Iris Dahan

Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients: A Randomized Controlled Trial (IMPEDANCE-HF Trial)

BACKGROUND Previous investigations have suggested that lung impedance (LI)-guided treatment reduces hospitalizations for acute heart failure (AHF). A single-blind 2-center trial was performed to evaluate this hypothesis (ClinicalTrials.gov-NCT01315223). METHODS The study population included 256 patients from 2 medical centers with chronic heart failure and left ventricular ejection fraction ≤35% in New York Heart Association class II-IV, who were admitted for AHF within 12 months before recruitment. Patients were randomized to a control group treated by clinical assessment and a monitored group whose therapy was also assisted by LI, and followed for at least 12 months. Noninvasive LI measurements were performed with a new high-sensitivity device. Patients, blinded to their assignment group, were scheduled for monthly visits in the outpatient clinics. The primary efficacy endpoint was AHF hospitalizations; the secondary endpoints were all-cause hospitalizations and mortality. RESULTS There were 67 vs 158 AHF hospitalizations during the first year (P < .001) and 211 vs 386 AHF hospitalizations (P < .001) during the entire follow-up among the monitored patients (48 ± 32 months) and control patients (39 ± 26 months, P = .01), respectively. During the follow-up, there were 42 and 59 deaths (hazard ratio 0.52, 95% confidence interval 0.35-0.78, P = .002) with 13 and 31 of them resulting from heart failure (hazard ratio 0.30, 95% confidence interval 0.15-0.58 P < .001) in the monitored and control groups, respectively. The incidence of noncardiovascular death was similar. CONCLUSION Our results seem to validate the concept that LI-guided preemptive treatment of chronic heart failure patients reduces hospitalizations for AHF as well as the incidence of heart failure, cardiovascular, and all-cause mortality.

Usefulness of Lung Impedance-Guided Pre-Emptive Therapy to Prevent Pulmonary Edema During ST-Elevation Myocardial Infarction and to Improve Long-Term Outcomes

Patients sustaining an ST-segment elevation myocardial infarction (STEMI) frequently develop pulmonary congestion or pulmonary edema (PED). We previously showed that lung impedance (LI) threshold decrease of 12% to 14% from baseline during admission for STEMI marks the onset of the transition zone from interstitial to alveolar edema and predicts evolution to PED with 98% probability. The aim of this study was to prove that pre-emptive LI-guided treatment may prevent PED and improve clinical outcomes. Five hundred sixty patients with STEMI and no signs of heart failure underwent LI monitoring for 84 ± 36 hours. Maximal LI decrease throughout monitoring did not exceed 12% in 347 patients who did not develop PED (group 1). In 213 patients LI reached the threshold level and, although still asymptomatic (Killip class I), these patients were then randomized to conventional (group 2, n = 142) or LI-guided (group 3, n = 71) pre-emptive therapy. In group 3, treatment was initiated at randomization (LI = -13.8 ± 0.6%). In contrast, conventionally treated patients (group 2) were treated only at onset of dyspnea occurring 4.1 ± 3.1 hours after randomization (LI = -25.8 ± 4.3%, p <0.001). All patients in group 2 but only 8 patients in group 3 (11%) developed Killip class II to IV PED (p <0.001). Unadjusted hospital mortality, length of stay, 1-year readmission rate, 6-year mortality, and new-onset heart failure occurred less in group 3 (p <0.001). Multivariate analysis adjusted for age, left ventricular ejection fraction, risk factors, peak creatine kinase, and admission creatinine and hemoglobin levels showed improved clinical outcome in group 3 (p <0.001). In conclusion, LI-guided pre-emptive therapy in patients with STEMI decreases the incidence of in-hospital PED and results in better short- and long-term outcomes.

Prediction of readmissions and mortality in patients with heart failure: lessons from the IMPEDANCE‐HF extended trial

Readmissions for heart failure (HF) are a major burden. We aimed to assess whether the extent of improvement in pulmonary fluid content (ΔPC) during HF hospitalization evaluated by lung impedance (LI), or indirectly by other clinical and laboratory parameters, predicts readmissions.

NON-INVASIVE LUNG IMPEDANCE-GUIDED PREEMPTIVE TREATMENT IN CHRONIC HEART FAILURE PATIENTS: A RANDOMIZED CONTROLLED TRIAL (IMPEDANCE-HF TRIAL)

Previous investigations have suggested that lung impedance (LI)-guided treatment reduces hospitalizations for acute heart failure (HF). A single-blind two-center trial was performed to evaluate this hypothesis. Study population included 256 patients from 2 medical centers with CHF and LVEF ≤35%

Lung Impedance-Guided Therapy of Patients with Chronic Heart Failure Improves Clinical Outcome

