Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human and experimental heart failure is characterized by increases in type-1 protein phosphatase activity, which may be partially attributed to inactivation of its endogenous regulator, protein phosphatase inhibitor-1. Inhibitor-1 represents a nodal integrator of two major second messenger pathways, adenosine 3',5'-cyclic monophosphate (cAMP) and calcium, which mediate its phosphorylation at threonine 35 and serine 67, respectively. Here, using recombinant inhibitor-1 wild-type and mutated proteins, we identified a novel phosphorylation site in inhibitor-1, threonine 75. This phosphoamino acid was phosphorylated in vitro by protein kinase Calpha independently and to the same extent as serine 67, the previous protein kinase Calpha-identified site. Generation of specific antibodies for the phosphorylated and dephosphorylated threonine 75 revealed that this site is phosphorylated in rat and dog hearts. Adenoviral-mediated expression of the constitutively phosphorylated threonine 75 inhibitor-1 in isolated myocytes was associated with specific stimulation of type-1 protein phosphatase activity and marked inhibition of the sarcoplasmic calcium pump affinity for calcium, resulting in depressed contractility. Thus, phosphorylation of inhibitor-1 at threonine 75 represents a new mechanism of cardiac contractility regulation, partially through the alteration of sarcoplasmic reticulum calcium transport activity.
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PMID:Identification of a novel phosphorylation site in protein phosphatase inhibitor-1 as a negative regulator of cardiac function. 1704 26

Renin-angiotensin (RAS) system activation is associated with an increased risk of sudden death. Previously, we used cardiac-restricted angiotensin-converting enzyme (ACE) overexpression to construct a mouse model of RAS activation. These ACE 8/8 mice die prematurely and abruptly. Here, we have investigated cardiac electrophysiological abnormalities that may contribute to early mortality in this model. In ACE 8/8 mice, surface ECG voltages are reduced. Intracardiac electrograms showed atrial and ventricular potential amplitudes of 11% and 24% compared with matched wild-type (WT) controls. The atrioventricular (AV), atrio-Hisian (AH), and Hisian-ventricular (HV) intervals were prolonged 2.8-, 2.6-, and 3.9-fold, respectively, in ACE 8/8 vs. WT mice. Various degrees of AV nodal block were present only in ACE 8/8 mice. Intracardiac electrophysiology studies demonstrated that WT and heterozygote (HZ) mice were noninducible, whereas 83% of ACE 8/8 mice demonstrated ventricular tachycardia with burst pacing. Atrial connexin 40 (Cx40) and connexin 43 (Cx43) protein levels, ventricular Cx43 protein level, atrial and ventricular Cx40 mRNA abundances, ventricular Cx43 mRNA abundance, and atrial and ventricular cardiac Na(+) channel (Scn5a) mRNA abundances were reduced in ACE 8/8 compared with WT mice. ACE 8/8 mice demonstrated ventricular Cx43 dephosphorylation. Atrial and ventricular L-type Ca(2+) channel, Kv4.2 K(+) channel alpha-subunit, and Cx45 mRNA abundances and the peak ventricular Na(+) current did not differ between the groups. In isolated heart preparations, a connexin blocker, 1-heptanol (0.5 mM), produced an electrophysiological phenotype similar to that seen in ACE 8/8 mice. Therefore, cardiac-specific ACE overexpression resulted in changes in connexins consistent with the phenotype of low-voltage electrical activity, conduction defects, and induced ventricular arrhythmia. These results may help explain the increased risk of arrhythmia in states of RAS activation such as heart failure.
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PMID:Cardiac-restricted angiotensin-converting enzyme overexpression causes conduction defects and connexin dysregulation. 1733 99

