Clinical Research In Cardiology Research Articles

ANMCO Position paper: States General 2023 - Role of ANMCO in the setting of clinical research in Cardiology in Italy: current state and future perspectives

For over 40 years, clinical research has been one of the most important aims of the Italian Association of Hospital Cardiologists (ANMCO), being an essential tool in pursuing promotion and fulfillment of good clinical practices in prevention, treatment and rehabilitation of cardiovascular diseases. Since 1992, with the creation of the Research Center (now part of the Heart Care Foundation), ANMCO is capable of independently and professionally managing all the aspects related to planning, management, and publication of the results of clinical studies. The other strength of ANMCO is the network built in Cardiology Departments on the whole territory of Italy, a human capital that allows ANMCO to deal with the new scientific challenges, in a context of profound changes in the social, economic, technological, and methodological setting. This document is based on the debate about the state of clinical research in Italy and the role of ANMCO in this setting that took place during the 2023 ANMCO States General.

Variability in research culture across busy catheterisation labs in the Asia-Pacific region.

Information related to research culture in the busy catheterisation (cath) labs across the Asia-Pacific (APAC) region is sparse. The aims of this study were to examine the variability in research culture in busy cath labs in the APAC region and to propose a roadmap for hospitals to develop in-house research capabilities in conjunction with industry and academia. Data related to research practices in the APAC region were collected from busy cath labs (at least 250 angioplasty/year) and analysed. Results were shared with research experts to understand the challenges in institutional research and create a roadmap for hospitals to develop research capabilities. A total of 220 respondents from 62 cath labs (88.6%) across 13 APAC countries participated in the survey. A wide variation was noted in research culture across APAC countries. Well-established infrastructure was reported in Australia, New Zealand, South Korea, Singapore, and Japan. Large multicentre trials were common in South Korea, while routine follow-ups were common in Japan. Linking medical records across hospitals/states was considered challenging. Research exposure and training were limited in the APAC region. The experts suggested a roadmap, including creating a conducive regulatory environment, forming synergistic goals, training programs for the professionals involved in research, and leveraging best practices, for improving the research culture in APAC. Clinical research in cardiology has grown significantly in the APAC region, with a huge research potential in China and India. Implementing measures to improve research training and involvement of the industry will boost the research culture in the APAC region.

Improvement in the Prediction of Coronary Heart Disease Risk by Using Artificial Neural Networks.

Cardiovascular diseases, such as coronary heart disease (CHD), are the main cause of mortality and morbidity worldwide. Although CHD cannot be entirely predicted by classic risk factors, it is preventable. Therefore, predicting CHD risk is crucial to clinical cardiology research, and the development of innovative methods for predicting CHD risk is of great practical interest. The Framingham risk score (FRS) is one of the most frequently implemented risk models. However, recent advances in the field of analytics may enhance the prediction of CHD risk beyond the FRS. Here, we propose a model based on an artificial neural network (ANN) for predicting CHD risk with respect to the Framingham Heart Study (FHS) dataset. The performance of this model was compared to that of the FRS. A sample of 3066 subjects from the FHS offspring cohort was subjected to an ANN. A multilayer perceptron ANN architecture was used and the lift, gains, receiver operating characteristic (ROC), and precision-recall predicted by the ANN were compared with those of the FRS. The lift and gain curves of the ANN model outperformed those of the FRS model in terms of top percentiles. The ROC curve showed that, for higher risk scores, the ANN model had higher sensitivity and higher specificity than those of the FRS model, although its area under the curve (AUC) was lower. For the precision-recall measures, the ANN generated significantly better results than the FRS with a higher AUC. The findings suggest that the ANN model is a promising approach for predicting CHD risk and a good screening procedure to identify high-risk subjects.

