The Genetic Architecture of a Congenital Heart Defect Is Related to Its Fitness Cost.

In newborns, severe congenital heart defects are rarer than mild ones. This epidemiological relationship between heart defect severity and incidence lacks explanation. Here, an analysis of ~10,000 Nkx2-5+/- mice from two inbred strain crosses illustrates the fundamental role of epistasis. Modifier genes raise or lower the risk of specific defects via pairwise (G×GNkx) and higher-order (G×G×GNkx) interactions with Nkx2-5. Their effect sizes correlate with the severity of a defect. The risk loci for mild, atrial septal defects exert predominantly small G×GNkx effects, while the loci for severe, atrioventricular septal defects exert large G×GNkx and G×G×GNkx effects. The loci for moderately severe ventricular septal defects have intermediate effects. Interestingly, G×G×GNkx effects are three times more likely to suppress risk when the genotypes at the first two loci are from the same rather than different parental inbred strains. This suggests the genetic coadaptation of interacting G×G×GNkx loci, a phenomenon that Dobzhansky first described in Drosophila. Thus, epistasis plays dual roles in the pathogenesis of congenital heart disease and the robustness of cardiac development. The empirical results suggest a relationship between the fitness cost and genetic architecture of a disease phenotype and a means for phenotypic robustness to have evolved.

Risk of neurological decompression sickness in the diver with a right-to-left shunt: literature review and meta-analysis.

OBJECTIVE: Literature review and meta-analysis to review the evidence of relationship between the presence of right-to-left shunts (RLSs) and the occurrence of neurological decompression sickness (DCS) in divers. DATA SOURCES: MEDLINE, Google Scholar, and Health Technology Assessment databases. STUDY SELECTION: Five case-control studies in which the prevalence of a RLS in a group of divers with neurological DCS was compared with that of a group of divers with no history of DCS, 3 cross-transversal studies in which the prevalence of RLS was measured in divers with neurological DCS, and 4 cross-transversal studies in which the prevalence of RLS was measured in divers with no history of DCS were reviewed. DATA EXTRACTION: Only case-control studies were retained for meta-analysis. DATA SYNTHESIS: This meta-analysis gathers 5 studies and 654 divers. The combined odds ratio of neurological DCS in divers with RLS was 4.23 (3.05-5.87). The meta-analysis including only large RLS found a combined odds ratio of 6.49 (4.34-9.71). CONCLUSIONS: Because of a low incidence of neurological DCS, increase in absolute risk of neurological DCS due to RLS is probably small. Thus, in recreational diving, the systematic screening of RLS seems unnecessary. In professional divers, because of a chronic exposition and unknown consequences of cerebral asymptomatic lesions, these results raise again the benefit of the transcranial Doppler in the screening and quantification of the RLS, independently of their location.

Noninvasive cardiac flow assessment using high speed magnetic resonance fluid motion tracking.

Cardiovascular diseases can be diagnosed by assessing abnormal flow behavior in the heart. We introduce, for the first time, a magnetic resonance imaging-based diagnostic that produces sectional flow maps of cardiac chambers, and presents cardiac analysis based on the flow information. Using steady-state free precession magnetic resonance images of blood, we demonstrate intensity contrast between asynchronous and synchronous proton spins. Turbulent blood flow in cardiac chambers contains asynchronous blood proton spins whose concentration affects the signal intensities that are registered onto the magnetic resonance images. Application of intensity flow tracking based on their non-uniform signal concentrations provides a flow field map of the blood motion. We verify this theory in a patient with an atrial septal defect whose chamber blood flow vortices vary in speed of rotation before and after septal occlusion. Based on the measurement of cardiac flow vorticity in our implementation, we establish a relationship between atrial vorticity and septal defect. The developed system has the potential to be used as a prognostic and investigative tool for assessment of cardiac abnormalities, and can be exploited in parallel to examining myocardial defects using steady-state free precession magnetic resonance images of the heart.

