Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF) in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling,
neurohormonal activation, etc.
Journal of Stem Cell Research and Transplantation is an international, open access, peer reviewed, scholarly journal committed to publish articles in diversified fields of transplantations and applications of stem cell research. The aim of the academic journal is to provide a platform for researchers, scientists, physicians, and other health professionals to find latest research information in the areas of stem cell research, transplantations such as stem cell transplantation, transplantation immunology, kidney transplantation and its treatment. It is a wide-ranging Open Access peer reviewed scientific journal that covers multidisciplinary fields.
Journal of Stem Cell Research and Transplantation accepts original research articles, letter to editor, review articles, mini reviews, case reports, editorials, scientific data, technical reports, rapid communication, and short communications, etc. on all the aspects of stem cells. The Journal of Stem Cell Research and Transplantation publishes latest scientific information, and is generously accessible across the world through internet to go halves the innovations of the researchers for intellectual advancement in this field. Austin also brings universally peer reviewed scientific journals under one roof thereby promoting knowledge sharing, collaborative and promotion of multidisciplinary science.
Causes for syncope are multifaceted. Hormonal etiology, specifically hypothyroidism, is associated with cardiac arrhythmias [1]. Sinus bradycardia, low voltage, nonspecific T-wave changes and dissociative atrioventricular (AV) abnormalities are some of descriptive electrocardiographic features [2]. In the majority of well know clinical presentations complete AV block requires the insertion of a permanent pacemaker. However hypothyroidism related bradycardia and consequential symptomatic AV blocks could be reversible with timely and proper management.
We report a case of severe hypothyroidism resulting in insertion of transient pacemaker with favorable clinical course and fully reversible complete AV block after accordant pharmacological hormonal substitution.
A case report on Rheumatoid Arthritis with sickle cell traitPARUL UNIVERSITY
A female patient aged 6 years, a suspected case of sickle cell trait (SCT) having symptoms of Rheumatoid arthritis (RA),
while evaluating joint complaints in adult sickle cell disease (SCD) patients, a number of sickle cell-based entities come
to mind such as avascular necrosis, osteomyelitis, bone infarcts, and septic arthritis. RA is a chronic systemic
inflammatory disease, many reports highlighted the occurrence of RA in SCD presenting as diagnostic challenges for
cases with chronic inflammatory arthritis, SCT also have appeared to persist in some populations at a perplexingly high
rate given the degree of early mortality of homozygosity of SCD, our case report showed that not only SCD but if a patient
has SCT they can develop RA as complication. Our case report concludes that during the evaluation of a SCT patient who
presents with chronic synovitis, one should strongly consider the possibility of coexistence of RA and SCT.
Journal of Stem Cell Research and Transplantation is an international, open access, peer reviewed, scholarly journal committed to publish articles in diversified fields of transplantations and applications of stem cell research. The aim of the academic journal is to provide a platform for researchers, scientists, physicians, and other health professionals to find latest research information in the areas of stem cell research, transplantations such as stem cell transplantation, transplantation immunology, kidney transplantation and its treatment. It is a wide-ranging Open Access peer reviewed scientific journal that covers multidisciplinary fields.
Journal of Stem Cell Research and Transplantation accepts original research articles, letter to editor, review articles, mini reviews, case reports, editorials, scientific data, technical reports, rapid communication, and short communications, etc. on all the aspects of stem cells. The Journal of Stem Cell Research and Transplantation publishes latest scientific information, and is generously accessible across the world through internet to go halves the innovations of the researchers for intellectual advancement in this field. Austin also brings universally peer reviewed scientific journals under one roof thereby promoting knowledge sharing, collaborative and promotion of multidisciplinary science.
Causes for syncope are multifaceted. Hormonal etiology, specifically hypothyroidism, is associated with cardiac arrhythmias [1]. Sinus bradycardia, low voltage, nonspecific T-wave changes and dissociative atrioventricular (AV) abnormalities are some of descriptive electrocardiographic features [2]. In the majority of well know clinical presentations complete AV block requires the insertion of a permanent pacemaker. However hypothyroidism related bradycardia and consequential symptomatic AV blocks could be reversible with timely and proper management.
We report a case of severe hypothyroidism resulting in insertion of transient pacemaker with favorable clinical course and fully reversible complete AV block after accordant pharmacological hormonal substitution.
A case report on Rheumatoid Arthritis with sickle cell traitPARUL UNIVERSITY
A female patient aged 6 years, a suspected case of sickle cell trait (SCT) having symptoms of Rheumatoid arthritis (RA),
while evaluating joint complaints in adult sickle cell disease (SCD) patients, a number of sickle cell-based entities come
to mind such as avascular necrosis, osteomyelitis, bone infarcts, and septic arthritis. RA is a chronic systemic
inflammatory disease, many reports highlighted the occurrence of RA in SCD presenting as diagnostic challenges for
cases with chronic inflammatory arthritis, SCT also have appeared to persist in some populations at a perplexingly high
rate given the degree of early mortality of homozygosity of SCD, our case report showed that not only SCD but if a patient
has SCT they can develop RA as complication. Our case report concludes that during the evaluation of a SCT patient who
presents with chronic synovitis, one should strongly consider the possibility of coexistence of RA and SCT.
Systemic Hypertension (HTN) accounts for the largest amount of attributable Cardiovascular (CV) mortality worldwide. There are several factors responsible for the development of HTN and its CV complications. Multicenter trials revealed that risk factors responsible for Micro Vascular Disease (MVD) are similar for those attributable to Coronary Artery Disease (CAD) which include tobacco use, unhealthy cholesterol levels, HTN, obesity and overweight, physical inactivity, unhealthy diet, diabetes, insulin resistance, increasing age and genetic predisposition. In addition, the defective release of Nitric Oxide (NO) could be a putative candidate for HTN and MVD. This study reviewed the risk stratification of hypertensive population employing cardiac imaging modalities which are of crucial importance
in diagnosis. It further emphasized the proper used of cardiac imaging to determine patients at increased CV risk and identify the management strategy. It is now known that NO has an important effect on blood pressure, and the basal release of endothelial Nitric Oxide (eNOS) in HTN may be reduced. Although there are different forms of eNOS gene allele, there is no solid data revealing the potential role of the polymorphism of the eNOS in patients with HTN and coronary vascular diseases. In the present article, the prevalence of eNOS G298 allele in hypertensive patients with micro vascular angina will be demonstrated. This review provides an update on appropriate and justified use of non-invasive imaging tests in hypertensive patients and its important role in proper diagnosis of MVD and CAD. Second, eNOS gene allele and its relation to essential hypertension and angina pectoris are also highlighted.
Aim: of the study was to conduct a comparative analysis of inflammatory markers in patients with coronary heart disease of stable and unstable flow. Methods: 78 patients aged 36 to 75 years were enrolled in this study (mean age 58.2±12.6 years). Laboratory and instrumental data were obtained and assessed. IL-6, TNF-α in blood plasma was carried out by the method of enzyme immunoassay on a solid-phase analyzer «Humareader Single». Statistical processing of the obtained results was carried out using vibrational statistics methods recommended for biomedical research on the IBM PC AT Pentium IV. Results: In patients with unstable angina (UA), the frequency of elevated levels of CRP, TNF-α, and leukocytes was statistically significantly higher than in the group with stable ischemic heart disease (P<0.05). The mean levels of these markers were statistically significantly higher in patients with UA compared with patients with stable form of coronary heart disease (CHD, P<0.05): CRP (4.3 ± 2.4 and 2.9 ± 2.3 mg / L, p <0.05, respectively), TNF-α (10.5 ± 2.5 and 7.7 ± 3.4 pg / ml, p <0.05) and leukocytes (9.2 ± 2.5 6.9 ± 2.3x109 / l, p <0.05). The level of interleukin-6 in patients with UA was higher in comparison with patients with stable angina (SA, 3.4 ± 1.7 and 2.9 ± 0.5 pg/ml), but the difference was statistically not significant (p> 0.05 ). There were no significant differences in the level of fibrinogen and ESR between patients with UA and SA. Conclusion: It was noted that the signs of inflammation are detected both in patients with unstable forms and in patients with stable form of CHD, but the degree of inflammation in patients with UA (level of TNF-α, CRP and leukocytes) is higher than in patients with stable ischemic heart disease.
Introduction: Chronic Kidney Disease (CKD) is a worldwide public health problem and it is increasing over time. Cardiovascular disease is a major concern for patients with end stage renal disease, especially those on hemodialysis. It is the leading cause of death among patients with chronic kidney
disease, particularly in dialysis population.
