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A patient with acute right ventricular infarction who showed hyposecretion of atrial natriuretic peptide (ANP) in spite of abnormally high right atrial pressure and who died of a severe low cardiac output syndrome is reported. Right atrial infarction, which was proven at autopsy, may be responsible for this endocrine failure.
This study examined whether the adenosine potentiator, 5-aminoimidazole-4-carboxamide riboside (AICAr), could limit tissue necrosis during acute myocardial infarction in rabbit hearts with minimal coronary collateral flow. Forty-four rabbits underwent 45 min of ischemia with or without coronary reperfusion for 180 min. Five groups were studied. Saline or AICAr (20 mg/kg, i.v.) was administered as a bolus either 10 min before coronary occlusion or 10 min before the onset of coronary reperfusion. The anatomic risk zone size was assessed by radiolabeled microsphere autoradiography and the area of tissue necrosis was defined using the tetrazolium staining method. Coronary collateral flow in the central ischemic zone was assessed using the radiolabeled microsphere technique. No differences were observed for tissue necrosis (normalized to risk zone size) for saline- and AICAr-treated rabbits (66.2 +/- 10.9% vs. 70.8 +/- 19.9%, p = NS) subjected to 45 min of coronary occlusion without reperfusion. Similarly, tissue necrosis in rabbit hearts with 45 min of coronary occlusion followed by 180 min of reperfusion was not significantly reduced when AICAr was administered either 10 min before ischemia or 10 min before reperfusion (79.8 +/- 17.5 and 76.4 +/- 8.1%, respectively) compared to saline-treated controls (68.1 +/- 22.7%). Coronary collateral flow in these hearts was almost nonexistent. The risk zone size and cardiac hemodynamics were similar between the treatment groups. These results demonstrate that AICAr was unable to limit myocyte necrosis when administered either before ischemia or before coronary reperfusion in this experimental preparation of acute myocardial infarction.
PURPOSE: Previous studies on PON1 gene polymorphism and the risk of coronary atherosclerotic diseases have been inconsistent. This may be in part due to population difference in prevalence of high oxidative stress and its modifying effect on the association. Diabetes and obesity are two major risk factors of myocardial infarction (MI) and associated with high oxidative stress. We investigated the association between PON1 Q192R polymorphism and the risk of myocardial infarction (MI) and in particular, whether the association can be modified by diabetes mellitus (DM) and obesity. METHODS: We conducted a case-control study, including 154 MI cases and 154 controls enrolled in Beijing, China. Epidemiological and clinical data and PON1 Q192R genotype were obtained from each subject. RESULTS: Without considering the modifying effect of DM and obesity, PON1 Q192R polymorphism was not associated with MI. When simultaneously examining the joint association of this polymorphism, DM, and obesity with MI, as compared to subjects with QQ genotypes and without DM and obesity, subjects with QR/RR genotypes and with either DM or obesity had significantly higher risk of MI (OR = 3.6, 95% CI: 1.5-8.7). CONCLUSION: Our data suggest that PON1 Q192R polymorphism was not independently associated with MI but further increased the risk of MI among the subjects with DM, obesity, or both, the conditions associated with high oxidative stress.
The present study tested the hypothesis that the increased risk in patients with exercise-provoked ST-segment depression recovering from acute myocardial infarction could by abolished by anti-ischaemic medical intervention. Prior to discharge a symptom-limited exercise test was carried out. Patients were then double-blindly randomized to treatment with either verapamil 120 mg t.i.d. or placebo, and observed for up to 18 months (mean 17 months). End-point was first major event; i.e. non-fatal reinfarction or death. Two-hundred-and-ninety-eight patients were included. Forty-four patients with and 111 without exercise-induced ischaemia were randomized to verapamil and 39 and 104 respectively, to placebo. The overall number of events was 12.5%. In patients without ST-segment depression, 12.5% in the placebo group (hazard = 1) and 12.6% in the verapamil group (hazard = 1.13) had an event (NS). In patients with ST-segment depression 15.4% in the placebo group (hazard = 1.20) and 9.1% in the verapamil group (hazard = 0.85) had an event (NS). The latter reduction (41%) supports the hypothesis that patients with ST-segment depression, i.e. residual myocardial ischaemia, are those who benefit from anti-ischaemic intervention after myocardial infarction.