Clinical profile of patients with obstructive sleep apnea syndrome in a cardiology hospital

Obstructive sleep apnea syndrome (OSAS) is an important medical and social problem due to its high prevalence and impact on quality of life. The relationship between OSAS and cardiovascular pathology has been proven by many studies, which confirms the necessity for early diagnosis of OSAS and its treatment for the prevention of fatal and non-fatal events. to study epidemiological and clinical profile of the patients referred by a cardiologist to a specialized sleep laboratory to verify the diagnosis of OSAS. Object of study 527 patients aged 56.912.5 years who were hospitalized to the Myasnikov Clinical Cardiology Research Institute from 20162018 and had OSAS risk factors. Initially, complaints, medical history, anthropometric data were collected. As a screening survey, questionnaires were conducted using questionnaire scales. Verification of the diagnosis of OSAS and determination of the severity was carried out by cardiorespiratory or respiratory monitoring. Subsequently, 4 groups were formed depending on the presence and severity of OSAS. The prevalence of OSAS among patients in a cardiology hospital referred to a verification study was 88.6%. A comparative analysis of the groups revealed a progressive increase in the values of anthropometric indicators with increasing severity of OSAS. No differences were found between the groups by gender and daytime sleepiness on the Karolinska Sleepiness Scale. The average score on the Epworth sleepiness scale was statistically significantly lower only in the group of patients without OSAS when compared with the group with a severe degree of OSAS, and is comparable with the scores in the groups of mild and moderate degrees of OSAS. In a multivariate model of logistic regression, independent predictors of OSAS were identified as: age over 45 years, indications of loud intermittent snoring, frequent nightly urination, overweight or obesity. According to the results of assessing the incidence of various cardiovascular diseases in patients referred to the sleep laboratory, no significant differences were detected. At the same time, a significant difference was found in the frequency of obesity in patients with severe OSAS compared with other groups, as well as the frequency of type 2 diabetes mellitus or impaired glucose tolerance when compared with groups without OSAS, and with mild OSAS. In one-factor logistic regression models, it was found that the likelihood of having a severe degree of OSAS increases with increasing both comorbidity and age. High prevalence of OSAS in patients of a cardiological hospital, referred to a sleep laboratory for verification study, was confirmed. Considering the data that early diagnosis and treatment of OSAS can affect the course of both nosologies, the quality of life and prognosis of these patients, it is advisable to routinely screen and verify the diagnosis of OSAS in patients with cardiovascular diseases.

Factors associated with refusal or acceptance of older patients (≥ 65years) to provide consent to participate in clinical research in cardiology: a qualitative study.

Clinical research is an essential step in the successful translation of knowledge from basic research into concrete clinical applications, yet many people are reluctant to provide consent when actually approached to actively participate in clinical trials. We investigated the factors that influence older patient's (≥ 65years) decisions to accept or refuse to participate in a prospective randomized clinical trial in secondary prevention after acute coronary syndrome. Qualitative approach based on individual semi-structured interviews with patients who were approached for consent to participate in a currently ongoing clinical trial was adopted. Patients were interviewed after the consent process (8 accepted; 8 refused the trial). Interviews were analysed using grounded theory methodology. Sixteen patients aged ≥ 65years participated. The main concept to emerge from these interviews is that the actual trial itself does not appear to be the primary determinant in the decision to participate in clinical research. Rather, patients' decisions to participate (or not) in clinical research appear to be primarily determined by their capacity to deal with the current health event that has disrupted their life, and by their available mental and physical resources. Older patients display varying levels of engagement in their own health, ranging from low engagement with high trust in the medical profession, to high engagement mirrored by distrust of the medical profession. Structural conditions, such as personal benefit from trial participation, or logistic barriers to participation, seem to affect both accepters and refusers in the same manner.

Moving beyond regression techniques in cardiovascular risk prediction: applying machine learning to address analytic challenges.

Risk prediction plays an important role in clinical cardiology research. Traditionally, most risk models have been based on regression models. While useful and robust, these statistical methods are limited to using a small number of predictors which operate in the same way on everyone, and uniformly throughout their range. The purpose of this review is to illustrate the use of machine-learning methods for development of risk prediction models. Typically presented as black box approaches, most machine-learning methods are aimed at solving particular challenges that arise in data analysis that are not well addressed by typical regression approaches. To illustrate these challenges, as well as how different methods can address them, we consider trying to predicting mortality after diagnosis of acute myocardial infarction. We use data derived from our institution's electronic health record and abstract data on 13 regularly measured laboratory markers. We walk through different challenges that arise in modelling these data and then introduce different machine-learning approaches. Finally, we discuss general issues in the application of machine-learning methods including tuning parameters, loss functions, variable importance, and missing data. Overall, this review serves as an introduction for those working on risk modelling to approach the diffuse field of machine learning.

