Surgical revision after percutaneous mitral valve repair by edge-to-edge device in high-risk patients.

BACKGROUND: Patients scheduled for surgery after unsuccessful MitraClip® intervention present increasingly with multiple comorbidities, and they are often referred to the heart team to suggest the most appropriate intervention. The publication of successful results of initial patient cohorts treated with the MitraClip device has resulted in recruitment of more seriously ill patients, who otherwise would have been denied catheter-based/surgical treatment. There has been increasingly reports on conventional surgery after failed mitral valve repair with the MitraClip device. However, data on such procedures remain scarce and mostly focused on individual case studies. The inevitable increase in use of MitraClip, however, will raise the number of patients in need of surgery post MitraClip, making it imperative for surgeons to understand challenges and outcome data related with surgery in this patient cohort. We present our long-term institutional experience with surgery after MitraClip intervention in highest risk patients. METHODS: Eighteen patients underwent surgery of the mitral valve at our Institution between January 2015 and June 2020. These patients developed recurrent mitral regurgitation grade more than 2° at various intervals after MitraClip. Mitral valve repair was performed where possible and gross examination Valve/MitraClip were intra-operatively documented. Implanted MitraClip devices were analyzed histopathologically to evaluate the healing process and rule out inflammation. Regular patient follow-up was performed. RESULTS: Mean patient age was 74 (±9 years) and MitraClip implantation was performed at various tertiary institutions. Sixteen out of eighteen (16/18) patients received mitral valve replacement, whereas the remaining two patients received mitral valve repair and extracorporal membrane oxygenation, respectively. Four patients died of sepsis and intractable multi organ failure in-hospital. The remaining patients were discharged alive out of hospital to different rehabilitation centers. Follow-up was complete in all patients. CONCLUSIONS: Surgery is demanding when patients require surgery for persistent or recurrent mitral regurgitation after MitraClip therapy and can be successfully implemented as a possible therapy option for selective cases as an interdisciplinary approach despite calculated high perioperative mortality risk. These patients should not be denied surgery outright.

Gender-Dependent Clinical Outcome and Other Predictors of In-Hospital Mortality Following Out-Of-Center Extracorporeal Membrane Oxygenation and Extracorporeal Life Support: A Single Center Experience.

BACKGROUND: Out-of-center extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) implantation for the treatment of acute cardiorespiratory failure with subsequent transport to a tertiary care center has been introduced successfully into the medical practice. However, due to the very specific and resource intensive nature of this therapeutic concept, it seems important to generate algorithms for adequate patient selection. The aim of our study was to analyze the impact of patients' gender on early clinical outcome in this specific therapeutic scenario. METHODS: Ninety-seven consecutive patients treated by out-of-center ECMO/ECLS implantation and subsequent transport and treatment in our tertiary care cardiovascular center within the Hallesche Extracorporeal Life Support Program (HELP) retrospectively were analyzed, regarding the impact of patients' gender on early clinical outcome. RESULTS: Mechanical circulatory support successfully was weaned in two-thirds of the male patients. This result was achieved in only one-third of the female patients (59.4% in male vs. 33.3% in female, P = .0267). Overall survival significantly was higher in the male group (62.5% in male versus 30.3% in female, P = .0052). In uni- and multivariate logistic regression analysis, female gender was an independent predictor of in-hospital mortality (uni: OR:3.833, CI:1.597-9.745, P = .0034; multi: OR:3.477, CI:1.146-11.494, P = .0322). Worse outcome also was associated with following independent predictors, age, SOFA score, lactate and ventilation time pre-ECMO/ECLS implantation. CONCLUSION: The current study demonstrates a worse early survival for women, following emergent out-of- center ECMO/ECLS implantation and subsequent transport and treatment in our tertiary care cardiovascular center. Gender should be included in patient selection algorithms while basic research approaches are needed to better understand the mechanisms underlying these gender- specific outcome disparities.

Alterations of protein expression of phospholamban, ZASP and plakoglobin in human atria in subgroups of seniors.

