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)

The purpose of this study was to examine the histopathological findings of right ventricular endomyocardial biopsies from ten patients less than 60 years of age (47 +/- 9.8 (mean +/- SD) years) with documented atrioventricular block but without apparent heart disease. They underwent electrophysiological testing, echocardiography, coronary angiography, and right ventricular endomyocardial biopsy. Biopsy specimens were assessed for morphologic changes in myocyte diameter, fibrosis, disarray, and degeneration. Electrophysiological testing demonstrated atrioventricular nodal block in 2, intra-His bundle block in 2, and infra-His bundle block in 6 patients. Histology revealed evidence of myocardial fibrosis with either myocyte hypertrophy or disarray in 7 of the 10 patients. The results of electrophysiological testing did not correlate with the histopathological findings or severity. In one patient, heart failure appeared during the follow-up period. We conclude that patients with atrioventricular block of unknown etiology have histological abnormalities of the ventricular endomyocardium in addition to the conduction system disturbances. We consider such cases as constituting one of the disease groups of cardiomyopathy, and suggest that it is necessary to follow up the clinical course in these patients.
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PMID:Endomyocardial biopsy findings in patients with atrioventricular block in the absence of apparent heart disease. 1077 20

Clearly, sudden cardiac death syndrome in heart failure is linked to severely perturbed neurohumoral, hemodynamic, and mechanical systems. Routine antiarrhythmic drug therapy has not proven beneficial and, therefore, there is no justification for using these agents in unselected heart failure patients who are without significant symptomatic ventricular arrhythmia. Aggressive treatment of the failure syndrome seems most important. Because many of the problematic arrhythmias arise from triggering automaticity, which is known to occur in excessive ventricular stretch and wall stress, systemic vascular "unloading" with vasodilators and angiotensin-converting enzyme inhibitors is likely helpful. The most recent American College of Cardiology/American Heart Association Guidelines regarding therapeutic management of heart failure suggest that aggressive pharmacologic treatment of asymptomatic ventricular arrhythmias is best avoided. To be considered strongly for pharmacologic prescription or for implantation of a tachyarrhythmia termination device, a patient should have symptomatic ventricular tachycardia with an episode of syncope or sudden cardiac death syndrome rather than simply having palpitations of asymptomatic, unsustained ventricular tachycardia. Indeed, aggressively treating congestive heart failure with medication often eliminates potentially life-threatening arrhythmias. Appropriate use of vasodilators and, particularly, angiotensin-converting enzyme inhibitors is important. Correction of fluid balance and electrolyte disorders may be helpful to address symptoms and certainly is likely to decrease the potential for morbidity and mortality. On occasion it may be necessary to consider bradyarrhythmia pacemaker insertion or the use of atrioventricular nodal-ablation techniques with subsequent ventricular or atrioventricular pacer insertion. Obviously, sudden cardiac death due to sudden heart block or asystole might be attenuated with this strategy.
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PMID:Sudden cardiac death syndrome and pump dysfunction: the link. 1101 84

A patient with congestive heart failure and an ICD had undergone atrioventricular nodal ablation and optimization of heart failure medical therapy. Intracardiac T wave sensing by the ICD drew attention to the new development of asymptomatic hyperkalemia. Surface ECG features of hyperkalemia were not readily identified due to pacemaker dependence.
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PMID:Hyperkalemia diagnosed by implantable cardioverter defibrillator T wave sensing. 1138 16

Vascular transformation of lymph node sinuses is an uncommon condition and only isolated cases have been reported. It is characterized by conversion of nodal sinuses into capillary-like channels, often accompanied by fibrosis. Venous or lymphatic obstruction is thought to be the underlying mechanism, and in most cases factors that may contribute to lymphovascular obstruction can be identified such as tumour in the vicinity, vascular thrombosis, heart failure, previous surgery or radiotherapy. Most cases involve abdominal lymph nodes, and head and neck involvement is rare. We present two cases of vascular transformation of lymph node sinuses presenting only as cervical lymphadenopathy, without an obvious cause of lymphovascular obstruction.
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PMID:Vascular transformation of lymph node sinuses. 1156 14

