days of admission vary from 30% to 60%, depending on the population studied [2-8]. A significant proportion of heart failure (HF) patients do not undertake any device implant strategy since they do not meet the guidelines criteria [2]. Very little, if any, monitored information exists in those patients experiencing AHF with modest left ventricle impairment or with HF with preserved left ventricular ejection fraction (LVEF). Timely information might allow interventions that then avoid major cardiovascular (CV) events and possible progressive worsening of the disease leading to hospitalization. The availability of implantable devices to continuously monitor cardiac trends may provide early warning of changes in cardiac status, which would then allow early clinical management and possibly reduce the number of HF hospitalizations. The CARdiac RhYthm monitorING after acute decompensatiON for Heart Failure (CARRYING ON for HF) trial was designed to assess the efficacy of implantable loop recorders (ILRs) in the early detection of prespecified clinical and arrhythmic events in this patient population.


    Methods

    Study Design and Patient Population

    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.

    Figure 1. Study design.
    View this figure

    Statistical Analysis

    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).


    Results

    Baseline Characteristics

    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.

    Table 1. Baseline characteristics of study population.
    View this table

    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.

    Clinical Outcomes

    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.

    Table 2. Type and frequency of clinical and arrhythmic events that occurreda.
    View this table

    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).

    Figure 2. Clinical and arrhythmic events incidence and distribution.
    View this figure
    Figure 3. Kaplan-meier analysis for clinical and arrhythmic events.
    View this figure

    Discussion

    The main finding from this study, which might carry significant clinical implications, is that continuous ECG and HR monitoring by loop recorders might contribute to the early recognition of cardiac rhythm abnormalities contributing to an observed very high incidence of major CV (72%) events. Such high event risk is known to occur in patients with LVEF < 40% who are not eligible for ICD implant within 6 months after an HF hospitalization. The study population, despite its small size, was representative of the clinical reality: elderly patients, prevalently NYHA class II, with a mean CHADS2 score of 3. The high morbidity detected in the study was not unexpected, but the clinical information provided by the CARRYING ON for HF study deserves specific attention. We can conjecture that the appropriate use of remote monitoring as part of a more comprehensive approach to such patients may decrease the observed high re-hospitalization rate after an AHF. The CARRYING-ON HF study was designed to record events but did not prescribe any specific intervention. It is, however, reasonable to believe that the early detection of rhythm and conduction disturbances by ILR will allow clinicians to react appropriately in a more timely manner, avoiding quick progression of the disease and worst outcomes.

    In fact, half of the study population had an AHF during the study period. These patients were being treated with a suboptimal HF medical strategy and the continuous monitoring led to subsequent optimal medical titration for HF, arrhythmia management, and stroke prevention. This should be understood in view of the CRYSTAL AF study [9] indicating that stroke may be the first clinical manifestation of AF. The analysis of the time to first combined event (Figure 3) and of the cumulative combined events provides further important information. The first is that a 6-month-long monitoring period is not sufficient to detect a first significant event in all the patients who are bound to have them. Secondly, beyond 6 months a small proportion of combined events occurred possibly because of the fatal event on one side and the optimization of patient management induced by the monitoring device on the other. In this context it is noteworthy that 16/18 (89%) patients had an optimal nocturnal HR (less < 70 bpm). Thus, it may not be incidental that the only 2 patients with an overnight inappropriate HR had clinical events while this occurred in only 3/16 (19%) patients with controlled nocturnal HR. This observation is indeed coherent with the predictive value of HR and its circadian variation [10-11]. Furthermore the ILR detected episodes of sustained VT that met the criteria for 2 CRT-D implants. In a third case, a detection of a life-threatening event occurred: nocturnal long pauses (> 8 sec) were discovered. In this patient, the concomitant presence of LVEF < 35% and the AV conduction disturbance led to a single chamber ICD implant. These 3 cases were diagnosed by the ILR and allowed the timely intervention that prevented a potential life-threatening event.

    Limitations

    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.

    Conclusions

    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.

    Acknowledgments

    We would like to thank Sabrina De Cicco and Melissa Gioia for their support in data collection. We also thank Alessio Marseglia and Marco Vimercati for the management of data. This work was supported by Medtronic Italia.

    Conflicts of Interest

    Alessandra Gentili and Silvia Bisetti are Medtronic employees. There are no other conflicts of interest.