Study on the Health Related Quality of Life of Patients with Ischemic strokeiosrjce
The work entitled, “Study on the health related quality of life of patients with ischemic stroke” was
conducted in the department of Neurology at a multispecialty hospital. After receiving the official approval, the
study was conducted for a period of eight months from December 2013 to August 2014. A total of 278 cases with
Neurological disorders were found, of which 117(42 %) patients were with ischemic stroke. Hypertension (59%)
and Diabetes (53%) were the major co-morbid conditions found. The Health related quality of life of the
patients was assessed by direct interviewing of individual patients with a stroke specific questionnaire. The
Health related quality of life of the patients was assessed by direct interviewing of individual patients with a
stroke specific questionnaire. Quality of life assessments are done by various methods like taking the floor and
ceiling effects of the scores, average score calculation etc. Assessment of the floor and ceiling effect showed the
potential for floor effects in the most difficult domain(strength) and the possibility of a ceiling effect in the
communication domain. Assessment of stroke severity is done by taking the mean and SD of the individual domains
Management of Takotsubo Syndrome: A Comprehensive ReviewNicolas Ugarte
Takotsubo syndrome (TTS), also known as Takotsubo cardiomyopathy, is a transient left
ventricular wall dysfunction that is often triggered by physical or emotional stressors. Although
TTS is a rare disease with a prevalence of only 0.5% to 0.9% in the general population, it is
often misdiagnosed as acute coronary syndrome. A diagnosis of TTS can be made using Mayo
diagnostic criteria. The initial management of TTS includes dual antiplatelet therapy,
anticoagulants, beta-blockers, angiotensin-converting enzyme inhibitors or aldosterone
receptor blockers, and statins. Treatment is usually provided for up to three months and has a
good safety profile. For TTS with complications such as cardiogenic shock, management
depends on left ventricular outflow tract obstruction (LVOTO). In patients without LVOTO,
inotropic agents can be used to maintain pressure, while inotropic agents are contraindicated
in patients with LVOTO. In TTS with thromboembolism, heparin should be started, and
patients should be bridged to warfarin for up to three months to prevent systemic emboli. Our
comprehensive review discussed the management in detail, derived from the most recent
literature from observational studies, systematic review, and meta-analyses.
Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients. It is associated with reduced exercise capacity and physical well-being and reduced quality of life. Cutoff values have been identified for diagnosing iron deficiency in heart failure with reduced ejection fraction as serum ferritin, <100 μg/l, or ferritin, 100 to 300 μg/l, with transferrin saturation of <20%. Oral iron products have been shown to have little efficacy in heart failure, where the preference is intravenous iron products. Most clinical studies have been performed using ferric carboxymaltose with good efficacy in terms of improvements in 6-min walk test distance, peak oxygen consumption, quality of life, and improvements in New York Heart Association functional class. Data from meta-analyses also suggest beneficial effects for hospitalization rates for heart failure and reduction in cardiovascular mortality rates. A prospective trial to investigate effects on morbidity and mortality is currently ongoing. This paper highlights current knowledge of the pathophysiology of iron deficiency in heart failure, its prevalence and clinical impact, and its possible treatment options
Comparative Study of Hscrp in Chronic Kidney Diseaseiosrphr_editor
Chronic kidney disease (CKD) is a global threat to health mainly in developing countries because therapy is expensive and lifelong. over 1 million people worldwide are on dialysis or with a functioning graft. Early detection of Chronic kidney disease (CKD) and its consequent complications can prevent its grave complications . It causes not only significant morbidity but also it causes high mortality. Because of increase in incidence of Diabetes mellitus, hypertension, obesity and an aging population there is increase in progression of chronic kidney disease to end stage renal disease (ESRD). . Cardiovascular disease (CVD) is the major cause of mortality in haemodialysis patients and so it has become imperative to have a screening programme at all levels to detect CKD at an early stage and to initiate specific therapy to reduce the progression of renal disease and also the burden of ESRD (1). High sensitive C-Reactive protein (Hs CRP) assay is useful for sensitive detection of inflammatory state (2,3). This study aims at estimating Hs CRP as a marker of inflammation in CKD patients...
A patient with joint pains, skin changes and clubbingApollo Hospitals
Primary hypertrophic osteoarthropathy (PHO) is a rare syndrome with variable clinical and radiological presentations such as joint pains and swelling, clubbing, seborrheic and thickened facial skin and hyperostosis. We present such a case of PHO who was previously diagnosed and treated as inflammatory polyarthritis.
Hydatid cyst, caused by echinococcus granulosa, can produce tissue cyst everywhere in body. Skeletal cystic lesion is rare specially in long bones like femur and because of its unusual presentation, its diagnosis may easily be missed, unless be kept in mind. Hydatid disease is a parasitic infestation of the humans that can practically affect any part of the body. It commonly affects liver, lung and muscles. Bone hydatid is less common occurring in only 0.5–2% of cases and humans act as an intermediate host. In the patient evaluated by us, the plain x-ray showed multiple osteolytic lesions along the lower one third of the femur and the upper end of tibia.
46, XY complete gonadal dysgenesis (Swyer syndrome): Report of two different ...Apollo Hospitals
In 1955, Swyer first described two phenotypic women with
gonadal dysgenesis without the stigma of Turner syndrome
(46 XY pure gonadal dysgenesis, now known as Swyer syndrome). The chance of tumor development in Swyer syndrome is 20e30%. The most common tumor described is bilateral gonadoblastoma, but also seen are dysgerminoma and even embryonal carcinoma. Five percent of dysgerminomas are discovered in patients who are phenotypically females with abnormal gonads and 46 XY karyotye.
In this case report, we aimed to present a case with pure
gonadal dysgenesis who presented with complaints of primary amenorrhea and was detected to have bilateral dysgenetic gonads, 46, XY karyotype, as a rare cause of male pseudo-hermaphroditism.
Systemic Hypertension (HTN) accounts for the largest amount of attributable Cardiovascular (CV) mortality worldwide. There are several factors responsible for the development of HTN and its CV complications. Multicenter trials revealed that risk factors responsible for Micro Vascular Disease (MVD) are similar for those attributable to Coronary Artery Disease (CAD) which include tobacco use, unhealthy cholesterol levels, HTN, obesity and overweight, physical inactivity, unhealthy diet, diabetes, insulin resistance, increasing age and genetic predisposition. In addition, the defective release of Nitric Oxide (NO) could be a putative candidate for HTN and MVD. This study reviewed the risk stratification of hypertensive population employing cardiac imaging modalities which are of crucial importance
in diagnosis. It further emphasized the proper used of cardiac imaging to determine patients at increased CV risk and identify the management strategy. It is now known that NO has an important effect on blood pressure, and the basal release of endothelial Nitric Oxide (eNOS) in HTN may be reduced. Although there are different forms of eNOS gene allele, there is no solid data revealing the potential role of the polymorphism of the eNOS in patients with HTN and coronary vascular diseases. In the present article, the prevalence of eNOS G298 allele in hypertensive patients with micro vascular angina will be demonstrated. This review provides an update on appropriate and justified use of non-invasive imaging tests in hypertensive patients and its important role in proper diagnosis of MVD and CAD. Second, eNOS gene allele and its relation to essential hypertension and angina pectoris are also highlighted.
Aim: of the study was to conduct a comparative analysis of inflammatory markers in patients with coronary heart disease of stable and unstable flow. Methods: 78 patients aged 36 to 75 years were enrolled in this study (mean age 58.2±12.6 years). Laboratory and instrumental data were obtained and assessed. IL-6, TNF-α in blood plasma was carried out by the method of enzyme immunoassay on a solid-phase analyzer «Humareader Single». Statistical processing of the obtained results was carried out using vibrational statistics methods recommended for biomedical research on the IBM PC AT Pentium IV. Results: In patients with unstable angina (UA), the frequency of elevated levels of CRP, TNF-α, and leukocytes was statistically significantly higher than in the group with stable ischemic heart disease (P<0.05). The mean levels of these markers were statistically significantly higher in patients with UA compared with patients with stable form of coronary heart disease (CHD, P<0.05): CRP (4.3 ± 2.4 and 2.9 ± 2.3 mg / L, p <0.05, respectively), TNF-α (10.5 ± 2.5 and 7.7 ± 3.4 pg / ml, p <0.05) and leukocytes (9.2 ± 2.5 6.9 ± 2.3x109 / l, p <0.05). The level of interleukin-6 in patients with UA was higher in comparison with patients with stable angina (SA, 3.4 ± 1.7 and 2.9 ± 0.5 pg/ml), but the difference was statistically not significant (p> 0.05 ). There were no significant differences in the level of fibrinogen and ESR between patients with UA and SA. Conclusion: It was noted that the signs of inflammation are detected both in patients with unstable forms and in patients with stable form of CHD, but the degree of inflammation in patients with UA (level of TNF-α, CRP and leukocytes) is higher than in patients with stable ischemic heart disease.
Introduction: Chronic Kidney Disease (CKD) is a worldwide public health problem and it is increasing over time. Cardiovascular disease is a major concern for patients with end stage renal disease, especially those on hemodialysis. It is the leading cause of death among patients with chronic kidney
disease, particularly in dialysis population.
Study on the Health Related Quality of Life of Patients with Ischemic strokeiosrjce
The work entitled, “Study on the health related quality of life of patients with ischemic stroke” was
conducted in the department of Neurology at a multispecialty hospital. After receiving the official approval, the
study was conducted for a period of eight months from December 2013 to August 2014. A total of 278 cases with
Neurological disorders were found, of which 117(42 %) patients were with ischemic stroke. Hypertension (59%)
and Diabetes (53%) were the major co-morbid conditions found. The Health related quality of life of the
patients was assessed by direct interviewing of individual patients with a stroke specific questionnaire. The
Health related quality of life of the patients was assessed by direct interviewing of individual patients with a
stroke specific questionnaire. Quality of life assessments are done by various methods like taking the floor and
ceiling effects of the scores, average score calculation etc. Assessment of the floor and ceiling effect showed the
potential for floor effects in the most difficult domain(strength) and the possibility of a ceiling effect in the
communication domain. Assessment of stroke severity is done by taking the mean and SD of the individual domains
Management of Takotsubo Syndrome: A Comprehensive ReviewNicolas Ugarte
Takotsubo syndrome (TTS), also known as Takotsubo cardiomyopathy, is a transient left
ventricular wall dysfunction that is often triggered by physical or emotional stressors. Although
TTS is a rare disease with a prevalence of only 0.5% to 0.9% in the general population, it is
often misdiagnosed as acute coronary syndrome. A diagnosis of TTS can be made using Mayo
diagnostic criteria. The initial management of TTS includes dual antiplatelet therapy,
anticoagulants, beta-blockers, angiotensin-converting enzyme inhibitors or aldosterone
receptor blockers, and statins. Treatment is usually provided for up to three months and has a
good safety profile. For TTS with complications such as cardiogenic shock, management
depends on left ventricular outflow tract obstruction (LVOTO). In patients without LVOTO,
inotropic agents can be used to maintain pressure, while inotropic agents are contraindicated
in patients with LVOTO. In TTS with thromboembolism, heparin should be started, and
patients should be bridged to warfarin for up to three months to prevent systemic emboli. Our
comprehensive review discussed the management in detail, derived from the most recent
literature from observational studies, systematic review, and meta-analyses.
Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients. It is associated with reduced exercise capacity and physical well-being and reduced quality of life. Cutoff values have been identified for diagnosing iron deficiency in heart failure with reduced ejection fraction as serum ferritin, <100 μg/l, or ferritin, 100 to 300 μg/l, with transferrin saturation of <20%. Oral iron products have been shown to have little efficacy in heart failure, where the preference is intravenous iron products. Most clinical studies have been performed using ferric carboxymaltose with good efficacy in terms of improvements in 6-min walk test distance, peak oxygen consumption, quality of life, and improvements in New York Heart Association functional class. Data from meta-analyses also suggest beneficial effects for hospitalization rates for heart failure and reduction in cardiovascular mortality rates. A prospective trial to investigate effects on morbidity and mortality is currently ongoing. This paper highlights current knowledge of the pathophysiology of iron deficiency in heart failure, its prevalence and clinical impact, and its possible treatment options
Comparative Study of Hscrp in Chronic Kidney Diseaseiosrphr_editor
Chronic kidney disease (CKD) is a global threat to health mainly in developing countries because therapy is expensive and lifelong. over 1 million people worldwide are on dialysis or with a functioning graft. Early detection of Chronic kidney disease (CKD) and its consequent complications can prevent its grave complications . It causes not only significant morbidity but also it causes high mortality. Because of increase in incidence of Diabetes mellitus, hypertension, obesity and an aging population there is increase in progression of chronic kidney disease to end stage renal disease (ESRD). . Cardiovascular disease (CVD) is the major cause of mortality in haemodialysis patients and so it has become imperative to have a screening programme at all levels to detect CKD at an early stage and to initiate specific therapy to reduce the progression of renal disease and also the burden of ESRD (1). High sensitive C-Reactive protein (Hs CRP) assay is useful for sensitive detection of inflammatory state (2,3). This study aims at estimating Hs CRP as a marker of inflammation in CKD patients...
A patient with joint pains, skin changes and clubbingApollo Hospitals
Primary hypertrophic osteoarthropathy (PHO) is a rare syndrome with variable clinical and radiological presentations such as joint pains and swelling, clubbing, seborrheic and thickened facial skin and hyperostosis. We present such a case of PHO who was previously diagnosed and treated as inflammatory polyarthritis.
Hydatid cyst, caused by echinococcus granulosa, can produce tissue cyst everywhere in body. Skeletal cystic lesion is rare specially in long bones like femur and because of its unusual presentation, its diagnosis may easily be missed, unless be kept in mind. Hydatid disease is a parasitic infestation of the humans that can practically affect any part of the body. It commonly affects liver, lung and muscles. Bone hydatid is less common occurring in only 0.5–2% of cases and humans act as an intermediate host. In the patient evaluated by us, the plain x-ray showed multiple osteolytic lesions along the lower one third of the femur and the upper end of tibia.
46, XY complete gonadal dysgenesis (Swyer syndrome): Report of two different ...Apollo Hospitals
In 1955, Swyer first described two phenotypic women with
gonadal dysgenesis without the stigma of Turner syndrome
(46 XY pure gonadal dysgenesis, now known as Swyer syndrome). The chance of tumor development in Swyer syndrome is 20e30%. The most common tumor described is bilateral gonadoblastoma, but also seen are dysgerminoma and even embryonal carcinoma. Five percent of dysgerminomas are discovered in patients who are phenotypically females with abnormal gonads and 46 XY karyotye.
In this case report, we aimed to present a case with pure
gonadal dysgenesis who presented with complaints of primary amenorrhea and was detected to have bilateral dysgenetic gonads, 46, XY karyotype, as a rare cause of male pseudo-hermaphroditism.
Clinical genetics is one of the most rapidly advancing fields in medicine. Spectacular progress has been achieved in this century with unravelling of the entire draft sequence of the human genome. A major contribution of these advances has been in diagnosis, management and prenatal diagnosis of genetic disorders as treatment in most cases is difficult or impossible and where available beyond the means of most families. Genetic technology is advancing rapidly, bringing new, safer and more sensitive ways to diagnose genetic conditions pre- and postnatally. These advances will bring about profound changes in the way we deliver obstetric services to women and their families. Diagnosing a genetic disorder not only allows for disease-specific management options but also has implications for the affected individual's entire family. Hence, a working understanding of the underlying concepts of genetic disease is important for all practicing clinicians. Although it is impossible to know all aspects of clinical and molecular genetics, basic knowledge of certain topics is a must for all practicing obstetrician/gynecologists.
Closed plaster treatment of severe compound injuries – A report and revisitApollo Hospitals
A crushed injury of limb was treated with closed plaster method and elaborating the treatment protocol and follow-up. We should look behind the old treatment method again.
Melanotic schwannoma of adrenal gland - A rare entity/ diagnostic dilemmaApollo Hospitals
Melanotic schwannoma of adrenal gland is very rare entity with
only two series and less than 100 cases reported in literature. We report a case of melanotic
schwannoma.
Guidelines for the management of relapsed acute lymphoblasticApollo Hospitals
Considerable progress has been made in the treatment of newly diagnosed childhood acute lymphoblastic leukemia. With the use of intensive, risk-stratified multiagent chemotherapeutic protocols, over 80% of patients can hope to be long-term survivors. However, despite optimal treatment, about 20% of patients relapse. The treatment of these children poses a major challenge. The prognosis of these patients depends on a number of factors including time since diagnosis, the site of relapse and immunophenotype. The choice of postinduction therapy depends on these prognostic factors. Considerable work has been done to identify the subgroups of relapsed patients whose outcomes are significantly altered by allogeneic bone marrow transplant. In our scenario, the limited availability of allogeneic bone marrow transplant due to a host of factors renders the management of these children even more challenging.
Breast filariasis - A fine needle aspiration cytology report Apollo Hospitals
Filariasis is a major health problem in tropical countries. The disease is endemic in large areas of India. Lymphatic filariasis in human is commonly caused by Wuchereria bancrofti and Brugia malayi. Extranodal filariasis is a rare entity and the breast is an uncommon site for filariasis. We report a case of female who presented with lump in the left breast. Fine needle aspiration cytology of lump revealed numerous adult filarial worms.
A young female presented to us with chest complaints of 10 months duration. Imaging was done which revealed fat attenuation mass lesion in the mediastinum occupying both
Accepted hemithoraces. Provisional differential diagnosis of giant teratoma, mediastinal thymoli-poma, large pleural lipoma or a pulmonary lesion with effusion was kept. Patient under-went surgery, mass was resected and the patient discharged in good condition.
Despite major advances in the cardiovascular medicine in the 20th century, heart failure (HF) is an exceptional with estimated prevalence of >37.7 million globally caused by secondary aetiologies ultimately affecting their quality of life, including dyspnoea, poor exercise tolerance, fatigue, and fluid retention. Currently, angiotensin receptor blockers (ARBs), angiotensin converting enzyme (ACE) inhibitors, mineralocorticoid receptor antagonists, β blockers, angiotensin receptor blocker neprilysin inhibitors (ARNIs) and advanced device therapies have been administered to patients with reduced ejection fraction (EF).
Cardiovascular disease is the most prevalent class of diseases in the world. Every year more individuals die from cardiovascular diseases than any other illness. Diagnosis and treatment options are limited despite current and past efforts. The molecular mechanisms that lead to the onset and progression of detrimental phenotypes in the heart remain largely elusive. To battle against the ever-increasing number of cardiovascular disease-related deaths, major goals of cardiovascular proteomics studies include the development and
utilization of cutting-edge proteomics technologies to map the dynamic cardiac and vascular proteomes, elucidate cardiovascular disease mechanisms, identify candidate therapeutic targets and provide a clinically useful diagnosis as well as risk prediction. Current emphasis is given to promoting the development and adoption of quantitative protein assays targeting highly relevant cardiovascular proteins, such that translation of proteomics technologies may be expedited. Current proteomic approaches in cardiovascular proteomics are discussed.
Papua New Guinea has about seven active mining and exploration activities for minerals like gold, copper, and other minor minerals. Each is managed by different company and
together employs about ten thousand workers. A fifth of this would be foreign workers. Most of the Mine workers that are screened at the Employees Health and Wellness clinics tend to
have similar compounding health risks
Perspective of Cardiac Troponin and Membrane Potential in People Living with ...asclepiuspdfs
Background: Hypertension is an event in which the force of the blood against the artery walls is too high leading to severe health complications and increases the risk of heart disease, stroke, and sometimes death. Aim: This study was carried out to determine the levels of cardiac troponin 1 and membrane potential in hypertensive subjects in Owerri, Imo state. Materials and Methods: A total of 120 subjects within the age 30–70 years were recruited for this study. The study consists of 60 subjects who were diagnosed of hypertension and 60 were apparently healthy individuals who served as controls subjects of the same age bracket. The levels of cardiac troponin 1 and membrane potential were analyzed using enzyme-linked immunosorbent assay technique. Data were assessed using SPSS version 20, the mean value with P ˂ 0.05 was considered statistically significant. Results: The result revealed that the levels of cardiac troponin 1 in hypertension were significantly increased when compared with control subjects while the levels of membrane potential were significantly decreased when compared to control at P < 0.05. Conclusion: The increased serum level of cardiac troponin 1 and decreased membrane potential in hypertensive subjects may contribute some risk factors in patients with hypertension.