Introduction: Management of heart failure (HF) patients incorporates diuretic strategies to reduce congestion and prevent decompensation. Elevated cardiac filling pressures precede signs/symptoms that lead to decompensation; implantable hemodynamic monitoring (IHM) devices allow home monitoring of this signal. The CHAMPION trial found significant reductions in HF hospitalizations (HFH) in NYHA class III HF patients whose syndrome was managed using pulmonary artery pressure (PAP) from an IHM. We examined the potential benefit of PAP monitoring in patients with HF and chronic kidney disease (CKD), a difficult population to manage effectively. Hypothesis: When HF patients with CKD are managed using PAP monitoring, their HFH rates will be significantly reduced when compared to HF patients with CKD managed according to standard of care. Methods: CHAMPION was a prospective, randomized, single-blind study in patients with NYHA class III HF and a recent HF hospitalization. 550 patients were implanted with the IHM device and randomized to HF management with access to PAP (270) or standard of care management (280). Average follow-up was 18 months. CKD was defined as a GFR ! 60 mL/min/1.73m at baseline. Results: 150 treatment group patients and 147 control group patients had CKD at baseline. In controls, patients with CKD had a higher risk for HFH when compared to the overall control population (0.83 vs. 0.68, HR 1.21, p!0.05). When patients with CKD were managed using PAP monitoring, HFH rates were significantly reduced compared to patients with CKD managed according to standard of care (0.48 vs. 0.83, HR 0.58, p!0.001). Benefits of PAP monitoring observed in patients with CKD were consistent with the overall treatment effect (0.48 vs. 0.45, HR 1.05, p50.69). Changes in creatinine and GFR from baseline to 6 months in patients with CKD were similar for patients managed using either PAP monitoring or standard of care. Conclusions: CKD in patients with NYHA class III HF is a risk factor for HFH. Management based upon PAP monitoring significantly reduces HFH in HF patients with CKD and does not adversely affect renal function.

EVALUATION OF THE EFFECTIVENESS OF IN-HOSPITAL TREATMENT OF CHRONIC HEART FAILURE PATIENTS DURING EXACERBATION BY NON-INVASIVE NET LUNG IMPEDANCE MONITORING DURING ADMISSION

methods: CHF patients were monitored by a device that derives the net lung impedance (LI) from measured trans-thoracic impedance. This device is 25-fold more sensitive than existing ones. A decreasing LI reflects accumulation of lung fluid. Changes in the clinical status of patients and LI were recorded at each monthly outpatient visit. On the basis of LI measurements, clinical assessment, and chest X-ray, the optimal LI was determined for each patient. LI changes from this value are represented as percentage change,

LUNG IMPEDANCE-GUIDED PREEMPTIVE TREATMENT OF CHRONIC HEART FAILURE PATIENTS IN THE OUTPATIENT CLINIC DECREASES HOSPITALIZATIONS FOR ACUTE HEART FAILURE AND IMPROVES SURVIVAL

Results: 163 CHF patients (72±10 years) at NYHA II/III/IV (60/73/30) were randomized to LI-guided preemptive treatment (Group 1, n=82) or to conventional therapy administered by clinical evaluation (Group 2, n=81) according to current guidelines. A LI decrease >15% from baseline was used to initiate early preventive therapy since it has been shown previously that decompensation begins at this level of LI decrease. LVEF and NT-proBNP in groups 1 and 2 at study onset were 22±7%, 5714±2421 pg/ml, and 22±6% and 5752±2501 pg/ml, respectively (p=NS). Rate of re-hospitalizations was lower in group 1 (0.57 vs. 1.02/per patients per year, p<0.01). More patients in group 2 were hospitalized for AHF during the follow up period than in group 2 (45 vs.32%, p=0.08). During follow up period cardiovascular mortality in group 1 was lower than in group 2 (11 vs. 24, p<0.01, respectively). As a result of the higher mortality in group 2, follow up time was longer in group 1 (30.7±25.5 vs. 20.7±14.7 months, p<0.01).

Importance of Lung Impedance Monitoring in the Outpatient Clinic for Predicting and Preventing of Hospitalizations Patients With Chronic Heart Failure

Introduction: The role of B-type natriuretic peptide (BNP) in the diagnosis of acute heart failure and its elevation with left ventricular dysfunction (LVD) is well-established. However, recent studies show that BNP undergoes further biochemical processing and circulates in various forms. This study aims to evaluate if altered forms of BNP provide better diagnostic/prognostic information in patients presenting to the emergency department (ED) with dyspnea and chest pain. Methods: The Altered Forms study is an 18-month single-center prospective cohort study of 400 patients with dyspnea or chest pain. For dyspnea, patient blood was drawn on initial ED presentation, 12-24 hours later, and on discharge. For chest pain, blood was drawn on initial ED presentation, again within 6 hours, and on discharge. We assessed the quantity of 6 BNP forms with 6 developed assays: BNP 77-108, proBNP 1*-108, proBNP 3*-108, BNP 79*-108, BNP 77-108, & NTproBNP 1-76 calibrated with proBNP 1-76 (Hytest). Results: As an ongoing study, 168 samples from 62 patients were included in the analysis. All peptides were statistically significant and greater in patients with heart failure (HF) than in those with chest pain (P!0.001). NTproBNP 1-76 was the most abundant in all subgroups and as high as 871pM (P!0.001). HF patients showed a 2:1 ratio of peptides when compared to non-HF patients with LVD and a 3:1 ratio to patients without HF and no LVD. With treatment, NTproBNP 1-76 calibrated with proBNP 1-76 showed the greatest absolute decline across all subgroups of dyspnea (HF, no HF, no HF but LVD) with an average drop of 232.1pM (P!0.001). BNP 77-108 demonstrated the greatest mean fractional decline (52%) after treatment compared to 30% for NTproBNP 1-76 (P!0.001). proBNP 1*-108 quantity increased a mean of 10.6pM following treatment. Conclusion: New biomarkers (NTproBNP 1-76 calibrated with proBNP 1-76 and proBNP 1*-108) with assay specificity for specific terminal amino acids demonstrate utility in guiding HF diagnosis and treatment. Assessing the ratios of these forms on discharge may help validate improved prognosis after treatment.