In elderly patients, atrial fibrillation prevalence exceeds 10% and is commonly associated with heart failure rendering their management even more challenging. Therapies to be considered for heart failure related atrial fibrillation include appropriate treatment of underlying disease, prevention of thromboembolism, rate or rhythm control. The debate regarding rate versus rhythm control in the management of this group of patients has yet to be resolved. For old patients, the management requires an individual approach, which largely depends on comorbid conditions, underlying cardiac disease, and patient and physician preferences. Use of antiarrhythmic drug therapy for maintenance of sinus rhythm carries concerns of risk and limited efficacy. Catheter ablation for rhythm control is feasible for some patients, but further studies are needed to define the risks and benefits especially in older patients. Atrioventricular nodal ablation associated with pacing therapy is an effective non-pharmacological therapy in selected patients with medically refractory permanent high heart rate atrial fibrillation and heart failure. Several studies are ongoing and will provide more insight into the management of such patients.
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PMID:Management of atrial fibrillation in heart failure in the elderly. 1862 29

Heart failure (HF) and atrial fibrillation (AF), 2 of the most common cardiovascular disorders, often coexist in the same patient, as 1 condition can lead to the other. The best approach to AF management in patients with HF is currently under investigation, but there seems to be an abundance of evidence in support of cardiac resynchronization therapy (CRT) in this group of patients. In addition, CRT is emerging as a superior option to stand-alone right ventricular pacing in patients with structural heart disease. However, in patients with AF, an adequate rate control is critical for this therapy to be highly effective. As control of the ventricular response can be difficult to achieve in many of those patients, often a nonpharmacologic intervention is required, such as ablation of the atrioventricular node to create heart block. The definitive role for CRT with or without atrioventricular nodal ablation in patients with AF and HF is yet to be studied in large, well-designed, randomized, controlled clinical trials.
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PMID:Cardiac resynchronization therapy in patients with chronic atrial fibrillation. 1809 67

A 53-year-old man was admitted to our hospital for dyspnea, associated with atrial tachycardia. He underwent mitral valve replacement and Maze operation for mitral regurgitation and atrial fibrillation and since then he suffered from drug refractory atrial tachycardia followed by cardiogenic shock with systolic heart failure. Atrial tachycardia with rapid ventricular response was medically refractory, and radical catheter ablation was thought to be very difficult due to post Maze operation, mitral mechanical valve replacement and unstable hemodynamics. Thus, atrioventricular nodal ablation, which was s safe procedure compared to the radical ablation for this patient, and biventricular pacemaker implantation, which required coronary venoplasty, were performed. Combination therapy may be one of the treatments for heart failure patients with drug refractory tachyarrhythmias.
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PMID:Atrioventricular nodal ablation and biventricular pacing therapy with coronary venoplasty for severe heart failure with drug refractory atrial tachycardia. 1859 44

Atrial fibrillation (AF) and heart failure (HF) are two conditions regularly encountered in clinical practice. They share many common risk factors, and are often seen concurrently in an individual patient. Global aging of the population is likely to lead to an increase in the prevalence of both AF and HF alone, as well as in their combined state. The relationship between these two diseases is not simply coincidental; clinical and experimental data have defined multiple pathophysiological mechanisms to explain how either condition contributes to the de novo development of the other. The development of AF in the setting of HF, and vice versa, is associated with clinical deterioration and worsening prognosis, which indicates the need for an improved understanding of the clinical and pathological relationships between these conditions. Future research on pharmacologic therapies, such as antiarrhythmic medications, and nonpharmacologic strategies including atrioventricular nodal ablation and pulmonary vein isolation, will help to define the optimal therapeutic approach for concurrent AF and HF. This step is vital to improve both the outcomes of patients affected by these conditions and the cost-effectiveness of their care.
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PMID:Pathophysiology of concomitant atrial fibrillation and heart failure: implications for management. 1904 93