The learning speed of the feed forward neural
network takes a lot of time to be trained which is a major
drawback in their applications since the past decades. The
key reasons behind may be due to the slow gradient-based
learning algorithms which are extensively used to train the
neural networks or due to the parameters in the networks
which are tuned iteratively using some learning algorithms.
Thus, in order to eradicate the above pitfalls, a new learning
algorithm was proposed known as Extreme Learning Machines
(ELM). This algorithm tries to compute Hidden-layer-output
matrix that is made of randomly assigned input layer and
hidden layer weights and randomly assigned biases. Unlike the
other feedforward networks, ELM has the access of the whole
training dataset before going into the computation part. Here,
we have devised a new two-layer-feedforward network (TFFN)
for ELM in a new manner with randomly assigning the weights
and biases in both the hidden layers, which then calculates the
output-hidden layer weights using the Moore-Penrose generalized
inverse. TFFN doesn’t restricts the algorithm to fix the number
of hidden neurons that the algorithm should have. Rather it
searches the space which gives an optimized result in the neurons
combination in both the hidden layers. This algorithm provides a
good generalization capability than the parent Extreme Learning
Machines at an extremely fast learning speed. Here, we have
experimented the algorithm on various types of datasets and
various popular algorithm to find the performances and report
a comparison.
Malignant Mixed Mullerian Tumor – Case Reports and Review ArticleApollo Hospitals
Malignant mixed mullerian tumors are very rare genital tumors. They are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. In descending order of frequency they originate in the uterus, ovaries, fallopian tubes, cervix and vagina. Also they arise denovo from peritoneum. They are highly aggressive and tend to occur in postmenopausal low parity women. Because of rarity, there is as such no treatment guidelines available. Multimodality treatment in the form of radical surgery followed by adjuvant chemotherapy or radiotherapy or combined chemoradiation gives a better prognosis & outcome. Two case reports of such tumors, one from ovary and other from penitoneum are presented along with the review of literature.
Intra-Fetal Laser Ablation of Umbilical Vessels in Acardiac Twin with Success...Apollo Hospitals
To interrupt blood supply to the acardiac twin in a case of TRAP sequence of monochorionic diamniotic multiple pregnancy to allow for continuation of the normal twin.
Breast Cancer in Young Women and its Impact on Reproductive FunctionApollo Hospitals
Breast cancer is the most common cancer in women in developed countries. Chemotherapy for breast cancer is likely to negatively impact on reproductive function. We review current treatment; effects on reproductive function; breastfeeding and management of menopausal symptoms following breast cancer.
Turner syndrome (gonadal dysgenesis) is one of the most common chromosomal abnormalities occuring 1 in 2500 to 1 in 3000 live-born girls. It is an important cause of short stature in girls and primary amenorrhea in young women that is usually caused by loss of part or all of an X chromosome. This review briefly summarises the current knowledge about the syndrome and the management strategies.
Due to pregnancy thyroid economy is affected with changes in iodine metabolism, TBG and development of maternal goiter. The incidence of hypothyroidism in pregnancy is quite common with autoimmune hypothyroidism being the most important cause. Overt as well as subclinical hypothyroidism has a varied impact on maternal and neonatal outcome. After multiple studies also, routine screening in pregnancy for hypothyroidism can still not be recommended. Management mainly comprises of dosage adjustments as soon as pregnancy is diagnosed based on results of thyroid function tests. The aim should be to keep FT4 at the upper end of normal range.
Growth Hormone Deficiency (GHD) can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. Growth harmone (GH) therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.
Advances in the management of thalassemia have led to marked improvements in the life span and quality of life of children and young adults. This poses new challenges for the treating physicians. There is now increasing recognition that thalassemics have impaired bone health which is multifactorial in etiology. This paper aims to highlight the factors that predispose these patients to osteoporosis and suggests measures to minimise the impact on bone health.
Laparoscopic Excision of Foregut Duplication Cyst of StomachApollo Hospitals
Retroperitoneal gastric duplication cysts lined by ciliated columnar epithelium are extremely rare lesions and its presentation during adulthood is a diagnostic challenge for treating clinicians. This entity often resembles cystic pancreatic neoplasm, retroperitoneal cystic lesions and sometimes as an adrenal cystic neoplasm. Correct diagnosis on the basis of radiological investigation is difficult and histopathologic analysis. We report a case of gastric duplication cyst in a 16year old girl that mimicked as a retroperitoneal /pancreatic /adrenal cystic lesion and was successfully managed by laparoscopy.
Occupational Blood Borne Infections: Prevention is Better than CureApollo Hospitals
Viral infections like HIV, hepatitis Band C virus pose a big risk to the contacts of individuals with high risk behaviour as well as to the attending health care workers. Blood, semen, vaginal and other potentially infectious materials can transmit the infection to the susceptible contacts. Universal precautions should be strictly implemented during clinical examination, laboratory work and surgical procedures to prevent transmission to the health care providers. Health care workers should receive vaccination for hepatitis B infection. An inadvertent exposure should be managed with proper first aid and infectivity of the source and severity of exposure should be assessed. Severity of exposure is based on the nature and area of exposed surface, mode of injury and volume of infective material. Post-exposure prophylaxis (PEP) should be started as soon as possible after a proper counseling about the effectiveness of post-exposure prophylaxis, side effects and risk of carrying the infection to his familial contacts and its prevention.
Evaluation of Red Cell Hemolysis in Packed Red Cells During Processing and St...Apollo Hospitals
Storage of red cells causes a progressive increase in hemolysis. Inspite of the use of additive solutions for storage and filters for leucoreduction some amount of hemolysis is still inevitable. The extent of hemolysis however should not exceed the permissible threshold for hemolysis even on the 42nd day of storage.
Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the tr...Apollo Hospitals
Various drugs used to treat pemphigus can cause remission, but none can provide permanent remission as relapses are common. With the introduction of DCP in pemphigus in 1984, patients started being in prolonged/permanent remission. This study was done to compare the efficacy of DCP to oral corticosteroids and cyclophosphamide in combination.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)Apollo Hospitals
Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30–35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5–15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. It is characterised by fever, rash and internal organ involvement. Prompt diagnosis is vital, along with identification and early withdrawal of suspect medicines and avoidance of re-exposure to the responsible agent is essential. Cross-reactivity to structurally-related syndrome caused by Carbamazepine medicines is common, thus first-degree relatives may be predisposed to developing this syndrome. We report a case of DRESS secondary to use of Carbamazepine.
Difficult Laparoscopic Cholecystectomy-When and Where is the Need to Convert?Apollo Hospitals
Laparoscopic cholecystectomy has now become the treatment of choice for the gall bladder stone. With increasing experience, surgeon has started to take more difficult cases which were considered relative contra indications for laparoscopic removal of gall bladder few years back.
We conducted this study at our hospital and included all laparoscopic cholecystectomy done from May'08 to January'10. Total time taken in surgery, conversion rate and complication rate were analysed. Factors making laparoscopic cholecystectomy difficult were also analysed. We defined difficult laparoscopic cholecystectomy when we found -dense fibrotic adhesions in and around Callot's triangle, gangrenous gall bladder, empyma, large stone impacted at gall bladder neck, contracted gall bladder, Mirrizi's syndrome, h/o biliary pancreatitis, CBD stones, acute cholecystitis of <72 hrs duration.
Out of 206 cases done during above period, 56 cases were considered difficult. Only two cases were converted to open.
With growing experience and technical advancement surgery can be completed in most of the difficult cases. This is important because recently it is shown in literature that laparoscopic cholecystectomy is associated with less morbidity than open method irrespective of duration of the surgery.
Deep vein thrombosis prophylaxis in a tertiary care center: An observational ...Apollo Hospitals
Deep vein thrombosis (DVT) is a major health problem with substantial mortality and morbidity in medically ill patients. Prevention of DVT by risk factor stratification and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is the most rational means of reducing morbidity and mortality.
The spread of dengue and dengue haemorrhagic fever is increasing, atypical manifestations are also on the rise, although they may be under reported because of lack of awareness. We report two such cases of dengue hemorrhagic fever with hepatitis, intraocular hemorrhage, ARDS and myocarditis.
A 71-year-old male presented in ENT department with dysphagia for last three weeks, more to solids than liquids. He had a hard bony bulge in the posterior pharyngeal wall on palpation and hence was referred for an Orthopaedic opinion. Lateral radiograph of the cervical spine revealed diffuse ossification of the anterior longitudinal ligament. This ossification was extending almost half the width of the cervical body from its anterior body at C1 and C2 vertebra level.
