[Edge-to-edge repair : What has changed compared to the position paper in 2013?] / "Edge-to-edge repair" : Was hat sich geändert zum Positionspapier 2013?

This short review article aims to explain the changes in the treatment strategies of interventional care designed to treat secondary mitral valve regurgitation with edge-to-edge repair in comparison to the position paper published in 2013 by the German Society of Cardiology and the German Society of Thoracic and Cardiovascular Surgery. To this end the current data situation with respect to the European Society of Cardiology (ESC) guidelines from 2017, the intraprocedural assessment of mitral valve regurgitation and new technical developments are discussed.

Intraprocedural assessment of mitral regurgitation during the mitraclip procedure: Impact of continuous left atrial pressure monitoring.

INTRODUCTION: Intraprocedural assessment of mitral regurgitation (MR) is a challenging issue during the MitraClip procedure, which might influence not only the position but also the number of MitraClips implanted. Though transesophageal echocardiography (TEE) is the predominant tool used during the MitraClip procedure, MR assessment might be facilitated by a multimodality approach including continuous and simultaneous determination of left atrial and left ventricular (LV) pressure. METHODS: 86 consecutive patients (76.5 ± 8 years) who qualified for the MitraClip procedure were included into the study. In all patients, the multimodal assessment of MR (TEE, LV angiogram, TEE bubble evaluation, left atrial (LA) pressure => MitraScore) was performed after introducing the MitraClip guide catheter. In the first 42 patients (group A, no CAP), left atrial (LA) pressure (peak pressure of V-wave) was determined only before and after MitraClip implantation, whereas, in the subsequent 44 patients (group B, with CAP), continuous left atrial pressure monitoring (CAP) was performed. RESULTS: Patients with CAP (group B) had similar total procedural durations and no increase in the complication rate. MitraScore decreased from 10.5 to 3.5 in group A compared to 10.7 to *2.8 in group B (*P = 0.021 vs. group B). Whether the significant improvement of intraprocedural MR in group B translated into superior MR reduction in the conscious patient, was analyzed by transthoracic echocardiography (TTE) in a blinded fashion. Again MR reduction was significantly greater (P = 0.03) in group B (MR grade 2.8 to 0.9) as compared to group A (MR grade 2.8 to 1.3) and 2D vena contracta decreased from 0.54 ± 0.15 cm to 0.17 ± 0.10 in group B compared to group A (0.56 ± 0.19 cm to *0.23 ± 0.12; *P = 0.01 vs. group B). CONCLUSIONS: Multimodality assessment of intraprocedural MR supported by continuous left atrial pressure monitoring was associated with superior intraprocedural results translating into improved MR reduction also at the end of the hospital stay. © 2016 Wiley Periodicals, Inc.

[Wasp-sting-induced pheochromozytoma crisis with stress-related cardiomyopathy (Takotsubo)]. / Wespenstichinduzierte sympathikotone Krise mit Stresskardiomyopathie (Takotsubo) bei Phäochromozytom.

This article presents the case of a patient with sudden onset of heart failure caused by transient severe left ventricular dysfunction with the typical pattern of stress-induced cardiomyopathy (takotsubo cardiomyopathy) who had wasp sting a few hours before admission in the presence of a previously asymptomatic pheochromocytoma. There seems to be correlation between the wasp-venom-induced pheochomocytoma crisis and acute onset of heart failure. Once pheocromocytoma is diagnosed, medical therapy is preferable before surgical treatment. This case demonstrates that a previously asymptomatic pheochromocytoma can become clinically relevant by catecholamine-releasing wasp venom causing stress-related cardiomyopathy and that patient history is mandatory for evaluating the cause of sudden clinical outcome.

Percutaneous interventional mitral regurgitation treatment using the Mitra-Clip system.

