Georg Lutter

The future of transcatheter mitral valve interventions: competitive or complementary role of repair vs. replacement?

Transcatheter mitral interventions has been developed to address an unmet clinical need and may be an alternative therapeutic option to surgery with the intent to provide symptomatic and prognostic benefit. Beyond MitraClip therapy, alternative repair technologies are being developed to expand the transcatheter intervention armamentarium. Recently, the feasibility of transcatheter mitral valve implantation in native non-calcified valves has been reported in very high-risk patients. Acknowledging the lack of scientific evidence to date, it is difficult to predict what the ultimate future role of transcatheter mitral valve interventions will be. The purpose of the present report is to review the current state-of-the-art of mitral valve intervention, and to identify the potential future scenarios, which might benefit most from the transcatheter repair and replacement devices under development.

Percutaneous Transcatheter Mitral Valve Replacement An Overview of Devices in Preclinical and Early Clinical Evaluation

Mitral regurgitation (MR) is one of the most prevalent valvular heart diseases in Western countries. The current estimated prevalence of moderate and severe MR in the United States is 2 to 2.5 million, and it is expected that this number will rise to 5 million by 2030.1 Surgical intervention is recommended for symptomatic severe MR or asymptomatic severe MR with left ventricular (LV) dysfunction.2 Treatment of degenerative MR has evolved from mitral valve (MV) replacement to MV repair because of superior long-term outcomes after repair.2–4 For functional MR, however, the benefit over MV replacement is less certain.5 In addition, minimally invasive MV surgery has become a well-established and increasingly used option for managing patients with MV pathology.6 Although surgery remains the gold standard treatment for significant MR, MV surgery is deferred in a large number of patients because of high surgical risk.7 The decrease in the prevalence of rheumatic valve disease, in combination with an increased life expectancy, has led to a high prevalence of degenerative MR. As a consequence, patients are older and present with comorbidities that increase operative mortality and morbidity risks.8 In octogenarians, there has been reported a mortality and morbidity rate of 17.0% and 35.5%, respectively, following MV surgery.9 This results in denial or nonreferral for surgery in a large group of patients with significant MR—the Euro Heart Survey revealed that up to 50% of patients hospitalized with symptomatic severe MR are not referred for MV surgery, mainly because of advanced age, comorbidities, and LV dysfunction. In patients aged ≥80 years, surgical treatment was performed in only 15% compared to 60% in patients aged ≤70 years.8,10 The observation that a significant number of patients are not referred for MV surgery and the desire …

Transmyocardial laser revascularization (TMLR) in patients with unstable angina and low ejection fraction

OBJECTIVE Does perioperative use of the intraaortic balloon pump (IABP) improve the postsurgical outcome of patients presenting with endstage coronary artery disease, unstable angina and low ejection fraction transferred for transmyocardial laser revascularization (TMLR)? METHODS TMLR, as sole therapy combined with the perioperative use of an intraaortic balloon pump has been assessed in seven patients with endstage coronary artery disease, unstable angina and low ejection fraction (EF < 35%). Six out of seven patients had signs of congestive heart failure. These patients are compared with 23 patients with endstage coronary artery disease, stable angina and EF > 35%, who were treated with TMLR as sole therapy without the use of IABP. The creation of transmural channels was performed by a CO2-laser. All patients were evaluated by hybrid positron emission tomography (perfusion SPECT and viability PET) and ventriculography preoperatively. Echocardiography, clinical status and hemodynamic assessment by Swan Ganz catheter were performed perioperatively. RESULTS The perioperative mortality of this combined procedure (TMLR and IABP) was zero. Three out of seven patients had pneumonia with complete recovery. Swan Ganz catheter examinations showed deterioration of LV-function after TMLR intraoperatively and improvement after 2 h and further after 6 h on ICU (P < 0.05). In contrast, a decrease of LV-function in sole TMLR patients with an EF > 35%) has not been observed. Patients with EF < 35% needed the IABP for 2.3 days and moderate dose catecholamines for a mean of 3.0 days. The postoperative EF and resting wall motion score index (WMSI) of all analysed LV segments (evaluated by echocardiography) did not change compared to baseline (EF 31.3+/-2.6 preop. to 32.8+/-3.2 postop.; WMSI: 1.75+/-0.14 at baseline to 1.71+/-0.17 postop.). The average Canadian Angina Class at the time of discharge decreased from 4.0+/-0 (baseline) to 2.3+/-0.5 (P < 0.05) and the NYHA-Index from 3.9+/-0.3 to 2.7+/-0.5. No patient had signs of angina pectoris, whereas two patients still had signs of congestive heart failure. CONCLUSIONS The reported data support our concept to start IABP preoperatively in patients with reduced LV contractile reserve in order to provide cardiac support during the postoperative phase of reversible decline of LV-function induced by TMLR.

