Jordan Bauman

Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial

BACKGROUND In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group. METHODS The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. FINDINGS Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55-0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40-0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported. INTERPRETATION Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure. FUNDING St Jude Medical Inc.

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.

Interventions Linked to Decreased Heart Failure Hospitalizations During Ambulatory Pulmonary Artery Pressure Monitoring

OBJECTIVES This study sought to analyze medical therapy data from the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in Class III Heart Failure) trial to determine which interventions were linked to decreases in heart failure (HF) hospitalizations during ambulatory pulmonary artery (PA) pressure-guided management. BACKGROUND Elevated cardiac filling pressures, which increase the risk of hospitalizations and mortality, can be detected using an ambulatory PA pressure monitoring system before onset of symptomatic congestion allowing earlier intervention to prevent HF hospitalizations. METHODS The CHAMPION trial was a randomized, controlled, single-blind study of 550 patients with New York Heart Association functional class III HF with a HF hospitalization in the prior year. All patients undergoing implantation of the ambulatory PA pressure monitoring system were randomized to the active monitoring group (PA pressure-guided HF management plus standard of care) or to the blind therapy group (HF management by standard clinical assessment), and followed for a minimum of 6 months. Medical therapy data were compared between groups to understand what interventions produced the significant reduction in HF hospitalizations in the active monitoring group. RESULTS Both groups had similar baseline medical therapy. After 6 months, the active monitoring group experienced a higher frequency of medications adjustments; significant increases in the doses of diuretics, vasodilators, and neurohormonal antagonists; targeted intensification of diuretics and vasodilators in patients with higher PA pressures; and preservation of renal function despite diuretic intensification. CONCLUSIONS Incorporation of a PA pressure-guided treatment algorithm to decrease filling pressures led to targeted changes, particularly in diuretics and vasodilators, and was more effective in reducing HF hospitalizations than management of patient clinical signs or symptoms alone.

Pulmonary hypertension related to left heart disease: Insight from a wireless implantable hemodynamic monitor

BACKGROUND Pulmonary hypertension (PH) associated with left heart disease (World Health Organization [WHO] Group II) has previously been linked with significant morbidity and mortality. However, there are currently no approved therapies or hemodynamic monitoring systems to improve outcomes in WHO Group II PH. METHODS We conducted a retrospective analysis of the CHAMPION trial of an implantable hemodynamic monitor (IHM) in 550 New York Heart Association (NYHA) Functional Class III HF patients, regardless of left ventricular ejection fraction (LVEF) or heart failure (HF) etiology. We evaluated clinical variables, changes in medical therapy, HF hospitalization rates and survival in patients with and without WHO Group II PH. RESULTS Data were obtained for 314 patients (59%) who had WHO Group II PH. Patients without PH were at significantly lower risk for mortality than PH patients (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.19 to 0.52, p < 0.0001). PH patients had higher HF hospitalization rates than non-PH patients (0.77/year vs 0.37/year; HR 0.49, 95% CI 0.39 to 0.61, p < 0.001). In patients with and without PH, ongoing knowledge of hemodynamic data resulted in a reduction in HF hospitalization for PH patients (HR 0.64, 95% CI 0.51 to 0.81, p = 0.002) and for non-PH patients (HR 0.60, 95% CI 0.41 to 0.89, p = 0.01). Among PH patients, there was a reduction in the composite end-point of death and HF hospitalization with ongoing knowledge of hemodynamics (HR 0.74, 95% CI 0.55 to 0.99, p = 0.04), but no difference in survival (HR 0.78, 95% CI 0.50 to 1.22, p = 0.28). CONCLUSIONS WHO Group II PH is prevalent and identifies HF patients at risk for adverse outcomes. Ongoing knowledge of hemodynamic variables may allow for more effective treatment strategies to reduce the morbidity of this disease.