Endovascular treatment of acute limb ischemia caused by an intravascularly deployed bioabsorbable plug of a vascular closure device

Case reportEndovascular treatment of acute limb ischemia caused by an intravascularly deployed bioabsorbable plug of a vascular closure deviceDaniel Maxien, Barbara Behrends, Karla M. Eberhardt, Tobias Saam, Sven F. Thieme, Maximilian F. Reiser, and Marcus TreitlDaniel Maxien Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany Search for more papers by this author, Barbara Behrends Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany Search for more papers by this author, Karla M. Eberhardt Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany Search for more papers by this author, Tobias Saam Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany Search for more papers by this author, Sven F. Thieme Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany Search for more papers by this author, Maximilian F. Reiser Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany Search for more papers by this author, and Marcus Treitl Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany Search for more papers by this authorPublished Online:March 13, 2013https://doi.org/10.1024/0301-1526/a000260PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit SectionsMoreFiguresReferencesRelatedDetailsCited byEndovascular foreign body removal of a MynxGrip polyethylene glycol (PEG) sealant embolus using a cerebral stent retriever1 March 2021 | CVIR Endovascular, Vol. 4, No. 1Successful bailout procedure for acute popliteal artery occlusion associated with EXOSEAL® vascular closure device: a case report21 March 2019 | Journal of Medical Case Reports, Vol. 13, No. 1Large-scale experience with an anchorless vascular closure device in a real-life clinical setting8 October 2014 | Clinical Research in Cardiology, Vol. 104, No. 2A Novel Technique to Retrieve a Maldeployed Vascular Closure Device1 February 2015 | Journal of Endovascular Therapy, Vol. 22, No. 1 Volume 42Issue 2March 2013ISSN: 0301-1526eISSN: 1664-2872 InformationVasa (2013), 42, pp. 144-148 https://doi.org/10.1024/0301-1526/a000260.© 2013Hogrefe AGKeywordsVessel occlusionvascular closure deviceExoSealendovascular treatmentendovascular interventionacute limb ischemiaPDF download

The 2010 impact factor: the position of the Netherlands Heart Journal within Europe

In June 2011, the impact factors of the main journals were announced for the year 2010. These data can be found at http://isiknowledge.com/jcr (access limited to subscribers only). As previously indicated in this journal [1–3], the impact factor in a specific year consists of the average number of citations of publications in the previous two years divided by the number of publications (citable items) in these two years. Consequently, the impact factor of NHJ 2010 is the number of citations to NHJ articles published in 2008 and 2009, divided by the number of citable NHJ articles published in 2008 and 2009. The total number of citations over 2008 and 2009 was 191 (2008: 118 citations, 2009: 72 citations), whereas the total number of citable articles in this period was 132 (2008: 64, 2009: 68). As a result, the 2010 NHJ impact factor was calculated as 191/132 = 1.447 (almost 1.5). Although this is just a small step forward compared with the 2009 impact factor (1.392), it is still a significant achievement for a national journal that has only been listed by PubMed since January 2007 [4, 5]. It is encouraging to observe that the number of citations is steadily increasing over time (1 citation in 2007, 58 in 2008, 200 in 2009, 288 in 2010, and halfway through 2011 already 238 citations). At the same time, the number of citable items per year has remained fairly constant over the years, varying from 61 to 68, at least suggesting improvement in impact factor in the forthcoming years. What about the position of NHJ within Europe with particular emphasis on the role of NHJ as a Journal of a National Society (i.e. the Netherlands Society of Cardiology)? Several years ago the European Society of Cardiology (ESC) launched an Editors Network comprising all European National Society Cardiovascular Journals [6]. The main goals of the Editors Network were defined as 1) to increase collaboration among the Chief Editors of the National Society Journals, 2) to enhance editorial standards, 3) to improve quality requirements, 4) to preserve publication ethics, 5) to guarantee scientific credibility, and 6) to expand dissemination of scientific knowledge. At present, the Editors Network consists of 46 National Society Journals belonging to 40 ESC National Societies (some countries have more than one National Society Journal: Germany has 4 national journals, Russia 3). Of those 46 European journals, only 10 (22%) have an impact factor at this moment. When we list these journals according to impact factor, we get the following picture (journal, country, impact factor 2010, respectively): Basic Research in Cardiology, Germany, 6.128 Heart, United Kingdom, 4.706 Clinical Research in Cardiology, Germany, 3.466 Revista Espanola de Cardiologia, Spain, 2.157 Netherlands Heart Journal, Netherlands, 1.447 Archives des Maladies du Coeur et des Vaisseux, France, 1.207 Hellenic Journal of Cardiology, Greece, 1.172 Journal of Cardiovascular Medicine, Italy, 0.786 Acta Cardiologica, Belgium, 0.650 Kardiologia Polska – Polish Heart Journal, Poland, 0.523 What do we learn from these facts? First, it is an achievement in itself for a national society journal to have an impact factor, and second, the NHJ takes a very acceptable position among those national society journals that do have an impact factor. To conclude, we again thank all authors for their excellent contributions to the NHJ. Apparently, the quality of the papers was of such a level that they were read and -more importantly-cited by other authors. To improve our 2011 impact factor we hope to receive many more fine articles that deserve to be cited. In summary, the NHJ has again taken an important step on the way to international recognition.

