bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical treatment of ventricular tachycardia after surgical repair of tetralogy of Fallot. Relation between intraoperative mapping and histological findings.
Authors: Misaki T , Tsubota M , Watanabe G , Watanabe Y , Matumoto Y , Ishida K , Iwa T , Okada R
Published: June 2012

BACKGROUND

The mechanism of ventricular tachycardia (VT) after correction of tetralogy of Fallot (TF) is poorly understood. The purpose of this study was to examine the histopathology of the arrhythmogenic area detected by intraoperative mapping.

METHODS AND RESULTS

The patients were three men who underwent radical surgery for TF at age 3, 3, or 5 years, respectively. VT developed at 8, 9, or 11 years, respectively, after surgery, and shock developed during VT in every case. The ECG revealed monomorphic VT in two cases and polymorphic VT in one case. Induction of VT resulted in a wide left-axis deviation-pattern QRS with cycle lengths varying between 260 and 330 milliseconds. The VT origin was identified at the right ventricular outflow tract (RVOT). A radical operation was performed with the patient under cardiopulmonary bypass. On epicardial mapping, delayed activation of the RVOT was recorded during sinus rhythm, and clockwise circus movement of the macroreentry current during VT on the right ventricular free wall was documented in each case. The VTs were treated successfully by surgical resection and cryoablation of the myocardium. In every patient, histology of the myocardial specimens showed degeneration, adiposis, fibrosis, inflammatory cell infiltration, and scattered myocyte islets. These lesions corresponded anatomically to the area of myocardium in which delayed activation was evident during epicardial mapping.

CONCLUSIONS

The results of this study indicate that patients with VT after radical correction of the TF have abnormal histopathological findings at the site of the prior right ventriculotomy scar. These lesions were noted within the region of delayed activation found during epicardial mapping and were found to be a part of the reentrant circuit.
Acute myocarditis. Rapid diagnosis by PCR in children.
Authors: Martin A B , Webber S , Fricker F J , Jaffe R , Demmler G , Kearney D , Zhang Y H , Bodurtha J , Gelb B , Ni J
Published: June 2012

BACKGROUND

The diagnosis of viral myocarditis remains difficult and generally depends on clinical and histological criteria. Viral cultures and serology are often unrewarding, with low yields. The purpose of this study was to analyze the usefulness of polymerase chain reaction (PCR) in the rapid diagnosis of acute myocarditis in children.

METHODS AND RESULTS

PCR was used to analyze 38 myocardial tissue samples from 34 patients with suspected acute viral myocarditis and 17 control patients with congenital heart disease (14) or hypertrophic cardiomyopathy (3). Myocardial samples were obtained at the time of right ventricular biopsy (13 samples), from explanted hearts (18 samples) at transplantation, and from cardiac autopsy specimens (24 samples) and were evaluated for the presence of enterovirus, cytomegalovirus (CMV), adenovirus, and herpes simplex virus (HSV) using PCR primers designed to consensus and unique sequences of these viral genomes. Blood also was obtained at the time of biopsy (11) or transplant (18). In 26 of 38 myocardial samples (68%), viral genome was detected by PCR (15 adenoviral, 8 enteroviral, 2 HSV, 1 CMV), whereas all control myocardial samples and blood samples were negative. Four patients had positive viral cultures, and these matched the PCR findings. Disagreement with histopathology occurred in 13 of 26 PCR-positive specimens, usually associated with adenovirus.

CONCLUSIONS

PCR offers a rapid, sensitive diagnostic method for myocardial viral infection. While enterovirus is an important etiological agent, adenovirus was more prevalent in this series and should be evaluated when etiology is sought. PCR used in conjunction with standard endomyocardial biopsy appears to enhance the likelihood of detecting viral genome in the myocardium of patients with clinical evidence of myocarditis.
Cardiovascular status in young patients with insulin-dependent diabetes mellitus.
Authors: Kimball T R , Daniels S R , Khoury P R , Magnotti R A , Turner A M , Dolan L M
Published: June 2012

BACKGROUND

Although the existence of diabetic cardiomyopathy in adults is firmly established, the presence of cardiac abnormalities in young diabetic patients is not universally accepted. We sought to determine the early stages of cardiac derangement and whether they are associated with renal dysfunction.

