TITLE:

Home Telemonitoring for the Management of Heart Failure

AUTHOR:

Jeffrey A. Tice, MD Assistant Professor of Medicine Division of General Internal Medicine Department of Medicine University of California San Francisco

PUBLISHER:

California Technology Assessment Forum

DATE OF PUBLICATION:

June 29, 2011

PLACE OF PUBLICATION:

San Francisco, CA

HOME TELEMONITORING FOR THE MANAGEMENT OF HEART FAILURE A Technology Assessment INTRODUCTION The California Technology Assessment Forum (CTAF) was asked to assess the evidence for the use of home telemonitoring devices for the management of heart failure (HF). HF is a common chronic disease that is expensive to manage and subject to frequent episodes of decompensation requiring hospitalization. There is an extensive literature on HF disease management programs, telephone support programs, and home visiting programs that are intended to help patients and their physicians identify worsening heart failure early and take corrective actions in order to avoid hospitalizations and improve patients quality of life. Numerous companies have developed programs and medical devices intended to facilitate home monitoring of patients with HF.

BACKGROUND Heart failure (HF) Heart failure (HF) is a major public health problem in the United States. Over five million patients in this country have HF and 670,000 patients are diagnosed with HF for the first time each year.1 Nearly 300,000 patients die of HF as a primary or contributory cause each year. Survival has improved over time, but the five-year mortality is still approximately 50%.1 The approach that is most commonly used to quantify the degree of functional limitation imposed by HF is one first developed by the New York Heart Association (NYHA).2,3 This system assigns patients to one of four functional classes, depending on the degree of effort needed to elicit symptoms: patients may have symptoms of HF at rest (class IV), on less-than-ordinary exertion (class III), on ordinary exertion (class II), or only at levels of exertion that would limit normal individuals (class I). Medical therapies, such as angiotensin converting enzyme (ACE) inhibitors, beta blockers, and spironolactone, have led to improvements in both symptom control and overall survival in patients with heart failure.4 Implanted devices, such as biventricular pacemakers, also improve survival in appropriate 2

patients.5,6 Despite recent advances in therapy, patients with HF suffer from repeat hospitalizations due to some combination of the progression of their disease, poor adherence to diet and medical therapy, and limited support.7-9 Because of the complexities of self-care and medical care involved in the optimal management of HF, recent guidelines support a multidisciplinary care approach.10-12 Randomized trials have demonstrated that nursing-led multidisciplinary teams focusing on patient and family education about diet and medications combined with close follow-up reduces hospital readmission rates and overall healthcare costs while improving quality of life for patients.13,14 Regular communication between patients with heart failure and their care team is thought to improve outcomes for patients. Home Telemonitoring Devices Telemonitoring is defined by the transmission of physiologic parameters and symptoms from patients at home to their health care provider. For HF, the parameters most frequently measured include the patients weight, blood pressure, heart rate, oxygen saturation, and responses to questions about symptoms. In addition, some devices allow transmission of either one or three lead ECGs for the evaluation of cardiac rhythm, sounds via an electronic stethoscope, and videoconferencing. The goal is to facilitate frequent measurement of these parameters in order to identify changes signaling heart failure decompensation earlier than would have been possible without telemonitoring. Home telemonitoring might be a cost-efficient approach to intensive follow-up of heart failure patients that reduces mortality, hospitalizations, and costs while improving patients quality of life. Prior meta-analyses have suggested that home telemonitoring reduces all-cause mortality and hospitalizations15,16, but the studies included in these and other metaanalyses have been criticized for including many small, poor quality trials in which neither death nor hospitalization was a primary outcome.17,18 TECHNOLOGY ASSESSMENT (TA) TA Criterion 1: The technology must have final approval from the appropriate government regulatory bodies. Electronic monitoring systems used in disease management programs and/or in patient homes under the guidance of a clinician are subject to regulatory oversight by the FDA and generally classified under Class II. The FDA database was searched for the product codes for approved telemonitoring devices with the following results: DRG (Transmitters and Receivers, Physiological Signal, Radiofrequency), DXN (System,

Measurement, Blood-Pressure, Non-invasive), and MWI ((Monitor, Physiological, Patient [Without Arrhythmia Detection or Alarms) with the following results: DRG (Transmitters & Receivers, Physiological Signal, Radiofrequency): 112 products DXN (System, Measurement, Blood Pressure, Non-invasive): 500 products MWI (Monitor, Physiological, Patient (Without Arrhythmia Detection or Alarms): 144 products

The approved products feature capabilities relating to the collection and transmission of patient data to a clinician for nonemergency review including blood pressure, weight, glucose monitoring, and oxygen saturation. TA Criterion 1 is met.

