Implantable Hemodynamic Monitoring for Heart Failure Patients

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 70, NO. 3, 2017

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2017.05.052

REVIEW TOPIC OF THE WEEK

Implantable Hemodynamic Monitoring for Heart Failure Patients William T. Abraham, MD,a Leor Perl, MDb,c,d

ABSTRACT Rates of heart failure hospitalization remain unacceptably high. Such hospitalizations are associated with substantial patient, caregiver, and economic costs. Randomized controlled trials of noninvasive telemedical systems have failed to demonstrate reduced rates of hospitalization. The failure of these technologies may be due to the limitations of the signals measured. Intracardiac and pulmonary artery pressure–guided management has become a focus of hospitalization reduction in heart failure. Early studies using implantable hemodynamic monitors demonstrated the potential of pressure-based heart failure management, whereas subsequent studies confirmed the clinical utility of this approach. One large pivotal trial proved the safety and efficacy of pulmonary artery pressure–guided heart failure management, showing a marked reduction in heart failure hospitalizations in patients randomized to active pressure-guided management. “Next-generation” implantable hemodynamic monitors are in development, and novel approaches for the use of this data promise to expand the use of pressure-guided heart failure management. (J Am Coll Cardiol 2017;70:389–98) © 2017 by the American College of Cardiology Foundation.

H

eart failure is a leading cause of morbidity

by 2030 (6). Two-thirds of the cost of heart failure

and mortality, and it results in a substantial

care is attributable to managing episodes of acute

economic burden to the health care system.

decompensation in the hospital. A reduction of heart

It is particularly characterized by a very high rate of

failure hospitalizations is thus a major focus of the

hospital admission and readmission. Heart failure is

Centers for Medicare and Medicaid Services, and is

the primary diagnosis in more than 1 million hospital-

currently considered a major unmet clinical need.

izations annually in the United States alone (1), and it is associated with the highest rate of hospital read-

LIMITATIONS OF CURRENT HEART FAILURE

missions when compared with all other medical or

MONITORING SYSTEMS

surgical causes of hospitalization (2). Importantly, the number of decompensation events predicts

Current attempts to estimate changes in volume sta-

increased rates of morbidity and mortality in patients

tus and, in turn, the risk for impending heart failure

with heart failure, independent of age and renal

exacerbation are mostly dependent upon identifying

function (3,4). Despite advancements in diagnostic

worsening heart failure signs and symptoms and

and therapeutic modalities, these rates have not

changes in body weight. However, these signals

changed in recent years (5). In terms of financial

appear late and are relatively unreliable (i.e., insen-

burden, the costs of heart failure in the United States

sitive) markers of clinical status in patients with heart

are currently estimated at just over $30 billion a year,

failure. Daily measurement of body weight, for

and they are expected to exceed $70 billion annually

example, has a sensitivity of only 9% for the

Listen to this manuscript’s audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.

From the aDepartments of Medicine, Physiology, and Cell Biology, Division of Cardiovascular Medicine, and the Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio; bCardiology Department, Rabin Medical Center, Petah Tikva, Israel; cSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and the dDivision of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California. Dr. Abraham has received consulting fees from Medtronic, St. Jude Medical, and Vectorious Medical Technologies. Dr. Perl has received consulting fees from Vectorious Medical Technologies. Manuscript received May 23, 2017; accepted May 24, 2017.

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Implantable Hemodynamic Monitoring

ABBREVIATIONS

development of a new heart failure exacer-

combined

AND ACRONYMS

bation (7,8). Although blood tests, such as

telemonitoring, including daily electronic collection

B-type natriuretic peptide, are useful in

of blood pressure, heart rate, symptoms, and weight.

