Aortic stenosis that occurs during fetal development results in added stress on the left ventricle in utero. This can eventually lead to decreased perfusion through the left ventricle which is believed to inhibit ventricular growth. Pathophysiology
At birth, the ductus arteriosus is still open, and there is higher than normal resistance to blood flow in the lungs. This allows for adequate oxygenation via mixing between the atria and a normal appearance at birth. When the ductus begins to close and pulmonary vascular resistance decreases, blood flow through the ductus is restricted and flow to the lungs is increased.In typical anatomy, the left side of the heart receives oxygen-rich blood from the lungs and pumps it to the rest of the body. Patients with HLHS can have a number of cardiac malformations that ultimately lead to a diminutive left ventricle that is unable to supply sufficient blood flow to the rest of the body. There are three main anatomic variants of the disease differentiated by either stenosis or atresia of the aortic and mitral valve.Mitral atresia and aortic atresia (MA-AA) subtype is the most severe form of HLHS resulting in no blood flow entering the left ventricle at all resulting in no possibility of left ventricular output. In the mitral stenosis and aortic atresia (MS-AA) subtype blood is able to fill the left ventricle, however it is unable to be supplied to the systemic circulation via the hypoplastic ascending aorta. Lastly, the mildest form is the mitral stenosis and aortic stenosis (MS-AS) subtype.
Copanlisib (trade name Aliqopa  AL-ih-KOH-pah; codenamed BAY 80-6946) is a drug which is approved by US FDA for the treatment of adult patients experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies.Copanlisib has been shown to have an effect against survival and spread of cancerous B-cells. Efficacy resulting in the approval of copanlisib was based on the subgroup of 104 patients with follicular lymphoma from a Phase 2 clinical trial. Of these, 59 percent had a complete or partial shrinkage of their tumors that lasted about 12 months. To assess the safety of the drug, data from 168 adults with follicular lymphoma and other hematologic malignancies treated with copanlisib were evaluated.Copanlisib is administered as intravenous infusion on a weekly but intermittent schedule (three weeks on and one week off). Copanlisib is currently approved only in the United States. Adverse effects
Data for safety and efficacy of copanlisib are described in the consumer-targeted FDA Drug Trial Snapshot. Copanlisib can cause serious side effects including infections, hyperglycemia, hypertension, pneumonitis, neutropenia and skin rashes. The most common side effects of copanlisib are hyperglycemia, diarrhea, decreased general strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory tract infections and thrombocytopenia. Copanlisib can cause harm to unborn babies. Patients with reproductive potential are thus advised to use effective contraception. Lactating patients are advised to not breastfeed. Mechanism of action
Copanlisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3K-α and PI3K-δ isoforms expressed in malignant B-cells.