DNA

DNA is the building block of human life . Its double helical structure is deceptively simple, yet the rules encoded within this structure specify the form and function of all cells within an organism. DNA consists of two long strands of polydeoxyribonucleotides that twist around each other clockwise to form an unbroken double helix. Alternating deoxyribose-phosphate groups form the backbone of the helix, with the phosphate group making a 5′-3′ phosphodiester bond between the fifth carbon of one pentose ring and the third carbon of the next pentose ring . Nucleic acid bases attached to the sugar groups of each strand face each other within the helix, perpendicular to the strand axis. The order of the nucleic acids specifies the eventual sequence of the protein product of the gene. Only four bases exist: the purines adenine and guanine (A and G) and the pyrimidines cytosine and thymine (C and T). During assembly of the double helix, a purine can pair only with a pyrimidine, and a pyrimidine with a purine. Each base pair (bp) forms one of the rungs in the twisted ladder of the DNA molecule, which can be millions of bases long. The two strands of DNA, which are held together by hydrogen bonds between complementary base pairs, have opposite chemical polarities. One strand is oriented in a 5′ to 3′ direction, while the other is in a 3′ to 5′ direction. Enzymes that recognize specific DNA sequences also recognize the polarity of the strand. An enzyme “reads” the nucleotide sequences on the two strands in opposite directions. Because the structure of the helical backbone is invariant, enzymes responsible for DNA copying, cleavage, and repairing strand breaks can act anywhere along the length of the DNA strand.

ABNORMALITIES OF RIGHT VENTRICULAR INFLOW

The right ventricular inflow tract and tricuspid valve are visualized using the apical and subcostal four-chamber views, the short-axis view at the base, and the medially angulated parasternal long-axis view. The most important congenital pathologic entities involving the tricuspid valve are Ebstein anomaly and tricuspid atresia (discussed subsequently). Ebstein anomaly consists of apical displacement of the septal and posterior (and sometimes the anterior) leaflets of the tricuspid valve into the right ventricle. Typically, the leaflets are elongated and redundant with abnormal chordal attachments. This results in atrialization of the basal portion of
the right ventricle as the functional orifice is displaced apically relative to the anatomic anulus. Ebstein anomaly is a spectrum of abnormalities, depending on the extent of apical displacement of the valve, the distal attachments of the leaflets, the size and function of the remaining right ventricle, the degree of tricuspid regurgitation, and the presence of right ventricular outflow tract obstruction (usually from the redundant anterior tricuspid valve leaflet).

The best echocardiographic view for the evaluation of Ebstein anomaly is the four-chamber view. The characteristic features identified in this plane are shown schematically in Figure 18.7. Of principal importance is the accurate recording of the level of insertion of the septal leaflet of the tricuspid valve relative to the anulus. Apical displacement of this insertion site is optimally assessed in this view and is the key to diagnosis (Fig. 18.8). Because the tricuspid valve is normally positioned more apically than the mitral valve, abnormal apical displacement is relative, and some investigators have suggested measuring the distance between insertion sites of the two atrioventricular valves. When normalized for body surface area, a distance of greater than 8 mm/m² is indicative of Ebstein anomaly. Other investigators have advocated a maximal displacement of more than 20 mm as the diagnostic criterion in adults.

The four-chamber and medially angulated parasternal views may be used to assess the severity of Ebstein anomaly and to determine surgical options. The degree of atrialization of the ventricle, the extent of leaflet tethering, and the magnitude of deformity or dysplasia of the valve leaflets are important features with implications for surgical repair (Fig. 18.9). The extent of chordal attachments between the anterior leaflet and the anterior free wall should be assessed in multiple views. If tethering is significant, valve replacement rather than repair may be required. The greater the degree of atrialization is, the worse the prognosis. If the area of the functional right ventricle is less than one-third of the total right ventricular area, overall prognosis is poor. Because of the complexity of right ventricular geometry, an accurate measure of the size of the functional right ventricle is difficult, and all available views should be used (Fig. 18.10). Doppler echocardiography should be used to detect tricuspid regurgitation, which is commonly seen in patients with Ebstein anomaly (Fig. 18.11). A redundant anterior tricuspid valve leaflet may cause functional right ventricular outflow tract obstruction, which can also be detected with Doppler imaging. In severe cases, pulmonary atresia may be present, although it is rarely seen in adults.

FIGURE 18.7. Schematic of anatomic abnormalities in Ebstein anomaly. RA, right atrium; LA, left atrium; LV, left ventricle; MV, mitral valve; MVA, mitral valve anulus; TVA, tricuspid valve anulus; AnRV, anatomic right ventricle; FRV, functional right ventricle; AtRV, atrialized right ventricle

FIGURE 18.8. A four-chamber view from a patient with Ebstein anomaly is shown. The arrows indicate the degree of apical displacement of the tricuspid valve (TV), which had restricted motion. Note that the functional portion of the right ventricle (RV) is fairly well preserved. LV, left ventricle; RA, right atrium.


