Impedance Cardiography in the Evaluation of Patients with Arterial Hypertension

Mailing Address: Rodrigo Nazário Leão Av. Oscar Monteiro Torres, n 49, 1A. Postal Code: 1000-216, Areeiro, Lisbon Portugal. E-mail: rodrigoromaoleao@gmail.com; rodrigoromaoleao@hotmail.com Impedance Cardiography in the Evaluation of Patients with Arterial Hypertension Rodrigo Nazário Leão1,2 and Pedro Marques Da Silva1,3 Faculdade de Ciências Médicas, Universidade Nova de Lisboa;1 Lisbon Portugal Hospital de São José, Centro Hospitalar de Lisboa Central,2 Lisbon Portugal Hospital de Santa Marta,3 Lisbon Portugal


Introduction
Hypertension is a condition characterized by elevated blood pressure (BP).A comprehensive definition, published by the American Society of Hypertension in 2005, describes hypertension as "a progressive cardiovascular syndrome (CV) arising from complex and interrelated etiologies".Early markers of this syndrome are often present before blood-pressure (BP) elevation occurs; thus, hypertension cannot be solely classified by discreet blood-pressure thresholds.Disease progression is strongly associated with cardiac and vascular functional and structural abnormalities that damage the heart, kidneys, brain, vasculature and other organs, leading to early morbidity and mortality. 1 is estimated that hypertension affects approximately 1 billion individuals and causes more than 7 million deaths annually worldwide (13% of overall mortality).In Portugal, the prevalence of hypertension in the adult population aged 18 to 90 years is 42.2% (44.4% in men and 40.2% in women). 2 According to the World Health Organization (WHO), BP greater than 115 mmHg (systolic BP) is responsible for 62% of cerebrovascular diseases and 49% of ischemic cardiac pathologies, with little variation between the genders.These BP values are considered by the WHO as the main risk factor for mortality worldwide. 3,4though BP control is a growing concern, with a consequent increase in the number of treated and controlled patients, there is still a large percentage of treated patients who do not reach their therapeutic targets.8][9] The choice of antihypertensive therapy based on hemodynamic systems is not new, but it has progressively become more accessible through the noninvasive hemodynamic parameters of the ICG.This is based on the knowledge that elevated BP results from changes in its hemodynamic components (cardiac output -CO, peripheral vascular resistance and/or blood volume).ICG is a non-invasive, operator- Source: adapted from Cybulski et al. 14

Review Article
independent and low-cost hemodynamic monitoring tool that allows defining the patients' hemodynamic profiles, leading to a more adequate selection of the antihypertensive therapy. 10

