Category: General

Ann Biomed Eng. 2023 Apr 18. doi: 10.1007/s10439-023-03199-w. Online ahead of print.

ABSTRACT

Blood-biomaterial compatibility is essential for tissue repair especially for endovascular biomaterials where small-diameter vessel patency and endothelium formation is crucial. To address this issue, a composite biomaterial termed PFC fabricated from poly (glycerol sebacate), silk fibroin, and collagen was used to determine if functionalization with syndecan-4 (SYN4) would reduce thrombogenesis through the action of heparan sulfate. The material termed, PFC_SYN4, has structure and composition similar to native arterial tissue and has been reported to facilitate the binding and differentiation of endothelial colony-forming cells (ECFCs). In this study, the hemocompatibility of PFC_SYN4 was evaluated and compared with non-functionalized PFC, electrospun collagen, ePTFE, and bovine pericardial patch (BPV). Ultrastructurally, platelets were less activated when cultured on PFC and PFC_SYN4 compared to collagen where extensive platelet degranulation was observed. Quantitatively, 31% and 44% fewer platelets adhered to PFC_SYN4 compared to non-functionalized PFC and collagen, respectively. Functionalization of PFC resulted in reduced levels of complement activation compared to PFC, collagen, and BPV. Whole blood clotting times indicated that PFC_SYN4 was less thrombogenic compared with PFC, collagen, and BPV. These results suggest that syndecan-4 functionalization of blood-contacting biomaterials provides a novel solution for generating a reduced thrombogenic surface.

PMID:37071281 | DOI:10.1007/s10439-023-03199-w

Kyobu Geka. 2023 Apr;76(4):260-264.

ABSTRACT

Herein, we retrospectively review our experience with surgical treatment of active aortic valve infective endocarditis, particularly aortic annular abscess, and central nervous system complications. From 2012 to 2021, 46 consecutive patients underwent surgery during the active phase of infective endocarditis, 25 of which were performed at the aortic position. One patient died early (<30 days) due to low output syndrome and another 2 patients who were never discharged died because of general prostration. The actuarial survival rate was 84% at 1 year, and 80% at 3 and 5 years. Eleven patients [6 native valve endocarditis (NVE), 5 prosthetic valve endocarditis (PVE)] had valve annular abscess requiring removal of the infected tissue and reconstruction of a definite anatomic continuity, and aortic valve replacement was subsequently performed in 7 patients and aortic root replacement in 4 patients. Direct closure was performed in 4 patients with partial annulus defects, and reconstruction with an autologous nor bovine pericardium patch was performed in 6 patients with large annulus defects. Preoperative imaging revealed acute cerebral embolism in 10 patients. In eight cases, surgery was performed within 7 days after diagnosis of cerebral embolism. No patient had abnormal postoperative neurological findings. There were no reoperations and no recurrence of infective endocarditis.

PMID:36997172

2023 May 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–.

ABSTRACT

The aortic valve is a semilunar valve with three leaflets, which lies at the junction of left ventricle and aorta. It allows unidirectional blood flow from the left ventricle to the aorta and the rest of the body. Because of the highly complex and sophisticated cellular and molecular functions, the thin valve leaflet can withstand extreme mechanical and hemodynamic forces with every cardiac cycle. Various factors including age and congenital defects can compromise the normal valvular function leading to a wide variety of complications.

Although bicuspid aortic valves (BAV) are the most common congenital abnormality, congenital valve defects can range from aortic atresia (missing or incomplete closure of aortic valves) to a sub or supra-valvular stenosis. BAV is reported to have an incidence of 1 to 2% with a male predominance. Lack of microfibrillar proteins during valvulogenesis has been reported to affect the leaflet development where two leaflets are fused to form one large leaflet. It frequently correlates with aortic abnormalities such as aortic dilation (root, ascending and arch) and coarctation of the aorta. The bicuspid aortic valve leaflets can undergo accelerated calcific degeneration because of abnormal hemodynamic forces.

Congenital abnormalities including BAV can lead to various valvular complications including aortic stenosis and aortic regurgitation leading to an increased risk to infective endocarditis, which has a reported incidence of 12 to 39% in BAV. Unless severe, BAV generally remains asymptomatic until the age of 50 to 60 years.

Aortic stenosis (AS) is a narrowing of the valve aperture reducing the aortic valve area. Increased resistance to blood flow and transvalvular pressure gradient causes increased left ventricle workload causing hypertrophy. Its prevalence increases with age and can be as high as 4.6% in people greater than age 75 years. Being the most common valvular disease in Europe and America, estimates are that 3.5 million people in England alone will have AS by the year 2020. Calcific degeneration leading to stiffening and restriction motion of valve leaflet is the most common cause of AS. Disruption of endothelium lining on the aortic side caused by increased mechanical stress seem to be the inciting event. Posterior leaflets are reported to be affected the most. Rheumatic fever causing inflammation of the leaflets is still the leading cause of AS in developing countries.

