Inhibition of cusp and aortic wall calcification in ethanol- and aluminum-treated bioprosthetic heart valves in sheep: background,mechanisms, and synergism

BACKGROUND AND AIM OF THE STUDY: Calcification of bioprosthetic heart valves fabricated from glutaraldehyde (GA)-pretreated heterograft tissue is frequently responsible for the clinical failure of these devices. Stentless bioprostheses fabricated from GA-fixed porcine aortic valves pose an important challenge in this regard, as pathologic calcification can affect not only the bioprosthetic cusps, but also the aortic wall segment. METHODS: A synergistic approach was used to prevent bioprosthetic cusp and aortic wall calcification. Ethanol pretreatment of bioprosthetic heart valves was shown to inhibit cuspal calcification due to multiple mechanisms, including alterations of collagen structure and lipid extraction. AlCl3 pretreatment of bioprostheses to prevent calcification was also investigated; this alters elastin structure, inhibits alkaline phosphatase, and complexes with phosphoesters, thereby inhibiting aortic wall mineralization. RESULTS: Experimental data from rat subdermal implants and sheep mitral replacements showed successful synergism with co-pretreatment of porcine aortic valve bioprostheses with ethanol and AlCl3. Significant inhibition of both cusp and aortic wall calcification was achieved by differential pretreatments that restrict AlCl3 to only the aortic wall, and not the cusp, accompanied by ethanol cuspal exposure. Sequential exposure of bioprostheses, first to AlCl3 and then to ethanol, led to unexpectedly severe cuspal calcification. CONCLUSION: Differential pretreatment of stentless bioprostheses with ethanol and AlCl3 can effectively inhibit both cuspal and aortic wall calcification.     

Vibrational analysis of bioprosthetic heart valve leaflets using numerical models: effects of leaflet stiffening, calcification, and perforation

The fundamental natural frequency of the closed cusps of porcine bioprosthetic valves, fabricated from the normal leaflets of pig aortic valves, was estimated using a finite element model. Both normal and stiffened leaflets were considered in the vibrational analysis. The effects of conditions that simulated degeneration, such as stiffening, central perforation, a tear, calcium deposits in the commissural attachments, and combinations of these were determined. The primary frequency of vibration of the normal leaflets was within the range of the dominant frequency of the heart sounds determined clinically by spectral analysis of the recorded phonocardiogram. If only one leaflet was stiffened or calcified, there was only a marginal change of frequency. With stiffening and calcification of the commissures of all 3 leaflets, the frequency of vibration increased. Introduction of a tear in a single leaflet of a stiffened and calcified valve markedly reduced the fundamental frequency. In view of the relation between the frequency content of heart sounds and the frequency of valve vibration, this mathematical simulation establishes a possible basis for the observation of a varying dominant frequency of heart sounds in patients with bioprosthetic valves that are in the process of degenerating.     

Calcification of aortic versus mitral porcine bioprosthetic heart valves: a radiographic study comparing amounts of calcific deposits in valves explanted from the same patient

Calcium detected by radiography was compared in 10 pairs of aortic and mitral glutaraldehyde-treated porcine bioprosthetic heart valves explanted from 10 patients (7 men and 3 women), aged 19 to 68 years (mean 43). Both valves of 6 pairs of valves had undergone primary tissue failure (revealed by cardiac catheterization and angiography) and 1 valve of the other 4 pairs of valves had undergone primary tissue failure. These porcine valves had been implanted from 2 1/4 to 9 years (mean 5 3/4). All 20 explanted valves contained calcium. The grade of calcium was the same in 4 pairs of valves (grade 2+ or 3+), and 1 grade different in 4 pairs of valves (grade 1+ to 4+), with the greater calcium evenly divided between the 2 valve positions. There was more than 1 grade greater mitral valve calcium in 2 pairs of valves (grade 3+ and 4+ mitral vs 1+ and 2+ aortic, respectively). Thus, calcium is usually present in both aortic and mitral valve positions when bioprosthetic valves of this type in either valve position fail as a result of primary tissue failure, and radiographic calcium in porcine bioprosthetic valves is usually similar in grade in both the aortic and mitral valve positions.     