distinguishing heart failure from other cau-

Centralized

ses of shortness of breath in patients who are

reviews, protocolized actions, and telephone calls to

already presenting to the emergency depart-

patients. A total of 1,437 patients were randomized to

ment (9), they have yet to be proven helpful

the intervention group or to usual care. The primary

in the ongoing management of patients with

outcome was readmission for any cause within

Association

chronic heart failure (10). Moreover, heart

180 days after discharge. Secondary outcomes were

PAP = pulmonary artery

failure therapy guided by monitoring of

all-cause readmission within 30 days, all-cause mor-

pressure

signs, symptoms, weight, and biomarkers has

tality at 30 and 180 days, and quality of life at 30 and

PCWP = pulmonary capillary

not been shown to improve clinical out-

180 days. With the exception of the change in quality

wedge pressure

comes, even when incorporated into remote

of life over 180 days, none of these endpoints were

RV = right ventricle/ventricular

telemedicine systems.

improved by the intervention. That is, there were no

CIED = cardiac implantable electronic devices

LAP = left atrial pressure LVEDP = left ventricular end-diastolic pressure

NYHA = New York Heart

These

systems

nurses

telephone

conducted

calls

and

telemonitoring

improvements in any of the pre-specified clinical

communication between patients and their medical

outcomes measures in the intervention versus usual

providers with or without electronic data transfer of

care group. Regarding the modest, but statistically

physiological measurements, such as signs, symp-

significant improvement in quality of life observed,

toms, body weight, and other information generally

another randomized controlled trial evaluating a

collected

patient-centered disease management intervention

noninvasive

integrate

coaching

regular

by

generally

health

devices.

Although

a

systematic review published in 2010 (11) showed

failed to confirm any improvement in quality of life

reductions in the rates of death from any cause and in

with a similarly intense noninvasive disease man-

heart failure–related hospitalizations using such

agement program (15). Thus, noninvasive remote

noninvasive

telemedicine systems do not seem to make patients

telemonitoring

systems,

subsequent

randomized controlled telemonitoring trials using

feel better or keep them out of the hospital.

similar systems have failed to confirm these obser-

Once seen as promising, remote monitoring of

vations (12–15). For example, the multicenter ran-

heart failure patients with cardiac implantable elec-

domized

to

tronic devices (CIEDs) has not been proven to reduce

Improve Heart Failure Outcomes) trial examined

controlled

Tele-HF

(Telemonitoring

morbidity or mortality. The use of these devices is

whether telemonitoring would reduce the combined

based on the reported high predictive value of device-

endpoint of readmission or death from any cause

based assessment of physiological parameters, such

among 1,653 patients recently hospitalized for heart

as patient activity level, heart rate variability, and

failure (12). In the treatment group, data was

intrathoracic impedance. These parameters have

collected on a daily basis by telephone, and included

proven to be more sensitive than daily weight moni-

an interactive voice response system that collected

toring in predicting fluid accumulation (16) and useful

information about symptoms and an electronic scale

in risk-stratification of patients with heart failure (17);

that provided measurement of daily weight that was

however, randomized controlled trials using CIED-

reviewed by the patients’ clinicians so that treatment

based heart failure diagnostics have demonstrated

could be adjusted to keep the patient out of the

either no effect or a detrimental effect on clinical

hospital. After 180 days, there were no differences in

outcomes (18,19). The potential role of CIED-based

outcomes between the treatment group and the con-

diagnostics in heart failure is reviewed in more

trol (usual care) group, nor were there any differences

detail elsewhere (20).

in secondary endpoints, such as in the number of hospitalizations or number of days in the hospital.

The failure of these remote monitoring methods may have to do with the type of data collected, rather

More recently, the BEAT-HF (Better Effectiveness

than with the specific idea of remote management. As

After Transition–Heart Failure) randomized clinical

mentioned in the previous text, worsening signs and

trial evaluated a particularly robust approach to

symptoms of heart failure occur late in the natural

noninvasive telemonitoring of patients with heart

history

failure (14). The trial was performed at 6 academic

decompensation and hospitalization. In fact, studies

medical centers in California, all with great interest in

of implanted hemodynamic monitoring systems in

heart

acute

patients with ambulatory heart failure have shown

decompensated heart failure who were 50 years of

that signs, symptoms, and weight change are poor

age or older were enrolled and followed for 180 days

surrogates for ventricular filling pressures, and are not

after discharge from the hospital. The intervention

reliable predictors of impending hospitalization (21).

failure

management.