Pediatric Liver Transplant (LT) is now an established procedure for End Stage Liver Disease (ESLD) with biliary atresia being the commonest indication. Intensive pre-transplant evaluation, nutritional buildup and immunization are the fundamental pre-requisites of a successful LT. With improvement in surgical micro-anastomotic techniques and superior immunosuppressive regimens the success rate of pediatric LT is in excess of 90%. Most of the transplants in our country however are Living related, due to which a fairly large number of children expire awaiting a donor liver. There should be a concerted effort to evolve the cadaveric donation program, so that majority of the children are benefitted.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
2. i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/ihj
Sponsored Article
The Indian Consensus Document on cardiac
biomarker
I. Satyamurthy a,*, Jamshed J. Dalal b, J.P.S. Sawhney c, J.C. Mohan d,
Shubha A. Chogle e, Nagaraj Desai f, Shireesh P. Sathe g, Alan S. Maisel h
a
Director, Cardiology, Department of Cardiology at Apollo Hospitals, Chennai, India
Director, Centre for Cardiac Sciences, Kokilaben Dhirubhai Ambani Hospital, Mumbai, India
c
Chairman, Department of Cardiology and Member, Board of Management at Sir Gangaram Hospital,
New Delhi, India
d
Prof., Chief of Cardiology, Jaipur Golden Hospital, New Delhi, India
e
Clinical Biochemist Breach Candy Hospital, Mumbai, India
f
Professor and Advisor of Cardiology, SS Medical College and Hospital, Mysore, India
g
Consultant Cardiologist, Director e Cardiology, Deenanath Mangeshkar Hospital, Pune, India
h
Director, Coronary Care Unit and Heart Failure Program, VA San Diego, USA
b
abstract
Keywords:
Despite recent advances, the diagnosis and management of heart failure evades the cli-
Biomarkers
nicians. The etiology of congestive heart failure (CHF) in the Indian scenario comprises of
Heart failure
coronary artery disease, diabetes mellitus and hypertension. With better insights into the
Brain natriuretic peptide
pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and
NT-proBNP
prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological
derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling,
neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence,
degree of severity and prognosis of the disease, they may be employed in combination with
the present conventional clinical assessments. These make the biomarkers feasible
options against the present expensive measurements and may provide clinical benefits.
Copyright ª 2014, Cardiological Society of India. All rights reserved.
1.
Introduction
A variety of circulating molecules referred to as biomarkers
have been introduced in clinical cardiovascular research,
including heart failure (HF) research, because of basic science
discoveries and technological progress in the last decade.
Research papers related to biomarker research in HF have
been exponentially circulating over the last decade (Fig. 1).
The dissemination of knowledge about biomarkers in HF
clinical practice, however, is limited mostly to diagnostic uses
of B-type natriuretic peptide (BNP) or its precursor fragment,
N-terminal prohormone of brain natriuretic peptide (NTproBNP). Biomarkers in circulation include a variety of molecules that range from traditional protein-based markers to
newer markers and micro RNAs. Protein markers in circulation typically comprise hormones and prohormones with
vasoactive properties which include natriuretic peptides
Abbreviations: BNP, B-type natriuretic peptide; HF, heart failure.
* Corresponding author. Tel.: þ91 (0) 9840061262.
E-mail address: drismurthy@gmail.com (I. Satyamurthy).
0019-4832/$ e see front matter Copyright ª 2014, Cardiological Society of India. All rights reserved.
http://dx.doi.org/10.1016/j.ihj.2013.12.053
3. 74
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
Fig. 1 e “Biomarker” and “Heart failure” articles published
from 2001 to 2011.1
(NPs), endothelin, mid-regional pro-adrenomedullin, and
C-terminal provasopressin (copeptin); structural proteins
which include troponins; and various proteins with enzymatic
activities which include myeloperoxidase and galectin-3. The
current status of biomarker application for diagnosis and
management of HF is confusing. A general framework proposed for cardiovascular biomarkers exists and this framework can help to identify the challenges of biomarker
adoption for risk prediction, disease management, and treatment selection in HF.1
2.
Pathogenesis of heart failure
Heart failure is a multi-factorial disease with causes varying in
different parts of the world. Minimum 50% of the patients
with HF have a reduced ejection fraction (REF) i.e. HF-REF
which is the most understood type of HF in terms of the disease pathophysiology and treatment. In approximately twothirds of cases of systolic HF, coronary artery disease (CAD)
is the cause, although hypertension and diabetes are probable
contributing factors in many cases. Other factors responsible
for HF include a history of viral infections (known or unknown), chemotherapy (e.g., doxorubicin or trastuzumab),
alcohol abuse, and ‘idiopathic’ dilated cardiomyopathy (in
some of the cases the cause may be genetic).2
The epidemiological profile in HF with preserved ejection
fraction (HF-PEF) seems to be different from epidemiological
and etiological profile in HF-REF. The patient with HF-PEF
is older, and more often female and obese than those with
HF-REF. They are less likely to have coronary heart disease
and more likely to have hypertension and atrial fibrillation
(AF). As compared to patients with HF-REF, the patients with
HF-PEF have better prognosis.2
When LV systolic function is reduced, the maladaptive
changes occur in surviving myocytes and in extracellular
matrix after myocardial injury (e.g., myocardial infarction)
that lead to pathological ‘remodeling’ of the ventricle with
dilatation and impaired contractility, one measure of which is
a reduced EF. In cases of unmanaged systolic dysfunction,
there is progressive worsening of these changes over time
with an increased enlargement of the left ventricle and
declining EF, the patient may be symptomless initially.2
This progression occurs due to two mechanisms, of which
the first one is occurrence of further events leading to additional myocyte death (e.g., recurrent myocardial infarction).
The second mechanism is the systemic responses that are
induced by the decline in systolic function, particularly
neurohumoral activation. The renin-angiotensin-aldosterone
system and sympathetic nervous system are the two key
neurohumoral systems activated in HF. These systemic responses cause further myocardial injury; leading to detrimental effects on the blood vessels, kidneys, muscles, lungs,
and liver; and form a pathophysiological ‘vicious cycle’,
responsible for various clinical features of the HF syndrome,
including myocardial electrical instability.2
The basis of much of the effective treatment of HF is
interruption of these two key processes. The aforementioned
changes are associated with the clinical development of
symptoms and worsening of these over time. This results in
reduced quality of life, degrading functional capacity, recurring frank decompensation episodes leading to hospitalization and premature death, commonly as a result of
arrhythmias or pump failure. These patients have a limited
cardiac reserve which also is dependent on atrial contraction,
synchronized contraction of atriaeventricles and a normal
interaction between the right and left ventricles.2
Acute decompensation can result from intercurrent events
affecting any of these [e.g., the development of AF or conduction abnormalities, such as left bundle branch block
(LBBB)] or imposing an additional hemodynamic load on the
failing heart (e.g., anemia). The outcome of HF patients can be
improved with effective treatment, with a relative reduction
of 30e50% in hospitalization in recent years, and small but
significant decrease in mortality.2
3.
Incidence of heart failure: Indian scenario
Framingham study was a landmark study indicating that the
incidence of CHF increases with age and is higher in men than
in women. Although data on incidence of HF from India are
scarce, a 2013 study from India was conducted to measure the
burden of disease. This study was conducted in southern India
and it was found that 258 males (82%) and 137 females (73%)
had left ventricular HF predominantly, as compared to
biventricular HF. In this study, an interesting feature noted
was that multi-factorial cause was the commonest etiology
for CHF with CAD being the single most common factor
contributing to 66% of cases of HF. Out of all cases of CAD in
this study, 66% cases of HF were men and 34% were women.3
Coronary artery disease in the Framingham study, accounted
for only 46% of cases of HF in men and 27% of chronic HF cases
in women. Following CAD, hypertension was the leading
factor accounting for 65.6% of cases in this study, while 45.8%
of the population was diabetic. They are, however, not
mutually exclusive. In the Indian study, it was also found that
myocardial infarction in siblings was a significant risk factor.
69% of the patients in the present study had hypertension;
among them 61% were males and 39% were females. There
were 310 (62%) males and 190 (38%) females. The highest
incidence of HF was observed between 50 and 70 years in both
males and females. The researchers from the Indian study
4. i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
found that major etiology of CHF was a combination of CAD,
hypertension and diabetes mellitus, accounting for 23.4% of
the cases. The single commonest etiology for HF was CAD.3
4.
Multiple biomarkers used in heart
failure e clinical implications
Heart failure progression is complex and is driven by various
biological processes that include inflammation, oxidative
stress, neurohormonal activation, vascular remodeling,
myocyte injury, and renal impairment. Interest is increasing
in the measurement of a diverse biomarker profile, reflective
of the underlying biology of HF, in order to risk stratify patients and provide a better understanding of the underlying
pathophysiology. A recent study attempted to evaluate the
predictive utility of 8 biomarkers, each reflective of varied
biological pathways in HF: troponin I (TnI) (myocyte injury),
high-sensitivity C-reactive protein (hsCRP) (inflammation), Btype natriuretic peptide (BNP) (neurohormonal activation),
uric acid and myeloperoxidase (MPO) (oxidative stress), soluble toll-like receptor-2 (ST2) (myocyte stress), creatinine (renal
function) and soluble fms-like tyrosine kinase receptor-1 (sFlt1) (vascular remodeling), in a multicenter cohort of 1513
ambulatory chronic HF patients.4
The researchers hypothesized that a biomarker score
summarizing the activity of multiple pathways implicated in
HF would improve the ability to classify risk of adverse outcomes for ventricular assist device placement, cardiac transplantation, or death compared with a validated clinical risk
prediction algorithm, the Seattle Heart Failure Model (SHFM).4
A median follow up was done at 2.5 years and it was found
that there were 317 outcomes: 187 patients died; 99 were
transplanted; and 31 had a VAD placed. The patients in the
highest tertile of the multi-marker score had a 13.7-fold
increased risk of adverse outcomes compared with the
lowest tertile. The results from this study were in congruence
to the Braunwald’s hypothesis in 2008 that multiple biomarkers in combination, when classified into categories based
on their pathophysiologic effects in HF, would provide a
valuable means for risk stratification. A multi-marker score of
biomarkers, reflective of diverse biological axes, is a strong
predictor of risk and has significantly improved the prediction
of outcomes compared with the most commonly used clinical
risk score in HF, the SHFM.4
The patients who were in the highest multi-marker tertile
had around 14-fold unadjusted risk of death, transplant, or
VAD placement compared with the lowest tertile. This risk
remained nearly 7-fold after adjustment for the SHFM. A
substantial ability to discriminate individual patient risk at 1
year was shown by the multi-marker score that was again
superior to the SHFM. Multi-marker score in addition to the
SHFM appropriately reclassified a large proportion (24.1%) of
patients as higher risk.4
From these findings, it is evident that multiple biomarkers
are useful as a part of an algorithm for assessing prognosis in
HF. A score derived from multiple biomarkers, integrating
diverse biological pathways in ambulatory chronic HF patients, substantially improves prediction of adverse events
beyond current metrics.4
75
5.