The interventional treatment of mitral valve regurgitation by the MitraClip procedure has grown rapidly in Germany and Europe during the past years. The MitraClip procedure has the potential to treat high-risk patients with secondary mitral valve regurgitation and poor left ventricular function. Furthermore, patients with primary mitral valve regurgitation may be treated successfully by the MitraClip procedure in case of high surgical risk or in very old patients. At the same time it has been emphasised that the MitraClip interventional treatment is still at an early stage of clinical development. The largest clinical experience with the MitraClip procedure so far is probably present in some German cardiovascular centers, which here summarise their recommendations on the current indications and procedural steps of the MitraClip treatment. These recommendations of the AGIK and ALKK may present a basis for future development.

[Progressive dyspnoea in two patients with carcinoid syndrome]. / Progrediente Dyspnoe bei Karzinoidsyndrom.

In patients with carcinoid syndrome, there has always to be considered cardiac impairment. We report about two patients with hepatic and bone metastases of a neuroendocrine tumor of the midgut, who suffered from progressive dyspnea. This was caused in both cases by a right-to-left atrial shunt, in case 1 based on a patent foramen ovale (PFO), in case 2 based on a secundum atrial septal defect. Symptoms were significantly reduced by percutaneous closure of PFO and ASD, respectively. Right-to-left atrial shunt was facilitated by right-sided carcinoid induced endocardial fibrosis with the consequence of severe tricuspid regurgitation, leading to an increase of right atrial pressure.

Cardio-specific long-term gene expression in a porcine model after selective pressure-regulated retroinfusion of adeno-associated viral (AAV) vectors.

Cornerstone for an efficient cardiac gene therapy is the need for a vector system, which enables selective and long-term expression of the gene of interest. In rodent animal models adeno-associated viral (AAV) vectors like AAV-6 have been shown to efficiently transduce cardiomyocytes. However, since significant species-dependent differences in transduction characteristics exist, large animal models are of imminent need for preclinical evaluations. We compared gene transfer efficiencies of AAV-6 and heparin binding site-deleted AAV-2 vectors in a porcine model. Application of the AAVs was performed by pressure-regulated retroinfusion of the anterior interventricular cardiac vein, which has been previously shown to efficiently deliver genes to the myocardium (3.5 x 10(10) viral genomes per animal; n=5 animals per group). All vectors harbored a luciferase reporter gene under control of a cytomegalovirus (CMV)-enhanced 1.5 kb rat myosin light chain promoter (CMV-MLC2v). Expression levels were evaluated 4 weeks after gene transfer by determining luciferase activities. To rule out a systemic spillover peripheral tissue was analyzed by PCR for the presence of vector genomes. Selective retroinfusion of AAV serotype 6 vectors into the anterior cardiac vein substantially increased reporter gene expression in the targeted distal left anterior descending (LAD) territory (65 943+/-31 122 vs control territory 294+/-69, P<0.05). Retroinfusion of AAV-2 vectors showed lower transgene expression, which could be increased with coadministration of recombinant human vascular endothelial growth factor (1365+/-707 no vascular endothelial growth factor (VEGF) vs 38 760+/-2448 with VEGF, P<0.05). Significant transgene expression was not detected in other organs than the heart, although vector genomes were detected also in the lung and liver. Thus, selective retroinfusion of AAV-6 into the coronary vein led to efficient long-term myocardial reporter gene expression in the targeted LAD area of the porcine heart. Coapplication of VEGF significantly increased transduction efficiency of AAV-2.

Arterial T-graft in coronary surgery: comparison of selective coronary angiography and multi-slice computed tomography.

BACKGROUND: The main aim of our study was to compare the results and value of angiography and multi-slice computed tomography (MSCT) after coronary artery bypass grafting using complex arterial conduit combinations. METHODS: Twenty-six patients underwent coronary surgery. In all patients, we utilized a T-graft (free arterial graft centrally implanted into the left internal thoracic artery IN SITU). Postoperative coronary angiography and MSCT were carried out prior to discharge. The results were interpreted separately by two different investigators. RESULTS: One hundred and thirteen distal anastomoses using 59 grafts for T-graft combinations were performed in 26 patients. A mean of 3.5 peripheral anastomoses was established per patient. Angiography showed a bypass graft patency rate of 94.6 % (56/59). In angiography, the patency rate of anastomoses was 96.5 % (109/113). All occlusions were identified in sequential anastomoses. The bypass patency rate measured by MSCT was 100 % and the patency rate of anastomoses 100 %. Based on these results, MSCT showed a sensitivity of 98.9 %. The specificity was 50.8 %, the positive predictive value was 94.6 % and the negative predictive value had a level of 99.9 %. CONCLUSION: MSCT is a simple, less invasive and useful method of monitoring results after coronary surgery including anastomosis and graft patency after complex arterial grafts. Its value may be restricted for sequential anastomoses and angiography should be preferentially used in these cases.