["Real time"-3D-echocardiography: a valuable new tool in preoperative assessment of complex cardiac defects]. / "Real Time"-3D-Echokardiographie: Erfahrungen im Kindesalter. Fallbeispiel für die Einsatzmöglichkeit der dreidimensionalen Echtzeit-Echokardiographie in der präoperativen Abklärung angeborener Herzfehler.

Evaluating complex cardiac defects in small children preoperatively requires multiple diagnostic procedures including echocardiography, but also the invasive methods such as cardiac catheterisation, computer-tomography and magnetic resonance imaging. We tried to assess the complex anatomy of the atrioventricular valves in atrioventricular septal defect using bedside real-time three-dimensional echocardiography and comparing these results to the anatomic findings at the time of operation.

[Comparison between biventricular cine MRI and MR flow quantification in ascending aorta and pulmonary outflow tract for the assessment of intracardial shunt volumes]. / Vergleich von biventrikulärer MR-Volumetrie und MR-Flussmessungen in Aorta ascendens und Truncus pulmonalis zur intrakardialen Shuntbestimmung.

PURPOSE: Comparison between biventricular volumetric measurements and flow measurements in ascending aorta (Ao) and pulmonary outflow tract (Pu) for quantification of intracardial shunts, and evaluation of the combination of biventricular cine MRI with flow measurements for the assessment of RV and LV heart failure and valvular regurgitation (VR). MATERIAL AND METHODS: In 24 patients, right (RV) and left (LV) ventricular volumetric and flow measurements were performed in the Ao and Pu to assess the ratio of RV stroke volume (SV) or, respectively, pulmonary SV to LV SV or, respectively, systemic aortic SV (Qp/Qs). 34 patients without echocardiographically proven shunt or VR served as control group for measurement accuracy. Left-to-right shunt ratios were calculated from RV and LV SV, Pu and Ao SV, Pu and LV SV, and RV and Ao SV. Left ventricular VR was calculated by the difference of LV SV and Ao SV, and right ventricular VR by the difference of RV SV and Pu SV. Global systolic function was evaluated by biventricular cine MRI. RESULTS: Intracardial shunts with Qp/Qs > 1.16 can be quantified by flow measurements in Ao and Pu. Using biventricular volumetric measurements in cases without VR, requires a Qp/Qs > 1.21. 17 of 18 intracardiac shunts were identified on MRI, and all 8 hemodynamically significant shunts were quantitatively confirmed. The diagnosis of complete shunt closure or absent shunt was correctly made in all 6 cases. RV EF reduction was found in 6 of 24 patients. LV EF reduction was also found in 6 of 24 patients. CONCLUSION: Flow measurements in Ao and Pu are more accurate than biventricular cine MRI for the assessment of Qp/Qs ratios. Flow measurements in Ao and Pu combined with biventricular cine MRI enables the quantification of hemodynamic significant shunts, higher grade VR and biventricular global systolic function with a single examination.

[Comparative assessment of hemodynamic parameters in ventricular septal defect, obtained by Doppler echocardiography and catheterization of cardiac cavities]. / Sravnitel'naia otsenka pokazatelei gemodinamiki pri DMZhP, poluchennykh s pomoshch'iu doppleroékhokardiografii i kateterizatsii polosteí serdtsa.

The study was undertaken to assess hemodynamic parameters by Doppler echocardiography in patients with ventricular septal defect (VSD) and pulmonary hypertension. Seventy-two patients aged 5 months to 9 years (mean 2.5 years) who had isolated VSD were examined. The authors conclude that it is possible and necessary to assess hemodynamics in the lesser circulation by using Doppler echocardiography. The method permits monitoring the time course of changes in the right heart, which makes it possible to follow the natural history of disease without applying invasive studies.

A critical reappraisal of the oximetric assessment of intracardiac left-to-right shunting in adults.