OBJECTIVES: To determine coronary event and case fatality rates in an English population aged less than 80 years in Oxfordshire, and to compare these rates with those reported by the UK monitoring trends and determinants of cardiovascular disease (MONICA) centres in Scotland and Northern Ireland and those ascertained in Oxfordshire in 1966-67. DESIGN: A population wide surveillance study conducted in 1994-95 using prospective and retrospective case ascertainment. SETTING: A resident population in Oxfordshire of 568,800. SUBJECTS: Patients with suspected myocardial infarction or coronary death. OUTCOME MEASURES: A diagnosis of definite or possible myocardial infarction or coronary death using WHO MONICA diagnostic criteria based on symptoms, electrocardiograms, cardiac enzymes, necropsy findings, and past medical history. RESULTS: The annual rate for a first or recurrent coronary event per 100,000 population aged less than 65 years in 1994-95 was 273 for men and 66 for women after age adjustment to a standard world population. Rates in the age group 65-79 years were 1350 for men and 677 for women. Between 1966-67 and 1994-95, the age standardised event rate in the age group 30-69 years decreased significantly by 33% (95% confidence interval (CI) 44 to 21) in men, and there was a non-significant reduction of 8% (95% CI -33 to 17) in women. The age standardised 28 day case fatality rates also decreased significantly by 28% (95% CI 41 to 15) in men and by 32% (95% CI 55 to 9) in women. CONCLUSIONS: The coronary event rate in Oxfordshire was much lower than rates reported by MONICA centres in Glasgow and Belfast, and similar to rates reported by MONICA centres in France and northern Italy. The substantially lower event rate accounts for lower coronary heart disease mortality in Oxfordshire than in Scotland and Northern Ireland. The reduced coronary mortality in this region is attributable to declines in coronary event and case fatality rates.
Pulmonary and myocardial damage are frequently cited as manifestations of disseminated intravascular coagulation (DIC), but rarely as causes. Three elderly cases of severe DIC due to pulmonary and myocardial infarction are reported. All three patients died. Necropsy showed extensive pulmonary emboli in each case with large pulmonary infarcts in cases 1 and 2 and a ventricular aneurysm containing thrombus in cases 2 and 3. Early diagnosis and treatment of pulmonary embolism requires a high degree of clinical suspicion but may prevent progression to the irreversible stage of severe DIC.
The importance of heart rate for left ventricular remodeling and prognosis after myocardial infarction is not known. We examined the contribution of heart rate reduction by zatebradine, a direct sinus node inhibitor without negative inotropic effects on left ventricular function and dilatation, on mortality, energy metabolism, and neurohormonal changes in rats with experimental myocardial infarction (MI). Thirty minutes after left coronary artery ligation or sham operation, the rats were randomized to receive either placebo or zatebradine (100 mg x kg(-1) x day(-1) per gavage) continued for 8 wk. Mortality during 8 wk was 33.3% in the placebo and 23.0% in the zatebradine group (P < 0.05); MI size was 36 +/- 2% and 30 +/- 1% (means +/- SE, P < 0.05), respectively. Zatebradine improved stroke volume index in all treated rats but increased left ventricular volume in rats with small MI (2.43 +/- 0.10 vs. 1.81 +/- 0.10 ml/kg, P < 0.05) but not in rats with large MI (2.34 +/- 0.09 vs. 2.35 +/- 0.11 ml/kg, not significant). Zatebradine reduced left and right ventricular norepinephrine and increased left and right ventricular 3,4-dihydroxyphenyl ethylene glycol-to-norepinephrine ratio suggesting aggravation of cardiac sympathetic activation by zatebradine after MI. Creatine kinase and lactate dehydrogenase isoenzymes in rats with MI remained unchanged by zatebradine. Lowering heart rate per se reduces mortality and MI size in this model but induces adverse effects on left ventricular remodeling in rats with small MI.
