bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for an association between dehydroepiandrosterone sulfate and nonfatal, premature myocardial infarction in males.
Authors: Mitchell L E , Sprecher D L , Borecki I B , Rice T , Laskarzewski P M , Rao D C
Published: June 2012

BACKGROUND

Several studies indicate that endogenous hormones play a role in the etiology of coronary artery disease, either as independent risk factors or indirectly, via an effect on lipids, lipoproteins, or other heart disease risk factors.

METHODS AND RESULTS

The relation between endogenous hormone levels and premature (< 56-year-old patients) myocardial infarction was assessed in a retrospective study involving 49 male survivors of premature myocardial infarction and 49 age-matched, volunteer male controls. Serum samples were obtained for each subject the morning after a > or = 12-hour fast and frozen at -70 degrees C for subsequent hormonal analysis. Among the male patients, the average duration between the most recent myocardial infarction and blood sampling was 3.4 years (range, 0.7 to 19.2 years). Individuals reporting the use of any medications with the potential to alter lipid, lipoprotein, or hormone levels were excluded from these analyses. Dehydroepiandrosterone sulfate levels were significantly lower in the patients than in the control subjects. This association remained statistically significant even after accounting for the effects of total cholesterol, triglycerides, the ratio of total to high-density lipoprotein (HDL) cholesterol, HDL, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, and body mass index. There were no significant differences in the levels of estradiol, testosterone, or free testosterone or the ratio of estradiol to testosterone between patients and control subjects.

CONCLUSIONS

Our conclusions are limited by the retrospective nature of this study. However, these data indicate that serum dehydroepiandrosterone sulfate levels are inversely related to premature myocardial infarction in males and that this association is independent of the effects of several known risk factors for premature myocardial infarction.
Morning increase in ambulatory ischemia in patients with stable coronary artery disease. Importance of physical activity and increased cardiac demand.
Authors: Parker J D , Testa M A , Jimenez A H , Tofler G H , Muller J E , Parker J O , Stone P H
Published: June 2012

BACKGROUND

The morning increase in asymptomatic ambulatory ischemia may be due to heightened coronary tone, increased physical activity, or both. If ambulatory ischemia is primarily due to physical activity, then alterations in the schedule of physical activity should be reflected in a corresponding alteration in the occurrence of ischemia. This study was designed to examine the relation between activity patterns and the frequency of ambulatory ischemic episodes and the effect of nadolol on these relations.

METHODS AND RESULTS

A double-blind, randomized, placebo-controlled, crossover trial of nadolol versus placebo was performed in 20 patients with stable coronary artery disease. At the end of each 2-week treatment phase, patients were hospitalized for 48 hours. In the hospital, there was a regular activity day (awaken and assume normal activities at 8:00 AM) and a delayed activity day (awaken at 8:00 AM, arise at 10:00 AM, and begin normal activity at noon). Ambulatory ECG monitoring was performed throughout the hospitalization. On the regular activity day, there was a morning increase in heart rate and in the number of ischemic episodes during therapy with placebo that began at 8:00 AM. In contrast, on the delayed activity day, there was a 4-hour phase shift of the increases in heart rate and the increase in ischemic episodes (ie, at noon) corresponding to the onset of physical activities. Therapy with nadolol caused a 50% reduction in the total number of ischemic episodes (129 versus 65, placebo versus nadolol; P < .02). During nadolol therapy, there was no discernible circadian peak in the number of ischemic episodes on either activity day. During placebo treatment, 87% of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. Although nadolol caused a significant reduction in the total number of episodes preceded by a heart rate increase compared with placebo (99 versus 38 episodes, P < .04), this therapy was associated with a significant increase in the number of episodes not associated with a heart rate increase (15 versus 21 episodes, P < .002).

CONCLUSIONS

The morning increase in ambulatory ischemic episodes is due to physical activity patterns. The majority of ischemic episodes are preceded by a heart rate increase, and it is these episodes that are primarily responsible for the morning increase in ischemia. Therapy with nadolol caused a reduction in the total number of ischemic episodes solely by reducing those episodes preceded by a heart rate increase. In contrast, nadolol caused a significant increase in the number of ischemic episodes not associated with a heart rate increase, perhaps in part because it potentiated coronary vasoconstriction.
Evaluation of standard and active compression-decompression CPR in an acute human model of ventricular fibrillation.
Authors: Shultz J J , Coffeen P , Sweeney M , Detloff B , Kehler C , Pineda E , Yakshe P , Adler S W , Chang M , Lurie K G
Published: June 2012

BACKGROUND

The mechanisms that underlie cardiopulmonary resuscitation (CPR) in humans remain controversial and difficult to study. This report describes a new human model to evaluate CPR during the first 1 to 2 minutes after the onset of ventricular fibrillation (VF). With this model, standard CPR was compared with active compression-decompression (ACD) CPR, a method that uses a handheld suction device to actively compress and actively decompress the chest.