METHODS AND RESULTS

Thirty-nine patients (29 boys; mean age, 17.6 +/- 3.4 years) with insulin-dependent diabetes mellitus underwent echocardiography and timed overnight urine collection. Echocardiographic evaluation consisted of left ventricular mass, performance (shortening fraction, velocity of circumferential fiber shortening, stroke volume, and cardiac index), preload (end-diastolic dimension and volume), after-load (end-systolic wall stress and systemic vascular resistance), and contractility (velocity of fiber shortening relative to wall stress). Creatinine clearance and albumin excretion were measured from the urine sample. Glycosylated hemoglobin levels were measured; height and weight were measured; and Quetelet index (weight/height2) was calculated. These data were compared with control data. Left ventricular mass (26 +/- 6 versus 22 +/- 6 g/ht2.7, P < .01), the indexes of performance, blood pressure, and contractility (0.14 +/- 0.14 versus 0.003 +/- 0.03 circumference/s, P < .0003) were significantly higher in the diabetic patients than in control subjects. To evaluate the correlates of left ventricular mass and contractility in the diabetic patients, univariate and multiple regression analyses were performed. Significant univariate correlations of mass included albumin excretion (r = .36, P < .02), glycosylated hemoglobin (r = .35, P < .04), and stroke volume (r = .34, P < .03). A multivariate model included Quetelet index, albumin excretion, and duration of diabetes. Significant univariate correlations of contractility included insulin dosage (r = -.36, P < .02), creatinine clearance (r = .40, P < .02), and Quetelet index (r = .34, P < .03). A multivariate model included insulin dosage and creatinine clearance.

CONCLUSIONS

Early onset of diabetes mellitus is associated with increased left ventricular mass, performance, contractility, and blood pressure. These cardiovascular findings are correlated with increased creatinine clearance and microalbuminuria. These relations suggest that alterations in cardiovascular and renal function may occur in parallel in adolescents with insulin-dependent diabetes mellitus.
Induction of nitric oxide synthase gene by interleukin-1 beta in cultured rat cardiocytes.
Authors: Tsujino M , Hirata Y , Imai T , Kanno K , Eguchi S , Ito H , Marumo F
Published: June 2012

BACKGROUND

Impaired myocardial contractility in septic shock is protracting, which may be caused by cytokine-induced nitric oxide (NO) synthesis in the heart. However, the cellular mechanism by which cytokines induce nitric oxide synthase (NOS) in cardiocytes remains obscure.

METHODS AND RESULTS

We studied the effect of human recombinant interleukin-1 beta (IL-1 beta) on synthesis of NO2-/NO3- (NOx) and the expression of NOS mRNA and protein in cultured neonatal rat cardiocytes. IL-1 beta dose-dependently (0.1 to 10 ng/mL) stimulated NOx production as a function of time (6 to 48 hours). Northern blot analysis using complementary DNAs for rat brain-type constitutive (c) NOS and mouse macrophage-type inducible (i) NOS as probes showed that IL-1 beta induced expression of mRNA for iNOS but not for cNOS, starting after 6 hours and reaching a maximum after 48 hours in cardiocytes. IL-1 beta similarly induced iNOS mRNA expression in cultured adult rat cardiocytes in a time-dependent manner. Western blot analysis using specific antibody against the N-terminal fragment of mouse iNOS revealed the expression of 130-kD iNOS-like protein in IL-1 beta-treated cardiocytes. Northern blotting and immunocytochemical study revealed that IL-1 beta-induced iNOS mRNA and iNOS-like immunoreactivity were exclusively localized to cardiac myocytes but also to nonmyocytes, to a lesser extent. NG-mono-methyl-L-arginine, an NOS inhibitor, completely blocked the IL-1 beta-induced NOx production, whose effect was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited the IL-1 beta-induced NOx production as well as iNOS mRNA expression. Cycloheximide and actinomycin D completely inhibited the IL-1 beta-induced NOx production and iNOS mRNA expression. Neither a calmodulin inhibitor (W-7), a protein kinase C inhibitor (calphostin C), nor a Ca2+ channel antagonist (nicardipine) showed any effect on the IL-1 beta-induced NOx production.

CONCLUSIONS

These data demonstrate that IL-1 beta induces macrophage-type iNOS mRNA expression mainly by cardiac myocytes but also by nonmyocytes to a lesser extent, and subsequent de novo protein synthesis of iNOS leads to excessive local production of NO by cardiocytes.
Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.
Authors: Hodis H N , Mack W J , Azen S P , Alaupovic P , Pogoda J M , LaBree L , Hemphill L C , Kramsch D M , Blankenhorn D H
Published: June 2012

BACKGROUND

The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions > or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets.

METHODS AND RESULTS

Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate (< 50% S) and severe (> or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P < .05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the predominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDL-associated apolipoprotein C-III (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C was the predominant risk factor.

CONCLUSIONS

These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.
Radiofrequency thermal angioplasty maintains arterial duct patency. An experimental study.
Authors: Abrams S E , Walsh K P , Diamond M J , Clarkson M J , Sibbons P
Published: June 2012

BACKGROUND

Long-term maintenance of arterial duct patency by a catheter technique would be a valuable nonsurgical method of palliation for duct-dependent circulations. We used a new method: percutaneous radiofrequency thermal balloon angioplasty of neonatal lamb arterial ducts.

