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

In this narrative review of the current literature, we examine the central and peripheral mechanisms responsible for the exercise intolerance of chronic heart failure and highlight briefly the benefits of exercise training in the treatment of this debilitating disorder. Specifically, we identify the common finding of reduced cardiac output reserve during exercise conditions leading to decreased exercise tolerance. We also reveal that the stroke volume response to exercise varies depending on the individual patient, the presence of mitral regurgitation, and the aetiology of heart failure. Chronic heart failure patients with left ventricular systolic dysfunction appear able to use the Frank-Starling mechanism to compensate (in part) for their decreased contractile reserve. Patients with left ventricular diastolic dysfunction have normal contractile function; however, they are unable to make use of the Frank-Starling mechanism during exercise conditions. We also reveal that pericardial constraint may limit diastolic filling and exercise capacity in patients with chronic heart failure. It appears that interventions that reduce pericardial constraint and mitral regurgitation enhance diastolic filling and increase exercise tolerance. A series of peripheral muscle changes also occur, including changes in muscle mass, cellular structure, energy metabolism, and blood flow. Each of these factors is associated with decreased exercise capacity and the symptoms of chronic heart failure. Exercise training has been shown to improve both central haemodynamics and peripheral muscle function leading to improvements in exercise capacity, functional status, and overall quality of life in patients with chronic heart failure.
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PMID:Central haemodynamics and peripheral muscle function during exercise in patients with chronic heart failure. 1748 76

Although our current appreciation of the detrimental role of neurohumoral activation in heart failure (HF) has been intellectually appealing and has led to neurohumoral antagonism that has reduced morbidity and mortality from HF, the persisting disability and death rates remain unacceptably high. In the search for novel strategies to improve on these outcomes, we must reacquaint ourselves with basic cardiac physiology at levels ranging from the molecular to the systemic in order to identify new targets for the treatment of HF. This approach has already begun to yield results; in this review, two such aspects will be focused on: diastolic ventricular interaction and cardiac energetics. These two examples will be used to illuminate how fundamental research has elucidated age-old, although mechanistically elusive, principles (for example, the Frank-Starling law), explained why existing and emerging therapeutic approaches (for example, biventricular pacing in HF) have proved successful, and successfully identified novel therapy modes (for example, perhexiline as an energy augmentation agent).
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PMID:The pathophysiology of heart failure: a tale of two old paradigms revisited. 1847 70

Chronic heart failure is one of the most frequent causes of death in humans. Knockout of type 5 adenylyl cyclase (AC) in mice causes longevity and protection from cardiomyopathy, and an AC5 inhibitor reduces beta-adrenoceptor-stimulated Ca(2+) inward currents in isolated mouse cardiomyocytes. These data indicate that selective AC5 inhibitors may be beneficial in chronic heart failure. Therefore, we characterized AC in mouse heart membranes. Real-time polymerase chain reaction and immunoblot analysis suggested that AC5 is an important heart AC isoform. Enzyme kinetics of heart AC and recombinant AC5 in the presence of Mg(2+) were similar. Moreover, the inhibitory profile of eight 2'(3')-O-(N-methylanthraniloyl) (MANT)-nucleoside 5'-([gamma-thio])triphosphates on mouse heart in the presence of Mg(2+) was almost identical to that of AC5. MANT-ITP was the most potent inhibitor of heart AC and recombinant AC5, with K(i) values in the 15 to 25 nM range in the presence of Mg(2+) and in the 1 to 5 nM range in the presence of Mn(2+). However, in the presence of Mn(2+), we also noted differences between mouse heart AC and AC5 with respect to enzyme kinetics and forskolin analog effects. In conclusion, with regard to expression and kinetics and inhibition by MANT-nucleotides in the presence of Mg(2+), AC5 is an important AC isoform in heart, with MANT-ITP being an excellent starting point for the design of AC5-selective inhibitors. Unfortunately, a limitation of our study is the fact that immunologically and biochemically, AC5 and AC6 are quite similar, although they have different roles in heart. Moreover, lack of antibody specificity and Mn(2+) masking AC5 effects were problems.
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PMID:Characterization of mouse heart adenylyl cyclase. 1930 50

