[History of clinical electrophysiology in diagnosing and treatment monitoring of high ventricular vulnerability]. / Geschichte der klinischen Elektrophysiologie in Diagnostik und Therapiekontrolle ventrikulärer Vulnerabilität.

The paper presents the history of hope from 1980-1995 to predict the risk of sudden arrhythmic death using electrophysiologic techniques in individual patients. Even if this prediction seems possible in selected highly risk cohorts, many more patients will die in ventricular arrhythmia without fulfilling the criteria. Ultimately, high risk of sudden cardiac death can be predicted in selected patient groups, but not in the majority of patients at risk. It is a history of dashed hope.

The CINCH-FMR postmarket registry: Real-world long-term outcomes with percutaneous mitral valve repair with the Carillon Mitral Contour System®.

BACKGROUND: The Carillon® Mitral Contour System® has been studied in 4 prospective controlled studies in the treatment of functional mitral regurgitation (FMR) where it has been found to reduce mitral regurgitation, reduce left ventricular and atrial volumes, and be associated with improvements in clinical parameters. AIMS: The CINCH post-market registry is designed to evaluate immediate, mid-term and long-term outcomes from a post-approval study of the Carillon® device evaluated in real-world practice. METHODS: The CINCH post-market registry is a single-arm study of percutaneous mitral annuloplasty with the Carillon device in patients with functional (secondary) mitral regurgitation and symptomatic congestive heart failure when utilized in real-world conditions. Patient selection, echocardiographic hemodynamic measurements, and patient follow-up requirements were performed per standard of care at each institution. RESULTS: A total of 101 patients treated with the Carillon device at 13 sites in Germany were enrolled in the CINCH registry. The mean age was 75 ± 9 years, 57 % were male, and patient presentation included primarily NYHA class III (69 %) with MR grade 3 (68 %). Over 5 years of follow-up, all-cause mortality was 40.1 %, the incidence of HFH was 53.9 %, and the composite outcome of HFH or death was 66.4 %. At each follow-up interval through 5 years, statistically significant reductions in NYHA class (p < 0.05) and MR grade (p < 0.01) were reported. CONCLUSIONS: In this "real world" registry of the Carillon Mitral Contour System, procedural safety and medium-term follow-up outcomes is similar to the outcomes seen in the prospective, controlled clinical trials, despite being used in populations of patients that extend outside of those studied in the trials. The use of this therapy in patients with atrial functional mitral regurgitation, and heart failure with preserved ejection fraction, was notable, since these types of patients were excluded from the prospective, controlled trials. This supports possible additional patient populations who might benefit from this type of mechanical therapy. The safety profile of this therapy in this registry and in the earlier trials may support a potential role in earlier forms of secondary mitral regurgitation.

First case report of the use of two stents following coronary artery obstruction during indirect mitral annuloplasty.

The case of a 71-year-old male with end stage heart failure and severe mitral regurgitation is presented, where percutaneous indirect mitral annuloplasty was performed. During device implantation in the coronary sinus the circumflex artery was compromised at two anatomic locations, while the mitral regurgitation was efficiently reduced. After weighing risks and alternative therapeutic options, stent implantation was chosen as bailout strategy to leave the device in place and retain the efficient MR reduction. The anatomical proximity of Cx and coronary sinus in the mitral valve plane bears the risk of circumflex artery damage during surgical and interventional mitral repair. Usually, a device exchange solves the problem of arterial flow limitation in most cases. While stent implantation remains off label use in this setting and should not be performed without critical evaluation, it has been performed successfully in similar clinical settings as well (e.g. artery stenosis by surgical suture).

Echocardiographic analysis of acute effects of percutaneous mitral annuloplasty on severity of secondary mitral regurgitation.

