Jens Garbade

Fully Magnetically Levitated Left Ventricular Assist System for Treating Advanced HF: A Multicenter Study

BACKGROUND The HeartMate 3 left ventricular assist system (LVAS) is intended to provide long-term support to patients with advanced heart failure. The centrifugal flow pump is designed for enhanced hemocompatibility by incorporating a magnetically levitated rotor with wide blood-flow paths and an artificial pulse. OBJECTIVES The aim of this single-arm, prospective, multicenter study was to evaluate the performance and safety of this LVAS. METHODS The primary endpoint was 6-month survival compared with INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)-derived performance goal. Patients were adults with ejection fraction ≤ 25%, cardiac index ≤ 2.2 l/min/m(2) without inotropes or were inotrope-dependent on optimal medical management, or listed for transplant. RESULTS Fifty patients were enrolled at 10 centers. The indications for LVAS support were bridge to transplantation (54%) or destination therapy (46%). At 6 months, 88% of patients continued on support, 4% received transplants, and 8% died. Thirty-day mortality was 2% and 6-month survival 92%, which exceeded the 88% performance goal. Support with the fully magnetically levitated LVAS significantly reduced mortality risk by 66% compared with the Seattle Heart Failure Model-predicted survival of 78% (p = 0.0093). Key adverse events included reoperation for bleeding (14%), driveline infection (10%), gastrointestinal bleeding (8%), and debilitating stroke (modified Rankin Score > 3) (8%). There were no pump exchanges, pump malfunctions, pump thrombosis, or hemolysis events. New York Heart Association classification, 6-min walk test, and quality-of-life scores showed progressive and sustained improvement. CONCLUSIONS The results show that the fully magnetically levitated centrifugal-flow chronic LVAS is safe, with high 30-day and 6-month survival rates, a favorable adverse event profile, and improved quality of life and functional status. (HeartMate 3™ CE Mark Clinical Investigation Plan [HM3 CE Mark]; NCT02170363).

Minimally Invasive Versus Sternotomy Approach for Mitral Valve Surgery in Patients Greater Than 70 Years Old: A Propensity-Matched Comparison

BACKGROUND The goal of this study was to compare the outcome after mitral valve surgery through either standard sternotomy or right lateral minithoracotomy in elderly patients with higher perioperative risk. METHODS All 1,027 elderly patients (>70 years) who received isolated mitral valve surgery (± tricuspid valve repair) between August 1999 and July 2009 were analyzed for outcome differences due to surgical approach using propensity score matching. The etiology of mitral valve disease was degenerative (83%), endocarditis (6%), rheumatic (10%), and acute ischemic (<1%). Isolated stenosis was rare (3%); most patients had mitral valve regurgitation (72%) or combined mitral valve disease (25%). RESULTS The minimally invasive approach led to longer duration of surgery (186 ± 61 vs 169 ± 59 minutes, p = 0.01), cardiopulmonary bypass time (142 ± 54 vs 102 ± 45 minutes, p = 0.0001), and cross-clamp time (74 ± 44 vs 64 ± 28 minutes, p = 0.015). There were no differences between the matched groups in 30-day mortality (7.7% vs 6.3%, p = 0.82), combined major adverse cardiac and cerebrovascular events (11.2% vs 12.6%, p = 0.86), or other postoperative outcome. Only the number of postoperative arrhythmias and pacemaker implants was higher in the sternotomy group (65.7% vs 50.3%, p = 0.023 and 18.9% vs 10.5%, p = 0.059). Long-term survival was 66% ± 5.6% vs 56 ± 5.5% at 5 years and 35% ± 12% vs 40% ± 7.9% at 8 years, and did not show significant differences. CONCLUSIONS Minimally invasive mitral valve surgery through a right lateral minithoracotomy is at least as good and safe as the standard sternotomy approach in elderly patients.

ACE-inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation.

