Manuel Wilbring

Pushing the limits—further evolutions of transcatheter valve procedures in the mitral position, including valve-in-valve, valve-in-ring, and valve-in-native-ring

OBJECTIVE Transcatheter heart valve (THV) procedures are constantly evolving. We report our experience with valve-in-valve, valve-in-ring, and direct-view valve-in-native-ring implantation in the mitral position. METHODS Fourteen patients undergoing THV implantation in the mitral position were included. Clinical and postoperative data, including echocardiography and further follow-up, were analyzed. RESULTS Ten valve-in-valve and 2 valve-in-ring procedures were successfully performed using the transapical access route. For the third valve-in-ring procedure we used an antegrade left-atrial access via right anterolateral minithoracotomy. In 1 patient surgical mitral valve replacement was planned. Intraoperatively, the annulus appeared severely calcified and regular implantation of a bioprosthesis was not possible. As a last resort, a 29-mm Sapien XT valve (Edwards Lifesciences Inc, Irvine, Calif) was implanted under direct view. The initial result was satisfactory, but on the first postoperative day relevant paravalvular regurgitation occurred. Subsequently, the valve was fixed to an atrial cuff by 1 running suture. In this series 27-, 29-, and 31-mm bioprostheses and 28- and 30-mm annuloplasty rings were treated with 26- or 29-mm Sapien XT valves. Postoperative echocardiography on day 10 and after 6 weeks revealed good prosthesis function in all cases. In 2 valve-in-valve patients who solely received anticoagulation therapy with acetylsalicylic acid, signs of beginning valve thrombosis occurred after 8 weeks and 3 months, respectively. During further course, valve function was normalized using warfarin therapy. CONCLUSIONS Our results demonstrate feasibility of valve-in-valve and valve-in-ring THV procedures in the mitral position. Permanent anticoagulation therapy with warfarin seems to be necessary to prevent valve dysfunction. THV implantation in a calcified native mitral ring for bailout seems not to be reproducible and thus cannot be recommended.

Transapical Transcatheter Valve-in-Valve Implantation for Deteriorated Mitral Valve Bioprostheses

BACKGROUND The transcatheter valve-in-valve concept has been described for patients requiring redo valve surgery. We report our experience with transapical mitral valve-in-valve implantation. METHODS Since 2008, 301 patients were treated with transapical transcatheter valve implantation. Seven of these patients presented with a deteriorated mitral valve bioprosthesis and underwent transapical mitral valve-in-valve implantation. Median age was 79 years. Preoperatively, all patients presented in New York Heart Association functional class III. For risk estimation, The Society of Thoracic Surgeons and European System for Cardiac Operative Risk scores were used and predicted high mortality (mean ± standard error of mean: Society of Thoracic Surgeons mortality, 12.3% ± 2.1%; European System for Cardiac Operative Risk mortality, 58.0% ± 7.0%). Mean follow-up time was 93 ± 29 days, with a total of 21.6 patient-months. RESULTS Preoperatively, all patients who had deteriorated bioprostheses presented with severe regurgitation and increased transvalvular pressure gradients (maximal pressure gradient, 23.9 ± 0.9 mm Hg; mean pressure gradient, 11.3 ± 1.0 mm Hg). One patient was identified with mitral valve stenosis (effective orifice area, 0.25 cm(2)). All patients underwent successful transapical mitral valve-in-valve implantation. Sizes of previously implanted bioprostheses were 27, 29, and 31 mm; Edwards SAPIEN valves at sizes 26 and 29 mm were implanted. Postoperatively, echocardiography revealed excellent hemodynamics with no remaining mitral regurgitation in 5 patients and minimal regurgitation in 2 patients. Transvalvular pressure gradients decreased significantly (maximal pressure gradient, 13.8 ± 2.1 mm Hg; mean pressure gradient 5.7 ± 0.8 mm Hg, p < 0.05). One patient had fatal pneumonia on postoperative day 34. No patient died during further follow-up, and all patients remained in New York Heart Association class I or II. CONCLUSIONS Our results demonstrate the feasibility of transapical mitral valve-in-valve implantation for treatment of a degenerated bioprosthesis (size range, 27 to 31 mm) using the Edwards SAPIEN valve in sizes 26 and 29 mm.