An 81-year-old woman was referred to our hospital for surgical treatment for mitral valve regurgitation, tricuspid valve regurgitation and atrial fibrillatory bradycardia. The platelet count on admission was 4.9 x 10(4)/microl. and the results of other studies were compatible with idiopathic thrombocytopenic purpura. Although we performed high-dose transvenous immunoglobulin infusion (400 mg/kg/day) for 5 consecutive days, the platelet count showed no remarkable change. Because of progression of heart failure, we underwent cardiac operation under thrombocytopenic condition. Intra and post-operative platelet transfusion might contribute to postoperative course uneventful without bleeding tendency. In this case, high-dose immunoglobulin therapy was not effective. However the operative course was satisfactory with adequate surgical hemostasis and platelet transfusion.
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PMID:[Cardiac surgery in an octogenarian with idiopathic thrombocytopenic purpura: report of a case]. 1999 99

We describe a case of severe acute aortic regurgitation in a 60-year-old woman due to spontaneous avulsion of an aortic valve commissure. She presented with spontaneous bleeding and a platelet count of 4 000/microl caused by idiopathic thrombocytopenic purpura and developed acute heart failure and respiratory insufficiency. Preoperative transesophageal echocardiography was not diagnostic for the exact mechanism of aortic regurgitation. She received a 2-day course of intravenous immunoglobulin (0.5 mg/kg/d) to increase platelet count. At operation detachment (avulsion) of the commissure between the left and the right coronary cusp was evident. Aortic valve repair was performed with resuspension of the commissure. The postoperative course was uneventful. During a 24-month follow-up period, the patient has remained in NYHA class I.
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PMID:Repair of aortic regurgitation caused by spontaneous avulsion of aortic valve commissure in a patient with idiopathic thrombocytopenic purpura. 2007 76

Most elderly persons with heart failure have a preserved left ventricular (LV) ejection fraction (HFPEF). The pathophysiology of this disorder is not well understood, and there are conflicting data regarding the role of decreased LV distensibility. To assess LV distensibility over a range of preload conditions while minimizing the large, confounding changes in contractility, afterload, and heart rate characteristic of exercise, we measured LV end-diastolic volume (EDV), stroke volume (SV), and cardiac output (CO) using two-dimensional echocardiography in 48 elderly (mean age, 69 yr) HFPEF patients and 25 healthy age-matched controls during quiet supine rest, 45 degrees head-up tilt (HUT), and 45 degrees head-down tilt (HDT). As a result, when compared with controls, HFPEF patients had reduced percent changes in EDV (-7 +/- 2 vs. -17 +/- 2%; P = 0.003), SV (-7 +/- 3 vs. -27 +/- 2%; P = 0.003), and CO (-6 +/- 4 vs. -34 +/- 4%; P = 0.001) during the transition from supine to HUT. HFPEF also had reduced percent changes in EDV (8 +/- 2 vs. 15 +/- 2%; P = 0.02), SV (11 +/- 3 vs. 21 +/- 3%; P = 0.002), and CO (1 +/- 4 vs. 12 +/- 4%; P = 0.04) during the transition from HUT to HDT. In conclusion, HFNEF patients have reduced LV distensibility in response to postural change, resulting in blunted EDV, SV, and CO. This provides further support for the hypothesis that a blunted Frank-Starling mechanism may contribute to the pathophysiology of HFPEF.
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PMID:Decreased left ventricular distensibility in response to postural change in older patients with heart failure and preserved ejection fraction. 2056 34

Ventricular assist devices (VADs) are increasingly used for supporting blood circulation in heart failure patients. To protect or even to restore the myocardial function, a defined loading of the ventricle for training would be important. Therefore, a VAD control strategy was developed that provides an explicitly definable loading condition for the failing ventricle. A mathematical model of the cardiovascular system with an axial flow VAD was used to test the control strategy in the presence of a failing left ventricle, slight physical activity, and a recovering scenario. Furthermore, the proposed control strategy was compared to a conventional constant speed mode during hemodynamic changes (reduced venous return and arterial vasoconstriction). The physiological benefit of the control strategy was manifested by a large increase in the ventricular Frank-Starling reserve and by restoration of normal hemodynamics (5.1 L/min cardiac output at a left atrial pressure of 10 mmHg vs. 4.2 L/min at 21 mmHg in the unassisted case). The control strategy automatically reduced the pump speed in response to reduced venous return and kept the pump flow independent of the vasoconstriction condition. Most importantly, the ventricular load was kept stable within 1%, compared to a change of 75% for the constant speed. As a key feature, the proposed control strategy provides a defined and adjustable load to the failing ventricle by an automatic regulation of the VAD speed and allows a controlled training of the myocardium. This, in turn, may represent a potential additional tool to increase the number of patients showing recovery.
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PMID:Left ventricle afterload impedance control by an axial flow ventricular assist device: a potential tool for ventricular recovery. 2063 46

