Edited by: Gaetano Santulli, University of Naples Federico II, Italy
Reviewed by: Alessandro Capucci, Università Politecnica delle Marche, Italy; Gaetano Santulli, University of Naples Federico II, Italy; Uma Mahesh R. Avula, University of Michigan, USA
*Correspondence: Deirdre M. Mooney, Cardiovascular Institute, Maine Medical Center, Richards 8, 22 Bramhall Street, Portland, ME 04102, USA
This article was submitted to Cardiac Electrophysiology, a section of the journal Frontiers in Physiology
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Heart failure (HF) is a costly, challenging and highly prevalent medical condition. Hospitalization for acute decompensation is associated with high morbidity and mortality. Despite application of evidence-based medical therapies and technologies, HF remains a formidable challenge for virtually all healthcare systems. Repeat hospitalizations for acute decompensated HF (ADHF) can have major financial impact on institutions and resources. Early and accurate identification of impending ADHF is of paramount importance yet there is limited high quality evidence or infrastructure to guide management in the outpatient setting. Historically, ADHF was identified by physical exam findings or invasive hemodynamic monitoring during a hospital admission; however, advances in medical microelectronics and the advent of device-based diagnostics have enabled long-term ambulatory monitoring of HF patients in the outpatient setting. These monitors have evolved from piggybacking on cardiac implantable electrophysiologic devices to standalone implantable hemodynamic monitors that transduce left atrial or pulmonary artery pressures as surrogate measures of left ventricular filling pressure. As technology evolves, devices will likely continue to miniaturize while their capabilities grow. An important, persistent challenge that remains is developing systems to translate the large volumes of real-time data, particularly data trends, into actionable information that leads to appropriate, safe and timely interventions without overwhelming outpatient cardiology and general medical practices. Future directions for implantable hemodynamic monitors beyond their utility in heart failure may include management of other major chronic diseases such as pulmonary hypertension, end stage renal disease and portal hypertension.
Cardiovascular disease remains the leading cause of death in the United States and worldwide (Lim et al.,
To contain costs and standardize management of patients hospitalized for ADHF, the Centers for Medicare and Medicaid Services have recently introduced regulations to withhold or reduce payments for unnecessary hospitalizations for HF (
The recent development and clinical trials of implantable hemodynamic monitoring devices hold promise to reduce HF hospitalizations, with the potential to improve patient outcomes. The limited but emerging supportive evidence is encouraging further efforts to improve the patient experience with this clinically challenging medical condition. Leading experts in this field have acknowledged the difficulty of conducting clinical trials using cardiac monitoring embedded with therapeutic management to effect “hard” clinical outcomes and endpoints (Abraham et al.,
Early and accurate identification of impending and active ADHF is of paramount importance. Daily weight monitoring is a low-cost, easily accessible method of monitoring HF patients both in and out of the hospital. Unfortunately, weight as a reference value is easily confounded by changes in diet and muscle mass that are not related to intravascular volume status or filling pressures (Wolfel,
A gold standard measure of congestion in HF is not overall volume status (Verbrugge et al.,
Advancement in medical microelectronics and the advent of device-based diagnostics have been developed to enable monitoring of ambulatory HF patients (Table
OptiVol® Fluid Status Monitoring system (Medtronic, Inc., USA) | Ambulatory HF surveillance in patients who also meet indication for ICD therapy | Approved Nov 2004 | Intrathoracic impedance and heart rate variability | Pectoral muscle region | Patients without an indication for ICD therapy or limited thoracic venous access |
Chronicle® ICD and Chronicle® implantable hemodynamic monitor (Medtronic, Inc., USA) | Ambulatory HF surveillance in patients who also meet indication for ICD therapy | Not approved | RV systolic pressure, RV diastolic pressure (an estimate of PADP), maximum change in pressure over time (dP/dt and –dP/dt) | Right ventricle | Patients without an indication for ICD therapy or limited thoracic venous access |