Natriuretic peptides in heart failure e
relation to clinical outcomes (evidence review)
Over the last decade introduction of BNP started a new paradigm in the use of biomarkers in the evaluation and management of HF. B-type natriuretic peptide and NT-proBNP
belong to a family (Fig. 2) of naturally occurring hormones
known as NPs. High plasma BNP and NT-proBNP levels, synthesized in the cardiac ventricles, are very specific for elevated
filling pressures in the patients with left ventricular dysfunction, and can provide relatively reliable diagnostic and prognostic information.5
5.1.
Evidence review
Plasma BNP and NT-proBNP have been studied mostly as
diagnostic tools in HF patients. Two prospective multicenter
clinical trials established the role of BNP and NT-proBNP
testing in the initial evaluation of the HF patients.5
In the multicenter Breathing Not Properly Study, using
plasma BNP level of 100 pg/mL as “cut off” gave a sensitivity of
90%, specificity of 76% and a diagnostic accuracy of 81% which
was superior to clinical assessment alone in a series of 1586
patients presented to the emergency department (ED) with
acute dyspnea.5 Randomized controlled trials comparing a
diagnostic strategy involving plasma BNP testing versus clinical assessment alone, plasma BNP testing in the ED improved
the diagnosis and treatment of patients with acute dyspnea
and hence, reduced the time to discharge and the total
expenditure of treatment.5
Angurana et al7 measured BNP in 72 patients of HF with
dyspnea. B-type natriuretic peptide helped to distinguish
dyspnea of cardiac origin from non-cardiac causes. The mean
BNP concentration in patients with CHF (n ¼ 44) was found
significantly higher than in patients without CHF
(399 þ 289.2 pg/ml versus 84.9 þ 42.4 pg/ml) (p < 0. 001). Univariate analysis of plasma BNP level at different cut off levels
revealed that a value of 175 pg/ml had a sensitivity of 81.8%,
specificity of 96.4%, and accuracy of 87.5% for differentiating
CHF from lung disease. Congestive heart failure could be
predicted better by BNP measurements that added significant,
independent explanatory power to other conventionally used
clinical variables. The study suggested that rapid measurement of BNP could be a sensitive and specific test for
Fig. 2 e The processing cascade of natriuretic peptides.6
5. 76
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
differentiating the patients with HF from those without, in an
urgent care setting. Another study conducted by Krishna et al
included monitoring of the BNP levels after coronary stenting
in 100 patients suffering from acute coronary syndrome and
noted a significant rise in BNP levels post stenting (Table 1).5
Recent ACS, angiographic thrombus, raised basal troponin,
and presence of LV dysfunction were all associated with high
baseline as well as post PCI BNP levels. Elevated BNP levels
predicted recent ACS more accurately; in patients with
chronic stable angina the BNP levels increased after PCI.5
5.2.
BNP guided therapy versus clinically guided therapy
Randomized controlled trials were reviewed to produce a
recommendation on the use of NPs in the monitoring of HF
patients. The aim of the comparison was to review the
emergence of new studies on the use of NPs in monitoring
patients with HF. Three randomized trials compared BNP
guided therapy to clinically guided therapy (Table 2).5
5.3.
NT-proBNP e relation to clinical outcome
B-type natriuretic peptide is a member of a family comprising
4 NPs in human that share a common 17-peptide ring structure.7 Before its activation, BNP is stored as a 108eamino acid
polypeptide precursor, proBNP, in secretory granules in both
ventricles and, to a lesser extent, in the atria. After proBNP is
secreted in response to volume overload and resulting
myocardial stretch, it is cleaved to the 76-peptide, biologically
inert N-terminal fragment NT-proBNP and the 32-peptide,
biologically active hormone BNP. Natriuretic peptide receptors
and plasma end peptidases actively clear BNP from the circulation; the plasma half-life is thus short, approximately
20 min. No receptor-mediated clearance of NT-proBNP is
known to occur, and NT-proBNP has a correspondingly prolonged half-life of 60e120 min. Thus, plasma NT-proBNP
levels tend to be 3e5 times higher than BNP levels. B-type
natriuretic peptide and NT-proBNP are generally accepted to
be useful for the diagnostic evaluation of the patients with
acute dyspnea. Elevated BNP or NT-proBNP levels is associated
with increased cardiovascular risk as shown by a recent metaanalysis analyzing data from 40 long term prospective studies
involving a total of 10,625 incident cardiovascular outcomes
and 87,474 participants.11
5.4.
Interpretation and differential diagnosis of elevated
natriuretic peptide levels
Elevated concentrations of BNP or NT-proBNP are powerfully
associated with the presence of HF; however, neither is 100%
Table 1 e B-type natriuretic peptide levels in post PCI
patients.5
Pre PCI
Patients with baseline
BNP levels>100 pg/ml
Patients with baseline
BNP levels<100 pg/ml
diagnostic for HF. The BNP as well as NT-proBNP levels may
increase in different other disease states, and individual patient factors may influence results. Among the spectrum of HF
syndromes, HF-PEF and systolic dysfunction may raise BNP or
NT-proBNP levels; HF-PEF fraction may express lower levels of
both peptides in comparison to HF due to systolic dysfunction.
In addition, other relevant cardiac diagnoses, including right
ventricular failure (due to primary cardiac pathology, or secondary to pulmonary embolism or pulmonary hypertension),
valvular heart disease, and arrhythmias such as atrial fibrillation may cause elevation of BNP or NT-proBNP.12
Apart from cardiovascular variables, NP concentrations are
influenced by renal dysfunction and advancing age that may
generate higher values without overt HF; obesity on the other
hand may result in unexpectedly lower NP concentrations,
even in those with HF. To troubleshoot complex situations
such as renal disease, adjustment in cut off points may help
(Table 3).12
Another important situation is the patient with a gray zone
BNP or NT-proBNP value. Approximately, 20% of the patients
with acute dyspnea have BNP or NT-proBNP levels that are
above the cut off point to exclude HF but too low to definitively
identify it. Knowledge of the differential diagnosis of non-HF
elevation of NP, as well as interpretation of the BNP (Fig. 3)
or NT-proBNP (Fig. 4) value in the context of a clinical
assessment is essential; gray zone values are not without
prognostic meaning, however, and should be approached with
caution.13
In the patients with significant renal failure (estimated
glomerular filtration rate, 60 mL/min/1.73 m2) and body mass
index 35 kg/m2 different decision limits must be used (see
text).
Different decision limits must be used (see text).
6.
BNP levels in renal impairment, obesity
and gray zones
6.1.
Renal impairment
There is a high coincidence rate of CHF and chronic kidney
disease (CKD), also known as ‘cardioerenal interaction’.
Higher NP concentrations have been reported in HF patients
who are also suffering from CKD. The values of NT-proBNP
and glomerular filtration rate (GFR) have been noted to be
inversely and independently related. In the patients with
impaired renal function (GFR <60 ml/min/1.73 m2), a higher
NT-proBNP cut off point of 1200 pg/ml may effectively maximize sensitivity and specificity of HF diagnosis. So, in the case
of CHF and CKD coincidence, classic NP guided algorithms
may still be appropriate, though cut points need to be readjusted for renal function. A similar interaction has also been
noted between BNP and GFR.14
6.2.
Obesity
Post PCI
45% of patients with BNP >100 pg/ml
20% of patients with BNP >100 pg/ml
Natriuretic peptide values are remarkably lower in obese HF
patients than in non-obese patients. But, the implications of
these lowered concentrations are not yet well understood
(Table 4).15
6. Table 2 e Trials comparing BNP guided therapy with clinically guided therapy.5
Study
Beck-da-Silva, 20058
Population
-
-
Jourdain, 2007
STARS-BNP9
-
-
Pfisterer, 2009
TIME-CHF10
-
-
Dyspnea (New York Heart Association
class II with current therapy),
a history of hospitalization for HF
within the last year
Age (mean): 76 years
50% females
Age subgroups: 75 years; 75 years)
Intervention
Comparison
Implication
- b-blocker dosage up-titrated
according to plasma BNP
levels plus standard care
- b-blocker dosage
up-titrated according
standard care
A trend toward better quality of life was
seen in the BNP group as compared
to the clinically guided group
- Medical therapy was
increasingly used with the
aim of lowering plasma
BNP levels (target 100 pg/ml)
- Each class of therapy modified
according to the judgment of
the investigator
- BNP guided plus symptom
guided medical therapy
- Medical therapy to reduce BNP
levels to 2 times or less than the upper
limit of normal (400 pg/ml in
patients 75 years and 800 pg/ml
in patients 75 years) and
symptoms to NYHA class of II or less
- Medical therapy was
adjusted on the basis
of the physical
examination and usual
para clinical and
biological parameters
BNP guided strategy reduced the
risk of CHF-related death or
hospital stay for CHF
- Symptom guided
medical therapy
- Medical therapy to
reduce symptoms to
NYHA class of II or less
HF therapy guided by N-terminal
BNP did not improve overall clinical
outcomes or quality of life compared
with symptom guided treatment
HF therapy guided by N-terminal BNP
improved outcomes in patients
aged 60e75 years but not in those
aged 75 years or older
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
-
(LVEF) of 40% or less
Symptomatic HF
(New York Heart
Association class IIeIV)
for at least 3 months or
previous hospital admission
due to HF
Age (mean): 65 years.