Titin is a giant sarcomeric protein that extends from the Z-line to the M-line. Due to its location, it represents an important biomechanical sensor, which has a crucial role in the maintenance of the sarcomere structural integrity. Titin works as a "bidireactional spring" that regulates the sarcomeric length and performs adequate adjustments of passive tension whenever the length varies. Therefore, it determines not only ventricular rigidity and diastolic function, but also systolic cardiac function, modulating the Frank-Starling mechanism. The myocardium expresses two isoforms of this macromolecule: the N2B, more rigid and the isoform N2BA, more compliant. The alterations in the relative expression of the two titin isoforms or alterations in their state of phosphorylation have been implicated in the pathophysiology of several diseases, such as diastolic heart failure, dilated cardiomyopathy, ischemic cardiomyopathy and aortic stenosis. The aim of this study is to describe, in brief, the structure and location of titin, its association with different cardiomyopathies and understand how alterations in this macromolecule influence the pathophysiology of diastolic heart failure, emphasizing the therapeutic potential of the manipulation of this macromolecule.
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PMID:The role of titin in the modulation of cardiac function and its pathophysiological implications. 2135 82

An 83-year-old woman, who had suffered from idiopathic thrombocytopenic purpura (ITP), was admitted to our hospital because of cardiac heart failure and chest pain. The platelet was 42 x 10(4) in microl. Echocardiography revealed moderate aortic stenosis and regurgitation and left ventricular dysfunction. Preoperatively, we tapered oral steroid and administered high-dose immunoglobulin intravenously. Intraoperatively, we found quadricuspid aortic valve and the rudimentary accessory cusp was located between the right coronary cusp and noncoronary cusp. Aortic valve replacement was performed with bioprosthetic valve. The postoperative course was uneventful. Postoperative echocardiography revealed no perivalvular leakage. Preoperative administration of high-dose immunoglobulin and intraoperative platelet transfusion is very effective to minimize hemorrhagic complication in patients with ITP. We herein report an extremely rare quadricuspid aortic valve complicated with ITP.
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PMID:[Aortic valve replacement for quadricuspid aortic valve complicated with idiopathic thrombocytopenic purpura; report of a case]. 2138 23

Physiological role of creatine (Cr) became first evident in the experiments of Belitzer and Tsybakova in 1939, who showed that oxygen consumption in a well-washed skeletal muscle homogenate increases strongly in the presence of creatine and with this results in phosphocreatine (PCr) production with PCr/O(2) ratio of about 5-6. This was the beginning of quantitative analysis in bioenergetics. It was also observed in many physiological experiments that the contractile force changes in parallel with the alteration in the PCr content. On the other hand, it was shown that when heart function is governed by Frank-Starling law, work performance and oxygen consumption rate increase in parallel without any changes in PCr and ATP tissue contents (metabolic homeostasis). Studies of cellular mechanisms of all these important phenomena helped in shaping new approach to bioenergetics, Molecular System Bioenergetics, a part of Systems Biology. This approach takes into consideration intracellular interactions that lead to novel mechanisms of regulation of energy fluxes. In particular, interactions between mitochondria and cytoskeleton resulting in selective restriction of permeability of outer mitochondrial membrane anion channel (VDAC) for adenine nucleotides and thus their recycling in mitochondria coupled to effective synthesis of PCr by mitochondrial creatine kinase, MtCK. Therefore, Cr concentration and the PCr/Cr ratio became important kinetic parameters in the regulation of respiration and energy fluxes in muscle cells. Decrease in the intracellular contents of Cr and PCr results in a hypodynamic state of muscle and muscle pathology. Many experimental studies have revealed that PCr may play two important roles in the regulation of muscle energetics: first by maintaining local ATP pools via compartmentalized creatine kinase reactions, and secondly by stabilizing cellular membranes due to electrostatic interactions with phospholipids. The second mechanism decreases the production of lysophosphoglycerides in hypoxic heart, protects the cardiac cells sarcolemma against ischemic damage, decreases the frequency of arrhythmias and increases the post-ischemic recovery of contractile function. PCr is used as a pharmacological product Neoton in cardiac surgery as one of the components of cardioplegic solutions for protection of the heart against intraoperational injury and injected intravenously in acute myocardial ischemic conditions for improving the hemodynamic response and clinical conditions of patients with heart failure.
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PMID:Systems bioenergetics of creatine kinase networks: physiological roles of creatine and phosphocreatine in regulation of cardiac cell function. 2139 May 28


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