BACKGROUND: The findings of sympathetic remodeling and its electrophysiological implications force us to rerecognize the drugs presently used. The aim of this study was to investigate the effects of metoprolol on sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) after myocardial infarction (MI). METHODS: Forty rabbits were randomly assigned into two groups: MI group (n = 20), ligation of the anterior descending coronary; Metoprolol group (n = 20), ligation of the anterior descending coronary and administration of oral metoprolol 5 mg/kg/day. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, TDR and difference of TDR (deltaTDR) during sympathetic nerve stimulation were measured at the IBZ. The distribution and densities of growth associated protein 43 and tyrosine hydroxylase positive nerves at the IBZ were detected with immunohistochemical techniques. RESULTS: The study was completed in the 36 surviving animals (18 rabbits in each group). The densities of growth associated protein 43 and tyrosine hydroxylase positive nerves in the Metoprolol group (2,550 +/- 554 and 1,779 +/- 458 microm2/mm2, respectively) were lower than in the MI group (3,217 +/- 589 and 2,616 +/- 528 microm2/mm2, respectively; both p < 0.01). TDR at baseline, TDR and deltaTDR during sympathetic nerve stimulation were shorter in the Metoprolol group than in the MI group (p < 0.01 for all). CONCLUSION: Metoprolol can inhibit sympathetic remodeling and electrical remodeling at the IBZ after MI. The association of metoprolol with improved electrical remodeling may be partly related to the inhibition of sympathetic remodeling.
BACKGROUND: The aim of the current study was to assess the utility of transmurality of delayed enhancement on cardiac magnetic resonance imaging (MRI) in predicting functional recovery in patients with first ST-elevation myocardial infarction (MI) who had received thrombolysis. METHODS: Nineteen patients underwent cine and contrast-enhanced MRI 3 days and 8 weeks after MI. The transmural extent of infarction (TEI) was determined from the late enhancement component of the first scan. Segmental wall thickening was scored from the cine components of both the initial and follow-up scans. RESULTS: The TEI was inversely related to the likelihood of improvement in wall thickening; chi(2) test for trend = 53.9, p < 0.0001. Delayed enhancement with >50% transmurality predicted a lack of recovery with 82% sensitivity and 54% specificity. The equivalent values for >75% transmurality were 57 and 77%, respectively. The proportion of the left ventricular segments exhibiting functional recovery was related to the percentage of the left ventricle that was severely dysfunctional but had <or=50% TEI (r = 0.49, p = 0.03). In a backward conditional regression model this was the only independent predictor. CONCLUSION: These data suggest that TEI, determined by contrast-enhanced cardiac MRI, is a useful predictor of the likelihood, or otherwise, of functional recovery following acute MI treated with thrombolysis.
The purpose was to evaluate the 10-year mortality in patients with acute chest pain suspected of myocardial infarction with (AMI) and without (non-AMI) confirmed diagnosis and to determine risk factors from the medical history and the diagnosis at discharge. One-thousand eight-hundred and ninety-seven non-AMI patients and 1,401 patients with AMI consecutively admitted to 1 of 16 coronary care units participating in The Danish Verapamil Infarction Study were included. During follow-up, 630 deaths occurred among the non-AMI patients and 415 of these could be classified as cardiac deaths. Multivariate analysis identified the following risk factors containing independent prognostic information about mortality for non-AMI patients: age, previous AMI, sex, and diabetes. In patients with AMI the risk factors were: age, previous AMI, clinical heart failure, diabetes, and angina pectoris. By including the diagnosis at discharge for non-AMI patients in the Cox analysis, the prognostic significance was compared to the variables from the medical history. Only the diagnoses bronchopneumonia, musculoskeletal disorders and observatio sine indicatione therapiae added independent prognostic information. We conclude that non-AMI patients are at high risk for mortal events in the long term. High-risk patients can be identified from their medical history, whereas the diagnosis at discharge only adds limited prognostic information. All non-AMI patients should be carefully evaluated regarding coronary artery disease at the time of discharge in order to improve the risk stratification, treatment and prognosis.