METHODS AND RESULTS

Radiofrequency balloons 5 or 6 mm in diameter were introduced via the femoral vein of 32 neonatal lambs and inflated to 4 atm. In 28, a radiofrequency generator was used to heat the saline/contrast mixture in the balloon to 65 degrees C (n = 2), 75 degrees C (n = 2), 85 degrees C (n = 10), 100 degrees C (n = 8), and 120 degrees C (n = 6). In 4 lambs, angioplasty alone was performed. Lambs were recatheterized to assess patency at intervals up to 78 weeks. Immediate results showed the arterial duct to be patent in all cases, with a mean rise in systolic pulmonary artery pressure of 13 +/- 8 mm Hg and a mean rise in pulmonary artery oxygen saturation of 12 +/- 15%. With a mean follow-up of 45.7 +/- 28 weeks, 3 of the 4 (75%) angioplasty alone ducts closed, but only 5 of the 28 (18%) radiofrequency-treated ducts (P < .05). The mean rise in oxygen saturation between the superior vena cava and the pulmonary artery was 7.6 +/- 7% at last follow-up. Follow-up angiography of the arterial ducts showed the development of stenoses in all patent ducts.

CONCLUSIONS

Radiofrequency thermal balloon angioplasty leads to long-term arterial duct patency in lambs in > 80% of the treated group and is significantly more effective than balloon angioplasty alone.
Vasoreactivity of the culprit lesion in unstable angina.
Authors: Bogaty P , Hackett D , Davies G , Maseri A
Published: June 2012

BACKGROUND

Although abnormal vasoconstriction may be involved in the pathogenesis of the acute coronary syndromes, the vasoreactivity of the lesion responsible for unstable angina (culprit lesion) has not been directly investigated. It is also unknown if enhanced vasoreactivity is found downstream to this lesion or extends to uninvolved coronary arteries.

METHODS AND RESULTS

We studied seven unstable angina patients whose condition had sufficiently stabilized to allow ergometric bicycle exercise and a cold pressor test to be performed as provocative stimuli during coronary arteriography. We measured the luminal diameter of the culprit lesion, a normal-appearing distal segment, and the segment of an uninvolved coronary artery using quantitative coronary angiography. Seven stable angina patients served as controls. Antianginal medications were tapered and interrupted. The culprit lesion constricted significantly with exercise and the cold pressor test compared with a stable angina control lesion. The culprit lesion measured 1.41 +/- 0.07 mm at baseline and diminished to 1.09 +/- 0.07 mm with exercise (P = .001). It measured 1.26 +/- 0.07 mm before the cold pressor test and diminished to 1.09 +/- 0.03 mm with this test (P = .015). In contrast, the profile of the stable lesion in the stable angina control group differed significantly (P = .006). Its luminal diameter measured 1.42 +/- 0.17 mm at baseline and 1.48 +/- 0.21 mm with exercise (P = NS). It measured 1.57 +/- 0.18 mm before and 1.55 +/- 0.18 mm with the cold pressor test (P = NS). There were no significant changes to these stimuli in the uninvolved coronary artery segments in unstable angina and in the distal segments in both unstable and stable angina patients.

CONCLUSIONS

This study demonstrates increased vasoreactivity of the culprit lesion in unstable angina compared with a control lesion in stable angina. The lack of an effect either in the uninvolved coronary artery or downstream to the culprit lesion suggests that systemic neurohumoral or seeding mechanisms are not operative. This abnormal vasoreactivity might predispose to, or be a marker for, the recurrence of acute ischemia at this site.
In vivo magnetic resonance spectroscopy measurement of deoxymyoglobin during exercise in patients with heart failure. Demonstration of abnormal muscle metabolism despite adequate oxygenation.
Authors: Mancini D M , Wilson J R , Bolinger L , Li H , Kendrick K , Chance B , Leigh J S
Published: June 2012

BACKGROUND

Skeletal muscle metabolic abnormalities have been described in patients with heart failure that are independent of total limb perfusion, histochemical changes, and muscle mass. However, these skeletal muscle metabolic abnormalities may result from tissue hypoxia caused by maldistribution of flow. Myoglobin is an O2 binding protein that can indirectly assess tissue hypoxia.

