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)

This study examined the profile and management of acute myocardial infarction in patients hospitalized in the coronary care unit of Henry Ford Hospital to determine risk factors or treatments that best explained a decline in in-hospital mortality rates. During the 1980s and early 1990s, many therapeutic advances occurred in management of acute infarction. Overall and in-hospital mortality were observed also to decline, but little is known about the relation of newer treatments to clinical outcome. The study population consisted of 1798 patients with a confirmed diagnosis of myocardial infarction. Of these, 982 consecutive patients were hospitalized in the coronary care unit of Henry Ford Hospital from January 1981 through December 1984 and compared with the 816 consecutive patients hospitalized from January 1990 through October 1992. Data on baseline demographics, initial clinical features, in-hospital management, and in-hospital outcome were compared for the two groups. Logistic regression was used to define independent predictors of the improved outcome of the two groups. Demographic features of the earlier group were similar to those of the later cohort, with the exception of a greater incidence of diabetes and hypertension and a lesser incidence of angina and prior heart failure. The occurrence of non-Q wave infarction increased from 27% in the earlier to 39% in the later group, whereas the magnitude of peak creatine kinase elevation in serum was higher in the later group. Medical management differed significantly, with increased use of aspirin, thrombolytics, heparin, warfarin, nitrates, and beta-blockers and decreased use of antiarrhythmic agents, digoxin, and vasopressors in the later group. Coronary revascularization was performed during hospitalization in 6.4% of the earlier group of patients and 31.6% of the later group. In-hospital mortality was 14.7% in the earlier group and 7.4% in the later group. Multivariate logistic regression analysis showed that the difference in mortality between the two groups was best accounted for by increased use of beta-blockers, angioplasty, and thrombolytics, decreased incidence of cardiogenic shock and asystole, and decreased use of lidocaine. In conclusion, the presentation and in-hospital management of patients with acute myocardial infarction has changed from the early 1980s to the early 1990s. The improved hospital mortality rate may be associated with both the expanded use of effective therapies and a more favorable in-hospital course, although these are not mutually exclusive.
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PMID:Decline in the rate of hospital mortality from acute myocardial infarction: impact of changing management strategies. 857 16

An animal model was used to test the hypothesis that in heart failure the decrease in the ability to resynthesize ATP through the creatine kinase (CK) reaction (which we call energy reserve) contributes to the inability of the heart to maintain its normal function and contractile reserve. One-week-old turkey poults were fed furazolidone for 14 days to induce dilated cardiomyopathy. Isolated Langendorff-perfused hearts from these myopathic animals showed a 73% decrease in baseline isovolumic contractile performance. Neither increasing [Ca2+]o nor electrical pacing rate increased isovolumic contractile performance. Measured by 31P nuclear magnetic resonance magnetization transfer and chemical assay, ATP concentration was decreased by 23%, phosphocreatine concentration by 42%, CK enzyme activity by 34%, and the pseudo first-order rate constant for the CK reaction by 50%. Measured CK reaction velocity decreased by 71%. The reduced ability to increase cardiac performance in response to increasing [Ca2+]o in hearts with lower CK reaction velocity was reproduced in part by feeding a separate group of turkey poults beta-guanidino-propionic acid to specifically reduce CK reaction velocity by decreasing guanidino substrate concentration. These hearts had normal baseline performance but blunted contractile reserve. These observations provide further support for the hypothesis that a decrease in energy reserve via the CK system contributes to reduced cardiac function in the failing heart.
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PMID:Decreased energy reserve in an animal model of dilated cardiomyopathy. Relationship to contractile performance. 862 Jun 10