AS can be asymptomatic or can cause symptoms of syncope, angina and heart failure. Severe AS is fatal with a 50% mortality at 2 years. As per The American College of Cardiology/American Heart Association (ACC/AHA) guidelines, AS is graded severe when the orifice area is less than 1.0 cm, the mean gradient is greater than 40 mmHg or the jet velocity is greater than 4 m/s. Prognosis is poor in symptomatic or severe cases unless the valve is replaced. Up to 30% of patients aged > 75 do not undergo surgical valve replacement either because of technical reasons; this may include porcelain aorta, general frailty, refusal to undergo surgery, and serious comorbid conditions. The operative death risk for surgical aortic valve replacement (SAVR) is as high as 10% in patients with LV dysfunction, chronic renal disease, and advanced age. Trans-catheter aortic valve replacement and trans-catheter aortic valve implantation (TAVR/TAVI) have emerged as a more feasible and less risky option for patients not suitable for surgery.

Aortic regurgitation (AR) is the backflow of blood from the aorta to the left ventricle when the valve leaflets fail to coapt. Common causes include congenital defects, calcific degeneration, infective endocarditis, rheumatic fever, and trauma. Ventricular hypertrophy in chronic cases accommodates increased volume to maintain the normal stroke volume and end-diastolic pressure; hence, chronic AR can be asymptomatic for decades. In contrast, with acute cases of AR, ventricles do not have enough time to undergo the needed changes such as hypertrophy to accommodate increased volumes. Because of decreased stroke volume, the heart rate increases to maintain cardiac output but is insufficient to meet the demand resulting in increased left atrial pressure, pulmonary edema and cardiogenic shock.

On physical examination, AR murmur is blowing, high-pitched, diastolic, and decrescendo, beginning soon after the aortic component of S (A); it is loudest at the 3rd or 4th left parasternal intercostal space. It also has associations with various other murmurs including:

1. “Mid-systolic murmur” because of rapid ejection of an overload of blood from the left ventricle,

2. “Austin Flint” murmur is mid-to-late diastolic murmur due to partial closure of mitral valve during ventricular systole because of regurgitant flow from aortic valve,

3. “Cole-Cecil” is a diastolic murmur due to the fusion of an aortic murmur with the S3 because of simultaneous filling of the left ventricle from left atrium and AR

History of Valvular Surgery

Dr. Theodore Tuffier, in 1912, used his finger to free the fused leaflets of a stenosed aortic valve. Before the advent of cardiopulmonary bypass (CPB), mitral valve repair involved commissurotomy through access from the left atrial chamber. Thomas Homes Sellors performed first pulmonary valvulotomy in 1948 by using a tenotomy knife. Charles Hufnagel developed the first artificial valve based on a reciprocating ball and cage. It was used to prevent backflow of blood into the ventricles due to aortic insufficiency. CPB machine revolutionized the valve replacement in the anatomical position. Dr. Dwight Harken and his colleagues performed the first successful aortic valve replacement. Later that year, Drs. Albert Starr and Lowell Edwards performed mitral valve replacement. Bioprosthetic valves are closer in function to natural valves but have a limited life expectancy, whereas, Mechanical valves are more durable but require anticoagulation. The choice of valves, among other factors, depends upon the patient’s age and well-being.

Mechanical heart valves are known to last for approximately 25 years. Seventy different mechanical heart valves have been developed since 1960. Ball and cage, bi-leaflet, and tilting disc are the common ones. Modification of the ball valve by Dr. Albert Starr and Lowell Edwards entailed developing a cage made of lucite with a silicone elastomer ball. The cage material was later changed to stainless steel and then cobalt-chromium alloys. The Starr-Edward valve also has a Teflon sewing ring, which enabled suturing into mitral and later into the aortic position.

Increased thrombogenicity has been a significant issue, for which valves underwent several modifications such as measures to reduce metal contact by covering the struts with cloth and using Silastic shields. Other issues included hemolysis due to excessive rubbing of the ball against the sewing ring and occlusion of coronary ostia because of high profile. Despite these issues, these valves showed the feasibility of prosthetic valve enabling Starr-Edwards to draw design criteria. Basic points included that the valves should be chemically inert, biocompatible, a-traumatic to blood, and non-thrombogenic.