METHODS AND RESULTS

During routine inductions of VF as part of a transvenous lead cardioverter/defibrillator implantation procedure, CPR was performed in 21 patients if the first defibrillation shock failed and until a successful rescue shock was delivered. Compressions during CPR were performed according to American Heart Association guidelines. For ACD CPR, decompression was performed with up to -30 lbs. Radial arterial and right atrial pressures were measured in all patients. Esophageal pressures, intratracheal pressures, or minute ventilation was measured in the last 13 patients. Application of both CPR techniques increased arterial and right atrial pressures. The mean coronary perfusion pressure was increased throughout the entire CPR cycle with ACD CPR (compression, 21.5 +/- 9.0 mm Hg; decompression, 21.9 +/- 8.7 mm Hg) compared with standard CPR (compression, 17.9 +/- 8.2 mm Hg; decompression, 18.5 +/- 6.9 mm Hg; P < .02 and P < .02, respectively). Ventilation per compression-decompression cycle was 97.3 +/- 65.6 mL with standard CPR and 168.4 +/- 68.6 mL with ACD CPR (n = 7, P < .001). Negative inspiratory pressure was -0.8 +/- 4.8 mm Hg with standard CPR and -11.4 +/- 6.3 mm Hg with ACD CPR (n = 6, P < .04).

CONCLUSIONS

Patients undergoing multiple inductions of VF during cardioverter/defibrillator implantation with transvenous leads provide a well-controlled and reproducible model to study the mechanisms of CPR. Using this model, ACD CPR significantly increased arterial blood pressure, coronary perfusion pressure, minute ventilation, and negative inspiratory pressure compared with standard CPR.
Arterial imaging with a new forward-viewing intravascular ultrasound catheter, I. Initial studies.
Authors: Evans J L , Ng K H , Vonesh M J , Kramer B L , Meyers S N , Mills T A , Kane B J , Aldrich W N , Jang Y T , Yock P G
Published: June 2012

BACKGROUND

Intravascular ultrasound (IVUS) of arteries is limited by the inability of current instruments to visualize beyond the catheter tip. We have developed a prototype 4-mm-diameter forward-viewing IVUS catheter (Cardiovascular Imaging Systems, Sunnyvale, Calif) that has the ability to provide B-mode cross-sectional ultrasound data for a distance of up to 2 cm distal to the catheter tip.

METHODS AND RESULTS

To study the utility of this device, a 20-MHz forward-viewing IVUS catheter was used to examine 13 arterial segments (5 human femoral arteries, 1 human carotid artery, 7 canine arteries) in vitro and 1 phantom. After imaging, all data were compared with histology (Histo). In all cases, the IVUS catheter provided forward-viewing images corresponding to the arterial geometry and demonstrated vascular landmarks and atherosclerotic lesions. There was a good correlation between Histo-determined luminal diameters (LD) and IVUS-determined diameters for a distance of 14 mm ahead of the catheter tip: IVUS LD = 1.0 Histo LD + 1.3 (r = .87).

CONCLUSIONS

These preliminary data suggest that a forward-viewing IVUS catheter is feasible, accurate, and useful for evaluation of arterial geometry distal to the catheter tip.
Echocardiographic predictors of nonrheumatic atrial fibrillation. The Framingham Heart Study.
Authors: Vaziri S M , Larson M G , Benjamin E J , Levy D
Published: June 2012

BACKGROUND

Although structural heart disease is often present in patients with nonrheumatic atrial fibrillation, the echocardiographic precursors of atrial fibrillation have not been reported previously. In this elderly, population-based cohort, our objective was to examine prospectively the echocardiographic predictors of nonrheumatic atrial fibrillation.

METHODS AND RESULTS

Subjects in the Framingham Heart Study were routinely evaluated with M-mode echocardiography; 1924 subjects, ranging in age from 59 to 90 years, comprised the population at risk. Cox proportional hazards modeling was used to analyze the association of selected echocardiographic features with atrial fibrillation risk after adjustment for age, sex, hypertension, coronary heart disease, congestive heart failure, diabetes, and valvular heart disease. During a mean follow-up interval of 7.2 years, 154 subjects (8.0%) developed atrial fibrillation. Multivariable stepwise analysis identified left atrial size (hazard ratio [HR] per 5-mm increment, 1.39; 95% confidence interval [CI], 1.14 to 1.68), left ventricular fractional shortening (HR per 5% decrement, 1.34; 95% CI, 1.08 to 1.66), and sum of septal and left ventricular posterior wall thickness (HR per 4-mm increment, 1.28; 95% CI, 1.03 to 1.60) as independent echocardiographic predictors of atrial fibrillation. For each of the echocardiographic predictors, risk increased progressively over successive quartiles. Moreover, risk increased markedly when highest-risk-quartile measurements for these features were present in combination; the cumulative 8-year age-adjusted atrial fibrillation rates were 7.3% and 17.0%, respectively, when one and two or more highest-risk-quartile features were present, compared with 3.7% when none was present.