METHODS AND RESULTS

In vivo measurement of deoxymyoglobin was performed by use of proton (1H) magnetic resonance spectroscopy in 16 heart failure (HF) (left ventricular ejection fraction = 20 +/- 6%; VO2 = 14.5 +/- 5.1 mL/kg per minute) and 7 healthy (Nl) subjects. Simultaneous phosphorus (31P) magnetic resonance spectroscopy and near-infrared spectroscopy also were obtained to examine muscle metabolism and oxygenation. Supine calf plantarflexion was performed every 4 seconds. Incremental steady-state work was performed. A second exercise protocol studied rapid incremental (RAMP) exercise with plantarflexion every 2 seconds. Arterial occlusion at end exercise provided physiological calibration for myoglobin and hemoglobin signals. With steady-state exercise, the work slope, ie, inorganic phosphorus to phosphocreatine ratios versus work, was significantly greater in patients with heart failure (Nl: 0.18 +/- 0.08; HF: 0.40 +/- 0.32 W-1; P < .05). Intracellular pH was reduced significantly at end exercise in patients but not healthy subjects. Despite these metabolic abnormalities, muscle oxygenation derived from 760- to 850-nm absorption was comparable in both groups throughout exercise. The relation of inorganic phosphorus/phosphocreatine (P1/PCr) ratio and muscle oxygenation was shifted upward in patients with heart failure such that at the same muscle oxygenation, Pi/PCr ratio in these patients was increased. No deoxymyoglobin signals were observed at rest. At maximal exercise, 4 of the healthy subjects and 3 of the patients exhibited deoxymyoglobin (P = NS). With RAMP exercise, the work slope was again significantly greater in patients with heart failure (Nl: 0.21 +/- 0.10; HF: 0.57 +/- 0.32 W-1; P < .05). Intracellular pH again was significantly decreased at end exercise in patients but not healthy subjects. Five of the healthy subjects and 3 of the heart failure patients had deoxymyoglobin signal (P = NS). With arterial occlusion, deoxymyoglobin was seen in all subjects.

CONCLUSION

Abnormal skeletal muscle metabolism in patients with heart failure usually occurs in the absence of myoglobin deoxygenation, suggesting that the abnormalities are not a result of cellular hypoxia during exercise with minimal cardiovascular stress.
Diagnosing and managing unstable angina. Agency for Health Care Policy and Research.
Authors: Braunwald E , Jones R H , Mark D B , Brown J , Brown L , Cheitlin M D , Concannon C A , Cowan M , Edwards C , Fuster V
Published: June 2012

This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of an expert panel. Principal conclusions include the following. (1) Many patients suspected of having unstable angina can be discharged home after adequate initial evaluation. (2) Further outpatient evaluation may be scheduled for up to 72 hours after initial presentation for patients with clinical symptoms of unstable angina judged at initial evaluation to be at low risk for complications. (3) Patients with acute ischemic heart disease judged to be at intermediate or high risk of complications should be hospitalized for careful monitoring of their clinical course. (4) Intravenous thrombolytic therapy should not be administered to patients without evidence of ST segment elevation and acute myocardial infarction. (5) Assessment of prognosis by noninvasive testing often aids selection of appropriate therapy. (6) Coronary angiography is appropriate for patients judged to be at high risk for cardiac complications or death based on their clinical course or results of noninvasive testing. (7) Coronary artery bypass surgery should be recommended for almost all patients with left main disease and many patients with three-vessel disease, especially those with left ventricular dysfunction. (8) The discharge care plan should include continued monitoring of symptoms; appropriate drug therapy, including aspirin; risk-factor modification; and counseling.
Effects of heptanol, class Ic, and class III drugs on reentrant ventricular tachycardia. Importance of the excitable gap for the inducibility of double-wave reentry.
Authors: Boersma L , Brugada J , Abdollah H , Kirchhof C , Allessie M
Published: June 2012

BACKGROUND

Double-wave reentry (DWR) can be a mechanism for acceleration of ventricular tachycardia (VT) with a large excitable gap (EG). The purpose of this study was to determine the effects of heptanol, class Ic, and class III drugs on the inducibility of DWR.

METHODS AND RESULTS

In 11 Langendorff-perfused rabbit hearts, a thin ring of anisotropic left ventricular epicardium was created by a cryoprocedure. VT with a revolution time of 180 +/- 26 milliseconds and an EG of 106 +/- 8 milliseconds was induced by incremental pacing. During control, entrainment with 10 stimuli at a 99 +/- 15-millisecond interval terminated VT in seven hearts. In four hearts VT was accelerated from 205 +/- 24 to 115 +/- 14 milliseconds by introduction of a second circulating wave in the ring. In the seven VTs that could not be accelerated, 0.5 mumol/L Org7797 (class Ic) and 1.0 mmol/L heptanol (uncoupling agent) prolonged the cycle length of VT by 32% and 37%, respectively. Because the refractory period (RP) only increased by 11%, the EG prolonged by 71% and the ratio between EG and RP was increased from 0.66 to 1.00. Under these conditions, DWR could be induced in all seven hearts. In the four VTs that could be accelerated during control, administration of the class III drug D-sotalol (35 mumol/L) only slightly slowed VT by 6%. Because the RP was prolonged by 15%, the ratio between the EG and the RP decreased from 0.76 to 0.63. Entrainment now failed to accelerate VT in two of four hearts, whereas in the two other hearts, double-wave reentry self-terminated within eight cycles.