We investigated the usefulness of the plasma concentration of brain natriuretic peptide (BNP) for evaluating cardiac function in patients with Duchenne muscular dystrophy (DMD). The plasma BNP concentration was measured by immunoradiometric assay in 55 patients with DMD and in 34 healthy subjects. Cardiac function was evaluated by the cardiothoracic ratio (CTR) on chest roentgenogram, left ventricular end-diastolic dimension (LVDd) and fractional shortening (FS) on echocardiogram, and the ratio of ejection time to pre-ejection period (ET/PEP) on mechanocardiogram. The function of skeletal muscle was evaluated in terms of the disability of lower limb function, serum creatine kinase (CK) activity and % vital capacity (% VC). The plasma concentration of BNP was increased in patients with DMD (32.7 +/- 14.8 pg/ml, mean +/- SEM) compared with that in normal subjects (4.3 +/- 0.5 pg/ml). Two of the DMD patients had symptoms of heart failure, with markedly increased plasma BNP concentrations. The other DMD patients with increased plasma BNP concentrations showed abnormal cardiac function but no symptoms of heart failure. In addition, in patients with DMD, the plasma BNP concentration showed significant positive correlations with CTR and LVDd (p < 0.01), and negative correlations with ET/PEP and FS (p < 0.01). In severe DMD patients who had advanced disability and decreased CK activity, the plasma BNP concentration tended to be elevated. There was no significant correlation between the plasma BNP concentration and % VC. These findings suggest that the plasma BNP concentration is useful for evaluating cardiac dysfunction, whether manifest or latent, in patients with DMD, in whom accurate evaluation of cardiac function by conventional methods is difficult due to severe muscle atrophy and deformity of the thorax.
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PMID:[Estimation of cardiac function by plasma concentration of brain natriuretic peptide in patients with Duchenne muscular dystrophy]. 868 97

Coronary patency has been used as a measure of thrombolysis success after acute myocardial infarction (AMI). The Thrombolysis in Myocardial Infarction (TIMI) study grading scale for coronary perfusion has gained wide acceptance, but the significance of individual grades on clinical outcome has not been adequately tested. We hypothesized that optimal outcomes would be achieved only with early (and maintained) TIMI grade 3 (complete) perfusion compared with TIMI grade 2 (partial perfusion, previously classified as a reperfusion success) or grades 0 or 1 (occluded arteries). Five recent, angiographically controlled, prospectively performed studies of thrombolysis in AMI were identified, representing 3,969 patients. Odds ratios for mortality by early perfusion grades were calculated using the Mantel-Haenszel test and combined in a weighted fashion. Results for selected clinical and laboratory outcomes by patency grade were also assessed. Overall, mortality averaged 8.8% for TIMI grade 0/1, 7.0% for grade 2, and 3.7% for grade 3 perfusion. The odds ratio (OR) for early mortality was substantially reduced for grade 3 versus <3 perfusion (OR = 0.45, confidence interval [CI] 0.34 to 0.61, p <0.0001). In pairwise comparisons, grade 3 was clearly superior to grade 2 (OR = 0.54, CI) 0.37 to 0.78, p = 0.001) as well as grades 0/1 (OR = 0.41, CI 0.30 to 0.56, p <0.0001). Acute and convalescent ejection fraction, regional wall motion, time to enzyme peaks (creatine kinase [CK], creatine kinase myocardial bond [CK-MB]), peak enzyme levels [CK, lactate dehydrogenase [LDH], LDH-1), and risk of heart failure were each significantly less in patients achieving grade 3 than grade 2 (or lower grades) perfusion. Results were observed despite the frequent use of interventions after angiography. This meta-analysis demonstrates that early and complete (grade 3) flow is associated with superior survival and clinical outcome; grade 2 perfusion results in an inferior outcome, closer to that of an occluded than an open artery. The goal of reperfusion strategies should be early and maintained TIMI grade 3 perfusion.
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PMID:Metaanalysis of five reported studies on the relation of early coronary patency grades with mortality and outcomes after acute myocardial infarction. 871 96

