Pathophysiology of Pulmonary Circulation in Congenital Heart Disease
- 419 Downloads
There are several types of abnormalities in the integrated physiology of pulmonary circulation in congenital heart disease. The main pathology of Eisenmenger syndrome involves a change in pulmonary resistance and is the most commonly observed pathophysiology in pulmonary hypertension. Other diseases also present with the main pathophysiological characteristic of reduced pulmonary compliance, such as tetralogy of Fallot and multiple peripheral pulmonary stenosis. In addition, the cavo-pulmonary connection has the unique feature of both pulmonary circulation and regulation. According to the differences in the pathophysiological features of pulmonary circulation, therapeutic approaches may considerably differ between diseases and conditions. Physiology-based clinical insights with regard to pulmonary circulation in congenital heart disease will be discussed in this chapter.
KeywordsImpedance Wave reflection Characteristic impedance Compliance Pressure-volume relationships
This chapter discusses the pathophysiology of pulmonary circulation in congenital heart disease. This refers to the macrophysiology of cardiovascular hemodynamics, an understanding of which is essential for the treatment of patients with abnormal pulmonary circulation and congenital heart disease. We hope this chapter can provide some hints and insights for use in future research on pulmonary hypertension in congenital disease as well as in the fields of physiology and molecular and cellular biology.
We will first discuss how we comprehensively assess integrated pulmonary circulation in congenital heart disease in vivo. Subsequently, using methodology for comprehensive assessment, we will discuss the pathophysiological characteristics of pulmonary circulation in patients with various types of congenital heart disease.
15.2 Comprehensive Assessment of Integrated Pulmonary Circulation
15.2.1 Physiologic Components of Pulmonary Circulation
The elastic component is vascular compliance or capacitance. The pulmonary artery is not a rigid tube but has elasticity to buffer intermittent pulsatile flow ejected by the right ventricle. Pulmonary arterial capacitance is a vascular property in this buffering system and is determined by both arterial wall elasticity and vascular size or volume. Pulmonary compliance/capacitance is analogous to a capacitor or condenser in an electric circuit. An alternating current but not a direct current goes in and out of the capacitor. Similarly, only pulsatile flow goes in and out of the pulmonary vascular bed with capacitance and is associated with a change in pulse pressure. When pulmonary capacitance is decreased, in other words, when the pulmonary arterial wall is stiff and/or pulmonary vascular bed is small, blood pressure increases through an increase in pulse pressure without a change in mean blood pressure (Fig. 15.1b).
There is yet another property of the elastic component of the pulmonary vascular bed. This is termed characteristic impedance and represents wall stiffness in the proximal artery. In an electric circuit, characteristic impedance is described as resistance upstream of the resistor-capacitor parallel circuit. When characteristic impedance increases, in other words, when the proximal pulmonary arterial wall stiffens, blood pressure increases by an increase in pulse pressure above the diastolic pressure as shown in Fig. 15.1c.
The last major component is a reflective component. The pulmonary vascular bed is not an infinite system but has an end at the left atrium. The pulmonary vascular bed also has many bifurcations with caliber changes. In this type of system, blood flow and pressure waves produce reflections at the site of a bifurcation or vessel caliber change [1, 2]. Therefore, the measured pressure or flow we observe is the sum of forward and reflected waves, and thus augmentation of reflected waves causes significant pressure elevation (Fig. 15.1d).
Therefore, abnormalities in each component contribute differently to pressure elevation in patients with pulmonary hypertension. Resistance change increases pulmonary arterial pressure (PAP) by increasing mean arterial pressure, changes in capacitance and characteristic impedance increase arterial pressure by increasing pulse pressure, and wave reflection increases PAP by adding reflected pressure. Therefore, to better understand the pathophysiology of pulmonary hypertension, it is very important to identify to what extent each of these components is abnormal and contributes to pressure elevation in pulmonary hypertension.
15.2.2 Impedance Analysis
15.3 Pathophysiological Characteristics of Pulmonary Circulation in Congenital Heart Disease
Using impedance analysis, let us discuss the pathophysiological characteristics of pulmonary circulation in patients with various types of congenital heart disease.
15.3.1 Abnormal Resistance Is the Main Pathophysiology
In addition to each parameter of impedance, combining resistance and compliance as their product, RC, also provides useful information about the pulmonary circulation. RC represents the time required for diastolic pressure decay, and a longer RC indicates that the blood does not go through the pulmonary vascular bed smoothly .
Therefore, advanced PAH should be associated with higher RC values. In fact, although PVR alone could not clearly distinguish pulmonary hypertension patients with irreversible pulmonary vascular disease from those whose PAP normalized after ventricular septal defect closure, plots of RC against Qp/Qs clearly distinguished the two groups .