CONCLUSIONS

Drugs that increase the ratio of EG and RP enhance the susceptibility to acceleration of VT, whereas drugs that decrease this ratio prevent induction of sustained double-wave reentry.
Alpha-adrenoceptor stimulation with exogenous norepinephrine or release of endogenous catecholamines mimics ischemic preconditioning.
Authors: Bankwala Z , Hale S L , Kloner R A
Published: June 2012

BACKGROUND

Brief episodes of ischemia induced by proximal coronary artery occlusion can precondition the myocardium. Whether other stressful stimuli have the potential to protect the myocardium from subsequent ischemia remains controversial.

METHODS AND RESULTS

To study the hypothesis that transient alpha-adrenoceptor stimulation mimics preconditioning, for 5 minutes we administered 0.25 micrograms.kg-1.min-1 norepinephrine or saline 10 minutes before a 30-minute coronary occlusion and 4 hours of reperfusion in an in vivo rabbit model. The area of necrosis (AN) and area of risk (AR) were measured. We found that norepinephrine pretreatment caused a reduction in infarct size when compared with controls (AN/AR, 0.17 +/- 0.04 versus 0.31 +/- 0.04; P < .02). Ischemic preconditioning also reduced infarct size (AN/AR, 0.22 +/- 0.03). The protection observed with norepinephrine treatment was entirely eliminated by pretreatment with alpha-adrenergic blockade using prazosin (AN/AR, 0.42 +/- 0.06). Tyramine, an agent that causes release of endogenous catecholamines, was administered (1.5 mg/kg i.v.) 10 minutes before coronary occlusion in another group of rabbits. Tyramine pretreatment resulted in a smaller infarct size than in untreated controls (AN/AR, 0.16 +/- 0.04 versus 0.41 +/- 0.07; P < .01). Both norepinephrine and tyramine caused an increase in systemic arterial pressure during infusion; tyramine also increased heart rate. In rabbits pretreated with prazosin, heart rate and systemic pressure during the norepinephrine infusion were similar to baseline values. During coronary occlusion, the degree of ischemia was similar in all groups.

CONCLUSIONS

Exposure of the heart to either transient exogenous norepinephrine or endogenous release of norepinephrine and/or other catecholamines by tyramine can mimic the effects of ischemic preconditioning in rabbits.
Coronary artery disease regression. Convincing evidence for the benefit of aggressive lipoprotein management.
Authors: Superko H R , Krauss R M
Published: June 2012

BACKGROUND

Numerous reports suggest that coronary artery disease can regress with lipoprotein manipulation. Many of these reports lack control groups and contain relatively small numbers.

METHODS AND RESULTS

Ten randomized controlled clinical trials using coronary arteriography to assess the effect of lipoprotein manipulation on the rate of progression and regression of atherosclerosis have been either published or reported as an abstract at a national meeting. These studies were critically reviewed for individual differences and combined clinically applicable lessons. These trials involved a total of 2095 subjects and have consistently reported reduction in the percentage of patients arteriographically defined as progressing (mean, 23.6%) and an increase in the percentage regressing (mean, 20.0%) compared with control groups. Compared with large clinical trials using clinical end points, lipoprotein change was greater, achieving on average a 28% reduction in low-density lipoprotein cholesterol, 11% reduction in triglycerides, and 11% increase in high-density lipoprotein cholesterol compared with control groups. Four investigations used a nonpharmacological approach, and seven used single and multiple drug therapy combined with diet. Despite the relatively brief treatment time of often 2 to 4 years, clinical events were fewer in the treatment groups; within some studies, this reached statistical significance. Side effects from the different therapies were tolerated by most patients, and severe adverse clinical events were few.

CONCLUSIONS

These trials present convincing evidence that aggressive lipoprotein manipulation can result in improved arteriographic measurements and fewer cardiovascular events in a relatively short period of time of 2 to 4 years. Extrapolation of this information to the larger population with known coronary artery disease suggests that directed lipoprotein manipulation can reduce clinical events in a cost-effective manner.
Increased secretion of tumor necrosis factor-alpha and interferon-gamma by mononuclear leukocytes in patients with ischemic heart disease. Relevance in superoxide anion generation.
Authors: Vaddi K , Nicolini F A , Mehta P , Mehta J L
Published: June 2012

BACKGROUND

There is growing evidence for a pathogenic role for cytokines in atherogenesis. The presence of certain cytokines has been documented in human atherosclerotic vessels. This study was designed to investigate cytokine production by mononuclear leukocytes from patients with ischemic heart disease.