TA Criterion 2: The scientific evidence must permit conclusions concerning the effectiveness of the technology regarding health outcomes. The Medline database, Embase, Cochrane clinical trials database, Cochrane reviews database and the Database of Abstracts of Reviews of Effects (DARE) were searched using the key words telemonitoring, telemonitor, remote patient monitoring, telemedicine, telehealth, telecare, telehomecare, telecardiology, or remote physiological monitoring. The results were crossed with the results from a search on heart failure or congestive heart failure. The search was performed for the period from 1945 through May 2011. The bibliographies of systematic reviews15-25 and key articles were manually searched for additional references. References were also solicited from the manufacturers and local experts. The abstracts of citations were reviewed for relevance and all potentially relevant articles were reviewed in full. This assessment focuses on the randomized comparisons between telemonitoring interventions and either usual care or telephone support. This assessment includes only randomized trials of at least one hundred patients with heart failure. This assessment excludes trials of telephone support alone that did not also include a telemonitoring device and excludes studies that randomized patients without a diagnosis of heart failure. The search identified 917 potentially relevant studies (Figure 1). After elimination of duplicate and nonrelevant references including reviews and non-randomized studies the search identified 21 articles describing 17 trials.26-46 Small trials, trials of mixed populations including patients without HF, nonrandomized trials, ongoing trials, and trials of telephone support without any home device were excluded.4776

Figure 1: Selection of studies for inclusion in review

917 potentially relevant references screened 322 duplicate citations excluded 233 excluded: not randomized; reviews, abstracts only; other interventions 362 abstracts for assessment 95 studies excluded (Editorials, reviews, abstracts, no clinical outcomes) 67 studies for full text review 46 studies excluded: not randomized, < 100 participants, no telemonitoring, mixed population, ongoing study 21 studies included in assessment: 17 RCTs

Level of Evidence: 1 through 5. TA Criterion 2 is met. TA Criterion 3: The technology must improve net health outcomes. The most important outcomes for patients include mortality, the prevention of hospitalizations, and quality of life. Patients with HF have a high mortality and are hospitalized frequently, so these outcomes were routinely measured in the studies described below. Randomized trials Seventeen trials that randomized 6352 patients met the inclusion criteria for this assessment.26-46 The quality of the trials is summarized in Table 1. Table 2 summarizes the characteristics of the studies including a description of the telemonitoring intervention and the control group. Table 3 summarizes the main results of the studies.

Table 1: Randomized trials of telemonitoring in patients with heart failure Methodological Quality Study 2003 Benatar Randomization Yes Allocation concealment NR Groups comparable Yes Outcome assessment blinded NR Follow-up > 80% Yes Intention to treat analysis Yes Quality Fair