OBJECTIVE: Advanced glycation end products (AGEs), such as N(epsilon)-(carboxymethyl)lysine (CML), are implicated in vascular disease. We previously reported increased CML accumulation in small intramyocardial blood vessels in diabetes patients. Diabetes patients have an increased risk for acute myocardial infarction (AMI). Here, we examined a putative relationship between CML and AMI. METHODS AND RESULTS: Heart tissue was stained for CML, myeloperoxidase, and E-selectin in AMI patients (n=26), myocarditis patients (n=17), and control patients (n=15). In AMI patients, CML depositions were 3-fold increased compared with controls in the small intramyocardial blood vessels and predominantly colocalized with activated endothelium (E-selectin-positive) both in infarction and noninfarction areas. A trend of increased CML positivity of the intima of epicardial coronary arteries did not reach significance in AMI patients. In the rat heart AMI model, CML depositions were undetectable after 24 hours of reperfusion, but became clearly visible after 5 days of reperfusion. In line with an inflammatory contribution, human myocarditis was also accompanied by accumulation of CML on the endothelium of intramyocardial blood vessels. CONCLUSIONS: CML, present predominantly on activated endothelium in small intramyocardial blood vessels in patients with AMI, might reflect an increased risk for AMI rather than being a result of AMI.
BACKGROUND: Heart failure (HF) is an important predictor of poor outcome after acute myocardial infarction (AMI). However, limited data exist about the clinical significance of HF in the coronary reperfusion era and the impact of its timing on hospital outcomes. The objective of this study was to determine the clinical impact of HF complicating AMI in the National Registry of Myocardial Infarction (NRMI). A secondary objective was to determine differences in demographic and clinical characteristics, treatment, and hospital death rates in patients presenting with HF compared with those developing HF after presentation. METHODS AND RESULTS: The study sample consisted of patients with AMI and without a history of HF included in the NRMI. Of 606 500 cases included from July 1, 1994 to June 30, 2000, 123 938 (20.4%) patients had HF at the time of hospital presentation and 52 220 (8.6%) developed HF thereafter. Patients with HF were older, more likely female, had more comorbidities, and were less likely to receive effective cardiac medications compared with patients without HF. The multivariable adjusted odds for in-hospital death were higher for patients with HF at presentation and thereafter (3.1 and 5.5, respectively) than those without HF. CONCLUSIONS: Results from this nationwide registry suggest that the incidence and hospital death rates associated with HF complicating AMI remain high. Patients developing HF after hospital admission are at even greater risk than those presenting with HF. Effective cardiac therapies remain underutilized in these patients, and the reasons for this underutilization need to be explored.
