Posted in Frontiers in Cardiology and Cardiovascular Disorders, HTN, Medical Devices R&D and Inventions, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease, Scientist: Career considerations, Technology Transfer: Biotech and Pharmaceutical, tagged Cardiovascular Disorders, Conditions and Diseases, Heart disease, medicine, New England Journal of Medicine on August 16, 2012| 2 Comments »
http://nejm200.nejm.org/news-and-events/dialogues-in-medicine/?panel=4
Reporter: Aviva Lev-Ari, PhD, RN
Moderator:
Joseph Loscalzo
Panelists:
Emelia Benjamin
Eugene Braunwald
Desmond Jordan
Thomas Luscher
Craig Smith
Click on the Live Link Above, then click on the arrow to watch a 1:35 minutes VIDEO on Heart Disease
Posted in Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Frontiers in Cardiology and Cardiovascular Disorders, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease, tagged Atrial fibrillation, Cardiac dysrhythmia, Cardiology, Cardiovascular Disorders, Conditions and Diseases, health, medicine on August 8, 2012| 2 Comments »
Reporter: Aviva Lev-Ari, PhD, RN
World-class rowing champion Frederick Schoch
You probably know that regular, moderate exercise can result in many health benefits. But you may be surprised to learn that prolonged, intensive endurance exercise on an Olympian scale can actually damage your heart.
Scientists and doctors have demonstrated that long-term training and competition in extreme endurance sports such as marathons, iron-man triathlons, competitive rowing and long-distance bicycle races may cause structural changes to the heart and large arteries.
“Athlete’s heart syndrome” was first described more than 100 years ago as an apparently benign condition in which the elite athlete’s heart enlarges and thickens. For many years, doctors noted that abnormal electrocardiograms were common for extreme athletes, but no evidence pointed to an association with serious arrhythmias or sudden cardiac death. However, there is accumulating evidence that chronic extreme athletic activity may lead to potentially harmful changes in the heart in some individuals.
For example, a review published recently in the Mayo Clinic Proceedingsdemonstrated that approximately 12 percent of apparently healthy marathon runners showed microscopic areas of fibrosis, or scarring, in the heart chambers. The significance of these changes is not clear, but they could predispose the heart to abnormal rhythms in some cases.
A two-year follow-up revealed that the rate of coronary heart disease was significantly higher in extreme marathon runners than in moderate runners.
A 2011 Swedish study showed that elite cross-country skiers with long years of endurance training had a 29 percent higher risk of developing a variety of abnormal heart rhythms, some benign as well as some more serious.
High-profile professional athletes who are believed to have died of fatal arrhythmias include NFL star Reggie White, who died at 43 in 2004, and legendary ultra-marathoner Micah True, who died at 58 earlier this year.
Researchers believe high-endurance sports may promote the occurrence of atrial fibrillation in susceptible persons. This arrhythmia, which involves uncomfortable episodes of irregular, rapid heartbeat caused by faulty electrical signals in the heart, is usually not life-threatening. However, in about 5 percent of those with the condition, it can lead to heart failure and stroke.
“Physicians are becoming increasingly aware that extreme training regimens and endurance-style competitions can, in rare instances, lead to potentially dangerous abnormal cardiac rhythms,” says Alfred E. Buxton, MD, Director of the Clinical Electrophysiology Laboratory at Beth Israel Deaconess Medical Center’sCardioVascular Institute.
Physicians need to take into account the current research, follow new developments and be prepared to advise certain patients to make lifestyle changes based on the new data, he says.
Mark E. Josephson, MD
Mark E. Josephson, MD, Chief of Cardiovascular Medicine at the CardioVascular Institute — and an internationally recognized expert in electrophysiology and catheter ablation — has treated numerous rowers and other high-performance athletes who have suffered from atrial fibrillation. One example is Frederick Schoch, a world-class rowing champion and executive director of Boston’s celebrated annual Head of the Charles Regatta.
Schoch was diagnosed with paroxysmal atrial fibrillation in 2009 after he experienced heavy breathing and lightheadness following his crew’s fifth consecutive first-place finish in the Regatta’s 50 and older category. Schoch learned that atrial fibrillation can cause blood clots in the left atrium (upper chamber) and can lead to heart failure and stroke. Treatments may include medications (such as beta-blockers or anti-arrhythmic drugs), interventions (such as catheter ablation) and/or surgery.
To regulate his heart rate, Schoch’s primary care physician prescribed the drug diltiazem, but his episodes persisted and he feared he would never be able to compete again.
“Rowing is in my DNA,” says Schoch, whose father was an Olympic rower. “But with afib, I couldn’t even walk up the stairs.”
