Transient elevation of high-sensitive troponin T after Cardioband implantation.

BACKGROUND: The Cardioband system enables percutaneous surgical-like direct mitral valve annuloplasty and, thereby, repair of severe functional mitral valve regurgitation (MR) in patients with advanced systolic heart failure (HF) and dilation of the left ventricular (LV) annulus. Since the device is anchored by screws in the LV annulus, limited myocardial injury is likely to occur. METHODS AND RESULTS: Five patients (Society of Thoracic Surgeons score: 2.7 ± 0.7%) with severe HF (LV ejection fraction [LVEF]: 17 ± 1%; LV end-diastolic diameter [LVEDD]: 71 ± 3 mm) were treated with the Cardioband (sizes C-F) receiving 14-17 screws in the LV annulus region. Myocardial injury was monitored by measuring high-sensitive cardiac troponin T (hsTnT) levels and by echocardiography. All patients showed significant periprocedural increase in hsTnT levels. Peak hsTnT concentration was reached between day 1 and day 6 (593 ± 141 pg/ml). None of the patients showed clinical signs of myocardial infarction, ST-segment elevation, new onset of deteriorated myocardial wall motion, or new ventricular tachycardia. hsTnT levels normalized in all patients after 14 days (hsTnT on day 0: 34 ± 6 pg/ml vs. hsTnT on day 14: 36 ± 6 pg/ml; p = 0.604). This nonischemic hsTnT kinetics was compared to a sixth patient who experienced proximal damage of the left circumflex artery (LCX) and ST-segment elevation during the Cardioband procedure, followed by immediate repair of the LCX, avoiding structural damage of the LV. CONCLUSION: Cardioband implantation is accompanied by significant elevation of hsTnT without causing structural myocardial damage or clinical symptoms such as worsening of LV function, new-onset LV regions exhibiting reduced wall motion, or ventricular tachycardia.

[High-risk patients with aortic valve stenosis. Interventional therapy]. / Aortenklappenstenose bei erhöhtem Risiko. Interventionelle Therapie.

Aortic valve stenosis is the most prevalent, clinically significant valvular disorder in adult patients. Surgical valve replacement is the standard therapy for patients with symptomatic and severe aortic stenosis; however, many patients are suboptimal candidates for surgery due to age and co-morbidities. The development of transcatheter aortic valve implantation (TAVI) has broadened the therapeutic options, especially in high-risk patients. The first randomized study comparing surgical valve replacement with TAVI in operable high-risk patients show similar mortality and reduction in symptoms after a 2-year follow-up. These data support the use of this technique in high-risk patients with severe aortic stenosis.

High throughput echocardiography in conscious mice: training and primary screens.

PURPOSE: Genetic engineering techniques led to an exponential increase in the number of transgenic and knock-out mouse models. For many genetically modified mice, high throughput echocardiography is an essential part of a systematic screening workflow. Many researchers perform mouse echocardiography in conscious animals to avoid anesthesia-induced impairment of cardiac function. However, it has been controversially discussed whether mice need to be habituated to handling before their cardiac function can be assessed. The aim of this study was to test the influence of training on parameters assessed during conscious mouse echocardiography. In addition, we tested whether a simple and fast echocardiography protocol has sufficient sensitivity and specificity for primary screening. MATERIALS AND METHODS: Examined parameters include fractional shortening, heart rate and respiratory rate. A total of 139 mice were examined in this study with a total of 587 echocardiograms. 103 mice were examined on five consecutive days (with examinations on day 1 - 4 regarded as training), 36 mice were only examined on day 1 and 5. RESULTS: Fractional shortening, heart rate and respiratory rate did not show any statistically significant difference between day 1 and day 5 in both groups. The sensitivity and specificity of fractional shortening assessment for predicting a homozygote knock out genotype were 86 % and 97 %, respectively. CONCLUSION: We conclude that conscious mouse echocardiography can be performed in untrained mice. Fractional shortening measurements may suffice for correct phenotyping in a high throughput setting.