FIGURE 18.9. A more extreme form of Ebstein anomaly is demonstrated. The tricuspid valve (arrows) is markedly abnormal, and there is tethering of the leaflets, which prevented normal coaptation and resulted in significant tricuspid regurgitation. The right atrium (RA) is severely dilated. LV, left ventricle

Ebstein anomaly may be associated with a variety of other abnormalities that can be detected with echocardiography, namely, atrial septal defect, mitral valve prolapse, and left ventricular dysfunction. The etiology of the left ventricular dysfunction is not known, but its presence is associated with a poor prognosis. Surgical options in patients with Ebstein anomaly include tricuspid valve repair or replacement. After surgical repair, echocardiography plays a role in assessing the success of the procedure and the function of the tricuspid valve.

Role of Echocardiography in Mitral Valve Surgery

When performing transesophageal echocardiography for the purpose of assessing mitral valve anatomy before intended mitral valve repair, it is important that a thorough and detailed evaluation of the mitral valve be undertaken in a systematic fashion. The primary purpose of the examination is to determine the underlying anatomic abnormality responsible for the regurgitation or stenosis. It is important to recognize that there are three different viewing perspectives on mitral valve anatomy (Fig. 19.14). The surgeon will be viewing the mitral valve from within the left atrium so that the anterolateral commissures will be to the left of the field of view and the medial commissures to the right. When viewed with either transesophageal or transthoracic echocardiography, this orientation will be reversed (assuming traditional recommended viewing formats on a video screen). Also, depending on whether the reference is a transthoracic or transesophageal echocardiogram, the anterior and posterior leaflets of the mitral valve will vary in position compared with the surgical perspective. Figure 19.14 depicts all three perspectives of the mitral valve in relation to the aorta and left atrial appendage.

History of Echocardiography part 1

Many histories of diagnostic ultrasound, and cardiac ultrasound in particular, have been written.^1,2,3,4,5,6 They all seem to address this field from a different perspective. One can begin the history in the twentieth century, Roman times, or any of the centuries in between. It is stated that a Roman architect, Vitruvius, first coined the word echo.⁷ A Franciscan friar, Marin Mersenne (1588–1648), is frequently called the “father of acoustics” because he first measured the velocity of sound.⁷ Another early physicist, Robert Boyle (1627–1691), recognized that a medium was necessary for the propagation of sound.⁷ Abbe Lazzaro Spallanzani (1727–1799) is frequently referred to as the “father of ultrasound.”⁸ He demonstrated that bats were blind and in fact navigated by means of echo reflection using inaudible sound. In 1842, Christian Johann Doppler (1803–1853) noted that the pitch of a sound wave varied if the source of the sound was moving.⁹ He worked out the mathematical relationship between the pitch and the relative motion of the source and the observer. The ability to create ultrasonic waves came in 1880 with the discovery of piezoelectricity by Curie and Curie.^10,11 They noted that if certain crystalline materials are compressed, an electric charge is produced between the opposite surfaces. They then noted that the reverse was also true. If an electrical potential is applied to a crystal, it is compressed and decompressed depending on the polarity of the electric charge, and thus very high frequency sound can be produced. In 1912, a British engineer, L. F. Richardson, suggested that an echo technique could be used to de- tect underwater objects. Later during World War I, Paul Langevin was given the duty of detecting enemy submarines using sound, which culminated in the development of sonar.³ Sokolov¹² described a method for using reflected sound to detect metal flaws in 1929. In 1942, Floyd Firestone,¹³ an American engineer, began to apply this technique and received a patent. It is this flaw detection technique that ultimately was used in medicine.

An Austrian, Karl Dussik,¹⁴ was probably the first to apply ultrasound for medical diagnosis in 1941. He initially attempted to outline the ventricles of the brain. His approach used transmission ultrasound rather than reflected ultrasound. After World War II, many of the technologies developed during that war, including sonar, were applied for peaceful and medical uses. In 1950, W. D. Keidel,¹⁵ a German investigator, used ultrasound to examine the heart. His technique was to transmit ultrasonic waves through the heart and record the effect of ultrasound on the other side of the chest. The purpose of his work was to try to determine cardiac volumes. The first effort to use pulse-reflected ultrasound, as described by Firestone, to examine the heart was initiated by Dr. Helmut Hertz of Sweden. He was familiar with Firestone's observations and in 1953 obtained a commercial ultrasonoscope, which was being used for nondestructive testing. He then collaborated with Dr. Inge Edler who was a practicing cardiologist in Lund, Sweden. The two of them began to use this commercial ultrasonoscope to examine the heart. This collaboration is commonly accepted as the beginning of clinical echocardiography as we know it today.¹⁶

The original instrument (Fig. 1.1) was quite insensitive. The only cardiac structures that they could record initially were from the back wall of the heart. In retrospect, these echoes probably came from the posterior left ventricular wall. With some modification of their instrument, they were able to record an echo from the anterior leaflet of the mitral valve. However, they did not recognize the source of this echo for several years and originally attributed the signal to the anterior left atrial wall. Only after some autopsy investigations did they recognize the echo's true origin. Edler¹⁷ went on to perform a number of ultrasonic studies of the heart. Many of the cardiac echoes currently used were first described by him. However, the principal clinical application of echocardiography developed by Edler was the detection of mitral stenosis.¹⁸ He noted that there was a difference between the pattern of motion of the anterior mitral leaflet in patients who did or did not have mitral stenosis. Thus, the early studies published in the mid-1950s and early 1960s primarily dealt with the detection of this disorder.