CONCLUSIONS

In this elderly, population-based sample, left atrial enlargement, increased left ventricular wall thickness, and reduced left ventricular fractional shortening were predictive of risk for nonrheumatic atrial fibrillation. These echocardiographic precursors offer prognostic information beyond that provided by traditional clinical atrial fibrillation risk factors.
Cardiovascular health and disease in children: current status. A Special Writing Group from the Task Force on Children and Youth, American Heart Association.
Authors: Moller J H , Taubert K A , Allen H D , Clark E B , Lauer R M
Published: June 2012

More than 600,000 children in the United States have a congenital or acquired cardiac abnormality, and millions more are at risk of developing atherosclerotic disease in adulthood, a risk made particularly evident by the prevalence of cardiovascular risk factors in the young. There are barriers to optimum prevention and treatment of these conditions in children and youth. The AHA's Task Force on Children and Youth has described these barriers and outlined a series of recommendations and strategies to meet the challenges they impose. More research is needed, and research initiatives will be developed at scientific conferences designed to review critical areas of cardiac development and etiology of disease in children. Financial support for such research initiatives must be increased. Educational programs on cardiovascular risk factors will be extended to children and their families. When these programs are coordinated with efforts in the community and in schools, they will reduce the prevalence of cardiovascular risk factors. The task force recommends that various departments and committees of the AHA use their resources for the benefit of children: for example, by developing more research initiatives for funding by the AHA or NHLBI and increasing legislative and regulatory efforts in the areas such as mandatory school health programs and tobacco advertising. It is hoped that in the next decade, through research and educational efforts, many advances in the prevention and treatment of cardiovascular diseases in the young will be realized.
Dynamic training of skeletal muscle ventricles. A method to increase muscular power for cardiac assistance.
Authors: Guldner N W , Eichstaedt H C , Klapproth P , Tilmans M H , Thuaudet S , Umbrain V , Ruck K , Wyffels E , Bruyland M , Sigmund M
Published: June 2012

BACKGROUND

Skeletal muscle can be used for cardiac assistance after electrical stimulation over a period of several weeks. This will adapt it to do chronic work with no resulting fatigue. The result of this procedure, however, is a reduction of 80% in muscle power, > 60% in muscle mass, and approximately 85% in contractile speed. To minimize these disadvantages, the following study was done to develop and test a method to dynamically train skeletal muscle ventricles (SMVs).

METHODS AND RESULTS

Barrel-shaped SMVs were tested in 15 Jersey calves. They were made from the latissimus dorsi muscle, which was wrapped around an elastic silicone training device. Six SMVs were used extrathoracically in a single layer and nine intrathoracically in a double layer. With dynamic training preserving contractile speed, the output increased to approximately 5 L/min, the systolic pressure increased to > 200 mm Hg, and power developed to approximately 10 W after 3 months of dynamic training. The contractile speed of dynamically trained SMVs was between 250 and 700 mm/s. The diameter of the latissimus dorsi muscle increased to three times that of the corresponding contralateral muscle.

CONCLUSIONS

The combination of electrical conditioning with dynamic training of the SMVs resulted in a strong muscle pump that did not develop fatigue. Dynamic training for skeletal muscle represents a new and promising method for providing powerful autologous cardiac assist.
Correlates of left ventricular mass in a population sample aged 36 to 37 years. Focus on lifestyle and salt intake.
Authors: Kupari M , Koskinen P , Virolainen J
Published: June 2012

BACKGROUND

Echocardiographically determined left ventricular (LV) mass predicts adverse cardiovascular events in the general population. We have assessed the correlates of LV mass in a population-based study focusing on lifestyle and salt intake.

METHODS AND RESULTS

A random sample of 120 persons born in 1954 was invited; 93 (42 men) entered the study. The subjects' physical activity and alcohol, tobacco, and coffee consumption were quantified by 2-month dairy follow-up, and sodium intake was quantified by 7-day food records. Blood pressure was averaged for casual cuff measurements made 2 months apart. LV mass was determined by M-mode echocardiography, and stroke volume was determined by Doppler. Hematocrit and serum insulin were measured. In multiple linear regression analysis, LV mass was related positively and independently (P < .05) to body weight, systolic blood pressure, stroke volume, sodium intake, hematocrit, and energy expenditure in leisure-time physical activity. Additional analyses showed that the relation of LV mass to daily sodium intake depended on blood pressure (P < .001 for the interaction); the multiple regression coefficient (+/- SE) was 0.41 +/- 0.11 g.mEq-1 x d-1 (P = .001) in subjects with systolic blood pressure above the population median but statistically nonsignificant (-0.15 +/- 0.10 g.mEq-1 x d-1) in those with lower blood pressure. LV mass was clearly elevated only in persons with both blood pressure and sodium intake above the population medians.

CONCLUSIONS

Body weight, blood pressure, stroke volume, sodium intake, physical activity, and hematocrit are independent predictors of LV mass among unselected persons aged 36 to 37 years. The synergistic interaction of dietary salt with blood pressure suggests that high sodium intake may sensitize the heart to the hypertrophic stimulus of pressure load. Prospective studies are needed to confirm these cross-sectional associations.
A randomized comparison of the effects of gradual prolonged versus standard primary balloon inflation on early and late outcome. Results of a multicenter clinical trial. Perfusion Balloon Catheter Study Group.
Authors: Ohman E M , Marquis J F , Ricci D R , Brown R I , Knudtson M L , Kereiakes D J , Samaha J K , Margolis J R , Niederman A L , Dean L S
Published: June 2012

BACKGROUND

Observational studies have suggested that prolonged balloon inflation during coronary angioplasty is associated with a high clinical success rate. This randomized clinical trial sought to evaluate the impact of primary gradual and prolonged inflations versus standard short dilatations in patients undergoing elective angioplasty.