Frequency analysis approach to the origin of the first and second heart sounds

Catheter-tipped micromanometers were used to simultaneously record left ventricular and aortic pressures, and left ventricular and aortic internal phonocardiograms in order to determine if they had a common mode of origin and propagation. Spectrographic analysis showed that even with high-pass filtration the phonocardiogram obtained with a commonly used system (Millar) contained large amounts of energy in the subaudible frequency range (below 40 Hz). It was possible to derive close facsimiles of the phonocardiograms by double differentiation of the corresponding pressure pulse and conversely to derive the pressure pulse by double integration of the phonocardiograms. The propagation velocities of the first heart sound, second heart sound, and the foot of the aortic pressure pulse were found to be similar and were respectively, 4.3 ± 0.2, 4.6 ± 0.3, and 4.2 ± 0.2 m/sec (± SE). These data support the concept that the low frequency pressure variations produced by the heart, which predominate in the left ventricular and aortic pressure pulse waveforms, are generated and propagated in the same manner as the high frequency pressure variations, which are the first and second heart sounds.     

Determinants of the amplitude of the aortic component of the second heart sound in aortic stenosis

The characteristics of the aortic component of the second heart sound in calcific and congenital noncalcific aortic stenosis were studied to determine a cause for observed differences. Intraarterial pressure and sound were measured above the aortic valve in 20 patients utilizing catheter-tip micromanometers. Ten patients had a normally functioning aortic valve, six had calcific aortic stenosis and four had congenital noncalcific aortic stenosis. As expected, the aortic sound was diminished in patients with calcific aortic stenosis compared with that in patients with a normal valve (600 ± 200 versus 2,600 ± 200 dynes/cm² (P < 0.001). In patients with congenital aortic stenosis, sound amplitude was not reduced compared with that in patients with a normal valve. Measurement of sound produced by closure of normal and stenotic valves in an in vitro model of the circulatory system yielded comparable results. In vitro high speed (2,000 frames/sec) motion pictures of the diastolic motion of the closed cusps showed vibrations of comparable magnitude in the normal porcine and the simulated congenitally stenotic valve. The calcified stenotic valve showed no noticeable diastolic vibrations. These observations indicate an association between the amplitude of the second heart sound and diastolic vibrations of the closed cusps. A calcified stenotic valve, being thick and stiff, would have a diminished ability to vibrate and would therefore produce a diminished sound. A congenitally stenotic valve, in contradistinction, if not yet damaged by degenerative changes, would not be limited in its ability to vibrate during diastole and would therefore produce a normal second sound.     

Assessment of perceived mechanical heart valve sound level in patients

BACKGROUND AND AIM OF THE STUDY: When mechanical heart valves close, they generate an impulse that is transmitted to the patient's inner ear by two routes: (i) As acoustically transmitted sound waves; and (ii) as vibrations transmitted through bones and vessels. The aim of this study was to quantitate what patients perceive as sound from their mechanical heart valve prostheses - including both air-transmitted sound waves and bone-transmitted vibrations. METHODS: Thirty-four patients with implanted mechanical bileaflet aortic and mitral valves (St. Jude Medical and On-X) were included in the study. Measurements were performed in a specially designed sound-insulated chamber equipped with microphones, accelerometers, preamplifiers and a loud-speaker. The closing sounds measured by an accelerometer on the patient's chest were delayed 400 ms, amplified and played back to the patient through the loudspeaker. The patient adjusted the feedback sound to the same level as the 'real-time' clicks they perceived directly from their valve. In this way the feedback sound energy includes both the air- and bone-transmitted energies. Sound pressure levels (SPL) were quantitated in both dB(A) and in loudness units (sones) according to ISO 532B (Zwicker method). RESULTS: The mean air-transmitted SPL measured close to the patient's ear was 23 +/- 4 dB(A). The total air-and bone-transmitted sounds and vibrations were perceived by the patients as a SPL of 34 +/- 5 dB(A). There was no statistically significant difference in perceived sound from the two bileaflet valves investigated, and no difference between aortic and mitral valves. CONCLUSIONS: The study showed that the presented feedback method is capable of quantitating the perceived sounds and vibrations from mechanical heart valves, if the patient's hearing is not too impaired. Patients with implanted mechanical heart valve prostheses seem to perceive the sound from their valve two to four times higher than nearby persons, because of the additional bone-transmitted vibrations.     