BACKGROUND: Complete coronary artery reperfusion in acute myocardial infarction (AMI) has been shown to significantly improve survival. Electrical stability may be the decisive mechanism for this beneficial effect. Because electrical stability is largely dependent on ventricular repolarization, we sought to determine the impact of a modern reperfusion strategy (ie, direct percutaneous coronary intervention [PCI]) on QT dynamicity in AMI and examined its association with infarct-related artery flow. METHODS AND RESULTS: We prospectively investigated QT dynamicity in 128 patients undergoing direct PCI for a first AMI. Slopes and correlation coefficients of the linear QT/RR regression were determined in the time interval before reperfusion, within the initial hour after reperfusion, and within the remaining recording period from Holter ECG recordings, which were initiated on admission. Subgroup analysis based on TIMI 3 (n=100) and TIMI 2 (n=28) flow after PCI revealed no significant differences in QT/RR slope before PCI (0.145+/-0.12 versus 0.160+/-0.19,P=NS). After PCI, QT/RR slopes increased only in the TIMI 2 subgroup (P<0.05). In TIMI 2 patients, QT/RR slopes were significantly steeper in the hour after PCI and in the remaining recording period, respectively (0.155+/-0.12 versus 0.192+/-0.15,P<0.05, and 0.159+/-0.10 versus 0.210+/-0.17,P<0.01). CONCLUSIONS: Alterations of QT dynamicity in patients with incomplete reperfusion may suggest an altered electrical restitution, potentially providing a substrate for serious ventricular arrhythmias. Thus, our findings offer new insights into mechanisms by which complete reperfusion may affect electrical stability.
BACKGROUND: Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: In the TACTICS-TIMI 18, OPUS-TIMI 16, and TIMI 11 studies, baseline samples were analyzed in the Thrombolysis In Myocardial Infarction (TIMI) biomarker core laboratory. We examined the relationship between gender and elevated biomarkers. Of 1865 patients from TACTICS-TIMI 18, 34% were women. Fewer women had elevated creatine kinase-MB or troponins, whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide. Presence of ST-segment deviation and TIMI risk scores were not significantly different. This pattern was confirmed in TIMI 11 and OPUS-TIMI 16. The prognostic value of the markers in TACTICS-TIMI 18 was similar in women and men. When a multimarker approach was examined, a greater proportion of high-risk women were identified. Marker-positive patients of both genders had improved outcome with an invasive strategy; however, marker-negative women appeared to have improved outcomes with a conservative strategy. CONCLUSIONS: In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers. Men were more likely to have elevated creatine kinase-MB and troponins, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide. This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI, especially in women. Further research is necessary to elucidate whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes.
BACKGROUND: Low-molecular-weight heparins are attractive alternatives to unfractionated heparin (UFH) for management of unstable angina/non-Q-wave myocardial infarction (UA/NQMI). METHODS AND RESULTS: Patients (n=3910) with UA/NQMI were randomized to intravenous UFH for >/=3 days followed by subcutaneous placebo injections or uninterrupted antithrombin therapy with enoxaparin during both the acute phase (initial 30 mg intravenous bolus followed by injections of 1.0 mg/kg every 12 hours) and outpatient phase (injections every 12 hours of 40 mg for patients weighing <65 kg and 60 mg for those weighing >/=65 kg). The primary end point (death, myocardial infarction, or urgent revascularization) occurred by 8 days in 14.5% of patients in the UFH group and 12.4% of patients in the enoxaparin group (OR 0.83; 95% CI 0.69 to 1.00; P=0. 048) and by 43 days in 19.7% of the UFH group and 17.3% of the enoxaparin group (OR 0.85; 95% CI 0.72 to 1.00; P=0.048). During the first 72 hours and also throughout the entire initial hospitalization, there was no difference in the rate of major hemorrhage in the treatment groups. During the outpatient phase, major hemorrhage occurred in 1.5% of the group treated with placebo and 2.9% of the group treated with enoxaparin (P=0.021). CONCLUSIONS: Enoxaparin is superior to UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of UA/NQMI patients without causing a significant increase in the rate of major hemorrhage. No further relative decrease in events occurred with outpatient enoxaparin treatment, but there was an increase in the rate of major hemorrhage.