2003 Goldberg WHARF 2004 Capomolla

Yes

NR

Yes

Yes

Yes

Yes

Fair

Yes

NR

Yes

NR

NR

Yes

Fair

2005 Cleland TEN-HMS 2008 Balk

Yes

Yes

Yes

NR

Yes

Yes

Fair

Yes

Yes

N, TM fewer HF hospitalization, p=0.001 Yes

NR

NR

Yes

Poor

2008 Dansky

2008 Schwarz

Yes, but baseline differences in group size unexplained Yes

Yes

Yes

NR

NR

Poor

NR

No, TM more education: 82% vs. 49% Yes

NR

Yes

Yes

Poor

2008 Soran HFHC 2009 Dar

Yes

NR

NR

Yes

Yes

Fair

Yes

Yes

Yes

NR

Yes

Yes

Good

Study 2009 Giordano

Randomization Yes

Allocation concealment NR

Groups comparable N, TM more beta blockers: 85% vs. 60%. Yes

Outcome assessment blinded NR

Follow-up > 80% Yes

Intention to treat analysis Yes

Quality Fair

2009 Mortara HHH 2009 Scherr MOBITEL 2010 Tompkins

Yes

Yes

Yes

Yes

Yes

Good

Yes

NR

Yes

NR

Yes

Fair

Yes

NR

Yes

NR

Yes

NR

Poor

2010 Chaudhry Tele HF 2010 Piotrowicz

Yes

NR

Yes

NR

Yes

Yes

Good

Yes

Yes

No, dropout 24% vs. 2.6% Yes

NR

No

NR

Poor

2010 Weintraub PAN-CHF II 2011 Koehler TIM-HF

Yes

Yes

NR

Yes

Yes

Fair

Yes

Yes

Yes

NR

Yes

Yes

Good

Table 2: Randomized trials of telemonitoring in patients with heart failure - Study Characteristics Study 2003 Benatar N 216 Location # sites United States 2 2003 Goldberg WHARF 2004 Capomolla 133 280 United States 18 Italy 1 2005 Cleland TEN-HMS 2008 Balk 214 426 UK, Germany, Netherlands 16 Netherlands 8 2008 Dansky 284 United States 10 2008 Schwarz 168 United States 1 2008 Soran HFHC 2009 Dar 182 315 United States 3 UK 3 WT, BP, HR, O2, SX. Daily UC Yes, at randomization II, III, or IV 95% 6 WT, SX Daily UC Yes, within 6 months 40% 97% 6 HF hospital admission or death Any hospital admission WT, SBP, HR, SX Daily WT, BP, HR, ECG1. Twice daily WT, BP, HR, SX. Daily WT, BP, HR Daily video WT, SX Daily UC Yes, at randomization Yes, within 6 weeks No 81% 12 NR Intervention WT, BP, HR, O2. Daily WT, SX Twice daily Control Home Nurse 912 visits UC Hospitalization for inclusion? Yes, at randomization Yes, at randomization NYHA Class EF for inclusion Adherence NR FU, mo 3 1 endpoint NR

III or IV

35%

98%

Any hospital admission

TS 1/mo Or UC UC

< 40%

81% 1/day 55% 2/day

Any hospital admission or death NR

NR

NR

Usual homecare UC

NR

NR

NR

Yes, at randomization

II, III, or IV

91%

Any hospital admission

Study 2009 Giordano

N 460

Location # sites Italy 5

Intervention ECG1 + TS Weekly WT, SBP, HR, SX Daily WT, BP, HR. Daily WT, BP, HR, O2. Daily WT, SX Daily ECG3, SX Daily WT, BP, HR, SX. Daily WT, BP, HR, ECG1. Daily

Control UC

Hospitalization for inclusion? Yes, at randomization + 1 prior No

NYHA Class II, III, or IV II, III, or IV -

EF for inclusion < 40%

Adherence NR

FU, mo 12

1 endpoint Any hospital admission HF hospital admission Any hospital admission or death NR