[Prediction of serious cardiovascular events by determining coronary artery calcification measured by multi-slice computed tomography]. / Prädiktion kardiovaskulärer Ereignisse durch Koronarkalkbestimmung mit der Mehrzeilen-Computertomographie.

BACKGROUND: The efficacious prophylaxis of myocardial infarction requires an accurate identification of patients at risk. Conventional risk stratification is often insufficient for this. We therefore examined the predictive value of coronary calcifications for future cardiovascular events. METHODS: We determined the extent of coronary calcification by multi-slice computed tomography in 924 patients (443 men, 481 women, aged 59.4 +/- 18.7 years) after coronary artery disease had been excluded by coronary angiography. To quantify coronary calcifications the volume score was calculated. After an observation period of 36 months was calculated the incidence of coronary revascularisation, myocardial infarction, and cardiac death. RESULTS: During the observation period the event rates for coronary revascularization (5.4 %/ year vs. 2.9 %/ year), myocardial infarction (3.8 %/ year vs. 1.8 %/ year), and cardiac death (2.1 %/ year vs. 1.0 %/ year) in patients with volume scores above the 75th percentile were significantly higher compared to the total study group. Correspondingly the scores in patients with revascularization (397 +/- 187), myocardial infarction (412 +/- 176), and cardiac death (422 +/- 184) were significantly higher compared to patients without cardiovascular events (218 +/- 167). In addition future cardiovascular events were excluded in patients without coronary calcifications. CONCLUSIONS: By determining coronary calcifications it was possible to identify patients at risk for myocardial infarction could be identified. Future cardiovascular events could not be observed in patients without coronary calcifications.

Catheter-based septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: follow-up results of the TASH-registry of the German Cardiac Society.

INTRODUCTION: In late 1997, the German Cardiac Society set up a multicenter registry to evaluate the acute and mid-term course of all patients (pts.) treated with septal ablation for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). An analysis of the acute results has already been published. We now report on the mid-term course (3-6 months) of 242 pts. registered through September 1999. RESULTS: Follow-up was 92% complete (n=222). During follow-up (mean: 4.9+/-2.3 months), an additional 3 pts. died (in-hospital mortality: 3 pts.). A satisfactory clinical effect was reported by 195 pts. (88%); 27 pts. (12%) remained in NYHA classes III and IV. Overall symptomatic improvement (NYHA class: from 2.8+/-0.7 to 1.7+/-0.7) paralleled the outflow gradient (LVOTG) reduction which was further accentuated as compared with the acute result (Doppler measurement at rest: from 57+/-31 to 25+/-25 mmHg to 20+/-21 mmHg; with provocation: from 107+/-53 to 49+/-40, to 44+/-40 mmHg, p<0.001, resp.). Left atrial (LA) diameter (from 46+/-8 to 44+/-7 mm) and septal thickness (from 20+/-5 to 15+/-5 mm; p<0.001, resp.) were also reduced. Comparing the methods for target vessel selection (i.e., with contrast echo monitoring vs pressurefluoroscopy guidance), at followup clinical improvement and hemodynamic measurements were comparable. CONCLUSION: Clinical success can be achieved by septal ablation, both with the echocontrast guided and gradient-fluoroscopy guided method, in 88% of highly symptomatic HOCM pts. At mid-term follow-up, symptoms, left atrial size and septal thickness are reduced, and outflow gradients are further improved as compared to the acute result.