15.3.2 Right Ventricular Function and Coupling to PA Load
In addition to the precise assessment and understanding of pathophysiological changes in the pulmonary vascular bed as shown thus far, an accurate assessment of intrinsic right ventricular (RV) contractility and its relation to the pulmonary artery (PA) load is essential for refining risk stratification and optimizing treatment in pulmonary hypertension because prognosis in PAH is now known to be strongly related to RV compensation rather than to the degree of the vascular injury itself as reported by many investigators [6, 7, 8]. Therefore, we will briefly introduce the method of assessing RV-PA interaction or RV-PA coupling.
15.3.3 Abnormalities of Compliance Is the Main Pathophysiology
15.3.4 Non-pulsatile Pulmonary Flow Is the Main Pathophysiology
There are many studies indicating activation of endothelin-1 or the renin-angiotensin system in Fontan circulation [29, 30, 31]. A significant correlation between endothelin-1 and PVR after the Fontan operation was also reported . In addition, an endothelin receptor antagonist effectively reduced PVR in Fontan patients and improved exercise tolerance and quality of life . Therefore, even in good Fontan status, pulmonary dilators targeting NO and endothelin pathways may have some role in improving Fontan pulmonary circulation and thereby improving the long-term outcome.
Let us briefly think about the role of pulmonary compliance or capacitance in the Fontan circulation. Theoretically, as we explained earlier, only pulsatile flow goes into capacitance, and thus, in the Fontan pulmonary circulation where pulmonary flow is basically non-pulsatile, PAP is determined predominantly by the PVR . Nonetheless, pulmonary vascular capacitance still possesses important pathophysiological roles in the Fontan circulation. First, because of the direct connection of systemic and pulmonary circulation, pulmonary vascular capacitance serves as part of the total vascular impedance from the aorta to the pulmonary vascular bed . Total vascular impedance is afterload to the Fontan single ventricle. As shown here, total vascular impedance, or ventricular afterload, increases with an increase in pulmonary vascular capacitance . Second, perhaps more importantly, our computer simulation clearly indicated that smaller pulmonary vascular capacitance is related to a more marked increase in CVP in response to changes in pulmonary blood volume, which can occur with exercise and excessive water intake [33, 34]. Therefore, CVP variation during daily life should be pronounced in Fontan patients with decreased pulmonary capacitance. As in the original “10 Commandments” or indications for Fontan surgery , pulmonary arterial size, which is related to pulmonary capacitance, is important, independent of PVR, for the establishment of stable Fontan hemodynamics.
Similar to the effects of pulmonary artery capacitance, systemic venous capacitance is important and is an even more important hemodynamic parameter to establish lower levels of CVP in the Fontan circulation [34, 36].
In addition, we newly applied this strategy to 20 patients at an average 7 years postoperatively. The venous capacitance measured by the dye-dilution technique significantly increased after 6 months of this therapy. Importantly, with this change in venous capacitance, CVP again significantly and consistently decreased after the therapy without changes in heart rate and cardiac index.
We will close this chapter by presenting a case of protein-losing enteropathy (PLE) in which super-Fontan strategy was very effective. The patient was a 16-year-old boy with asplenia syndrome, major atrio-pulmonary collateral arteries, and atrioventricular valve regurgitation who underwent TCPC at the age of 7 but developed PLE after the TCPC. Every possible medication had been prescribed. He was referred to our hospital and underwent the super-Fontan strategy, which effectively reduced CVP from 21 to 15 mmHg and, more importantly, resolved the PLE.
In summary, comprehensive assessment of changes in the pulmonary vascular bed and their coupling to RV function is important. Impedance analysis and determination of pressure-volume relationships are ideal methods for this purpose. There are several disease entities with abnormal pulmonary circulation in congenital heart disease characterized by abnormalities of resistance, compliance, and flow pulsatility. Venous capacitance as well as pulmonary resistance can be an important therapeutic target to improve Fontan prognosis.
- 13.Senzaki H, Miyagawa K, Kishigami Y, Sasaki N, Masutani S, Taketazu M, Kobayashi J, Kobyashi T, Asano H, Kyo S, Yokote Y. Inferior vena cava occlusion catheter for pediatric patients with heart disease: For more detailed cardiovascular assessments. Catheter Cardiovasc Interv. 2001;53:392–6.CrossRefGoogle Scholar
- 29.Ishida H, Kogaki S, Ichimori H, Narita J, Nawa N, Ueno T, Takahashi K, Kayatani F, Kishimoto H, Nakayama M, Sawa Y, Beghetti M, Ozono K. Overexpression of endothelin-1 and endothelin receptors in the pulmonary arteries of failed fontan patients. Int J Cardiol. 2012;159(1):34–9.CrossRefGoogle Scholar
- 34.Liang F, Senzaki H, Kurishima C, Sughimoto K, Inuzuka R, Liu H. Hemodynamic performance of the fontan circulation compared with a normal biventricular circulation: A computational model study. Am J Physiol. 2014;307:H1056–72.Google Scholar
Open Access This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.
The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.