Regenerative Medicine in Brazil: Small but Innovative

Although Brazil has received attention for conducting one of the world's largest stem cell clinical trials for heart disease, little has been published regarding Brazil's regenerative medicine (RM) sector. Here we present a comprehensive case study of RM in Brazil, including analysis of the current activity, the main motivations for engaging in RM and the remaining challenges to development in this field. Our case study is primarily based on semi-structured interviews with experts on RM in Brazil, including researchers, policymakers, clinicians, representatives of firms and regulators. Driven by domestic health needs and strategic government support, Brazil is producing innovative RM research, particularly for clinical research in cardiology, orthopedics, diabetes and neurology. We describe the main RM research currently taking place in Brazil, as well as some of the economic, regulatory and policy events that have created a favorable environment for RM development. Brazilian RM researchers need to overcome several formidable challenges to research: research funding is inconsistent, importation of materials is costly and slow, and weak linkages between universities, hospitals and industry impede translational research. Although Brazil's contribution to the RM sector is small, its niche emphasis on clinical applications may become of global importance, particularly if Brazil manages to address the challenges currently impinging on RM innovation.

Human Embryonic and Induced Pluripotent Stem Cells in Basic and Clinical Research in Cardiology

Human Embryonic or pluripotent stem cells hold many promises in regenerative medicine. They also provide the scientific community with powerful models of early human development including cardiogenesis under normal or pathological (congenital and genetic diseases) situations. Furthermore their cardiac derivatives turn out to be very useful to study human cardiac electrophysiology, pharmacology or cardiac toxicology. The current overview provides the basic knowledge on developmental biology of the heart which can be applied to stem cell research to study early cardiogenesis. We summarize both the cardiogenic transcriptional network and the role of morphogens involved in early cardiogenesis. We review protocols of cardiac differentiation of pluripotent stem cells so far available. We finally discuss the translation of basic stem cell research into clinical applications.

Cardiac Contusion in a Professional Soccer Player

We report here the case of a 30-year-old professional soccer player who presented to our hospital after sustaining a blunt chest trauma. To the best of our knowledge, this is the first reported case of cardiac contusion when acute myocardial edema and subsequent chronic myocardial injury were visualized with cardiac magnetic resonance (CMR) imaging. A professional soccer player presented to our hospital with persistent chest pain and fatigue after being hit in the chest by a soccer ball during a national league game. The hospital admission was 10 hours after the accident and onset of symptoms. The patient had no medical history and no recent history of infectious disease. The initial workup revealed elevated cardiac troponin T of 0.576 μg/L (normal range, 0.00 to 0.03 μg/L) and creatine kinase-MB levels of 25.4 U/L (normal range, 0 to 25 U/L); the markers of inflammation proved to be negative (C-reactive protein level, 0.9 mg/L [normal range, 0 to 5.0 mg/L]; white blood cell count, 7.0×103/μL [normal range, 4 to 10×103/μL]). The patient underwent a performance-enhancing drug screening 8 days before the event as part of the regular doping control protocol of professional soccer players, which proved to be negative. Furthermore, the toxicology panel testing for 7 drugs (phencyclidine, barbiturates, cannabinoids, amphetamines, benzodiazepines, …