Angiographic and clinical outcome for the treatment of in-stent restenosis with sirolimus-eluting stent compared to vascular brachytherapy.

BACKGROUND: With the use of coronary stents for the treatment of coronary artery disease, in-stent restenosis became a major clinical problem. In this non-randomized study, we examined the use of stent-based delivery of sirolimus (rapamycin) for the treatment of in-stent restenosis in comparison to intracoronary beta-brachytherapy, regarding the clinical effectiveness and the angiographic results for the treatment of in-stent restenosis after 6-9 months. METHODS AND RESULTS: Between July 2001 and May 2002, 28 patients (65+/-11 years) with instent restenosis were treated with intracoronary brachytherapy. Consecutively, between May 2002 and April 2003, 28 patients (65+/-10 years) with in-stent restenosis were treated with the implantation of a sirolimus-eluting stent (SES). Patients with in-stent restenosis treated by implantation of a SES had significantly lower incidence of in-stent restenosis (1/28 (3.6%) vs 10/28 (36%); p=0.007) and insegment restenosis (4/28 (14%) vs 14/28 (50%); p=0.013) compared to patients treated with brachytherapy. Target lesion and target vessel revascularization rate tended to be lower in the SES group (14 vs 25%) but did not yet reach statistical significance. One patient died in the group treated by implantation of a SES eight months after stenting, one patient suffered from myocardial infarction due to a subtotal in-stent restenosis after brachytherapy. Two patients after brachytherapy underwent surgical revascularization due to recurrent in-stent restenosis similar to the patient with in-stent restenosis after SES implantation. CONCLUSION: In this study we show the feasibility and safety of the treatment of in-stent restenosis by implantation of sirolimus-eluting stents and demonstrate a lower incidence of recurrent in-stent restenosis as well as lower late luminal loss compared to treatment by intravascular brachytherapy.

Catheter-based therapy for hypertrophic obstructive cardiomyopathy. First in-hospital outcome analysis of the German TASH Registry.

BACKGROUND: Registry results of the new catheter-based method in the treatment for HOCM are missing so far. In 1997, the Transcoronary Ablation of Septal Hypertrophy Registry (TASH Registry) was established by the German Cardiac Society (GCS) as a multicenter, national registry of patients with HOCM undergoing the new catheter interventional therapy. This is the report of the in-hospital outcome of patients who underwent the procedure during the first two years of data collection in the registry. METHODS AND RESULTS: Information was based on three standard forms for each patient, with a total of 86 variables. Information was collected on an "intention to treat" basis. The TASH Registry includes the establishment of a data base in the data collecting center. Ten centers participated. Enrollment forms were received for 264 patients out of 279 patients registered up to January 2000. There was a history of medical treatment of 3.6+/-3.9 years. The vast majority of patients (91%) were treated in three centers. The Vasalva maneuver and the exercise Doppler echocardiography were used for noninvasive stress testing. Exercise Doppler echocardiography induced a significantly higher augmentation of the baseline gradient (70.1% vs 133.4%; p<0.01). The echo-contrast guided technique was used for the intervention in 50.8% and the pressure angiography guided technique in 49.2%. On the average 2.8+/-1.3 ml of alcohol were injected. Before the procedure, the gradient measured by catheterization was 60.4+/-38.6 mmHg at baseline and 142.7+/-46.2 mmHg following the extrasystolic beat. At the end of the session it was reduced significantly by 75% and 67%. The peak phosphocreatine kinase activity was 482.5+/-246.4 U/L. Major complications occurred in 15.6% including a mortality rate of 1.2% and a permanent pacemaker implantation rate because of total heart block in 9.6%. There was an early in-hospital improvement of dyspnoe corresponding to a significant decrease of NYHA functional class from 2.8+/-0.7 to 1.8+/-0.6 (p<0.001). Similar hemodynamic and clinical benefit was found in patients with and without resting gradient at baseline. CONCLUSION: This analysis for the first time gives a comprehensive overview of clinical characteristics, technique, procedural data, in-hospital outcome and complications in a large number of patients with HOCM who were treated by the new catheter-based method and prospectively enrolled in a registry. The results contribute considerably to critical evaluation and validation of the new technique. This analysis supports the catheter-based method to constitute a new therapeutic option for very symptomatic patients, to be effective both in patients with and without intraventricular pressure gradient at rest and to be an alternative to surgical treatment, as has been stated recently.

