Coronary intravascular lithotripsy and rotational atherectomy for severely calcified stenosis: Results from the ROTA.shock trial.

BACKGROUND: Severely calcified coronary lesions present a particular challenge for percutaneous coronary intervention. AIMS: The aim of this randomized study was to determine whether coronary intravascular lithotripsy (IVL) is non-inferior to rotational atherectomy (RA) regarding minimal stent area (MSA). METHODS: The randomized, prospective non-inferiority ROTA.shock trial enrolled 70 patients between July 2019 and November 2021. Patients were randomly (1:1) assigned to undergo either IVL or RA before percutaneous coronary intervention of severely calcified coronary lesions. Optical coherence tomography was performed at the end of the procedure for primary endpoint analysis. RESULTS: The primary endpoint MSA was lower but non-inferior after IVL (mean: 6.10 mm2 , 95% confidence interval [95% CI]: 5.32-6.87 mm2 ) versus RA (6.60 mm2 , 95% CI: 5.66-7.54 mm2 ; difference in MSA: -0.50 mm2 , 95% CI: -1.52-0.52 mm2 ; non-inferiority margin: -1.60 mm2 ). Stent expansion was similar (RA: 0.83 ± 0.10 vs. IVL: 0.82 ± 0.11; p = 0.79). There were no significant differences regarding contrast media consumption (RA: 183.1 ± 68.8 vs. IVL: 163.3 ± 55.0 mL; p = 0.47), radiation dose (RA: 7269 ± 11288 vs. IVL: 5010 ± 4140 cGy cm2 ; p = 0.68), and procedure time (RA: 79.5 ± 34.5 vs. IVL: 66.0 ± 19.4 min; p = 0.18). CONCLUSION: IVL is non-inferior regarding MSA and results in a similar stent expansion in a random comparison with RA. Procedure time, contrast volume, and dose-area product do not differ significantly.

[Future of interventional cardiology : Does everything revolve around AI and robotics?] / Zukunft der interventionellen Kardiologie : Dreht sich alles um KI und Robotik?

In recent years, software-assisted imaging systems, such as computed tomography, have contributed to the improvement of noninvasive options for the diagnostics of coronary heart disease (CHD). In addition, the possibilities of individual morphological and functional atherosclerotic plaque evaluation could be further refined, e.g. by the use of optical coherence tomography or the quantitative flow ratio (QFR). Due to the development of robotic-assisted catheter systems, it has been possible to make coronary interventions more precise and with less radiation exposure for the examiner. It is to be expected that in the future even better algorithms will be developed by the analysis of very large amounts of data. These will enable a more exact, dynamic and personalized prediction of, e.g. treatment success or individual risk profiles, in order to positively and sustainably influence the treatment of patients with cardiovascular diseases.

Everolimus- vs. novolimus-eluting bioresorbable scaffolds in patients with acute coronary syndrome.

BACKGROUND: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb). METHODS: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed. RESULTS: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure. CONCLUSION: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.

[Heart valve disesases : How sufficient is the knowledge of the German population?] / Herzklappenerkrankungen : Wie aufgeklärt ist die deutsche Bevölkerung?

To evaluate the awareness and knowledge of the German population regarding diseases in general, a survey of 1446 people aged 60 years or older was conducted in 14 German towns. The focus was on heart valve diseases with special emphasis on aortic valve stenosis (AS). While cancer was the disease that respondents were most concerned about (25.2%), only 3.3% were concerned about heart valve diseases. In this respect, the knowledge was broadly limited: only 7.4% of participants claimed to have some familiarity with heart valve diseases and only 12.5% could correctly describe the symptoms of AS. Even so, 35.0% of the participants could correctly name the number of human heart valves, 71.6% knew at least one therapy option for AS and 30.6% were familiar with transcatheter aortic valve implantation (TAVI). After providing a brief clarification of the prevalence, symptoms and course of AS, 45.6% of respondents were more concerned about the condition, 15.7% wanted to know more about the symptoms of AS and 4.7% even recognized the typical symptoms in themselves. Most of the participants would like to seek more information preferably in discussion with a specialist physician (77.2%), with their general practitioner (43.2%) or using the internet (29.7%). Despite its high prevalence, high morbidity and mortality, the vast majority of the German population were neither concerned nor fully aware of treatment options for AS. There is a strong case for public awareness campaigns that provide better knowledge of AS, and support check-ups that enable timely treatment and the avoidance of unnecessary hospitalization and death.

Temporal trends in transcatheter and surgical aortic valve replacement : An analysis of aortic valve replacements in Germany during 2012-2014.