The mature mammalian myocardium contains composite junctions (areae compositae) that comprise proteins of adherens junctions as well as desmosomes. Mutations or deficiency of many of these proteins are linked to heart failure and/or arrhythmogenic cardiomyopathy in patients. We firstly wanted to address the question whether the expression of these proteins shows an age-dependent alteration in the atrium of the human heart. Right atrial biopsies, obtained from patients undergoing routine bypass surgery for coronary heart disease were subjected to immunohistology and/or western blotting for the plaque proteins plakoglobin (γ-catenin) and plakophilin 2. Moreover, the Z-band protein cypher 1 (Cypher/ZASP) and calcium handling proteins of the sarcoplasmic reticulum (SR) like phospholamban, SERCA and calsequestrin were analyzed. We noted expression of plakoglobin, plakophilin 2 and Cypher/ZASP in these atrial preparations on western blotting and/or immunohistochemistry. There was an increase of Cypher/ZASP expression with age. The present data extend our knowledge on the expression of anchoring proteins and SR regulatory proteins in the atrium of the human heart and indicate an age-dependent variation in protein expression. It is tempting to speculate that increased expression of Cypher/ZASP may contribute to mechanical changes in the aging human myocardium.

Transaortic Transcatheter Aortic Valve Implantation: Learning Curve, Perioperative, and Midterm Follow-Up Results of a Single Center.

BACKGROUND: We present our initial institutional experience with transaortic (TAo) transcatheter aortic valve implantation (TAVI) using a self-expanding aortic bioprosthesis. METHODS: A total of 106 patients underwent TAo TAVI with Medtronic CoreValve through a small partial upper sternotomy. We focus our analysis on the overall perioperative results, procedural learning curve (first 30 patients), and midterm follow-up outcomes. RESULTS: VARC-2 device success was achieved in 95 patients (89%), and there were no intraoperative deaths. Nine patients (8.4%) required a second valve and conversion to standard surgery was required in 2 patients (1.8%). The final aortic insufficiency was grade 0 in 65 patients (62%) and grade 1 in 39 (37%). Although patients treated in the TAo TAVI learning phase required a significantly longer radiation time and contrast agent use, device success (93.4% versus 88.2%, P = .7) and prostheses hemodynamics were similar. All-cause mortality at 30 days was 12% (13/106). At a median follow-up of 392 days (IQR: 216-494 days) estimated overall 1-year survival was 72%. No significant differences were reported in terms of 30-day and 1-year observed mortality, and estimated 1-year survival in the learning and later phase of TAo TAVI. CONCLUSION: TAo TAVI can be performed safely even in the very early phase of the learning curve. Although satisfactory results can be achieved from the beginning, a significant reduction in contrast agent use and radiological exposure are expected as the technique is mastered. Good hemodynamics have been documented and should be further improved with modifications achieved in the TAVI self-expandable valves technology.

Age-Dependent Protein Expression of Serine/Threonine Phosphatases and Their Inhibitors in the Human Cardiac Atrium.

Heart failure and aging of the heart show many similarities regarding hemodynamic and biochemical parameters. There is evidence that heart failure in experimental animals and humans is accompanied and possibly exacerbated by increased activity of protein phosphatase (PP) 1 and/or 2A. Here, we wanted to study the age-dependent protein expression of major members of the protein phosphatase family in human hearts. Right atrial samples were obtained during bypass surgery. Patients (n=60) were suffering from chronic coronary artery disease (CCS 2-3; New York Heart Association (NYHA) stage 1-3). Age ranged from 48 to 84 years (median 69). All patients included in the study were given ß-adrenoceptor blockers. Other medications included angiotensin-converting enzyme (ACE) or angiotensin-receptor-1 (AT1) inhibitors, statins, nitrates, and acetylsalicylic acid (ASS). 100 µg of right atrial homogenates was used for western blotting. Antibodies against catalytic subunits (and their major regulatory proteins) of all presently known cardiac serine/threonine phosphatases were used for antigen detection. In detail, we studied the expression of the catalytic subunit of PP1 (PP1c); I1 PP1 and I2 PP1, proteins that can inhibit the activity of PP1c; the catalytic subunit of PP2A (PP2Ac); regulatory A-subunit of PP2A (PP2AA); regulatory B56α-subunit of PP2A (PP2AB); I1 PP2A and I2 PP2A, inhibitory subunits of PP2A; catalytic and regulatory subunits of calcineurin: PP2BA and PP2BB; PP2C; PP5; and PP6. All data were obtained within the linear range of the assay. There was a significant decline in PP2Ac and I2 PP2A expression in older patients, whereas all other parameters remained unchanged with age. It remains to be elucidated whether the decrease in the protein expression of I2 PP2A might elevate cardiac PP2A activity in a detrimental way or is overcome by a reduced protein expression and thus a reduced activity of PP2Ac.

A new technique to implant a transcatheter inflatable, fully repositionable prosthesis in aortic stenosis with severe asymmetric calcification.

