Jerry Braun

In situ hybridization: A new technique to determine the origin of fibroblasts in cryopreserved aortic homograft valve explants

Tissue degeneration reduces the durability of cryopreserved homografts. Earlier studies indicated that the presence of fibroblasts in homograft leaflets may contribute to increased valve longevity. These fibroblasts may be of recipient origin or represent surviving donor cells. We developed a method, based on in situ hybridization, to determine the origin of fibroblasts in homograft explants. In young pigs we performed aortic valve replacement with a cryopreserved porcine aortic homograft. A male homograft was implanted in a female pig, whereas two male recipients received a female homograft. After 3 to 4 months the homografts were explanted. Frozen sections were made and alternately examined with hematoxylin-eosin staining and in situ hybridization. With a biotinylated porcine Y chromosome-specific deoxyribonucleic acid probe, male fibroblasts could be clearly distinguished from female fibroblasts. In all leaflets we observed both donor and recipient fibroblasts. The distribution of these populations was marked in schematic drawings. Recipient fibroblasts mostly spread onto the leaflet surface but also penetrated the leaflet tissue. Remaining donor fibroblasts did not show morphologic signs of decreased viability on hematoxylin-eosin staining. In situ hybridization may become a useful technique in homograft research. In this porcine model, the fibroblasts in the aortic homograft explants were of both donor and recipient origin.

Echocardiographic Parameters of the Freestyle Stentless Bioprosthesis in Aortic Position: The European Experience

The objective of this study was to determine normal Doppler and 2-dimensional characteristics of the Freestyle stentless aortic bioprosthesis. The Freestyle aortic bioprosthesis is a new type of aortic xenograft, and experience is limited. We therefore determined the normal range of echocardiographic and Doppler examinations of this valve. Three hundred thirty-nine consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1, 2, and 3 years. With a valve size from 19 to 27 mm, mean gradients decreased from 7.9 +/- 5.1 mm Hg at discharge to 5.5 +/- 3. 8 mm Hg after 3 to 6 months (P <.001). Thereafter, gradients remained stable. Effective orifice area 1 year after implantation was 1.59 +/- 0.58 cm(2) for the 21-mm valves, 1.92 +/- 0.74 cm(2) for the 23-mm valves, 2.03 +/- 0.64 cm(2) for the 25-mm valves, and 2.52 +/- 0.72 cm(2) for the 27-mm valves (P <.001). The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro, increased from 67% +/- 20% at discharge to 82% +/- 29% after 1, 2, and 3 years. Performance index was especially very high in the smaller-sized valves. After implantation with the subcoronary technique or root-inclusion technique, small cavities could be seen between the native aortic root and the Freestyle valve. Doppler values were evaluated for the Freestyle stentless porcine bioprostheses in the aortic root. Gradients appear to be close to those measured in native valves over a time period of 3 years.

Identification of host and donor cells in porcine homograft heart valve explants by fluorescence in situ hybridization

The pathogenesis of the primary tissue degeneration that limits the life‐span of aortic and pulmonary homografts has still not been revealed. Histopathological studies on homograft explants have not given definitive insight into the eventual fate of donor cells, nor have they demonstrated the assumed importance of host cell ingrowth into the graft tissue. In this experimental study, fluorescence in situ hybridization (FISH) is introduced as a new approach to examine the distribution of host and donor cells in homograft explants. Aortic valve replacement was performed with a cryopreserved porcine aortic homograft in three pigs; donor and recipient were of opposite sex. After 4 months, the grafts were explanted and examined by FISH using a biotinylated porcine Y‐chromosome‐specific library probe. Following probe detection with FITC‐conjugated avidin, a clear distinction could be made between cells of host and donor origin without distorting the histological integrity of the explants. There was ingrowth of donor cells into the graft aortic wall and into the valve leaflet, to some extent. In all explants, remaining donor cells were present, though decreased in number. The introduction of FISH in homograft heart valve research provides a powerful tool to study the fate of recipient and donor cellular elements in situ, and may therefore contribute to a better understanding of the histopathological processes that take place in transplanted homograft valves.