Patients

with

of

worsening

heart

failure,

leading

to

Abraham and Perl

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Implantable Hemodynamic Monitoring

C ENTR AL I LL U STRA T I O N The Concept of Pressure-Guided Heart Failure Therapy

Abraham, W.T. et al. J Am Coll Cardiol. 2017;70(3):389–98.

(Top) The usual-care approach to heart failure management is depicted, wherein the clinician relies on worsening symptoms and other noninvasive signals, such as weight change, to treat clinical congestion, in the absence of knowledge about pre-symptomatic worsening of hemodynamics (called hemodynamic congestion). Unfortunately, because the manifestations of clinical congestion present late in the course of heart failure decompensation, hospitalization is often inevitable, so the usual-care approach can only be considered as reactive or too late to avert a heart failure hospitalization. (Bottom) By treating hemodynamic congestion during the pre-symptomatic phase of worsening heart failure, a proactive approach to heart failure management is enabled, averting the risk of a future heart failure hospitalization.

To the contrary, increases in ventricular filling

pulmonic valve opening, could estimate the pulmo-

pressures, in both diastolic and systolic heart failure

nary artery diastolic pressure. A first study of this

patients, occur weeks before hospitalization for heart

method, based on micromanometers implanted in the

failure (21). Thus, by targeting day-to-day mainte-

RVs and pulmonary arteries of 10 patients, was done

nance of normal ventricular filling pressures, a heart

as a comparison with conventional pulmonary artery

failure management system using ambulatory intra-

catheter pressure measurement, and showed good

cardiac or pulmonary artery pressure monitoring

correlation (22). Next, 32 patients with heart failure

might succeed in keeping patients out of the hospital

were tested with the implanted device, eventually

where

CIED-based)

called the Chronicle IHM (Medtronic, Inc., Minneap-

approaches have failed (Central Illustration). Several

olis, Minnesota), which collected RV systolic and

approaches to chronic implantable hemodynamic

diastolic

monitoring have been evaluated, and newer sensors

derivatives. During 36 volume-overload events in

and systems are on the horizon.

these patients, RV systolic pressures increased by

other

(noninvasive

and

pressures,

heart

rate,

and

pressure

25% (p ¼ 0.05). There was an increase in pressure in 9

THE CHRONICLE RIGHT VENTRICULAR

of 12 hospitalization events approximately 4 days

PRESSURE MONITORING SYSTEM

before the exacerbation. There was also a 57% reduction (p < 0.01) in admission rate after hemody-

The first major breakthrough in the implantable

namic data was used as an aid in patient management

monitoring device arena was a right ventricular (RV)

(23). This study was followed by the COMPASS-HF

sensor,

(Chronicle Offers Management to Patients with

which,

by

measuring

pressure

during

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Implantable Hemodynamic Monitoring

F I G U R E 1 The Major Components of the CardioMEMS HF System

A

B

C Fixed

Auto From: 03-06-2017 To: 04-09-2017

Date Range: 30 days

90 days

180 days All 140

100

120 80

80 60

40

bpm

mm Hg

100 60

40 20

N

20

N

N 0

0 03-07-2017

05-2016

03-10-2017

06-2016

PA Metrics and Events

03-13-2017

07-2016 PA Systolic Medications

03-16-2017

08-2016

03-19-2017

09-2016

PA Systolic Trend Hospitalizations

03-22-2017

10-2016

PA Mean Notes

03-25-2017

11-2016

PA Mean Trend

03-28-2017

12-2016 PA Diastolic

03-31-2017

01-2017

04-03-2017

02-2017

PA Diastolic Trend

04-06-2017

03-2017

04-09-2017

04-2017

Heart Rate from PA Sensor

Suspect Readings

(A) The MEMS-based pulmonary artery pressure sensor (Abbott, Sylmar, California). (B) The home electronics system that simultaneously powers and interrogates the sensor, relaying pressure data to (C) a secure website for clinician review.