Transcatheter aortic valve implantation in nonagenarians: insights from the German Aortic Valve Registry (GARY).

OBJECTIVE: The aim of this study was to compare the outcome of nonagenarians (≥ 90 years) with that of younger (< 90 years) patients undergoing transcatheter aortic valve implantation (TAVI) in current practice. METHODS: Data are collected from the German Aortic Valve Registry (GARY), which was designed to evaluate current practice in the invasive treatment of patients with aortic valve diseases in Germany. Data were analyzed regarding procedural outcome, 30-day, and 1-year outcomes of nonagenarians in comparison to that of younger patients. RESULTS: Between 2011 and 2015, 2436/33,051 (7.3%) nonagenarians underwent TAVI and were included in GARY. Nonagenarians were significantly more often male (45.2% vs. 40.0%, p < 0.001), frail (38.7% vs. 34.7%, p < 0.001), and had higher EuroSCORE scores than younger patient group (23.2% vs. 17.0%). Nonagenarians were significantly less often treated via transapical access (16.3% vs. 22.3%, p < 0.001). Procedure was performed significantly less often in general anesthesia (58.2% vs. 60.7%, p = 0.02) in nonagenarians, while necessity of pacemaker implantation was significantly higher in nonagenarians (27.2% vs. 24.8%, p > 0.001). The incidence of other typical postprocedural complications such as severe bleeding events and vascular complications were comparable between groups. However, 30-day (5.2% vs. 3.9%) and 1-year (22.7% vs. 17.7%) mortality rates were significantly higher among nonagenarians and age ≥ 90 years could be identified as an isolated risk factor for mortality. CONCLUSION: TAVI is a highly standardized procedure that can be performed safely with high procedural success even in very old patients. Although mortality is significantly higher in these patients-most probably due to the intrinsic higher risk profile of the very old patients-the results are still acceptable. To optimize outcome, especially elderly patients seem to profit from a procedure under local anesthesia or conscious sedation, to minimize the rate of postoperative delirium and the length of stay and to facilitate early mobilization.

Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

Augmentation of AAV-mediated cardiac gene transfer after systemic administration in adult rats.

Adeno-associated virus (AAV)-6 or -9-pseudotyped vectors are suitable for efficient cardiac gene transfer after intravenous injection in mice. However, a systemic application in larger animals or humans would require very high doses of viral particles. Therefore, the aim of our study was to test if ultrasound-targeted microbubble destruction could augment cardiac transduction of AAV vectors after intravenous administration in rats. To analyze efficiency and specificity of gene transfer, microbubbles loaded with AAV-6 or -9 harboring a luciferase or enhanced green fluorescent protein (EGFP) reporter gene were infused into the jugular vein of adult Sprague-Dawley rats. During the infusion, high mechanical index ultrasound was administered to the heart. Control rats received the same amount of virus without microbubbles, but with ultrasound. After 4 weeks, organs were harvested and analyzed for reporter gene expression. In contrast to low cardiac expression after systemic transfer of the vector solution without microbubbles, ultrasound-targeted destruction of microbubbles significantly increased cardiac reporter activities between 6- and 20-fold. Analysis of spatial distribution of transgene expression using an AAV-9 vector encoding for EGFP revealed transmural expression predominantly in the left ventricular anterior wall. In conclusion, ultrasound targeted microbubble destruction augments cardiac transduction of AAV vectors in rats. This approach may be suitable for efficient, specific and noninvasive AAV-mediated gene transfer in larger animals or humans.

Intraluminal ultrasound imaging of the fallopian tube wall: results of standardized in vitro investigations of pig and human tubal specimens.