AbstractObjectiveChronic atrial fibrillation (AF) is characterized by a remodeling process which involves the development of fibrosis. Since angiotensin II has been suspected to be involved in this process, the aim of our study was to investigate a possible influence of an ACE–I therapy in patients with chronic AF regarding the occurrence of left atrial structural remodeling.MethodsAtrial tissue samples were obtained from patients with lone chronic AF or sinus rhythm (SR). Collagen I, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expression were measured by quantitative Western Blotting techniques and calculated as mean ± SEM. Histological tissue samples were used for calculating microvessel density (microvessel/mm2 ± SEM).ResultsIn AF, the collagen amount was higher (1.78 ± 0.21; p = 0.01) vs. SR (0.37 ± 0.07) accompanied by declining microcapillary density (AF: 145 ± 13 vs. SR: 202 ± 9; p = 0.01). Additionally, a negative correlation (p = 0.01) between collagen content and microcapillary density was observed. To investigate the influence of an ACE–I therapy on this remodeling process, patient groups were divided into AF and SR both with or without ACE–I. Interestingly, there was a significantly lower expression of collagen I in AF with ACE–I (1.04 ± 0.26) vs. AF without ACE–I treatment (2.07 ± 0.24, p = 0.02). The microcapillaries were not diminished in AF with ACE–I (180 ± 15) vs. SR with ACE–I (196 ± 9), but there was a significant rarification in AF without ACE–I (123 ± 18; p = 0.03). The expression of VEGF and bFGF did not reveal any significant differences.ConclusionIn patients undergoing ACE–I treatment: atrial structural remodeling was attenuated and the loss of atrial microcapillaries was prevented.

Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides

Co-ordinated electrical activation of the heart is maintained by intercellular coupling of cardiomyocytes via gap junctional channels located in the intercalated disks. These channels consist of two hexameric hemichannels, docked to each other, provided by either of the adjacent cells. Thus, a complete gap junction channel is made from 12 protein subunits, the connexins. While 21 isoforms of connexins are presently known, cardiomyocytes typically are coupled by Cx43 (most abundant), Cx40 or Cx45. Some years ago, antiarrhythmic peptides were discovered and synthesised, which were shown to increase macroscopic gap junction conductance (electrical coupling) and enhance dye transfer (metabolic coupling). The lead substance of these peptides is AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-CONH2), a peptide with a horseshoe-like spatial structure as became evident from two-dimensional nuclear magnetic resonance studies. A stable d-amino-acid derivative of AAP10, rotigaptide, as well as a non-peptide analogue, gap-134, has been developed in recent years. Antiarrhythmic peptides act on Cx43 and Cx45 gap junctions but not on Cx40 channels. AAP10 has been shown to enhance intercellular communication in rat, rabbit and human cardiomyocytes. Antiarrhythmic peptides are effective against ventricular tachyarrhythmias, such as late ischaemic (type IB) ventricular fibrillation, CaCl2 or aconitine-induced arrhythmia. Interestingly, the effect of antiarrhythmic peptides is higher in partially uncoupled cells and was shown to be related to maintained Cx43 phosphorylation, while arrhythmogenic conditions like ischaemia result in Cx43 dephosphorylation and intercellular decoupling. It is still a matter of debate whether these drugs also act against atrial fibrillation. The present review outlines the development of this group of peptides and derivatives, their mode of action and molecular mechanisms, and discusses their possible therapeutic potential.

Early angiographic control of perioperative ischemia after coronary artery bypass grafting

OBJECTIVE To assess the impact of immediate angiography in patients with defined clinical and laboratory criteria of perioperative myocardial infarction after coronary artery bypass operation. PATIENTS AND METHODS Between January 1999 and December 1999 2052 patients underwent coronary artery bypass grafting in our institution. Out of this cohort 131 (6.4%) patients met the criteria of perioperative myocardial ischemia, which was defined as: (a) increase in the isoenzyme ratio of creatinine phosphokinase (CK/CK-MB] above 10%; (b) ischemic electrocardiographic episodes (defined as a new onset of elevated ST-segment change lasting at least 1 min and involving a shift from baseline of greater than or equal to 0.1 mV of ST-depression and a new association of a postoperative Q; (c) recurrent episodes of, or sustained ventricular tachyarrhythmia as well as ventricular fibrillation; (d) hemodynamic deterioration despite adequate inotropic support. RESULTS Angiography was performed in 108 patients (5.3%, group A) whereas 23 patients (1.1%, group B) were immediately re-operated due to severely compromised hemodynamics. Angiographic results in group A showed regular grafts in 45 patients (2.2%); 63 patients (3.1%) had either an occlusion (n=41), incorrect anastomosis (n=29), graft stenosis (n=14), graft spasm (n=6), displaced graft (n=6), poor distal run-off (n=5) or incomplete revascularization (n=2). In group A 43 patients underwent a re-operation (34 patients) or an early angioplasty (nine patients). Due to poor coronary artery status no intervention was performed in the remaining 20 patients with angiographic findings. Operative findings in group B showed graft occlusion in ten patients (43.5%), incorrect anastomosis in five patients (21.7%), bleeding, stretched graft, venous graft spasm and displaced graft in one patient (4.3%) each, and no patho-morphological finding in 4 patients (17.4%). Thirty-day mortality rate was ten patients in group A (9.3%), all of them with angiographic findings, as opposed to nine patients (39.1%) in group B. CONCLUSION ST-change and elevated CK/CK-MB enzyme ratio is highly indicative for possible graft failure and should be followed early angiographic control to assess the need for reintervention.

