Beyond the four quadrants: the critical and emerging role of impedance cardiography in heart failure.

Abstract

Heart failure (HF) is a disorder characterized by hemodynamic abnormalities including a reduction in the heart's ability to deliver oxygenated blood to the body. HF is also associated with important neurohormonal abnormalities, including activation of the renin-angiotensin-aldosterone and sympathetic nervous systems and their resulting effects on the heart and vascular endothelium. Our understanding of the neurohormonal role in the progression of HF has greatly improved in the past 10 years,1 and many of the therapies that significantly improve the symptoms and prognosis of patients with HF now target the underlying neurohormonal abnormalities. As shown in Figure 1, neurohormonal activation can lead to progression of hemodynamic abnormalities resulting in reduced cardiac output (CO); increased filling pressures; and ultimately worsening symptoms of fatigue, dyspnea, and decreased exercise tolerance. Although the neurohormonal mechanisms may cause progression of the disease process, nearly all medications used in HF treatment have demonstrable effects on hemodynamics. Current acute HF treatment is aimed directly at stabilizing and improving a patient's short-term hemodynamic condition; chronic HF treatments can alter short-term and improve long-term hemodynamics. Neurohormonal activation and resultant hemodynamic and symptom changes. RAS=renin-angiotensin-aldosterone system Specific hemodynamic measurements such as CO and systemic vascular resistance are generally obtained for only the most critically ill HF patients, in large part due to the risk, discomfort, and cost of invasive procedures such as pulmonary artery catheterization.2 Nonetheless, understanding and measuring the factors that affect CO are central to the assessment, prognosis, and treatment of patients with HF. The four determinants of CO are the rate of the pump (heart rate), the volume of blood available to pump (preload), the pumping strength (contractility), and the force the heart must overcome to pump (afterload, generally approximated by systemic vascular resistance). Symptoms—physical findings like vital signs—and laboratory findings such as blood tests and chest radiographs are imprecise measures of hemodynamic function. Unfortunately, they are the only data many clinicians have at their disposal when making important decisions in the care of patients with HF. The direct cost of treating HF is estimated to be $56 billion per year in the United States3 and the number of HF patients in this country may reach 10 million by 2010.4 A significant portion of the cost of HF care is the high cost of hospitalizations for patients with acute decompensation. Through careful surveillance of patients with chronic HF using improved methods for measuring hemodynamic and neurohormonal status, primary care physicians and cardiologists may be able to intervene in a timely manner and prevent acute episodes leading to hospitalization, major morbidity, or death. Warner-Stevenson5 has developed and popularized the concept of categorizing HF patients by hemodynamic subset based on perfusion with CO (warm vs. cold) and congestion with pulmonary artery wedge pressure (wet vs. dry). The four quadrants, representing the four hemodynamic classes, are shown in Figure 2. Studies have suggested that these profiles provide a useful framework to risk stratify patients with HF, predict outcomes, and identify therapeutic options. However, this framework is based on invasive pulmonary artery catheterization, with its requisite risk and cost, or on physical examination and patient history, which have been shown to lack sensitivity and specificity, even in the hands of experienced clinicians.6 HF management using hemodynamic subsets could be substantially improved by the existence of more objective data with which to classify patients and evaluate the effectiveness of subsequent pharmacologic and implantable interventions. Clinical profiles in heart failure. PND=paroxysmal nocturnal dyspnea; JV=jugular vein; ACE=angiotensin-converting enzyme. Adapted from J Am Coll Cardiol. 