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)

We report the case of an 80-year-old man affected by hypertensive cardiomyopathy and already admitted to our Division for recurrent episodes of heart failure. He was eventually hospitalized for septic shock secondary to disseminated pneumonia with concomitant left pleural effusion. At 2D-echo examination, a highly echo-reflectant mass was detected in the retrocardiac space. As the patient died notwithstanding the intensive pharmacological care, an autoptic procedure was performed which showed a massive thrombosis of the right atrial appendage. We discuss the 2D-echo imaging and advance a pathogenetic hypothesis after a review of the current literature.
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PMID:[Thrombosis of the right atrial appendage. The two-dimensional echocardiographic aspect and the autopsy finding]. 148 40

The incidence of sudden death is estimated to be 0.25%/year in the industrialized world. 30 to 40% of patients are known to be at major risk before they succumb sudden death. Etiology is usually coronary heart disease (75%), dilated and hypertensive cardiomyopathy as well as valvular disease. 75% of patients dying suddenly die from ventricular fibrillation. The most common mechanism of sudden cardiac death in heart failure is sustained ventricular tachycardia deteriorating into ventricular fibrillation, the initiating factors being single ventricular beats, ventricular pairs or nonsustained ventricular tachycardia (trigger mechanism). At least 50% of patients dying during Holter monitoring have been on antiarrhythmic treatment during the time of sudden death and this percentage is increased to 70% in patients dying from torsade de pointes ventricular tachycardia. The question that has arisen is whether suppression of such arrhythmias by antiarrhythmic agents will reduce the incidence of sudden cardiac death. Unfortunately, the patient group at highest risk - low ventricular ejection fraction and high incidence of nonsustained ventricular tachycardia episodes during 24 hour-monitoring and thus, the group most in need of arrhythmia suppression - has the lowest responder rate as well as the highest incidence of serious toxicity. Until the suppression of those arrhythmias by antiarrhythmic agents is demonstrated to improve prognosis in this patient group, routine use of antiarrhythmic agents cannot be recommended in this patient population.
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PMID:[Arrhythmia and anti-arrhythmia therapy as prognostic risks]. 182 Feb 98

Acute or chronic heart failure may be caused by one or more of a variety of abnormalities including changes in excitation-contraction coupling processes (i.e. decreased availability of activator Ca2+ or a change in myofilament Ca2+ responsiveness), a change in myocardial energetics, or a change in extracellular factors, such as connective tissue content. Most of the animal and human models of acute cardiac failure that we have studied in our laboratory (i.e. negative inotropic responses to drugs, hypoxia, acidosis and ischaemia) appear to involve changes in excitation-contraction coupling as the predominant cause of dysfunction. On the other hand, the models of chronic cardiac dysfunction that we have studied (i.e. chronic right ventricular pressure overload in ferrets, hypertrophic cardiomyopathy in Syrian hamsters, hypertensive cardiomyopathy in rats, hypothyroidism in ferrets, end-stage dilated and hypertrophic cardiomyopathy in man) predominantly appear to reflect a combination of changes involving abnormalities in both excitation-contraction coupling and extracellular factors involving myocyte drop-out and increases in connective tissue content. However. In most of these models of acute and chronic heart failure, abnormal intracellular Ca2+ handling appears to be a major cause of both systolic and diastolic dysfunction.
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PMID:Abnormal intracellular calcium handling in acute and chronic heart failure: role in systolic and diastolic dysfunction. 218 44

We studied the hemodynamic effects of dobutamine in 10 patients with severe chronic heart failure due to congestive cardiomyopathy in 5, to ischemic heart disease in 4 and to hypertensive cardiomyopathy in 1. Dobutamine was injected during three periods of 30 min each alternated with equal periods of placebo at doses of 2,5-5 and 7,5 mcg/Kg/min respectively. The most favorable hemodynamic effects, obtained at an infusion rate of 5 mcg/Kg/min, was characterized by a significant inn 4 and to hypertensive cardiomyopathy in 1. Dobutamine was injected during three periods of 30 min each alternated with equal periods of placebo at doses of 2,5-5 and 7,5 mcg/Kg/min respectively. The most favorable hemodynamic effects, obtained at an infusion rate of 5 mcg/Kg/min, was characterized by a significant increase of the cardiac index and of the left ventricle stroke work index, accompanied by a significant decrease of the left ventricular filling pressure and of the systemic and pulmonary vascular resistance. The hemodynamic monitoring showed that the pharmacological effects of the drug subsided about 5-10 min after the interruption of infusion. At the infusion rate of 7,5 mcg/Kg/min we observed a significant increase of premature ventricular beats in 3 patients. We conclude that dobutamine at the dose of 5 mcg/Kg/min shows a powerfull positive inotropic action not accompanied by apparent side effects.
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PMID:[Hemodynamic effects of dobutamine in patients with severe low-output heart failure (author's transl)]. 719 52