In 2010, a fellow rower referred Schoch to Dr. Josephson, who has treated more than 1,000 cardiac arrhythmia patients.
After hearing Schoch’s story, Dr. Josephson performed a catheter ablation, an interventional procedure that reduces the frequency of paroxysmal atrial fibrillation symptoms about 70 percent of the time. The procedure typically lasts two hours and involves inserting a catheter through the groin and puncturing the membrane between the heart’s right and left atria. Catheters are placed at the pulmonary veins (which are the source of atrial fibrillation triggers in 90 percent of paroxysmal afib cases), while the cardiologist delivers a high-frequency, low-voltage current to the site. This burns the tissue to isolate the pulmonary vein from the atrius so that triggers can’t initiate atrial fibrillation.
Schoch spent one night at BIDMC and returned to work two days later. He resumed his training, and in 2011, just one year after his procedure, he led his team to their sixth first-place finish in the Regatta’s senior division. Currently, he is serving as a television analyst, commenting on rowing at the 2012 Summer Olympics. He is also training for the next Head of the Charles Regatta in October.
“I am eternally grateful to Dr. Josephson,” says Schoch. “I hope that my experience can be helpful to others.”
While the findings cited here are unsettling, they shouldn’t discourage anyone from being physically active. For most adults, the American Heart Associationrecommends 150 minutes of moderate exercise a week (30 minutes a day on five days), or 75 minutes per week of vigorous exercise. Exercise is almost as effective when divided into several shorter periods during the day for convenience.
The result will be increased physical capacity and mental well-being, and a significant reduction in cardiovascular disease risk factors such as high blood pressure, excess weight and unhealthy cholesterol levels. Regular exercise helps fend off not only heart disease and stroke, but also many cancers, osteoporosis, diabetes, arthritis and depression.
“Moderate exercise is certainly good for your heart and your overall health,” says Dr. Buxton. “However, as is usually the case in life, moderation should be the guideline. Beyond 30 to 60 minutes per day, you may reach a point of diminishing returns. So don’t overdo it, but take comfort in knowing that with the right diagnosis and treatment, atrial fibrillation can be managed successfully.”
Above content provided by the CardioVascular Institute at Beth Israel Deaconess Medical Center. For advice about your medical care, consult your doctor.
Posted August 2012
Posted in Cardiac & Vascular Repair Tools Subsegment, Cardiovascular Pharmacogenomics, Personalized and Precision Medicine & Genomic Research, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, tagged Cardiac surgery, cardiomyocytes, Cardiovascular Disorders, dermal fibroblast, embryonic stem cells, heart attack myocardial infarction, Heart disease on August 1, 2012| 5 Comments »
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Heart attack patients could one day have their heart repaired using their own skin cells. This research focused on the potential use of human pluripotent stem cells such as human embryonic stem cells for the treatment of post-myocardial infarction heart failure and on the utilization of genetically-engineered cell grafts for the treatment of cardiac arrhythmias by modifying the electrophysiological properties. Myocardial cell replacement therapies are hampered by a paucity of sources for human cardiomyocytes and by the expected immune rejection of allogeneic cell grafts. The ability to derive patient-specific human-induced pluripotent stem cells (hiPSCs) may provide a solution to these challenges. That is using a patient’s own cells would avoid the problem of patients’ immune systems rejecting the cells as ‘foreign’. It was aimed to derive hiPSCs from heart failure (HF) patients, to induce their cardiomyocyte differentiation, to characterize the generated hiPSC-derived cardiomyocytes (hiPSC-CMs), and to evaluate their ability to integrate with pre-existing cardiac tissue. Dermal fibroblasts from HF patients were reprogrammed by retroviral delivery of Oct4, Sox2, and Klf4 or by using an excisable polycistronic lentiviral vector. The resulting HF-hiPSCs displayed adequate reprogramming properties and could be induced to differentiate into cardiomyocytes with the same efficiency as control hiPSCs (derived from human foreskin fibroblasts). Gene expression and immunostaining studies confirmed the cardiomyocyte phenotype of the differentiating HF-hiPSC-CMs. Multi-electrode array recordings revealed the development of a functional cardiac syncytium and adequate chronotropic responses to adrenergic and cholinergic stimulation. That is the resulting stem cells were able to differentiate to become heart muscle cells (cardiomyocytes) just as effectively as those that had been developed from healthy, young volunteers who acted as controls for the study. Next, functional integration and synchronized electrical activities were demonstrated between hiPSC-CMs and neonatal rat cardiomyocytes in co-culture studies. Finally, in vivo transplantation studies in the rat heart revealed the ability of the HF-hiPSC-CMs to engraft, survive, and structurally integrate with host cardiomyocytes. That is it was possible to make the cardiomyocytes develop into heart muscle tissue, which was joined together with existing cardiac tissue and within 48 hours the tissues were beating together. Human-induced pluripotent stem cells thus can be established from patients with advanced heart failure and coaxed to differentiate into cardiomyocytes, which can integrate with host cardiac tissue. This novel source for patient-specific heart cells may bring a unique value to the emerging field of cardiac regenerative medicine. This technology needs to be refined before it can be used for the treatment of patients with heart failure, but these findings are encouraging and take us a step closer to the goal of identifying an effective means of repairing the heart and limiting the consequences of heart failure.