Although the oximetric analysis of blood from the right heart chambers is the most commonly used method for assessing the presence of intracardiac left-to-right shunting, the data the analysis is based on are limited. In addition, uncertainty exists concerning the best way of estimating the mixed venous oxygen content in subjects with intraatrial left-to-right shunting. In 102 adults without left-to-right shunting, blood was obtained from the venae cavae and right heart chambers to measure oxygen content. The limits of normality of oxygen content differences were 0.5 ml/dl from venae cavae to right atrium, 0.6 ml/dl from right atrium to right ventricle, and 0.9 ml/dl from right ventricle to pulmonary artery. The pulmonary arterial oxygen content was best estimated by combining the superior and inferior vena caval oxygen contents according to the formula (2[SVC] + 3[IVC]) divided by 5, where SVC is the superior vena cava and IVC is the inferior venae cava. These data provide new oximetric criteria for establishing the presence of intracardiac left-to-right shunting in adults.

Right atrial tumor arising on an atrial septal aneurysm. Assessment by MR imaging.

An elderly women presenting with transient ischemic events underwent transesophageal echocardiography, which detected an aneurysm of the interatrial septum. A tumor protruding from the right atrial aspect of the aneurysm also was found incidentally. Not only was magnetic resonance (MRI) imaging helpful in better characterizing the aneurysm, but also the use of gadolinium diethylaminetriamine pentaacetic acid permitted differentiation between the tumor and adherent thrombus. To the best of our knowledge, this represents the first report of a tumor arising from an atrial septal aneurysm.

Assessment of intracardiac shunts with gadolinium-enhanced ultrafast MR imaging.

Dye dilutional techniques are widely accepted for the assessment of intracardiac shunts, but current techniques require arterial access or radioisotope injection. Ultrafast (less than 500 msec) magnetic resonance (MR) imaging is ideally suited for the evaluation of an indicator during passage through the heart. Twenty patients were studied, including 13 with shunts. Four-chamber, T1-weighted images were obtained during bolus injection of gadopentetate dimeglumine. A single image was obtained in 420 msec, with repetitive images acquired after each QRS complex. After the contrast material was injected, there was pronounced signal intensity enhancement in the right atrium, followed by the right ventricular cavity, left atrium, left ventricular cavity, and descending aorta. Patients with substantial intracardiac shunts demonstrated early recirculation. First-pass contrast material-enhanced MR imaging is a promising new technique for the rapid assessment of intracardiac shunts. Combined with anatomic and functional MR imaging techniques, it can help provide a comprehensive noninvasive evaluation of suspected intracardiac shunts or provide follow-up in patients with known shunts.

Two-dimensional echocardiographic assessment of intracardiac masses in infants and children.

We studied six infants and children with intracardiac masses of different causes. The diagnosis was made noninvasively using two-dimensional echocardiography in all six patients. In five patients, surgical excision of the mass was undertaken with good results. Two-dimensional echocardiography is an excellent noninvasive diagnostic tool that allows the clinician to determine the size and location of intracardiac masses in infants and children.

Assessment of the sensitivity of hydrogen inhalation in the detection of left-to-right shunting.

For the detection of left-to-right intracardiac shunting, the oximetric and standard indocyanine green techniques are relatively insensitive, in that neither can reliably detect a shunt with a ratio of pulmonary to systemic flow (Qp/Qs) less than 1.3 (percentage shunt, 23%). Although the hydrogen inhalation method is said to be much more sensitive in this regard, no previous study has measured its sensitivity. Accordingly, in 15 patients (4 men, 11 women, aged 38 to 67 years) without intracardiac shunting, hydrogen inhalation was performed 1) without and 2) with an artificially created femoral arteriovenous shunt of known size, and cardiac output was measured by thermodilution. For the 15 subjects with cardiac outputs of 3.64 to 8.10 liters/min, shunts of 22 to 248 ml/min were created, so that the shunts ranged from 0.5% to 3.3%. Hydrogen inhalation detected all shunts greater than or equal to 1.3% (Qp/Qs greater than or equal to 1.01). Of the 10 shunts less than 1.3%, it detected 5, with the smallest being 0.7%. Thus, the hydrogen inhalation technique is extremely sensitive in identifying the presence of left-to-right shunting, far more sensitive than the oximetric and standard indocyanine green methods.