This analysis of the data of the obligatory quality assurance programme AQUA shows the perioperative risk as well as the procedural outcome evaluated by the observed versus expected in-hospital mortality ratio (O/E ratio) of 62,872 patients undergoing isolated surgical (sAVR), transcatheter transvascular (TV-), or transapical (TA-) aortic valve replacement (TAVI) from 2012 to 2014 in Germany. The number of TAVI procedures increased from 9,352 in 2012 to 13,278 in 2014, whereas the number of sAVR remained constant (2012: 9,949; 2014: 9,953). Between 2012 and 2014, the number of TAVI implanted in patients with a logistic EuroScore I (logESI) of ≤10 % (2012: 21 %; 2014: 26 %) as well as with a logESI <20 % (2012: 57 %; 2014: 64 %) increased. In-hospital mortality in TAVI patients decreased from 5.2 % (TV: 5.0 %; TA: 7.4 %) in 2012 to 4.2 % (TV: 3.8 %; TA: 5.5 %) in 2014, whereas it was stable for sAVR patients (2012: 2.8 %; 2014: 2.6 %). The O/E ratio of TAVI patients decreased from 0.91 (TV: 0.79; TA: 1.2) to 0.73 (TV: 0.69; TA: 0.89), whereas this ratio remained constant for sAVR patients (2012: 0.92; 2014: 0.93). In summary, estimated surgical risk, in-hospital mortality, as well as the O/E ratio for patients undergoing TAVI declined constantly during the last 3 years.

[Computed tomography in patients with chronic stable angina : Fractional flow reserve measurement]. / Computertomographie bei Patienten mit stabiler Angina Pectoris : Messung der fraktionellen Flussreserve.

Coronary computed tomography angiography (cCTA) has been established for the non-invasive diagnosis of coronary artery disease (CAD). Previous studies demonstrated the high diagnostic accuracy of cCTA, particularly for ruling out CAD. As a known limitation of cCTA a large number of visually significant coronary stenoses are found to be hemodynamically not relevant by invasive fractional flow reserve (FFR). CT-based FFR (CT-FFR) builds on recent advances in computational fluid dynamics and image simulation techniques. Along with CT myocardial perfusion imaging, CT-FFR is a promising approach towards a more accurate estimation of the hemodynamic relevance of coronary artery stenoses. CT-FFR is derived from regular CT datasets without additional image acquisitions, contrast material, or medication. Two CT-FFR techniques can be differentiated. The initial method requires external use of supercomputers and has gained approval for clinical use in the USA. Furthermore, a prototype-software has been introduced which is less computationally demanding via integration of reduced-order models for on-site calculation of CT-FFR. The present article reviews these methods in the context of available study results and meta-analyses. Furthermore, limitations and future concepts of CT-FFR are discussed.

[Bifurcation lesions : How should they be assessed and treated?] / Bifurkationsläsionen : Wie beurteilen ­ wie vorgehen?

Bifurcation lesions are a therapeutic challenge in the interventional treatment of coronary artery disease. Thus, consideration of anatomical aspects and selection of the most appropriate strategy for an individual bifurcation have an impact on the interventional outcome. Accordingly, assessment of the type of bifurcation stenosis, including the relevance of the side branches, vessel diameter and the angle between the two branches are critical for the optimal choice of interventional strategy. The fractional flow reserve (FFR) is a parameter that provides a measure of the severity of coronary stenosis and despite some limitations, FFR can be applied to bifurcation lesions. In addition, intravascular imaging tools, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can be used to determine anatomical configurations.

[Myocardial revascularization]. / Myokardrevaskularisation.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality in western countries and is of significant socio-economic importance due to its increasing prevalence. Until percutaneous coronary interventions (PCI) were established, CAD could only be treated by surgical revascularization or pharmacological therapy. In-stent restenosis remains a major problem after stent implantation. However, the use of new materials and stent coatings have led to a significant reduction in in-stent restenosis. Thus, surgical revascularization and PCI are currently of equal value for the treatment of CAD. The decision-making for PCI or surgical revascularization depends on various factors such as number of diseased vessels, complexity of the coronary stenoses, concomitant diseases, and the patient's general condition. The therapeutic regime of every patient should be adjusted to the recommendations of the European and German Society for Cardiology, while controversial and complex cases should be discussed in an interdisciplinary case conference ("heart team").

[Transcatheter aortic valve implantation (TAVI)]. / Transkatheteraortenklappenersatz (TAVI).