Cardiac dysfunction and its correlation with skeletal muscle dysfunction were examined in 16 definite female gene carriers of Duchenne muscular dystrophy (DMD). Five out of 16 carriers (31.3%) had cardiac symptoms and 8 carriers (50.0%) showed an increased cardio-thoracic ratio on chest X-ray. Electrocardiographic abnormalities including a high R:S ratio (> or = 1.0) in the V1 lead, deep Q wave (> 3 mm) in the I, II, aVL, V5, and V6 leads, complete right bundle branch block and premature ventricular beats, were observed in 9 carriers (56.3%). On echocardiographic examination, an increase in the end-diastolic dimension of the left ventricle and a decrease in the ejection fraction suggestive of dilated cardiomyopathy were found in 12 carriers (75.0%). Tl-201 myocardial SPECT scan was performed in 2 symptomatic carriers and showed an area of hypoperfusion in the inferio-posterior wall. These findings were similar to previously reported findings in DMD patients. A biopsy of the myocardium was obtained in one carrier with her informed consent for the biopsy. Immunohistochemical staining demonstrated that 75.4% of the myocardial fibers were negative for dystrophin, suggesting that her cardiac dysfunction is caused by the abnormal expression of dystrophin in the cardiac muscle. On examination of the skeletal muscle function, none of the carriers had clinical evidence of muscle weakness or atrophy. However serum creatine kinase activity was elevated in 14 of 16 carriers (87.5%). Computed tomography (CT) of the lower limb muscles demonstrated widened spaces among muscles and moss-eaten appearance of low density areas within muscles and CT value was decreased, suggesting the subclinical involvement of the skeletal muscle. In the carriers without cardiac symptoms, there was a negative correlation (p < 0.05) between the end-diastolic dimension of the left ventricle and the CT value of the biceps femoris muscle (a muscle with the lowest CT value among the lower limb muscles). This indicates that there was an apparent correlation between the cardiac and skeletal muscle dysfunction. These findings suggest a high frequency of clinical and subclinical involvement of the cardiac and skeletal muscles in DMD carriers. To protect them from cardiac failure, cardiac dysfunction in DMD carriers needs to be examined closely and treated appropriately before the carriers become symptomatic.
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PMID:[Cardiac dysfunction in female gene carriers of Duchenne muscular dystrophy]. 872 Mar 27

To study the contribution of myocardial energy reserve to the deterioration of cardiac function during the development of heart failure, we defined energy reserve via the creatine kinase (CK) reaction and the isovolumic contractile performance in hearts of cardiomyopathic hamsters at the ages of 1.5, 4, 17, 30 and 43 weeks and in age-matched normal hamsters. Energy reserve via the CK reaction was estimated by the product of total CK activity and the content of total creatine in the heart. Isovolumic contractile performance was measured as rate pressure product (RPP, 10(3) mmHg/min) in isolated hearts. Contractile reserve was assessed as the increase of RPP elicited by high calcium stimulation. Compared to the controls, decreases in total CK activity and content of total creatine were observed in hearts of 17-, 30- and 43-week-old cardiomyopathic hamsters. These changes were not observed in the skeletal muscle. Although the decrease of baseline RPP first occurred at the age of 30 weeks (11.5 +/- 0.9 v 20.5 +/- 0.8, P < 0.05), the contractile reserve was already reduced at the age of 17 weeks (9.9 +/- 1.3 v 23.6 +/- 1.9, P < 0.05). A linear relationship was found between the energy reserve via creatine kinase reaction and the contractile reserve of the heart (r2 = 0.85). Furthermore, concomitant decreases in the CK reaction velocity and the contractile reserve were observed in cardiomyopathic hearts, suggesting that depletion of energy reserve may contribute to the development of heart failure.
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PMID:Depletion of energy reserve via the creatine kinase reaction during the evolution of heart failure in cardiomyopathic hamsters. 873 3