50% males
Symptomatic (New York Heart
Association functional class IIeIII)
systolic HF defined by left ventricular
ejection fraction (LVEF) 45%
Age (mean): 65 years
50% females
77
7. 78
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
Table 3 e Suggested cut off points for BNP and NT-proBNP use in several situations.12
Cutoff value pg/mL
To exclude ADHF
BNP
NT-proBNP
To identify ADHF
Single cut off point strategy
BNP
NT-proBNP
Multiple cut point strategy
BNR, gray zone approach
Sensitivity %
Specificity %
PPV %
NPV %
30e50
300
97
99
62
68
71
62
96
99
100
900
90
90
76
85
79
76
89
94
90
73
75
90
a
a
a
a
63
90
91
84
86
88
74
66
88
89
63
72
83
74
72
94
90
90
91
87
86
77
77
70
76
90
78
77
70
79
85
90
90
91
90
95
100 to exclude; 100e400:
gray zone 400 to rule in
450 for age 50 years
NT-proBNP, age-stratified
900 for age 50e75 years 1800
approach
for age 75 years
Special situations: renal dysfunction (GFR 60 mL min 1.73 m2)
BNP
200
NT-proBNP
1200, all ages
Or
Age-stratified approach,
above
Obesity
BNP
170 for BMI 25 kg/m2
110 for 8MI 25e35 kg/m2
54 for BMI 35 kg/m2
NT-proBNP
900, no adjustment for BMI
Age-stratified cut points,
no adjustment for BMI
PPV indicates positive predictive value; NPV, negative predictive value; ADHF, acutely decompensated heart failure; BNP, brain natriuretic
peptide; NT-proBNP amino-terminal pro-B-type natriuretic peptide; GFR, glomerular filtration rate; and BMI, body mass index.
a
Indicates not applicable.
6.3.
Gray zone
Identification of a single cut off point to empirically rule in or
rule out every dyspneic patient with HF is a challenge. The
clinically prevalent algorithms are non-specific and customarily inappropriate as ‘black or white’ diagnoses can’t be made
based on them. So, to adequately screen patients, two cut off
points are necessary: one to effectively rule out HF in mildly
dyspneic patients and eliminate unneeded hospitalizations,
and another to rule in diagnosis and administer prompt,
appropriate treatment. The ‘gray zone’ between these two cut
off points in which NP concentrations cannot be utilized as
summarily to guide management decisions is the problem
area.4 A gray zone NP value should not be considered entirely
Fig. 3 e Brain natriuretic peptide interpretation in the
patients with acute dyspnea without severe renal failure.13
uninformative, though it is often not as revealing in HF diagnosis. Rather, an intermediate NP value indicates the need for
further clinical examination, and may still aid in patient
prognosis (Table 5).14
7.
Role of BNP testing in emergency
department
Natriuretic protein assays should be used as tools and not as
absolute thresholds for making decisions. A variety of
Fig. 4 e N-terminal proBNP interpretation in the patients
with acute dyspnea without severe renal failure.13
8. 79
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
Table 4 e Interpretation of NP levels in special
situations.15
Causes of elevated NP levels other than CHF
LV dysfunction
Previous heart failure
Advanced age
Renal dysfunction
Acute coronary syndrome
Pulmonary disease (e,g., acute respiratory distress syndrome,
lung disease with right heart failure)
Pulmonary embolism
High output states (e.g., sepsis, cirrhosis, hyperthyroidism)
Atrial fibrillation
NP levels lower than expected
Obesity
Flash pulmonary edema
Heart failure etiology upstream from LV (e.g., acute mitral
regurgitation, mitral stenosis)
Cardiac tamponade
Pericardial constriction
CHF, congestive heart failure; LV, left ventricle; NP, natriuretic
peptide.
conditions other than CHF can lead to increased levels: acute
coronary syndrome, pre existing structural heart disease,
right ventricular strain, critical illness, or end-stage renal
failure.16
B-type natriuretic peptide independently predicts high left
ventricular end-diastolic pressure and capillary pulmonary
artery pressure. These pressures correlate well to the NYHA
(New York Heart Association) classification of severity of HF,
and inversely correlate to left ventricular ejection fraction. It
has been shown by some studies that BNP and NT-proBNP can
reliably predict the presence or absence of left ventricular
dysfunction on echocardiography in symptomatic and
asymptomatic HF patients presenting to ED.17
Last decade has seen that BNP has the potential clinical
usefulness for differential diagnosis of dyspnea and for risk
stratification of the patients with CHF. The European Society
of Cardiology Task Force has recommended that the algorithm for HF diagnosis should include an NP assay as the first
step along with electrocardiography (ECG) and chest X-ray.17
The key symptom of CHF and of many other respiratory
diseases, with high associated morbidity and mortality, is
acute dyspnea. It is unfortunate to observe that emergency
physicians’ accuracy in diagnosing CHF is about 60%. In the
EPIDASA study, conducted on patients older than 65 years
with acute dyspnea, the in-hospital mortality was 16%, with a
higher mortality (21%) in the patients with CHF. The treatment
in ED was inappropriate in 32% patients, and led to a higher
mortality, highlighting the importance of accurate diagnosis
and early accurate treatment in the ED. The initial general
practitioner diagnosis of HF was confirmed in only 34% of the
cases in a prospective study in UK. The clinical indecision at
the ED leads to inappropriate hospitalization and use of
potentially dangerous therapy. The ED physician is uncertain
of the diagnosis (intermediate probability) in one-third of
patients.18
Many studies have evaluated and validated both NP in the
diagnosis of CHF in acute dyspnea. Maisel et al19 performed
the largest studies for BNP and Januzzi et al20 for NT-proBNP.
Following few observations are worth noting from these
studies:
A BNP concentration 100 pg/mL is a strong independent
predictor of CHF
Accuracy of BNP (83%) was more than either the NHANES
criteria (67%) or the Framingham criteria (73%), two
commonly used sets of criteria for diagnosing CHF
The diagnostic accuracy of BNP at a cut off of 100 pg/ml was
83.4%
The negative predictive value of this threshold was
particularly high (98%)
The patients who presented in the ED with dyspnea were
included in the PRIDE (ProBNP Investigation of Dyspnea in the
Emergency Department) study. N-terminal proBNP was found
to be highly sensitive and specific for the diagnosis of acute
CHF, with an optimal cut off of 900 pg/ml. The strongest independent predictor of a final diagnosis of acute CHF was
increased NT-proBNP. Clinical judgment alone for diagnosing
acute CHF was inferior to NT-proBNP testing alone.
8.
Neurobiomarkers in heart failure:
galectin-3
Galectins are part of a family of lectins which bind b-galactosides. These galectins are expressed in vertebrates as well as
in invertebrates and even in lower organisms, such as sponge
Table 5 e Diagnostic value of BNP (TriageBNPÒ): Study summaries.21
Logeart22
Number of patients
Mean age
Acute CHF (%)
Male (%)
Threshold value (pg/ml)
Sensitivity (%)
Specificity (%)
Dao23
Lainchbury24
Maisel19
Ray25
166
67
70
67
300
88 [NA]
87 [NA]
250
ND
39
94
100
94 [89e97]
94 [89e97]
205
70
34
49
208
94 [NA]
70 [NA]
1586
64
47
56
100
90 [88e92]
76 [73e79]
308
80
46
50
250
78 [71e84]
90 [84e93]
MA: not available.
Grossly, the higher is the mean age of the population evaluated, the higher is the threshold value of BNP and NT-proBNP; 95% CI for sensitivity
and specificity were given when available [CI].
9. 80
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
Fig. 5 e Galectin-3 pathway.27
and fungus, which suggest an important role in biology.
Presently, 15 members of the galectin family have been
observed in vertebrates. In a seminal paper by Sharma et al26 it
was observed that galectin-3 is increased in decompensated
HF. The authors of the paper opined that galectin-3 may be a
factor that should be considered as a novel target for intervention in HF due to the observation that galectin-3 was
upregulated well before the transition to overt HF.24
10. i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 7 3 e8 2
Galectin-3 has many effects in various organs. It has been
shown that activated macrophages secrete galectin-3 in the
failing or stressed heart. Increased expression levels of
galectin-3 are associated with the tendency to develop
decompensated HF, and in clinical cohorts, increased plasma
galectin-3 levels are linked with worse prognosis. Consequently, galectin-3 may be proclaimed as a novel biomarker,
but it may also be in the pathophysiologic circle of HF (“culprit
biomarker”), and therefore it may also be a target for intervention. The suggested pathways of galectin-3 are displayed
in Fig. 5.26
But, uncertainties are present in proclaiming galectin-3 as
a novel biomarker. Regulation of galectin-3 is unknown at a
transcriptional and translational level in the heart. It has been
demonstrated in mechanistic studies that cardiac fibroblasts
and macrophages are the main sources for galectin-3, and
that the TGF-b/Smad pathway is involved. Regulation is also
governed by inflammatory signals. But, it is confusing as to
which signals govern the production and secretion of galectin3. Also, proof-of-principle experiments (e.g., in galectin-3
deficient mice or in pharmacologic studies), to show that
galectin-3 is unequivocally contributing to the onset and
progression of cardiac remodelling are lacking. Again, data on
therapeutic aspects involving galectin-3 expression and
signaling are lacking.26
Available clinical data suggest that plasma and/or serum
galectin-3 is increased in acute and chronic HF. Galectin-3
could be of value to predict prognosis in HF patients.