Flow characteristics of bioprosthetic heart valves

A review of the in vivo and in vitro fluid dynamic performance of three bioprosthetic heart valves is presented. Data on Hancock porcine valves (standard models 242 aortic and 342 mitral and modified orifice model 250 aortic), Carpentier-Edwards porcine valves (model 2625 aortic and 6625 mitral), and the Ionescu-Shiley pericardial valve are reviewed. These valves were chosen because of their past or present popularity in clinical use and because of the variation in fluid dynamic performance reported by different investigators. The flow parameters that are reported include in vivo and in vitro mean pressure drop, cardiac output or cardiac index, regurgitant volume, effective orifice area, and performance index. These data provide a framework for differentiation of normal and abnormal bioprosthetic valve function.     

Doppler hemodynamic evaluation of prosthetic (Starr-Edwards and Bj?rk-Shiley) and bioprosthetic (Hancock and Carpentier-Edwards) cardiac valves

One hundred thirty-four patients with prosthetic or bioprosthetic heart valves were investigated with Doppler echocardiography to determine normal values for commonly used prosthetic valves and to test the specificity of abnormal Doppler findings. In 70 patients the aortic valves had been replaced and in 64 the mitral valves had been replaced. Gradients across prostheses in the aortic position were calculated from maximal velocity. Peak calculated aortic transvalvular gradients in normal subjects were 22 +/- 10 mm Hg in 33 Bj?rk-Shiley valves, 23 +/- 10 mm Hg in 27 porcine valves and 29 +/- 13 mm Hg in 6 Starr-Edwards valves. Mild aortic regurgitation was seen in 42% of Bj?rk-Shiley valves, 26% of porcine valves and 2 of 6 Starr-Edwards valves. Mitral valve orifice was calculated by the pressure half-time method. In clinically normal patients with mitral valve prostheses, the effective mitral valve orifice was 2.5 +/- 0.8 cm2 in 35 Bj?rk-Shiley valves, 2.1 +/- 0.7 cm2 in 17 porcine valves, and 2.0 +/- 0.3 cm2 in 10 Starr-Edwards valves. Mitral regurgitation was found in 11% of Bj?rk-Shiley valves, 19% of porcine valves and 30% of Starr-Edwards valves. Repeat studies at 2 weeks to 14 months revealed no difference in 8 aortic and 14 mitral prostheses. Seven aortic and 4 mitral valves functioned abnormally as determined by Doppler, and the abnormal function was confirmed in each at surgery or at cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Indication of cavitation in mechanical heart valve patients

