Model-Based Comparison of the Normal and Fontan Circulatory Systems-Part III.

BACKGROUND: For patients with the Fontan circulatory arrangement, angiotensin-converting enzyme inhibition, guanylate cyclase activation, phosphodiesterase 5 inhibition, and endothelin receptor antagonism have so far resulted in little or no improvement in [Formula: see text] or peak cardiac index (CI), suggesting that our understanding of the factors that most impact the exercise hemodynamics is incomplete. METHODS: To facilitate comparisons with clinical reports of the exercise performance of preadolescent Fontan patients, we rescaled our previously reported computational models of a two-year-old normal child and similarly aged Fontan patient, extended our Fontan model to capture the nonlinear relationship between flow and resistance quantified from previous computational fluid dynamic analyses of the total cavopulmonary connection (TCPC), and added respiration as well as skeletal muscle contraction. RESULTS: (1) Without respiration, the computational model for both the normal and the Fontan cannot attain the values for CI at peak exercise reported in the clinical literature, (2) because flow through the TCPC is much greater during inspiration than during expiration, the effect on the CI of the dynamic (flow-related) TCPC resistance is much more dramatic during exercise than it is in breath-hold mode at rest, and (3) coupling breathing with skeletal muscle contraction leads to the highest augmentation of cardiac output, that is, the skeletal muscle pump is most effective when the intrathoracic pressure is at a minimum-at peak inspiration. CONCLUSIONS: Novel insights emerge when a Fontan model incorporating dynamic TCPC resistance, full respiration, and skeletal muscle contraction can be compared to the model of the normal.

Model-Based Comparison of the Normal and Fontan Circulatory Systems-Part II: Major Differences in Performance Characteristics.

BACKGROUND: In the absence of an accessible chronic animal model of the Fontan circulation, computational modeling can provide insights into this unique circulatory arrangement, especially how differently it behaves from the normal mammalian circulation. Many groups have focused on refining a single element of the entire Fontan circulation-the total cavopulmonary connection (TCPC). Yet, only modest improvements in transplant-free survival have resulted. From an engineering perspective, optimizing the performance of a complex, multiparameter system requires an understanding of how the performance is affected by the full set of system parameters. METHODS: We evaluated the hemodynamic impact of nine physiological perturbations in the two-year-old (yo) patient with hypoplastic left heart syndrome having a Fontan rearrangement (using our previously described lumped-parameter multicompartment model of both pulmonary and systemic circulations). In cases where comparison is appropriate, we evaluated the hemodynamic impact of analogous pathophysiologies in the normal two-year-olds. We operated the model in open-loop mode in order to expose the magnitude of the impact of uncompensated physiological perturbations. RESULTS: Without the benefit of compensatory mechanisms, a valvar regurgitant fraction of 50% is sufficient to drop the cardiac index (CI) to 2.0 L/min/m(2) or less. Aortopulmonary collateral flow of 0.6 L/min (1.1 L/min/m(2)) or 0.5 L/min (0.9 L/min/m(2)), sufficient to raise the ratio of pulmonary flow to systemic flow (Qp/Qs) to no higher than 1.2 or 1.5 (fenestration present or absent, respectively), is the maximum which could be tolerated (CI = 2.0 L/min/m(2)) without the help of compensatory mechanisms. Ventricular end-diastolic elastance (stiffness) changes have dramatic effects on CI in a Fontan circulatory arrangement. CONCLUSIONS: Several components of the Fontan circulation other than the TCPC actually have equal, or greater, impact on CI under certain conditions.

Model-Based Comparison of the Normal and Fontan Circulatory Systems: Part I: Development of a General Purpose, Interactive Cardiovascular Model.

BACKGROUND: Every year, approximately 1,000 Fontan operations are performed in the United States. Transplant-free, 30-year survival is only 50%. Although some performance characteristics may be universal among Fontan survivors, others may be patient specific and tunable; in either case, a quantitatively rigorous understanding of the Fontan circulatory arrangement would facilitate improvements in patient surveillance and management. METHODS: To create a computational model of a normal two-year-old and a two-year-old patient with hypoplastic left heart syndrome (HLHS) following staged surgical palliations, we extensively modified the lumped parameter model developed by Clark, a multicompartment model of both pulmonary and systemic circulations. RESULTS: With appropriately scaled parameter values, we achieved a maximum relative error (against target values for clinically realistic hemodynamic variables for the normal two-year-old) of 2.8% and an average relative error of 0.9%. Employing the model of a Fontan operation, we achieved a maximum relative error of 2.0% and the average relative error of 0.8%. CONCLUSIONS: Even with >200 model parameters, once we identified an acceptable set of values for the normal, only 12 required modification in order to attain clinically plausible hemodynamics in the HLHS after Fontan. When placed within the broad context of our extensive model, the impact on cardiac output of the resistance of the total cavopulmonary connection is found to be significantly affected by ventricular elastance and to be much lower in the two-year-old than in patients with markedly lower end-diastolic elastance (higher end-diastolic compliance).

Insights after 40 years of the fontan operation.