Advanced Signs and Symptoms of Heart Failure)

the treatment group actually had more decompensa-

study, which was the first randomized controlled trial

tion events compared with NYHA functional class IV

for the assessment of implantable hemodynamic

control subjects. These results, and the observation in

monitoring in patients with heart failure (24). A total

this study that high filling pressures precede the

of 274 New York Heart Association (NYHA) functional

appearance of heart failure symptoms and predict

class III and ambulatory class IV patients were ran-

hospitalizations for heart failure, were a motivation

domized to the Chronicle IHM device management

for the next generations of implantable devices.

algorithm versus usual care. There was a nonsignifi-

Several important lessons were learned from the

cant 21% reduction in the combined sum of heart

COMPASS-HF trial: 1) the main hemodynamic variable

failure hospitalizations and emergency department or

that correlated with events was diastolic pulmonary

urgent clinic visits requiring intravenous therapy.

artery pressure (PAP), which usually rose gradually,

However, a retrospective analysis of the time to first

rather than abruptly (21); 2) pressure-guided therapy

HF hospitalization showed a 36% reduction (p ¼ 0.03)

was effective only if physicians actually modified

in the relative risk of heart failure hospitalizations in

therapy in response to PAP, even in the absence of

the treatment group, and the potential efficacy of

signs and symptoms of worsening heart failure (24);

pressure-guided therapy in this study appeared to be

3) the absence of pre-specified pressure targets

greatest in the NYHA functional class III patients. In

allowed clinicians to leave PAPs in a range high above

fact, NYHA functional class IV patients randomized to

normal in many patients; and 4) NYHA functional

Abraham and Perl

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Implantable Hemodynamic Monitoring

class IV patients did not benefit from PAP-guided

37% in the relative risk of heart failure hospitaliza-

heart failure management. In the latter instance,

tions compared with the control group. There was

low glomerular filtration rates and/or diuretic agent

also a significant reduction in PAP, a significant

resistance may have prevented effective outpatient

increase in the number of days alive and out of the

treatment of elevated PAPs, necessitating hospitali-

hospital for heart failure, a significant reduction in

zation for intravenous therapies.

the proportion of patients hospitalized for heart failure, and a significant improvement in quality of

THE CardioMEMS PAP MONITORING SYSTEM

life in treatment versus control patients. Freedom from device- or system-related complications was

To date, the most significant advancement in the

98.6%, and overall freedom from pressure-sensor

arena

failures was 100% (26).

of

implantable

hemodynamic

monitoring

capabilities was taken with a novel, wireless, battery-

An important pre-specified subgroup analysis of

free, PAP monitoring system called the CardioMEMS

the CHAMPION trial demonstrated significant efficacy

HF System (Abbott, Sylmar, California) (Figure 1). In

in patients with heart failure and a preserved ejection

the CHAMPION (CardioMEMS Heart Sensor Allows

fraction (28). Of the 550 patients enrolled in the

Monitoring of Pressure to Improve Outcomes in

CHAMPION study, 119 had left ventricular ejection

NYHA Class III Heart Failure Patients) trial (25,26),

fraction $40% (average: 50.6%). The primary efficacy

550 patients, regardless of left ventricular ejection

endpoint of heart failure hospitalization rate at

fraction, were randomized to 2 groups, one in which

6 months for patients with preserved ejection fraction

the clinicians used daily measurement of PAP in

was 46% lower in the treatment group compared with

addition to standard of care (treatment group;

the control group (p < 0.0001). After an average of

n ¼ 270) versus standard of care alone (control group;