AIMS: Percutaneous mitral annuloplasty (PMA) represents a new treatment option for secondary mitral regurgitation (SMR) being associated with higher morbidity and mortality. The present study was aimed to evaluate whether or not acute effects on SMR severity can quantitatively be assessed after PMA. METHODS AND RESULTS: PMA was performed in 30 patients (mean age 76 ± 9; 37% males) with moderate (n = 14) or severe (n = 16) SMR. Vena contracta (VC), left ventricular (LV) velocity-time-integral ratio (VTIMV/LVOT ), effective regurgitant orifice area (EROA) by two-dimensional proximal isovelocity surface area (PISA), regurgitant volume (RVolPISA ) and regurgitant fraction (RFPISA ) by PISA, RVolvolume and RFvolume by LV volume analyses, and parameters describing LV morphology, function, and cardiac performance were assessed by transthoracic echocardiography prior to and after PMA. According to RFPISA /RFvolume , 14 patients showed mild, 15 moderate, and 1 severe SMR after PMA. Mean RF, RVol, EROA, VC, and VTIMV/LVOT were lower directly after PMA (RFPISA : 49% ± 11 vs. 34% ± 13, P < 0.001; RFvolume : 46% ± 10 vs. 34% ± 13, P < 0.001; RVolPISA : 33 mL ± 13 vs. 25 mL ± 12, P < 0.001; RVolvolume : 28 mL ± 17 vs. 20 mL ± 14, P < 0.05; EROAPISA : 0.24 cm2  ± 0.1 vs. 0.19 cm2  ± 0.1, P < 0.05; VC: 5.2 ± 0.1 vs. 4.1 ± 0.2, P < 0.001; VTIMV/LVOT : 1.9 ± 0.4 vs. 1.6 ± 0.5, P < 0.05). Parameters of LV morphology, function, and cardiac performance did not change directly after PMA. CONCLUSIONS: PMA leads to a reduction of MR severity in >80% of SMR patients. Acute effects of PMA can quantitatively be assessed by transthoracic echocardiography.

[History of catheter ablation]. / Geschichte der Katheterablation.

After His bundle electrography was established in 1967, the step from invasive electrophysiologic diagnosis of arrhythmias to interventional treatment by catheter ablation was imminent. The time interval of 15 years between the diagnosis and treatment of arrhythmias was even shorter than the 19 years between the first selective coronary angiography in 1958 at the Cleveland Clinic in the USA and the first percutaneous coronary intervention in 1977 in Zurich. During each time period, a great amount of knowledge was gained in cardiac surgery, which proved to be very helpful for the development of the interventional treatment. The history of endovascular treatment is an impressive reminder that the preparation and support of cardiovascular surgeons and their handling of complications played a decisive role in the further development of cardiovascular internal medicine. The history of catheter ablation teaches us that the joint work of cardiologists and cardiovascular surgeons is of great importance for the choice and further development of the best possible treatment as for future development of the techniques of therapy.

Five-year effectiveness of low-dose-rate brachytherapy: comparisons with nomogram predictions in patients with non-metastatic prostate cancer presenting significant control of intra- and periprostatic disease.

PURPOSE: To assess the effectiveness of low-dose-rate (LDR) brachytherapy in patients with localized prostate cancer and to compare the outcome with predictions from Kattan and Partin nomograms at 60 months after seed implantation. MATERIAL AND METHODS: One thousand, one hundred and eighty-seven patients with localized prostate cancer at low-, intermediate-, or high-risk of progression received LDR brachytherapy using iodine-125 seeds with curative intent, applied as monotherapy or in combination with external beam radiation therapy (EBRT), and/or androgen deprivation therapy (ADT). At 60 months after seed implantation, data of 1,064 patients (1,058 alive + 6 who died of prostate cancer) were analyzed for biochemical progression-free survival (bPFS) based on prostate-specific antigen (PSA) levels using the Phoenix definition. Five-year bPFS probabilities were determined for various risk group classifications (d'Amico, Mt. Sinai, MSKCC/Seattle, NCCN). Outcomes were also compared to patient-individualized nomogram predictions of 5-year bPFS (Kattan 2002) and probability of organ-confined disease (Kattan 2002, Partin 2007). RESULTS: Overall, 93.3% (993/1,064) of the patients were free of biochemical progression within 5 years, while the average 5-year bPFS probability according to the Kattan nomogram was significantly lower (85%, p < 0.001). Outcomes were significantly better than Kattan nomogram predictions in the subgroup of patients with monotherapy as well as in patients additionally treated with EBRT. Comparison of the overall outcome with nomogram predictions for organ-confined disease (Kattan nomogram: 50%; Partin nomogram: 65%) revealed a significant probability of LDR brachytherapy to destroy periprostatic tumor spread (p < 0.001) in all risk group constellations, even in high-risk patients. CONCLUSIONS: The results indicate high effectiveness of LDR brachytherapy in all risk groups, significantly better than predicted with the Kattan nomogram in most subgroups. The significant superiority of LDR brachytherapy compared to nomogram predictions of organ-confined disease suggests that LDR brachytherapy effectively controls both intra- and periprostatic disease.

Analysis of chronic aortic regurgitation by 2D and 3D echocardiography and cardiac MRI.

