Helge Möllmann

The German Aortic Valve Registry (GARY): in-hospital outcome

Background Aortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis. Methods and results A total of 13 860 consecutive patients undergoing repair for aortic valve disease [conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques] have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI). Conclusion The in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients.

Mechanisms of stress (Takotsubo) cardiomyopathy

Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy, transient apical ballooning or broken heart syndrome, is a disorder associated with transient left ventricular dysfunction. Symptoms include acute chest pain and dyspnea accompanied by electrocardiographic changes, such as ST-segment elevation and T-wave inversions, minimal elevation of cardiac enzyme levels and transient wall-motion abnormalities in the absence of substantial coronary artery obstruction. Complete recovery of contractile function has been documented in nearly all cases, but the mechanisms of disease remain unclear and the cause has not been established. Coronary artery vasospasm, microcirculation dysfunction, and transient obstruction of the left ventricular outflow tract have been proposed as possible causes of this disorder. An excessive release of catecholamines also seems to have a pivotal role in the development of stress cardiomyopathy. This Review summarizes published data on stress cardiomyopathy, focusing primarily on the most likely causes of this cardiac entity.

Perioperative Results and Complications in 15,964 Transcatheter Aortic Valve Replacements

BACKGROUND Transcatheter aortic valve replacement (TAVR) has evolved into a routine procedure with good outcomes in high-risk patients. OBJECTIVES TAVR complication rates were evaluated based on prospective data from the German Aortic Valve Registry (GARY). METHODS From 2011 to 2013, a total of 15,964 TAVR procedures were registered. We evaluated the total cohort for severe vital complications (SVCs), including the following: death on the day of intervention, conversion to sternotomy, low cardiac output that required mechanical support, aortic dissection, and annular rupture; technical complications of the procedures (TCOs), such as repositioning or retrieval of the valve prosthesis and embolization of the prosthesis; and other complications. RESULTS Mean patient age was 81 ± 6 years, 54% of the patients were women, the median logistic Euroscore I was 18.3, the German aortic valve score was 5.6, and the Society of Thoracic Surgeons score was 5.0. Overall in-hospital mortality was 5.2%, whereas SVCs occurred in 5.0% of the population. Independent predictors for SVCs were female sex, pre-operative New York Heart Association functional class IV, ejection fraction <30%, pre-operative intravenous inotropes, arterial vascular disease, and higher degree of calcifications. TCOs occurred in 4.7% of patients and decreased significantly from 2011 to 2013. An emergency sternotomy was performed in 1.3% of the patients; however, multivariate analysis did not identify any predictors for conversion to sternotomy. CONCLUSIONS The all-comers GARY registry revealed good outcomes after TAVR and a regression in complications. Survival of approximately 60% of patients who experienced SVCs or who required sternotomy underlines the need for heart team-led indication, intervention, and follow-up care of TAVR patients.

MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry

A substantial percentage of patients with mitral regurgitation (MR) in need of mitral valve repair are currently considered not suitable for conventional surgery. In Germany, the largest cohort of patients studied to date has been treated using a percutaneous, catheter‐based approach. We report the acute outcomes of patients enrolled in the investigator‐initiated German transcatheter mitral valve interventions (TRAMI) registry.

Transcatheter Aortic Valve Implantation for Pure Severe Native Aortic Valve Regurgitation

OBJECTIVES This study sought to collect data and evaluate the anecdotal use of transcatheter aortic valve implantation (TAVI) in pure native aortic valve regurgitation (NAVR) for patients who were deemed surgically inoperable BACKGROUND Data and experience with TAVI in the treatment of patients with pure severe NAVR are limited. METHODS Data on baseline patient characteristics, device and procedure parameters, echocardiographic parameters, and outcomes up to July 2012 were collected retrospectively from 14 centers that have performed TAVI for NAVR. RESULTS A total of 43 patients underwent TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) at 14 centers (mean age, 75.3 ± 8.8 years; 53% female; mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation), 26.9 ± 17.9%; and mean Society of Thoracic Surgeons score, 10.2 ± 5.3%). All patients had severe NAVR on echocardiography without aortic stenosis and 17 patients (39.5%) had the degree of aortic valvular calcification documented on CT or echocardiography. Vascular access was transfemoral (n = 35), subclavian (n = 4), direct aortic (n = 3), and carotid (n = 1). Implantation of a TAVI was performed in 42 patients (97.7%), and 8 patients (18.6%) required a second valve during the index procedure for residual aortic regurgitation. In all patients requiring second valves, valvular calcification was absent (p = 0.014). Post-procedure aortic regurgitation grade I or lower was present in 34 patients (79.1%). At 30 days, the major stroke incidence was 4.7%, and the all-cause mortality rate was 9.3%. At 12 months, the all-cause mortality rate was 21.4% (6 of 28 patients). CONCLUSIONS This registry analysis demonstrates the feasibility and potential procedure difficulties when using TAVI for severe NAVR. Acceptable results may be achieved in carefully selected patients who are deemed too high risk for conventional surgery, but the possibility of requiring 2 valves and leaving residual aortic regurgitation remain important considerations.