METHODS AND RESULTS

We measured kinetics of secretion of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) by mononuclear leukocytes from 8 control subjects, 10 patients with stable angina pectoris, and 10 patients with unstable angina pectoris. Mononuclear leukocytes were isolated and incubated with or without the plant lectin mitogen concanavalin A for 48 hours. TNF-alpha and IFN-gamma secretion were measured by ELISA. The effect of TNF-alpha and IFN-gamma on superoxide radical generation by neutrophils was also examined. Secretion of both TNF-alpha and IFN-gamma by mononuclear leukocytes increased progressively over 48 hours, and it was consistently higher (P < .02) in patients compared with control subjects. A similar increase in cytokine secretion was observed in patients with stable or unstable angina pectoris. In addition, there was no relation between the severity of coronary artery disease by angiography and cytokine secretion. Basal neutrophil superoxide radical generation was increased in patients with ischemic heart disease, and incubation with cytokines failed to further stimulate superoxide generation in these patients.

CONCLUSIONS

Similar increases in cytokine secretion by mononuclear leukocytes in stable or unstable angina pectoris indicate that the increased cytokine release is not a nonspecific inflammatory response in acute myocardial ischemia. Increased cytokine secretion in ischemic heart disease may play a role in superoxide radical generation, endothelial injury, deposition and activation of cellular elements on the vessel wall, and possibly in the progression of atherosclerosis.
Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker.
Authors: Tomai F , Crea F , Gaspardone A , Versaci F , De Paulis R , Penta de Peppo A , Chiariello L , Gioffrè P A
Published: June 2012

BACKGROUND

Brief episodes of ischemia render the heart more resistant to subsequent ischemia; this phenomenon has been called ischemic preconditioning. In some animal species, myocardial preconditioning appears to be due to activation of ATP-sensitive K+ (KATP) channels. The role played by KATP channels in preconditioning in humans remains unknown. The aim of this study was to establish whether glibenclamide, a selective KATP channel blocker, abolishes the ischemic preconditioning observed in humans during coronary angioplasty following repeated balloon inflations.

METHODS AND RESULTS

Twenty consecutive patients undergoing one-vessel coronary angioplasty were randomized to receive 10 mg oral glibenclamide or placebo. Sixty minutes after glibenclamide or placebo administration, patients were given an infusion of 10% dextrose (8 mL/min) to correct glucose plasma levels or, respectively, an infusion of saline at the same infusion rate. Thirty minutes after the beginning of the infusion, both patient groups underwent coronary angioplasty. The mean values (+/- 1 SD) of ST-segment shifts on the surface 12-lead ECG and the intracoronary ECG were measured at the end of the first and second balloon inflations, both 2 minutes long. In glibenclamide-treated patients, the mean ST-segment shift during the second balloon inflation was similar to that observed during the first inflation (23 +/- 13 versus 20 +/- 8 mm, P = NS), and the severity of cardiac pain was greater (55 +/- 21 versus 43 +/- 23 mm on a scale of 0 to 100, P < .05). Conversely, in placebo-treated patients the mean ST-segment shift during the second inflation was less than that during the first inflation (9 +/- 5 versus 23 +/- 13 mm, P < .001), as was the severity of cardiac pain (15 +/- 15 versus 42 +/- 19 mm, P < .01). Blood glucose levels were significantly reduced 60 minutes after glibenclamide compared with those at baseline (53 +/- 9 versus 102 +/- 10 mg/100 mL, P < .001) in the glibenclamide group; however, before coronary angioplasty, blood glucose levels increased to 95 +/- 19 mg/100 mL, a value similar to that found in placebo group (96 +/- 11 mg/100 mL, P = NS).

CONCLUSIONS

In humans, ischemic preconditioning during brief repeated coronary occlusions is completely abolished by pretreatment with glibenclamide, thus suggesting that it is mainly mediated by KATP channels.
Double-blind efficacy and safety study of a novel anti-ischemic agent, ranolazine, versus placebo in patients with chronic stable angina pectoris. Ranolazine Study Group.
Authors: Thadani U , Ezekowitz M , Fenney L , Chiang Y K
Published: June 2012

BACKGROUND

Ranolazine modulates the metabolism of ischemic myocardial cells and improves the efficiency of oxygen use. This study was conducted to evaluate the antianginal and anti-ischemic effects and safety of different doses of ranolazine administered three times daily (tid) compared with placebo in patients with stable angina pectoris.