METHODS AND RESULTS

In phase 1 of the study, patients were randomized to receive two to four standard (1 minute) dilatations or one or two prolonged (15 minutes) dilatations after a perfusion balloon had been placed across a single target lesion. Patients with unsuccessful angiographic appearance after phase 1 dilatations had further dilatations in phase 2. Patients were followed for 6 to 12 months after the procedure. Of 478 patients, 242 received a median of one prolonged dilatation of 15 minutes' duration, and 236 received three dilatations for a median of 1 minute. Patients assigned to prolonged dilatations had a higher success rate (< or = 50% residual visual stenosis) (95% versus 89%; P = .016), less severe residual stenosis by quantitative angiography (median [25th and 75th percentiles], 35% [26%, 42%] versus 38% [30%, 46%]; P = .001), and a lower rate of major dissections (3% versus 9%; P = .003) at the end of phase 1. A total of 114 patients had further dilatations in phase 2-43 in the prolonged arm and 71 in the standard arm. The final procedural success rate was 98% with both primary dilatation strategies, which included additional maneuvers such as prolonged dilatations in the patients randomized to the primary standard dilatation. Overall, 320 of 416 patients (77%) who were discharged after a successful procedure without any in-hospital event (death, myocardial infarction, coronary artery bypass graft surgery, abrupt closure, or repeat angioplasty in target vessel) returned for follow-up angiography. The restenosis rate (> 50% residual visual stenosis) was 44% (95% confidence interval, 37% to 52%) in the prolonged dilatation group and 44% (36% to 52%) in the standard dilatation group. The primary angiographic end point of failure at the end of phase 1, abrupt closure, or restenosis throughout the study period was similar in both groups (prolonged, 51%; standard, 49%; P = .62). The secondary end point of absence of clinical events (death, nonfatal myocardial infarction, coronary artery bypass graft surgery, or repeat angioplasty in target vessel) also was similar (prolonged, 66%; standard, 74%; P = .15).

CONCLUSIONS

Primary gradual and prolonged dilatations caused less arterial trauma with a modestly larger arterial lumen compared with standard dilatations. This initial improvement in angiographic appearance did not lead to a significant reduction in restenosis or clinical adverse events during follow-up.
Enhanced cholinergic cutaneous vasodilation in Raynaud's phenomenon.
Authors: Khan F , Coffman J D
Published: June 2012

BACKGROUND

Vasodilator function was determined in patients with Raynaud's phenomenon during intra-arterial infusions of the endothelium-dependent and -independent vasodilators, methacholine and sodium nitroprusside, respectively. Reactive hyperemia, induced by 5 minutes of arterial occlusion with exercise, was also measured.

METHODS AND RESULTS

Total blood flow was measured in the fingertip and forearm by venous occlusion plethysmography, and blood flow in the forearm skin was determined with laser Doppler flowmetry. Basal fingertip blood flow was not significantly different between control subjects and patients with Raynaud's phenomenon. Infusions of methacholine had no significant effect on fingertip blood flow in control subjects, whereas patients with Raynaud's phenomenon showed a significant increase in fingertip blood flow. Basal total forearm blood flow was significantly lower in patients with Raynaud's phenomenon than in control subjects. Infusions of methacholine and sodium nitroprusside produced dose-related increases in total forearm blood flow that were of similar magnitudes in the two groups, as were the reactive hyperemic responses. Laser Doppler measurements of forearm skin blood flow, however, showed a significantly greater vasodilator response to methacholine in patients with Raynaud's phenomenon than in control subjects. Infusions of sodium nitroprusside produced a relatively small vasodilator response in the skin of the forearm that was smaller than that to methacholine and not significantly different between the two groups.

CONCLUSIONS

In Raynaud's phenomenon, a greater vasodilator response to infusions of methacholine in the fingertip, where changes in blood flow mainly reflect those of skin, and in the skin of the forearm may reflect increased responsiveness of cutaneous blood vessels to stimulation of the endothelium. The mechanism involved is unclear but may result from a general abnormality of blood vessels in the skin, which is related to the pathophysiology of cutaneous vasospasm.
Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion.
Authors: Richard V , Kaeffer N , Tron C , Thuillez C
Published: June 2012

BACKGROUND

Repetitive, brief periods of ischemia and reperfusion ("preconditioning") increase the resistance of myocardial tissue to subsequent prolonged ischemic episodes and limit infarct size. We investigated whether preconditioning also protects against coronary endothelial dysfunction induced by ischemia and reperfusion.

METHODS AND RESULTS

Experiments were performed in four groups of rats (n = 8 in each group): group 1 rats underwent sham surgery, group 2 rats were subjected to 20 minutes of left coronary artery occlusion without reperfusion, group 3 rats underwent 20 minutes of occlusion followed by 1 hour of reperfusion, and group 4 rats (preconditioning group) underwent the same protocol as group 3 rats, preceded by three cycles of 5 minutes of ischemia and 5 minutes of reperfusion. At the end of the experiments, coronary segments (internal diameter, 250 to 300 microns) were removed distal to the occlusion site and mounted in wire myographs for isometric tension recording. Relaxations induced by increasing concentrations of acetylcholine, the calcium ionophore A23187, or the nitric oxide (NO) donor SIN-1 were determined in arteries precontracted by serotonin. Basal NO release was estimated by measuring contractions to NG-nitro L-arginine methyl ester (L-NAME). In addition, we determined the effect of preconditioning on infarct size in two additional groups that were subjected to the same protocols as those of groups 3 and 4. In those animals, area at risk (India ink injection) and infarct size (triphenyltetrazolium stain) were determined by computerized analysis of enlarged sections after video acquisition. Preconditioning markedly limited infarct size (percent of area at risk: controls, 57 +/- 2; preconditioning, 2.2 +/- 0.6; P < .01). Ischemia (without or with reperfusion) or preconditioning did not affect the coronary responses to L-NAME, serotonin, A23187, or SIN-1. Ischemia without reperfusion did not modify the relaxations to acetylcholine (maximal relaxation: sham, 58 +/- 4%; ischemia, 56 +/- 7%; P = NS). In contrast, ischemia followed by reperfusion markedly impaired the response to acetylcholine (26 +/- 6%; P < .01 versus sham). This impaired response was restored by preconditioning (maximal relaxation: 59 +/- 9%; P = NS versus sham; P < .01 versus ischemia/reperfusion).