2003;41(10):1797–1804.5 Impedance cardiography (ICG) is a noninvasive method of determining hemodynamic status. In the past, studies questioned the reliability of ICG technology,7, 8 leading some to conclude that the technology did not have value in clinical decision making. However, refinements in signal processing and CO algorithms have greatly improved the reliability of ICG technology. The latest generation of ICG devices (BioZ ICG Monitor, CardioDynamics, San Diego, CA; and BioZ ICG Module, GE Medical Systems Information Technologies, Milwaukee, WI) are both highly reproducible and accurate in a number of clinical settings, including HF.9-11 A recent search of the literature failed to show a single citation since US Food and Drug Administration 510(k) clearances of these particular devices that suggests they are not valid for clinical applications. ICG is a form of plethysmography that utilizes changes in thoracic electrical impedance to estimate changes in blood volume in the aorta and changes in fluid volume in the thorax. As shown in Figures 3 and 4, the ICG procedure involves the placement of four dual sensors on a patient's neck and chest. A low-amplitude, high-frequency alternating current is delivered from the four outer sensors and the four inner sensors detect instantaneous changes in voltage. As suggested by Ohm's law, when a constant current is applied to the thorax, the changes in voltage are directly proportional to the changes in measured impedance. The overall thoracic impedance, called base impedance (Z0) is the sum of the impedances of the components of the thorax, including fat, cardiac and skeletal muscle, lung and vascular tissue, bone, and air. Changes from Z0 occur due to changes in lung volumes with respiration and changes in the volume and velocity of blood in the great vessels during systole and diastole. The rapidly changing component of chest impedance (ΔZ) is filtered to remove the respiratory variation, leaving the impedance changes due to ventricular ejection. Figure 5 details the elements contributing to Z0 and ΔZ, and Figure 6 illustrates how the first derivative of the impedance waveform (ΔZ/Δt) is used with an electrocardiogram to determine the beginning of electrical systole, aortic valve opening, maximal deflection of the ΔZ/Δt waveform, and the closing of the aortic valve. From these fiducial points, a variety of measured and calculated parameters (Table I) are continuously displayed on the ICG device screen for monitoring purposes, or in a printed report for review (Figure 7). Front view of impedance cardiography method Lateral view of impedance cardiography method Contributing elements to thoracic impedance. Z0=baseline impedance; ΔZ=change in impedanceAdapted from Osypka MJ, Bernstein DP. Electrophysiologic principles and theory of stroke volume determination by thoracic electrical bioimpedance. AACN Clin Issues. 1999;10(3):385–399. Fiducial points derived from electrocardiogram (ECG) and impedance waveforms. ΔZ=change in impedance; ΔZ/Δt=first derivative of the impedance waveform; PEP=preejection period; LVET=left ventricular ejection time Impedance cardiography hemodynamic status report (BioZ ICG Monitor, CardioDynamics, San Diego, CA) The hemodynamic parameters derived from ICG can aid in the diagnostic and prognostic evaluation of patients with HF. Using ICG, a clinician is able to evaluate direct or indirect measures of each of the four major determinants of CO (preload, afterload, contractility, and heart rate). Figure 8 is a conceptual diagram of CO and its determinants, ICG parameters associated with the determinants, and the effects of pharmacologic agent classes on each determinant. Due to greater acceptance of ICG in clinical and research settings, clinicians are now able to use ICG-derived hemodynamic data to help decide when to initiate and titrate these types of medications. A summary of applications of ICG in HF is presented in Table II, demonstrating its broad clinical applicability. Pharmacologic agent effect on cardiac output determinants and impedance cardiography parameters. CO=cardiac output; CI=cardiac index; HR=heart rate; SV=stroke volume; SI=stroke index; ΔTFC=change in thoracic fluid content; SVR=systemic vascular resistance; SVRI=systemic vascular resistance index; VI=velocity index; PEP=preejection period; ACI=acceleration index; LVET=left ventricular ejection time; STR=systolic time ratio In this supplement to Congestive Heart Failure, we seek to further define the role of ICG through a series of original contributions. The study by Yung et al. (p. 7) validates the accuracy of ICG in patients with pulmonary hypertension by comparing ICG to both direct Fick method and thermodilution CO. In doing so, the authors demonstrate the potential hazard of using thermodilution as the only reference standard for CO measurement. Parrott et al. (p. 11) compare changes in ejection fraction by echocardiography to changes in ICG parameters in established HF patients. Their findings demonstrate the ability of ICG to simply and cost-effectively identify changes in ventricular function. While pulmonary artery catheterization in patients with HF has been criticized and is largely unproven by