Impedance cardiography
Biological tissues are complex anisotropic conductors with reactive and resistive components.The bioimpedance value depends on the type of tissue analyzed and can be altered by translocation of organs or tissues, by changes in shape or structure, by the volume or location of intracellular fluids, or by the frequency of the current used.The ICG consists in the evaluation of the electrical properties of the biological tissues of the chest. 11The bioimpedance measures the way the tissues conduct the alternating electric current and varies according to the amount of body fluids.Thus, the chest impedance increases or decreases, depending on the changes in intrathoracic fluid with each heartbeat. 12,13e most common technique uses four electrodes, two of which are the current electrodes and the two that detect voltage changes.Since the current amplitude is constant, the detected voltage is proportional to the tissue impedance. 14Figure 1 represents the four-pole impedance measurement scheme.The effective evaluation of the chest impedance during a cardiac cycle is hindered by several factors, such as chest size and shape, obesity, body weight, position and posture, thoracic circulation and respiratory rate.7][18][19] Current technology, with data processing and modeling techniques, has demonstrated that ICG has a high correlation, reproducibility and precision when compared to invasive hemodynamic monitoring techniques and echocardiography -which was considered more time-consuming, operatordependent and technically demanding.[22][23][24][25] The ICG detects, analyzes, and records hemodynamic changes by measuring electrical resistance changes in the thorax, graphically translating them as impedance and electrocardiography waves (Figure 2).It allows the calculation of several hemodynamic parameters such as systolic volume (SV), cardiac output (CO), systemic vascular resistance (SVR), velocity and acceleration indexes, thoracic fluid content (TFC), pre-ejection period, left ventricular ejection time, systolic time ratio, left cardiac work, heart rate and mean BP. 26 The assessed parameters and respective formulas are shown in table 1.
The first derivative of the waveform (ΔZ) describes fluid velocity and is a smooth wave, which corresponds to the systole, called S wave.The initial slope of the S Point A coincides with the electrocardiogram (ECG) p-wave and marks the beginning of the end of diastolic filling.The A wave only exists in the presence of an atrial contraction, being small and round, with its end clearly separated from the beginning of the S wave.The basal impedance corresponds to point B. Point C defines the maximum acceleration of blood output from the ventricles.The slope corresponding to the rise from point B to point C is associated with cardiac contractility: the steeper the upward curve, the greater the cardiac contractility.After reaching point C, there is a rapid deceleration to point X, which represents the inversion point of the intrathoracic fluid and corresponds to the closure of the aortic valve.After point X, the wave returns to the baseline and starts to form an early diastolic wave, associated with the opening of the mitral valve, the O wave.The moment of greatest opening of the mitral valve is represented by the peak of the S wave -point O.This interval between points X and O corresponds to the time of isovolumetric relaxation. 28[31][32][33][34][35][36][37][38][39] ICG is a technique that has evolved in recent years and has become an attractive and cost-effective method of improving patients' clinical approach.

Arterial hypertension and impedance cardiography
Classically defined as an increase in BP, this parameter alone is an incomplete indicator of the cardiovascular system status, particularly in patients with resistance to drug therapy or hypervolemic ones. 7The mean BP consists of the product of two hemodynamic parameters (CO and SVR), and arterial hypertension is the result of a disorder in one or both hemodynamic variables. 402][43][44][45] Historically, the use of BP as an indicator of cardiovascular status in hypertensive patients comes from the fact that hemodynamic parameters are assessed using invasive techniques. 46More recently, echocardiography has been used to accurately estimate CO, but when compared with ICG, the latter was considered more time-consuming and technically demanding. 19Thus, ICG emerges as a non-invasive, simple, accurate and inexpensive method to evaluate patients hemodynamically, characterizing the profile and guiding the therapeutic optimization in hypertensive patients. 44,45,47e use of ICG can improve our knowledge about arterial hypertension, especially regarding its hemodynamic characteristics and consequences.Hypertensive cardiopathy is a continuum, involving structural changes (myocardial fibrosis) and left ventricular geometry (hypertrophy and concentric remodeling), which progressively develop into systolic and/or diastolic function disorder. 48Close to its end, the IMPEDDANS study (ClinicalTrials.gov;Identifier: NCT03209141) intends to verify the ability to screen for left ventricular diastolic dysfunction in its asymptomatic phase in hypertensive patients, which may allow an early diagnosis, as well as the study of the disease evolution and therapeutics.The growing interest in hemodynamic changes in arterial hypertension and orthostatic and emotional stress responses, led researchers to use ICG to study autonomic dysfunction in hypertension.The technological evolution of the ICG, with the development of monitors for the assessment of outpatients, is a new area of research in arterial hypertension.[51][52][53]

Antihypertensive therapy guided by impedance cardiography
Hypertension management includes lifestyle measures such as sodium restriction and weight loss, and, in most cases, the use of one or more antihypertensive drugs.Considering this approach to arterial hypertension as a hemodynamic pathology, drugs are proposed according to the pathophysiological mechanism responsible for BP increase (Figure 3).D r u g s a r e s e l e c t e d a c c o r d i n g t o e l e v a t e d hemodynamic parameters.Therefore, it is first necessary to evaluate the hemodynamic variables to be able to target the therapy at a high cardiac or SVR index.Likewise, if any of these parameters is decreased, the drug responsible for the effect should be identified, its dose reduced, or the drug withdrawn (Figure 4). 10,25,44,45Several studies have highlighted the apparent superiority -although never assessed in long-term studies -of the personalized therapeutic approach to the hemodynamic profile, both regarding its efficacy and cost-effectiveness (Table 2).