Previous studies have shown an association between distortion of the terminal portion of the QRS (QRS[+] pattern: emergence of the J point > or = 50%. of the R wave in leads with qR configuration or disappearance of the S wave in leads with an Rs configuration) on admission and in-hospital mortality in acute myocardial infarction (AMI). However, the mechanism for this association is not known. We assessed the relation between QRS(+) pattern and coronary angiographic findings, infarct size, and long-term prognosis in the Thrombolysis In Myocardial Infarction 4 trial. Patients were allocated into 2 groups based on the presence (QRS[+], n = 85) or absence (QRS[-], n = 293) of QRS distortion. The QRS(+) patients were older (mean +/- SD: 61.1 +/- 10.6 vs 57.5 +/- 10.6 years, p = 0.004), had more anterior AMI (49% vs 37%, p = 0.04), and less previous angina (42% vs 54%, p = 0.05). QRS(+) patients had larger infarct size as assessed by creatine kinase release over 24 hours (209 +/- 147 vs 155 +/- 129, p = 0.003), and predischarge sestamibi (MIBI) defect (17.9 +/- 15.9% vs 11.2 +/- 13.4%, p <0.001). When adjusting for difference in baseline characteristics, p values for the differences in 24-hour creatine kinase release were 0.03 and 0.64 for anterior and nonanterior AMI, respectively, and for MIBI defect size 0.03 and 0.02, respectively. One-year mortality (18% vs 6%, p = 0.03) was higher and the weighted end point of death, reinfarction, heart failure, or left ventricular ejection fraction <40% (0.33 +/- 0.37 vs 0.24 +/- 0.32, p = 0. 13), tended to be higher in the anterior AMI patients with QRS(+). No difference in clinical outcome was found in patients with non-anterior AMI. These findings suggest that this simple electrocardiographic definition of presence of QRS(+) pattern on admission may provide an early estimation of infarct size and long-term prognosis, especially in anterior AMI.
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PMID:Distortion of the terminal portion of the QRS on the admission electrocardiogram in acute myocardial infarction and correlation with infarct size and long-term prognosis (Thrombolysis in Myocardial Infarction 4 Trial). 875 82

Patients who cannot be reperfused after thrombolytic therapy have a high mortality rate. Noninvasive clinical markers of reperfusion have been widely studied, yet their prognostic significance remains unclear. To assess the prognostic value of commonly used noninvasive clinical markers of early reperfusion we studied 327 patients who received intravenous thrombolytic treatment (1.5 MU streptokinase in 1 hour or 100 mg alteplase in 3 hours) within 6 hours of acute infarction. Successful clinical reperfusion (SCR) was defined as the presence of at least two of the following criteria at 2 hours after thrombolytic treatment: (1) significant relief of pain (a 5-point reduction on a 1 to 10 subjective scale), (2) > or =50% reduction of sum of ST segment elevation, and (3) abrupt initial increase of creatine kinase levels (more than twofold over the upper-normal or baseline elevated values). Clinical variables that were significantly associated by univariate analysis were tested by multivariate analysis to obtain independent predictors of 30-day mortality rate. SCR was present in 210 (64%) patients (group 1), and absent in 117 (36%) patients (group 2). The groups were similar for most baseline characteristics, although group 2 patients were slightly older (mean 60 vs 57 years, p < 0.02). Thirty-day outcomes for group 2 patients compared with group 1 patients were heart failure in 23.1% and 10.5% (p < 0.005), progression to cardiogenic shock in 12.8% and 0.5%, (p < 0.00001), and death in 16.2% and 3.8% (p < 0.0001), respectively. By multivariate analysis the Killip class at admission (p < 0.00001), the absence of SCR (p = 0.017), anterior infarct location (p = 0.021), and age (p = 0.03) were independent predictors of mortality rate, and sex (p = 0.051) had borderline significance. The absence of SCR defined a group of patients with significantly higher mortality rate (odds ratio 4.89, 95% confidence interval 2.07 to 11.57). Three simple noninvasive clinical criteria of successful reperfusion may be used to identify a group of patients with poor prognosis after thrombolytic therapy in whom alternative strategies could be applied.
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PMID:Prognostic value of clinical markers of reperfusion in patients with acute myocardial infarction treated by thrombolytic therapy. 935 29