HeartPod® (St Jude Medical, Inc., USA) | Ambulatory HF surveillance | Not approved | Mean left atrial pressure | Left atrium | Patients unable to perform Valsalva maneuvers and maintain an airway pressure >39 mmHg for 8 s (required for periodic device calibration) |
CardioMEMS™ HF System (CardioMEMS, Inc./St Jude Medical, Inc., USA) | Ambulatory surveillance in HF patients with NYHA III symptoms who have preserved EF or reduced EF on OMT, who have had a HF hospitalization in the previous year | Approved May 28, 2014 | Systolic, diastolic, and mean pulmonary artery pressure | Left pulmonary artery (ideally, basal segmental branch) | Based on CHAMPION trial criteria, patient should not have any of the following: History of recurrent (>1) pulmonary embolism or deep vein thrombosis Inability to tolerate a right heart catheterization Recent major cardiovascular event (e.g., myocardial infarction, stroke) within 2 months of screening visit Recent CRT implanted ≤ 3 months prior to enrollment eGFR < 25 ml/min who are non-responsive to diuretic therapy or who are on chronic renal dialysis High likelihood of undergoing heart transplantation within 6 months of screening visit Congenital heart disease or mechanical right heart valve(s) Known coagulation disorders Hypersensitivity or allergy to aspirin, and/or clopidogrel |
Early investigational, implantable heart function monitoring devices piggybacked on the existing implantable cardioverter defibrillator (ICD) technology which had already established the safety of right ventricular pacing leads and was being used in the target population. Early devices used innovative transvenous lead technology to provide mixed venous oxygen saturation and pressures in the right ventricle (RV) (Ohlsson et al.,
Intrathoracic impedance monitoring was also evaluated as an adjunct to monitoring heart failure patients with an indication for an ICD or cardiac resynchronization therapy defibrillator (CRT-D) (Braunschweig et al.,
Ambulatory monitoring of intrathoracic impedance has not had the clinical impact that was initially anticipated, with statistically non-significant results from several contemporary trials (Conraads et al.,
In contrast to prior efforts that combined HF monitoring therapies with therapeutic EP devices, the left atrial pressure (LAP), and pulmonary artery pressure (PAP) ambulatory heart failure monitoring implantable devices were developed as purely diagnostic devices (Figures
Device | HeartPOD® | CardioMEMS™ |
Access | Venous (femoral and subclavian vein) | Venous (usually femoral) |
Approach | Transseptal puncture | Via PA |
Accessories | Brockenbrough needle through 8 Fr sheath, 11 Fr delivery sheath in LA | 12 Fr introducer sheath, dilators with access guidewire, 110-cm PA catheter, 0.018′′ x 260–300 cm fixed core guidewire with straight or angled tip |
Intraprocedural anticoagulation | Heparin 5000 IU, intravenous | None |
Imaging | Fluoroscopy, echocardiography (including TEE, TTE, ICE) | Fluoroscopy, pulmonary arteriography |
Method and location of sensor deployment | Cinching and fixation of device anchors to inter-atrial septum | Release of preloaded sensor from over-the-wire delivery catheter |
Associated implantable components | Coil antenna and lead | None |
Duration of procedure | >1 h | 20 min |
Device interrogation | Transcutaneous detection of implanted sensor lead-antenna coil signal using handheld patient advisory module (PAM) | Transcutaneous detection of sensor-released energy in response to radiofrequency pulse from patient electronics unit |
Post-procedural antithrombotics | Aspirin and warfarin for 30 days, then aspirin indefinitely | Aspirin and P2Y12 inhibitor (clopidogrel) for 1 month, then aspirin indefinitely; warfarin may substitute for aspirin after the first month if chronic anticoagulation therapy is required |
Duration of implantation | Lifelong | Lifelong |
Monitoring of PAP has been used for decades by cardiologists to detect early signs of HF in the intensive care setting (Rutherford et al.,
The Chronicle features a programmable device that bears resemblance to a pacemaker pulse generator, which is implanted to process and store information from the pressure sensor near the tip of the transvenous lead (Bourge et al.,
The device characteristics and key aspects of deployment of the HeartPOD and CardioMEMS are summarized in Table
CardioMEMS is a battery-free, leadless sensor (15 mm × 3 mm) consisting of a coil and capacitor encased in silicone, with a nitinol wire loop at each end of the sensor (Figure
Patients enrolled in the CHAMPION trial were asked to make daily measurements of their PAPs using their portable electronic unit and a special pillow containing an antenna to take daily sensor readings which are transmitted through a modem or cellphone to a secure patient database (Adamson et al.,