OBJECTIVES: In contrast to stented transcatheter aortic valves, the Direct Flow Medical (DFM) valve is a stentless bovine aortic bioprosthesis mounted in a non-metallic inflatable frame. Hence, severe asymmetric annular calcification may result in residually elevated transaortic pressure gradients after DFM implantation. We present a novel intraprocedural dilatation (IDIL) technique for successful implantation of the DFM valve in the presence of complex annular calcification. METHODS: Between January 2014 and May 2015, 55 patients underwent DFM valve-based transcatheter aortic valve implantation at our institution. Of these, 5 patients required an IDIL technique due to a residual intraoperative transaortic pressure mean gradient above 15 mmHg. The mean patient age was 73 ± 8.2 years; the mean logistic EuroSCORE was 24.5 ± 8.2% and the mean Society of Thoracic Surgeons score was 6.3 ± 4.3%. RESULTS: The IDIL technique immediately attenuated transvalvular mean pressure gradients from 20 ± 2 mmHg to 6 ± 1 mmHg. The results remained stable during the 30-day observation period at 10 ± 3 mmHg. Minimal paravalvular aortic regurgitation (trace) was detected in 2 patients. No in-hospital deaths were observed. CONCLUSIONS: The IDIL technique facilitates safe DFM valve implantation in patients with complex asymmetric annular calcification without adverse side effects on valve structure or performance in short-term follow-up.

One-Year Outcomes of Transcatheter Aortic Valve Implantation Using the Direct Aortic Approach.

BACKGROUND: The direct aortic (DA) approach allows for transcatheter aortic valve implantation (TAVI) in patients with difficult peripheral vascular anatomy. The CoreValve ADVANCE Direct Aortic (ADVANCE DA) study was performed to assess the outcomes of DA TAVI with the CoreValve System (Medtronic, Minneapolis, MN) in routine practice. METHODS: Patients were selected for the DA approach by local cardiac surgical teams, and TAVI was performed with patients under general anesthesia. Safety events were adjudicated according to the Valve Academic Research Consortium-2 definitions by an independent clinical events committee. All imaging data, including that from multislice computed tomography and follow-up echocardiography, were analyzed by an independent core laboratory. RESULTS: From September 2012 to February 2014, 100 patients were enrolled (52.0% male, age 81.9 ± 5.9 years, The Society of Thoracic Surgeons Score 5.9 ± 3.2%) at 9 centers in Europe. Peripheral vascular disease was present in 51.0% of patients, and 38.0% had diabetes. Of the 100 patients enrolled, 92 underwent TAVI. At 30 days after TAVI, 98.1% were free of moderate or severe paravalvular leak. At 1 year, 16 patients had died (Kaplan-Meier rate 17.9%), 1 (1.1%) patient had had a stroke, classified as nondisabling, and 15 (17.0%) patients had received a permanent pacemaker. Most patients experienced improved quality of life as measured by the Kansas City Cardiomyopathy Questionnaire overall summary score (mean change from baseline to 1 year, 39.6 ± 26.3; p < 0.01). CONCLUSIONS: The DA approach provides a feasible alternative for patients with challenging anatomic features that may otherwise preclude use of the TAVI procedure.

Direct aortic access for transcatheter aortic valve replacement with a fully repositionable and retrievable nonmetallic valve system.