CONCLUSIONS

In addition to protecting myocardial cells, preconditioning also protects coronary endothelial cells against ischemia/reperfusion injury.
Exposure to environmental tobacco smoke increases myocardial infarct size in rats.
Authors: Zhu B Q , Sun Y P , Sievers R E , Glantz S A , Parmley W W , Wolfe C L
Published: June 2012

BACKGROUND

Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. In this study, we evaluated the influence of 3 days, 3 weeks, and 6 weeks of ETS exposure on myocardial infarct size in a rat ischemia/reperfusion model.

METHODS AND RESULTS

Sprague-Dawley rats exposed to ETS (four Marlboro cigarettes per 15 minutes, 6 hours per day, 5 days per week) for 3 days (n = 24), 3 weeks (n = 21), or 6 weeks (n = 12) and control rats (n = 24, n = 21, and n = 12, respectively) were subjected to 35 minutes of left coronary artery occlusion and 2 hours of reperfusion. Infarct size and risk area were determined by triphenyltetrazolium chloride and phthalocyanine blue staining, respectively. Air nicotine, carbon monoxide, and total particulates were measured during ETS exposure. Serum lipids, plasma carbon monoxide hemoglobin (COHb), nicotine, and cotinine concentrations were measured in additional groups (6 to 13 rats each) exposed to 3 days, 3 weeks, or 6 weeks of ETS and controls. Average air nicotine, carbon monoxide, and total particulate concentrations were 1103 micrograms/m3, 92 ppm, and 60 mg/m3 for the ETS-exposed rats. Infarct size (infarct mass/risk area x 100%) increased significantly in the ETS groups compared with the control groups in a dose-dependent manner (P = .023), with longer exposure associated with larger infarct size. Infarct size nearly doubled with 6 weeks of ETS exposure (61 +/- 5% versus 34 +/- 3% for control, mean +/- SEM). Plasma COHb, nicotine, and cotinine levels increased significantly in the ETS groups in a dose-dependent manner (all P < .001).

CONCLUSIONS

Exposure to passive smoking increases myocardial infarct size in a rat model of ischemia and reperfusion. This increase of infarct size exhibited a dose-response relation. These results are consistent with epidemiological studies demonstrating that ETS increases the risk of heart death.
Dietary iron intake and risk of coronary disease among men.
Authors: Ascherio A , Willett W C , Rimm E B , Giovannucci E L , Stampfer M J
Published: June 2012

BACKGROUND

We prospectively studied iron intake in relation to the incidence of coronary disease in a 4-year follow-up of 44,933 men (with no previous history of cardiovascular disease) aged 40 to 75 years in 1986 who completed a food frequency questionnaire at baseline.

METHODS AND RESULTS

We documented 844 incident cases of coronary disease (249 nonfatal myocardial infarctions, 137 coronary disease fatalities, and 458 bypass operations or angioplasties). After adjustment for established risk factors, there was no significant association between total iron intake and risk of coronary heart disease. Men in the highest quintile of total intake (median, 37 mg/d) had a relative risk (RR) of fatal coronary disease or nonfatal myocardial infarction of 0.73 (95% confidence intervals [CI], 0.51, 1.06) compared with men in the lowest quintile of intake (median, 11 mg/d). Dietary intake of heme iron--mainly from red meat--also was not significantly associated with risk of coronary heart disease. However, incidence of fatal coronary disease or nonfatal myocardial infarction was higher among men in the top quintile of heme iron intake compared with men in the lowest quintile (RR, 1.42; 95% CI, 1.02, 1.98). This association remained after adjustment for dietary cholesterol and fats. Heme iron but not total iron intake was positively correlated with serum ferritin among 123 members of the cohort who participated in a validation study.

CONCLUSIONS

These results do not support the hypothesis that dietary iron in general increases coronary risk in men; they are consistent, however, with an increased risk of myocardial infarction among men with higher intake of heme iron, which is itself positively associated with iron stores.
Temporal trends (1975 through 1990) in the incidence and case-fatality rates of primary ventricular fibrillation complicating acute myocardial infarction. A communitywide perspective.
Authors: Chiriboga D , Yarzebski J , Goldberg R J , Gore J M , Alpert J S
Published: June 2012

BACKGROUND

As part of a population-based study of acute myocardial infarction, we examined changes over time in the incidence and in-hospital case-fatality rates of primary ventricular fibrillation complicating acute myocardial infarction.