clinical trial, an estimated 2 million such catheters are sold worldwide each year.12 Springfield et al. (p. 14) illustrate the role of ICG in the differential diagnosis of patients with dyspnea. Although B-type natriuretic peptide testing has gained wide attention recently as an aid to diagnose HF in the emergency department,13 ICG may also have a diagnostic role and provides additional value because of its ability to identify appropriate therapeutic options and monitor the response to therapy in real time. Silver et al. (page 17) report on the ability of ICG to replace pulmonary artery catheterization, which has tremendous cost implications for hospitals caring for such patients. Vijayaraghavan et al. (page 22) demonstrate the prognostic role of ICG in patients with chronic HF, and show strong association of ICG changes to changes in functional status and quality-of-life measures. Summers et al. (page 28) provide a series of case reports that illustrate ICG's practical role in the initiation and titration of neurohormonal agents and their patient-specific hemodynamic effects. This compilation of studies adds to the growing body of data supporting the role of ICG in the management of patients with HF. Within a year, the results of two multicenter trials studying key roles for ICG should be available: Prospective Evaluation and identification of Decompensation by Impedance Cardiography Test (PREDICT), conducted in patients with chronic HF; and the BioImpedance cardioGraphy (BIG) substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE).14 PREDICT specifically addresses the ability of ICG-derived hemodynamic data to identify patients at risk for death, hospitalization, or emergency department visit. The BIG substudy will evaluate the diagnostic and prognostic role of ICG in both arms of a randomized, controlled trial in pulmonary artery catheter—hemodynamic-guided management of patients admitted with an acute episode of HF. There is now a compelling body of literature that demonstrates the validity of ICG using the most current technology. More and more studies have shown the value of ICG in clinical settings in addition to HF, including dyspnea,15 hypertension,16 and atrioventricular sequential pacemakers.17 The studies presented in this issue of Congestive Heart Failure further define the role of this valuable, noninvasive technology in clinical medicine. It is likely that these and other studies of ICG in HF will be used to refine our understanding and ability to assess patients and predict prognosis, expanding on the concept of the four quadrants presented in Figure 2. The impact of adding ICG hemodynamic data to the four quadrants is depicted in Figure 9. Knowledge of stroke index, cardiac index, systemic vascular resistance index, and changes in fluid with thoracic fluid content would likely provide more quantitative, objective, and sensitive measurements of hemodynamic factors, and has significant implications for the management of patients with HF. Model for clinical profiles in heart failure utilizing impedance cardiography hemodynamic measurements Incorporating this model of assessment into a proposed therapeutic algorithm is shown in Figure 10. Ideally, a baseline measurement of ICG in addition to other standard clinical variables would be collected and utilized in combination to more precisely assess a patient's perfusion, congestion, and vasoactive status. This assessment would lead to a categorization of the patient's absolute or relative change in hemodynamic profile, facilitating assessment of short-term risk for adverse HF-related events. The change in hemodynamic status and assessment of higher risk may lead to increased clinical surveillance or a decision to intervene to prevent a negative patient outcome. In addition, ICG parameters may aid in the assessment of a stable, low-risk hemodynamic profile toward the initiation and up-titration of neurohormonal agents that are often under-prescribed but are known to improve event-free survival. Therapeutic algorithm for incorporating impedance cardiography (ICG) parameters into clinical assessment of heart failure. SI=stroke index; CI=cardiac index; TFC=thoracic fluid content; SVRI=systemic vascular resistance index; ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin-receptor blocker Note: This supplement to Congestive Heart Failure contains articles dealing with ICG. Readers are reminded that positive statements about the clinical utility of ICG, and the BioZ ICG Monitor in particular, are solely the opinions of the authors and do not represent an official endorsement by Congestive Heart Failure, its Editors or Editorial Board, or the Heart Failure Society of America.