OBJECTIVE: The standard procedure of transcatheter aortic valve implantation involves transfemoral access. Nevertheless, the use of this access route is limited by the vessel diameter, calcification, and tortuosity, making a subgroup of patients ineligible for peripheral access. We report the first use of direct aortic transcatheter aortic valve implantation with the Direct Flow Medical valve (Direct Flow Medical, Inc, Santa Rosa, Calif) in 15 patients at the Halle-Wittenberg University. METHODS: Between January 2014 and May 2015, 55 patients with severe aortic valve disease underwent transcatheter aortic valve implantation with the Direct Flow Medical valve at the Halle-Wittenberg University. Subgroups of 15 patients were treated using direct aortic access because of small vessel diameter, excessive calcification, or extreme tortuosity of the iliofemoral vessels. RESULTS: The mean patient age was 79.1 ± 6.72 years, and 10 patients (66%) were male. The mean logistic European System for Cardiac Operative Risk Evaluation was 23.4% ± 16.9%, and the mean Society of Thoracic Surgeons score was 7.8% ± 6.8%. Access related to redo-sternotomy during transcatheter aortic valve implantation was required in 4 patients (27%). Valve retrieval was performed in 2 patients (13%). There was no conversion to surgical aortic valve replacement and no incidence of major stroke. The postimplant mean gradient was 9.3 ± 2.5 mm Hg. No patient had moderate or severe paravalvular leakage. All patients survived the first 30 days. CONCLUSIONS: Direct aortic access seems to be a feasible and safe endovascular alternative for implantation of the Direct Flow Medical valve. This access provides direct and accurate control of the entire implantation procedure.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): first annual report.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) was founded on 10 December 2009 with the initiative of Roland Hetzer (Deutsches Herzzentrum Berlin, Berlin, Germany) and Jan Gummert (Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany) with 15 other founding international members. It aims to promote scientific research to improve care of end-stage heart failure patients with ventricular assist device or a total artificial heart as long-term mechanical circulatory support. Likewise, the organization aims to provide and maintain a registry of device implantation data and long-term follow-up of patients with mechanical circulatory support. Hence, EUROMACS affiliated itself with Dendrite Clinical Systems Ltd to offer its members a software tool that allows input and analysis of patient clinical data on a daily basis. EUROMACS facilitates further scientific studies by offering research groups access to any available data wherein patients and centres are anonymized. Furthermore, EUROMACS aims to stimulate cooperation with clinical and research institutions and with peer associations involved to further its aims. EUROMACS is the only European-based Registry for Patients with Mechanical Circulatory Support with rapid increase in institutional and individual membership. Because of the expeditious data input, the European Association for Cardiothoracic Surgeons saw the need to optimize the data availability and the significance of the registry to improve care of patients with mechanical circulatory support and its potential contribution to scientific intents; hence, the beginning of their alliance in 2012. This first annual report is designed to provide an overview of EUROMACS' structure, its activities, a first data collection and an insight to its scientific contributions.

Protein glycation - Between tissue aging and protection.

UNLABELLED: Non-enzymatic formation of advanced glycation endproducts (AGEs) is associated with degenerative diseases. Chronic accumulation of AGEs with age in tissues especially in the extracellular matrix is well known and at least in part responsible for e.g., collagen crosslinking, tissue stiffening and thus induction of high blood pressure or diastolic heart failure. Binding of soluble AGEs to the receptor for AGEs, RAGE, induces an inflammatory response whereas the soluble form of RAGE (sRAGE) can inhibit inflammatory tissue injury like arteriosclerosis in mouse models. However, there are a number of indications that AGEs have protective effects as well. AGEs may inhibit lung tumor growth, glyoxal induced AGE modification of human heart muscle can reduce an ischemia reperfusion injury and AGEs from nutrition can reduce ROS induced cell damage. CONCLUSIONS: In summary, this indicates that protein glycation behaves like a double-edged sword. It induces tissue aging and degenerative diseases on the one hand, on the other hand, may also have protective effects, indicating a hormetic response.

A positive inotropic effect of UTP in the human cardiac atrium.

In the cardio-vascular system extracellular UTP can induce receptor-mediated vasoconstriction via smooth muscle cells and vasodilatation via endothelial cells. We evaluated inotropic effects of UTP in preparations from human heart. Contractile effects were studied in atrial preparations from patients undergoing cardiac bypass surgery. For comparison, contractility in isolated spontaneously beating right atrial and paced left atrial preparations from mice was investigated. UTP and UTPγS concentration-dependently exerted a positive inotropic effect with a maximum at 100 µM UTP that amounted to 156% of pre-drug value (n=13) without changing time parameters of contraction. UTP was able to partially attenuate the positive inotropic effect of ß-adrenoceptor stimulation. UTP did not change the beating rate in right atrial mouse preparations. The positive inotropic effect of UTP could not be blocked by the P2 purinoceptor antagonists suramin (100 µM and 500 µM), PPADS (50 µM) and reactive blue (100 µM). Likewise inhibitors of PLC activity (U73122) and of adenylyl cyclase activity (SQ22563; 10 µM each) failed to affect the effects of UTP. In summary, we describe a novel positive inotropic effect of UTP on force contraction in the isolated human atrium. We tentatively suggest that UTP might act via P2Y2- or P2Y4-like receptors.

Mechanisms of infective endocarditis: pathogen-host interaction and risk states.