Atrial fibrillation (AF) affects about 2% of the general population and 8%-11% of those older than 65 years. The demand for effective therapeutic strategies for AF is anticipated to increase substantially as the proportion of the elderly population increases. Atrioventricular nodal ablation accompanied by permanent pacemaker implantation is an established option in elderly patients with intractable arrhythmia and poor ventricular rate control. However, it renders most patients pacemaker dependent and does not eliminate symptoms associated with loss of atrial transport or reduce the risk of stroke. The considerable limitations of rhythm or rate control strategies prompted interest in preventative atrial pacing, which may reduce the incidence of AF by either eliminating the triggers and/or by modifying the substrate of AF. Atrial or dual-chamber pacing has been proven to prevent or delay progression to permanent AF in elderly patients with sinus node dysfunction as compared with ventricular pacing. Patients with advanced atrial conduction delay may benefit from atrial resynchronization pacing. There may be additional benefits associated with the use of particular sites of pacing, specific pacing algorithms designed to target potential triggers of AF, and pace-termination of atrial tachycardia. Preventive and antitachycardia pacing algorithms incorporated in implantable cardioverter-defibrillators and pacemakers are currently under investigation and may offer a valuable alternative to antiarrhythmic drug therapy in elderly patients with left ventricular dysfunction at high risk of proarrhythmia or worsening heart failure. The evolution of hybrid therapy, in which two or more different strategies are employed in the same patient, may be the most effective approach to management of AF.
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PMID:Atrial pacing for the prevention and termination of atrial fibrillation. 1241 45

Focal junctional tachycardia (FJT) is characterized by a rapid often irregular narrow complex tachycardia with episodes of atrioventricular (AV) dissociation. This uncommon arrhythmia is most likely due to abnormal automaticity or triggered activity. The patients are often quite symptomatic and if left untreated may develop heart failure particularly if their tachycardia is incessant. In patients refractory to medical management, the role of radiofrequency ablation involves either (1) selective ablation of the tachycardia focus while preserving AV conduction or as a last resort (2) AV junction ablation followed by pacemaker implantation. The clinician should first assess whether ventriculoatrial (VA) conduction is present or absent during tachycardia. If present, radiofrequency ablation should be applied at the site of earliest retrograde atrial activation. In the absence of VA conduction and hence an atrial target site, sequential lesions should be applied in the posterior septum (slow pathway region) followed by lesions applied in midseptum and anteroseptum respectively if tachycardia persists. To further minimize the risk of AV nodal block, some authors delivered radiofrequency energy during atrial overdrive pacing to assess AV conduction during ablation. Others recommended mapping the perinodal region and applying radiofrequency ablation at the site where catheter manipulation resulted in tachycardia termination. Using this ablative approach, the risk of AV block is around 5-10%.
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PMID:Role of invasive electrophysiologic testing in the evaluation and management of adult patients with focal junctional tachycardia. 1243 24

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure. 5. Serial assessment of serum digoxin levels is unnecessary in most patients. The radioimmunoassay was developed to assist in the evaluation of toxicity, not the efficacy of the drug. There appears to be little relationship between serum digoxin concentration and the drug's therapeutic effects. 6. Digoxin toxicity is commonly associated with serum levels >2 ng/mL but may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist. Likewise, the concomitant use of agents such as quinidine, verapamil, spironolactone, flecainide, and amiodarone can increase serum digoxin levels and increase the likelihood of digoxin toxicity. 7. For patients with heart failure and atrial fibrillation with a rapid ventricular response, the administration of high doses of digoxin (>0.25 mg daily) for the purpose of rate control is not recommended. When necessary, additional rate control should be achieved by the addition of beta-blocker therapy or amiodarone (strength of evidence = C). If amiodarone is added, the dose of digoxin should be reduced. Digitalis preparations are now entering their fourth century of clinical use for the treatment of chronic heart failure symptoms. Its clinical efficacy can no longer be doubted and its safety has been verified by the multicenter DIG trial. Future advances in pharmacogenetics should facilitate identification of those patients most likely to benefit from its pharmacologic effects.
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PMID:Digoxin remains useful in the management of chronic heart failure. 1269 28

To unravel the complex disease phenotype of heart failure, we are utilizing an integrative approach employing genomics, physiology, and mouse genetics to identify nodal pathways for specific physiological end points such as myocyte stretch activation responses, contractility and electrical conduction. A new class of genetic pathways for cardiac sudden death and associated arrhythmias has been based on transcription factors that control conduction system lineages, including HF1b/SP4 and NKX2.5. Previous studies have established that HF1b plays a critical role in conduction system lineage formation and the loss of HF1b leads to a confused electrophysiological identity in Purkinje and ventricular cell lineages, resulting in cardiac sudden death and marked tachy and brady arrhythmias. Utilizing Hf1b and Nkx2.5 floxed alleles, we now have identified the primary pathways which link these transcription factors with cardiac arrythmogenesis. Mice which harbour a neural crest restricted knockout of HF1b display marked arrhythmogenesis and conduction system defects, implicating neural crest cues in conduction system development and disease. Mice which harbour a ventricular-restricted knockout of Nkx2.5 display completely normal conduction at birth, but a hypoplastic atrioventricular (AV) node. During maturation, progressive complete heart block ensues, associated with a selective dropout of distal AV nodal cell lineages at the boundaries of the penetrating His bundle. Single cell analyses examining individual nodal cells within AV node of ventricular restricted Nkx2.5 knockout mice clearly document a cell autonomous requirement for NKX2.5 within AV nodal lineages per se. Micro-electrophysiological AV nodal mapping indicates a selective conduction defect at the boundary of the distal AV node and His bundle. HF1b and NKX2.5 reflect new cardiac cell non-autonomous and autonomous pathways for conduction system lineage defects and associated cardiac arrythmogenesis.
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PMID:Defects in cardiac conduction system lineages and malignant arrhythmias: developmental pathways and disease. 1295 35