17.6 months of blinded follow-up, the hospitalization

n ¼ 280) to manage patients. The CardioMEMS PAP

rate was 50% lower (p < 0.0001). Other important

sensor, previously shown to be safe (27), requires no

subgroups of CHAMPION patients have been analyzed

leads or batteries, and is concurrently powered and

retrospectively.

interrogated via an external antenna. It is implanted

demonstrate

into a branch of the pulmonary artery during right

PAP-guided heart failure therapy in patients with

heart catheterization, using a specialized delivery

secondary pulmonary hypertension (29) and chronic

system. Pressure applied to the sensor causes

obstructive pulmonary disease (30), and in those with

deflections of the pressure-sensitive surface, result-

a history of myocardial infarction, chronic kidney

Taken

the

together,

safety

and

these

analyses

effectiveness

of

ing in a characteristic shift in the resonant frequency.

disease, and atrial fibrillation. In addition, a recent

Electromagnetic coupling is achieved by an external

report

antenna, which is held against the patient’s body or

extended efficacy of PAP-guided heart failure therapy

embedded in a pillow.

over 18 months of randomized follow-up and the

In

the

CHAMPION

in

examined

the

clinical effect of open access to pressure information for an additional 13 months in patients formerly in the

and

were

control group, demonstrated sustained efficacy and

mandated by protocol to ensure adequate testing of

confirmed the original CHAMPION trial findings (31).

the hypothesis. Patients were considered hyper-

After PAP information became available to guide

volemic and at risk for heart failure hospitalization if

therapy in the control group during open access

their pressures were above the range of 15 to

(mean 13 months), rates of admissions to hospital for

35 mm Hg for systolic PAP, 8 to 20 mm Hg for diastolic

heart failure in the former control group were

PAP, and 10 to 25 mm Hg for mean PAP, and were

reduced by 48% (p < 0.0001), compared with rates of

treated by initiation or intensification of diuretic

admissions in the control group during randomized

agents, initiation or intensification of long-acting

access. Another recent CHAMPION analysis examined

nitrates, and/or initiation or intensification of edu-

the effect of PAP-guided heart failure therapy on

cation regarding dietary salt and fluid restrictions.

30-day readmissions in Medicare-eligible patients,

The primary endpoint was the rate of heart failure

demonstrating a 49% reduction in total heart failure

hospitalization over 6 months. There was a significant

hospitalizations and a 58% reduction in all-cause

reduction of the primary endpoint, from a rate of 0.44

30-day readmissions (32).

algorithms

contrast

which

COMPASS-HF, there were specific pressure targets treatment

and

CHAMPION,

to

suitable

trial

from

that

in the control group to 0.32 in the treatment group

A detailed accounting of the pressure-guided

(relative risk reduction: 28%; p ¼ 0.0002) (26). For the

medication

entire single-blinded follow-up period, which aver-

outcomes in the CHAMPION trial has recently been

aged more than 17 months, there was a reduction of

published (33), and may serve as a guide to the

interventions

that

led

to

improved

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Implantable Hemodynamic Monitoring

“real-world” (post-approval) use of PAP-guided heart

heart failure hospitalization in the CHAMPION trial,

failure management. (In May 2014, the U.S. Food and

other implantable hemodynamic monitoring systems

Drug Administration approved the CardioMEMS HF

are focused on direct measurement of left atrial

System for use in patients with NYHA functional class

pressure (LAP).

III heart failure who had at least 1 heart failure hospitalization in the 12 months before implantation of the device.) Since approval, data on the general use of PAP-guided heart failure management has been accrued. Although results from the ongoing CardioMEMS post-approval study (NCT02279888) are not available, a recent publication reports the general use experience in 2,000 patients (34). Deidentified data from the remote monitoring database were used to examine PAP trends from the first consecutive 2,000 patients with at least 6 months of follow-up. The findings showed that these patients had higher PAPs at baseline and experienced a greater reduction in PAP over time compared with the pivotal CHAMPION clinical trial. In addition, this study showed excellent patient and clinician adherence to the CardioMEMS system, in that patients routinely adhered to the taking of prescribed daily measurements

and

clinicians

responded

by

adjusting

medications to lower PAPs. Another recent evaluation of the post-approval CardioMEMS experience retrospectively studied a cohort of patients undergoing PAP sensor implantation between June 1, 2014, and December 31, 2015, using U.S. Medicare claims data (35). This analysis demonstrated that the use of ambulatory hemodynamic monitoring in clinical practice was associated with reductions in heart failure hospitalizations and in comprehensive heart failure costs.