BACKGROUND: Elevation of the white blood cell (WBC) count during acute myocardial infarction (AMI) is associated with adverse outcomes. We examined the relationship between the WBC count and angiographic findings to gain insight into this relationship. Results and Methods-We evaluated data from 975 patients in the Thrombolysis In Myocardial Infarction (TIMI) 10A and 10B trials. Patients with a closed artery at 60 and 90 minutes had higher a WBC count than patients with an open artery (P:=0.02). Likewise, the presence of angiographically apparent thrombus was associated with a higher WBC count (11.5+/-5.2x10(9)/L, n=290, versus 10.7+/-3. 5x10(9)/L, n=648; P=0.008). In addition, a higher WBC count was associated with poorer TIMI myocardial perfusion grades (4-way P=0.04). Mortality rates were higher in patients with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 4.9% for WBC count 5 to 10x10(9)/L, 3.8% for WBC count 10 to 15x10(9)/L, 10.4% for WBC count >15x10(9)/L; P=0.03). The development of new congestive heart failure or shock was also associated with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 5.2% for WBC count 5 to 10x10(9)/L, 6.1% for WBC count 10 to 15x10(9)/L, 17.1% for WBC count >15x10(9)/L; P<0.001), an observation that remained significant in a multivariable model that adjusted for potential confounding variables (odds ratio 1.21, P=0.002). CONCLUSIONS: Elevation in WBC count was associated with reduced epicardial blood flow and myocardial perfusion, thromboresistance (arteries open later and have a greater thrombus burden), and a higher incidence of new congestive heart failure and death. These observations provide a potential explanation for the higher mortality rate observed among AMI patients with elevated WBC counts and helps explain the growing body of literature that links inflammation and cardiovascular disease.
Dogs 3-7 days following ligation of the anterior descending coronary artery representing a remarkably stable model for re-entrant ventricular arrhythmias (RVA) and allowed detailed electrophysiologic studies of the re-entrant mechanism. In these dogs, we could regularly illustrate the presence of continuous electrical activity originating from the infarction zone (IZ) and bridging the diastolic interval between the initiating and re-entrant beats as well as between consecutive re-entrant beats. Conduction in the IZ was highly complex, with multiple potentially re-entrant pathways, functionally dissociated areas, and areas of localized ventricular fibrillation. Conduction disorders in ischemic myocardium were consistently tachycardia-dependent with the spontaneous onset of RVA specifically associated with a Wenckebach-like conduction pattern in a potentially re-entrant pathway. Both manifest and concealed re-entry, as well as re-entrant beats with regular extrasystolic grouping, constant or variable coupling, uniform multiform and bidirectional QRS configurations, were related to characteristic conduction patterns in the IZ. In summary, the study provides the first direct in vivo evidence of ventricular re-entry and demonstrates propensity for RVA and sudden death in the late myocardial infarction period.
Acute left anterior descending coronary artery occlusion was produced in 21 conscious, chronically instrumented dogs. Forty minutes after coronary occlusion, nine dogs were given i.v. teprotide, 25 micrograms/kg/min, followed by oral doses of captopril, 10 mg/kg every 8 hours for 24 hours. The remaining 12 dogs served as saline-infused controls. In all dogs, acute coronary occlusion increased plasma renin activity and peripheral vascular resistance and reduced cardiac output, but did not change mean aortic blood pressure significantly. Teprotide significantly (p less than 0.05) decreased peripheral vascular resistance (from 3804 +/- 1158 to 2876 +/- 816 dy-sec-cm-5) (+/- SD) and mean aortic pressure (from 117 +/- 12 to 107 +/- 15 mm Hg), and increased cardiac output (from 2.63 +/- 0.67 to 3.12 +/- 0.74 l/min). Teprotide also produced a relative increase in flow to the renal and splanchnic circulations compared with the saline-treated controls. There were, however, no differences in segmental systolic shortening, blood flow in the normal or ischemic myocardium, or infarct size. These results indicate that the renin-angiotensin system may play an important role in dogs with acute coronary occlusion and that blockade of this system lowers systemic blood pressure and improves cardiac output. However, direct effects of renin-angiotensin system blockade on the myocardium are lacking; there were no changes in myocardial blood flow, myocardial mechanics or infarct size.