Off-pump transapical mitral valve replacement

OBJECTIVE Percutaneous valve replacement was recently introduced, and reports of early clinical experience have already been published. To date, this technique is limited to the replacement of pulmonary and aortic valves in a strictly selected group of patients. The aim of this study was to analyse a self-expanding valved stent for minimally invasive replacement of the mitral valve in animals. METHODS A newly designed nitinol stent was specially designed for this experimental acute study. It comprised of a left ventricular tubular stent with star shaped left atrial anchoring springs and carried a trileaflet bovine pericardial valve. A polytetrafluoroethylene membrane was sutured to envelop the atrial springs and the outside of the ventricular stent. The ventricular anchoring system was the same as in our previously reported results with a similar mitral valved stent. Seven pigs underwent minimally invasive off-pump mitral valved stent implantation. This was performed through a lower mini-sternotomy and a standard transapical approach under transoesophageal echocardiographic (TEE) guidance was used. RESULTS The valved stent is fully retrievable and precise deployment and accurate adjustment of its intra-annular position is achievable to eliminate paravalvular leakage. The deployment time ranged from 127 to 255s and the blood loss from 70 to 220cc. One animal died of intractable ventricular fibrillation. Mitral regurgitation in all surviving animals was minimal (trace in 5/6 and mild in 1/6 during echo examination; on the contrast ventriculogram no mitral insufficiency was observed except in one documented as mild paravalvular regurgitation). These animals remained haemodynamically stable (6/6) and without TEE or ventriculographic changes for 1h. CONCLUSION Implantation of a tricuspid bovine pericardial valved stent in the mitral position is feasible in pigs through a transcatheter approach. This was possible through a smaller delivery system than previously reported. Additional studies are required to demonstrate long-term feasibility, durability, and heart function.

Collateral growth: cells arrive at the construction site

Coronary artery disease (CAD) and peripheral artery occlusion disease are the most common diseases in the Western world which are treated by pharmacological and surgical therapies. However, patients in the endstage of the disease are not suitable candidates for bypass surgery. Alternative therapies that boost the endogenous collateralization are required. Two mechanisms are naturally activated after onset of ischemia: 1. angiogenesis, sprouting of capillaries, and 2. arteriogenesis, enlargement of small preexisting arterioles. In the first part of this review, we describe the sequence of events during the development of collateral vessels. The second part focuses on two types of cells which are crucial for the development of collateral circulation, and which migrate to the site of vessel growth via peripheral blood: monocytes/macrophages and endothelial progenitor cells. The role of these cells and the implications for their use in treating ischemic diseases of cardiac and sceletal muscle are discussed.

Durability of Bioprosthetic Cardiac Valves

INTRODUCTION The choice of type of heart valve prosthesis is determined by the patients age since bioprostheses have a limited lifespan. This article reviews current recommendations and the literature on cardiac valve replacement. METHODS Selective literature search in Medline/PubMed back to 1996 and review of current national and international recommendations from specialist societies. RESULTS The recommendations guiding the type of heart valve replacement have been revised in recent years. Of particular interest are the new generation of biological prostheses with extended durability, a growing use of stentless bioprostheses, a decrease in mortality of reoperation and an increase in life expectancy. Comorbidities such as chronic renal insufficiency or chronic atrial fibrillation are no longer contraindications to bioprosthesis. The number of heart valve replacements in recent years rose despite a concomitant increase in valve repairs. Aortic valves are being increasingly replaced by bioprostheses. DISCUSSION The choice of heart valve prosthesis should be tailored to each patient taking into account the patients age, life expectancy, comorbidities, and life style. Different decisions may be made now than those based on earlier recommendations resulting in an individualized treatment, in patients over the age of 65 or 70.

Successful orthotopic pig heart transplantation from non-heart-beating donors.

BACKGROUND With the aim to expand the severely limited donor pool by use of non-heart-beating donors we developed a technique for successful transplantation of hearts after 30 minutes of normothermic ischemia without donor pretreatment. METHODS In control groups hearts were transplanted in a conventional fashion using crystalloid cardioplegia (Group I, n = 6) or BCP (Group II, n = 8) for induction of cardiac arrest. In the ischemic groups hearts were harvested after 30 minutes of normothermic ischemia, perfused with blood cardioplegia (BCP) (Group III, n = 9) or BCP containing the Na(+)-H(+)-exchange inhibitor HOE 642 (Group IV, n = 8) and transplanted orthotopically. RESULTS All animals could be weaned from cardiopulmonary bypass. Low dose inotropic support was necessary in the ischemic groups only. Recovery of the maximal left ventricular stroke work index (LVSWImax) in Groups I vs II was 62.6+/-19.6% vs 73.3+/-23.3% (NS), maximal right ventricular stroke work index (RVSWImax) averaged 61.1+/-18.8 vs 87.8+/-31.7% (NS) as compared to the preoperative level. In the ischemic groups (III vs IV) LVSWImax was 27.3+/-11.7 vs 59.5+/-32.4% (p = 0.038), RVSWImax was 27.4+/-20.9 vs 64.2+/-46.6% (NS). CONCLUSIONS The results indicate that (a) successful pig heart transplantation after 30 minutes of normothermic ischemia is possible without donor pretreatment, and (b) that HOE 642 improves posttransplant LVSWImax significantly.

