The Congestion Apnea and Right Ventricular Dysfunction in Acute Heart Failure (CARVD-AHF) study is a prospective clinical translational (NIH T2) observational study evaluating a proposed relationship between three important factors in patients treated acutely for heart failure.
Congestion, or the elevation of pressures in the heart, lungs, and central circulation, is the core physiologic feature of new or acutely worsening symptoms of heart failure. Unfortunately, research shows that congestion is inadequately treated before hospital discharge in about half of acute heart failure (AHF) patients. Those patients who are undertreated have a roughly six times higher rate of short-term rehospitalization for heart failure or death.
Right ventricular dysfunction (RVD) typically occurs in the setting of elevated back pressure from the left ventricular and pulmonary circulation, on account of the RV being sensitive and poorly adaptive to significant elevations in filling pressures. RVD is one of the strongest predictors of both short and long term morbidity and mortality among patients hospitalized for AHF, and recently our group showed an independent relationship between RVD and severity of pulmonary congestion on Lung Ultrasound during AHF treatment.
Cheyne-Stokes Respiration (CSR) is a type of central apnea which occurs frequently in patients with HF in which the patient experiences rapid respiratory effort followed by periods where breathing stops spontaneously for 10 seconds of more. Unlike the more commonly known obstructive sleep apnea, apnea from CSR is generally underdetected (i.e. lacking obvious signs such as snoring), is not effectively treated with positive pressure ventilation (e.g. CPAP), and (based on our groups' preliminary data) appears to occur even in AHF patients who are awake. Pilot data suggests that both RVD and CSR may be related to the severity of pulmonary congestion, as measured on LUS.
If congestion itself is a primary cause of RVD and CSR acutely it would allow an unprecedented avenue to treat both through addressing the aforementioned typical under treatment of congestion during heart failure hospitalization. However, it is unclear if CSR in turn worsens (mediates) RVD or is simply a confounding phenomenon in a congestion-RVD relationship.
The primary goal of CARVD-AHF is to better elucidate the conceptual model linking these three factors through advanced statistical methods for causal inference in observational data, such as mediation analysis. Patients receive echocardiography at ED arrival within 0-3 hours of initial ED evaluation and treatment, daily lung ultrasound to measure changes in congestion, daily monitoring for CSR using validated sleep apnea monitors, and daily biomarker analysis. Two additional echocardiograms are performed at discharge from the hospital and at 90 day outpatient follow-up.
The study is expected to help the investigators refine the hypothesized causal pathway, which will in turn directly inform a pilot clinical trial using LUS-guided decongestion to hopefully ameliorate RVD, CSR, or both along with patient centered-clinical outcomes like rehospitalizations and death.