OTHER PAP MONITORING SYSTEMS

RATIONALE FOR THE DEVELOPMENT OF LAP MONITORING SYSTEMS Presuming that management of LAP or, perhaps more properly stated, LAP as a direct reflection of left ventricular filling pressure is the primary pressure target for the management of heart failure, direct measurement of LAP may potentially provide more clinical information in the management of heart failure than measurement of right-sided pressures or PAPs. Evidence from animals regarding manipulation of pressure and the resultant pulmonary consequences

has

demonstrated

strong

correlation

between increases in LAP and pulmonary congestion. In dogs, a rise in LAP over 11 mm Hg has been directly correlated with interstitial fluid leak (36). In rats, an increase in LAP over 15 cm water inhibits the lungs’ ability to reabsorb fluid by 50% (37). This process is reversible: a decrease in LAP from 15 to 0 cm water results in normalization of lung permeability to solutes and alveolar fluid reabsorption. In assessing left ventricular function in human subjects, LAP was shown to correlate well with left ventricular enddiastolic pressure (LVEDP) when measured at the correct timing (at the “z point,” the foot of the left atrial c-wave) (38). Although all pressures should theoretically be equal during diastole, studies have shown conflicting results. In 1970, an invasive study that measured the relationship between mean LAP and end-diastolic PAP showed a significant correlation between the 2; however, the correlation proved

Other PAP measurement systems are in development.

to be inaccurate when the pulmonary vascular resis-

One such pressure monitoring system is in develop-

tance was elevated (39). Although both systolic and

ment at Medtronic, Inc. (Minneapolis, Minnesota).

diastolic PAP were shown to correlate relatively well

This small, implanted sensor has a battery in the

with pulmonary capillary wedge pressure (PCWP)

capsule and talks through intrabody communication

(38,40,41), in patients with advanced heart failure,

to a Reveal LINQ Insertable Cardiac Monitor device

left- and right-sided filling pressures were found to be

coimplanted in the patient. Together, the 2 devices

mismatched (42,43). Moreover, this discordance was

can monitor not only PAP, but also cardiac arrhyth-

related to an increased risk of poor outcomes (44).

mias, patient activity, and heart rate, among other

Finally, PAP fails to correlate with LVEDP in a variety

physiological trends. The sensor is part of a larger

of acute conditions, including in some patients with

management system that uses Bluetooth technology

acute heart failure (45,46).

and a patient’s cellular phone to provide data to

Importantly, pulmonary hypertension, a common

patients and clinicians, and to improve clinical

condition affecting 25% to 83% of patients with heart

outcomes. Another system appears to be similar to

failure, depending on the population examined, is a

the CardioMEMS HF System, except for a different

significant factor that affects the reliability of PAP

external user interface (Endotronix, Inc., Woodridge,

measurement for estimating left-sided filling pres-

Illinois). Although PAP-guided heart failure therapy

sure. It is critical to know what the pulmonary resis-

was proven to be effective in reducing the risk of

tance is, or more accurately, the gradient between

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Implantable Hemodynamic Monitoring

F I G U R E 2 First- and Second-Generation LAP Sensors

(A) The HeartPOD left atrial pressure monitoring system (Abbott, Sylmar, California), which consists of a lead and a subcutaneous antenna coil. (B) The VLAP left atrial pressure sensor, which includes advanced onboard application-specific integrated circuit–based technologies that incorporate a novel drift compensation mechanism. LAP ¼ left atrial pressure.