Aortic valve stenosis (AS) is the most common acquired valve disease in the industrialized countries. Most patients--especially young and low-risk patients--can be safely and effectively operated with aortic valve replacement. Due to increasing life expectancy, however, the number of elderly patients with AS and various concomitant diseases will increase in the coming decades. For those elderly high-risk patients, transfemoral or transapical aortic valve implantation (TAVI) has evolved as a valuable alternative to conventional surgery. The TAVI approach has been shown to be superior to standard medical treatment in these high-risk patients. All patients considered for TAVI should be discussed in a consensus conference consisting of cardiac surgeons and cardiologists (heart team). Furthermore, for successful treatment with transcatheter techniques, sophisticated pre-interventional imaging is required to screen patients. Available data on TAVI from randomized trials and large-scale registries demonstrate that this method is very promising.

[Transcutaneous aortic valve implantation]. / Kathetergestützte Aortenklappenimplantation.

Due to increasing life expectancy in the coming decades the number of elderly patients with aortic valve stenosis (AS) and various concomitant diseases will increase. Conventional surgical aortic valve replacement represents the treatment of choice in patients with severe and symptomatic AS. Transfemoral and transapical aortic valve implantation (T-AVI) has evolved as a standard procedure for patients with severe AS who are technically inoperable or at very high risk for surgical valve replacement. The T-AVI approach has been shown to be superior to the standard medical treatment in these high-risk patients. All patients to be considered for T-AVI should be discussed in a consensus conference consisting of cardiac surgeons and cardiologists (heart team).

[Myocardial revascularization]. / Myokardrevaskularisation.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality in western countries and is of significant socio-economic importance due to its increasing prevalence. Until percutaneous coronary interventions (PCI) were established, CAD could only be treated by surgical revascularization or pharmacological therapy. In-stent restenosis remains a major problem after stent implantation. However, the use of new materials and stent coatings have led to a significant reduction in in-stent restenosis. Thus, surgical revascularization and PCI are currently of equal value for the treatment of CAD. The decision-making for PCI or surgical revascularization depends on various factors such as number of diseased vessels, complexity of the coronary stenoses, concomitant diseases, and the patient's general condition. The therapeutic regime of every patient should be adjusted to the recommendations of the European and German Society for Cardiology, while controversial and complex cases should be discussed in an interdisciplinary case conference ("heart team").

Stem cell-mediated natural tissue engineering.

Recently, we demonstrated that a fully differentiated tissue developed on a ventricular septal occluder that had been implanted due to infarct-related septum rupture. We suggested that this tissue originated from circulating stem cells. The aim of the present study was to evaluate this hypothesis and to investigate the physiological differentiation and transdifferentiation potential of circulating stem cells. We developed an animal model in which a freely floating membrane was inserted into each the left ventricle and the descending aorta. Membranes were removed after pre-specified intervals of 3 days, and 2, 6 and 12 weeks; the newly developed tissue was evaluated using quantitative RT-PCR, immunohistochemistry and in situ hybridization. The contribution of stem cells was directly evaluated in another group of animals that were by treated with granulocyte macrophage colony-stimulating factor (GM-CSF) early after implantation. We demonstrated the time-dependent generation of a fully differentiated tissue composed of fibroblasts, myofibroblasts, smooth muscle cells, endothelial cells and new blood vessels. Cells differentiated into early cardiomyocytes on membranes implanted in the left ventricles but not on those implanted in the aortas. Stem cell mobilization with GM-CSF led to more rapid tissue growth and differentiation. The GM-CSF effect on cell proliferation outlasted the treat ment period by several weeks. Circulating stem cells contributed to the development of a fully differentiated tissue on membranes placed within the left ventricle or descending aorta under physiological conditions. Early cardiomyocyte generation was identified only on membranes positioned within the left ventricle.

Calcium-dependent signalling is essential during collateral growth in the pig hind limb-ischemia model.

We investigated the effect of pharmacological activation of the Ca(2+)-channel transient receptor potential cation channel, subfamily V, member 4 (TRPV4) on collateral growth in a pig hind limb-ischemia model thereby identifying subcellular mechanisms. Domestic pigs received femoral artery ligature and were randomly assigned to one of the following groups (each n=6): (1) 4alpha-phorbol 12,13-didecanoate (4alphaPDD) treatment; (2) treatment with an arterio-venous shunt (AV-shunt) distal to the occlusion; or (3) implantation of NaCl-filled minipump. Six sham-operated pigs acted as controls. Aortic and peripheral mean arterial pressure (MAP) measurements were performed to assess the collateral flow index (CFI). Tissue was isolated from M. quadriceps for immunohistochemistry and from isolated collateral arteries for quantitative real time PCR (qRT-PCR). Shortly after ligature the CFI dropped from 0.96+/-0.02 to 0.21+/-0.02 in all ligature-treated groups. In ligature-only-treated pigs CFI increased to 0.56+/-0.03 after 7days. Treatment with 4alphaPDD led to an enhancement of CFI compared with ligature alone (0.73+/-0.03). CD31-staining showed improved arteriolar density. Increased Ki67 staining in collaterals indicated proliferation. qRT-PCR and Western blot analysis showed upregulation or modulation of Ca(2+)-dependent transcription factors nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), Kv channel interacting protein 3, calsenilin (KCNIP3/CSEN/DREAM), and myocyte enhancer factor 2C (MEF2C) in 4alphaPDD- and AV-shunt-treated pigs compared with controls. Improved CFI after 4alphaPDD treatment identifies TRPV4 as an initial fluid shear-stress sensor and collateral remodelling and growth trigger. Subcellularly, modulation of Ca(2+)-dependent transcription factors indicates a pivotal role for Ca(2+)-signalling during arteriogenesis.