Zwi-Dantsis L, Huber I, Habib M, Winterstern A, Gepstein A, Arbel G, Gepstein L. 2012. Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients. Eur Heart J. [Epub ahead of print] (http://www.ncbi.nlm.nih.gov/pubmed?term=Derivation%20and%20cardiomyocyte%20differentiation%20of%20induced%20pluripotent%20stem%20cells%20from%20heart%20failure%20patients)
Yankelson, L., Feld, Y., Bressler-Stramer, T., Itzhaki, I., Huber, I., Gepstein, A., Aronson, D., Marom, S., Gepstein, L. 2008. Cell therapy for modification of the myocardial electrophysiological substrate. Circulation 117, 720-731. (http://www.ncbi.nlm.nih.gov/pubmed/18212286)
Caspi, O., Huber, I., Kehat, I., Habib, M., Arbel, G., Gepstein, A., Yankelson, L., Aronson, D., Beyar, R., Gepstein, L. 2007. Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50, 1884-1893. (http://www.ncbi.nlm.nih.gov/pubmed?term=Transplantation%20of%20human%20embryonic%20stem%20cell-derived%20cardiomyocytes%20improves%20myocardial%20performance%20in%20infarcted%20rat%20hearts)
Huber, I., Itzhaki, I., Caspi, O., Arbel, G., Tzukerman, M., Gepstein, A., Habib, M., Yankelson, L., Kehat, I., Gepstein, L. 2007. Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB J 21, 2551-2563. (http://www.ncbi.nlm.nih.gov/pubmed/17435178)
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Posted in Cardiovascular Pharmacogenomics, Infectious Disease & New Antibiotic Targets, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, tagged Blood culture, british society of antimicrobial chemotherapy, Cardiovascular Disorders, Conditions and Diseases, Diagnosis, ESC, Fungal, health, medicine, Patient, research, science, staphylococcus aureus on May 29, 2012| Leave a Comment »
Guidelines for the Diagnosis and Treatment of Endocarditis
from
British Society of Antimicrobial Chemotherapy (BSAC)
Clinicians who care for patients diagnosed with infective endocarditis (IE) are (un)fortunate to be able to refer to several guidelines about its diagnosis and treatment. The guidelines vary considerably, especially with regards to antibiotic prescribing recommendations, which generally reflect local practice and expert opinion in light of largely observational data. All guidelines recommend a multidisciplinary approach to the management of IE.
Infective endocarditis (Photo credit: Wikipedia)
Echocardiography remains a cornerstone of IE diagnosis but is neither 100% sensitive nor specific and multiple scans may be needed to identify vegetations. Echocardiography should also be used in all patients with Staphylococcus aureus bacteraemia. The prevalence of IE among patients with S aureus bacteraemia is variable but was reported as 13% in one large prospective US study and 22% in a recent European study. Clinical assessment is unreliable in diagnosing IE in patients with S aureus bacteraemia and without echocardiography the diagnosis may be missed. Transoesophageal echocardiography is now recommended in most cases of suspected or confirmed IE but may be unnecessary in patients with right-sided valve involvement.
Establishing a microbiological diagnosis in an era of increasingly complex infections with unpredictable resistance patterns is important. However, traditional recommendations for blood culture sampling have been amended for patients with suspected IE and severe sepsis or septic shock. In this situation, two (rather than three) sets of blood cultures, taken at different times within an hour before the start of empirical treatment, are now advised. This is a pragmatic recommendation to avoid undue delay in starting empirical antimicrobial treatment. In other patients, the usual need for three sets of blood cultures is recommended but with at least 6 h between sampling times; an important aim of multiple sampling is to demonstrate the presence of a sustained or persistent bacteraemia, which is characteristic of IE. Identification of atypical micro-organisms using serology in culture-negative cases should be limited to Coxiella and Bartonella in the first instance—a reflection of the extremely small numbers of reported cases of IE caused by Mycoplasma, Brucella and Legionella.