diastolic PAP and mean PCWP, because that value is

associated with left ventricular enlargement and

less dependent upon blood flow, stroke volume, and

dysfunction. Earlier studies that directly measured

change in PCWP itself, but will reflect changes in

the degree of mitral regurgitation and LAP showed

compliance and distensibility of the pulmonary

good correlation between the 2 during both angi-

arteries. In fact, tests have shown that there is a high

ography and surgery (51,52). Moreover, although

gradient

(over

the enhanced LAP V-wave is generally not appre-

5 mm Hg) in approximately one-half of all patients

ciated from the PAP waveform, it is readily seen

with heart failure (47–50). This implies, on a physio-

when pressure is measured directly in the left

logical level, that PAP measurement alone may be an

atrium. Another instance is the dynamic rise in

inaccurate indicator of LVEDP for many patients with

LAP seen during cardiac ischemia. In 1 example,

heart failure, especially for those who also experience

the detection of acute ischemia and subsequent

contributing factors, such as lung disease and

revascularization of a coronary artery was on the

thromboembolism. At the very least, any difference

basis of findings from an implanted LAP monitoring

between PAP and LAP must be taken into account in

system (53).

between

PAP

and

mean

PCWP

treatment decisions. It is possible that the frequency and timing of

THE HeartPOD LAP MONITORING SYSTEM

pressure monitoring have an influence on the efficiency of heart failure management according to PAP.

The HeartPOD (Abbott, formerly St. Jude Medical/

Although algorithms based on infrequent or 1-time

Savacor, Inc.), a system that allowed for direct mea-

PAP or PCWP measurement using right heart cathe-

surement of LAP in patients with ambulatory heart

terization seem to be inefficient in improving

failure, was studied over the past decade (54–56).

outcomes (43), daily measurements conducted on an

This system was on the basis of an implantable sensor

outpatient basis can improve outcomes (26), mainly

lead coupled to a subcutaneous antenna coil, a pa-

because they enable identification of a slow rise in

tient advisory module, and remote clinician access

pressure over longer periods of time, the indicator

via

that best correlates with HF hospitalization risk.

(Figure 2). The tip of the sensor system lead was

secure

computer-based

data

management

Finally, there are specific cases in which LAP

implanted transvenously into the left atrium via the

monitoring might contribute valuable information

atrial septum. The implant was powered and interro-

regarding

with

gated through the skin by wireless transmissions from

heart failure. An important example is functional

the patient advisory module. A prospective, observa-

(or

tional,

conditions

secondary)

frequently

mitral

associated

regurgitation,

which

is

first-in-human

study of

this

monitoring

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Implantable Hemodynamic Monitoring

system, using a physician-directed patient self-

information to a web-based database. This data can

management paradigm, demonstrated improved he-

be analyzed with next-generation decision-support

modynamics, symptoms, and outcomes in patients

software systems to extract patient-specific physio-

with advanced heart failure (56). A prospective ran-

logical data, such as heart rate variability, the

domized controlled outcomes study, the LAPTOP-HF

presence of valvular pathologies, early warning for

(Left Atrial Pressure Monitoring to Optimize Heart

arrhythmias, and diastolic and exercise hemody-

Failure Therapy) trial, examined the safety and effi-

namics. In animal studies, the device was implanted

cacy of the system in ambulatory NYHA functional

in a transseptal approach; it was safe, and was

class III patients who either were hospitalized for heart

shown to communicate well with the external

failure during the previous 12 months or had an

belt at depths of up to 30 cm. Another micro-

elevated B-type natriuretic peptide level, regardless of

electromechanical systems–based LAP monitoring

ejection fraction (57). LAP was measured twice daily,

system is implanted surgically, rather than trans-

and LAP-guided therapy was compared with a control

septally (Integrated Sensing Systems, Inc., Ypsilanti,

group receiving optimal medical therapy alone.