Purpose The study compares the feasibility of the quantitative volumetric and semi-quantitative approach for quantification of chronic aortic regurgitation (AR) using different imaging modalities. Methods Left ventricular (LV) volumes, regurgitant volumes (RVol) and regurgitant fractions (RF) were assessed retrospectively by 2D, 3D echocardiography and cMRI in 55 chronic AR patients. Semi-quantitative parameters were assessed by 2D echocardiography. Results 22 (40%) patients had mild, 25 (46%) moderate and 8 (14%) severe AR. The quantitative volumetric approach was feasible using 2D, 3D echocardiography and cMRI, whereas the feasibility of semi-quantitative parameters varied considerably. LV volume (LVEDV, LVESV, SVtot) analyses showed good correlations between the different imaging modalities, although significantly increased LV volumes were assessed by cMRI. RVol was significantly different between 2D/3D echocardiography and 2D echocardiography/cMRI but was not significantly different between 3D echocardiography/cMRI. RF was not statistically different between 2D echocardiography/cMRI and 3D echocardiography/cMRI showing poor correlations (r < 0.5) between the different imaging modalities. For AR grading by RF, moderate agreement was observed between 2D/3D echocardiography and 2D echocardiography/cMRI and good agreement was observed between 3D echocardiography/cMRI. Conclusion Semi-quantitative parameters are difficult to determine by 2D echocardiography in clinical routine. The quantitative volumetric RF assessment seems to be feasible and can be discussed as an alternative approach in chronic AR. However, RVol and RF did not correlate well between the different imaging modalities. The best agreement for grading of AR severity by RF was observed between 3D echocardiography and cMRI. LV volumes can be verified by different approaches and different imaging modalities.

[Electrophysiologic procedure complications in the elderly]. / Komplikationen elektrophysiologischer Eingriffe im Alter.

Published registries give limited information on age-dependent complication rates. There are several reasons for this, including limited numbers of patients in subgroups (e.g., contractility management), experience-dependent procedures (e.g., catheter ablation), or in changing indications (e.g., resynchronization). Finally, severely ill and very old patients with limited prognosis are often excluded from electrophysiologic procedures. Therefore, published data are difficult to interpret. Meta-analyses of randomized trials give more precise information on included patient cohorts, but do not necessarily reflect daily practice because elderly patients are often excluded from trials. Therefore, the individual risk of elderly patients has to be estimated on an individual case basis. In summary, the age of patients is not relevant regarding possible complications; thus, there is no age limit for electrophysiologic interventions. Therefore, there is no alternative to the individual estimation of procedural risks of interventions of an informed patient by an experienced cardiologist.

Thrombus aspiration in non-ST-elevation myocardial infarction - 12-month clinical outcome of the randomised TATORT-NSTEMI trial.

BACKGROUND: In the randomised TATORT-NSTEMI trial routine thrombus aspiration in comparison with standard percutaneous coronary intervention (PCI) did not reduce the primary endpoint of microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with non-ST-elevation myocardial infarction (NSTEMI). So far, no data on long-term outcome of head-to-head comparisons between both treatment strategies in NSTEMI patients have been reported. METHODS: The prospective, controlled, multicentre, randomised, open-label TATORT-NSTEMI trial assigned patients with NSTEMI and thrombus-containing lesions to aspiration thrombectomy plus PCI ( n=221) or standard PCI only ( n=219). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events defined as the composite of death, myocardial reinfarction, target vessel revascularisation, and new congestive heart failure at 12-month follow-up. In addition, functional outcome and quality of life were assessed. RESULTS: At one year, major adverse cardiac events occurred in 19 patients in the thrombectomy arm and 29 patients in the standard PCI group (8.7% vs. 13.4%, relative risk 0.63, 95% confidence interval 0.35-1.12, p=0.11). The individual components of the combined endpoint such as death ( p=0.20), myocardial reinfarction ( p=0.73), target vessel revascularisation ( p=0.42), and congestive heart failure ( p=0.18) were similar in both groups. Functional outcome and quality of life did not differ significantly between both groups (Canadian Cardiovascular Society class: p=0.68, New York Heart Association class: p=0.70 and EuroQol5D score: p=0.96). Post-hoc analyses revealed consistent results with regard to the occurrence of major adverse cardiac events across a wide range of subgroups (all p>0.05). CONCLUSIONS: In this first randomised trial on thrombectomy in NSTEMI patients, routine thrombus aspiration before PCI did not improve clinical outcome at 12-month follow-up.

Mitral Annuloplasty Device Implantation for Non-Surgical Treatment of Mitral Regurgitation: Clinical Experience After the Approval Studies.