Transapical mitral valved stent implantation: A survival series in swine

OBJECTIVE To assess short-term survival after transcatheter mitral valve replacement using a unique mitral valved stent design and anchoring system. METHODS The new nitinol self-expandable valved stent houses a trileaflet glutaraldehyde-preserved bioprosthesis and contains atrial and ventricular fixation systems. Eight pigs underwent transesophageal echocardiogram-guided transapical mitral valved stent implantation through a lower mini-sternotomy. Intracardiac pressure gradients were estimated by transesophageal echocardiogram. RESULTS The mean mitral annulus size was 24.6 +/- 1.4 mm, and the valved stent size was 26.0 +/- 2.6 mm. The average mean transvalvular gradient across the valved stent immediately after deployment, at 6 hours, and after 1 week remained low. The gradient across the neighboring left ventricular outflow tract was not affected. Average animal survival was 7.3 days (8 hours to 29 days). Animals that died before 1 week (n = 4) were found at necropsy to have valved stent malpositioning. Animals that survived 1 week or more had accurate deployment and only trace post-deployment paravalvular leak. The causes of death in this latter group were endocarditis (n = 1), failure of atrial fixation (n = 2), and failure of ventricular fixation (n = 1). There was no valved stent embolization in any of the animals. CONCLUSION Adequate function and effective anchoring of the new mitral valved stent allowed for short-term animal survival after transapical mitral valved stent implantation.

Percutaneous pulmonary valve replacement: autologous tissue-engineered valved stents

AIMS Percutaneous implantation has already been used clinically and is a great option for treating young patients. The use of autologous tissue-engineered valved stents might solve the problem of degeneration and limited durability of biological heart valves. METHODS AND RESULTS Porcine pulmonary heart valves and small intestinal submucosa were obtained from a slaughterhouse. The intestinal submucosa was used to cover the inside of the porcine pulmonary valved stents. Endothelial cells (ECs) and autologous myofibroblasts (MFs) were used from carotid artery segments of juvenile sheep. After MF seeding, constructs were placed in a dynamic bioreactor system and cultured for 16 days. After additional EC seeding, tissue-engineered valved stents were percutaneously deployed into the annulus of the pulmonary valve (n = 9). Angiography was performed at implantation and 4-week follow-up. Constructs were analysed radiographically, by post-mortem examination, and microscopically. In all but one case, orthotopic positioning of the stents (n = 6) at the time of implantation and explantation was observed angiographically, macroscopically, and by computer tomography scan and demonstrated normal valve function (n = 7). Gross morphology confirmed excellent opening and closure characteristics of all leaflets after 4 weeks (n = 7). Strong expression of α-smooth muscle actin in neo-interstitial cells and of von Willebrand factor and PECAM-1 in ECs was revealed by immunocytochemistry. CONCLUSION Good functioning and morphological characteristics were observed after percutaneous tissue-engineered valved stent implantation with autologous cells. This implantation of autologous tissue-engineered valved stents will become a valid future option in adolescents.

Is there really a clinical benefit of using minimized extracorporeal circulation for coronary artery bypass grafting

BACKGROUND Minimized extracorporeal circulation is intended to reduce the negative effects associated with cardiopulmonary bypass. This prospective study was performed to evaluate whether minimized extracorporeal circulation has a clinical benefit for coronary artery surgery patients compared to standard extracorporeal circulation. METHODS Sixty patients were randomized into two study groups: 30 patients underwent coronary artery bypass grafting using minimized extracorporeal circulation and 30 patients were operated using standard extracorporeal circulation. Baseline characteristics, intraoperative details, postoperative data, perioperative blood chemistry determinations of hematocrit, platelets, muscle-brain fraction of the creatine kinase, cardiac troponin T and colloid osmotic pressure as measurements of intrathoracic blood volume index and extravascular lung water index were compared. RESULTS Baseline characteristics and intraoperative details of both groups were similar. Patients who underwent minimized extracorporeal circulation showed more short-term dependency on norepinephrine ( P < 0.01). Their maximal postoperative muscle-brain fraction of the creatine kinase was lower ( P < 0.05) and their hematocrit on arrival in the intensive care unit was higher ( P < 0.01). No other significant differences were found. In both collectives, values for hematocrit ( P < 0.001), platelets ( P < 0.001), colloid osmotic pressure ( P < 0.001) and intrathoracic blood volume index ( P < 0.05) decreased, while the extravascular lung water index did not change significantly during cardiopulmonary bypass. CONCLUSIONS A clinical advantage of minimized over standard extracorporeal circulation was not found. Furthermore, a higher number of patients in the minimized extracorporeal circulation group required postoperative norepinephrine infusions for hemodynamic stabilization. In summary, the presumed superiority of minimized extracorporeal circulation for coronary artery bypass grafting in standard patients could not be confirmed.