Restrictive mitral annuloplasty in refractory cardiogenic shock with acute postinfarction mitral insufficiency and intact papillary muscle

Acute severe mitral insufficiency after myocardial infarction usually results from rupture of a papillary muscle, which should be treated on an emergency basis with mitral valve repair or replacement. In the case of acute postinfarction mitral regurgitation with intact papillary muscle, no consensus exists, even with regard to the indication for surgery. Restrictive mitral annuloplasty (RMA) has been applied in chronic ischemic mitral insufficiency, with encouraging midterm results. 1,2 In this report, we describe 2 patients in whom RMA was applied as a lifesaving procedure in the presence of refractory cardiogenic shock in postinfarction mitral insufficiency with intact papillary muscle. Clinical Summaries PATIENT 1. A 55-year-old woman had an acute inferior wall infarction with cardiogenic shock. She received an intra-aortic balloon pump (IABP) and inotropes and was intubated. Coronary angiography revealed occlusion of the right coronary and circumflex arteries. Transesophageal echocardiography (TEE) showed grade 4 mitral insufficiency resulting from systolic restrictive motion of both leaflets (Carpentier type IIIb; Figures 1 and 2). The regurgitation jet was slightly eccentric because of the more restrictive posterior leaflet. Because of further hemodynamic deterioration, we decided to attempt correction of the mitral regurgitation as a lifesaving procedure. During the operation, a fresh infarction of the posterolateral wall involving the posterior papillary muscle was observed. The subvalvular apparatus was intact, and there was no structural anomaly of the mitral valve leaflets. RMA was performed with a size 28 Carpentier-Edwards Physioring (Baxter Healthcare Corporation CardioVascular Group, Irvine, Calif), thereby downsizing the prosthetic ring by two sizes. Tentative revascularization of the circumflex and right coronary artery territory was performed with a sequential saphenous vein graft. The patient was weaned from extracorporeal circulation with inotropic support (epinephrine at 0.22 g/kg/min, dobutamine at 15 g/kg/min, dopamine at 8 g/kg/min, and enoximon at 4 g/kg/min). Intraoperative TEE showed trivial mitral regurgitation with a mean transvalvular mitral gradient of 3 mm Hg (mitral valve surface area 2c m 2 ) and

Right ventricular dysfunction affects survival after surgical left ventricular restoration.

Objective: Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. Methods: A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all‐cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Results: Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was −24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88–0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66–0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05–1.26; P < .01) were independently associated with 30‐day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30‐day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64–4.87, P < .01 per additional impaired parameter). Conclusions: Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration.

Stentless bioprostheses have ideal haemodynamics, even in the small aortic root

Objective: To determine normal Doppler and 2D gradients and flow characteristics of the Freestyle® stentless aortic bioprosthesis related to valve size. Background: The Freestyle® stentless aortic bioprosthesis is one of the newer aortic xenografts. Only limited data are available of the echocardiographic flow characteristics during a mid-term follow-up period of this valve. Therefore valve performance related to valve size was measured during a follow-up period of two years. Methods: 175 consecutive patients with a Freestyle® aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1 and 2 years. Results: With a valve size from 19 to 27 mm mean gradients decreased from 8.0 ± 5.1 mmHg at discharge to 5.8 ± 3.8 mmHg after 3–6 months (p < 0.001). Thereafter gradients remained stable. The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro increased from 69 ± 20% at discharge to 79 ± 29% after one, two and three years. Performance index was especially very high in the smaller sized valves with a performance index of 85 ± 17% for the 21 mm valve. During follow-up mean gradients remained below 10 mmHg even in the 21 mm valve. Conclusion: Stentless xenografts have ideal haemodynamics, even in the small aortic root.

