Field Of Cardiovascular Medicine Research Articles

Murine models of myocardial and limb ischemia: Diagnostic end-points and relevance to clinical problems

Ischemic disease represents the new epidemic worldwide. Animal models of ischemic disease are useful because they can help us to understand the underlying pathogenetic mechanisms and develop new therapies. The present review article summarizes the results of a consensus conference on the status and future development of experimentation in the field of cardiovascular medicine using murine models of peripheral and myocardial ischemia. The starting point was to recognize the limits of the approach, which mainly derive from species- and disease-related differences in cardiovascular physiology. For instance, the mouse heart beats at a rate 10 times faster than the human heart. Furthermore, healing processes are more rapid in animals, as they rely on mechanisms that may have lost relevance in man. The main objective of the authors was to propose general guidelines, diagnostic end points and relevance to clinical problems.

Application of Hematopoietic Cells to Therapeutic Angiogenesis

Despite considerable progress in the field of cardiovascular medicine and surgery, ischemic heart disease is still the leading cause of death in advanced countries. In this context, it is no wonder why therapeutic angiogenesis, a way to ameliorate ischemic tissue from suffering dysfunction by increasing new blood vessels, gains so much attention from both clinicians and patients. In this review, we will briefly go through a decade of history in therapeutic angiogenesis including unraveling of its mechanisms, results obtained from clinical trials, and lessons learned from earlier investigations. We will then focus on an emerging, yet rapidly evolving field of hematopoietic cell therapy. Recent excellent studies seem to have brought us to the place where we might save so many patients from burden of ischemia, we should be aware that there are some controversies, and sometimes misunderstandings, regarding how or why this treatment does actually work, and what better way should we explore in order to get the best of its efficacy. With these caveats in mind, we will investigate the works elucidating the mechanisms and clinical efficacies of hematopoietic cell therapy.

Does Blood Pressure Control Contribute to a More Successful Aging?

In developed countries, life expectancy at birth dramatically increased from 47 years at the beginning of the 20th century to ≈80 years at the beginning of the 21st century. This astonishing change in survival patterns was primarily attributable to the very significant decrease in infant mortality and to the eradication of infectious diseases, both of which are strongly related to the improvement of life conditions and to the progress of modern medicine. At the same time, although to a lesser degree, the progress in diagnosis, treatment, and prevention, especially of cancer and cardiovascular diseases, has also contributed to increased life expectancy at more advanced ages. A significant increase in life expectancy leads to an important increase in the number of subjects who are frail, incapacitated, and have reduced autonomy. The perspectives of a greater increase in life expectancy raises several biological, ethical, medical, and socioeconomic questions that go far beyond the scope of this article. Nevertheless, one of the major issues of modern medicine is how to increase disease-free and incapacity-free life expectancy. The progressive reduction in functional reserves and the deterioration of cognitive, cardiovascular, sensorial, and osteomuscular systems are the most frequent causes of frailty, incapacity, and loss of autonomy in the elderly. Assessment of clinical and biological markers and factors associated with morbidity and mortality has become a major issue that has considerable medical, social, and economic consequences. This concept, which evolved primarily in the field of cardiovascular medicine, led …

Culture of skeletal myoblasts from human donors aged over 40 years: dynamics of cell growth and expression of differentiation markers

BackgroundLocal myogenesis, neoangiogenesis and homing of progenitor cells from the bone marrow appear to contribute to repair of the infarcted myocardium. Implantation into heart tissues of autologous skeletal myoblasts has been associated with improved contractile function in animal models and in humans with acute myocardial ischemia. Since heart infarction is most prevalent in individuals of over 40 years of age, we tested whether culture methods available in our laboratory were adequate to obtain sufficient numbers of differentiated skeletal myoblasts from muscle biopsy specimens obtained from patients aged 41 to 91.Methods and resultsNo matter of donor age, differentiated skeletal muscle cells could be produced in vitro in amounts adequate for cellular therapy (≥300 millions). Using desmin as a cytoplasmic marker, about 50% cultured cells were differentiated along myogenic lineages and expressed proteins proper of skeletal muscle (myosin type I and II, actin, actinin, spectrin and dystrophin). Cytogenetic alterations were not detected in cultured muscle cells that had undergone at least 10 population doublings. Molecular methods employed for the screening of persistent viral infections evidenced that HCV failed to replicate in muscle cells cultured from one patient with chronic HCV infection.ConclusionThe proposed culture methods appear to hold promise for aged patients not only in the field of cardiovascular medicine, but also in the urologic and orthopedic fields.