Transapical transcatheter aortic valve implantation vs conventional aortic valve replacement in high-risk patients with previous cardiac surgery: a propensity-score analysis

OBJECTIVES The present analysis compared clinical and mid-term outcomes of patients with previous cardiac surgery undergoing transapical transcatheter aortic valve implantation (TAVI) with propensity-matched patients undergoing conventional redo aortic valve replacement (cAVR). METHODS Since 2008, 508 patients were treated with TAVI. Fifty-three of these patients presented with a history of cardiac surgery and underwent transapical TAVI using the Edwards SAPIEN bioprosthesis. A propensity-matched control group of 53 patients receiving cAVR was generated out of the hospitals database. The mean age for all the patients was 77.8 ± 4.5 years. The logistic EuroSCORE was 28.4 ± 13.6% in mean, and mean EuroSCORE II was 8.56 ± 3.93%. The mean follow-up time was 245 ± 323 days, which equated to a total of 700 patient-months. RESULTS The observed hospital mortality did not differ significantly between TAVI and cAVR (TAVI: 9.4% and cAVR: 5.7%; P = 0.695). Six-month survival was 83.0% for the TAVI and 86.8% for the cAVR patients (P = 0.768). Postoperative bleedings (TAVI: 725 ± 1770 ml and cAVR: 1884 ± 6387; P = 0.022), the need for transfusion (TAVI: 1.7 ± 5.3 vs cAVR: 6.2 ± 13.7 units packed red blood cells (PRBC); P = 0.030), consecutive rethoracotomy (TAVI: 1.9% vs cAVR: 16.9%; P = 0.002) and postoperative delirium (TAVI: 11.5% vs cAVR: 28.3%; P = 0.046) were more common in the cAVR patients. The TAVI patients suffered more frequently from respiratory failure (TAVI: 11.3% vs cAVR: 0.0%; P = 0.017) and mean grade of paravalvular regurgitation (TAVI: 0.8 ± 0.2 vs cAVR: 0.0; P = 0.047). Although primary ventilation time (P = 0.020) and intensive care unit stay (P = 0.022) were shorter in the TAVI patients, mean hospital stay did not differ significantly (P = 0.108). CONCLUSIONS Transapical TAVI as well as surgical aortic valve replacement provided good clinical results. The pattern of postoperative morbidity and mortality was different for both entities, but the final clinical outcome did not differ significantly. Both techniques can be seen as complementary approaches by means of developing a tailor-made and patient-orientated surgery.

Coronary surgery for acute coronary syndrome: which determinants of outcome remain?

BackgroundThe mortality risk associated with coronary artery bypass grafting (CABG) after acute myocardial infarction remains controversial. The objective of the present study was therefore to analyze the outcome and predictors of in-hospital mortality in patients (pts) referred to CABG with acute coronary syndrome (ACS).Patients and methodsBetween January 2003 and May 2005, a total of 3,127 pts underwent primary isolated CABG at our institution, including 220 pts with ACS. Out of these, unstable angina pectoris was present in 88 pts (group I), 97 pts (group II) had non-ST-elevation infarction, whereas 35 pts (group III) had ST-elevation infarction. Clinical data, in-hospital morbidity and mortality were recorded and studied retrospectively.ResultsOverall in-hospital mortality was 6.4% (n = 14) in the complete cohort, being 2.2% in group I (n = 2), 9.2% in group II (n = 9) and 8.5% (n = 3) in group III (P < 0.05). Logistic regression and receiver operating characteristic analyses identified age, NYHA, ejection fraction < 45%, catecholamine support, cardiogenic shock, renal disease and the additive EuroSCORE > 10 (P < 0.0001) as significant predictors related to in-hospital mortality. The mean time from the onset of symptoms to revascularization differed significantly between survivors (5.1 ± 2.7 h) and no survivors (11.4 ± 3.2 h) (P < 0.0007) in the STEMI group. Preoperative cTnI did not provide any prognostic information.ConclusionCABG in pts with ACS can be performed with good clinical results. The clinical outcome is particular depending on the different groups of ACS. Therefore an individual risk stratification of each pts in ACS is necessary. The time interval of 6 h seems to be crucial as prognostic variable in the STEMI-group.

Relaxin protects rat lungs from ischemia-reperfusion injury via inducible NO synthase: role of ERK-1/2, PI3K, and forkhead transcription factor FKHRL1.

