Twin Twin Transfusion Syndrome

TTTS - Hemodynamic evaluation and management by Dr. Anie Lapointe

Presentation by Dr Ida Whiteman and Mrs Kristina Huber in the context of Neonatal Cardiology Rounds on TTTS on March 13, 2024

Case of Pulmonary Stenosis in the recipient twin

Case of significant hypertrophy in the context of a recipient twin

Important Articles

Case - January 2024 - TTTS with hypovolemia

Case - January 2025 - RVOT obstruction in TTTS

The receiver often has congestive heart failure. The donor often has hypertrophic heart failure. For the recipient, there is increased preload (volume) with an absolute increase in circulating volume compared to that of the donor, with significantly higher cardiac output. The recipient is also subjected to an increased afterload in the form of increased resistance. The renin-angiotensin system (RAS) is ‘downregulated’ in the recipient's kidneys, but work has shown that the levels are as high as in the donor; it is assumed that this is mainly due to transfer from the donor. All these factors explain the development of significant myocardial ventricular hypertrophy, out of proportion to simple volume overload. A consequence of this progressive cardiomyopathy is an increase in overall heart size, a reduction in myocardial compliance, atrioventricular valvar regurgitation, and abnormal venous Dopplers. RVOT anomalies in the recipient may be in the form of valvar dysplasia, stenosis, regurgitation, or functional atresia; early involvement of the RVOT may be demonstrated by observing that the pulmonary valve annulus is equal in size to or smaller than that of the aortic valve, and this can progress to produce significant valvar pathology. It is not clear whether RVOT anomalies mirror the severity of the TTTS process, or whether the anomalies are simply due to altered hemodynamics or are a consequence of the vasoactive mediators. The prevalence of RVOT anomalies varies in different series but may be seen in some form in up to 20% of MC/DA twins, but only in recipient twins; between 9 and 12.5% had persistent anomalies requiring postnatal treatment, in spite of otherwise successful treatment for the TTTS.

Reference for Data and Figure: Manning N, Archer N. Cardiac Manifestations of Twin-to-Twin Transfusion Syndrome. Twin Res Hum Genet. 2016 Jun;19(3):246-54. doi: 10.1017/thg.2016.20. Epub 2016 Apr 18. PMID: 27087122.

In Twin-to-Twin Transfusion Syndrome (TTTS), congenital heart disease (CHD) can develop in one of the twins primarily due to physiological stress and altered hemodynamics related to the shared placenta. In TTTS, one fetus (the "donor") transfuses blood to the other (the "receiver") through placental anastomoses. The receiver fetus becomes fluid overloaded and "intoxicated" by hypertensive substances, such as those from the renin-angiotensin system, and also experiences problems with placental resistance. This leads to the receiver fetus becoming hypertensive, larger, and having more amniotic fluid. The increased arterial hypertension and resistance impact both ventricles, leading to cardiac changes. The right ventricle (RV) frequently becomes hypertrophied. This hypertrophy occurs because the RV, to normalize its strain under the increased afterload (due to elevated pulmonary and systemic resistances), thickens significantly. As a consequence of the RV hypertrophy and its reduced filling, an obstruction to pulmonary outflow can develop, leading to pulmonary stenosis. In some rarer cases, this can progress to pulmonary atresia with an intact septum in the receiver fetus. The left ventricle can also experience issues related to hypertension. These cardiac abnormalities in TTTS are considered acquired CHDs that are purely physiological in origin, rather than being related to primary morphogenetic or genetic processes. The distinct physiological conditions and circulatory differences between the two fetuses contribute to the development of these heart conditions.

The donor twin experiences a unique set of cardiac and vascular challenges distinct from those of the recipient twin. Due to an unbalanced blood flow through placental vascular anastomoses, the donor twin is characteristically hypovolemic, receiving less blood volume than necessary. This reduced blood volume triggers compensatory physiological changes that affect the donor's cardiovascular system. The donor twin's heart typically does not show severe structural cardiac abnormalities during fetal echocardiographic assessment, unlike the recipient twin, which often exhibits signs of volume overload and cardiomegaly. However, the donor twin suffers from increased afterload caused by elevated placental vascular resistance. This increased resistance arises partly because the donor twin’s share of the placenta is often smaller or less functional, leading to a higher vascular resistance that the heart must work against. Consequently, the donor twin’s heart faces a sustained increase in pressure load. The hemodynamic stress on the donor heart is compounded by hypovolemia, which results in decreased renal perfusion and activation of maladaptive neurohormonal mechanisms. These include increased production of vasoactive substances such as angiotensin II and endothelin I, which contribute to systemic vasoconstriction, vascular remodeling, and arterial wall thickening. The outcome is a persistent alteration in arterial structure, with changes such as collagen deposition, smooth muscle hypertrophy, and vascular stiffness, not only affecting fetal circulatory function but also predisposing the donor twin to long-term vascular issues after birth. Although congenital heart defects are less common in donor twins than in recipients, altered blood flow during fetal life may increase the risk of specific structural anomalies. Among these potential conditions is coarctation of the aorta or hypoplastic aortic arch, which are thought to be related to the chronic reduced blood flow and increased resistance affecting the left heart and systemic circulation. With a combination of high resistances and low preload, there is a net drop in antegrade blood flow through the arch and aortic isthmus, leading to underdevelopment of the aorta. The donor’s cardiovascular system is thus in a state of high afterload with low preload, which can impair cardiac output and promote remodeling and dysfunction over time.

TTTS - Hemodynamic evaluation and management by Dr. Anie Lapointe

TTTS_NHRC_FINAL3.pdf

Presentation by Dr Ida Whiteman and Mrs Kristina Huber in the context of Neonatal Cardiology Rounds on TTTS on March 13, 2024

TTTS Final.pdf

Case of Pulmonary Stenosis in the recipient twin

Parasternal long axis B-Mode. There is a sweep anteriorly. One may appreciate the RV hypertrophy with the significant narrowing of the RVOT and underlying pulmonary stenosis (with small pulmonary valvular annulus)

PLAX with acceleration of flow in at the pulmonary valve (aliasing seen at a velocity filter/Nyquiest of -1.14 m/s)

PDA is seen left to right, potentially contributing to pulmonary blood flow.

PDA measured at 2.2 mm in 2D.

Modified view where one may appreciate that the pulmonary valve is doming and that its opening is narrowed - outlining some 2D evidence of underlying pulmonary stenosis.

Turbulence of flow / alliasing in the RVOT by colour.

2D view clip and 2D still frame with measurement of the pulmonary valvular annulus.

Parasternal short axis with colour and B-mode. The colour showcases aliasing from the turbulence of flow created by the pulmonary stenosis. One may also appreciate some of the PDA flow feeding into the branche pulmonary arteries.

Apical view sweep from posterior to anterior where we can appreciate the RVOT and pulmonary valve. The Pulmonary valve annulus is measured at 0.31 cm.

Colour flow through the RVOT into the branch pulmonary arteries.

Gradient obtained from the Parasternal Long axis view outlining a RV-MPA gradient of 128 mmHg (stenosis of the pulmonary valve). There is a dagger-shaped high-velocity Doppler spectra outlining there is a dynamic component to the obstruction.

Subcostal view with CW-Doppler in the RVOT with a gradient of 133.7 mmHg RV to PA, outlining significant pulmonary stenosis.

Subcostal view with 2D sweep and colour (outlining an inter-atrial shunt that is bidirectional, but significantly right to left due to increase RV end-diastolic pressure).