RARE DISEASE
Univentricular heart
Univentricular heart
Univentricular heart
Synonyms: Double inlet atrioventricular connection
Synonyms: Double inlet atrioventricular connection
Synonyms: Double inlet atrioventricular connection
Drug discovery
4
drugs
With orphan designations
Overview
Univentricular Heart (UVH) encompasses congenital cardiac defects where both atria connect to a single functional ventricle, often accompanied by complex anatomic variations. Clinical manifestations include congestive heart failure, cyanosis, and systemic hypoxemia due to unbalanced circulations. Management involves staged palliative surgeries (e.g., Fontan procedure) to optimize hemodynamics, though long-term complications like arrhythmias, ventricular dysfunction, and multiorgan impacts persist [1][6][11].
Burden
Mortality: Up to 61% in untreated cases; 5-year survival post-palliation ~77%, with attrition from arrhythmias and heart failure [4][7][9].
Long-term morbidity: 40–50% develop heart failure, 7–39% arrhythmias, and protein-losing enteropathy [9][13][14].
Psychosocial strain: Families report high stress due to neurodevelopmental delays and recurrent hospitalizations [14][16].
Therapies
Staged surgical palliation (Norwood, Glenn, Fontan) to establish passive pulmonary blood flow [3][8][16].
Adjuvant therapies: Pulmonary artery banding, Damus-Kaye-Stansel anastomosis, and mechanical circulatory support for high-risk cases [3][6][15].
Heart transplantation reserved for Fontan failure or end-stage disease [9][13].
Categories: rare cardiac malformations, rare developmental anomalies during embryogenesis
Research Papers
1,957 drug discovery papers about Univentricular heart, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,957 drug discovery papers about Univentricular heart, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-05-29 | Perinatal brain development in congenital heart disease
This thesis shows that children with critical congenital heart disease (CCHD) have altered brain growth trajectories that begin during fetal life and continue after neonatal cardiac surgery. These changes are not limited to a single brain region, but affect multiple brain structures. The timing and pattern of altered brain growth differ between CCHD subtypes. In transposition of the great arteries, brain growth abnormalities are diffuse and already visible early in the third trimester of pregnancy. In contrast, in univentricular heart defects and aortic arch anomalies, cerebral vulnerability appears to be more region-specific and emerges later in development. The mechanisms underlying delayed brain development are likely complex and multifactorial. Besides altered oxygen delivery and cerebral blood flow, both during fetal life and around the time of cardiac surgery, placental dysfunction, disruption of the insulin-like growth factor axis, and maternal health and stress may also contribute. Importantly, disturbances in early brain development appear to have long-term consequences, as neonatal brain volumes and brain injury are strongly associated with brain structure at school-age. At the same time, some regions, particularly the white matter, remain vulnerable beyond the neonatal period, especially in children who undergo additional cardiac interventions. The findings of this thesis highlight the importance of the perinatal period as a window for neuroprotection. Prenatally, optimizing placental function, treating maternal conditions, and reducing maternal stress may help support fetal brain development. Postnatally, allopurinol may offer opportunities to reduce brain injury around birth and neonatal cardiac surgery. In the future, it will also be important to investigate neuroprotective strategies for cardiac interventions beyond the neonatal period.
2026-05-01 | The Benefits of a Standardized Approach in Fontan Patients–an Effective Approach for Tailoring Treatment to Individual Needs
Although being a great achievement for patients with univentricular heart (UVH), the Fontan circulation remains a matter of discussion. As a standardized and reproducible surgical method, the extracardiac conduit using a PTFE conduit (TCPC) has demonstrated excellent results.1 Patients with UVH have the prospect of living a long and satisfying life with the Fontan pathway. However, the variety of diagnoses, the type of systemic ventricle and additional burden such as neurologic sequelae, render it difficult to predict the outcome of an individual patient. Furthermore, unresolved questions remain, such as the need for a fenestration or the optimal size of the extracardiac conduit. Most large studies analysing long-term data of patients after TCPC do not find consistent results for all patients. Knowing this discrepancy in results and acknowledging the heterogeneity of patients, it seems more than logic to treat patients depending on their personal underlying physiology. What seems evident can be a challenge in the everyday care of patients with UVH. Benli et al.2 have designed a protocol, structuring the treatment of patients undergoing a TCPC depending on preoperative haemodynamic findings. Starting with a congenital cardiac surgery registry used at 4 centres in 2 countries, the procedure involved a physiology-anchored assessment before Fontan completion, a haemodynamic-driven intraoperative decision on selective fenestration, and a standardised perioperative management protocol including an escalation strategy regarding pleural effusion.
2026-04-14 | Biological tissue engineering for Fontan failure using decellularized extracellular matrix: a systematic review.
BACKGROUND: Functional univentricular heart disease is the most severe congenital condition, managed by Fontan surgery, which is life-sustaining by creating a non-contractile conduit yet limited by long-term complications. Decellularized ECM (dECM) scaffolds reseeded with contractile human cells offer a promising solution, but key factors for such a biological tube remain undefined. AIM: To evaluate the potential of cardiac dECM as a scaffold for recellularization in the development of a contractile Fontan conduit. METHODS: A systematic review was performed of studies identified in PubMed, Embase, Web of Science, and the Cochrane Library on human or porcine cardiac tissue engineering. Decellularization outcome parameters included efficiency of DNA removal, ECM preservation, and cytocompatibility; recellularization parameters focused on cell viability, co-culture strategies, maturation, and contractility. RESULTS: Fifty-eight studies on decellularization of porcine or human cardiac tissue were included; 13 also investigated recellularization. Most studies reported more than 90% reduced DNA content and preserved ECM architecture, though quantitative ECM analyses and toxicity assessments were not often reported. Recellularization with cardiomyocyte (like) cells showed high viability, especially in slice monocultures. Co-culture with other cell types improved organization and sarcomere maturation. Functionality assessment in most studies showed spontaneous and synchronized contractions however remaining under normal physiological values. CONCLUSION: Cardiac dECM scaffolds hold promise for contractile Fontan conduits; however, standardized decellularization protocols, enhanced recellularization strategies, and integration of vascular and supportive cells are needed to advance clinical translation.
