Intracardiac Pressures Measured Using an Implantable Hemodynamic Monitor: Relationship to Mortality in Patients With Chronic Heart Failure.

BACKGROUND: The purpose of this analysis was to examine whether implantable hemodynamic monitor-derived baseline estimated pulmonary artery diastolic pressure (ePAD) and change from baseline ePAD were independent predictors of all-cause mortality in patients with chronic heart failure. METHODS AND RESULTS: Retrospective analysis used data from 3 studies (n=790 patients; 216 deaths). Baseline ePAD was related to mortality using a multivariable model including baseline and demographic data. Changes in ePAD defined as change from baseline to 6 months and from baseline to 14 days before death or exit from study were related to subsequent mortality, and analysis was adjusted for baseline ePAD. Area under the pressure versus time curve during 180 days before death or exit from study was related to mortality. Baseline ePAD, independent of other covariates, was a significant predictor of mortality (hazard ratio=1.07; 95% confidence interval=1.05-1.09; P<0.0001). Change in ePAD was an independent predictor of mortality (hazard ratio=1.07; 95% confidence interval=1.05-1.100; P=0.0008). Increased ePAD of 3, 4, or 5 mm Hg from baseline to 6 months was associated with increased mortality risk of 23.8%, 32.9%, or 42.8%. Change in ePAD from baseline to 14 days before death or exit from study was higher in patients who died (3.0±8 versus 1.7±10 mm Hg; P=0.003). Area under the pressure versus time curve in the final 180 days before death or exit from study was higher in patients who died versus those alive at end of study (185±668 versus 17±482 mm Hg.days; P=0.006). CONCLUSIONS: Implantable hemodynamic monitor-derived baseline ePAD and change from baseline ePAD were independent predictors of mortality in chronic heart failure patients.

Prediction of All-Cause Mortality Based on the Direct Measurement of Intrathoracic Impedance.

BACKGROUND: Intrathoracic impedance-derived OptiVol fluid index calculated using implanted devices has been shown to predict mortality; direct measurements of impedance have not been examined. We hypothesized that baseline measured impedance predicts all-cause mortality; changes in measured impedance result in a change in the predicted mortality; and the prognostic value of measured impedance is additive to the calculated OptiVol fluid index. METHODS AND RESULTS: A retrospective analysis of 146,238 patients within the Medtronic CareLink database with implanted devices was performed. Baseline measured impedance was determined using daily values averaged from month 6 to 9 after implant and were used to divide patients into tertiles: group L = low impedance, ≤ 65 ohms; group M = medium impedance, 66 to 72 ohms; group H = high impedance, ≥ 73 ohms. Change in measured impedance was determined from values averaged from month 9 to 12 post implant compared with the 6- to 9-month values. OptiVol fluid index was calculated using published methods. All-cause mortality was assessed beginning 9 months post implant; changes in mortality was assessed beginning 12 months post implant. Baseline measured impedance predicted all-cause mortality; 5-year mortality for group L was 41%, M was 29%, and H was 25%, P < 0.001 among all groups. Changes in measured impedance resulted in a change in the predicted mortality; the prognostic value of measured impedance was additive to the OptiVol fluid index. CONCLUSIONS: Direct measurements of intrathoracic impedance using an implanted device can be used to stratify patients at varying mortality risk.

Hemodynamic factors associated with acute decompensated heart failure: part 2--use in automated detection.