Current Trends in Implantable Left Ventricular Assist Devices

The shortage of appropriate donor organs and the expanding pool of patients waiting for heart transplantation have led to growing interest in alternative strategies, particularly in mechanical circulatory support. Improved results and the increased applicability and durability with left ventricular assist devices (LVADs) have enhanced this treatment option available for end-stage heart failure patients. Moreover, outcome with newer pumps have evolved to destination therapy for such patients. Currently, results using nonpulsatile continuous flow pumps document the evolution in outcomes following destination therapy achieved subsequent to the landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure Trial (REMATCH), as well as the outcome of pulsatile designed second-generation LVADs. This review describes the currently available types of LVADs, their clinical use and outcomes, and focuses on the patient selection process.

Pharmacodynamics of T-cell function for monitoring immunosuppression

Abstract.  Objectives: Recent studies show that measuring pharmacodynamic (PD) effects offers a unique possibility to predict immunosuppression. Thus, in this study we have monitored the PD properties of immunosuppressants on diverse T‐cell functions in heart transplant (HTx) recipients. Materials: PDs and blood concentrations (PK) of three different basis‐immunosuppressive drugs were studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T‐cell function was analysed by expression of proliferating cell nuclear antigen (PCNA) labelling, expression of cytokines (IL‐2, IFN‐γ) and surface antigen (for example, CD25) by FACS analysis. Results: In group I, at time points C0 and C2, increased CsA‐PK significantly inhibited expression of IL‐2, IFN‐γ, PCNA and CD25 (P < 0.05). Correlations (r2) at C2 between inhibition of T‐cell functions (PD) with PK and with drug doses were: CsA‐PK: 0.71–0.91 and CsA‐dose: 0.73–0.87. In group II, increased TRL‐PK over time did not further inhibit expression of CD25, but inhibited PCNA expression more on day 3, and IL‐2 and IFN‐γ expression was significantly higher on days 2 and 3 compared to PD effects of CsA (P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL‐PK category, whereas expression of CD25 was higher and expression of cytokines was lower than PD effects of CsA. Conclusions: Our results show that PD effects on T‐cell function can be used to monitor immunosuppression bringing potential to increase the efficacy and safety of immunosuppressive therapy after HTx.

Outcome of Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation and Graft Recovery

BACKGROUND Indications for extracorporeal membrane oxygenation (ECMO) use in lung transplantation are (1) temporary assistance as a bridge to transplantation, (2) stabilization of hemodynamics during transplantation in place of cardiopulmonary bypass, and (3) treatment of severe lung dysfunction and primary graft failure after transplantation. This study compares the survival of lung transplant recipients requiring ECMO support with survival of patients without ECMO. METHODS A retrospective database review was performed for 108 consecutive patients who underwent single-lung or bilateral-lung transplantation at our center between 2002 and 2009. RESULTS Of 108 transplant recipients, 27 (25%) required venoarterial ECMO compared with 81 patients who did not. Nine patients required ECMO preoperatively (87±102 hours), and ECMO was continued for 5 patients during the lung transplant operation. Seven additional patients received ECMO during transplantation. Six patients required early (<7 days) and 5 patients delayed (≥7 days) postoperative ECMO for treatment of allograft dysfunction. The subgroup with support showed the most favorable patient discharge rate (66.7%). ECMO support was a significant risk factor for death (p<0.001). Survival was significantly reduced with the use of ECMO: 30-day, 90-day, 1-year, and 5-year survival was 97%, 91%, 83%, and 58% in the patients without ECMO compared with 63%, 44%, 33%, and 21% in those with ECMO, respectively. CONCLUSIONS Survival after lung transplantation was significantly reduced with ECMO. However, patients who survived the first year showed similar long-term survival as those patients who did not need perioperative ECMO support.