2009 Mortara HHH 2009 Scherr MOBITEL 2010 Tompkins

461

Poland, UK, Italy 11 Austria 8

TS monthly UC

40%

81 to 92%

12

120

Yes, within 4 weeks No

95%

390

United States 1 health plan

UC

NR

2010 Chaudhry Tele HF 2010 Piotrowicz

1653

United States 33

UC

Yes, within 30 days Yes, at randomization Yes, within 2 weeks No

90% week 1 55% week 52 NR

Any hospital admission or death NR

152

Poland 1

UC with cardiac rehab TS

II or III

40%

2010 Weintraub SPAN-CHF II 2011 Koehler TIM-HF

188

United States 4

NR

HF hospital admission Death

710

Germany 165

UC

II or III

35%

81%

26

Table 3: Randomized trials of telemonitoring in patients with heart failure - Study outcomes Study 2003 Benatar TM, n Control, n 108 108 2003 Goldberg WHARF 2004 Capomolla 138 142 67 66 2005 Cleland TEN-HMS 2008 Balk 168 TM 173 TS 85 UC 101 113 2008 Dansky 45 TM+V 127 TM 85 UC 51 51 2008 Soran HFHC 2009 Dar 160 155 91 91 CVD Hosp, % NR NR 8% 12% p=.28 NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR Any Hosp, % NR NR 19% 20% p=.28 NR NR 47% 49% 54% p NR NR at the patient level. Total n TM 103 vs. UC 96, p NR 36% 38% 40% p NS 32% 33% p=.90 47% 42% p=.44 36% 25% p=.30 Death, % NR NR 8% 18% p=.003 7% 11% p NR 17% 16% 24%* 9% 7% p NR Not significant, results NR 8% 14% p NR 7% 11% p=.24 NR NR Not significant, results NR 27 27 p=.98 MLHF NR NR p>.50 for MLHF and EQ5D Quality of life 52 58 p=.47, MLHF -28 -23 p=.22 MLHF NR NR NR NR NR P for difference > .6 on SF36 and MLHF HF Hosp, % 12% 22% p<.001 NR NR NR NR 25% 20% 28% p NR NR NR NR NR NR NR NR 19% 24% p=.31 19% 11% p=.01 NR NR NR NR NR 48% 46% p=.66 NR NR Any Hosp or Death, % NR NR ~54% ~62% p NS at 180 days 36% 68% p NR 51% 54% 56% p NR Other Difference in HF hospitalization NS at 12 months

Total event count lower in TM group (32 versus 103, p<.001) NS differences in days lost to hospitalization or death 9.4 7.0 p=.29 Days in hospital

2008 Schwarz

10

Study 2009 Giordano

TM, n Control, n 230 230

CVD Hosp, % 24% 36% p=.006 NR NR NR NR NR NR NR NR NR NR NR NR NR NR 28% 26% p=.58

Any Hosp, % 29% 42% p=.03 30% 35% 36% 35% 17% 31% IRR 0.87 P NS No CI given 49% 47% p=.45 NR NR 54% 53% p=.30 44% 39% p=.29

Death, % 9% 14% p NR NR NR NR NR 0% 2% p NR NR NR 11% 11% p=.88 NR NR 1% 4% p=.21 15% 15% p=.87

Quality of life NR NR NR NR NR NR NR NR NR NR NR NR 70 69 p NS, SF36 NR NR 54 52 p=.30 for SF36 physical functioning at 24 months

HF Hosp, % 19% 32% p=.001 18% 17% 18% 18% NR NR NR NR 27% 27% p=.81 NR NR 13% 32% p=.05 11% 13% p=.32

Any Hosp or Death, % NR NR NR NR NR NR 17% 33% p=.06 NR NR 52% 51% p=.75 NR NR NR NR NR NR

Other -

2009 Mortara HHH 2009 Scherr MOBITEL 2010 Tompkins 2010 Chaudhry Tele HF 2010 Piotrowicz

101 TS+V+ECG 94 TS+V 106 TS 160 UC 66 54 193 197 826 827 77 75

IRR for urgent care visits 1.60 p<.01 -

2010 Weintraub PAN-CHF II 2011 Koehler TIM-HF

95 93 354 356

15% 17% p=.44 for HF hospitalization or death

*Comparisons at 240 days not analyzed statistically, but by Kaplan Meier rank sum test, the telemonitoring and telephone support groups did not differ; the usual care group had significantly worse overall mortality than the other two arms (p=.04).