METHODS AND RESULTS

Patients with stable angina pectoris took part in the study. Previous antianginal drugs were discontinued under medical supervision. Three hundred nineteen patients received single-blind placebo for up to 18 days, and 318 stopped exercise because of angina of moderate severity, had evidence of myocardial ischemia (> or = 1-mm ST segment depression), and were randomized to one of four study groups in a double-blind manner: ranolazine 30 mg tid (n = 81), ranolazine 60 mg tid (n = 81), ranolazine 120 mg tid (n = 78), and placebo tid (n = 79). After the 4-week double-blind phase, symptom-limited exercise tests were repeated at 1 hour (peak test) and 8 hours (trough test) after the study medication was administered. In addition, patients kept an angina diary throughout the study and wore a Holter monitor for 48 hours. Total exercise duration at baseline (+/- SEM) was 5.9 +/- 0.2 minutes for the placebo group and 6.4 +/- 0.3, 5.9 +/- 0.3, and 6.6 +/- 0.2 minutes for the ranolazine 30-, 60-, and 120-mg groups, respectively (P = NS). After 4 weeks of double-blind therapy, compared with baseline values, at 1 hour after the study medication was administered (peak effect), total exercise duration (+/- SEM) increased by 0.45 +/- 0.2 minutes in the placebo group and by 0.3 +/- 0.2, 0.6 +/- 0.2, and 0.5 +/- 0.2 minutes in the ranolazine 30-, 60-, and 120-mg groups, respectively (placebo versus ranolazine, P = NS). Times to 1-mm ST segment depression at baseline were similar in the four groups and, after 4 weeks of therapy in each group, increased significantly by similar magnitudes at 1 hour after the administration of the medications. Similar changes were seen for the time to onset of angina. Eight hours after administration (trough effect), no differences in total exercise time or any other exercise variables were observed between the placebo and the ranolazine groups. Compared with the baseline values, the number of anginal attacks per week and the number and duration of ischemic episodes per 48 hours during Holter monitoring decreased significantly by similar magnitudes in the placebo and ranolazine groups.

CONCLUSIONS

Therapy with ranolazine 30, 60, and 120 mg tid was not superior to placebo. Our study does not support the published beneficial effects of similar doses of ranolazine on either myocardial ischemia or exercise performance or on anginal attacks during daily life in patients with angina pectoris.
Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.
Authors: Maes A , Flameng W , Nuyts J , Borgers M , Shivalkar B , Ausma J , Bormans G , Schiepers C , De Roo M , Mortelmans L
Published: June 2012

BACKGROUND

In patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology.

METHODS AND RESULTS

We studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11 +/- 6 vol% fibrosis and 25 +/- 13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35 +/- 25% fibrosis and 24 +/- 15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8 +/- 4% fibrosis and 12 +/- 8% glycogen-accumulating cells.

CONCLUSIONS

It can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.
Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST)
Authors: Pepine C J , Cohn P F , Deedwania P C , Gibson R S , Handberg E , Hill J A , Miller E , Marks R G , Thadani U
Published: June 2012

BACKGROUND

Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia.

METHODS AND RESULTS

A multicenter, randomized, double-blind, placebo-controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/- SD, 3.6 +/- 4.2 versus 1.7 +/- 4.6 episodes, P < .001) and average duration (30 +/- 3.3 versus 16.4 +/- 6.7 minutes, P < .001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4 +/- 4.6 to 3.1 +/- 6.0 episodes and 36.6 +/- 4.1 to 30 +/- 5.5 minutes). Event-free survival improved in atenolol-treated patients (P < .0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P = .001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P = .175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol.

CONCLUSIONS

Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.
Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture.
Authors: Moreno P R , Falk E , Palacios I F , Newell J B , Fuster V , Fallon J T
Published: June 2012

BACKGROUND

Rupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes.

METHODS AND RESULTS

Hematoxylin and eosin and immunostaining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myocardial infarction. Total plaque area was 417 +/- 87 mm2 x 10(-2) in patients with stable angina, 601 +/- 157 mm2 x 10(-2) in patients with unstable angina, and 499 +/- 87 mm2 x 10(-2) in patients with non-Q-wave myocardial infarction (P = NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61 +/- 18 mm2 x 10(-2)) and non-Q-wave myocardial infarction (87 +/- 32 mm2 x 10(-2)) than in plaques from patients with stable angina (14 +/- 5 mm2 x 10(-2)) (P = .024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 +/- 5.6%) and non-Q-wave myocardial infarction (14.6 +/- 4.6%) than in patients with stable angina (3.14 +/- 1%) (P = .018). Macrophage-rich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67 +/- 30 mm2 x 10(-2)) and unstable angina (55 +/- 19 mm2 x 10(-2)) than in patients with stable angina (11.5 +/- 4.1 mm2 x 10(-2)) (P = .046). Macrophage-rich atheromatous gruel was also largest in patients with non-Q-wave myocardial infarction (15 +/- 4 mm2 x 10(-2)) than in patients with unstable angina (3.3 +/- 1.7 mm2 x 10(-2)) or stable angina (2.4 +/- 1.2 mm2 x 10(-2)) (P = .026).