Michigan). The surgical implantation approach limits

Randomization to the treatment or control group was

the use of this sensor to patients undergoing cardiac

accomplished using a 1:1 ratio in 3 strata based on the

surgery; thus, it has been evaluated in first-in-man

ejection fraction (left ventricular ejection fraction

studies in patients undergoing implantation of a

>35% or #35%) and the presence of a de novo cardiac

left

resynchronization therapy device indication. Enroll-

surgery.

ment in the LAPTOP-HF trial was stopped early, due to

feasibility of the approach.

a perceived excess of implant-related complications. Preliminary results were presented during a Late Breaking Clinical Trials Session at the 2016 Heart Failure Society of America meeting (58). The overall trial result was negative, demonstrating no reduction in a combined endpoint of recurrent heart failure hospitalizations and complications of heart failure therapy. However, when the results were analyzed using the CHAMPION trial endpoint of recurrent heart failure hospitalizations, the results of the LAPTOP-HF trial were similar to those of CHAMPION. Thus, although not a definitive evaluation of the efficacy of LAP-guided

heart

failure

therapy,

LAPTOP-HF

demonstrated its potential and stimulated ongoing technology development in this arena.

ventricular These

assist

device

studies

have

or

other

cardiac

demonstrated

the

SUMMARY The proximate cause of worsening heart failure leading to hospitalization is an increase in intracardiac pressure and PAP. Noninvasive telemedicine systems and CIED-based diagnostics provide only poor surrogates for these pressure changes, and management based on such systems has failed to reduce the risk of heart failure hospitalization. Newer technologies, such as the CardioMEMS HF system, enable day-to-day remote management of intracardiac pressure and PAP using implantable hemodynamic monitoring systems. In the CHAMPION trial, this approach was shown to significantly reduce the rate of heart failure hospitalizations in patients with heart failure, regardless of their ejec-

OTHER LAP MONITORING SYSTEMS

tion fractions. That is, the efficacy of pressureThe V-LAP system (Vectorious Medical Technologies,

guided therapy was demonstrated in heart failure

Tel Aviv, Israel) is an example of the next generation

patients with either a reduced or a preserved ejec-

of implantable LAP monitoring systems, and uses

tion fraction. In this regard, the CardioMEMS HF

advanced

circuit–

System has revolutionized the management of heart

based technologies. It is a miniature percutaneous

failure by directing attention away from treating

left atrial pressure sensor that is robust, wireless,

signs and symptoms alone to managing the under-

and leadless, and includes a novel drift compensa-

lying cause of symptomatic and worsening heart

tion mechanism. The device is implanted perma-

failure. To date, the reported real-world experience

nently in the septum using a transseptal approach. It

with this system has been encouraging. Additional,

has the advantage of a very low-profile design

more technologically-advanced, implantable hemo-

(14 mm in length and 2.5 mm in diameter). The

dynamic monitoring systems are in development,

application-specific

technology

and newer approaches to the use of this data (such

allows for onboard drift compensation. The system

as a physician-directed, patient self-management

also includes an external wearable belt that remotely

approach)

powers the implant, displays pressure readings

management of patients with heart failure. Such

to

technologies provide a future platform for chronic

the

application-specific

patient,

integrated

and

integrated

circuit

transmits

LAP

waveform

may

yet

again

revolutionize

the

Abraham and Perl

JACC VOL. 70, NO. 3, 2017 JULY 18, 2017:389–98

Implantable Hemodynamic Monitoring

disease management that will allow us to look for other clinical applications of objective data collec-

ADDRESS FOR CORRESPONDENCE: Dr. William T.

tion from within the cardiovascular system as we

Abraham, Division of Cardiovascular Medicine, The

move into the age of connected health, and thus,

Ohio State University, 473 West 12th Avenue, Suite

hopefully

110P,

additionally

reduce

patient

and mortality.

morbidity

Columbus,

Ohio

43210.

E-mail:

william.

[email protected].

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KEY WORDS disease management, hospitalization, patient readmission, pulmonary artery pressure, telemedicine