Abstract

Due to the absence of a sub-pulmonary ventricle, the Fontan circulation is sensitive to respiration-induced changes in intrathoracic pressure. However, the importance of a ‘respiratory pump’ in creating forward flow remains controversial. We aimed at evaluating the effect of respiration on ventricular filling during exercise using clinical data and computational modeling predictions. Ten Fontan patients (6 male, 20 ± 4 years) underwent ungated cardiac magnetic resonance (CMR) imaging at rest and during supine bicycle exercise to evaluate systemic ventricular volumes (end-diastolic volume index (EDVi), end-systolic volume index (ESVi) and stroke volume index (SVi)) during normal respiration and a Valsalva maneuver. Respiratory-dependent SV was calculated. Clinical results were compared to predictions made by a closed-loop lumped-parameter (LPN) computational model of Fontan circulation. Inspiration resulted in increased EDVi (98 ± 16 to 103 ± 15 mL, P = 0.001), SVi (55 ± 9 to 59 ± 9 mL, P = 0.001) and cardiac index (3.9 ± 0.7 to 4.2 ± 0.8 L/min, P = 0.002), whereas ESVi (P = 0.096) remained unchanged. The effect of inspiration on EDVi (mean effect + 6 ± 1 mL, P < 0.0001) and SVi (+ 4 ± 1 mL, P < 0.0001) was maintained during exercise. Respiratory-dependent SVi tended to increase during exercise (3 ± 2% to 5 ± 3%, P = 0.084). Valsalva resulted in decreased EDVi (P = 0.001), ESVi (P = 0.003) and SVi (P = 0.005). Computational modeling indicated higher EDV and SV at end-inspiration and expiration, showing a phased time delay between peak caval vein flow and peak SV. In Fontan patients, inspiration resulted in increased ventricular filling at rest and during exercise. Results were confirmed using a computational model indicating a phased time delay between peak SV and peak caval vein flow.

Abstract

AL amyloidosis and multiple myeloma result in extracellular deposition of insoluble fibrillary protein in tissue and organs. Untreated median survival is very poor, and even worse with cardiac involvement. Chemotherapy and peripheral blood stem cell transplantation (PBSCT) have been shown to dramatically improve survival, with hematologic remission documented. Regression of cardiac changes has previously been shown, as assessed by echocardiography (TTE) and cardiac magnetic resonance imaging (CMR). This study is a comparison of TTE and CMR in long-term survivors of cardiac amyloidosis with regression. Four long-term survivors with cardiac amyloidosis and regression of cardiac features on TTE were identified. Mean age was 60 years and average survival was 139 months from the time of diagnosis of cardiac involvement. Statistically significant regression of the cardiac features of cardiac amyloidosis were demonstrated on TTE. In these survivors, post-PBSCT structural assessments were similar between TTE and CMR. Classical strain imaging features of cardiac amyloidosis were only present in 50%. All patients had diffuse, patchy gadolinium enhancement on CMR after PBSCT. Treatment of cardiac amyloidosis with chemotherapy and PBSCT may result in regression of abnormalities on TTE with marked improvement in survival. Post treatment, TTE and CMR structural assessments appear similar. Gadolinium imaging suggests that microscopic residual infiltration persists despite macroscopic regression. Significant cardiac improvements with prolonged survival are seen nonetheless. Multimodality imaging has a vital role in the management of cardiac amyloidosis.