Patients with infective endocarditis (IE) form a heterogeneous group, ranging from those who are successfully treated with no adverse events, to those with severe complications and a high mortality. In this Review, we highlight pathogen-host interactions and the mechanisms underlying various risk factors for patients with IE. A temporal trend in the pattern of IE has been observed in high-income countries within the past 5 decades, with patients contracting IE at an increasingly old age, and a growing incidence of health-care-associated staphylococcal IE. Consequently, prevention strategies should no longer focus on prophylaxis of streptococcal bacteraemia during dental procedures, but instead encourage a more-general approach to reduce the incidence of health-care-associated IE. Much knowledge has been gained about the mechanisms of vegetation formation, growth, and embolization on damaged or inflamed cardiac valves, and on cardiac devices. Improved understanding of these mechanisms will help to combat the increasing problem of antimicrobial resistance. Two mechanisms of IE should increasingly be the focus of future research: the role of immunosenescence in elderly patients with IE, particularly after transcatheter aortic valve implantation, and the mechanisms that trigger septic shock, a condition that leads to a substantial increase in the risk of death in patients with IE.

Advanced glycation end product associated skin autofluorescence: a mirror of vascular function?

Advanced glycation end products (AGEs) seem to be involved in aging as well as in the development of cardiovascular diseases. During aging, AGEs accumulate in extracellular matrix proteins like collagen and contribute to vessel stiffness. Whether non-invasive measurement of AGE accumulation in the skin may reflect vessel function and vessel protein modification is unknown. Herein we set out to analyze the AGE-modifications in the collagens extracted from residual bypass graft material, the skin autofluorescence reflecting the accumulation of AGEs in the body as well as the pulse wave velocity reflecting vessel stiffness. Collagen types I and III (pepsin digestible collagen fraction) were isolated from the veins of 52 patients by proteolysis. The residual collagen fraction was further extracted by collagenase digestion. Collagen was quantified by hydroxyproline assay and AGEs by the AGE intrinsic fluorescence. Skin autofluorescence was measured with an autofluorescence reader; pulse wave velocity with the VICORDER. The collagen AGE autofluorescence in patient vein graft material increased with patient age. The pepsin digestible collagen fraction was significantly less modified in comparison to the collagenase digestible fraction. Decreasing amounts of extracted collagenase digestible collagen correspond with increasing AGE autofluorescence. Skin autofluorescence and vessel stiffness were significantly linked to the AGE autofluorescence of the collagenase digestible collagen fraction from graft material. In conclusion we have found that skin autofluorescence and pulse wave velocity as non-invasive parameters significantly correlate with the AGE contained in graft material and therefore are strong predictors of vessel AGE modifications in patients with coronary heart disease. Whether the analysis of the skin autofluorescence leads to an improvement of the risk stratification in patients suffering from cardiovascular disease has to be further tested.

Intra-aortic balloon counterpulsation in the treatment of infarction-related cardiogenic shock--review of the current evidence.

The European ST-elevated myocardial infarction (STEMI) guideline suggested the intra-aortic balloon pump (IABP) with a recommendation level I and a level of evidence C as an effective measure in combination with balloon angioplasty in patients with cardiogenic shock (CS), stent implantation, and inotropic and vasopressor support. Similarly, upon mechanical complication due to myocardial infarction (MI), the guideline suggests that in patients with a ventricular septal defect or in most patients with acute mitral regurgitation, preoperative IABP implantation is indicated for circulatory support. The American College of Cardiology/American Heart Association STEMI guideline recommends the use of the IABP with a recommendation level I and a level of evidence B if CS does not respond rapidly to pharmacological treatment. The guideline notes that the IABP is a stabilizing measure for angiography and early revascularization. Even in MI complications, the use of preoperative IABP is recommended before surgery. Within this overview, we summarize the current evidence on IABP use in patients with CS complicated by MI. From our Cochrane data analysis, we conclude that in CS due to acute MI (AMI) treated with adjuvant systemic fibrinolysis, the IABP should be implanted. In patients with CS following AMI, treated with primary percutaneous coronary intervention (PCI), the IABP can be implanted, although data are not distinctive (i.e., indicating positive and negative effects). In the future, randomized controlled trials are needed to determine the use of IABP in CS patients treated with PCI. When patients with CS are transferred to a PCI center with or without thrombolysis, patients should receive mechanical support with an IABP. To treat mechanical MI complications-in particular ventricular septal defect-patients should be treated with an IABP to stabilize their hemodynamic situation prior to cardiac surgery. Similar recommendations are given in the German Austrian guidelines on treatment of infarction-related CS patients (http://www.awmf.org/leitlinien/detail/ll/019-013.html).