Fungal causes of IE should be considered in culture-negative IE if serology is non-diagnostic and the patient is immunocompromised, has a prosthetic valve, is an intravenous drug user or is not responding to empirical antibacterial treatment. The application of broad-range (16S ribosomal RNA gene) PCR on surgically resected valves or embolic material should be used when culture has failed. False-negative 16S ribosomal RNA gene PCR reactions can occur in the presence of inhibitors of the DNA polymerase within clinical samples or as a result of the vagaries of sampling (ie, processing a piece of tissue that does not contain any bacteria). Bacterial DNA has been shown to be present within cardiac tissue several years after successful treatment of IE, so results should be interpreted with caution in a patient with a previous diagnosis of IE. Application of 16S ribosomal gene PCR to blood in patients with IE is problematic owing to the low levels of bacteria present (1–10 fu/ml) and subsequent difficulty in DNA extraction; as a result it is not currently available for routine clinical use.
Empirical treatment (that started before obtaining a microbiological diagnosis) is generally discouraged, except in those who are acutely unwell or shocked. There is no clear evidence that speeding up the diagnosis, and instigation of treatment, improves outcomes, although this would seem intuitive. Early treatment (started within days of onset of symptoms rather than weeks) is a laudable aim, but the few days delay in hospital while appropriate echocardiographic and microbiological tests are undertaken on a stable patient are unlikely to have a negative impact on outcome. Conversely, the administration of broad-spectrum antibiotics when the diagnosis of IE has not been considered (and often when inadequate samples have been obtained) may have considerable impact on the ability to establish the diagnosis and subsequently deliver effective treatment.
Outpatient antibiotic treatment (OPAT) for IE is included in the BSAC guidelines in response to increasing efforts to expand these services and manage more patients outside hospital. Patients who might be considered for OPAT include those who are stable and responding well to treatment, are without signs of heart failure and without any indications for surgery or uncontrolled extracardiac foci of infection. Delivery of OPAT requires appropriate funding, support and infrastructure, coupled with the ability to rapidly access inpatient services and obtain urgent expert advice if needed. This has been proved to be feasible and safe in the UK, even in high-risk IE cases.
Although the guidelines include recommendations for most causes of IE, the predominant pathogens remain staphylococci, streptococci and enterococci. Routine addition of gentamicin to flucloxacillin for the treatment of native valve staphylococcal IE is no longer recommended (see Table 1). This recommendation is unchanged from previous BSAC guidelines but the ESC continue to include gentamicin as an optional addition. Further evidence of the toxicity of gentamicin has been published, based on findings from a randomised controlled trial comparing daptomycin with either vancomycin or cloxacillin plus gentamicin for the treatment of S aureus bloodstream infection or IE Recommendations for meticillin-resistant staphylococci also differ from those of the ESC; although vancomycin is the primary agent in both sets of guidelines, rifampicin is recommended by BSAC in place of gentamicin because of concerns about efficacy and toxicity. Daptomycin, a recently licensed lipopeptide, is also recommended as an alternative agent for patients who are intolerant to vancomycin or have infection caused by vancomycin-resistant isolates.
Previous recommendations for treatment of streptococcal IE have been simplified, with greater emphasis placed on benzylpenicillin rather than amoxicillin as the primary agent to reduce risk of Clostridium difficile infection. Enterococcal treatment regimens are largely consistent with the ESC guidelines, though a low threshold for withdrawing gentamicin in patients with deteriorating renal function or other signs of toxicity is advised, based on observational data that shorter gentamicin courses are not associated with worse outcomes.
The timing of cardiac surgery in IE should be evaluated by the multidisciplinary team on a case by case basis. Attempts to advise whether cardiac surgery should be emergent, urgent or elective can seem artificial. The traditional indications for surgery in IE are well established but it is becoming apparent that patients with IE caused by S aureus, or patients with evidence of systemic embolisation, should also be considered for early surgery, which may confer a mortality benefit.
Device-related infections have been deliberately omitted from the current BSAC guidance as the challenges in preventing, diagnosing and treating cases of intracardiac device IE are different from ‘traditional’ native or prosthetic valve IE. Further specific device-related guidance is likely to be published in the future and a joint working party involving the BSAC, BCS and Heart Rhythm UK has been established. IE guidelines are always imperfect owing to the difficulties in studying this relatively uncommon condition and the scarcity of randomised trials. At present, we are uncertain of the incidence, risk factors, causative micro-organisms (and their antimicrobial sensitivities), and patient outcomes in IE affecting the UK population. A recently established national endocarditis database may help to answer some of these questions, but its success will be crucially determined by the degree of support and national participation. See http://www.neemo.leedsth.nhs.uk/ (only via the N3 network) for details.
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Reported by: Dr. V. S. Karra, Ph.D
2012pharmaceutical
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