BACKGROUND AND AIM OF THE STUDY: Cavitation may cause erosion of prosthetic heart valve material. The phenomenon has been extensively studied in vitro, and an association between the presence of cavitation bubbles and high-frequency pressure fluctuations (HFPF) has been established. In-vivo studies examining this phenomenon are scarce; hence, the study aim was to compare HFPF in patients with native, bioprosthetic or mechanical aortic valves, using both invasive and non-invasive measuring techniques. METHODS: Measurements were carried out in 16 patients implanted with a St. Jude Medical aortic valve; two control groups comprised 10 patients with normal aortic valves after coronary artery bypass surgery, and five patients implanted with a Carpentier-Edwards pericardial aortic bioprosthesis. HFPF were measured intraoperatively using a hydrophone placed near the aortic annulus, and postoperatively using the same hydrophone mounted in a specially designed water-filled sound chamber. The frequency spectrum was evaluated using Fast Fourier transformation, and the root mean square (RMS) value of the pressure signals was calculated in the frequency range 50-150 kHz. RESULTS: HFPF with intensities significantly above the noise floor were registered using both methods in the vicinity of mechanical heart valves. The RMS values of the HFPF for all three patient groups measured intra- and postoperatively disclosed a significant difference between the mechanical valves and the two control groups, indicating that there is no cavitation in the vicinity of the biological or the native valves. CONCLUSION: HFPF are present in the vicinity of mechanical aortic valves and can be measured in patients, both invasively and non-invasively. This indication of cavitation was not observed in patients with either native or bioprosthetic aortic valves.     

Non-invasive assessment by Doppler ultrasound of 155 patients with bioprosthetic valves: a comparison of the Wessex porcine, low profile Ionescu-Shiley, and Hancock pericardial bioprostheses

One hundred and fifty five patients with 167 bioprosthetic valves (68 Wessex porcine, 54 Hancock pericardial, and 45 low profile Ionescu-Shiley pericardial valves) were studied by Doppler ultrasound. Valve gradients were calculated from the mitral and aortic flow velocities by the modified Bernoulli equation. Mean mitral gradients were significantly smaller across the Ionescu-Shiley valves than across the Wessex porcine or Hancock pericardial valves. Mitral pressure half time was, however, significantly longer in the Hancock pericardial than in the Wessex porcine or Ionescu-Shiley valves. No significant differences were seen among the groups of aortic bioprostheses, though the comparable size of Wessex porcine valves showed significantly higher gradients. Bioprosthetic regurgitation was detected in 13 of 103 mitral and 11 of 59 aortic valves, though it was suspected clinically in only 12 mitral and six aortic bioprostheses. Doppler ultrasound is a repeatable non-invasive method of acquiring haemodynamic information in vivo from a variety of bioprostheses and it can detect bioprosthetic regurgitation at an early stage.     

Non-invasive assessment by Doppler ultrasound of 155 patients with bioprosthetic valves: a comparison of the Wessex porcine, low profile Ionescu-Shiley, and Hancock pericardial bioprostheses.

One hundred and fifty five patients with 167 bioprosthetic valves (68 Wessex porcine, 54 Hancock pericardial, and 45 low profile Ionescu-Shiley pericardial valves) were studied by Doppler ultrasound. Valve gradients were calculated from the mitral and aortic flow velocities by the modified Bernoulli equation. Mean mitral gradients were significantly smaller across the Ionescu-Shiley valves than across the Wessex porcine or Hancock pericardial valves. Mitral pressure half time was, however, significantly longer in the Hancock pericardial than in the Wessex porcine or Ionescu-Shiley valves. No significant differences were seen among the groups of aortic bioprostheses, though the comparable size of Wessex porcine valves showed significantly higher gradients. Bioprosthetic regurgitation was detected in 13 of 103 mitral and 11 of 59 aortic valves, though it was suspected clinically in only 12 mitral and six aortic bioprostheses. Doppler ultrasound is a repeatable non-invasive method of acquiring haemodynamic information in vivo from a variety of bioprostheses and it can detect bioprosthetic regurgitation at an early stage.     