OBJECTIVE: To investigate to what extent anatomic structures of the tubal wall can be identified reproducibly and whether altered areas can be detected and delimited by intraluminal ultrasound. DESIGN: Standardized in vitro experiment with descriptive evaluation of findings, comparative analysis of apparative and morphologic data, and determination of interobserver variability (video documentation, blinded reviewer). SETTING: Department of Gynecology and Obstetrics, University of Heidelberg, Germany. SPECIMEN(S): Seventy-two human and pig fallopian tubes. INTERVENTION(S): Catheterization with a 2.9F or 3.2F ultrasound catheter and sonographic depiction of the fallopian tube, with either simultaneous manual and sonographic wall-thickness measurement or coagulation of the tubal wall. MAIN OUTCOME MEASURE(S): A correlation coefficient of r = 0.76 for manual and sonographic tubal wall measurements and K = 0.88 (with 95% confidence interval of 0.74-1.0) for interobserver variability in recognizing coagulated areas. RESULT(S): Tubal wall anatomy and artificially altered (coagulated) areas were displayed reproducibly with intraluminal ultrasound, thus giving a characteristic, recognizable pattern of the tubal wall. CONCLUSION(S): These in vitro experiments provide evidence that intraluminal ultrasound may expand the current diagnostic possibilities in cases of tubal pathology, providing nonsurgical access to the tubal wall.

Influence of catheter position and equipment-related factors on the accuracy of intravascular ultrasound measurements.

BACKGROUND: Intravascular ultrasound (IVUS) is frequently used as an adjunct to coronary angiography to guide revascularization procedures and, more recently, to estimate atherosclerotic plaque volumes. Although accuracy of IVUS imaging and analysis is crucial for these measurements, available data are scarce. The purpose of this in vitro study is to determine the extent to which transducer position and equipment-related factors influence measurement accuracy. METHODS: Cross-sectional views of tubular vessel phantoms (diameter 2-14 mm) were acquired using 3.2 French catheters in coaxially centered, eccentric and oblique positions. Catheters were sequentially connected to two different ultrasound systems (A and B) to estimate equipment-related variability. In system B, two software versions were used to analyze ultrasound images. Longitudinal views of phantom segments were reconstructed to document transducer misplacement. RESULTS: Oblique transducer positioning resulted in a non-linear overestimation of phantom areas that was independent of lumen size and also resulted in dramatic distortions of three-dimensionally reconstructed phantom geometry. Eccentric positioning did not significantly influence measurement accuracy. In coaxial positioning, differences between measured and true areas increased non-linearly from 0.36 to 4.5 mm2 in system B and in a linear fashion from -0.01 to 2.68 mm2 in system A with increasing phantom diameters. Relative differences decreased from 11.4% to 2.9% with increasing reference areas in system B (positive off-set error). When using updated software in system B, the off-set error was negative and relative error diminished from -1.34% to 0.44% with increasing phantom size. CONCLUSION: Transducer position and equipment-related factors influence the accuracy of intravascular ultrasound, which may lead to misinterpretation of vessel size and geometry even in straight vessel segments. Transducer position may be controlled by the reconstruction of longitudinal images. Ultrasound equipment should be calibrated before using it for quantitative measurements.

[Disappearing borders between cardiology and cardiothoracic surgery: status quo]. / Schwindende Fachgrenzen zwischen Kardiologie und Kardiochirurgie: Status quo.

Cardiology and cardiothoracic surgery are closely related so that collaboration and communication are required to offer optimal therapy for patients. During the last decades many innovations have reduced the borders between cardiology and cardiothoracic surgery. Today, cardiologists may perform coronary interventions with good results that would have previously been the domain of coronary bypass surgery. In addition new valvular interventions have been developed, such as transfemoral or transapical aortic valve implantation and endovascular mitral valve reconstruction. New developments in cardiothoracic surgery have led to less invasive procedures and many surgical procedures can now be performed with minimally invasive techniques and without a cardiopulmonary bypass. To enable optimal therapy for patients, closer collaboration between cardiologists and cardiothoracic surgeons is required setting the stage for individualized therapy in the future.