[Historical and current pathophysiological concepts of stress (Tako-Tsubo) cardiomyopathy]. / Historische und gegenwärtige pathophysiologische Konzepte der Tako-Tsubo-Kardiomyopathie.

Tako-Tsubo cardiomyopathy (TTC), also referred to as stress cardiomyopathy (SCM), was first described in the 1990s and is characterized by transient left ventricular dysfunction. Its incidence represents 1-2% of all acute coronary syndromes (ACS). In most cases extreme emotional or physical stress precedes this syndrome. The majority of patients affected are postmenopausal women. Since its first description, various hypotheses regarding the pathophysiology of TTC have been discussed. From a historical perspective, coronary vasospasm has often been proposed as a possible cause of this disorder. However, reviews from numerous registries were able to demonstrate that coronary vasospasm plays only a minor role in the pathogenesis of TTC. Several groups showed disturbances in myocardial microcirculation and energy metabolism in the acute phase of TTC. Nevertheless, with regard to the data currently available, it cannot be differentiated whether these changes are the cause or rather the result of TTC. However, recent concepts include an excessive catecholamine overload and morphological changes which are unequivocally documented in TTC. The relation between elevated catecholamine levels and myocardial dysfunction analogous to TTC could be confirmed in animal experiments.In summary, it can be assumed that TTC is caused by an excessive cardiotoxic release of catecholamines. Ventricular dysfunction can be explained by increased numbers of ß-adrenergic receptors in the apex, leading to greater vulnerability to catecholamine overload. Individual anatomical differences in the sympathoadrenergic system and distribution from ß-adrenergic receptors are presumably responsible for the interindividual occurrence of wall motion abnormalities in TTC.

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.

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 alpha, interleukin 6, interleukin 1beta) 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 alpha, 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.

Desynchronization: a novel model to induce heart failure.

BACKGROUND: Previous large animal heart failure models led to inhomogeneous results. Therefore, we developed a novel model combining rapid pacing with forced ventricular desynchronization. METHODS: Heart failure was induced in 20 pigs during a pacing period of 21 days. Group A (n = 10) received one right ventricular lead (220 bpm). In group B (n = 10), two leads were implanted in different right ventricular regions with beat-to-beat alternation of activation sites (each lead 110 bpm). Sham-operated pigs (n = 6) served as controls. Hemodynamics were invasively evaluated and tissue was analyzed by immunohistochemistry and zymography. RESULTS: Hemodynamics were significantly more impaired in group B with an increase of pulmonary capillary wedge and central venous pressure and a reduction of cardiac index (control 4.3 +/- 0.1 l/min/m (2); A 3.6 +/- 0.2; B 2.9 +/- 0.2, P < 0.05). Heart-to-body weight ratio was significantly higher in group B. Histological analyses showed a significant increase of cell diameters and interstitial fibrosis with significantly higher collagen contents in group B. CONCLUSION: The new model with a combination of rapid pacing and forced desynchronization of the ventricular contraction is superior to traditional heart failure models induced solely by rapid pacing.

Effects of 2-deoxy-D-glucose on proliferation of vascular smooth muscle cells and endothelial cells.

2-Deoxy-D-glucose (2-DG) is a glucose analogue that has been proposed for cancer therapy due to its cytostatic properties. Its effect on the proliferation of smooth muscle cells and endothelial cells has not been fully clarified. The aims of this study were to investigate the effects of 2-DG on the proliferation of porcine aortic endothelial cells (PAEC) and porcine smooth muscle cells (PSMC), to establish an overview of its dose-dependent inhibitory capacity and to examine whether the short-term incubation of cells with 2-DG has an impact on cell proliferation in culture. Our results showed a dose-dependent significant inhibitory effect on proliferation, which was more pronounced in PSMC than in PAEC. Even after short-term incubation of cells with 2-DG, relevant inhibition of proliferation was documented. The clinical application of 2-DG might be a promising concept by inhibiting cells that show a potentially rapid proliferation in response to non-malignant stimuli, such as smooth muscle cells after intracoronary stenting.