BACKGROUND AND AIMS: One option for interventional treatment of secondary mitral regurgitation is the placement of an indirect mitral annuloplasty device (Carillon Mitral Contour System) cinching the mitral annulus to facilitate coaptation of the mitral leaflets. The aim of this study is to evaluate the implantation success and hemodynamic results. METHODS AND RESULTS: Seventeen consecutive patients (11 females, 6 males) suffering from moderate to severe secondary mitral regurgitation (40% ischemic, 59% non-ischemic) received a Carillon Mitral Contour System device, which was evaluated prospectively in a single-center setting. The mean procedure time was 95.5 ± 2.1 minutes, fluoroscopy time was 13.1 ± 6.1 minutes, and the amount of contrast dye was 120.6 ± 39.3 mL. The mitral regurgitation grade was reduced from 2.8 ± 2.4 to 1.9 ± 0.8 acutely (P<.01), with an additional improvement seen after 3 months to 1.5 ± 0.75 (P<.01 to baseline). In 41.2% of patients, acute reduction of coronary artery flow was seen and managed with a stepwise approach: (1) intracoronary nitroglycerin was administered; (2) release of device tension; (3) a new device was changed and placed at a different location; and (4) the device was left in place and a stent was implanted in the coronary artery. Only 1 patient (5.8%) could not receive the device due to coronary compression. No periprocedural myocardial infarction occurred. CONCLUSION: Indirect mitral annuloplasty is feasible outside of controlled trials, and is associated with successful improvement of mitral regurgitation. Although coronary compromise needs to be addressed as part of the implantation procedure, this issue limits implantation of the device in only a small percentage of cases.

Early detection of cardiotoxicity by 2D and 3D deformation imaging in patients receiving chemotherapy.

The aim of the present study was to find out whether early cardiac changes in patients receiving chemotherapy can be detected by the conventional and deformation parameters of 2D and 3D echocardiography. Twenty-five healthy subjects with normal regional left ventricular function (group 1) and 25 patients receiving chemotherapy (group 2) underwent 2D and 3D transthoracic echocardiography (Toshiba Artida Medical System). All patients (group 2) were examined before and during cardiotoxic chemotherapy at a 3-month follow-up. Left ventricular volumes, ejection fraction, muscle mass, global longitudinal, global radial, global circumferential strain, and rotation were analyzed with 2D and 3D echocardiography, while twist and time-to-peak-intervals were analyzed with 3D echocardiography. For left ventricular volumes and muscle mass, no significant differences were seen between the two study groups (P<0.05). According to our results, myocardial dysfunction induced by cardiotoxic chemotherapy can be detected by 2D global radial strain. Detecting myocardial dysfunction by global longitudinal and circumferential strain requires more than 3 months follow-up. Changes in rotation, twist or time-to-peak intervals could not be verified at the 3-month follow-up in the present study. 2D global radial strain seems to be the most sensitive and robust parameter to detect early myocardial damage during chemotherapy. 3D echocardiography is not yet an established method to detect myocardial damage in clinical practice due to lower spatial and temporal resolution.

Feasibility of proximal right coronary artery imaging by 2D and 3D echocardiography in comparison to coronary angiography.

The present study was carried out to test the feasibility of proximal right coronary artery (RCA) imaging and to detect proximal RCA narrowing and occlusion by 2D and 3D transthoracic echocardiography in comparison to coronary angiography (CA). Standardised 2D and 3D echocardiography were performed prior to CA in 97 patients with sinus rhythm. The following parameters were determined: the longest longitudinal detectable RCA segment, the minimum and maximum width of the RCA, the area and number of detectable narrowing >50% of the proximal RCA and the correlation between the echocardiographic and angiographic findings. The visualisation of the proximal RCA and the detection of coronary artery narrowing in the proximal RCA are generally possible. Differences in width and area were not statistically significant between 2D and 3D echocardiography, but showed significant differences between echocardiography and CA. For the detection of proximal RCA narrowing, higher sensitivity and specificity values were obtained by 2D than by 3D echocardiography. However, in patients with sufficient image quality 3D echocardiography permits a more detailed visualisation of the anatomical proportions and an en-face view into the RCA ostium. The visualisation of the proximal RCA is feasible and narrowing can be detected by 2D and 3D echocardiography if image quality is sufficient. CA is the gold standard for the detection of coronary artery stenoses. However, the potential of this new approach is clinically important because crucial findings of the proximal RCA can be presumably detected non-invasively prior to CA.

Single application of high-intensity focused ultrasound as primary therapy of localized prostate cancer: Treatment-related predictors of biochemical outcomes.