Conclusion
Hemodynamic-guided therapy can be valuable in the evaluation and management of hypertensive patients.Impedance cardiography is a cost-effective assessment that allows the diagnosis, therapeutic optimization, and follow-up of hypertensive patients, helping them to achieve therapeutic targets, even in those with resistant hypertension.This therapeutic approach, which focuses on the cause of blood pressure increase and its pathophysiological mechanism, allows better blood pressure control and a potential reduction in cardiovascular events, mortality and costs associated with arterial hypertension.
Future studies in the ICG area should broaden our understanding of the pathophysiology and hemodynamic changes of arterial hypertension and demonstrate that early diagnosis and treatment of hemodynamic characteristics have a positive impact on patient outcomes, reducing morbidity and mortality associated with high blood pressure.

Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.

Sources of Funding
There were no external funding sources for this study.

Study Association
This article is part of the thesis of Doctoral submitted by Rodrigo Nazário Leão, from Universidade Nova de Lisboa.

Figure 1 -
Figure 1 -Schematic illustration of impedance cardiography application, four-pole technique.A1 and A2 correspond to the currentapplying electrodes; R1 and R2 to the current-receptor electrodes.Source: adapted from Cybulski et al.14

MAP
Mean pressure exerted by the blood on the arterial walls 84-100 mmHg Manual = ((SBP-DBP) x KP) + DBP Automatic (oscillometric method) = MAP is measured directly through SBP and DBP CO Amount of blood pumped by the left ventricle per minute 4.5-8.5 L/min CO = EjV x HR CI Standard CO for BSA 2.5-4.7 L/min/m2 CI = CO/BSA SV Amount of blood pumped by the left ventricle per heartbeat 60-130 mL/heartbeat SV = VEPT x LVET x VI (Z MARC ® Algorithm) SI Standard stroke volume for BSA 35-65 mL/heartbeat/m 2 SI = SV/BSA SVR Resistance of circulating blood to the arterial system 742-1,378 dynes sec/cm 5 SVR = 80 x ((MAP -CVP)/CO) SVRI Standard SVR for BSA 1,337-2,483 dynes.sec.m 2 /cm 5 SVRI = 80 x ((MAP -CVP)/ CI) AI Initial acceleration of blood in the aorta that occurs within the first 10-20 milliseconds after opening of the aortic valve Male: 70-150/100 sec 2 Female: 90-170/100 sec 2 AI = (d2Z/dt2Max)/ TFC VI in the aorta Peak velocity of blood flow in the aorta 33-65/1,000 sec VI = (dZ/dtMax)/ TFC TFC Electrical conductivity of the thoracic cavity (determined by intravascular, interalveolar and interstitial fluid) Male: 30-50/kohm Female: 21-37/kohm TFC = 1/ TFI LCW Indicator of the amount of work exerted by the left ventricle in each minute to pump blood into the systemic circulation 5.4-10 kg.m LCW = (MAP -PAOP) x CO LCW index Standard LCW for BSA 3.0-5.5 kg m/m 2 LCW index = (MAP -PAOP) x CI PEP The time interval from the beginning of electrical stimulation of the ventricles to the opening of the aortic valve (electrical systole) Depends on HR, contractility and resistance to diastolic filling Time interval between the beginning of the Q wave on the ECG and the B point on the dZ/dt wave (aortic valve opening) LVET Time interval from the opening to the closing of the aortic valve (mechanical systole) Depends on HR, contractility and resistance to diastolic filling