Angiogenic therapy for coronary artery and peripheral arterial disease

Neovascularization in chronically ischemic adult cardiac and skeletal muscle results from the processes of angiogenesis, arteriogenesis and vasculogenesis. Therapeutic angiogenesis describes an emerging field of cardiovascular medicine whereby new blood vessels are induced to grow to supply oxygen and nutrients to cardiac or skeletal muscle rendered ischemic as a result of progressive atherosclerosis. Various techniques have been utilized to promote new blood vessel growth in the heart and extremities, including mechanical means such as surgical or percutaneous myocardial laser revascularization, angiogenic growth factor therapies involving members of the vascular endothelial growth factor and fibroblast growth factor families, and more recently, cellular-based therapies using stem cells known as endothelial progenitor cells or angioblasts. The following review discusses each of these treatment strategies in detail including both preclinical and clinical data for their use in peripheral arterial and coronary artery disease.

Harold J.C. (Jeremy) Swan, MD, PhD (1923–2005)

Our editorial space in this issue is devoted to remembering a giant in the field of cardiovascular medicine who died earlier this year. Dr. Swan made monumental contributions that radically altered the management of patients with heart and vascular disease and continue to beneficially influence the practice of cardiology today. Dr. Swan's name is repeated daily in critical care settings in relation, of course, to the catheter that he and his colleague, Dr. William Ganz, developed to provide continuous, bedside hemodynamic monitoring. The availability of quantitative hemodynamic assessment afforded new understanding of circulatory function in critically ill patients and ushered in the era of rational, physiologically based cardioactive drug therapy. Although best remembered for the Swan-Ganz catheter, his scientific contributions are extensive and have been recognized by numerous major citations, including the Distinguished Scientific Achievement Award of the American College of Cardiology and awards by the American Heart Association, the British Medical Association, the American College of Chest Physicians, and the State of Israel. A past president of the American College of Cardiology, Dr. Swan is credited with developing the outstanding Division of Cardiology at Cedars Sinai Medical Center in Los Angeles, which he led for 22 years. His leadership is reflected by the many outstanding cardiologists he mentored during his fruitful period at the Mayo Clinic (14 years), to which he came from his native Ireland, and his highly productive scientific and personal leadership at Cedars Sinai. During the latter part of his career, Dr. Swan was a thought leader on the importance of preventive cardiology and was a past Chair of the Preventive Cardiology Committee of the American College of Cardiology. Through his association with this Journal, with which he was a member of the founding editorial board, I had the privilege of personally experiencing his wisdom, insight, and generous support. We are, indeed, very fortunate to have his unique perspectives in his contribution to the Journal.1, 2 Although he is no longer with us, Dr. Swan left his positive, indelible mark on cardiovascular medicine and on all of us who strive to reduce the burden of cardiovascular disease.

Cardiovascular Gene Therapy: Angiogenesis and Beyond

Recent advances in understanding the mechanisms of disease have produced many new targets for gene therapy. However, it has been difficult to convert these new insights into clinically useful applications. In the field of cardiovascular medicine, most clinical studies of gene therapy have focused on angiogenesis as a treatment for ischemia. Initial enthusiasm was supported by small, uncontrolled, phase 1 trials. However, several large efficacy studies have recently been published that have not shown clinically significant improvement, and a few well-publicized complications of gene therapy have cast a pall over the entire field. In this review, we will summarize specific technical aspects of cardiovascular gene therapy, examine the recent series of clinical studies, and explore the direction of future work for the principal cardiovascular diseases.

Investigator barriers and preferences to conduct clinical drug trials in Finland: a qualitative study.

To explore investigator barriers, preferences, and attitudes towards conducting clinical trials in Finland. In-depth, semi-structured interviews with 20 clinicians working in the field of cardiovascular medicine were performed. The interviews were audiotaped, transcribed verbatim and analysed qualitatively. Twenty clinicians from all (five) university hospitals in Finland and from three subgroups: 1) with long experience, 2) with limited experience and 3) reluctant to carry out clinical trials, were sampled purposefully. Barriers and (de)motivating factors in carrying out clinical trials and need for training in Good Clinical Practice (GCP). Overall, the investigators had a positive attitude towards conducting clinical trials. The major barriers seemed to occur at the beginning of the trial: bureaucracy, lack of time and laboriousness. The informants hoped for more specific inhouse rules and flexibility in hospitals. The greatest investigator barriers were insufficient financial incentives, trial-related reasons and administrative affairs/bureaucracy. The smallest barriers were reported in subject recruitment, clinical work, documentation, investigational product logistics and communication with ethics committees. Financial incentives, a possibility to incorporate a personal sub-study or other benefits for personal research and scientific and clinical interest in the trial were reported as the most motivating factors. Carrying out studies in practice and an opportunity to participate in a trial during one's postgraduate specialist education were considered beneficial. Training in GCP, mainly in the course of postgraduate education, and a certificate or equivalent were generally considered necessary, although a voluntary system was preferred. The interviews of clinicians provide valuable information about the barriers and preferences related to the practical implementation of clinical trials. If the trial is scientifically/clinically interesting and involves a small administrative burden and sufficient financial compensation, investigators are motivated to participate. The barriers and preferences should be considered in decision-making, to meet the various needs of all parties involved and to produce high-quality GCP-compliant clinical drug research. This would ensure the availability of sufficient conditions to carry out clinical trials also in the future.