Outcome of patients suffering from acute type B aortic dissection: a retrospective single-centre analysis of 135 consecutive patients

OBJECTIVES Acute uncomplicated Stanford type B aortic dissection (TBAD) is optimally managed with medical treatment. However, surgery and thoracic endovascular aortic repair (TEVAR) are occasionally indicated, particularly when end-organ ischaemia develops. This study assesses the perioperative and long-term outcomes of medical, interventional and surgical management of acute TBAD. METHODS A total of 135 consecutive patients with acute TBAD treated at our institution between 2000 and 2008 were analysed. Of these patients, 84 were treated medically (group A, median age: 65 years, interquartile range (IQR): 34-90), 46 patients received TEVAR (group B, median age: 65, IQR: 23-83) and five patients underwent open surgical management (group C, median age: 60 years, IQR: 44-69). Clinical data and information on complications, re-intervention and acute and long-term mortality were retrospectively collected and examined. Follow-up was made on 98% of patients with a median time span of 1107 days (IQR: 870-1343). RESULTS There were no significant differences in age, gender, body mass index or co-morbidities among the three treatment groups. Group B patients had the highest rate of ruptures (n=7) and impending ruptures (n=19). Indications for surgery in group C were impending rupture with malperfusion (n=1), rupture (n=2) and refractory pain (n=2). The maximal diameter of dissection was significantly higher in group C (mean: 52.6mm, IQR: 36-82, p<0.05) than in group B (mean: 42.0mm, IQR: 20-74) and group A (mean: 40.6, IQR: 23-66). The 30-day and 5-year mortality rates, respectively, were 8.5% and 27.9% for group A, 20.0% and 43.7% for group B (p=0.018 for group A) and 20.0% for both time points for group C patients. The rate of re-intervention was significantly higher in group A (A: 22/84, 26.2% vs B: 8/46, 17.4%; p=0.049, and group C: 1/5, 20%). The rate of major complications (e.g., stroke, paraplegia and/or vascular problems) did not differ among groups. CONCLUSIONS Medical, interventional and surgical management for acute TBAD result in acceptable survival rates. Although stent implantation and surgery were reserved for patients with complications of TBAD in the current study, results were good for both treatment modalities. Randomised prospective trials should be performed to determine whether conservative, TEVAR or surgical management is most advantageous for complicated acute TBAD patients.

Minimally invasive mitral valve surgery is a very safe procedure with very low rates of conversion to full sternotomy.

OBJECTIVES Over the past 10 years, minimally invasive mitral valve surgery (MI-MVS) has become the standard approach for treatment of atrio-ventricular valve disease in specialized centres. This approach uses a right lateral mini-thoracotomy and femoral cannulation for cardiopulmonary bypass. In a very low number of patients, conversion to full sternotomy may be necessary. METHODS A total of 3125 patients underwent MI-MVS between 1999 and 2010 at our institution. Conversion to full sternotomy was required in 1.0% (n=34) of all patients. Patient data, including intraoperative course and postoperative outcome, were collected. Follow-up data were collected in a prospective database and analysed retrospectively. RESULTS A total of 34 patients underwent conversion to full sternotomy during MI-MVS. The mean age of patients was 67.9±9.5 years, and 17 patients were female (50%). The main reasons for conversion were as follows: major bleeding in 18 patients (52.9%); severe pulmonary adhesions in six patients (17.6%); and aortic dissection in five patients (14.7%). The clinical outcome of these patients was impaired, with the development of acute renal failure in 13 patients (38.2%) and respiratory failure in 10 patients (29.4%). Operative mortality (30 days) was 23.5% (eight patients). The reason for death in all these patients was low cardiac output syndrome with subsequent multi-organ failure. CONCLUSIONS This large series shows that MI-MVS can be performed with very low complication rates. In the experience of this large single-centre study, conversion to full sternotomy was necessary in only 1% of all patients. If conversion is indicated, however, it is associated with a high operative mortality.