[Diminishing borders between cardiology and cardiothoracic surgery: quo vadis?]. / Schwindende Fachgrenzen zwischen Kardiologie und Kardiochirurgie: Quo vadis?

UNLABELLED: Increasingly complex techniques in cardiovascular medicine lead to a competitive partnership between cardiology and cardiac surgery. Common challenges will arise in the fields of coronary heart disease, heart valves, heart failure and rhythm therapy. For instance, coronary revascularization in acute myocardial infarction is no longer considered to exclusively be an interventional option. In comparison, the implantation of heart valves is increasingly carried out by cardiologists using interventional techniques. The latest designs of sutureless valves try to combine the benefits of conventional and transcatheter heart valves. Heart failure is the most common reason for hospital admission and thus an important therapeutic target for cardiology and cardiac surgery. New approaches in diagnostics, heart assist devices and cellular therapy meet this challenge. CONCLUSION: In the future only a sensitive and transparent collaboration across transsectoral borders will offer optimal therapy in cardiovascular medicine.

Therapeutic use of ultrasound targeted microbubble destruction: a review of non-cardiac applications.

The development of second generation ultrasound contrast agents has extended the diagnostic scope of ultrasound imaging. Due to their physical characteristics, a therapeutic application of such microbubble based contrast agents has been promoted. Recently, several groups have demonstrated that ultrasound targeted microbubble destruction (UTMD) may deliver drugs or gene therapy vectors to organs accessible by ultrasound, thus providing a new technique for non-invasive, organ specific delivery of bioactive substances. Most applications in this field have been tested in cardiac models, but other organs can be treated as well. This article will give an overview of the background of UTMD and its non-cardiac applications.

Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

OBJECTIVE: To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. METHODS AND RESULTS: Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). CONCLUSION: MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

Intravascular ultrasound for evaluation of initial vessel patency and early outcome following directional coronary atherectomy.

Elastic recoil and thrombus formation may potentially occur following directional coronary atherectomy (DCA) confounding the assessment of late vascular remodeling. Since intravascular ultrasound (IVUS) data on early outcome of DCA is not available, we used IVUS to investigate whether elastic recoil or thrombus formation can affect early (4 hr) outcome. Quantitative coronary angiography (QCA) and IVUS were performed in high-grade coronary lesions in 32 consecutive patients before, immediately after, and 4 hr after DCA. Late clinical follow-up was obtained after a maximum interval of 2 years. Significant acute elastic recoil was observed by both IVUS (19%+/-14%) and QCA (19%+/-12%), but there was no further recoil after 4 hr. DCA reduced plaque area by 51%+/-13%, an effect that was stable after 4 hr, indicating the absence of relevant thrombus formation. Residual area stenosis by IVUS was not related to the occurrence of late clinical events (n = 8). Mechanical recoil or thrombus formation do not hamper initial lumen gain achieved by DCA. Although QCA significantly underestimated residual plaque burden after DCA when compared to IVUS, the degree of residual area stenosis did not identify patients suffering from cardiac events on follow-up.

Aortic pressure-diameter relationship assessed by intravascular ultrasound: experimental validation in dogs.

Intravascular ultrasound (IVUS) has emerged as an important diagnostic method for evaluating vessel diameter and vessel wall motion. To evaluate the validity of IVUS in assessing changes in the pressure-diameter relationship we compared measurements of abdominal aortic diameters derived from IVUS with those simultaneously obtained at the same site using implanted sonomicrometers in five chronically instrumented conscious dogs and in seven acutely instrumented anesthetized dogs. Five hundred eighty beats were analyzed to obtain peak systolic and end-diastolic diameters and to calculate aortic compliance at different blood pressure levels induced either by an aortic pneumatic cuff or by intravenous injections of nitroglycerin or norepinephrine. IVUS agreed closely with sonomicrometer measurements at different blood pressure levels. However, IVUS slightly but significantly underestimated aortic diameters by 0.6 +/- 0.7 mm for systolic diameters (P < 0.001) and by 0.7 +/- 0.6 mm for diastolic diameters (P < 0.001) compared with the sonomicrometer measurements. We conclude that IVUS is a feasible and reliable method to measure dynamic changes in aortic dimensions and has the potential to provide ready access to assess aortic compliance in humans.