CONCLUSIONS

Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.
Use of aortic counterpulsation to improve sustained coronary artery patency during acute myocardial infarction. Results of a randomized trial. The Randomized IABP Study Group.
Authors: Ohman E M , George B S , White C J , Kern M J , Gurbel P A , Freedman R J , Lundergan C , Hartmann J R , Talley J D , Frey M J
Published: June 2012

BACKGROUND

Aortic counterpulsation has been observed to reduce the rate of reocclusion of the infarct-related artery after patency has been restored during acute myocardial infarction in observational studies. To evaluate the benefit-to-risk ratio of aortic counterpulsation during the early phase of myocardial infarction, a multicenter randomized clinical trial was performed.

METHODS AND RESULTS

Patients who had patency restored during acute cardiac catheterization within the first 24 hours of onset of myocardial infarction were randomly assigned to aortic counterpulsation for 48 hours versus standard care. Intravenous heparin was used similarly in both groups and was continued for a median (25th, 75th percentile) of 5 (2,7) days. A total of 182 patients were enrolled; 96 were assigned to aortic counterpulsation and 86 to standard care. Repeat cardiac catheterization was performed at a median of 5 (4,6) days after randomization in 89% of patients assigned to aortic counterpulsation and in 90% of control patients. Patients randomized to aortic counterpulsation had similar rates of severe bleeding complications (2% versus 1%), number of units of blood transfused (mean, 1.3 +/- 2.6 versus 0.9 +/- 1.8 units), and vascular repair or thrombectomy (5% versus 2%) compared with patients treated in a conventional manner. Patients randomized to aortic counterpulsation had significantly less reocclusion of the infarct-related artery during follow-up compared with control patients (8% versus 21%, P < .03). In addition, there was a significantly lower event rate in patients assigned to aortic counterpulsation in terms of a composite clinical end point (death, stroke, reinfarction, need for emergency revascularization with angioplasty or bypass surgery, or recurrent ischemia): 13% versus 24%, P < .04.

CONCLUSIONS

This randomized trial showed that careful use of prophylactic aortic counterpulsation can prevent reocclusion of the infarct-related artery and improve overall clinical outcome in patients undergoing acute cardiac catheterization during myocardial infarction.
Echocardiographic prediction of survival after surgical correction of organic mitral regurgitation.
Authors: Enriquez-Sarano M , Tajik A J , Schaff H V , Orszulak T A , Bailey K R , Frye R L
Published: June 2012

BACKGROUND

Left ventricular dysfunction is a frequent cause of death after successful surgical repair of mitral regurgitation. The role of preoperative echocardiographic left ventricular variables in the prediction of postoperative survival and thus their clinical implications remain uncertain.

METHODS AND RESULTS

The survival of 409 patients operated on between 1980 and 1989 for pure, isolated, organic mitral regurgitation and with a preoperative echocardiogram (within 6 months of operation) was analyzed. The overall survival was 75% at 5 years (90% of expected), 58% at 10 years (88% of expected), and 44% at 12 years (73% of expected). Operative mortality was 6.6% and markedly improved from 1980 to 1984 (10.7%) to 1985 to 1989 (3.7%). Multivariate analysis showed that age (P = .0003), date of operation (P = .003), and functional class (P = .016) but not left ventricular function were predictors of operative mortality. In the most recent period (1985 to 1989), operative mortality was 12.3% in patients age 75 years or older and 1.1% in patients younger than 75 years. Late survival was analyzed in the operative survivors. Multivariate analysis showed that the most powerful predictor was echocardiographic ejection fraction (EF) (P = .0004), followed by age (P = .0031), creatinine level (P = .0062), systolic blood pressure (P = .0164), and presence of coronary artery disease (P = .0237). The late survival at 10 years was 32 +/- 12% for patients with EF < 50%, 53 +/- 9% for EF 50% to 60%, and 72 +/- 4% for EF > or = 60%. The hazard ratio compared with EF > or = 60% was 2.79 (95% confidence interval, 1.65 to 4.72) for EF < 50% and 1.81 (95% confidence interval, 1.11 to 2.95) for EF 50% to 60%. Echocardiographic EF remained the best predictor of late survival, even when combined with left ventricular angiographic variables. The survival of patients with EF > or = 60% was 100% of expected at 10 years but was better in patients in class I or II than in those in class III or IV (82 +/- 6% versus 59 +/- 6%, respectively, at 10 years; P = .0021). The preoperative predictors of operative and late mortality remained significant independent of the type of surgical correction performed in combined multivariate analyses.

CONCLUSIONS

In organic mitral regurgitation, (1) operative mortality has markedly decreased recently, being at a low 1.1% in patients younger than 75 years, and is predicted by age and symptoms and not by left ventricular function, and (2) left ventricular EF measured by echocardiography is the most powerful predictor of late survival. These results suggest that surgical treatment should be considered early, even in the absence of severe symptoms, in patients with severe mitral regurgitation, before left ventricular dysfunction occurs.