Prognostic value of left ventricular reverse remodelling and recurrent mitral regurgitation after personalized surgical treatment of patients with non-ischaemic cardiomyopathy and functional mitral regurgitation†

OBJECTIVESnThe aim of this study was to determine the prevalence of left ventricular reverse remodelling (LVRR) and recurrent mitral regurgitation (MR) at mid-term follow-up (1-2u2009years after surgery) in patients after personalized surgical treatment of heart failure and functional MR due to non-ischaemic cardiomyopathy and to assess their prognostic impact on long-term clinical outcomes.nnnMETHODSnConsecutive patients with refractory heart failure and non-ischaemic MR, who underwent mitral valve surgery with or without additional procedures, were identified. Patients with complete preoperative and mid-term echocardiographic data were included. LVRR (≥15% decrease in indexed left ventricular end-systolic volume) and recurrent MR (≥ Grade 2) were echocardiographically assessed at mid-term follow-up, and the primary end point was a composite of all-cause mortality and heart transplantation (HTx-free survival).nnnRESULTSnThe prevalence of LVRR was 38%, and the prevalence of recurrent MR was 20% at mid-term follow-up. The absence of LVRR and the presence of recurrent MR-which were highly correlated-were significantly associated with worse HTx-free survival. HTx-free survival 1 and 3u2009years after mid-term follow-up were 100% and 88u2009±u20096% in patients with LVRR (nu2009=u200929), 82u2009±u20097% and 68u2009±u20098% in patients without LVRR and without recurrent MR (nu2009=u200934), and 49u2009±u200914% and 33u2009±u200913% in patients without LVRR and with recurrent MR (nu2009=u200914).nnnCONCLUSIONSnPatients with LVRR at mid-term follow-up showed favourable HTx-free survival, whereas HTx-free survival was significantly worse in patients without LVRR and without recurrent MR and extremely poor in patients without LVRR and with recurrent MR. Close echocardiographic monitoring is warranted for timely identification of this latter subgroup of patients, in order to re-evaluate additional treatment options and improve their prognosis.

Functional Mitral Regurgitation: The Surgeons’ Perspective

Physicians who are involved in heart failure treatment are regularly confronted with patients who present with functional mitral regurgitation (MR), occurring in a setting of ischaemic or non-ischaemic cardiomyopathy. For these patients, the current guidelines do not offer clear treatment algorithms, and mitral valve surgery is often not advised. This is however not a proper representation of the currently available literature on this topic, and may lead to patients not being evaluated for an intervention from which they may benefit. This chapter deals with the surgical perspective of functional mitral regurgitation. Topics covered are pathophysiology (with its implications for surgical techniques and annuloplasty ring choice), patient assessment and a critical appraisal of the outcome of different surgical approaches. While the focus lies on the results of undersized restrictive annuloplasty, various additional techniques are discussed in order to provide a tailored medico-surgical approach to this difficult subset of patients.

Postoperative Regression of Left Ventricular Hypertrophy

Long lasting valvular heart disease can result in damage to the cardiac muscle. However, if valve surgery is performed before the ventricular myocardium has been irreversibly damaged, myocardial structure and function will return to normal. If the valvular defect is repaired too late, left ventricular dysfunction will persist. Specific changes of left ventricular function and regression of left ventricular hypertrophy are dependent on the affected valve, the type of valve disease and the duration of valvular disease. In the current chapter, postoperative regression of left ventricular hypertrophy is described for aortic valve stenosis, aortic insuffiency and mitral valve regurgitation.

Dynamic obstruction, an unusual complication after aortic valve replacement with a stentless porcine valve

In the early nineties, the stentless porcine aortic bioprosthesis has been reintroduced successfully. Because of the limited experience, knowledge of clinical complications is limited. Therefore, we describe an unusual complication of dynamic obstruction after aortic valve replacement with a stentless porcine valve in a 70 year old man 18 months after implantation. We discuss the complications of stentless aortic prostheses known so far, describe operative techniques used and their characteristic two dimensional echocardiographic images.