Introduction Early allograft dysfunction following lung transplantation is mainly an ischemia/reperfusion (IR) injury. We showed that relaxin-2 (relaxin) exerts a protective effect in lung IR, attributable to decreases in endothelin-1 (ET-1) production, leukocyte recruitment, and free radical generation. Here, we summarize our investigations into relaxin’s signalling. Materials and Methods Isolated rat lungs were perfused with vehicle or 5 nM relaxin (n = 6–10 each). Thereafter, experiments were conducted in the presence of relaxin plus vehicle, the protein kinase A inhibitors H-89 and KT-5720, the NO synthase (NOS) inhibitor L-NAME, the iNOS inhibitor 1400W, the nNOS inhibitor SMTC, the extracellular signal-regulated kinase-1/2 (ERK-1/2) inhibitor PD-98059, the phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin, the endothelin type-B (ETB) antagonist A-192621, or the glucocorticoid receptor (GR) antagonist RU-486. After 90 min ischemia and 90 min reperfusion we determined wet-to-dry (W/D) weight ratio, mean pulmonary arterial pressure (MPAP), vascular release of ET-1, neutrophil elastase (NE), myeloperoxidase (MPO), and malondialdehyde (MDA). Primary rat pulmonary vascular cells were similarly treated. Results IR lungs displayed significantly elevated W/D ratios, MPAP, as well as ET-1, NE, MDA, and MPO. In the presence of relaxin, all of these parameters were markedly improved. This protective effect was completely abolished by L-NAME, 1400W, PD-98059, and wortmannin whereas neither PKA and nNOS inhibition nor ETB and GR antagonism were effective. Analysis of NOS gene expression and activity revealed that the relaxin-induced early and moderate iNOS stimulation is ERK-1/2-dependent and counter-balanced by PI3K. Relaxin-PI3K-related phosphorylation of a forkhead transcription factor, FKHRL1, paralleled this regulation. In pulmonary endothelial and smooth muscle cells, FKHRL1 was essential to relaxin-PI3K signalling towards iNOS. Conclusion In this short-time experimental setting, relaxin protects against IR-induced lung injury via early and moderate iNOS induction, dependent on balanced ERK-1/2 and PI3K-FKHRL1 stimulation. These findings render relaxin a candidate drug for lung preservation.

Even short-time storage in physiological saline solution impairs endothelial vascular function of saphenous vein grafts

OBJECTIVES A faultless endothelial layer is decisive for vascular function and therewith grafts patency. Functional impairment of the endothelium increases risk of graft thrombosis, intimal hyperplasia, and consecutive accelerated graft atherosclerosis. Storage solutions for intra-operatively harvested saphenous vein segments (SVS) might have significant impact on endothelial function. We investigated the impact of short-time storage in physiological saline solution (PSS) and a potassium-chloride- and N-acetylhistidine-enriched storage solution on venous endothelial function. METHODS Intra-operatively isolated SVSs (n=19) were stored in different storage solutions for 90 min. They were then immediately studied in tissue bath at 36°C with continuous oxygen insufflation. Following preconstriction with norepinephrine, dose-response relaxation curves of bradykinine (Brad) and sodium nitroprusside (SNP) were determined. We compared developed maximum wall tension, vessel constriction kinetics, endothelial cell- and smooth muscle cell (SMC)-dependent vasodilatory function. RESULTS Maximum vessel wall tension was reduced significantly in PSS-stored vessels (10.1 ± 9.8 mN mm(-1) vs 3.5 ± 3.4 mN mm(-1); p=0.0372). Endothelium-derived vasodilatory function was likewise significantly reduced after short-time storage (20.6 ± 34.4% vs 35.0 ± 27.0%; p=0.0437). SNP-mediated SMC-vasodilatory function was maintained equally well in both groups (88.2 ± 21.8% vs 83.0 ± 30.6% in PSS; p=n.s.). CONCLUSION Even short-time storage in PSS significantly impairs endothelial vascular function. Concerning the essential role of a faultless endothelial layer, the quite common use of PSS as a storage solution for SVSs in CABG surgery has to be discussed critically.

Lactococcus garvieae causing zoonotic prosthetic valve endocarditis.