The year 2009 in Clinical Research in Cardiology

Clinical Research in Cardiology is going to enter its fourth year as the journal of the German Cardiac Society with a focus on scientific aspects of clinical research and clinical education in cardiology. It is a member of the Journals’ Club of the European National Societies, who reported their principles of publication in 2008 [1]. Compared to the year 2008 [2], the journal has further improved its visibility as shown by the latest data from the Institute for Scientific Information (ISI). As evidenced by the increased number of submitted manuscripts, there is evidence that there is an increased acceptance in the scientific community of clinical cardiology. From 1 December 2008 until 30 November 2009, 372 papers were submitted (including 39 resubmissions from 2008). The acceptance rate was 30.5% corresponding to 69.5% rejection rate. Time to first decision was 31.4 days. During the last year, 692 reviews were invited. Among those, 453 reviewers completed their reviews and 138 declined to review the manuscripts. 34 reviewers did not respond to the invitation. The majority of manuscripts were accepted or rejected after initial submission or after first revision. The details can be viewed in Table 1. Figure 1 shows the number of impact factor relevant articles from 2006 to 2009. These types of articles only include reviews and original papers but not clinical correspondence contributions, editorials and abstracts. There was a decline in the number of published reviews and original papers, whereas the number of clinical correspondence articles, editorials and abstracts remained similar (not shown). In parallel, citations steadily increased from 2006 to 2009 from 31 to 726 (the column in 2009 covered all articles which were published until 30 November 2009). These citations also include the impact factor relevant articles as well as clinical correspondence articles, which also contribute to the impact factor in a positive way when they are cited. The number of citations includes all citations of previously published articles in Clinical Research in Cardiology. For the impact factor 2009 (which will be published in 2010) only the citations to articles of the publication years 2007 and 2008 will be relevant. Figure 2 summarizes the impact factor of the ‘‘Zeitschrift fur Kardiologie’’ (left panel) and of Clinical Research in Cardiology (right panel). The impact factor in 2008 is already higher than those ever achieved by the ‘‘Zeitschrift fur Kardiologie’’. However, much to our satisfaction, the impact factor 2008, published in 2009 by the Institute for Scientific Information was 2.418 indicating that the development of the journal’s visibility reflected by citations of articles of the relevant years is improving. Again, there was a list of well-published articles. In Table 2, the ten best cited articles from the years 2007 and 2009 are listed. It can be seen that those articles published already in 2007 tended to have higher citation numbers. However, some articles are also well cited after the first years of publication [5, 9, 10]. Among the best publications, there were not only original articles [3, 6, 8, 9, 12] but also reviews [4, 5, 10, 11] and one article as a meeting update [7]. In particular, from those recently published M. Bohm (&) H. Katus Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Kirrberger Str. 1, 66424 Homburg/Saar, Germany e-mail: boehm@uks.eu

A Novel Measurement Index for Antihypertensive Medication Burden and Its Use

To the Editor: With the widespread use of blood pressure medications, it has become extremely difficult to assess the effects of elevated blood pressure on physiological and pathological phenomena without the confounding effects of antihypertensives. In both observational studies and randomized clinical trials, attempts to account for the antihypertensive effects have ranged from overly simplified dichotomous measures (either on or not on treatment) to tedious formulas that, in most instances, cannot be calculated in the population studied. Here, we propose a novel yet simple measurement index that not only takes into consideration whether an individual is on treatment but also accounts for the number and doses of each antihypertensive medication taken. We are suggesting that this measure maybe superior to the dichotomous measure and can be used to prospectively assess changes in blood pressure treatment. The developed measure was used in an ongoing trial, the Antihypertensive and Vascular, Endothelial, …