Nkx2.5 is a conserved homeodomain (HD) containing a transcription factor essential for early cardiac development. We generated several mutations modeling some patients with congenital heart disease. Transgenic mice (tg) expressing the wildtype Nkx2.5 under beta-myosin heavy chain (MHC) promoter died during the embryonic stage. However, tg mice expressing this mutation under beta-MHC promoter (beta-MHC-TG(I183P)), the wildtype Nkx2.5 (alpha-MHC-TG(wild)), and a putative transcriptionally active mutant (carboxyl-terminus deletion, alpha-MHC-TG(DeltaC)) under alpha-MHC promoter showed postnatal lethal heart failure. Given the profound atrioventricular conduction abnormalities we recently demonstrated in beta-MHC-TG(I183P) mice, the aim of this study was to determine whether alpha-MHC-TG(wild) and alpha-MHC-TG(DeltaC) mutant mice display similar cardiac electrophysiological phenotypes. Surface ECG recordings and in vivo electrophysiology studies were performed in alpha-MHC-TG(wild) mice and controls at 6 weeks of age, and in alpha-MHC-TG(DeltaC) mice and controls at 10 weeks of age. Ambulatory ECG recordings in alpha-MHC-TG(wild) and controls were obtained using an implantable radiofrequency telemetry system. PR prolongation and atrioventricular nodal dysfunction were detected in alpha-MHC-TG(wild) and alpha-MHC-TG(DeltaC) mice. Bradycardia and prolonged PR interval were seen in ambulatory ECG of alpha-MHC-TG(wild) mice compared to controls. Several alpha-MHC-TG(wild) mice died of bradycardia. Fetal and neonatal mutant Nkx2.5 expression causes severe cardiac conduction failure. Postnatal overexpression of nonmutant (wild) Nkx2.5 also causes conduction abnormalities, although the onset is after the neonatal stage. Bradycardia and AV conduction failure may contribute to the lethal heart failure and early mortality.
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PMID:Cardiac electrophysiological phenotypes in postnatal expression of Nkx2.5 transgenic mice. 1459 38

The cardiac pacemaker is a sino-atrial (SA) nodal cell. The signal induced by this pacemaker is distributed over the heart surface by a specialised conduction system and is clinically recorded as the ECG. The SA nodal cells are highly resistant to cardiac failure and ischemia. Under calcium overload conditions, some dysrythmias of SA nodal cells occur easily. Morphological analysis under these conditions shows swelling of the cisternae of the Golgi apparatus, with little or no other histological change or damage being observed. The rate of sinus rhythm is quite different between various species. The investigations of SA nodal cells have so far clarified the pacemaker mechanisms involved. A number of ionic channel currents or pacemaker currents, contribute to the depolarization of the pacemaker potential (phase 4). This will not occur with a single current. Recent experiments have identified several novel pacemaker currents and have also revealed several differences in the pacemaker currents between species. The marked hyperpolarization-activated inward current (I(f)) appears in SA nodal cells of most species, while the inwardly rectifying K+ current (I(K1)) with masked I(f) current is found in those of the rat and monkey. In addition, the rapidly activated current (I(Kr)) and slowly activated current (I(Ks)) of the delayed rectifier K+ current (I(K)) contribute to the pacemaker potential in guinea pig SA nodal cells, with only the I(Ks) current in porcine SA nodal cells and only the I(Kr) current in the rat and rabbit. These differences in ionic channels presumably result from differences in gene expression. Some smooth muscle cells also possess the capacity to beat spontaneously. Uterine smooth muscle cells also exhibit an I(f) current. The basal mechanism for spontaneous activity in both SA nodal cells and smooth muscle cells is almost the same, but some differences in the ionic channels and their genetic expression may contribute to their respective pacemaker currents.
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PMID:Sino-atrial nodal cells of mammalian hearts: ionic currents and gene expression of pacemaker ionic channels. 1469 28


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