Pulmonary Artery Pressure–Guided Heart Failure Management Reduces 30-Day Readmissions

Background—This study examines the impact of pulmonary artery pressure–guided heart failure (HF) care on 30-day readmissions in Medicare-eligible patients. Methods and Results—The CardioMicroelectromechanical system (CardioMEMS) Heart Sensor Allows Monitoring of Pressures to Improve Outcomes in New York Heart Association Class III Heart Failure Patients (CHAMPION) Trial included 550 patients implanted with a permanent MEMS-based pressure sensor in the pulmonary artery. Subjects were randomized to a treatment group (uploaded pressures were made available to investigators) or a control group (uploaded pressures were not made available to investigators). This analysis focuses on the 245 Medicare-eligible subjects for whom compliance with daily transmissions was 93% compared with 88% for the overall population. Medications were changed more often in the treatment group using pressure information compared with the control group using symptoms and daily weights alone. During the 515 days follow-up after implant, the overall rate of HF hospitalizations was 49% lower in the treatment group (60 HF hospitalizations, 0.34 events/patient-year) compared with control (117 HF hospitalizations, 0.67 events/patient-year; hazard ratio 0.51, 95% confidence interval 0.37–0.70; P<0.0001). Of the 177 HF hospitalizations, 155 qualified as an index HF hospitalization. All-cause 30-day readmissions were 58% lower in the treatment group (0.07 events/patient-year) compared with 0.18 events/patient-year in the control group (hazard ratio 0.42, 95% confidence interval 0.22–0.80; P=0.0080). Conclusions—Pulmonary artery pressure–guided HF management in Medicare-eligible patients led to a 49% reduction in total HF hospitalizations and a 58% reduction in all-cause 30-day readmissions. Clinical Trial Registration—http://www.clinicaltrials.gov. Unique identifier: NCT00531661.

Limitations of right heart catheterization in the diagnosis and risk stratification of patients with pulmonary hypertension related to left heart disease: Insights from a wireless pulmonary artery pressure monitoring system

BACKGROUND Although right heart catheterization (RHC) remains the gold standard for assessment of hemodynamics in patients with known or suspected pulmonary hypertension (PH), there are significant limitations to this type of assessment. The current study evaluates the limitations of RHC in the diagnosis of left heart-related PH (World Health Organization group II) among patients enrolled in the CHAMPION trial and discusses insights into patient risk from home implantable hemodynamic monitor (IHM) data that were not identified at the time of the RHC procedure. METHODS The CHAMPION trial enrolled 550 New York Heart Association functional class III patients who had been hospitalized for heart failure (HF) in the previous year, regardless of left ventricular ejection fraction or etiology. Hemodynamic data obtained during baseline RHC were compared with IHM data obtained during the first week of home readings. HF hospitalization rates and mortality were analyzed to assess patient risk. RESULTS The study population for this retrospective analysis comprised 537 patients with available IHM data. For 320 patients in the PHRHC group, home IHM data confirmed the RHC findings with similar mean pulmonary artery pressures obtained from both methods (36 mm Hg vs 36 mm Hg, p = 0.5066). However, of the 217 patients in the No PHRHC group, 106 patients (48.8%) exhibited PH based on the home IHM data (PHIHM group). The remaining 111 patients (51.2%) in the No PHRHC group had no evidence of PH on the IHM data (No PHIHM group). Patients in the No PHRHC/PHIHM group had significantly higher mean PA pressures on IHM than patients in the No PHRHC/No PHIHM group (31 mm Hg vs 18 mm Hg, p < 0.0001). Patients in the No PHRHC/No PHIHM group had significantly lower HF hospitalization rates than patients in the No PHRHC/PHIHM group (0.25 vs 0.49, incidence rate ratio = 0.51, 95% confidence interval = 0.33-0.77, p = 0.0007). CONCLUSIONS Using only RHC, World Health Organization group II PH may be significantly under-diagnosed. In patients with left-sided HF and resting mean PA pressure ≤25 mm Hg during RHC, more frequent PA pressure monitoring using an IHM device can provide additional data for improved diagnosis and patient risk stratification compared with a single RHC alone.