METHODS AND RESULTS

Patients with validated acute myocardial infarction hospitalized at 16 hospitals in the Worcester, Mass, metropolitan area between 1975 and 1990 comprised the study sample. During the 15-year study period, 5.1% of patients developed primary ventricular fibrillation in the setting of uncomplicated acute myocardial infarction, with this rate remaining relatively constant over time. Both age- and multivariable-adjusted analyses showed no significant trend in the incidence rates of primary ventricular fibrillation during the study period. The in-hospital case-fatality rate for patients with primary ventricular fibrillation was significantly elevated compared with the rate for those without primary ventricular fibrillation and uncomplicated acute myocardial infarction (48.3% versus 1.5%, P < .001). No significant change over time was noted in in-hospital case-fatality rates associated with primary ventricular fibrillation while controlling for a variety of short-term prognostic factors.

CONCLUSIONS

The results of this communitywide observational study suggest that neither the incidence nor the prognosis associated with primary ventricular fibrillation resulting from acute myocardial infarction has improved over time.
Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women.
Authors: Losordo D W , Kearney M , Kim E A , Jekanowski J , Isner J M
Published: June 2012

BACKGROUND

The relative absence of coronary atherosclerosis in premenopausal women has been established. Estrogen is presumed to play a role in the protection of coronary arteries from atherosclerosis, and part of this protective effect appears to be mediated by amelioration of serum lipid profiles. However, all of the atheroprotective effect of estrogen is not explained by alteration of serum lipids. In this study, we attempt to identify evidence of estrogen receptors in coronary artery specimens of female patients and in human vascular smooth muscle cells.

METHODS AND RESULTS

Postmortem coronary artery specimens were obtained from premenopausal (n = 18) and postmenopausal (n = 22) women who died with significant coronary artery disease (n = 19) and from noncardiac causes with normal coronary arteries (n = 21). Sections were examined for evidence of estrogen receptor expression using a monoclonal antibody stain. Radioligand binding assays for estrogen receptors were performed on human vascular smooth muscle cells in culture, and gel retardation assays were performed to confirm the presence of functional estrogen receptors. Estrogen receptor expression was identified by immunostaining in a total of 21 coronary arteries, with the majority of normal arteries (15 positive of 21 total, P = .0117) demonstrating evidence of estrogen receptor expression. Conversely, a minority (6 of 19, P = NS) of atherosclerotic arteries were positive for estrogen receptor expression. Furthermore, the relation between estrogen receptor expression and absence of coronary atherosclerosis was most evident in premenopausal subjects, with 10 of 12 normal arteries in this group demonstrating evidence of estrogen receptors, whereas only 1 of 6 atherosclerotic coronary arteries was positive (P = .0062). Radioligand binding assays confirmed the presence of estrogen receptors at significant concentrations in intact human vascular smooth muscle cells. Gel retardation assays also documented the presence of functional estrogen receptors in extracts from human vascular smooth muscle cells.

CONCLUSIONS

This investigation provides evidence of estrogen receptors in smooth muscle cells from human coronary arteries. The demonstrated relation between the presence of the receptors and the absence of atherosclerosis in premenopausal women suggests that these receptors may play a functional role in coronary atheroprotection.
Localization of insulin-like growth factor I and inhibition of coronary smooth muscle cell growth by somatostatin analogues in human coronary smooth muscle cells. A potential treatment for restenosis?
Authors: Grant M B , Wargovich T J , Ellis E A , Caballero S , Mansour M , Pepine C J
Published: June 2012

In this study, we demonstrate, for the first time, the localization of insulin-like growth factor I (IGF-I) in de novo and restenotic human coronary atherectomy plaques by using immunocytochemical techniques. Smooth muscle cells (SMCs) exhibiting the synthetic phenotype contained a statistically significant higher concentration of IGF-I than SMCs of the contractile phenotype or SMCs from normal coronary arteries. In addition, we provide data to suggest that the long-acting somatostatin analogues octreotide and angiopeptin inhibit IGF-I- and basic fibroblast growth factor (b-FGF)- induced human coronary artery SMC proliferation. Platelet-derived growth factor (PDGF)-stimulated cultures were minimally affected by the addition of octreotide but were significantly inhibited by angiopeptin. All three growth factors stimulated SMC migration in a dose-dependent manner. The somatostatin analogues tested had no effect on growth factor-stimulated SMC migration. Our data suggest that by reducing SMC proliferation, somatostatin analogues may have clinical usefulness in reducing the high incidence of restenosis observed after percutaneous transluminal coronary artery interventions.
Recombinant hirudin for unstable angina pectoris. A multicenter, randomized angiographic trial.
Authors: Topol E J , Fuster V , Harrington R A , Califf R M , Kleiman N S , Kereiakes D J , Cohen M , Chapekis A , Gold H K , Tannenbaum M A
Published: June 2012

BACKGROUND

Coronary artery thrombosis plays an important pathophysiological role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or consistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thrombus in a manner superior to heparin.