Classically and alternatively activated macrophages contribute to tissue remodelling after myocardial infarction

An important goal in cardiology is to minimize myocardial necrosis and to support a discrete but resilient scar formation after myocardial infarction (MI). Macrophages are a type of cells that influence cardiac remodelling during MI. Therefore, the goal of the present study was to investigate their transcriptional profile and to identify the type of activation during scar tissue formation. Ligature of the left anterior descending coronary artery was performed in mice. Macrophages were isolated from infarcted tissue using magnetic cell sorting after 5 days. The total RNA of macrophages was subjected to microarray analysis and compared with RNA from MI and LV‐control. mRNA abundance of relevant targets was validated by quantitative real‐time PCR 2, 5 and 10 days after MI (qRT‐PCR). Immunohistochemistry was performed to localize activation type‐specific proteins. The genome scan revealed 68 targets predominantly expressed by macrophages after MI. Among these targets, an increased mRNA abundance of genes, involved in both the classically (tumour necrosis factor α, interleukin 6, interleukin 1β) and the alternatively (arginase 1 and 2, mannose receptor C type 1, chitinase 3‐like 3) activated phenotype of macrophages, was found 5 days after MI. This observation was confirmed by qRT‐PCR. Using immunohistochemistry, we confirmed that tumour necrosis factor α, representing the classical activation, is strongly transcribed early after ligature (2 days). It was decreased after 5 and 10 days. Five days after MI, we found a fundamental change towards alternative activation of macrophages with up‐regulation of arginase 1. Our results demonstrate that macrophages are differentially activated during different phases of scar tissue formation after MI. During the early inflammatory phase, macrophages are predominantly classically activated, whereas their phenotype changes during the important transition from inflammation to scar tissue formation into an alternatively activated type.

Valve-in-Valve Transcatheter Aortic Valve Implantation for Degenerated Bioprosthetic Heart Valves

OBJECTIVES We sought to analyze outcomes of patients with degenerated surgically implanted bioprosthetic heart valves undergoing valve-in-valve (viv) transcatheter aortic valve implantation (TAVI). BACKGROUND Redo cardiac surgery for degenerated bioprosthetic heart valves is associated with increased risks, particular in elderly patients with comorbidities. For these patients, TAVI may be an attractive, less invasive treatment option. METHODS Data from 47 patients age 64 to 97 years (logistic euroSCORE: 35.0 ± 18.5%) undergoing transfemoral (n = 25) or transapical (n = 22) viv-TAVI for failed bioprosthetic aortic valves 113 ± 65 months after initial surgery at 9 clinical sites in Germany and Switzerland were analyzed. RESULTS Valve-in-valve TAVI was technically successful in all patients, with 2 patients requiring bailout implantation of a second TAVI prosthesis for severe regurgitation during the procedure. There was 1 procedural death as the result of low-output failure. Valvular function after viv-TAVI was excellent with respect to valve competence, but increased transvalvular gradients ≥20 mm Hg were noted in 44% of patients. Vascular access complications occurred in 6 (13%) patients, and 5 (11%) patients required new pacemaker implantation after viv-TAVI. Renal failure requiring dialysis occurred in 4 (9%) patients. Mortality at 30 days was 17% (1 procedural and 7 post-procedural deaths), with 3 of 8 fatalities the result of non-valve-related septic complications. CONCLUSIONS Valve-in-valve TAVI can be performed with high technical success rates, acceptable post-procedural valvular function, and excellent functional improvement. However, in these predominantly elderly high-risk patients with multiple comorbidities, viv-TAVI was associated with 17% mortality, often because of septic complications arising in the post-operative phase.

