Mark F. Aaron

Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial

BACKGROUND Results of previous studies support the hypothesis that implantable haemodynamic monitoring systems might reduce rates of hospitalisation in patients with heart failure. We undertook a single-blind trial to assess this approach. METHODS Patients with New York Heart Association (NYHA) class III heart failure, irrespective of the left ventricular ejection fraction, and a previous hospital admission for heart failure were enrolled in 64 centres in the USA. They were randomly assigned by use of a centralised electronic system to management with a wireless implantable haemodynamic monitoring (W-IHM) system (treatment group) or to a control group for at least 6 months. Only patients were masked to their assignment group. In the treatment group, clinicians used daily measurement of pulmonary artery pressures in addition to standard of care versus standard of care alone in the control group. The primary efficacy endpoint was the rate of heart-failure-related hospitalisations at 6 months. The safety endpoints assessed at 6 months were freedom from device-related or system-related complications (DSRC) and freedom from pressure-sensor failures. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. FINDINGS In 6 months, 83 heart-failure-related hospitalisations were reported in the treatment group (n=270) compared with 120 in the control group (n=280; rate 0·31 vs 0·44, hazard ratio [HR] 0·70, 95% CI 0·60-0·84, p<0·0001). During the entire follow-up (mean 15 months [SD 7]), the treatment group had a 39% reduction in heart-failure-related hospitalisation compared with the control group (153 vs 253, HR 0·64, 95% CI 0·55-0·75; p<0·0001). Eight patients had DSRC and overall freedom from DSRC was 98·6% (97·3-99·4) compared with a prespecified performance criterion of 80% (p<0·0001); and overall freedom from pressure-sensor failures was 100% (99·3-100·0). INTERPRETATION Our results are consistent with, and extend, previous findings by definitively showing a significant and large reduction in hospitalisation for patients with NYHA class III heart failure who were managed with a wireless implantable haemodynamic monitoring system. The addition of information about pulmonary artery pressure to clinical signs and symptoms allows for improved heart failure management. FUNDING CardioMEMS.

Transition From Chronic Compensated to Acute Decompensated Heart Failure Pathophysiological Insights Obtained From Continuous Monitoring of Intracardiac Pressures

Background— Approximately half of all patients with chronic heart failure (HF) have a decreased ejection fraction (EF) (systolic HF [SHF]); the other half have HF with a normal EF (diastolic HF [DHF]). However, the underlying pathophysiological differences between DHF and SHF patients are incompletely defined. The purpose of this study was to use echocardiographic and implantable hemodynamic monitor data to examine the pathophysiology of chronic compensated and acute decompensated HF in SHF versus DHF patients. Methods and Results— Patients were divided into 2 subgroups: 204 had EF <50% (SHF) and 70 had EF ≥50% (DHF). DHF patients had EF of 58±8%, end-diastolic dimension of 50±10 mm, estimated resting pulmonary artery diastolic pressure (ePAD) of 16±9 mm Hg, and diastolic distensibility index (ratio of ePAD to end-diastolic volume) of 0.11±0.06 mm Hg/mL. In contrast, SHF patients had EF of 24±10%, end-diastolic dimension of 68±11 mm, ePAD of 18±7 mm Hg, and diastolic distensibility index of 0.06±0.04 mm Hg/mL (P<0.05 versus DHF for all variables except ePAD). In SHF and DHF patients who developed acute decompensated HF, these events were associated with a significant increase in ePAD, from 17±7 to 22±7 mm Hg (P<0.05) in DHF and from 21±9 to 24±8 mm Hg (P<0.05) in SHF. As a group, patients who did not have acute decompensated HF events had no significant changes in ePAD. Conclusions— Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.

CHAMPION∗ Trial Rationale and Design: The Long-Term Safety and Clinical Efficacy of a Wireless Pulmonary Artery Pressure Monitoring System

BACKGROUND Decompensated heart failure (HF) is associated with unacceptable morbidity and mortality risks. Recent implantable technology advancements allow frequent filling pressure monitoring and provide insight into HF pathophysiology and a new tool for HF management. METHODS The CHAMPION trial is a prospective, multicenter, randomized, single-blind clinical trial testing the hypothesis that HF management guided by frequently assessed pulmonary artery pressures is superior to traditional methods. A total of 550 subjects with New York Heart Association (NYHA) functional class III HF were enrolled at 64 sites in the United States. All subjects received the CardioMEMS HF sensor as a permanent pulmonary artery implant and were randomized to the treatment or the control group before discharge. The treatment group received traditional HF management guided by hemodynamic information from the sensor. The control group received traditional HF disease management. Safety endpoints include freedom from device/system-related complications and freedom from HF sensor failure at 6 months. The efficacy endpoint is a reduction in the rate of HF-related hospitalizations in the treatment group versus the control group at 6 months. CONCLUSIONS The CHAMPION trial will investigate the safety and clinical efficacy of the CardioMEMS hemodynamic monitoring system and may establish this management strategy as a new paradigm for the medical management of patients with symptomatic HF.