In 1965, Kay-Shiley’s non-rotating disc valve replaced the ball with a single disc but demonstrated poor hemodynamics and hemolysis and was discontinued. Bjork-Shiley in 1969 developed a tilting-disc valve, which overcame the problems with the single-disc valve. Free rotation of disc between metal struts allows it to open by tilting at a 60-degree angle. Bjork-Shiley replaced the flat with the convexo-concave disc to create a larger orifice in 1975 but were the object of a recall due to fracture of welded struts.

Medtronic Hall valve developed by Dr. Karl Hall and Robert Kaster is the most common tilting disc valve. Perforation in the middle of the disc served as a guide and an improved tilting angle. In 1977, St Jude Medical developed Bi-leaflet valve, which comprised two semi-circular flaps with hinges close to the center of the orifice. Stagnation of blood flow leading to thrombus formation around the hinge region was a problem with the bi-leaflet valve. A newly developed valve resolved this issue with a valve in which the continuous 360-degree rotation around the central axis of the valve ensured an even distribution of blood flow and prevent thrombus formation.

Predisposition for thrombosis, embolism, need for lifelong anticoagulation therapy are drawbacks of mechanical valves.

Bioprosthetic valves can either be an allograft (cadaver or Ross procedure) or, a xenograft (native or pericardium). The Ross procedure involves replacing the diseased aortic valve with the patient’s own pulmonary valve (autograft) and replace the pulmonary valve with aortic or pulmonary allograft. The pulmonary autograft grows with the patient and does not induce an immunologic response. The most common xenografts are porcine aortic valves and bovine pericardial valves.

Lonescu-Shiley developed xenograft valves by using bovine pericardium on a titanium stent in 1971 but was later withdrawn in 1987 due to structural failure including abrasive tears because of fabric-tissue interface and leaflet calcification. Carpentier-Edwards bovine pericardial valve overcame those issues by making some structural modifications, like stitching pericardium to the inside of the fabric and using flexible stent posts.

Although biological valves have better hemodynamics compared to mechanical valves, they have a shorter lifespan because of calcification, which stiffens the valve leaflets.

Tissues engineering, a field in regenerative medicine restores and maintains the function of living tissues. Skin graft for burn victims is an example. Tissue engineered heart valves (TEHV) are perceived to be non-thrombogenic, and infection resistant. With advancement in material science and culturing techniques, there is the possibility of a TEHV valve that is capable of growing, remodeling and repairing itself as the patients grow.

Polymeric valves have been around for over 50 years, but because the earlier versions were prone to calcification and degradation, they were not widely used and instead only used in bridge devices like artificial hearts and left ventricular assist devices. Besides the advantage that they can be produced in various shapes and sizes, they are known to combine the durability of mechanical valves and the hydrodynamic function of bioprosthetic valves. The earliest polymeric valve implanted in a 44-year-old female in 1958 at the mitral position was a polyurethane design with Teflon chordae tendinae. Polyurethane valves have been found to have better hemodynamics compared to bioprosthetic valves and a lower incidence of thrombogenicity than mechanical valves. With advances in material sciences, the future of polymeric valves seems promising.

PMID:30725821 | Bookshelf:NBK537136

Int J Artif Organs. 2023 Jun;46(6):361-369. doi: 10.1177/03913988231177319. Epub 2023 May 22.

ABSTRACT

Acellular scaffold is mainly composed of collagen, which is sensitive to temperature. The denaturation of collagen, whether immediately or lately after implantation will lead to profound influence on the micro-structure, biological activities of acellular scaffold, and tissue repairing process. However, the in situ thermal stability of acellular scaffold had rarely been investigated previously. In this study, the thermal stability of two acellular scaffolds, acellular bovine pericardium (S1) and acellular bovine dermis (S2), were investigated by in situ dura repairing experiments. The in situ dura repairing results showed that both samples could successfully integrate with Beagles’ dura tissue after 1 month of implantation. S1 remained stable during the 6-month implantation period and no obvious denaturation or degradation was found. However, S2 remained stable only in the first month and denatured at the 2-month dissection timepoint. S2 was completely degraded at 6-month dissection timepoint and no new dura tissue was regenerated. The study showed that maintain thermal stability was important for acellular scaffold after surgical implantation. Denaturation of the acellular scaffold led to dramatic changes in the microenvironment of the host tissue. The long-term thermal stability should also not be ignored even though successful integration between the acellular scaffold and the defect tissue was established. Maintaining thermal stability of the acellular scaffold was conducive to tissue repairing or regeneration process.

PMID:37212064 | DOI:10.1177/03913988231177319