Both the HeartPOD and CardioMEMS systems use a physician-guided self-management model that is intuitive and conceptually sound. However, experts in the field have universally acknowledged the challenges in conducting implantable monitoring trials to demonstrate impacts on clinical outcomes, particularly with how the interrogated physiologic data are handled (Abraham et al.,
When using surrogate measures to direct therapy, it is crucial to understand exactly what is being measured. While mean PAP and LAP are both considered adequate surrogates for filling pressures, they are two different measurements and neither is the gold standard measurement (LVEDP). The PCWP is often considered to reflect left ventricular preload and pulmonary capillary hydrostatic pressure, however, there is ongoing debate about the validity of this assumption in the setting of various conditions including chronic pulmonary disease, mechanical ventilation and pulmonary venous scarring. In principal, the LAP would be a more accurate measurement as it is physically and physiologically closer to the gold standard, LVEDP, however it is more invasive to measure. A brief literature review did not reveal any studies comparing the three measurements simultaneously, however there are a few studies comparing LAP and PCWP. In 1962, the PAP, PCWP, and LAP measurements of 11 patients with either clinically normal hearts or suspected mitral valve disease were studied with right heart catheterization in a control state, during a norepinephrine infusion, and during positive and negative intraalveolar pressures (Luchsinger et al.,
With IHM, it is not only the sites from which data are collected but the manner in which they are recorded, stored and reported. In the HOMEOSTASIS trial, subjects were requested to make two LAP measurements a day with additional measurements during symptoms (Troughton et al.,
As already seen with implantable cardiovascular devices, there is a wealth of data that can be harnessed through minimally invasive means and transmitted to a secure data repository via remote wireless technology. Newer implantable cardiac monitoring devices for HF offer the ability to provide individualized data trends and ideally predict clinical events before they occur. However, isolated device alerts need to be used in conjunction with other clinical data to avoid overutilization of health care resources and increased hospitalizations. Successful translation of remote device based monitoring into successful clinical management of these patients will require simple prospectively validated algorithms that indicate how to use raw data from individual devices to make timely and appropriate changes in clinical management without overburdening staff. At this time, despite a wealth of smaller studies evaluating these devices (Table
Fluid accumulation status trial (Abraham et al., |
Evaluate the sensitivity and unexplained detection rate associated with changes in intrathoracic impedance and with changes in daily weight and to compare the performance of these two measures | • Primary outcome: number of subjects with at least 30 days of daily impedance measurements; |
Multicenter non-randomized, prospective, double-blinded investigation | Increased sensitivity and decreased unexplained alarms in comparison to weight based protocol | • Subjects with one of the following ICDs: InSync Marquis™, InSync II Marquis™, Marquis® DR, or InSync III Marquis™ placed in the upper part of the left or right side of their chest |
• Enrolled in another clinical study |
|
OptiVol fluid index predicts acute decompensation of heart failure with a high rate of unexplained events (Yang et al., |
Compare unplanned healthcare evaluation for a patient detected audible device alerts with or without proof of cardiac decompensation | Primary outcome: signs and symptoms of HF on physical examination and serologic evaluation | Prospective observational single site study | OptiVol fluid index had high sensitivity and high unexplained detection rate | Consecutive patients at a single center with HFREF (≤ 35%) NYHA III–IV on OMT for ≥3 months undergoing implantation of either a CRT-D (InSync Marquis 7298; Concerto C174AWK) or an ICD (Virtuoso VR D164VWC; Virtuoso DR D164AWG) from Sep. 2010 to Oct. 2012 | • Life expectancy of less than 1 year |
|
Program to access and review trending information and evaluate correlation to symptoms in patients with heart failure (Partners-HF) (Whellan et al., |
Evaluate predictive ability of a monthly review of HF device diagnostic data to identify patients at higher risk for HF hospitalizations within 30 days | • Primary outcome: occurrence of HF related adverse event. |
Prospective multi-center observational cohort study | Monthly review of HF device diagnostic data to identify patients at increased risk for HF hospitalizations within 30 days | • Meet ICD indications |