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Most of the studies were of overall fair to good quality. Most did not describe any allocation concealment and blinding of the outcome assessment was rarely reported. It was not possible to blind the study participants, but the most important outcomes, mortality and hospital admission, were objective and less likely to be biased because patients knew their treatment assignment. Subjective outcomes, such as quality of life questionnaires are more likely to have biased results due to the lack of participant blinding. There was significant heterogeneity in the studies themselves. Almost all of the studies used different devices and measures as part of the telemonitoring intervention. Some had participants take measurements twice a day and others once a day. Most, but not all studies, measured weight and symptoms, but the symptom questions differed between studies. Other measures included blood pressure and heart rate (65%), ECG (24%), oxygen saturation (18%), and video monitoring (6%). Seven of the trials required patients to have a reduced ejection fraction (most commonly 35%). Twelve of the trials required patients to have had a recent hospitalization and seven trials randomized patients as they were being discharged from the hospital. Follow-up varied from three to twenty-six months with only three trials reporting one year outcomes and only one trial reporting outcomes beyond one year. Mortality varied from 2% to 24% in the control arm of the trials, highlighting the variability in the patient populations studied. Mortality was nominally lower in the telemonitoring (TM) group in seven trials, but was at least as high as that of the control group in 4 of the trials. Six trials did not report their mortality data. Similarly, the rate of hospitalization was lower in the TM group in eight trials, but higher in six trials. Because of significant heterogeneity, no meta-analysis was performed. The three largest studies impacting clinical practice are described in detail below.

Trans-European Network Home Care Management System (TEN-HMS) Study The Trans-European Network Home Care Management System (TEN-HMS) study was the first large, multicenter randomized trial to evaluate home telemonitoring for HF.31 The study was implemented at 16 hospitals in the United Kingdom, Germany and the Netherlands. These centers were chosen because they lacked a comprehensive heart failure management program. The study randomized patients hospitalized for heart failure as well as those hospitalized in the six weeks prior to randomization. All patients had an ejection fraction 40% and were taking at least 40 mg of furosemide or an equivalent loop diuretic dose. The study randomized participants in a 2:2:1 ratio to telemonitoring (TM), telephone support (TS), or usual care (UC). Telemonitoring included twice-daily measurement of weight, blood pressure, heart rate, and single lead ECG rhythm. All measures were electronically transmitted to study centers without patients calling or typing in any of the information. Significant changes in any of the measurements triggered nursing 12

review of the data and either counseling of patients or medication changes. Patient in the TM group also received the same telephone support as patient in the TS group. Patients randomized to the telephone support group received a monthly phone call from a nurse who specialized in heart failure care. They were also given a number to call to reach the nurse-specialist, though in emergencies they were instructed to call their primary care provider or the ambulance service. The primary outcome of the study was unusual: days lost due to hospitalization or death during 450 days of follow-up. Symptoms and all-cause mortality were secondary outcomes. The study planned to randomize 500 patients, but it was stopped early by the data safety and monitoring committee because of excess deaths in the usual care group.31 At that time only 426 patients had been randomized and follow-up only allowed evaluation of the primary outcome through 240 days in most patients. Baseline characteristics differed somewhat across the three groups and no statement was made that the characteristics were similar across groups. No p-values were reported for baseline comparisons. Examples of characteristics with large differences included the percentage of women in each group (20% TM, 28% TS, 18% UC), the percentage with prior heart attacks (56% TM, 52% TS, 67% UC), the percentage with EF < 25% (48% TM, 50% TS, 57% UC), and the median brain natriuretic protein (BNP) level (3873 TM, 2909 TS, 2309 UC). The last is almost certainly statistically significant, but would tend to bias the outcomes in favor of the UC group and against the TM group because a higher BNP level is associated with more severe heart failure. During a median of 484 days of follow-up, only four patients were lost to follow-up and an additional 12 did not comply with home telemonitoring. Only 64% of the randomized patients had data available for the originally planned 450 day analysis. At 240 days, there were no statistically significant differences between any of the groups in the primary outcome of days lost to death or hospitalization.31 There was a trend towards 8 fewer days lost in the TM group compared to the TS group and an additional 8 fewer days lost comparing TS to UC. In the subset of patient with data for the primary outcome at 450 days (64% of randomized patients), both the TM and TS groups had lost significantly fewer days compared to the UC group. The difference between the TM and TS group was not significant, but favored the TS group by 6 days. The p-value for differences in mortality was not calculated at any time point, but was consistently lowest in the TS group and highest in the UC group (240 days TM 17%, TS 16%, UC 24%; 450 days TM 34%, TS 31%, UC 51%; overall in study TM 22%, TS 20%, UC 33%). In the TEN-HMS study, telemonitoring reduced mortality compared to usual care.31 However twice daily monitoring of five parameters (weight, systolic and diastolic blood pressure, heart rate, and rhythm) transmitted without patient input was no more effective than monthly telephone support from a nurse that 13