    References

    1. Fonarow GC, ADHERE Scientific Advisory Committee. The Acute Decompensated Heart Failure National Registry (ADHERE): opportunities to improve care of patients hospitalized with acute decompensated heart failure. Rev Cardiovasc Med 2003;4 Suppl 7:S21-S30. [Medline]
    2. McMurray John J V, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Lip Gregory Y H, Task Force for the DiagnosisTreatment of AcuteChronic Heart Failure 2012 of the European Society of Cardiology, Ben Lamin Hisham A, ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012 Aug;14(8):803-869. [CrossRef] [Medline]
    3. Di LA, Scherillo M, Maggioni AP, Acquarone N, Ambrosio GB, Annicchiarico M, et al. Current presentation and management of heart failure in cardiology and internal medicine hospital units: a tale of two worlds--the TEMISTOCLE study. Am Heart J 2003 Oct;146(4):E12. [CrossRef] [Medline]
    4. Oliva F, Mortara A, Cacciatore G, Chinaglia A, Di LA, Gorini M, et al. Acute heart failure patient profiles, management and in-hospital outcome: results of the Italian Registry on Heart Failure Outcome. Eur J Heart Fail 2012 Nov;14(11):1208-1217. [CrossRef] [Medline]
    5. Tavazzi L, Senni M, Metra M, Gorini M, Cacciatore G, Chinaglia A, IN-HF (Italian Network on Heart Failure) Outcome Investigators. Multicenter prospective observational study on acute and chronic heart failure: one-year follow-up results of IN-HF (Italian Network on Heart Failure) outcome registry. Circ Heart Fail 2013 May;6(3):473-481 [FREE Full text] [CrossRef] [Medline]
    6. O'Connor CM, Stough WG, Gallup DS, Hasselblad V, Gheorghiade M. Demographics, clinical characteristics, and outcomes of patients hospitalized for decompensated heart failure: observations from the IMPACT-HF registry. J Card Fail 2005 Apr;11(3):200-205. [Medline]
    7. Cleland J G F, Swedberg K, Follath F, Komajda M, Cohen-Solal A, Aguilar JC, van Gilst W H, Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J 2003 Mar;24(5):442-463 [FREE Full text] [Medline]
    8. Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M, Greenberg BH, et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry. J Am Coll Cardiol 2007 Aug 21;50(8):768-777 [FREE Full text] [CrossRef] [Medline]
    9. Sanna T, Diener H, Passman RS, Di LV, Bernstein RA, Morillo CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014 Jun 26;370(26):2478-2486. [CrossRef] [Medline]
    10. Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010 Sep 11;376(9744):875-885. [CrossRef] [Medline]
    11. Adamson PB, Smith AL, Abraham WT, Kleckner KJ, Stadler RW, Shih A, InSync III Model 8042Attain OTW Lead Model 4193 Clinical Trial Investigators. Continuous autonomic assessment in patients with symptomatic heart failure: prognostic value of heart rate variability measured by an implanted cardiac resynchronization device. Circulation 2004 Oct 19;110(16):2389-2394 [FREE Full text] [CrossRef] [Medline]


    Abbreviations

    ACE: angiotensin-converting enzyme
    AF: atrial fibrillation
    AHF: acute heart failure
    ARB: angiotensin receptor blocker
    AV: atrioventricular
    bpm: beats per minutes
    CAD: coronary artery disease
    CARRYING ON for HF: The CARdiac RhYthm monitorING after acute decompensatiON for Heart Failure
    CRT-D: cardiac resynchronization therapy with defibrillator back-up device
    CV: cardiovascular
    ECG: electrocardiogram
    HF: heart failure
    HR: heart rate
    ICD: implantable cardioverter defibrillator
    ILR: implantable loop recorder
    IV: intravenous
    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
    VT: ventricular tachycardia


    Edited by G Eysenbach; submitted 26.02.15; peer-reviewed by F Leyva; comments to author 23.10.15; revised version received 18.11.15; accepted 28.01.16; published 26.04.16

    ©Emilio Vanoli, Andrea Mortara, Paolo Diotallevi, Giuseppe Gallone, Barbara Mariconti, Edoardo Gronda, Alessandra Gentili, Silvia Bisetti, Giovanni Luca Botto. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 26.04.2016.

    This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included.