A clinical pathophysiological classification of hypertensive cardiomyopathy has been established on the basis of the degree to which the heart is affected by chronic, systemic arterial hypertension: Degree I: Asymptomatic patients without left ventricular hypertrophy but with left ventricular diastolic dysfunction according to Doppler mitral inversion relation (E/A < 0.9) or to gamma scintigraphy (peak filling rate reduction < or = 2.7 EDC.s-1. These patients are classified as Group 1. Degree II: Asymptomatic or mildly symptomatic patients (New York Heart Association class I) with echocardiographic left ventricular hypertrophy; classified as Group IIA or IIB according to whether weight-adjusted maximal oxygen uptake is normal or below normal, respectively. Degree III: The basic characteristic is the presence of congestive heart failure with normal ejection fraction (EF > or = 50%). Two subsets can be distinguished on the basis of degree of hypertrophy: Group IIIA, with a mass/volume index > 1.8, and IIIB with a mass/volume index < 1.8. The differences between the two are as follows: patients classified as IIIA had a lower rate of regional ischaemia, a higher ejection fraction, a more frequently audible fourth sound, rarely a third sound and a cardiothoracic ratio < 0.5; IIIB patients had a higher prevalence of regional ischaemia (thallium-positive), a frequently audible third sound and a cardiothoracic ratio > 0.5. Degree IV: This category is characterized by the presence of depressed contractility, which could cause heart failure, by an ejection fraction < 50% and an increase in ventricular volumes. Echocardiography shows increased distance between mitral point E and the septum.
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PMID:Classification of hypertensive cardiomyopathy. 828 72

31P-NMR was used to monitor myocardial bioenergetics in compensated and failing SHHF/MCC-fa(cp) (SHF) rat hearts. The SHHF/Mcc-fa(cp) (spontaneous hypertension and heart failure) rat is a relatively new genetic model in which all individuals spontaneously develop congestive heart failure, most during the second year of life. Failing SHF rat hearts displayed a pronounced decrease in resting PCr:ATP ratios (P<0.001), which was explained by a significant (P<0. 0001) drop in total creatine (47.2+/-3.1 nmol/mg protein) v age matched controls (106+/-3 nmol/mg protein). In end stage failure, NMR determined PCr was 2.9+/-0.1 micro mol/g wet weight under basal conditions. In contrast, 6- and 20-month-old controls and compensated SHFs had PCr values of 5.3+/-0.1, and 5.1+/-0.5 and 5. 1+/-0.2 micro mol/g wet weight. Both compensated and failing SHF hearts were metabolically compromised when the rate pressure product (RPP) was increased, as evidenced by an increase in Pi and a drop in PCr. Compensated SHF hearts, however, were able to increase rate pressure products (RRP, mmHg X beats/min) from 44.5+/-1.4 to 66.6+/-3. 4 K with dobutamine infusion, whereas hearts in end-stage failure were able to increase their RPP from baseline values of 27+/-4 K to only 37+/-7 K. The data indicate that a pronounced decline in PCr and total creatine signals the transition from compensatory hypertrophy to decompensation and failure in the SHF rat model of hypertensive cardiomyopathy.
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PMID:31P-NMR analysis of congestive heart failure in the SHHF/Mcc-facp rat heart. 951

This is a brief overview of experimental and clinical studies exploring the hemodynamic functions of the alpha2A and alpha2B adrenergic receptor (AR) subtypes in animals submitted to genetic manipulations or gene treatment, as well as the clinical effects of central sympathetic suppression with the alpha2-AR agonist clonidine in patients with ischemic heart disease and/or heart failure. The animal experiments have led us to conclude that the sympathetic outflow is regulated by activation of the presynaptic alpha2A-AR subtype, which is the predominant alpha2-AR subtype in the central nervous system and exerts a sympathoinhibitory (hypotensive) action; on the contrary, activation of the central alpha2B-AR elicits a sympathoexcitatory response (such as seen in salt-induced hypertension, which requires functionally intact alpha2B-AR). Since there are no selective pharmacologic agents yet capable of discriminating among alpha2-AR subtypes, clinical studies utilize clonidine, the central sympathetic suppressant effect of which has been used for 35 years to treat hypertension. In small clinical trials, clonidine was used successfully for treatment of acute or chronic heart failure, acute myocardial infarct or hypertensive cardiomyopathy with subclinical diastolic dysfunction. We speculate that future development of agents capable of selectively activating the alpha2A-AR or blocking the alpha2B-AR may further improve our capability to treat hypertension, ischemic heart disease and heart failure.
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PMID:The alpha2 -adrenergic receptors in hypertension and heart failure: experimental and clinical studies. 1172 52