Degeneration of bioprosthetic heart valve cusp and wall tissues is initiated during tissue preparation: an ultrastructural study

BACKGROUND AND AIM OF THE STUDY: Chronic tissue degeneration is a major factor in the failure of porcine bioprosthetic heart valves. Stabilization with glutaraldehyde (GA) has become the standard in preparation of bioprosthetic heart valves, but there is increasing evidence that GA does not effectively stabilize all tissue structures, specifically glycosaminoglycans (GAGs). The study aim was to establish the status of GAGs in bioprosthetic heart valves and to ascertain whether degeneration of the extracellular matrix (ECM) is initiated during preparation of porcine tissues for use as bioprosthetic heart valves. METHODS: Stentless porcine bioprosthetic heart valves were prepared by tissue harvesting, 24 h of storage in cold saline, and 14 days' fixation in buffered 0.6% GA. Tissue samples obtained from fresh and fixed aortic cusps and wall conduit were analyzed for ECM integrity and GAG localization by transmission electron microscopy combined with toluidine blue staining. RESULTS: Major degenerative changes occurred in the ECM ultrastructure of both porcine cusp and wall during tissue preparation for use as bioprosthetic heart valves. Modifications in the aortic cusp included loss of GAGs from the interfibrillary space and from the surface of the collagen fibers. In the aortic wall, GAGs were lost from the interfibrillary space and from the surface of collagen fibers. In addition, the surface of wall elastic fibers exhibited marked paucity of GAGs and elastin-associated microfibrils. CONCLUSION: The typical steps involved in the preparation of porcine aortic bioprosthetic heart valves induce, or cannot fully prevent, degeneration of some components of the ECM. Controlling the extent of this pre-implantation deterioration will open new gateways for improvement of the quality and durability of future cardiovascular bioprostheses.     

Investigation of failure modes of explanted porcine valves in the mitral position

BackgroundPorcine valves are used for mitral valve replacement, but the limited long-term durability has restricted the application in younger patients. Degenerated porcine mitral valves were explanted to analyze the failure modes and damage characteristics.MethodsTwelve porcine valves were explanted via secondary mitral valve replacement surgery. Microcomputed tomography scanning, morphological and pathological examinations were performed to classify the cusp tears, calcification, and pannus formation. The causes of valve deterioration were subsequently analyzed.ResultsThe mean age at first implantation was 45.42±19.58 years (range, 11–64 years). The mean duration of implantation was 9.39±4.14 years (range, 4.25–18.75 years). The indications for first surgery were rheumatic heart disease in 8 patients (66.67%), infective endocarditis in 2 patients (16.67%), degenerative valvular disease in one patient (8.33%), and congenital heart disease in one patient (8.33%). Type I cusp tears and commissural dehiscence that occurred near the stent post position were found in 6 (50%) and 5 (41.67%) valves, respectively. Calcification was detected in 6 (50%) cases, and pannus was found in most valves (91.67%).ConclusionsLeaflet damage occurred near the stent posts area was the main failure mode of porcine mitral valves in this study. Patients who undergo the first surgery at younger age, the higher prevalence rate of rheumatic heart disease, the structure of bioprosthetic porcine valve, and left ventricular stresses could be considered as the main factors causing valve deterioration.     

Pregnancy in patients with a porcine valve bioprosthesis

Seven patients who became pregnant after valve replacement with a Hancock bioprosthesis were followed up during 8 pregnancies. Six had undergone isolated mitral valve replacement, and 1 had mitral and aortic valve replacement. Their age at the time of operation ranged from 14 to 31 years (average 24); delivery occurred 21 to 88 months (average 51.3) after valve replacement. All women were in sinus rhythm at the time of gestation, and administration of oral anticoagulants was avoided in all. No embolic episodes occurred either after operation or during pregnancy, labor, or puerperium. The only major complication during pregnancy was cardiac failure in 1 patient, associated with onset of atrial fibrillation.Four women had vaginal delivery and 3 required cesarean section. All but 1 delivered a normal, healthy baby. One premature infant died soon after birth because of respiratory distress. No maternal or fetal hemorrhagic complications were observed. One patient died 3 months after delivery in severe heart failure caused by diffuse calcification of both mitral and aortic xenografts. Another woman underwent successful reoperation soon after the second pregnancy because of calcific stenosis of the mitral porcine valve.It is concluded that (1) bioprosthetic valves can be considered the most suitable devices employed in women of childbearing age because anticoagulants can be avoided, therefore eliminating the risks related to inappropriate administration of oral anticoagulants as well as the hazards associated with the potential teratogenic effect of coumarin drugs; and (2) pregnancy might favor calcification of porcine heterografts, leading to bioprosthetic failure. Until further data are available to support this suspicion, close clinical and echocardiographic follow-up study of these patients is recommended after pregnancy.     