BACKGROUND: The purpose of this study was to develop an automated surveillance system, using pressure-based hemodynamic factors that would detect which patients were making the transition from compensated to decompensated heart failure before they developed worsening symptoms and required acute medical care. METHODS AND RESULTS: Intracardiac pressures in 274 patients with heart failure were measured using an implantable hemodynamic monitor (IHM) and were analyzed in a retrospective manner. An automated pressure change detection (PCD) algorithm was developed using the cumulative sum method. The performance characteristics of the PCD algorithm were defined in all patients who developed a heart failure-related event (HFRE); patients without HFRE served as controls. Optimal PCD threshold values were chosen using a receiver operator curve analysis. Each of the pressures measured with the IHM were evaluated using the PCD analysis. All had sensitivities ≥80% and false-positive rates <4.7/patient-year; however, estimated pulmonary artery diastolic pressure (ePAD) had the best performance. An ePAD based on the optimized PCD threshold of 6.0 yielded a sensitivity of 83% and a false-positive rate of 4.1/patient-year for detecting patients making the transition from compensated to decompensated heart failure. These performance characteristics were not significantly different for patients with an ejection fraction > vs. <50%, estimated glomerular filtration rate > vs. <60 mL/min/1.73 m(2), or age > vs. <60 years. CONCLUSIONS: The automated PCD algorithm had high sensitivity and acceptable false-positive rates in detecting the development of decompensated heart failure before the patient developed worsening symptoms and required acute medical care. These data support the development of a prospective study to examine the utility of adding an automated PCD algorithm to IHM-based management strategies to prevent decompensated heart failure.

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.

Chronic ambulatory intracardiac pressures and future heart failure events.

BACKGROUND: Intracardiac pressures in heart failure (HF) have been measured in patients while supine in the hospital but change at home with posture and activity. The optimal level of chronic ambulatory pressure is unknown. This analysis compared chronic intracardiac pressures to later HF events and sought a threshold above which higher pressures conferred worse outcomes. METHODS AND RESULTS: Median pressures were measured every 24 hours from continuous 8-minute segments for 6 months after implantation of hemodynamic monitors in 261 patients with New York Heart Association class III-IV HF in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure Study. Baseline and chronic daily medians of estimated pulmonary artery diastolic, right ventricular systolic, and right ventricular end-diastolic pressures were compared with HF event rate. The group median for chronic 24-hour estimated pulmonary artery diastolic pressure was 28 mm Hg (excluding 7 days before and after events). Despite weight-guided management, events occurred in 100 of 261 (38%) patients. Event risk increased progressively with higher chronic 24-hour estimated pulmonary artery diastolic pressure, from 20% at 18 mm Hg to 34% at 25 mm Hg and 56% at 30 mm Hg, with similar relations for right ventricular pressures. Among patients with baseline day median estimated pulmonary artery diastolic pressures of ≥25 mm Hg, event risk was 1.10/6 mo when they remained chronically ≥25 mm Hg, but risk fell to 0.47 when 24-hour pressures declined to <25 mm Hg for more than half of the days. CONCLUSIONS: Despite current management, many patients with advanced HF live on a plateau of high filling pressures from which later events occur. This risk is progressively higher with higher chronic ambulatory pressures. It is not known whether more targeted intervention could maintain lower chronic ambulatory pressures and better outcomes.

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.

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 >or=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.

Continuous hemodynamic monitoring in patients with pulmonary arterial hypertension.

BACKGROUND: The purpose of this study was to determine whether an implantable hemodynamic monitor (IHM) could be used to judge the response of pulmonary arterial hypertension (PAH) patients to changes in therapy. METHODS: A prospective, non-randomized, multi-center study evaluated physical examination, functional class, echocardiography, brain natriuretic peptide (BNP) levels, exercise capacity assessed by 6-minute walk and cardiopulmonary exercise tests, and quality of life at baseline and at 12 weeks. IHM measurements were continuously available to clinicians between clinic visits. Based on a priori, pre-specified analyses, the relationships between hemodynamic values, PAH treatments and clinical parameters were tracked in an observational fashion. RESULTS: Twenty-four PAH patients underwent IHM implantation prior to a change in PAH therapy. IHM data identified 13 of the 15 patients who improved their 6-minute walk distance by >30 m at 12 weeks (+48 +/- 65 m, p < 0.05), whereas the others walked less (-78 +/- 115 m, not statistically significant). In addition, peak Vo(2), BNP levels and Minnesota Living with Heart Failure Questionnaire scores only improved in the former group. The change in mean pulmonary artery pressure correlated with the change in 6-minute walk distance at 12 weeks (r = -0.71, p < 0.001). Device-related adverse events were comparable to those known to occur with a pacemaker-like device. CONCLUSIONS: Changes in ambulatory continuous hemodynamic measurements predicted changes in 6-minute walk distance after the start or addition of PAH therapy. The IHM also identified patients who had improved exercise tolerance, BNP levels and quality of life. The IHM appeared to be well tolerated and allowed rapid hemodynamic feedback between clinic visits.

