Loss of Ventricular Function After Bidirectional Cavopulmonary Connection: Who Is at Risk?

Vincenti, Marie; Qureshi, Muhammad Yasir; Niaz, Talha; Seisler, Drew K.; Nelson, T. J. N.; Cetta, Frank

doi:10.1007/s00246-020-02433-9

Cited by 9 publications

(7 citation statements)

References 44 publications

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“…This temporarily impaired ventricular performance is a known phenomenon that has previously been reported for several CHD diagnoses [16]. Recently, Vincenti et al reported that ventricular impairment-assessed by ejection fraction obtained during cardiac catheterization-at hospital discharge and up to the months following PCPC was more severe for patients with a dominant right ventricle compared to those with a dominant left ventricle [17]. Our present study confirms this finding.…”

Section: Discussionsupporting

confidence: 90%

Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study

Ven

Kamphuis

Bosch

et al. 2023

JCDD

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Fontan patients undergo multiple cardiothoracic surgeries in childhood. Following these procedures, ventricular function is temporarily decreased, and recovers over months. This is presumably related to cardiopulmonary bypass, but this is incompletely understood. Throughout the Fontan palliation, cardiac function is also affected by volume unloading. We aimed to gain insight into the biological processes related to impaired ventricular function and recovery following Fontan palliations using a panel of biomarkers. Furthermore, we described changes in ventricular function across the Fontan palliation due to volume unloading. We performed a prospective multicenter observational study in patients undergoing partial (PCPC) or total cavo-pulmonary connection (TCPC). Patients underwent assessment—including echocardiography and blood sampling—before surgery (T1), at first follow-up (T2), and 1 year after their procedures (T3). Blood samples were analyzed using a biomarker panel (OLINK CVD-III). Ninety-two biomarkers were expressed as principal components (PC) to limit multiple statistical testing. We included 32 PCPC patients aged 7.2 [5.3–10.3] months, and 28 TCPC patients aged 2.7 [2.2–3.8] years. The single ventricular longitudinal strain (SV GLS) temporarily decreased for PCPC patients at T2 (−15.1 ± 5.6 (T1) to −13.5 ± 5.2 (T2) to −17.3 ± 4.5 (T3), p < 0.047 for all differences), but not following TCPC. The serum biomarkers were expressed as 4 PCs. PC1, including biomarkers of cell–cell adhesion, was not related to any patient characteristic. PC2, including biomarkers of superoxide anion regulation, increased at T2. PC3, including biomarkers of cardiovascular development, related to the stage of Fontan palliation. PC4 was of uncertain biological or clinical significance. No PC was found that related to ventricular performance. The SV GLS was temporarily diminished following PCPC, but not following TCPC. Several biomarkers were related to post-operative stress and adaptation to the PCPC or TCPC circulation, but none were related to the outcome.

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Section: Discussionsupporting

confidence: 90%

Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study

Ven

Kamphuis

Bosch

et al. 2023

JCDD

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“…This trial enrolled patients with normal RVEF at baseline. Consistent with previous natural history studies, RVEF drops following the stage II BDCPA due to loading condition alterations, but remains in the normal range (41). It is estimated that∼10% of children develop frank RV failure and require transplantation or die, with less than half of the children having transplant free survival to 15 years of age (42).…”

Section: Discussionsupporting

confidence: 89%

Intramyocardial cell-based therapy during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: The ELPIS phase I trial

Kaushal

Hoffman

Boyd

et al. 2022

Preprint

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Background: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction for the right ventricle (RV) to provide systemic circulation. This leads to substantially increased loads on the RV, wall stress, maladaptive remodeling and dysfunction, which in turn can increase risk of death or transplantation. Objectives: We conducted a phase I multicenter trial to assess safety and feasibility of intra-operative MSC injection in HLHS patients to boost RV performance in the systemic position. Methods: Allogeneic MSCs were directly administered by intramyocardial injections during the second stage palliative operation. The primary endpoint was safety Results: Ten patients received intramyocardial injections of allogeneic MSCs (Lomecel-B). No patients experienced major adverse cardiac events (MACE). All subjects were alive and transplant-free at 1 year following, and experienced growth comparable to healthy control historical data. Cardiac magnetic resonance imaging (CMR) revealed improving tricuspid regurgitant fraction (Baseline: 0.45 ± 0.19; 6 mo.: 0.32 ± 0.06; 12 mo.: 0.06 ± 0.09), while global longitudinal strain (Baseline: -24.39 ± 6.99; 6 mo.: -20.55 ± 3.05, p > 0.05 vs baseline; 12 mo.: -23.88 ± 4.6, p>0.05 vs baseline) and RV ejection fraction (EF; baseline: 62.62 ± 5.99; 6 mo.: 53.69 ± 9.56; 12 mo.: 52.31 ± 5.63: p=NS for change over time) were unchanged. Computational modeling identified 167 derived RNAs specific to tcirculating exosomes originating from transplanted MSCs corresponding to RVEF changes and identifying potential mechanistic underpinnings. Conclusions: Intramyocardial MSCs appear safe in HLHS patients, and may favorably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway.

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“…The RVs had a decreased mean EF after bidirectional cavopulmonary connection (BDCPC) compared with single morphologic LVs, which remained stable 5,6,36 . Moreover, Vincenti et al recently published sim ilar results, especially in the HLHS population subset 37 .…”

Section: Discussionmentioning

confidence: 95%

Autologous Umbilical Cord Blood–Derived Mononuclear Cell Therapy Promotes Cardiac Proliferation and Adaptation in a Porcine Model of Right Ventricle Pressure Overload

et al. 2022

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Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood–derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

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Loss of Ventricular Function After Bidirectional Cavopulmonary Connection: Who Is at Risk?

Cited by 9 publications

References 44 publications

Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study

Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study

Intramyocardial cell-based therapy during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: The ELPIS phase I trial

Autologous Umbilical Cord Blood–Derived Mononuclear Cell Therapy Promotes Cardiac Proliferation and Adaptation in a Porcine Model of Right Ventricle Pressure Overload

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