Is the "candy-wrapper" effect of (32)P radioactive beta-emitting stents due to remodeling or neointimal hyperplasia? Insights from intravascular ultrasound.

A recognized limitation of radioactive stents is the development of restenosis at the stent edges, known as the "candy-wrapper" effect. The mechanisms of this effect remain incompletely understood and controversial. The aim of this study is to assess the effect of endovascular irradiation on neointima formation and vascular remodeling. (32)P Palmaz-Schatz stents (1.5-4 microCi) were implanted in 11 patients with restenosis after previous percutaneous transluminal coronary angioplasty (PTCA). Intravascular ultrasound (IVUS) images of target sites and adjunct vessel segments were acquired both during intervention and after 6 months. The angiographic restenosis rate was 54%, and the MLD decreased from 2.21 +/- 0.6 mm to 1.38 +/- 0.4 mm at follow-up (P < 0.01). IVUS analysis demonstrated that late lumen loss was the result of neointimal tissue proliferation, which was nonuniformly distributed and exaggerated at both the central articulation and the distal stent edges. Negative remodeling did not contribute to restenosis. In contrast, we found a linear relationship between increase of area stenosis and a positive remodeling index (r = 0.84, P < 0.0001). Restenosis after implantation of (32)P Palmaz-Schatz stents was mainly the result of neointimal tissue proliferation which tended to be nonuniformly distributed in the stent articulation and edges. Negative remodeling or stent recoil was not observed. Cathet Cardiovasc Intervent 2001;54:41-48.

Real-time myocardial contrast echocardiography for the detection of stress-induced myocardial ischemia. Comparison with 99mTc-sestamibi single photon emission computed tomography.

BACKGROUND: Real-time contrast echocardiography (MCE) is a new promising technique for assessing myocardial perfusion. The purpose of this study was to test whether realtime MCE can be used to detect functionally significant coronary artery stenosis in patients with known or suspected coronary artery disease. Myocardial contrast echocardiographic studies were compared with nearly simultaneous 99mTc-sestamibi single photon emission computed tomography (SPECT) as a clinical standard reference to evaluate regional myocardial perfusion defects. METHODS: Real-time MCE based on continuous infusion of Optison (8-10 ml/h) was performed in 66 patients during standard 99mTc-SPECT dipyridamole (0.56 mg/kg x 4 min) stress testing. Images were obtained in apical 4- and 2-chamber views, each divided into 6 segments. Tracer uptake and myocardial opacification were visually analyzed for each segment by two pairs of blinded observers and graded as normal, mildly reduced, severely reduced, or absent. In 792 myocardial segments, myocardial opacification by MCE was uninterpretable in 143 (18%) segments and tracer uptake by SPECT was not clearly defined in 92 (12%) segments. Interobserver variability for MCE was good with concordance rates of 83% (kappa=0.72) for rest- and 86% (kappa=0.76) for stress images. Overall concordance between MCE and SPECT was good (83%, kappa=0.63) at a segmental level. In the diagnosis of fixed and reversible defects, and of normal perfusion, concordance rates were 73, 65 and 83%, respectively. When analysis was performed at the regional level, we found comparable levels of concordance rates for LAD (83%, kappa=0.59), LCX (86%, kappa=0.64) and RCA (80%, kappa=0.68) perfusion territories. CONCLUSIONS: These findings suggest that realtime MCE is a clinically acceptable method to evaluate myocardial perfusion defects during dipyridamole stress testing.