Heart failure continues to be a major public health problem with high morbidity and mortality rates, despite the advances in medical treatment. Advanced heart failure patients have severe persistent symptoms and a poor quality of life. Cardiac resynchronization therapy (CRT), an invasive therapy which involves synchronized pacing of both right and left ventricles, improves ventricular conduction delay and left ventricular performance. Several clinical trials of CRT in medically refractory heart failure patients with wide QRS (> 120 ms), left ventricular ejection fraction <or=35% and New York Heart Association (NYHA) class III and IV have shown improved quality of life, NYHA class, left ventricular ejection fraction and reduced mortality. About 30% of heart failure patients who receive CRT do not respond to treatment. Mechanical dyssynchrony may play a role in identifying patients who may respond better to CRT treatment. However, recent large scale clinical trials PROSPECT and RethinQ have challenged this concept. The role of CRT in heart failure patients with narrow QRS (< 120 ms), NYHA class I and II, atrioventricular nodal ablation in patients with atrial fibrillation and triple site pacing are evolving. Our review discusses the current evidence, indications, upcoming trials and future directions.
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PMID:Cardiac resynchronization therapy in heart failure patients: an update. 1943 93

It is well established that gene expression patterns are substantially altered in cardiac hypertrophy and heart failure, but the reasons for such differences are not clear. MicroRNAs (miRNAs) are short noncoding RNAs that provide a novel mechanism for gene regulation. The goal of this study was to comprehensively test for alterations in miRNA expression using human heart failure samples with an aim to build signaling pathway networks using predicted targets for the miRNAs and to identify nodal molecules that control these networks. Genome-wide profiling of miRNAs was performed using custom-designed miRNA microarray followed by validation on an independent set of samples. Eight miRNAs are significantly altered in heart failure of which we have identified two novel miRNAs that are yet to be implicated in cardiac pathophysiology. To gain an unbiased global perspective on regulation by altered miRNAs, predicted targets of eight miRNAs were analyzed using the Ingenuity Pathways Analysis network algorithm to build signaling networks and identify nodal molecules. The majority of nodal molecules identified in our analysis are targets of altered miRNAs and are known regulators of cardiovascular signaling. A heart failure gene expression data base was used to analyze changes in expression patterns for these target nodal molecules. Indeed, expression of nodal molecules was altered in heart failure and inversely correlated to miRNA changes validating our analysis. Importantly, using network analysis we have identified a limited number of key functional targets that may regulate expression of the myriad proteins in heart failure and could be potential therapeutic targets.
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PMID:Unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks. 2742 78

We present a 57-year old male patient with thalassemia intermedia and right heart failure. He had a 30-year history of anemia and short-term iron therapy without blood transfusion. Hemoglobin level was 7.1 g/dl and hematocrit was 22.7%. White blood-cell and platelet counts, and serum ferritin level were normal. Electrocardiography showed irregular narrow QRS bradyarrhythmia, suggesting slow atrial fibrillation at a mean rate of 35 beats/min. Echocardiographic examination revealed dilatation of the right atrium and ventricle, depressed systolic right ventricular function, advanced tricuspid regurgitation, and mild pericardial effusion. In the electrophysiologic study, no electrical activity was recorded in the right atrium. It was inexcitable at multiple sites and no retrograde conduction to the right atrium could be elicited by ventricular pacing. His bundle (HB) recording showed fixed retrograde HB activation with ventricular rhythm originating from different foci. Retrograde V-H conduction time during ventricular rhythm was 95 msec and did not change. There was no retrograde nodal conduction. A VVIR pacemaker was implanted. During a six-month follow-up, he felt well, his functional capacity was NYHA class II, and his basic rhythm was widened QRS arrhythmia with a rate of 20 beats/min. To the best of our knowledge, atrial electrical inactivity together with right-heart failure and pericarditis confined to the right heart chambers has hitherto not been reported in thalassemic disorders.
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PMID:Persistent atrial standstill and idioventricular rhythm in a patient with thalassemia intermedia. 1971 59

This report describes a 3-month-old boy with isolated left ventricular noncompaction admitted to a medical facility due to heart failure and dysrhythmia. His electrocardiogram showed a short PR interval and a normal QRS complex after abortion of supraventricular tachycardia in favor of Lown-Ganong-Levine syndrome or enhanced atrioventricular nodal conduction.
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PMID:Lown-Ganong-Levine syndrome in a 3-month-old infant with isolated left ventricular noncompaction. 1985 65


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