Continuous Hemodynamic Monitoring in Patients With Mild to Moderate Heart Failure: Results of the Reducing Decompensation Events Utilizing Intracardiac Pressures in Patients With Chronic Heart Failure (REDUCEhf) Trial

Clinical trial results support the hypothesis that implantable hemodynamic monitoring (IHM) systems may reduce hospitalizations among patients with chronic heart failure (HF). The Reducing Decompensation Events Utilizing Intracardiac Pressures in Patients With Chronic Heart Failure (REDUCE hf  ) study was a prospective, randomized, multicenter, single-blinded trial that enrolled patients with New York Heart Association class II or III symptoms, an indication for an implantable cardioverter-defibrillator (ICD), and a previous HF hospitalization. A combination IHM-ICD was implanted and patients were randomly assigned to a treatment group in which hemodynamic information was used or a control group in which hemodynamic information was not available. Patients were followed for 12 months to evaluate the primary efficacy end point of HF hospitalizations, emergency department visits, or urgent clinic visits. The trial was designed to enroll 1300 patients, but stopped at 400 patients because of IHM lead failures experienced from previous trials. A total of 202 treatment patients and 198 controls were randomized for 12-month follow-up. The primary safety end point was met, but the rate of HF equivalents was not different between groups. REDUCE hf was unable to test clinical efficacy end points adequately. The device combining IHM-ICD technology was safe and functioned appropriately. Patients at high risk for decompensated HF have high baseline filling pressures and demonstrate consistent increases as the process of congestion worsens to the time of hospitalization.

Application of Implantable Hemodynamic Monitoring in the Management of Patients With Diastolic Heart Failure : A Subgroup Analysis of the COMPASS-HF Trial

BACKGROUND Nearly half of all patients with chronic heart failure (HF) have a normal ejection fraction (EF), and abnormal diastolic function (ie, diastolic heart failure [DHF]). However, appropriate management of DHF patients remains a difficult and uncertain challenge. METHODS AND RESULTS The Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial was designed to evaluate whether an implantable hemodynamic monitor (IHM) was safe and effective in reducing the number of heart failure-related events (HFRE) in patients with chronic HF. The current study presents data on a prespecified and planned subgroup analysis from the COMPASS-HF trial: 70 patients with an EF > or =50% (ie, DHF). As such, this represents a subgroup analysis of the COMPASS-HF Trial. DHF patients were randomized to IHM-guided care (treatment) vs. standard care (control) for 6 months. All 70 patients received optimal medical therapy, but the hemodynamic information from the IHM was used to guide patient management only in the treatment group. The HFRE rate in DHF patients randomized to treatment was 0.58 events/6 months compared with DHF patients randomized to control, which was 0.73 events/6 months; this represented a 20% nonsignificant reduction in the overall HFRE rate in the treatment group (95% CI = -46, 56, P = .66). There was a 29% nonsignificant reduction in the relative risk of a HF hospitalization in the DHF patients randomized to treatment compared with DHF patients randomized to control (95% CI = -69, 70, P = .43). CONCLUSIONS The IHM was shown to be safe and was associated with a very low system-related and procedure-related complication rate in DHF patients. However, in this subgroup analysis limited to 70 DHF patients, the addition IHM-guided care did not significantly lower the rate of HFR events. The results of this subgroup analysis in DHF patients, for whom there are currently no proven, effective management strategies, will be used to design future studies defining the effects of IHM-guided care in patients with DHF.

Safety and accuracy of a wireless pulmonary artery pressure monitoring system in patients with heart failure.

BACKGROUND Implantable hemodynamic monitoring to guide heart failure (HF) therapy is a promising area of active research. The goal of this investigation was to evaluate the safety and technical performance of a novel wireless pulmonary artery pressure monitoring system in 17 patients with symptomatic HF. METHODS The monitoring system consists of a sensor, delivery catheter, interrogator, and home monitoring device. The HF sensor was implanted into a distal branch of the pulmonary artery. Pulmonary artery pressures were monitored using the external device, which powers the HF sensor and transmits the hemodynamic data from the patients home to a secure Internet database. The accuracy of the system was assessed by comparison with standard right heart catheterization (RHC). RESULTS The HF sensor was safely and successfully implanted in all patients. Agreement between the HF sensor and RHC for systolic, diastolic, and mean pulmonary artery pressures was excellent, with correlation coefficients of 0.94, 0.85, and 0.95, respectively (all P < .0001). Using Bland-Altman plots, the average differences for systolic, diastolic, and mean pulmonary artery pressures for the HF sensor vs RHC were -4.4 ± 0.3, 2.5 ± 1.0, and -0.8 ± 1.3 mm Hg, respectively. There were no serious device-related adverse events. A postmortem analysis of the HF sensor in a patient who died 12 months after implant demonstrated complete endothelialization and no evidence of thrombosis. CONCLUSIONS This trial supports the safety and accuracy of this pulmonary artery pressure monitoring system in patients with HF and the conduct of randomized trials of implantable hemodynamic monitoring in HF, using this system.