Right ventricular pressure waveform and wave reflection analysis in patients with pulmonary arterial hypertension.

BACKGROUND: Cardiac index is an important determinant of outcome in patients with idiopathic pulmonary artery hypertension (IPAH). An implantable hemodynamic monitor (IHM) [Chronicle; Medtronic; Minneapolis, MN; a system limited to investigational use only] that records right ventricular (RV) pressure waveforms continuously may increase our understanding of IPAH and improve therapeutic selections and outcomes. The aim of this study was to investigate whether the RV pressure waveform utilizing an IHM can be used to estimate the magnitude of pressure wave reflection and cardiac index in patients with IPAH in acute settings. METHODS: In eight patients with pulmonary arterial hypertension, RV pressure waveforms were recorded utilizing the IHM, and breath-by-breath cardiac index was recorded during acute IV epoprostenol infusion at 3, 6 and 9 ng/kg/min. Late systolic pressure augmentation and cardiac index were estimated using the RV pressure waveforms and correlated with direct measurement of cardiac index. RESULTS: At baseline, the cardiac index was 2.1 +/- 0.2 L/min/m(2), total pulmonary resistance index was 38 +/- 2 Wood U/m(2), and RV systolic pressure was 92 +/- 4 mm Hg. Wave reflection accounted for 29 +/- 1 mm Hg of the RV systolic pressure. During epoprostenol infusion, total pulmonary resistance index and wave reflection decreased (- 15 +/- 4 Wood U/m(2), p < 0.001, and - 5 +/- 2 mm Hg, p < 0.05, respectively). The breath-by-breath cardiac index correlated with the RV pressure waveform cardiac index estimates (r(2) = 0.95). CONCLUSIONS: RV pressure waveform analysis provides continuous hemodynamic assessments including cardiac index in acute settings. Once confirmed in long-term settings, this information may prove useful in optimizing a treatment regimen in patients with IPAH.

A right ventricular pressure waveform based pulse contour cardiac output algorithm in canines.

Tracking changes in stroke volume or cardiac output (CO) can be useful in the diagnosis and treatment of various cardiac illnesses. Existing arterial pressure waveform based pulse contour CO algorithms perform poorly during altered systemic hemodynamics. In this study, a right ventricular pressure waveform based pulse contour CO algorithm was developed to estimate the amplitude and duration of a hypothetical triangular flow waveform in the pulmonary artery. This algorithm was tested against gold standard blood flow measurements in ten canines during acute perturbations to preload (inferior vena caval occlusion (IVCO), rapid saline infusion), afterload (descending aortic occlusion (DAO), serotonin, angiotensin II, sodium nitroprusside infusion), and cardiac contractility (dobutamine and propranolol infusion). The algorithm correctly predicted the changes in CO (r2 = 0.82) that varied from - 45 to 31% of the baseline levels. To explain this finding both the pulmonary arterial (PA) and the ascending aortic (AA) input impedances were modeled as three element windkessels. In the AA the peripheral resistance (from - 61 to 191%), characteristic impedance (from - 59 to 20%) and total arterial compliance (from - 49 to 34%) varied significantly with these perturbations. In contrast, these parameters in the PA changed little. In particular, except serotonin infusion, the characteristic impedance of the PA deviated only 6% (SD/mean) from baseline values. This suggests right ventricular pressure waveform based estimate of CO is possible during acute changes in left ventricular hemodynamics.