[Technique and possibilities of cardiac computed tomography]. / Kardiale Mehrzeilen-Computertomographie. Koronarangiographie--ein Auslaufmodell?

Electron beam computed tomography no longer has a role to play in Germany. In contrast, multidetector spiral CT has great potential for replacing some coronary catheter studies, in particular for the exclusion of coronary artery disease, and this in particular since the forthcoming introduction of a 64-slice MDCT scanner promises a further improvement in temporal and special resolution. Currently, however it is no alternative to invasive angiography, since quantification of coronary stenoses is not possible; nor can a diagnostic evaluation be made in the presence of coronary calcifications or intracoronary stents. In particular, however, before applying CT angiography to the heart, the patient groups that can benefit from this method must be defined, especially in light of the fact that radiation exposure is three times as high as with diagnostic coronary catheterization.

[Coronary calcifications and the diagnosis of coronary artery disease]. / Screeningmethode bei asymptomatischen Risikopatienten. Kalkscore als früher Marker der Koronarsklerose.

Coronary calcium is a sensitive marker of coronary atherosclerosis, even at an early stage. With the aid of multislice computed tomography, noninvasive visualization of the microcalcification is possible. This enables the identification of asymptomatic patients at risk of developing future cardiovascular disease, and the initiation of effective preventive measures. In addition, in symptomatic patients, CT angiography with calcium scoring is of high negative predictive value in the exclusion of coronary artery disease.

[Detection and characterization of atherosclerotic coronary plaques with multislice spiral computed tomography]. / Kardiale Risikostratifizierung: Den atherosklerotischen Plaque im Blick.

Provided that adequate image quality is achieved, contrast-enhanced multislice spiral computed tomography enables the identification and characterisation of calcified and non-calcified coronary plaques. This is a major advance in the non-invasive assessment of coronary atherosclerosis that promises to open up new opportunities for a better understanding and risk stratification of this condition, with visualization of non-calcified hypodense lesions in particular appearing to be of prognostic importance. Current limitations of the technique relating mainly to temporal and spatial resolution may be eliminated by the introduction of a new generation of scanners enabling 64 slices and more.

[Detection of coronary calcinosis with multislice spiral computerized tomography: an alternative to electron beam tomography]. / Detektion von Koronarkalk mit der Mehrschicht-Spiral-Computertomographie: Eine Alternative zur Elektronenstrahltomographie.

Electron-beam CT (EBT) has been used for years as the gold standard to quantify coronary artery calcification as a marker of coronary atherosclerosis. With the introduction of Multi-Slice Spiral CT (MSCT) technology in 1999, EBT is now challenged in the determination of coronary calcium. The aim of this study was to determine the diagnostic accuracy of MSCT for the assessment of coronary calcium, comparing this new technique to EBT. The study population consisted of 54 male patients, aged 58 +/- 11 years with suspected coronary artery disease. For EBT, 40 axial slices (scan time = 100 ms, slice thickness = 3 mm) were acquired in one breath-hold (35 +/- 5 s) using an ECG-trigger at 80% of the RR interval. For MSCT, simultaneous acquisition of four axial slices (scan time = 250 ms, slice thickness = 2.5 mm) allowed the entire heart (40 slices) to be covered in one breath-hold (25 +/- 5 s) using a prospective ECG-trigger (R--450 ms). For quantification of coronary calcium the Agatston and the Volumetric calcium score (VCS) were applied. Mean Agatston score of the study group was calculated as 88 +/- 111 (median = 45), which is between the 25th and 75th age-corrected percentile of asymptomatic patients. For the Volumetric calcium score, number of lesions, calcium mass and density, no statistical difference was found between both imaging modalities. Agatston and Volumetric calcium score were statistically different between and within both scans. Mean variability of VCS of the two methods was calculated as 24% and was in the range of repeated EBT studies (14-44.9%). The Multi-Slice Spiral CT scanner is equivalent to EBT for the determination of coronary calcium and can, therefore, be used for calcium screening. Using a prospective ECG-trigger technique, the application of the Agatston method delivers statistically different results in comparison to EBT. With the application of the spiral mode technique, retrospective ECG-trigger and thinner slice thickness, further improvement in variability can be expected, thus allowing for follow-up studies to determine progression or regression of atherosclerosis with high accuracy.