Careers in Basic Cardiovascular Research

Received August 2, 2008; accepted January 28, 2009. The opportunities in basic science for graduating PhD students and for aspiring physician-scientists have never been so extraordinary. The sequencing of the human genome and the development of the human haplotype map have enabled scientists to begin to unravel the basis of complex multigenic disorders. Rapid developments in stem cell biology are affecting many areas of cardiovascular biology and may enable repair of injured myocardium. High-throughput chemical genetic screening, proteomics, and metabolomics are changing the approaches with which investigators characterize novel signal transduction pathways and develop new therapeutic paradigms. Rapidly evolving molecular imaging technologies are noninvasively illuminating the fundamental processes contributing to cardiovascular diseases. New insights into the mechanisms involved in cardiac myocyte hypertrophy and dysfunction have important therapeutic implications for an expanding population of patients with congestive heart failure. For the young scientist looking to the future, there are major benefits in pursuing a basic science career including the excitement of discovery, the opportunity for life-long learning, and the potential to broadly affect cardiovascular science and medicine. On the other hand, the young investigator considering a basic science career is confronted by many challenges. The budget of the National Institutes of Health (NIH) has remained essentially unchanged for 5 years (when the impact of inflation is considered). The success rate of R01 grant applications has consistently declined since 2000, and the average age when an investigator receives a first R01 grant (or equivalent) increased to 42.6 in 2007 (NIH Extramural Data Book at www.report.nih.gov/index.aspx). At the same time, the increased costs of undergraduate and medical school educations have burdened potential young investigators with ever-increasing financial commitments. Many academic leaders have suggested that an entire generation of young scientists is “at risk” (www.BrokenPipeline. org). Long hours at the laboratory bench are compensated …

The year in Clinical Research in Cardiology

The year in Clinical Research in Cardiology

Implications and Treatment of Acute Hyperglycemia in the Setting of Acute Myocardial Infarction

A 52-year-old obese male without a prior history of diabetes mellitus (DM) presented with angina and an anterior ST-segment–elevation myocardial infarction (STEMI). Physical examination and chest x-ray were consistent with congestive heart failure. Admission glucose was 230 mg/dL. Coronary angiography revealed an occluded left anterior descending coronary artery, and stenting reestablished TIMI grade 2 flow in that artery within 90 minutes of symptom onset. Left ventricular ejection fraction was 35% with severe anterior hypokinesis. Peak creatine kinase was 600 IU. The next day, fasting glucose was 180 mg/dL. An echocardiogram performed 6 weeks after discharge revealed an ejection fraction of 35% without change in the anterior wall motion. Fasting glucose as an outpatient was 156 mg/dL. The scenario described above is commonly encountered and illustrates how hyperglycemia can affect the outcome of patients with STEMI. Hyperglycemia could have affected the following features of this case: (1) Congestive heart failure was present despite only modest myocardial injury by creatine kinase level; (2) despite successful percutaneous coronary intervention, subnormal coronary perfusion was observed; and (3) left ventricular recovery after STEMI did not occur. Cardiologists need to be cognizant of the hazards associated with hyperglycemia in this setting because these patients will be encountered more frequently as a result of the increasing prevalence of insulin resistance syndromes. Acute hyperglycemia is common in patients with STEMI even in the absence of a history of type 2 DM. Hyperglycemia is encountered in up to 50% of all STEMI patients, whereas previously diagnosed DM is present in only 20% to 25% of STEMI patients.1 The prevalence of type 2 DM or impaired glucose tolerance may be as high as 65% in MI patients without prior DM when oral glucose tolerance testing is performed.2 Elevated …

Parvovirus B19–Associated Active Myocarditis With Biventricular Thrombi Results of Endomyocardial Biopsy Investigations and Cardiac Magnetic Resonance Imaging

A previously healthy 39-year-old man was admitted to our department with biventricular cardiac decompensation (New York Heart Association class IV) and acute onset of angina pectoris after a flulike disease 1 week earlier. The ECG on admission displayed ST elevations in II, III, and aVF. Troponin T on admission was increased (2.20 mg/L, normal value<0.03 mg/L), with increased creatine phosphokinase (503 U/L; normal value<171 U/L) and creatine phosphokinase myocardial band (45 U/L; normal value=10 U/L). N-terminal pro-brain natriuretic peptide was highly elevated (15,848 pg/mL; normal value<125 pg/mL). Coronary artery disease was excluded by coronary angiography. Multiple nonsustained ventricular tachycardias were recorded by Holter monitoring and telemetry. Endomyocardial biopsies obtained from the right ventricular septum demonstrated active myocarditis by histological investigations according to the Dallas criteria (Figure 1A). By immunohistological staining of endomyocardial biopsies1 and quantification using digital image analysis, highly increased focal lymphocytic (CD3+: 267.4/mm2, CD11a/LFA-1+: 498.9/mm2; Figure 1B) and macrophage infiltrates (CD11b/Mac-1+: 481.6/mm2), sarcolemmal human leukocyte antigen class I expression (area fraction of human leukocyte antigen class I=35.6%; Figure 1C), and focal abundance …