From Vulnerable Plaque to Vulnerable Patient

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

The European Heart Journal—the challenge of the next years

Over the last 7 years, under the Editorship of Kim Fox, the European Heart Journal has becomean increasingly important international clinical journal in the field of cardiovascular medicine. This has been reflected in an increase in the official ISI impact factor from 1.682 in 1995 to 5.131 in 2001, making it the third most important clinical journal in cardiovascular medicine. The increasing impact of the Journal has parallelled the growing importance of the European Society of Cardiology in global cardiovascular medicine today. Both in the domains of research (through its Working Groups …

Evaluating the costs and effectiveness of cardiovascular therapies: who cares about economic analyses?

The field of cardiovascular medicine is providing important insights about how the costs and effectiveness of diagnostic and therapeutic technologies are managed. As health-care budgets have taken up more of the economy and as employers and patients have become concerned about the escalating costs of health care, we have entered an era in which individual practitioners must become concerned with the costs of a service relative to its benefits. Further, increasing numbers of effective therapies in a time when finances are notably constrained, we clearly cannot use all effective therapies in all patients. Increasingly, therefore, we must assess the value derived from spending incremental money on health care products and services. This exercise has been termed cost-effectiveness analysis. The case of the platelet glycoprotein IIb/IIIa inhibitor, abciximab, is used to illustrate many of the issues surrounding the collection, interpretation, and (mis) application of cost-effectiveness data.

Book Review

Markers in Cardiology: Current and Future Clinical Applications Edited by Adams Jesse E., with Apple Fred S., Jaffe Allan S., and Wu Alan H.B. , 272 pages Armonk, NY : Futura Publishing Co. ; 2001 $79. ISBN 0879934727 The field of proteomics has paved the way for renewed investigative activity in biomarkers in cardiovascular medicine. The past few years have noted a paradigm shift in the use of such biomarkers; they have extended beyond their narrow use in the realm of acute coronary syndromes to burgeoning interest across a more expansive landscape of cardiovascular disorders, including vascular risk assessment, detection of silent heart failure, and identifying cardiac toxicity from drugs and traumatic cardiac interventions, as in cardiac surgery. In this regard, the book Markers in Cardiology fulfills an unmet clinical need to provide the cardiovascular health care professional with a concise yet comprehensive review of the emerging and manifest technology with cardiac biomarkers. The bulk of the book focuses in detail on the clinical place of troponins, and the chapters on the analytic issues related to laboratory variation and the resultant clinical sensitivity and specificity are well covered and must be read by everyone who decides to read this book. As clinicians, we tend to gloss over details of laboratory variations that can eventually influence our clinical decisions. Undoubtedly, the focus on troponins is well founded, since this particular assay is our most practical assay for detecting myocardial damage. Yet, the field of cardiovascular medicine has sprinted to a greater understanding of cardiac disease with the development of proteomic biomarkers that seek to define inflammation and cardiac stress. Thus, this book has appropriately included chapters on the emerging markers C-reactive protein and B-type natriuretic peptide in cardiac illness. In addition, novel markers, such as nuclear factor kappa B and fatty acid binding protein, as well as markers of lipid metabolism, have been covered, expanding the depth and breadth of this monograph series. If there is a limitation of this book, it is in the fact that the older markers, such as creatine kinase-MB and myoglobin, have been given little stage presence. Another caveat relates to the potential for portions of this book to become extinct, which will soon require revision and update. Nevertheless, this book is a welcome addition to a sparse literature pool dealing with the rapidly expanding field of proteomic biomarkers.–Mandeep R. Mehra, MD, Ochsner Clinic Foundation, New Orleans, LA

Antiplatelet therapies in combination for the treatment of patients with stable and unstable coronary artery disease.

There have been several recent trials of antiplatelet therapy that are relevant to the management of patients with coronary artery disease. The CURE, PCI-CURE, ESPRIT, TACTICS-TIMI 18, and TARGET studies were all major randomized clinical trials that have advanced the field of cardiovascular medicine tremendously. Additionally, the CREDO trial will soon be presented. It is evident from these trials that clopidogrel therapy improves upon the results seen with aspirin alone in patients with acute coronary syndromes. This is true even of patients undergoing an invasive approach, which is clearly the preferred strategy in moderate and high risk patients with acute coronary syndromes. It is imperative that this invasive approach be coupled with intravenous blockade of the glycoprotein IIb/IIIa receptor. The benefits of clopidogrel and glycoprotein IIb/IIIa inhibitors appear complementary. Questions remain about the optimal duration of clopidogrel treatment after elective stenting and of the particular choice of glycoprotein IIb/IIIa inhibitor both in acute and elective settings.