Isovolumic relaxation period in man

Isovolumic relaxation period (IRP) was measured noninvasively from the onset of the aortic component of the second heart sound on the phonocardiogram to the point of separation of the mitral leaflets on the echocardiogram. IRP was measured in 83 patients: 10 normal subjects and 73 patients with different cardiac diseases.The duration of IRP was 58 ± 11 msec. in normal subjects. It was prolonged in hypertension (p < 0.001), HOCM (p < 0.001), aortic stenosis (p < 0.05), and aortic incompetence (p < 0.01), and was shortened in congestive cardiomyopathy (p < 0.05) and mitral stenosis (p < 0.01). In patients with coronary artery disease and normal over-all systolic LV function, IRP was prolonged (p < 0.001); IRP was shortened in four patients with coronary disease who had severe LV dysfunction and severe additional mitral incompetence.IRP was related to systemic blood pressure, percentage shortening of the LV in systole, and to the mitral EF slope. It tended to increase with increasing heart rate and a regression equation was developed for predicting IRP in relation to blood pressure and heart rate in normal subjects. There was no relation to the PR-AC time or to isovolumic contraction time. IRP is a useful measurement of LV dynamics in early diastole.     

Non-invasive assessment of the Ionescu-Shiley pericardial xenograft heart valve

This study was undertaken to describe the auscultatory, phonocardiographic, M-mode and two-dimensional echocardiographic features of the Ionescu-Shiley prosthesis in a group of unselected subjects. Twenty-seven valves were studied - 15 aortic, 10 mitral and 2 tricuspid. An opening sound was noted by phonocardiography and auscultation from the majority of valves in the three positions. A mid-systolic murmur was heard from 14 aortic valves and two had regurgitant murmurs. Three mitral valves had apical diastolic murmurs and two of these had mitral regurgitation. Two-dimensional echocardiography provided important spatial information but M-mode allowed superior resolution of valve leaflets. Calcification was seen in one four year old aortic valve and dehiscence of the sewing ring in another leading to severe aortic regurgitation. These data indicate that an opening sound is a frequent normal feature of an Ionescu-Shiley prosthetic valve and a mid systolic murmur is normal for aortic valves. In the three valve positions, the normal M-mode pattern resembles a native aortic valve. Abnormal features which can be recognized include calcification of valve cusps and dehiscence of the sewing ring.     

Evaluation of stentless kangaroo aortic valves in the mitral position of juvenile sheep

BACKGROUND AND AIM OF THE STUDY: The performance and longevity of bioprosthetic heart valves are limited by tissue calcification and degeneration after implantation. Experimental valve replacement in large animal models forms an important component of the preclinical evaluation of these bioprosthetic heart valves. The study aim was to assess the feasibility of a mitral model for stentless valves and to evaluate the calcification behavior of stentless glutaraldehyde-preserved kangaroo heart valves in the mitral position of a sheep model. METHODS: Medtronic Freestyle (n = 10) and kangaroo (n = 11) stentless aortic valves were implanted in the mitral position of juvenile sheep and retrieved after a maximum of 200 days. Retrieved stentless valves were examined for morphological changes and calcification of the valve tissue, using radiological screening, Von Kossa's staining and atomic absorption spectrophotometry. RESULTS: Four sheep (40.0%) with Medtronic Freestyle and 10 sheep (90.9%) with kangaroo valves could be weaned from bypass and mechanical ventilation. Two animals (20.0%) with Medtronic Freestyle and six animals (54.5%) with kangaroo prostheses survived more than 30 days postoperatively. No significant difference (p >0.05) was seen between the calcification potential of Medtronic Freestyle valve leaflets (3.21 +/- 1.67 microg/mg) after 93 days and kangaroo valve leaflets (2.39 +/- 0.80 microg/mg) after 200 days. CONCLUSION: The present results suggest that implantation of a stentless valve in the mitral position of sheep is possible, but technically difficult. The calcification potential of kangaroo valve tissue is comparable to that of Freestyle valve tissue in the mitral position of sheep.     