Retroinfusion of NFkappaB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs.

Myocardial reperfusion injury is partially mediated by postischemic inflammation. Beyond acute PMN recruitment, postischemic inflammation comprises subacute PMN adhesion, eg via NFkappaB activation. In a pig model of 60-min LAD occlusion by PTCA ballon inflation and 1 to 7 days of reperfusion, we investigated the impact of targeted NFkappaB decoy oligonucleotide (ODN) transfection in the area at risk (AAR) on infarct size and regional myocardial function. After 55 min of LAD occlusion, liposomes containing NFkappaB ODN were selectively retroinfused into the anterior interventricular vein for 5 min. Then, retroinfusion was stopped and reperfusion was initiated. Where indicated, CD18 antibody IB4 was infused systemically at 30 min of ischemia. Methylen blue and tetrazolium-red staining were used for quantification of the infarct size. Subendocardial segment shortening (SES) by sonomicrometric crystals in infarct area and AAR was assessed under pacing (expressed as % of control region). NFkappaB decoy ODN retroinfusion reduced infarct size (36 +/- 4% versus 49 +/- 5% in control hearts at day 7), whereas functional reserve of the AAR (SES 73 +/- 17% versus 46 +/- 18% at 180/min) tended to improve. Similar effects were observed after IB4 infusion (38 +/- 5% infarct size, 85 +/- 7% SES at 180/min). A combination of NFkappaB decoy ODN retroinfusion and IB4 infusion further decreased infarct size (26 +/- 2%) and improved functional reserve (SES 94 +/- 6% at 180/min). We conclude that NFkappaB decoy ODN transfection by retroinfusion is feasible in pig hearts and provides postischemic cardioprotection in addition to CD18 blockade.

Pressure-guided nonsurgical myocardial reduction induced by small septal infarctions in hypertrophic obstructive cardiomyopathy.

OBJECTIVES: We sought to assess the safety and efficacy of pressure-guided nonsurgical myocardial reduction (NSMR) with the induction of small septal infarctions in patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Nonsurgical myocardial reduction has been shown to decrease left ventricular outflow tract (LVOT) obstruction and to improve symptoms in patients with HOCM. Infarct sizes differ considerably among studies published so far. METHODS: In 50 patients, the LVOT gradient was invasively determined at the time of the intervention, four to six months (n = 49) and 12 to 18 months (n = 25) after NSMR. New York Heart Association functional class and quality of life were assessed by using a standard questionnaire. Exercise capacity was tested by spiro-ergometry. Left ventricular (LV) mass was determined by electron beam computed tomography. RESULTS: Small septal infarctions (mean creatine kinase value 413 +/- 193 U/l) resulted in a sustained decrease in LVOT gradients, from 80 +/- 33 to 18 +/- 17 mm Hg after four to six months (p < 0.001, n = 49) and to 17 +/- 15 mm Hg (p < 0.001, n = 25) after 12 to 18 months. Nonsurgical myocardial reduction was followed by a decrease in LV hypertrophy, which was associated with a sustained increase in exercise capacity, as well as improvement in quality of life. CONCLUSIONS: Pressure-guided NSMR inducing small septal infarctions was sufficient to result in a sustained decrease in LVOT obstruction and to improve symptoms. The incidence of complications, such as complete heart block with necessary permanent pacemaker implantation (<10%), seems to be diminished by minimizing the infarct size.