Tako-tsubo cardiomyopathy (apical ballooning)

In recent years, a new cardiac syndrome with transient left ventricular dysfunction has been described in Japanese patients. This new entity has been referred to as “tako-tsubo cardiomyopathy” or “apical ballooning”, named for the particular shape of the end-systolic left ventricle in ventriculography.1 To date, tako-tsubo cardiomyopathy has also been reported to occur in the western population. The following clinical characteristics of this phenomenon must be met: (1) transient akinesis or dyskinesis of left ventricular wall motion abnormalities (ballooning) with chest pain; (2) new electrocardiographic changes (either ST elevation or T wave inversion); (3) no significant obstructive epicardial coronary artery disease; (4) absence of recent significant head trauma, intracardial bleeding, phaeochromocytoma, myocarditis, and hypertrophic cardiomyopathy.2 Emotional or physical stress usually precedes this cardiomyopathy. A unifying mechanistic explanation responsible for this acute but rapidly reversible contractile dysfunction is still lacking. Multivessel epicardial coronary artery vasospasm, coronary microvascular dysfunction or spasm, impaired fatty acid metabolism, transient obstruction of the left ventricular outflow, and catecholamine-mediated myocardial dysfunction have been proposed as potential mechanisms.3–6 The optimal treatment of patients presenting with this syndrome depends primarily on the haemodynamic conditions and remains rather symptomatic in nature. This article primarily addresses the clinical setting of tako-tsubo cardiomyopathy and describes a broad spectrum of diagnostic tools. Moreover, currently proposed pathophysiological mechanisms are discussed in detail, providing more insight into this new cardiac entity. Tako-tsubo cardiomyopathy is characterised by acute onset of chest pain and a completely reversible regional contractile dysfunction. In left ventriculography typical wall motion abnormalities, such as apical and mid-ventricular akinesia and a hypercontractile basis, can be documented. Coronary angiography reveals no relevant epicardial coronary artery disease (fig 1). Recently, several cases of transient ballooning involving the mid-ventricular part, sparing the apical and basal segments, have also been documented.7 …

Abnormalities in intracellular Ca2+ regulation contribute to the pathomechanism of Tako-Tsubo cardiomyopathy

AIMS The Tako-Tsubo cardiomyopathy (TTC) is characterized by a transient contractile dysfunction that has been assigned to excessive catecholamine levels after episodes of severe emotional or physical stress. Several studies have indicated that beta-adrenoceptor stimulation is associated with alteration in gene expression of Ca(2+)-regulatory proteins. Thus, the present study investigated the gene expression of crucial proteins [sarcoplasmic Ca(2+) ATPase (SERCA2a), sarcolipin (SLN), phospholamban (PLN), ryanodine receptor (RyR2), and sodium-calcium exchanger (NCX)] involved in the Ca(2+)-regulating system in TTC. METHODS AND RESULTS In 10 consecutive patients, TTC was diagnosed by coronary angiography, ventriculography, and echocardiography. Endomyocardial biopsies were taken during the phase of severely impaired left ventricular (LV) function and after functional recovery. Non-diseased LV tissue from three donor hearts not used for transplantation served as healthy controls. Expression levels of Ca(2+)-regulatory proteins were analysed by means of real-time PCR, western blot, and immunohistochemistry. SLN, predominantly expressed in the atrial component, showed a remarkable ventricular expression in TTC patients. Gene expression of SERCA2a was significantly down-regulated. Conversely, PLN/SERCA2a ratio was increased. For PLN, dephosphorylation was documented using western blot and immunostaining of PLN-Ser(16) and PLN-Thr(17). No changes could be documented for NCX and RyR2. CONCLUSION In TTC, ventricular expression of SLN and dephosphorylation of PLN potentially result in a reduced SERCA2a activity and its Ca(2+) affinity. Thus, the TTC is associated with specific alteration of Ca(2+)-handling proteins, which might be crucial for contractile dysfunction.

Immunohistological basis of the late gadolinium enhancement phenomenon in tako-tsubo cardiomyopathy

AIMS Tako-tsubo cardiomyopathy is characterized by transient contractile dysfunction after emotional or physical stress. Only few patients show late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (MRI). It was the purpose of this study to elucidate the histological basis of this phenomenon. METHODS AND RESULTS The study included 15 patients. Tako-tsubo cardiomyopathy was diagnosed by coronary angiography and ventriculography. Cardiac MRI was performed within 24 h of admission. Endomyocardial biopsies were taken during the acute phase and after recovery. The content of fibrosis was determined by immunohistochemical staining of collagen-1. In the acute phase, cardiac MRI revealed LGE in five patients. This was completely reversed at follow-up [14, inter-quartile range (IQR) 11-14.5 days]. All patients showed a significant increase of collagen-1 compared with control tissue. Moreover, the amount of collagen-1 was significantly higher in LGE positive patients (LGE positive: 18.84, IQR 13.82-19.75 AU/microm(2); LGE negative: 7.57, IQR 5.41-9.19 AU/microm(2), P = 0.001). The presence of LGE was not associated with poorer left ventricular function. CONCLUSION The presence of LGE cannot rule out tako-tsubo cardiomyopathy. Instead it defines a special subgroup of patients with a disproportionate increase of extracellular matrix.