included nursing availability for patient-initiated calls. Mortality was nominally lower in the telephone support group (20.3% versus 21.8%). There was a trend towards fewer days lost to hospitalization or death with TM at 240 days, but this trend was reversed by 450 days. Thus, intensive home telemonitoring that required minimal patient involvement failed to benefit patients any more than monthly telephone support from trained nurses in this study population. Both telemonitoring and telephone support tended to produce better outcomes than usual care.

Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) The Tele-HF study is the largest randomized trial of home telemonitoring that has been published to date.29,30 The study randomized 1653 patients from 33 cardiology practices in the United States to either home telemonitoring or usual care. Home telemonitoring required the patients to call a toll free number once daily and answer five questions on heart failure symptoms, two questions on their general health, and input their weight. A two-question depression scale was completed monthly. Any new heart failure symptoms, depression, or a three-pound change in weight generated a message to the patients clinical site. Staff at the site were required to call the patient to discuss the symptoms or weight change and to document treatment decisions flowing from these calls. The primary endpoint of the study was any death or hospitalization within 180 days of randomization. There were no significant differences between the two groups at baseline.30 The participants median age was 61 years, 42% were female, and 39% were black. Follow-up was 100% for the primary outcome. There were no differences between the two groups in all cause mortality (11.1% versus 11.4%, p=0.88), hospitalization (49% versus 47%, p=0.45), HF hospitalization (27% versus 27%, p=0.81), days in the hospital (7.2 versus 7.0, p=0.27), or the primary outcome: death or any hospitalization (52.3% versus 51.5%, p=0.75) with only the trend in deaths favoring the telemonitoring arm. Using survival analysis, the primary outcome was slightly more common in the telemonitoring group (HR 1.04, 95% CI 0.91 to 1.19). In six reported subgroup analyses, there were significant interactions with sex and NYHA class. Women tended to benefit more than men (HR 0.87 versus 1.18, p for interaction = 0.02) and patients in NYHA Class I or II tended to do better than those in Class III or IV (HR 0.88 versus 1.15, p for interaction = 0.05). There were no significant interactions with age, race, ejection fraction, or site enrollment. The results from the Tele-HF study30 contrast with those from the TEN-HMS study31 described above. In the Tele-HF study, there was absolutely no benefit in the telemonitoring group compared to the usual care group. The authors speculate that it may be the lack of regular communication with a provider that explains 14

the negative results of this study. In a prior, small trial, the same investigators found a 44% reduction in readmission rates in patients with HF who were randomized to an intervention consisting of education and support.13 The intervention also required more of the patients as they were required to enter their weight into the system via the telephone, while the telemonitoring system used in TEN-HMS simply required the patient to get on the scale twice a day: the data was automatically transmitted. The system was underused 16% of patients randomized to telemonitoring never used the system and by the last week of the study, only 55% of the patients were using the system three times a week or more. However, even if only half of the patients were using the system regularly, some trends towards improved outcomes should have been observed if the system was effective. No such trends were observed.

Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial The most recent, large randomized trial to be published was the TIM-HF trial.36,37 The study randomized 710 patients from 165 cardiology, internal medicine, or general medicine practices in Europe to either home telemonitoring or usual care. Home telemonitoring consisted of once daily wireless, automatic transmission of weight, blood pressure, heart rate, and 3-lead ECG data via a wireless personal digital assistant (PDA) to the telemedical center. Daily health status was assessed using the PDA. In addition, patients randomized to the TM group received a personal emergency response system that connected the patient to a physican at the telemedical center in cases of emergency. This system also allowed for live ECG monitoring and oxygen saturation monitoring. The primary endpoint of the study was all-cause mortality. There were no significant differences between the groups at baseline. The participants average age was 67 years, 21% were female, 50% had NYHA Class III symptoms, and their average EF was 27%. Follow-up was 99.7% complete for the primary outcome through a median follow-up of 26 months. There were no differences between the two groups in all cause mortality (TM 15% or 8.43 per 100 person-years versus UC 15% or 8.68 per 100 person years; HR 0.97, 95% CI 0.67 to 1.41, p=0.87). In addition to the primary outcome, there were no significant differences between the two groups for cardiovascular mortality, hospitalization, hospitalization for cardiovascular disease, hospitalization for HF, change in NYHA class or symptoms of depression. The SF-36 physical functioning subscale was higher at the one-year follow-up in the TM group (54.3 versus 49.9, p=0.01), but the difference was no longer significant at two years (53.8 versus 51.7, p=0.30). In contrast to the Tele-HF study, the TIM-HF study automated the transfer of the measured parameters and included blood pressure, heart rate, and a 3-lead ECG tracing in addition to weight. Despite the inclusion of 15

