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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of oedema in cor pulmonale remain unexplained. On the basis of a small number of studies, cor pulmonale is not caused by cardiac muscle failure, at least in early oedematous phases. Progressive and persistent elevation of pulmonary vascular resistance may exceed the pumping capacity of the right ventricle in later stages. Alternative explanations for the sharp fall in renal blood flow as oedema appears should be sought. The renin-angiotensin-aldosterone system seems causally related to oedema. The curious position of hypercapnia remains an enigma. Surprisingly few studies of hypercapnia, renal blood flow and renal hormones are reported. Redistribution of body water from intracellular to the extracellular space may be in part due to the need to buffer extracellular respiratory acidosis caused by hypercapnia. It provides an explanation for one form of hypercapnic oedema. Cyclical loss and gain of tissue mass seems more evident in cor pulmonale than ischaemic or valvular heart failure.
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PMID:Oedema in cor pulmonale. 703 67

Dementia in the elderly used to be rare, but why has it become a major social threat today? There can be many potential answers, but an ultimate one is clear: the longer life expectancy today. This knowledge indicates that "advanced aging" is a primary suspect in the origin of senile dementia. If so, then why can many elderly remain healthy at the same old age? We know, for example, that elderly people commonly have a certain degree of atherosclerosis and osteoporosis, but only some of them develop severe clinical symptoms at the same age. These different outcomes generally can be explained by "risk factors" in life (exercise, diet, individual background, etc). It thus appears to be a general pattern that advanced aging (after age 80) will set the stage for various senile disorders, but risk factors largely determine the onset age as well as individual specificity of their clinical manifestations. In this context, senile disorders including senile dementia would differ fundamentally from the pathogen-caused conventional diseases (AIDS, polio, cancer, Down's, etc.) by origin, incidence, and intervention strategy. This view would call into question the current definition of senile dementia as a conventional "disease" (Alzheimer's). The term "Alzheimer's disease" originally referred to "midlife" dementia, but it is defined today to be the same medical entity as senile dementia on the basis that they both display the same hallmarks and symptoms despite their onset age difference. Now, after in-depth scrutiny, we finally come to realize that they are not the same disease, but as different as heart failure at midlife versus the "same" failure at advanced age (i.e., a conventional disease versus a senile condition). Thus, by eliminating the age difference, the new definition has converted a senile condition into a conventional "disease", thereby changing the course of its scientific inquiry to miss the main targets. This may be why after extensive studies for 25 years, the origin of senile dementia has remained an enigma.
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PMID:Alzheimer movement re-examined 25 years later: is it a "disease" or a senile condition in medical nature? 1150 85

One of the scientific missions of the XXI century is the integration of the basic research with the clinical medicine. One example in the change of century is heart failure (HF). The macroscopic anatomy, the cardiac physiology and the molecular biology have modified and enriched the conception of HF. The enigma of cardiac architecture has been solved. The heart works as a piston of explosion machine, a piston in which its walls twisted while shortening ejecting the blood in systole and sucking the blood in diastole. The HF is a single process with three phases; umpired relaxation, diastolic failure and diastolic and systolic failure all together.
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PMID:[Architecture of the heart and heart failure]. 1461 41

The current understanding of dialysis-related amyloidosis has evolved over the past two decades. In the early 1980s, several researchers found amyloid deposits in the synovia of carpal tunnel syndrome (CTS), which have been recognized as a complication of chronic hemodialysis. The enigma was resolved in 1985, when beta2-microglobulin (beta2-m) with a molecular weight of 12,000 Da was identified as the major constitutional protein of this amyloid. Amyloid fibrils of this type that contain the sub-unit protein of human leukocyte antigens (HLA), beta2-m, deposit predominantly in osteoarticular tissues, inducing musculoskeletal symptoms such as CTS, polyarthralgia, bone cyst showing radiolucency at X-ray examination and destructive spondyloarthropathy. In addition, extra articular symptoms such as ischemic colitis, megaloglossia, and heart failure, that is, systemic involvement occasionally occur. We confirmed that the prevalence of CTS increases with duration of dialysis. Most patients with CTS associated with beta2-m amyloid deposits have undergone hemodialysis for 10 years or more. Up to 50% of patients had developed this complication after 20 years and the percentage was even higher after 25 years. General categories of therapeutic approaches for amyloidosis include prevention of onset or progression, symptomatic therapy (conservative treatment, orthopedic procedures, and physiotherapy), and renal transplantation. It is critical to elucidate the detail mechanisms of the amyloid fibril formation, and establish its radical treatment. It is also important to develop novel therapies such as cell implantation to compensate for normal kidney functions of uremic toxin protein metabolism.
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PMID:Current clinical aspects of dialysis-related amyloidosis in chronic dialysis patients. 1691 Nov 83

To this day the aetiology of sarcoidosis continues to elude definition. Partially as a consequence of this, little in the way of new therapies has evolved. The enigma of this condition is that, unusually for a disease with the potential for devastating consequences, many patients show spontaneous resolution and recover. Cardiac involvement can affect individuals of any age, gender or race and has a predilection for the conduction system of the heart. Heart involvement can also cause a dilated cardiomyopathy with consequent progressive heart failure. The most common presentation of this systemic disease is with pulmonary infiltration, but many cases will be asymptomatic and are detected on routine chest radiography revealing lymphadenopathy. Current advances lie in the newer methods of imaging and diagnosing this unusual heart disease. This review describes the pathology and diagnosis of this condition and the newer imaging techniques that have developed for determining cardiac involvement.
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PMID:Sarcoid heart disease. 1791 69