2026-05-29 | Perinatal brain development in congenital heart disease
This thesis shows that children with critical congenital heart disease (CCHD) have altered brain growth trajectories that begin during fetal life and continue after neonatal cardiac surgery. These changes are not limited to a single brain region, but affect multiple brain structures. The timing and pattern of altered brain growth differ between CCHD subtypes. In transposition of the great arteries, brain growth abnormalities are diffuse and already visible early in the third trimester of pregnancy. In contrast, in univentricular heart defects and aortic arch anomalies, cerebral vulnerability appears to be more region-specific and emerges later in development. The mechanisms underlying delayed brain development are likely complex and multifactorial. Besides altered oxygen delivery and cerebral blood flow, both during fetal life and around the time of cardiac surgery, placental dysfunction, disruption of the insulin-like growth factor axis, and maternal health and stress may also contribute. Importantly, disturbances in early brain development appear to have long-term consequences, as neonatal brain volumes and brain injury are strongly associated with brain structure at school-age. At the same time, some regions, particularly the white matter, remain vulnerable beyond the neonatal period, especially in children who undergo additional cardiac interventions. The findings of this thesis highlight the importance of the perinatal period as a window for neuroprotection. Prenatally, optimizing placental function, treating maternal conditions, and reducing maternal stress may help support fetal brain development. Postnatally, allopurinol may offer opportunities to reduce brain injury around birth and neonatal cardiac surgery. In the future, it will also be important to investigate neuroprotective strategies for cardiac interventions beyond the neonatal period.
2026-05-01 | The Benefits of a Standardized Approach in Fontan Patients–an Effective Approach for Tailoring Treatment to Individual Needs
Although being a great achievement for patients with univentricular heart (UVH), the Fontan circulation remains a matter of discussion. As a standardized and reproducible surgical method, the extracardiac conduit using a PTFE conduit (TCPC) has demonstrated excellent results.1 Patients with UVH have the prospect of living a long and satisfying life with the Fontan pathway. However, the variety of diagnoses, the type of systemic ventricle and additional burden such as neurologic sequelae, render it difficult to predict the outcome of an individual patient. Furthermore, unresolved questions remain, such as the need for a fenestration or the optimal size of the extracardiac conduit. Most large studies analysing long-term data of patients after TCPC do not find consistent results for all patients. Knowing this discrepancy in results and acknowledging the heterogeneity of patients, it seems more than logic to treat patients depending on their personal underlying physiology. What seems evident can be a challenge in the everyday care of patients with UVH. Benli et al.2 have designed a protocol, structuring the treatment of patients undergoing a TCPC depending on preoperative haemodynamic findings. Starting with a congenital cardiac surgery registry used at 4 centres in 2 countries, the procedure involved a physiology-anchored assessment before Fontan completion, a haemodynamic-driven intraoperative decision on selective fenestration, and a standardised perioperative management protocol including an escalation strategy regarding pleural effusion.
2026-04-14 | Biological tissue engineering for Fontan failure using decellularized extracellular matrix: a systematic review.
BACKGROUND: Functional univentricular heart disease is the most severe congenital condition, managed by Fontan surgery, which is life-sustaining by creating a non-contractile conduit yet limited by long-term complications. Decellularized ECM (dECM) scaffolds reseeded with contractile human cells offer a promising solution, but key factors for such a biological tube remain undefined. AIM: To evaluate the potential of cardiac dECM as a scaffold for recellularization in the development of a contractile Fontan conduit. METHODS: A systematic review was performed of studies identified in PubMed, Embase, Web of Science, and the Cochrane Library on human or porcine cardiac tissue engineering. Decellularization outcome parameters included efficiency of DNA removal, ECM preservation, and cytocompatibility; recellularization parameters focused on cell viability, co-culture strategies, maturation, and contractility. RESULTS: Fifty-eight studies on decellularization of porcine or human cardiac tissue were included; 13 also investigated recellularization. Most studies reported more than 90% reduced DNA content and preserved ECM architecture, though quantitative ECM analyses and toxicity assessments were not often reported. Recellularization with cardiomyocyte (like) cells showed high viability, especially in slice monocultures. Co-culture with other cell types improved organization and sarcomere maturation. Functionality assessment in most studies showed spontaneous and synchronized contractions however remaining under normal physiological values. CONCLUSION: Cardiac dECM scaffolds hold promise for contractile Fontan conduits; however, standardized decellularization protocols, enhanced recellularization strategies, and integration of vascular and supportive cells are needed to advance clinical translation.
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Drug Discovery Landscape
4 orphan drug designations for Univentricular heart.
4 orphan drug designations for Univentricular heart.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Macitentan [Opsumit] | small molecules | EMA | 2021-05-20 | — | Janssen Cilag International |
autologous mononuclear cells derived from umbilical cord blood | cell therapies | FDA | 2017-07-13 | — | HeartWorks |
Udenafil | small molecules | EMA | 2016-12-12 | — | ICON Clinical Research Limited |
udenafil | small molecules | FDA | 2015-08-31 | — | Mezzion Pharma Co. Ltd. |
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