• Acute MI, CABG or PTCA /stent within the last month |
|
Diagnostic outcome trial in heart failure DOT-HF (Van Veldhuisen et al., |
All-cause mortality or hospitalization for HF (time to first event) | • Primary endpoint: composite of all-cause mortality or heart failure hospitalization. |
Randomized open-label trial | Trial terminated early owing to slow enrolment and technological improvements; |
• HF NHYA II–IV |
• Post-heart transplant or actively listed on the transplant list and reasonable probability of undergoing transplantation in the next year |
|
Comparison of a radiofrequency-based wireless pressure sensor to Swan-Ganz catheter and echocardiography for ambulatory assessment of pulmonary artery pressure in heart failure (Verdejo et al., |
Correlation of PAP between wireless monitoring, PA catheterization and echocardiography at 0 and 60 days | Evaluate the accuracy of a new HF sensor, CardioMEMS, for PAP monitoring compared with PA catheterization and echocardiography in ambulatory HF patients at 0 and 60 days post-implantation | Single arm open enrolment with independent blind operators recording device measure-ments | Wireless PA monitoring correlated well with PA catheter and echocardio-graphic measurements | NYHA II–IV patients referred for ADHF with normal ventilation/perfusion lung scan and normal tricuspid regurgitation signal on echocardiography | • Recent ACS, CABG, or PTCA within last 3 months |
|
CardioMEMS heart sensor allows monitoring of pressure to improve outcomes in NYHA class III heart failure patients (CHAMPION) trial (Abraham et al., |
6-month HF hospital admission rate | • Primary outcomes: rate of HF hospitalizations, and freedom from device failures |
Prospective, multicenter, randomized, single-blind clinical trial | Patients allocated to the treatment arm had a significant reduction in HF related hospitalizations (84 vs. 120, HR 0.72, 95% confidence interval 0.60–0.65, |
• HF (HFpEF or HFrEF) ≥3 months |
• History of recurrent (>1) pulmonary embolism or deep vein thrombosis |
|
Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in HFpEF (Adamson et al., |
6-month hospital readmission rate | 6-month hospital readmission rate | Subgroup from a prospective, multicenter, randomized, single-blind clinical trial | 50% reduction in hospitalization, more changes in diuretic and vasodilator therapies | See CHAMPION trial | See CHAMPION trial | |
The reducing decompensation events utilizing intracardiac pressures in patients with chronic heart failure (REDUCEhf) trial (Adamson et al., |
Primary efficacy end point of HF hospitalizations, ED visits, or urgent clinic visits | Primary outcome: HF-related events (defined as hospitalizations >24 h or hospitalizations < 24 h requiring intravenous HF therapy, ED visits, or urgent clinic visits requiring IV therapy for HF) Primary safety end point: freedom from system-related complications at 6 months | Prospective, randomized, single blind (subject), parallel-controlled trial | Trial and enrollment stopped early due to lead failures in previous trials | • At least 18 years old |
• Existing implantable CRM device (except a single-chamber ICD being considered for upgrade to a Chronicle ICD) |
|
Chronicle offers management to patients with advanced signs and symptoms of heart failure (COMPASS-HF) (Bourge et al., |
Primary end points included failure, and reduction in the rate of HF-related events (hospitalizations and emergency or urgent care visits requiring intravenous therapy), freedom from system-related complications, freedom from pressure-sensor | • Primary outcome: efficacy of designated treatment strategies by demonstrating a reduction in the rate of all HF events in the treatment group compared to the control group |
Prospective, multicenter, randomized, single-blind (subject), parallel-controlled trial | The Chronicle group had a non-significant 21% lower rate of all HF-related events compared with the control group ( |
• NYHA III or IV |
• Likely to be transplanted within 6 months from randomization or will remain hospitalized until transplantation |
|
Direct left atrial pressure monitoring in ambulatory heart failure patients: initial experience with a new permanent implantable device (Ritzema et al., |
LAP correlation with simultaneous PCWP at 12 weeks | • Primary outcome: LAP correlation with simultaneous PCWP at 12 weeks |
Multicenter, non-randomized, open-label feasibility clinical trial (first human experience with a permanently implantable, direct LAP monitoring system) | Ambulatory monitoring of direct LAP with a new implantable device was well tolerated, feasible, and accurate at a short-term follow-up | • Established HF |
• Prior atrial septal surgery |
|