these additional measures, better compliance (81% of patients completed at least 70% of the daily measures), and longer follow-up, the use of TM did not reduce mortality or hospitalizations. Summary Despite initial promise, recent studies of a variety of approaches to home telemonitoring have failed to demonstrate significant benefits when used in patients with heart failure. There was significant heterogeneity in the early trials. The TEN-HMS trial found that telemonitoring was equivalent to monthly telephone support by a trained nurse.31 The two most recent trials (Tele-HF, TIM-HF) meet the current standards for high quality care of patients with HF and were the largest and highest quality trials reviewed.30,36 The results from both studies were definitively negative. Neither study had any important trends towards a reduction in either mortality or hospitalization for the telemonitoring group. TA Criterion 3 is not met.

TA Criterion 4: The technology must be as beneficial as any established alternatives. The management of HF is complex, particularly for patients with advanced disease. A wealth of large, high quality randomized trials have demonstrated that a number of drugs and devices increase long-term survival for patients with heart failure. In addition, multi-disciplinary team care focusing on patient and family education and close follow-up reduces repeat hospitalizations and improves the quality of life for patients hospitalized for worsening heart failure. The two largest randomized trials failed to demonstrate any additional improvements with the addition of home telemonitoring to high quality usual care.30,36 The earlier TEN-HMS trial did find benefits from telemonitoring, but only in patients treated at centers without an organized heart failure management program and telemonitoring in this trial was no better than monthly calls from a nurse. TA Criterion 4 is not met.

TA Criterion 5: The improvement must be attainable outside of the investigational setting. There are a wide variety of telemonitoring systems used in clinical practice across the world. They are designed to be easy for patients to use. However, they do require that systems and personnel be trained

16

and available to rapidly respond to any of the measured parameters that suggest worsening of heart failure. The published multicenter randomized trials as well as the many observational studies suggest that the logistics of telemonitoring are feasible outside of the investigational setting. However, the published data have not demonstrated significant improvements in net health outcomes, so TA criterion 5 is not met. TA Criterion 5 is not met.

CONCLUSION Heart failure is very common, progressive disease with frequent decompensation resulting in hospitalization and death. Approximately half of people diagnosed with heart failure die within five years of the diagnosis. When patients are discharged from hospitalization for heart failure up to 25% are readmitted within one month and 50% are readmitted within six months. Patient and family education about medications, diet, and heart failure combined with frequent follow-up has been shown to significantly reduce readmission and death following hospitalizations for heart failure. Home telemonitoring of signs and symptoms associated with heart failure is a promising approach to intensive follow-up of patients that places fewer demands on patients by decreasing the need for clinic visits and on fewer demands on nursing staff by reducing the need to travel for home visits. This systematic review of the literature identified 17 trials that randomized 6352 patients to evaluate the efficacy of home telemonitoring. The settings, patient populations, interventions, control groups, outcomes and length of follow-up varied widely between the studies. Because of the heterogeneity in the trials and their outcomes, no formal meta-analysis was performed. Two large, high quality trials that randomized 2363 patients were published in the past year (Tele-HF, TIM-HF). One used a simple intervention to capture weight and symptoms once a day using an automated telephone-based system. The second measured similar parameters and added daily blood pressure, heart rate, and ECG measures along with an emergency link to center physicians. Neither study found any benefit to home monitoring compared with usual care. Mortality was 11% in both groups in one study and 15% in both groups in the other study. In both studies, hospitalization rates were slightly higher in the home telemonitoring groups (Tele-HF 49% versus 47%; TIM-HF 44% versus 39%). Thus, there were not even trends in favor of home telemonitoring. There are at least two additional large studies that have yet to be published (TEHAF, OptiLink-HF), but preliminary results from one of the studies were negative. The strongly positive findings in some of the randomized trials suggest that there are subgroups of patients with HF who benefit from some form of telemonitoring. However, the published literature to date does not clearly identify which patients are most 17