Fontan's visionary operation and its modifications over the ensuing decades have re-established nonturbulent flow and substantially reduced cyanosis for patients with severe hypoplasia of one ventricle. However, a long list of largely unexpected sequelae has emerged over the last 40 years. Although it is not difficult to understand how care providers could become discouraged, a number of myths have arisen, which we will attempt to dispel with real-world counterexamples as well as with lessons learned from other disciplines: evolutionary, developmental, and computational biology. We argue that distinctive biochemical abnormalities pointing to dysfunction in multiple organs, including the largest organ system in the body, the endothelium, occur long before grossly observable changes in cardiac imaging can be recognized. With a rational redesign of both our surveillance scheme and our wellness strategies, we hope that Fontan survivors and their families, as well as physicians, nurses, and therapists, will see why Fontan's principle remains just as vibrant today as it was in 1971.

A computational model of cardiovascular physiology and heart sound generation.

A computational model of the cardiovascular system is described which provides a framework for implementing and testing quantitative physiological models of heart sound generation. The lumped-parameter cardiovascular model can be solved for the hemodynamic variables on which the heart sound generation process is built. Parameters of the cardiovascular model can be adjusted to represent various normal and pathological conditions, and the acoustic consequences of those adjustments can be explored. The combined model of the physiology of cardiovascular circulation and heart sound generation has promise for application in teaching, training and algorithm development in computer-aided auscultation of the heart.

The impact of computer-assisted auscultation on physician referrals of asymptomatic patients with heart murmurs.

BACKGROUND: As many as 50-70% of asymptomatic children referred for specialist evaluation or echocardiography because of a murmur have no heart disease. HYPOTHESIS: Computer-assisted auscultation (CAA) can improve the sensitivity and specificity of referrals for evaluation of heart murmurs. METHODS: Seven board-certified primary care physicians were evaluated both without and with use of a computer-based decision-support system using 100 prerecorded patient heart sounds (55 innocent murmurs, 30 pathological murmurs, 15 without murmur). The sensitivity and specificity of their murmur referral decisions relative to American College of Cardiology/American Heart Association (ACC/AHA) guidelines, and sensitivity and specificity of murmur detection and characterization (innocent versus pathological) were measured. RESULTS: Sensitivity for detection of murmurs significantly increased with use of CAA from 76.6 to 89.1% (p <0.001), while specificity remained unaffected (80.0 versus 81.0%). Computer-assisted auscultation improved sensitivity of correctly identifying pathological murmur cases from 82.4 to 90.0%, and specificity of correctly identifying benign cases (with innocent or no murmurs) from 74.9 to 88.8%. (p <0.001). Referral sensitivity increased from 86.7 to 92.9%, while specificity increased from 63.5 to 78.6% using CAA (p <0.001). CONCLUSIONS: Computer-assisted auscultation appears to be a promising new technology for informing the referral decisions of primary care physicians.

Computer-aided auscultation of the heart: from anatomy and physiology to diagnostic decision support.

There is a clear and present need for computer-aided auscultation of the heart which arises from the highly informative nature of heart sounds, the inherent difficulty of auscultation and increasing pressure in healthcare for rapid, accurate, objective, documented and cost-effective patient evaluation and diagnostic decision making. There are advanced signal processing technologies that hold promise for developing computer-aided auscultation solutions that are intuitive, efficient, informative and accurate. Computer-aided auscultation offers an objective, quantitative and cost-effective tool for acquiring and analyzing heart sounds, providing archival records that support the patient evaluation and referral decision as well as serial comparisons for patient monitoring. There is the further promise of new quantitative acoustic measures and auscultatory findings that have more precise correlation with underlying physiological parameters. These solutions are being developed with the benefits of a rich literature of clinical studies in phonocardiography, the added insights derived from echocardiography, and advances in signal processing technology.

Computer-assisted detection of systolic murmurs associated with hypertrophic cardiomyopathy: a pilot study.

A pilot study was conducted to ascertain the level of agreement between auscultatory findings derived from heart sound recordings by a cardiologist and the results of a computer-based heart sound analysis algorithm. Heart sound recordings were obtained from volunteer subjects previously diagnosed with hypertrophic cardiomyopathy. Twenty-second recordings were obtained at each of 4 standard auscultatory locations on the precordium in 2 postures: standing and reclining. Detailed auscultatory findings were derived by a cardiologist, who listened to the heart sound recordings and was blinded to the study design. The recordings were analyzed by an algorithm that detects heart sounds and murmurs, and derives associated timing and energy parameters. The algorithm results were compared with the auscultatory findings provided by the cardiologist and correlated with the medical histories provided by the volunteer subjects. A high degree of concordance between the medical histories, auscultatory findings, and computer analyses was obtained. The 1st and 2nd heart sounds were detected with high sensitivity (90.7%) and positive predictivity (93.0%). Systolic murmurs were detected with a sensitivity that increased from 50% for grade 1 to 100% for grades 2-3 and 3. The signal energy in the mid-frequency range correlated well with murmur grade judgments, and also agreed well with the cardiologist's judgments of the relative loudness of murmurs in standing versus reclining postures. The computer analysis algorithm thus instantiates the objective detection and identification of apical systolic murmurs that are louder in standing than in reclining postures; such murmurs are a cardinal sign of hypertrophic obstructive cardiomyopathy.