From clinical trials to public health policy: the path from imaging to screening

The abundance of new health-care technology is among the greatest achievements in today’s state-of-the-art field of cardiovascular medicine. Marked reductions in mortality have directly resulted from improved treatment and use of an array of imaging modalities in cardiovascular medicine.1 Although several available modalities are used for the assessment of ischemia in treating obstructive coronary disease, recent developments in imaging have focused on risk markers for the development of subclinical disease. Electron-beam computed tomography (EBCT) is such a modality and has been advocated as a new diagnostic test and screening tool over the past decade.2 Other imaging modalities that have been used for atherosclerosis detection include magnetic resonance imaging, intravascular ultrasound, and carotid ultrasound.

Nanotechnology needs for cardiovascular sciences

In medicine, the cardiovascular field is the most technically advanced discipline. The inherent technical challenges associated with the beating heart and the structure of the cardiovascular system has forced us to innovate from a biomedical engineering standpoint. Engineering achievements have helped us develop novel diagnostic and therapeutic technologies that provide safe and efficient solutions for our patients. In spite of such progress, cardiovascular disease remains the major cause of death, morbidity, and disability in the United States [1–3]. To eradicate heart disease within the next fifty years, substantial advances will be needed, and in particular, important technological hurdles need to be overcome. We foresee the progress in the field of nanotechnology could represent a major breakthrough in addressing some of our technical challenges. With this essay, we provide a glimpse at potentially important targets for nanotechnology in the field of cardiovascular medicine. By no means will this review attempt to be comprehensive but instead, it has been designed to trigger the interest of discoverers with substantial knowledge in the field of very small things.

Therapeutic angiogenesis with gene transfection for ischemic heart disease.

Recent advances in modern medicine have made it possible to understand disease processes at the genetic level and to apply this knowledge to new treatment strategies. Genetic engineering studies conducted in the field of cardiovascular medicine have led to the use of gene therapy as a new means for treating ischemic heart disease. The incidence of ischemic heart disease, with underlying conditions of diabetes mellitus and arteriosclerosis, has increased in recent years and is a major cause of myocardial infarction, cerebrovascular disease and death. Patients with these diseases often do not respond satisfactorily to conventional treatments. Consequently attention has turned to the area of revascularization therapy utilizing the introduction of genes. (c) 2001 Prous Science. All rights reserved.

Spectrum of use for the angiotensin-receptor blocking drugs.

The renin-angiotensin system (RAS) plays an important role in regulating blood pressure, and maintaining fluid and electrolyte balance. Angiotensin II is the principal mediator of the RAS and has been implicated in the development of hypertension as well as other forms of cardiovascular and renal disease. Angiotensin II-receptor antagonists are a new class of drugs that inhibit the RAS by selectively blocking the AT(1) receptor. These compounds therefore provide more specific and thorough blockade of the RAS by inhibiting the deleterious actions of angiotensin II at the receptor level, irrespective of how this peptide is formed. The increased specificity of action of angiotensin II-receptor antagonists may also circumvent unwanted side-effects normally associated with angiotensin-converting enzyme (ACE) inhibitors (eg, cough and angioedema) as these agents do not interfere with the metabolism of other peptides (eg, bradykinin, substance P, etc.). There is still some concern with angiotensin II-receptor antagonists and the long-term effects of hyper-stimulation of the unopposed AT(2) receptor that is caused by elevated levels of angiotensin II. However, it appears that stimulation of the AT(2) receptor may actually contribute to the beneficial effects of angiotensin II-receptor antagonists by counteracting the effects mediated by the AT(1) receptor. Angiotensin II-receptor antagonists display great therapeutic promise in the field of cardiovascular medicine and are currently being exploited as new antihypertensive agents. These drugs have demonstrated safety, efficacy, and tolerability; however, morbidity and mortality data are still lacking. Nonetheless, it is likely that angiotensin II-receptor antagonists will become part of the medical arsenal against cardiovascular and renal disease, thus consideration should be given to their future use as first-line antihypertensive agents.

Governmental Steering of Highly Specialized Medical Services

In Norway, highly specialized medicine has been under governmental steering since 1991. The Social and Health Department decides at which hospitals certain medical functions should be offered. In the field of cardiovascular medicine this has been experienced as mainly positive. The quality of the work has improved, and cooperation between hospitals has been stimulated.

Etymology of the Word “Stent”

Etymology of the Word “Stent”

New cardiovascular indications for old drugs

New indications may soon exist for liothyronine [triiodothyronine; T3] and adenosine in the field of cardiovascular medicine. Preliminary success with these agents was reported at the 15th Annual Meeting of the Society of Cardiovascular Anesthesiologists, held in San Diego, US, last month.