Two clinical trials will be reviewed, RALES(1) and ILLUMINATE.(2) In RALES, low-dose spironolactone in addition to standard of care, produced a 30% improvement in survival in progressive heart failure, commonly assumed to reflect deleterious effects of aldosterone, with spironolactone competing with aldosterone for cardiac mineralocorticoid receptors. Recent evidence, however, points to cortisol rather than aldosterone as the hormone activating cardiac mineralocorticoid receptors, under conditions of tissue damage, and spironolactone as acting by mechanisms other than receptor blockade. ILLUMINATE compared the effects of torcetrapib, a cholesterol ester transport protein inhibitor, in combination with atorvastatin vs. atorvastatin alone, and was terminated after excess mortality was found in the torcetrapib arm. Subjects receiving torcetrapib showed effects consistent with increased aldosterone secretion, subsequently confirmed on patient samples and in vitro. In animal experiments, the pressor effect of torcetrapib was abolished by adrenalectomy but not by administration of trilostane, an inhibitor of aldosterone secretion. Although aldosterone (and probably cortisol) excess is involved in the off-target effects of torcetrapib, they may also involve secretion of endogenous oubain from the adrenal glomerulosa. This possibility may explain the enigma of aldosterone being homeostatic in chronic sodium deficiency, but deleterious in the presence of inappropriate sodium levels.
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PMID:Aldosterone, hypertension and heart failure: insights from clinical trials. 2063 15

A wide variety of cardiac disease states can induce remodelling and lead to the functional consequence of heart failure. These complex disease states involve a plethora of parallel signal transduction events, which may be associated with tissue injury or tissue repair. Innate immunity is activated in hearts injured in different ways, evident as cytokine release from the heart, activation of toll-like receptors involved in recognizing danger, and activation of the transcription factor nuclear factor kappa B. Nuclear factor kappa B regulates gene programmes involved in inflammation as well as the resolution of inflammation. The impact of this is an enigma; while cytokines, toll-like receptors, and nuclear factor kappa B appear to elicit myocardial protection in studies of preconditioning, the literature strongly indicates a detrimental role for activation of innate immunity in studies of acute ischaemia-reperfusion injury. The impact of activation of cardiac innate immunity on the long-term outcome in in vivo models of hypertrophy and remodelling is less clear, with conflicting results as to whether it is beneficial or detrimental. More research using genetically engineered mice as tools, different models of evoking remodelling, and long-term follow-up is required for us to conclude whether activation of the innate immune system is good, bad, or unimportant in chronic injury models.
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PMID:Innate immunity and remodelling. 2069 32

Mixed lesion of Restrictive Cardiomyopathy and Constrictive Pericarditis is a rarely reported clinical entity which poses a diagnostic and therapeutic enigma to physicians. The management of both conditions differs markedly. Restrictive Cardiomyopathy is managed either conservatively or cardiac transplant may be offered. On the other hand, Constrictive Pericarditis can be surgically treated by pericardiectomy. We report a rare case of decompensated heart failure presenting with mixed features of both constrictive and restrictive cardiomyopathy.
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PMID:Mixed constrictive pericarditis and restrictive cardiomyopathy in a 36-year-old female. 2275 23

Heart failure with preserved ejection fraction (HFPEF) is responsible for half the disease burden of heart failure worldwide, yet there is still much we do not know about this syndrome. Its pathophysiology is classically attributed to diastolic dysfunction (thus "diastolic heart failure"), but accumulating evidence suggests that heterogeneous mechanisms contribute to HFPEF, including systolic abnormalities. Importantly, there remains no proven therapy for HFPEF. To date, clinical trials of neurohormonal blockade have failed to improve outcomes in HFPEF, despite their proven benefits in heart failure with reduced ejection fraction (HFREF). Therefore, it is still an urgent need to better understand the pathophysiology of HFPEF and identify new therapeutic targets. Such potential targets include the myocyte protein titin, intracellular calcium regulation, as well as modulation of the extracellular matrix. We also need to understand why the previous large trials have failed in HFPEF. Are we studying the right patients? How do we best diagnose this syndrome? Are we assessing the appropriate outcomes? Causes of mortality and morbidity differ between HFPEF and HFREF, and the high burden of comorbidities in HFPEF may contribute to noncardiovascular outcomes. Newer therapeutic approaches should be developed with these considerations in mind. In conclusion, HFPEF is still an enigma. New pathophysiological concepts, improved diagnostic strategies, and a better understanding of patient factors are needed to generate new therapeutic options in the future.
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PMID:Diastolic heart failure: What we still don't know. Looking for new concepts, diagnostic approaches, and the role of comorbidities. 2317 53

For decades, peripartum cardiomyopathy has remained an enigma. Despite extensive research, our understanding of how a previously healthy woman can develop lethal heart failure in the context of pregnancy remains vague. Recent work suggests that inadequacy of the cardiac microvasculature may be the primary abnormality and has implicated an antiangiogenic fragment of the nursing hormone prolactin as playing an important role. In this issue of the JCI, Halkein et al. explore signaling downstream of this prolactin fragment and demonstrate that miR-146a is a critical mediator of the antiangiogenic effects in endothelial cells. In addition, the study uncovers unexpected exosomal transfer of this microRNA to cardiomyocytes that may affect myocardial metabolism.
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PMID:A microRNA links prolactin to peripartum cardiomyopathy. 2361 65


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