The aim of this study was to evaluate ventricular arrhythmias occurring in recipients of the InSync ICD for the primary and secondary prevention of sudden death. The InSync ICD was implanted in 142 patients (128 men; mean age 65 +/- 10 years) with heart failure (mean NYHA functional Class 3.0 +/- 0.7) and wide QRS (mean 159 +/- 33 ms). The underlying etiology was ischemic in 55%, idiopathic in 33%, and valvular or hypertensive cardiomyopathy in 12% of patients. The numbers of arrhythmic episodes/100 patient-months was computed with their 95% CI, assuming a Poisson distribution. Implants were performed in 48 (34%) patients who did not have an ACC/AHA guidelines Class I indication for ICD therapy. A total of 104 patients were compliant for follow-up visits. During a 9-month median (range 0.1-24) follow-up of 104 compliant patients, 19 experienced a total of 94 ventricular arrhythmias, all successfully interrupted or self-terminated, with a median number of two separate episodes, corresponding to a rate of 10 episodes/100 person-month (95% CI 8-12). A rate of 12 episodes/100 person-months (95% CI 10-15) was measured in the subgroup of patients with ACC/AHA class I indications, versus two episodes/100 person-months (95% CI 1-5) in the remainder of the population. Among 12 deaths, 9 were due to heart failure, 1 to a non-cardiovascular cause, and 2 to unknown causes. The implantation of ICD in heart failure patients has been prominently extended to primary prevention. Patients without standard ICD indications experienced life-threatening arrhythmic events. The impact of ICD combined with cardiac resynchronization therapy on arrhythmic profile, mortality, and costs in this subgroup of patients need to be more precisely studied, with a particular focus on the various types of underlying heart disease.
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PMID:Cardiac resynchronization and implantable cardioverter defibrillator therapy: preliminary results from the InSync Implantable Cardioverter Defibrillator Italian Registry. 1268 1

Diabetes is a risk factor for coronary atherosclerosis, myocardial infarction, and ischemic cardiomyopathy. Insulin resistance is associated with left ventricular (LV) hypertrophy and hypertensive cardiomyopathy. Even in the absence of coronary artery disease or hypertension, "diabetic cardiomyopathy" can develop because of myocardial autonomic dysfunction or impaired coronary flow reserve. The relationship between insulin resistance and cardiomyopathy is bidirectional. Systemic and myocardial glucose uptake is compromised in heart failure independent of etiology. These abnormalities are associated with cellular deficits of insulin signaling. Insulin resistance in heart failure can be detrimental, because transcriptional shifts in metabolic gene expression favor glucose over fat as a substrate for high-energy phosphate production. Although preexisting diabetes accelerates this process of "metabolic death," insulin resistance can also develop secondary to cardiomyopathy-associated overabundance of neurohormones and cytokines. Insulin resistance and fatty acid excess are potential therapeutic targets in heart failure, striving for efficient myocardial substrate utilization. Peroxisome proliferator activator receptor gamma (PPARgamma) agonists are antidiabetic agents with antilipemic and insulin-sensitizing activity. Experimental studies suggest salutary effects in limiting infarct size, attenuating myocardial reperfusion injury, inhibiting hypertrophic signaling and vascular antiinflammatory actions through cytokine inhibition. However, clinical applicability in diabetic patients experiencing heart failure has been hampered because of increased edema and even fewer reports of exacerbation associated with these compounds. Evidence to date argues for peripheral mechanisms of edema unrelated to central hemodynamics. Nevertheless, they are currently contraindicated in New York Heart Association (NYHA) III-IV patients, particularly in combination with insulin. Investigations are underway to decipher mechanisms, risks, and benefits of PPARgamma agonists, as well as the role of the structurally related PPARalpha receptor on cardiovascular metabolism and function.
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PMID:Peroxisome proliferator activator receptors (PPAR), insulin resistance, and cardiomyopathy: friends or foes for the diabetic patient with heart failure? 1507 85

RhoA and Rho-kinase (ROCK) participate in a wide variety of cell signal functions such as cell growth, smooth and cardiac muscle contraction, cytoskeleton rearrangement, cell migration and proliferation. In vascular smooth muscle cells, RhoA and ROCK play an important role in Ca2+ sensitization and regulate vascular smooth muscle tone. In the heart, RhoA and ROCK mediate hypertrophic response leading to cardiac hypertrophy. Recent cellular and molecular biology studies using ROCK inhibitors such as Y-27632 and fasudil have indicated a pivotal role of the RhoA-ROCK cascade in many aspects of cardiovascular function such as cardiac hypertrophy and ventricular remodeling following myocardial infarction. Inhibition of the RhoA-ROCK signaling pathway may be a suitable target for a number of cardiovascular diseases including hypertension, atherosclerosis, diabetes and hypertrophic heart failure. This review focuses on the current understanding of the RhoA-ROCK signal pathway in heart diseases and discusses the use of ROCK inhibitors as therapeutic agents for heart diseases ranging from hypertensive cardiomyopathy to heart failure.
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PMID:Small guanine nucleotide-binding protein Rho and myocardial function. 1571 22


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