A 55-year-old amateur fish farmer with a history of mechanical tricuspid valve replacement was admitted to hospital due to progressive dyspnea. Additionally he suffered relapsing shivering attacks and fever of unknown origin of 2 weeks duration. The patient denied arthralgia, night perspiration or weight-loss. His family doctor started antibiotic treatment with cotrimoxazole. Physical examination showed loss of click/murmur of the mechanical valve prosthesis. Five years ago the patient underwent mechanical valve replacement because of seronegative tricuspide valve endocarditis in consequence of chronic parodontitis complicated by bacterial lung abscesses. Transesophageal echocardiography revealed a mobile vegetation of 7 9 9 mm diameter on the mechanical valve prosthesis (Fig. 1). Baseline laboratory tests showed a leukocyte count of 18.9 Gpt/l and increased C-reactive protein of 72.4 mg/l. An intravenous antibiotic therapy of gentamicin, vancomycin and rifampicin was initiated. Three consecutively taken blood cultures were positive for Lactococcus garvieae. Within 1 week fever and inflammation parameters declined to normal values. The patient then underwent prosthetic valve replacement (33 mm Carpentier Edwards SAV bioprosthesis). Intraand postoperative course were uneventful. The patient was released from hospital with an antibiotic therapy adapted to the antibiogram (levofloxacin, amoxicillin and clavulanic acid) for 8 weeks and an oral anticoagulative therapy for 3 months. The Lactococcus genus is different to other gram-positive cocci like Streptococci or Enterococci [1, 2]. The catalase-negative, facultatively anaerobic, serogroup N gram-positive Lactococcus garvieae is a distinct fishpathogen with a high virulence in fish with LD50 of 10 bacteria per fish. It is isolated in saltwater fish in Far East and also in European Rainbow Trout. In humans it is a rare pathogen and of low virulence—a review of literature reports 12 cases of infection in humans [3]. The case of native or prosthetic valve endocarditis caused by these bacteria is extremely unusual [4–6]. In the present case the M. Wilbring (&) H. Reichenspurner Department for Cardiovascular Surgery, University Heart Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany e-mail: manuel.wilbring@gmail.com

The impact of preoperative neurological events in patients suffering from native infective valve endocarditis

OBJECTIVES Infective native valve endocarditis (NVE) complicated by a preoperative neurological event still remains a surgical challenge. Particularly, great uncertainty exists with regard to the optimal timing of surgery. We call for a multidisciplinary team approach for individualized risk estimation and analysed our experience obtained over the past decade. METHODS Between 1997 and 2012, a total of 495 patients underwent valve surgery for the treatment of NVE. Of these, 70 (14.1%) patients suffered from NVE complicated by an acute neurological event and formed the study group. The remaining 425 (85.9%) patients served as the control group. The mean age of the predominantly male (80.0%) study population was 54 ± 14 years. EuroSCORE and EuroSCORE II predicted a high surgical risk (24.9 ± 6.8 and 10.8 ± 8.1%, respectively). The mean follow-up time was 4.0 ± 3.1 years, ranging up to 15.6 years with an interquartile range from 1.7 to 5.4 years. An interdisciplinary team consisting of a cardiac surgeon, a cardiologist and a neurologist made the decision for surgery. RESULTS Observed neurological deficits mainly consisted of ischaemic stroke (75.7%), meningoencephalitis (12.9%) and intracerebral haemorrhage (8.6%). The mean time interval between the neurological event and surgery was 8.7 ± 10.3 days for all patients, 8.0 ± 7.0 days for ischaemic stroke and 17 ± 24 days for intracerebral haemorrhage. Postoperatively, most of the patients experienced no change (22.9%) or even improvement (67.1%) of their neurological symptoms. Only 10.0% showed further deterioration of their neurological status. This was particularly true for patients suffering from intracerebral haemorrhage, with 33.3% experiencing further neurological impairment. The presence of a preoperative neurological event was identified as an independent risk factor for in-hospital mortality (OR 2.66; 95% CI: 1.02-6.78; P = 0.046) but not for mortality during further follow-up (P = 0.257). The hospital mortality rate was 17.2%; and the 1-, 5- and 10-year survival rates were 74.3, 68 ± 5.0 and 67.1 ± 9.0%, respectively. CONCLUSIONS NVE complicated by neurological events remains a challenging disease with high mortality and morbidity. Cardiac surgery seemed to be safe in the observed time interval, particularly for patients suffering from ischaemic stroke. A multidisciplinary approach is advocated for very individualized risk estimation.

Native infective endocarditis: Which determinants of outcome remain after surgical treatment?