Left ventricular regional wall motion and velocity of shortening in chronic mitral and aortic regurgitation

Left ventricular regional wall motion (percent systolic shortening) and velocity of shortening were studied in patients with heart failure due to chronic volume overloads of mitral and aortic regurgitation. Biplane left ventriculograms were analyzed by computer and divided into four regions: anterior, inferior, posterolateral and septal. The study patients included 12 normal subjects; 21 patients with aortic regurgitation (10 asymptomatic and 11 with congestive heart failure); and 11 patients with mitral regurgitation (4 asymptomatic and 7 with congestive heart failure). No patient had coronary artery disease. With heart failure, ejection fraction was decreased (p <0.05) in both aortic and mitral regurgitation (normal 62 ± 3 percent [mean ± standard error of the mean], aortic regurgitation 48 ± 3 and mitral regurgitation 51 ± 5). In mitral regurgitation with heart failure, the percent segment shortening in anterior (normal 42 ± 2, mitral regurgitation 27 ± 5) and posterolateral (normal 23 ± 3, mitral regurgitation 16 ± 4) regions was significantly decreased (p <0.05), whereas this value in the inferior (normal 32 ± 2, mitral regurgitation 28 ± 6) and septal (normal 46 ± 4, mitral regurgitation 47 ± 5) regions was normal. In aortic regurgitation with heart failure, anterior (27 ± 2), inferior (17 ± 3) and septal (5 ± 1) segment shortening was significantly decreased, whereas posterolateral segment shortening was normal (24 ± 3).In both groups with heart failure, mean shortening velocity showed regional variations similar to those of percent shortening, whereas peak instantaneous shortening velocity was not reduced in mitral regurgitation compared with normal values. In the asymptomatic group, shortening and mean shortening velocity were normal, whereas peak instantaneous shortening velocity was increased in mitral regurgitation. In aortic and mitral regurgitation with decreased left ventricular function demonstrated by a reduced ejection fraction, there are regional wall motion abnormalities that are not caused by coronary disease.     

Persistence of the third heart sound after resection of the native mitral and tricuspid valves. Evidence against the valvular theory of third sound origin.

A patient is described with severe rheumatic mitral and tricuspid insufficiency in whom both atrioventricular valves with their chordae tendineae and papillary muscles were resected and replaced with Hancock porcine grafts. This would appear to be the second such patient reported and the first described in detail in whom the third heart sound persisted postoperation. This occurrence documents the fact that a third heart sound can occur in the absence of native atrioventricular valve leaflets and the major portions of the subvalvular supporting apparatus, and argues against the theory that the third heart sound is generated by either the valvular leaflets of the subvalvular apparatus.     

The 6th heart sound]

The author describes a new sound in systole which he calls the V1th heart sound. This sound can be recorded in patients with pure aortic incompetence, but also in healthy subjects. It is not sufficiently loud to be heard on auscultation. It is visible only on the low frequency bands at 35 Hz, and rarely at 70 Hz. It is maximal at the apex and the endapex. It is characterised by 1 or 2 oscillations at the end of mesosystole and at the beginning or middle of end-systole. This sound may be physiological: it will then be of low amplitude, and further from the 2nd sound than in cases of pure aortic incompetence, in which it is pathological, and closer to the 2nd sound. The author puts forward two hypotheses for the origin of the VIth sound.