likely to benefit and what combination of home monitoring technologies are required to obtain optimal results. Newer, more invasive devices that monitor intracardiac or pulmonary artery pressure are on the horizon and preliminary studies suggest that some of them may reduce heart failure hospitalizations in patients with HF. RECOMMENDATION It is recommended that use of home telemonitoring for patients with heart failure does not meet CTAF TA Criterion 3 through 5 for safety, effectiveness and improvement in health outcomes.

The California Technology Assessment Forum panel voted to accept the recommendation as written.

June 29, 2011 This is the first review of this technology by the California Technology Assessment Forum

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RECOMMENDATIONS OF OTHERS Blue Cross Blue Shield Association (BCBSA) The BCBSA Technology Evaluation Center has not conducted an assessment of home telemonitoring for heart failure patients. Centers for Medicare and Medicaid Services (CMS) CMS does not have a national coverage code (NCD) for remote monitoring or telemonitoring. American Telemedicine Association The American Telemedicine Association did not provide an opinion regarding the use of this technology and no representative provided testimony at the meeting. American College of Cardiology/American Heart Association (ACC/AHA) ACC/AHA 2009 Focused Update on Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult did not mention remote monitoring. National Institute for Clinical Health and Excellence (NICE) The NICE guideline, Management of chronic heart failure in adulst in primary and secondary care from August 2010 stated that further research is required to determine whether monitoring has advantages over specialized multidisciplinary heart failure teams. Heart Failure Society of America (HFSA) The Executive Summary: HFSA 2010 Comprehensive Heart Failure Practice Guideline mentions telemonitoring within the context of disease management programs studies and care delivered in the home. No specific guideline for telemonitoring was mentioned. European Society of Cardiology (ESC) The ESC Guidelines for the management and treatment of acute and chronic heart failure 2008 mentions remote management as an emerging field in HF management programs such as telephone support and the use of telemonitoring equipment. Telemonitoring equipment installed at the patients home typically capture and record heart rate, ECG, oxygen saturation, weight, medication adherence, and blood pressure. However, there is no consensus on which factors should be monitored. 19

ABBREVIATIONS CTAF DARE RCT NR NS RR CI NNT IRR HF TM TS UC FU NYHA WT BP SBP HR SX California Technology Assessment Forum Database of Abstracts of Reviews of Effects Randomized Controlled Trial Not reported Not significant Relative Risk Confidence Interval Number needed to treat Incidence rate ratio Heart failure Telemonitoring Telephone support Usual Care Follow-up New York Heart Association Weight Blood pressure Systolic blood pressure Heart rate Symptoms 20

02 ECG ECG1 ECG3 EF CVD Hosp MLHF EQ5D SF36 Study names WHARF TEN-HMS HHH MOBITEL Tele-HF SPAN-CHF II TIM-HF

Oxygen saturation Electrocardiogram Electrocardiogram, one lead Electrocardiogram, three leads Ejection Fraction Cardiovascular disease Hospitalization Minnesota Living with Heart Failure Questionnaire: quality of life in heart failure EuroQOL 5D: a standard quality of life questionnaire Short Form 36: a standard quality of life questionnaire

Weight Monitoring in Heart Failure Trans-European Network Home Care Management System Home or Hospital in Heart failure MOBIle TELemonitoring in Heart Failure Patients Telemedical Interventional Monitoring in Heart Failure Specialized Primary and Networked Care in Heart Failure II Telemedical Interventional Monitoring in Heart Failure

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