Effects of Exercise on Left Ventricular Systolic and Diastolic Properties in Patients With Heart Failure and a Preserved Ejection Fraction Versus Heart Failure and a Reduced Ejection Fraction

Background—The purpose of the current study was to define exercise-induced changes in indices of left ventricular (LV) systolic and diastolic properties in patients with chronic heart failure (HF), compare these changes in patients with HF and a reduced ejection fraction (EF) versus HF and a preserved EF, and compare the hemodynamic responses to activities of daily living with symptom-limited upright exercise. Methods and Results—Subjects with HF and a preserved EF (n=8) and subjects with HF and a reduced EF (n=5) underwent symptom-limited Naughton protocol treadmill exercise tests. Implantable hemodynamic monitor data and echocardiographic data were obtained before exercise and at peak exercise. Implantable hemodynamic monitor data were obtained during activities of daily living during a 24-hour time period. In patients with HF and a reduced EF, limited exercise time (639±164 seconds) was associated with a marked rise in right ventricular systolic, diastolic, and estimated pulmonary artery diastolic (ePAD) pressures and an increase in LV end diastolic volume (EDV). LV systolic properties, namely EF, end systolic elastance, stroke work, and preload recruitable stroke work, all decreased. The ePAD/EDV ratio increased; to a large extent, this was dependent on an increase in EDV. By contrast, in HF and a preserved EF, limited exercise time (411±128 seconds) and the marked rise in right ventricular systolic, diastolic, and ePAD pressures were associated with no change in LV EDV. LV systolic properties increased or were unchanged; ePAD/EDV ratio increased during exercise, but the increase was independent of a change in EDV. The ranges of right ventricular systolic, diastolic, and ePAD pressures during activities of daily living were higher than the ranges of these values during the exercise stress test. Conclusions—Although exercise limitations were similar between HF and a reduced EF and HF and a preserved EF, there were significant differences in exercise-induced changes in LV systolic and diastolic properties. These differences likely reflect the different pathophysiologies of these clinical syndromes of HF.

Hemodynamic Factors Associated With Acute Decompensated Heart Failure: Part 1—Insights into Pathophysiology

BACKGROUND The purpose of this study was to determine which pressure-based hemodynamic factor was most closely associated with the transition from chronic compensated to acute decompensated heart failure. METHODS AND RESULTS Intracardiac pressures were retrospectively examined in 274 heart failure patients using an implantable hemodynamic monitor. The relationship between the development of a heart failure-related event (HFRE) and 3 pressure variables were analyzed: peak estimated pulmonary artery diastolic pressure (ePAD) at the time of an HFRE, change in ePAD from baseline to peak pressure, and the product of ePAD pressure and time (P×T) calculated as the area under the pressure-versus-time curve from baseline to peak pressure. Patients without an HFRE served as control subjects. Peak ePAD and change in ePAD were not closely associated with the development of an HFRE. In patients with an HFRE, P×T was 221 ± 130 mm Hg·days with only 4% of the P×T values <60 mm Hg·days. In contrast, in patients without an HFRE, the P×T was 5 ± 23 with only 4% of the P×T values >60 mm Hg·days. CONCLUSIONS The product of small increases in pressure that occur over an extended period of time (P×T) is the pressure-based hemodynamic factor most closely associated with the transition to acute decompensated heart failure.

Cost-benefit Analysis of Extended Antifungal Prophylaxis in Ventricular Assist Devices

This report defines the cost and benefit of extended antifungal prophylaxis in ventricular assist device (VAD) patients (pts). Extended antifungal prophylaxis is defined as prophylaxis with fluconazole or nystatin that is given until pts are extubated and off antibiotics. These data are compared with that obtained from earlier VAD patients who only received antifungal drugs for documented fungal colonization or infection. Thirty-six patients had HeartMate (n = 15) or Thoratec (n = 21) VADs between 1989 and 1997. Cultures positive for fungus (n = 52 cultures) were obtained from 16 of 36 patients (44% of patients). Forty-three fungal cultures were in the preprophylaxis and nine in the postprophylaxis era. There was one death attributable to fungal sepsis in the preprophylaxis era and none in the postprophylaxis era. The total cost of antifungal drugs in the preprophylaxis era was

Fungal infections in ventricular assist devices.

3,840 over 1,498 patient days (PD) (mean