METHODS AND RESULTS

Patients with rest ischemic pain, abnormal ECG, and baseline angiogram indicating a > or = 60% stenosis of a culprit coronary artery or saphenous vein graft with visual appearance of thrombus were randomized to one of two different doses of heparin (either a target activated partial thromboplastin time [aPTT] of 65 to 90 or 90 to 110 seconds) or one of four doses of hirudin (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 infusion) in a dose-escalating protocol. After 72 to 120 hours of study drug, a repeat coronary angiogram was obtained, and the paired studies underwent quantitative analysis. The primary end point was change in the average cross-sectional area of the culprit lesion. Other efficacy end points also involved changes in culprit lesion dimensions and TIMI flow grade. Recombinant hirudin led to a dose-dependent elevation of aPTT that appeared to plateau at the 0.2-mg/kg dose. A higher proportion of hirudin-treated patients had their aPTT within a 40-second range (16% heparin versus 71% hirudin, P < .001). Overall, the 116 patients treated with hirudin tended to show more improvement than the 50 patients receiving heparin relative to the primary efficacy variable--the average cross-sectional area (P = .08)--as well as minimal cross-sectional area (P = .028), minimal luminal diameter (P = .029), and percent diameter stenosis (P = .07).

CONCLUSIONS

Recombinant hirudin appears to be a promising antithrombotic intervention compared with heparin for inhibition of coronary artery thrombus. Large-scale comparative trials are warranted.
Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction.
Authors: Omland T , Lie R T , Aakvaag A , Aarsland T , Dickstein K
Published: June 2012

BACKGROUND

Plasma endothelin concentrations are increased in the acute phase of myocardial infarction and in chronic heart failure. Since endothelin may contribute to hemodynamic deterioration by potent vasoconstrictory and cardiotoxic actions, increased plasma levels may be associated with an unfavorable prognosis after myocardial infarction.

METHODS AND RESULTS

We tested the hypothesis that plasma endothelin determination in the subacute phase of myocardial infarction is related to subsequent survival and assessed whether plasma endothelin measurements provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma endothelin determination was obtained from 142 patients (average age +/- SD, 67.8 +/- 10.1 years) on day 3 after documented myocardial infarction and was related to 1-year mortality. Sixteen patients died during the follow-up period. In a univariate Cox proportional-hazards model, day 3 plasma endothelin concentrations were significantly related to mortality (P < .0001). Patient age, previous treatment for systemic hypertension, presence of clinical heart failure, and plasma atrial natriuretic factor levels were all related to mortality in univariate analysis but provided no additional prognostic information to that obtained from endothelin determination in a multivariate model.

CONCLUSIONS

Plasma endothelin concentrations are strongly related to outcome after myocardial infarction and provide prognostic information independent of clinical and biochemical variables previously associated with a poor prognosis.
Assessment of effects of autonomic stimulation and blockade on the signal-averaged electrocardiogram.
Authors: Goldberger J J , Ahmed M W , Parker M A , Kadish A H
Published: June 2012

BACKGROUND

Signal-averaged ECG is a noninvasive test designed to detect "late potentials." The effects of alterations in autonomic tone on the signal-averaged ECG have not been evaluated systematically.

METHODS AND RESULTS

The effects of autonomic stimulation and blockade on the signal-averaged ECG were evaluated in 14 healthy subjects (8 men and 6 women; age, 28.5 +/- 4.8 years) on 2 separate days. The signal-averaged ECG was recorded at baseline and after physiological and pharmacologic beta-adrenergic stimulation (tilt, exercise, and epinephrine and isoproterenol infusions), sequential and combined beta-adrenergic and parasympathetic blockade, and alpha-adrenergic stimulation before and after parasympathetic blockade. Analysis was performed with a bidirectional filter (40-Hz high-pass). Significant changes in the signal-averaged QRS duration from baseline (105.1 +/- 12.0 milliseconds) were noted with tilt (96.8 +/- 8.8 milliseconds), tilt after double blockade (97.5 +/- 9.0 milliseconds), epinephrine (110.5 +/- 11.8 milliseconds), and isoproterenol (99.6 +/- 12.6 milliseconds). Changes in the root-mean-square voltage of the terminal 40 milliseconds and the low-amplitude (< 40 microV) signal duration paralleled the changes in the QRS duration.

CONCLUSIONS

The signal-averaged ECG does not measure only "fixed" parameters but rather is altered under a variety of physiological and pharmacologic conditions. Upright tilt leads to shortening of the QRS duration before and after autonomic blockade; thus, the decrease in QRS duration with tilt may be related to factors other than changes in autonomic tone. These findings have implications for interpretation of the results of signal-averaged ECG.
High-density mapping of electrically induced atrial fibrillation in humans.
Authors: Konings K T , Kirchhof C J , Smeets J R , Wellens H J , Penn O C , Allessie M A
Published: June 2012

BACKGROUND

Mapping studies in animals have suggested that atrial fibrillation (AF) is based on multiple reentering wavelets. Little information is available about the patterns of activation during AF in humans. The objective of the present study was to reconstruct and classify the patterns of human right atrial (RA) activation during electrically induced AF.

METHODS AND RESULTS

AF was induced by rapid atrial pacing in 25 patients with Wolff-Parkinson-White syndrome undergoing surgery for interruption of their accessory pathway(s). The free wall of the RA was mapped using a spoon-shaped electrode containing 244 unipolar electrodes. The activation of the RA during AF showed large interindividual differences. Based on the complexity of atrial activation, three types of AF were defined. In type I (40% of patients), single broad wave fronts propagated uniformly across the RA. Type II (32%) was characterized by one or two nonuniformly conducting wavelets, whereas in type III (28%), activation of the RA was highly fragmented and showed three or more different wavelets that frequently changed their direction of propagation as a result of numerous arcs of functional conduction block. There were significant differences (P < .05) among the three types of AF in median intervals (174 +/- 28, 150 +/- 14, and 136 +/- 16 milliseconds), variation in AF intervals (P5-95) (54 +/- 25, 94 +/- 21, and 104 +/- 22 milliseconds), incidence of electrical inactivity (42 +/- 11%, 21 +/- 4%, and 8 +/- 4%) and reentry (3 +/- 7%, 36 +/- 28%, and 99 +/- 36%), and average conduction velocity during AF (61 +/- 6, 54 +/- 4, and 38 +/- 10 cm/s).