[Intraoperative diagnosis--measuring heart time volume and assessment of shunts]. / Intraoperative Diagnostik--Messung des Herz-Zeit-Volumens und Darstellung von Shunts.

Intraoperative measurement of hemodynamics provides objective data supporting improvement of surgical and anaesthesiological treatment. Several methods including the thermodilution method, application of ultrasonic flow meters, use of the computed pressure gradient technique, application of transoesophageal color flow mapping and other cardiovascular applications of ultrasound are discussed with respect to their benefits and limitations in a clinical routine environment in cardiac surgery. According to our experiences the application of intraoperative transoesophageal doppler echocardiography and use of electromagnetic flow measurements are today the methods of choice. However, methodological limitations have to be regarded and additional intraoperative and clinical data are necessary whenever semiquantitative measurements of ultrasound techniques are used as basis for intraoperative judgement on the hemodynamic situation.

[Importance of Doppler echocardiography in the assessment of heart defects]. / Die Bedeutung der Doppler-Echokardiographie in der Beurteilung von Herzfehlern.

Doppler ultrasound is now an established noninvasive method in cardiology. The most important indications are: 1. stenosis/insufficiencies of atrioventricular/semilunar valves, 2. dysfunction of artificial valves, 3. atrial and ventricular septal defects. The information obtained from Doppler ultrasound lends itself to quantitative or qualitative analysis. There is general consensus about the qualitative interpretation of Doppler ultrasound data, whereas quantitative analysis is still debated. A critical analysis of Doppler ultrasound data is a conditio sine qua non for correct interpretation.

Isolated anterior mitral cleft. Two dimensional echocardiographic assessment and differentiation from "clefts" associated with atrioventricular septal defect.

Five patients with isolated clefts in the anterior leaflet of the mitral valve, unassociated with atrioventricular septal defects, are described. All had significant mitral regurgitation, with the cleft being the only abnormality in three. Two patients had an associated ventricular septal defect, one with a straddling right atrioventricular valve. Angiocardiography in four showed moderate regurgitation, but was not able to delineate the aetiology. Two dimensional echocardiography showed a constant defect in the anterior leaflet, pointing towards the left ventricular outflow tract. This differed from 30 cases with atrioventricular septal defects where the "cleft" pointed towards the interventricular septum and was situated between the anterior and posterior bridging leaflets. All cases with isolated clefts had surgical correction, with minimal residual regurgitation on follow-up examination in two cases. Our current policy in patients with uncomplicated isolated cleft involves non-invasive assessment of these children and surgical correction if the regurgitation is significant.

[Evaluation of the electrocardiogram in tricuspid atresia]. / Valoración del electrocardiograma de la atresia tricuspídea.

Due to the broad behaviour variability of the tricuspid atresia by the defects to which it is associated, the authors propose another classification, based on the position of the great vessels and the characteristics of the pulmonary flow, in addition to the extent of the intracardiac septal defects (atrial septal defect and ventricular septal defect) and the presence of patent ductus arterious. Eleven patients with tricuspid atresia with situs solitus and heart normo-placed are studied for diagnosis confirmation by catheterism or autopsy. Electrocardiograms are studied and observed in two patients with transposition of the great vessels and pulmonary oligohemia, a more evident right auricular enlargement (P of greater voltage in DII and AP heading right in the front plane), the AQRS deviated to the right, up and backwards, with less evidence of the left ventricular power than in other varieties of tricuspid atresia. These characteristics gave a diagnosis useful for this variation. On those patients without transposition and pulmonary flow increase, it is observed that growing appearance of the left auricle is more evident and so is the power of the free wall of the right ventricle (high R in right precordial deviations), the AQRS heads left as in most of the cases, but forward and upwards also. This electrocardiographic information is considered to have great importance to establish a diagnosis of the variations of tricuspid atresia due to associated malformations. Common varieties have already been extensively described by other authors and are not subject to special study. Bibliography on this matter is reviewed.