We describe an improved procedure using a standard microplate immunoassay reader to measure the concentration of troponin T in human serum. We also describe an immunoassay for troponin I in serum. Only 160 microliters of serum are needed for a single analysis of each troponin. For comparison, creatine kinase MB mass analysis in serum was performed with a commercial luminometric method. From 95 apparently healthy people the following values were obtained: creatine kinase MB mass 2.6 +/- 1.2 micrograms/l, troponin T 0.027 +/- 0.025 microgram/l and troponin I 0.03 +/- 0.031 microgram/l. We compared the results of troponin T and troponin I methods with each other, as well as with those of creatine kinase MB mass measured in 48 patients with verified acute myocardial infarction and in 60 control patients with non-cardiac chest pain. The correlation between troponin T and troponin I values was 0.91 for the total material and 0.94 for 48 patients with acute myocardial infarction. Troponin I showed better earlier sensitivity than troponin T (p = 0.043). In nine patients in the control group, creatine kinase MB mass exceeded the reference limit of 5.0 micrograms/l, while in two patients the cut-off limit of 10.0 micrograms/l was also surpassed, pointing to non-specificity. In the group of infarct patients, the highest serum creatinine value was 193 mumol/l, whereas in the control group it was 406 mumol/l. The sera of patients with impaired renal function without any cardiac failure showed no increase in troponin T and troponin I values. In conclusion, serum creatine kinase MB mass and troponin I seem to confirm an acute myocardial infarction more rapidly than does troponin T; troponin I has the highest cardiac specificity.
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PMID:Comparison of the troponin T and troponin I ELISA tests, as measured by microplate immunoassay techniques, in diagnosing acute myocardial infarction. 936 95

Our purpose was to determine whether hearts from mice bioengineered to lack either the M isoform of creatine kinase (MCK-/- mice) or both the M and mitochondrial isoforms (M/MtCK-/- mice) have deficits in cardiac contractile function and energetics, which have previously been reported in skeletal muscle from these mice. The phenotype of hearts with deleted creatine kinase (CK) genes is of clinical interest, since heart failure is associated with decreased total CK activity and changes in the relative amounts of the CK isoforms in the heart. We measured isovolumic contractile performance in isolated perfused hearts from wild-type, MCK-/-, and M/MtCK-/- mice simultaneously with cardiac energetics (31P-nuclear magnetic resonance spectroscopy) at baseline, during increased cardiac work, and during recovery. Hearts from wild-type, MCK-/-, and M/MtCK-/- mice had comparable baseline function and responded to 10 minutes of increased heart rate and perfusate Ca2+ with similar increases in rate-pressure product (48+/-5%, 42+/-6%, and 51+/-6%, respectively). Despite a similar contractile response, M/MtCK-/- hearts increased [ADP] by 95%, whereas wild-type and MCK-/- hearts maintained [ADP] at baseline levels. The free energy released from ATP hydrolysis decreased by 3.6 kJ/mol in M/MtCK-/- hearts during increased cardiac work but only slightly in wild-type (1.7 kJ/mol) and MCK-/- (1.5 kJ/mol) hearts. In contrast to what has been reported in skeletal muscle, M/MtCK-/- hearts were able to hydrolyze and resynthesize phosphocreatine. Taken together, our results demonstrate that when CK activity is lowered below a certain level, increases in cardiac work become more "energetically costly" in terms of high-energy phosphate use, accumulation of ADP, and decreases in free energy released from ATP hydrolysis, but not in terms of myocardial oxygen consumption.
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PMID:Impaired cardiac energetics in mice lacking muscle-specific isoenzymes of creatine kinase. 957 9


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