CONCLUSIONS

During pacing-induced AF in humans, the RA is activated by one or multiple wavelets propagating in different directions. Three types of RA activation during AF were identified. From type I to type III, the frequency and irregularity of AF increased, and the incidence of continuous electrical activity and reentry became higher. These various types of AF in humans appear to be characterized by different numbers and dimensions of the intra-atrial reentrant circuits.
Innervation of the human cardiac conduction system. A quantitative immunohistochemical and histochemical study.
Authors: Crick S J , Wharton J , Sheppard M N , Royston D , Yacoub M H , Anderson R H , Polak J M
Published: June 2012

BACKGROUND

Cardiac conduction is influenced by peptidergic mechanisms as well as classic neurotransmitters. The distribution of peptide-containing nerves has not been well defined.

METHODS AND RESULTS

Immunofluorescence and histochemical techniques were used to visualize the innervation of the human conduction system and to distinguish nerve subpopulations according to their peptide and enzyme content. Nerve fibers and fascicles displaying immunoreactivity for protein gene product 9.5 (PGP 9.5) were more numerous in the sinus and atrioventricular nodes than in the penetrating bundle, bundle branches, and adjacent myocardium. The relative density of innervation was greater in the central region of the sinus node than in the peripheral regions. Nerve densities were also higher in the transitional region of the atrioventricular node compared with its compact region. Acetylcholinesterase (AChE)-positive nerves were the main subtype identified in the sinus and atrioventricular nodes, representing half to two thirds of the stained area occupied by PGP 9.5-immunoreactive nerves. Neuropeptide Y-immunoreactive nerves represented the main peptide-containing subpopulation and occurred throughout the conduction system, displaying a similar pattern of distribution and relative density to those demonstrating tyrosine hydroxylase immunoreactivity. Nerve fibers showing immunoreactivity for vasoactive intestinal polypeptide, somatostatin, substance P, or calcitonin gene-related peptide exhibited distinct patterns of distribution and comprised a relatively minor component of the innervation, the percentage of stained area being 10- to 40-fold lower than that occupied by neuropeptide Y- and PGP 9.5-immunoreactive nerves, respectively.

CONCLUSIONS

The innervation of human conduction tissues exhibits significant regional variation and comprises putative parasympathetic nerves and intrinsic neurons (AChE positive), sympathetic efferent nerves (neuropeptide Y- and tyrosine hydroxylase-immunoreactive nerves), and other peptide-containing nerves, some of which (substance P and calcitonin gene-related peptide containing) are considered to represent afferent nerves. Locally released peptides may be involved in the neural modulation of the human conduction system.
Independent predictors of long-term results after balloon pulmonary valvuloplasty. Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) Registry Investigators.
Authors: McCrindle B W
Published: June 2012

BACKGROUND

This study was performed to determine independent predictors of long-term outcome after percutaneous balloon dilation of congenital pulmonary valve stenosis. Smaller follow-up series of patients after balloon pulmonary valvuloplasty have shown inconsistent results regarding the independent relation between prognostic factors and long-term outcome, as many patient selection and technical factors are correlated.

METHODS AND RESULTS

Follow-up data were obtained for 533 patients from 22 institutions at up to 8.7 years after an initial balloon pulmonary valvuloplasty. Patients were grouped based on defined long-term outcomes, and the independent effects of patient selection and technical factors were sought in multivariate statistical analyses. At follow-up, 23% of patients were noted to have an outcome judged to be suboptimal because of either a residual right ventricle to pulmonary artery peak systolic gradient of > or = 36 mm Hg or further treatment of pulmonary stenosis requiring repeat balloon pulmonary valvuloplasty or surgical therapy. Significant independent predictors of a suboptimal long-term outcome included an earlier study year of the initial valvuloplasty (adjusted odds ratio, 0.71 per consecutive year), a small valve hinge point diameter (0.81 per 1-mm increase), and a higher immediate residual gradient (1.32 per 10 mm Hg increase). A smaller ratio of balloon to valve hinge point diameter significantly predicted suboptimal outcomes for patients with valve morphologies classified as typical (0.52 per 0.1 increase in ratio) and complex (primarily postsurgical valvotomy, 0.43) but not for patients with dysplastic (0.95) or combined morphologies (dysplasia with commissural fusion, 1.01). Patient age, the presence of Noonan's syndrome or associated cardiac lesions, pre-balloon valvuloplasty hemodynamic parameters, and the use of a simultaneous double-balloon technique did not independently predict follow-up outcomes.

CONCLUSIONS

Accurate prognostication after balloon pulmonary valvuloplasty depends on the careful determination of valvar anatomy. The use of an appropriate ratio of balloon to valve hinge point diameter in the setting of typical valve morphology will optimize the chance of long-term success.