Galectin-3 in clinical diagnosis and/or decision making is less
convincing as we do not have enough data available to support the use of the same for this purpose.27
Studies have indicated that standard treatment of HF is
related to lowering of galectin-3 expression and levels; it can
be argued that galectin-3 could be a potential target for therapy. In few small trials, galectin-specific agents have been
tested but these agents have not been evaluated in experimental or clinical HF. Results of studies testing targeted
therapy against galectins should stress for their value in this
devastating disease.27
9.
Multi-marker strategy for complex
patients
Heart failure is a major public health issue. In order to provide an accurate individualization of HF risk and care, the
approach should include a profile of laboratory data, in
addition to clinical and imaging data. It is clinically important to identify the most vulnerable patients, especially
considering that many therapeutic interventions are available today. Although many novel biomarkers have been
proposed and tested this goal has not been yet reached. The
complexity of the biochemical network involved in the
pathophysiology of HF suggests the ineffectiveness of a single marker to reflect all the features of this disease syndrome. Combining more markers would help in better
characterization of HF patients and thus create newer options for treatment and identification of patients that need a
close follow up.
81
The multi-marker approach, considering various
biochemical pathways simultaneously, bases its robustness
on a suitable choice of indices known to be individually
associated with HF. Biomarker combination choice is essential
to the performance of the multi-marker strategy.28
A major issue in choosing the biomarker profile is the
proportional increase in financial burden. Hence, for cost
effective evaluation, a biomarker combination has to be used.
Heavily influence results would appear from statistical analysis and analytical performance of the different elements of
the combination.28
10.
Conclusion
Use of NT-proBNP or BNP for management of HF is warranted
in view of the increasing prevalence of this serious condition
and the need to consider a broadening spectrum of dysfunction for treatment. In addition, the complexity of treatment is
increasing with a number of agents demonstrated as effective
through randomized controlled trials. B-type natriuretic peptide and NT-proBNP have comparable clinical utility, and both
help in excluding acute HF. Their use prior to discharge in
hospitalized patients aids risk stratification. In addition,
Galectin-3 may be a factor that should be considered as a
novel target for intervention in HF due to the observation that
galectin-3 was upregulated well before the transition to overt
HF. There will be variable clinical expertise available to diagnose and manage the increasing cohort of HF patients with
the passage of time, and an objective indicator to assist
optimal prescription of medications is necessary. At present,
plasma measurements of BNP or NT-proBNP, along with selective use of Galectin-3, constitutes the best candidate for
this function.
11.
Recommendations for physicians
B-type natriuretic peptide and NT-proBNP are not routinely
used for bedside diagnosis of CHF. This testing is very much
useful in the ED, particularly in patients presenting with
dyspnea when one is uncertain regarding diagnosis of HF.
Sometimes, there could be concurrence of CHF with respiratory failure or asthma like illness. In this scenario, serial
measurements of cardiac biomarkers can help to diagnose as
well as plan optimal therapeutic strategies in cases with CHF.
The measurement of cardiac biomarkers also helps to predict
the prognosis and optimal timing for discharging a patient.
B-type natriuretic peptide, in conjunction with Galectin-3,
may be used to identify those patients at higher risk of readmission or death thus allowing the physician to better match
the level of care to an individual patient’s needs. These biomarkers are helpful to physicians, emergency physicians, and
cardiologists in day-to-day practice.
Conflicts of interest
All authors have none to declare.
11. 82
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references
1. Kalogeropoulos AP, Georgiopoulou VV, Butler J. Clinical
adoption of prognostic biomarkers: the case for heart failure.
Prog Cardiovasc Dis. 2012;55:3e13.
2. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines
for the diagnosis and treatment of acute and chronic heart
failure 2012: the task force for the diagnosis and treatment of
acute and chronic heart failure 2012 of the European Society
of Cardiology. Developed in collaboration with the Heart
Failure Association (HFA) of the ESC. Eur Heart J.
2012;33:1787e1847.
3. Banumathy S, Rao VD, Joshi L, Govindarajan U. Etiology of
congestive heart failure in Indian population e an acute care
study of 500 cases. J Indian Coll Cardiol. 2013;3:43e48.
4. Ky B, French B, Levy WC, et al. Multiple biomarkers for risk
prediction in chronic heart failure. Circ Heart Fail.
2012;5:183e190.
5. Krishna A, Kapoor A, Kumar S, Tewari S, Garg N, Goel P.
Elevated B-type natriuretic peptide levels in patients
undergoing coronary stenting. J Invasive Cardiol.
2011;23:240e245.
6. van Kimmenade RR, Januzzi Jr JL. Emerging biomarkers in
heart failure. Clin Chem. 2012;58:127e138.
7. Angurana DK, Lone NA, Khan KA, et al. Rapid measurement
of B-type natriuretic peptide in the diagnosis of congestive
heart failure in patients presenting to the emergency
department with acute shortness of breath. Int J Med Med Sci.
2011;3:77e82.
8. Beck-da-Silva L, de Bold A, Fraser M, Williams K, Haddad H.
BNP-guided therapy not better than expert’s clinical
assessment for beta-blocker titration in patients with heart
failure. Congest Heart Fail. 2005;11:248e253.
9. Jourdain P, Jondeau G, Funck F, et al. Plasma brain natriuretic
peptide-guided therapy to improve outcome in heart failure:
the STARS-BNP Multicenter Study. J Am Coll Cardiol.
2007;49:1733e1739.
10. Pfisterer M, Buser P, Rickli H, et al, TIME-CHF Investigators.
BNP-guided vs symptom-guided heart failure therapy: the
trial of intensified vs Standard Medical Therapy in Elderly
Patients with Congestive Heart Failure (TIME-CHF)
randomized trial. JAMA. 2009;301:383e392.
11. Reddy S, Bahl A, Talwar KK. Congestive heart failure in
Indians: how do we improve diagnosis management? Indian
J Med Res. 2010;132:549e560.
12. Kim HN, Januzzi Jr JL. Natriuretic peptide testing in heart
failure. Circulation. 2011;123, 2015-9.
13. Thygesen K, Mair J, Mueller C, et al. Study Group on
Biomarkers in Cardiology of the ESC Working Group on acute
cardiac care. Recommendations for the use of natriuretic
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
peptides in acute cardiac care: a position statement from the
Study Group on Biomarkers in Cardiology of the ESC Working
Group on acute cardiac care. Eur Heart J. 2012;33:2001e2006.
Chen WC, Tran KD, Maisel AS. Biomarkers in heart failure.
Heart. 2010;96:314e320.
Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol.
2007;50:2357e2368.
Januzzi Jr JL. Natriuretic peptide testing: a window into the
diagnosis and prognosis of heart failure. Cleve Clin J Med.
2006;73:149e152, 155-7.
Ray P, Delerme S, Jourdain P, Chenevier-Gobeaux C.
Differential diagnosis of acute dyspnea: the value of B
natriuretic peptides in the emergency department. QJM.
2008;101:831e843.
Ray P, Birolleau S, Lefort Y, et al. Acute respiratory failure in
the elderly: etiology, emergency diagnosis and prognosis. Crit
Care. 2006;10:R82.
Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid
measurement of B-type natriuretic peptide in the emergency
diagnosis of heart failure. N Engl J Med. 2002;347:161e167.
Januzzi JL, Camargo CA, Anwaruddin S, et al. The N-terminal
Pro-BNP investigation of dyspnea in the emergency
department (PRIDE) study. Am J Cardiol. 2005;95:948e954.
Delermer S, Chenevier-Gobeaux C, Doumenc B, Ray P. The
diagnostic value of B natriuretic peptide in elderly patients
with acute dyspnea. Clin Med Cardiol. 2008:2115e2124.
Logeart D, Saudubray C, Beyne P, et al. Comparative value of
Doppler echocardiography and B-type natriuretic peptide
assay in the etiologic diagnosis of acute dyspnea. J Am Coll
Cardiol. 2002;40:1794e1800.
Dao Q, Krishnaswamy P, Kazanegra R, et al. Utility of
B-type natriuretic peptide in the diagnosis of congestive
heart failure in an urgent-care setting. J Am Coll Cardiol.
2001;37:379e385.
Lainchbury JG, Campbell E, Frampton CM, Yandle TG,
Nicholls MG, Richards AM. Brain natriuretic peptide and nterminal brain natriuretic peptide in the diagnosis of heart
failure in patients with acute shortness of breath. J Am Coll
Cardiol. 2003;42:728e735.
Ray P, Arthaud M, Lefort Y, et al. Usefulness of B-type
natriuretic peptide in elderly patients with acute dyspnea.
Intensive Care Med. 2004;30:2230e2236.
Sharma UC, Pokharel S, van Brakel TJ, et al. Galectin-3 marks
activated macrophages in failure-prone hypertrophied hearts
and contributes to cardiac dysfunction. Circulation.
2004;110:3121e3128.
De Boer RA, Yu L, van Veldhuisen DJ. Galectin-3 in cardiac
remodelling and heart failure. Curr Heart Fail Rep. 2010;7:1e8.
Giannessi D. Multimarker approach for heart failure
management: perspectives and limitations. Pharmacol Res.
2011;64:11e24.
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