OBJECTIVE: Recent reports on high-intensity focused ultrasound (HIFU) treatment of localized prostate cancer suggest that preoperative risk groups of tumor recurrence are strong predictors of oncological outcomes. The purpose of this study is to determine the prognostic significance of treatment-related factors in relation to patient characteristics for biochemical outcomes after HIFU. METHODS: This retrospective single-center study included patients treated from December 2002 to December 2010 for localized prostate cancer with two generations of Ablatherm® HIFU devices (A1 and A2). All the patients underwent single HIFU treatment session under the concept of whole-gland therapy. Prostate surgery was performed before HIFU to downsize enlarged glands. Androgen deprivation therapy (ADT) was discontinued before HIFU. Biochemical failure (BCF) was defined as prostate specific antigen (PSA) nadir + 1.2 ng/mL (Stuttgart definition). Predictors of BCF were determined using Cox regression models. As covariates, patient-related factors (age, tumor characteristics, ADT) were compared with treatment-related factors (prostate volume, HIFU device generation, conduct of therapy, prostate edema, patient movement, anesthetic modalities). RESULTS: Three hundred and twenty-three (98.8%) out of 327 consecutive patients were evaluable for BCF. Median (interquartile range) follow-up was 51.2 (36.6-80.4) months. The overall BCF-rate was 23.8%. In multivariate analyses, higher initial PSA-values (Hazard ratio [HR]: 1.03; p < 0.001) and higher D'Amico risk stages (HR: 3.45; p < 0.001) were patient-related predictors of BCF. Regarding treatment-related factors, the A2 HIFU device was associated with a decreased risk of BCF (HR: 0.51; p = 0.007), while prostate edema had an adverse effect (HR: 1.8; p = 0.027). Short follow-up and retrospective study design are the primary limitations. CONCLUSION: Success in a single HIFU session depends not merely on tumor characteristics, but also on treatment-related factors. Ablation is more efficacious with the technically advanced A2 HIFU device. Heat-induced prostate edema might adversely affect the outcome.

Effect of aspiration thrombectomy on microvascular obstruction in NSTEMI patients: the TATORT-NSTEMI trial.

BACKGROUND: Aspiration thrombectomy in ST-segment elevation myocardial infarction is recommended by current guidelines based on several randomized trials. There are no trials assessing thrombectomy in non-ST-segment elevation myocardial infarction (NSTEMI) patients. OBJECTIVES: The TATORT-NSTEMI (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non-ST-Elevation Myocardial Infarction) trial sought to assess the effect of aspiration thrombectomy on microvascular injury in patients with NSTEMI compared with standard percutaneous coronary intervention (PCI). METHODS: This prospective, controlled, multicenter study randomized 440 patients to adjunctive thrombectomy (n = 221) compared with conventional PCI (n = 219) in NSTEMI patients with thrombus-containing lesions. The primary endpoint of the extent of microvascular obstruction (MO) in the percentage of left ventricular mass (%LV) was assessed by cardiac magnetic resonance imaging within 4 days. Secondary endpoints included infarct size, myocardial salvage index, and angiographic parameters including myocardial blush grade and Thrombolysis In Myocardial Infarction flow grade. The combined clinical endpoint consisted of death, reinfarction, target vessel revascularization, and new congestive heart failure within 6 months. RESULTS: The primary endpoint of MO was not different between the thrombectomy and the standard PCI group with 2.0%LV (interquartile range [IQR]: 0.8 to 4.1) versus 1.4%LV (IQR: 0.7 to 2.6) (p = 0.17). Similarly, no significant differences were observed for infarct size (8.6%LV; IQR: 4.0 to 14.7 vs. 7.4%LV; IQR: 4.1 to 13.1; p = 0.46), myocardial salvage index (63.3; IQR: 35.4 to 87.2 vs. 65.6; IQR: 46.9 to 82.6; p = 0.45), or angiographic parameters such as blush grade (p = 0.63) and Thrombolysis In Myocardial Infarction flow grade (p = 0.66). Clinical follow-up at 6 months revealed no differences in the combined clinical endpoints (p = 0.22). CONCLUSIONS: Aspiration thrombectomy in conjunction with PCI in NSTEMI with a thrombus-containing lesion does not lead to a reduction in MO. (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non-ST-Elevation Myocardial Infarction [TATORT-NSTEMI]; NCT01612312).

[Medicinal treatment of atrial fibrillation in special situations]. / Medikamentöse Therapie des Vorhofflimmerns in speziellen Situationen.

The treatment of atrial fibrillation has to take into account the underlying cardiac and extracardiac diseases. A successful treatment of the underlying disease will only be sufficient treatment of atrial fibrillation in very rare situations. Therefore, this review focuses on the consequences of underlying heart disease, the hemodynamics and concomitant clinical situations on the treatment of atrial fibrillation.