Hemodynamically guided home self-therapy in severe heart failure patients (HOMEOSTASIS) trial (Troughton et al., |
LAP correlation with simultaneous PCWP at 3 and 12 months | Primary endpoints: LAP correlation with simultaneous PCWP at 3 and 12 months; freedom from Major Adverse Cardiac and Neurological Events at 6 weeks | Prospective, multicenter, observational open-label registry | LAP was highly correlated with simultaneous PCWP tracing; 82 out of 84 devices successfully implanted; 95% freedom from device failure | • Age >18 and < 85 |
• Intractable HF with resting symptoms despite maximal medical therapy or active listing for cardiac transplantation (< 6 months' survival expected) |
|
• Life expectancy < 1 year from malignancy, primary pulmonary hypertension, renal, hepatic, or neurological condition, etc |
|||||||
Left atrial pressure monitoring to optimize heart failure therapy (LAPTOP-HF) (Maurer et al., |
Plan for |
Safety and clinical effectiveness of a physician-directed, patient self-management therapeutic strategy based on LAP measured twice daily by a standalone implantable sensor or CRT-D compatible sensor, compared with a control group receiving OMT | • Primary outcome: reduction in relative risk of HF hospitalization |
Prospective, multicenter, randomized, controlled clinical trial | Ongoing, not recruiting participants | • Have ischemic or non-ischemic cardiomyopathy with either a history of reduced or preserved LVEF and HF for at least 6 months |
• Age < 18 years |
Future directions for remote implantable PAP and LAP devices are broad. In cardiac patients, one can easily imagine the role for these devices in better understanding exercise physiology. They could also aid in clarifying the hemodynamics in particularly challenging outpatients such as those with difficult to assess pulmonary pressures by echocardiography (e.g., rheumatic mitral valve disease, severe pulmonary hypertension, morbidly obese patients.) Furthermore, in advanced HF patients with known arrhythmias, there can be a role to assess the clinical impact of supraventricular arrhythmias such as atrial fibrillation and ventricular arrhythmias, as well as addressing the question of whether these rhythm disturbances are causal or secondary to ADHF. Additionally, with the pressure to avoid indwelling lines, invasive procedures and overburdening intensive care units, pre-existing internal devices that monitor filling pressures could facilitate the management of these particularly high risk patients when admitted for both cardiac and non-cardiac issues, including perioperative hemodynamic and fluid management.
In advanced HF patients with left ventricular assist devices (LVAD) who are recurrently admitted with symptoms of congestion and fluid overload, LAP and PAP monitors may potentially help to discern elevated left sided filling pressures from other causes of dyspnea, and volume overload (e.g., chronic kidney disease progression, hypoalbuminemia, protein-losing enteropathy). However, further clinical review and evaluation still may be necessary to exclude a failing right ventricle in response to LVAD placement and manage other non-cardiac etiologies for recurrent hospitalizations. These devices may also be able to detect low filling pressures in patients with LVADs who urgently need increased intravascular volume in order for optimal device function and cardiac output. It remains to be seen whether regulatory agencies and transplantation societies will endorse the use of implantable LAP or PAP monitors as an alternative to indwelling PA catheters in the pre-heart transplant setting, with the intent to obviate the need for hospitalization in the intensive care unit and periodic replacement of PA catheters that are associated with procedural and other risks including line infection, sepsis, and thromboembolism.
There are also innumerable non-cardiac scenarios in which continuous assessment of cardiac hemodynamics and filling pressures would be invaluable. A recently published substudy of the CHAMPION trial found that of the 217 patients who did not meet criteria for pulmonary hypertension during the implantation right heart catheterization, 48.8% (
The review was initially conceived of and manuscript outlined by all authors. DM prepared the first draft in collaboration with EF. RD and DS provided substantial revisions and contributions. DS contributed Figure
Rahul N. Doshi has served as a consultant for St. Jude Medical, Inc. David M. Shavelle is a consultant and received research support from St Jude Medical, Inc. Deirdre M. Mooney and Erik Fung declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
1CMS.gov.
2CardioMEMS HF System Post-Approval Study. NCT02279888.
3U.S. Food and Drug Administration announcement, recently-approved devices.