Left Main Coronary Revascularization at the Crossroads

Percutaneous revascularization of left main coronary artery (LMCA) disease has remained controversial for more than 25 years, since LMCA balloon angioplasty was first performed by Andreas Gruentzig in 1978. Summarizing his experience, Gruentzig concluded, “We have not been too successful with dilating left main stems…although the procedure is relatively simple, the potential complications are both sudden and serious.”1 Following the evolution of percutaneous catheter-based therapies to include both bare metal stent and, more recently, drug-eluting stent (DES) platforms in conjunction with advances in periprocedural and postprocedural adjunctive pharmacotherapies, interest in percutaneous LMCA revascularization, particularly unprotected left main, has been renewed. Although studies performed with bare metal stents demonstrated a low rate of in-hospital mortality, the incidence of late coronary restenosis remained high.2–6 In the Unprotected Left Main Trunk Intervention Multi-Center Assessment (ULTIMA) registry, which enrolled 279 patients with unprotected LMCA disease who had percutaneous coronary revascularization (69% bare metal stent), mortality at a 1-year follow-up was proportional to clinical risk stratification (40% in high-risk versus 3.5% in low-risk patient cohorts), and repeated revascularization was required in 34% of cases.6 The experience gleaned from these studies continued to support the American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations that in reasonable surgical candidates with LMCA disease, coronary bypass surgery is the preferred therapeutic option.7 After the introduction of DES, several small clinical series demonstrated the feasibility and short-term safety of LMCA stenting, while late clinical/angiographic outcomes appeared favorable as compared with historical (nonrandomized) patient cohorts treated with bare metal stents.3,8–11 The cumulative experience with DES treatment for LMCA demonstrated an apparent marked reduction in major adverse cardiovascular events, including target vessel revascularization, during 6 to 12 months of follow-up as compared with the precedent experience after bare metal stent deployment. Article p 2542 The clinical …

Life and Death of Cardiac Stem Cells

The recognition that myocyte mitosis occurs in the fetal, neonatal, adult, and hypertrophied heart and that a pool of primitive, undifferentiated cells is present in the myocardium has put forward a different view of the biology of the heart. The new paradigm suggests that myocyte formation is preserved during postnatal life, in adulthood or senescence, pointing to a remarkable growth reserve of the heart throughout the course of life of the organism. This article reviews a large body of novel information, which has been obtained in the last 2 decades, in favor of the notion that the mammalian heart has the inherent ability to continuously replace its parenchymal cells and that this unexpected characteristic has important implications in understanding myocardial homeostasis, cardiac aging, and tissue repair. The paradigm that the heart is a postmitotic organ incapable of regenerating parenchymal cells was established in the 1970s, and this dogma has profoundly conditioned basic and clinical research in cardiology for the last 3 decades. On the basis of this paradigm, cardiomyocytes undergo cellular hypertrophy1,2 but cannot be replaced either by entry into the cell cycle of a subpopulation of nonterminally differentiated myocytes or by activation of a pool of primitive cells that become committed to the myocyte lineage. The only response of cardiomyocytes to stress is hypertrophy and/or death. Therefore, a tremendous effort was made to identify the molecular mechanisms of myocyte hypertrophy and their genetic control. A sophisticated knowledge of various signaling pathways has been achieved, and our understanding of the biology of hypertrophic myocyte growth has advanced markedly.3 An array of new technologies has been introduced that has led to a scientific revolution in terms of questions, approaches, and interpretation of experimental results. Despite this enormous progress in our understanding of basic mechanisms of hypertrophy, however, very little …

Cast of Complex Congenital Heart Malformation in a Living Patient

Magnetic resonance imaging data of a 20-year-old male patient was used to produce, to the best of our knowledge, the first cast model of a beating heart. Imaging was performed at the German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology; data were transferred to the Department of Medical and Biological Informatics (German Cancer Research Center, Heidelberg). The patient had the diagnoses of dextrocardia, atrial and visceral situs inversus, L-looped ventricles, and L-malposition of the great arteries, with a large perimembranous ventricular septal defect and pulmonary atresia. A 3D whole-heart, navigator-corrected MRI data set …