SummarySurgical therapy of native infective endocarditis is still considered as a particular challenge, due to remaining morbidity and mortality up to 20%. Further risk analysis and characterization of clinical features is of great importance for further improvement of surgical results. The aim of this retrospective study was a risk analysis concerning clinical features of the pre–, intra– and postoperative period.Between 02/1997 and 12/2003, 165 patients (130 male, 35 female, age 55.5 ± 13.8 years) were referred for surgical therapy of infective endocarditis at our institution. Preoperative, intraoperative and postoperative features were evaluated for their influence on the early postoperative course and the mid–term follow–up. In the majority of patients (pts) the aortic valve was infected (n = 83, 50.3% of pts), followed by mitral valve (n = 33; 20.0%), tricuspid valve (n = 10, 6.0%) and pulmonary valve (n = 2; 1.2%). Double valve affection was recorded in 37 pts (22.4%). Streptococci (n = 66, 40.0%) and staphylococci (n = 66, 40.0%) were the most common pathogens. The overall hospital mortality rate was 10.9% (n = 18), during follow–up (mean follow–up 3.3 ± 2.5 years) a further 20 pts (12.1%) died.Main predictors for hospital mortality in multivariate analysis were older age (p = 0.01), prolonged ICU stay, prolonged intubation (p = 0.03; p = 0.02) and the continuous postoperative need of alpha–catecholamine medication (p < 0.01). Significant predictors of overall mortality were older age (> 70 years) and diabetes (p = 0.03; p = 0.03). Reinfection occurred in 6.1% of patients (n = 10). Actuarial freedom from recurrent infection was 97% at 1 year and 93.9% at 5 years. Surgical therapy of infective endocarditis is associated with good clinical results in the early and mid–term follow–up. Predictors of outcome particular include preoperative risk constellation or comorbidity (age, diabetes) and variables of the immediate postoperative course.

Transcatheter aortic valve implantation reduces grade of concomitant mitral and tricuspid valve regurgitation and pulmonary hypertension

OBJECTIVES The presence of concomitant mitral (MR) or tricuspid regurgitation (TR) is a common issue in patients undergoing transcatheter aortic valve implantation (TAVI). The objective was (i) to analyse the outcomes of patients with concomitant moderate or more severe MR, (ii) to compare the outcomes with those of TAVI patients without concomitant MR and (iii) to evaluate the impact of TAVI on grade of concomitant MR. METHODS For creating a homogeneous study group, the study was restricted to transapical (TA)-TAVI patients. Since 2008, 615 patients have undergone TAVI at our institution, 386 of these using the TA approach with the Edwards SAPIEN™ bioprosthesis. Out of these, 116 (30.1%) presented with concomitant moderate or more severe MR. Mean logistic European System for Cardiac Operative Risk (EuroSCORE) was 18.1 ± 11.5%, EuroSCORE II 5.4 ± 0.7%. Intra- and post-hospital course, change in grade of MR, TR, right ventricular systolic pressure (RVSP) and tricuspid annular plane systolic excursion (TAPSE) were particularly analysed. Outcomes were compared with those of the remaining TA-TAVI patients (n = 270). Mean follow-up time was 471 ± 391 days, giving a total of 135 patient-years. RESULTS Three patients (2.6%) died during primary hospital stay. Estimated 1-, 2-, 3- and 4-year survival rates were 76.7, 75.6, 68.3 and 50.6% for study and 78.1, 77.8, 61.1 and 55.0% for control groups, respectively. Postoperative morbidity and mortality did not differ significantly from those of the control group. Postoperatively, a significant reduction in MR (2.1 ± 0.2 to 1.5 ± 0.7; P < 0.01) and TR (1.9 ± 0.5 to 1.5 ± 0.7; P < 0.01) was observed. Likewise, RVSP decreased significantly from 46 ± 16 to 39 ± 15 mmHg (P < 0.01) and TAPSE non-significantly (21.9 ± 7.3 to 19.5 ± 5.5 mm; P = 0.07). After 3-6 months, 68.9% of the patients were at New York Heart Association (NYHA) Class I or II, 25% at Class III and 6.0% downgraded to Class IV. A reason for remaining in NYHA Class III or downgrading to NYHA Class IV could not be detected, and particularly, there was no impact of grade of MR/TR, left ventricular ejection fraction, TAPSE or right ventricular endsystolic pressure (RVESP) on outcomes or NYHA class. CONCLUSION TA-TAVI in patients with concomitant moderate or more severe MR provides results comparable with those of TA-TAVI in general. Concomitant MR had no significant impact on the short- and mid-term outcomes. A significant reduction in MR, TR and pulmonary hypertension was observed after TA-TAVI during short-term follow-up. Nonetheless, a relevant number of patients did not experience an improvement in NYHA class.