bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized trial of late elective angioplasty versus conservative management for patients with residual stenoses after thrombolytic treatment of myocardial infarction. Treatment of Post-Thrombolytic Stenoses (TOPS) Study Group.
Authors: Ellis S G , Mooney M R , George B S , da Silva E E , Talley J D , Flanagan W H , Topol E J
Published: June 2012

BACKGROUND

After thrombolytic therapy for patients with acute myocardial infarction (MI), percutaneous transluminal coronary angioplasty (PTCA) is frequently performed because of the presence of a "significant" infarct vessel stenosis demonstrated at predischarge coronary angiography. Several studies have shown PTCA performed early after thrombolysis to be unnecessary or even harmful. However, PTCA in these trials was generally performed 1-3 days after MI, when the milieu in the infarct artery may be unsuited for PTCA, and the incidence of major ischemic complications was high. To date, no trial has assessed whether delayed PTCA (4-14 days) should be performed in patients without evidence of ischemia on stress testing.

METHODS AND RESULTS

To test the hypothesis that delayed PTCA might provide clinical benefit compared with medical therapy alone, 87 patients treated within 6 hours of chest pain onset with thrombolytic therapy and with negative functional test were randomized between PTCA to be performed 4-14 days after MI versus no PTCA. Both groups received medical therapy. Patients with postinfarct angina or prior Q wave infarction in the infarct distribution were excluded. The primary study end point was increase in left ventricular ejection fraction with exercise measured by radionuclide studies 6 weeks after MI, a parameter known from other studies to correlate inversely with future ischemic events. Clinical outcome was also monitored for 12 months. There were no differences between the study groups for any prerandomization variable recorded. Mean age was 57 +/- 10 years, 84% of patients were male, 21% had prior MI, 36% had anterior MI, 7% had multivessel disease, and the infarct stenosis measured 70 +/- 17% before randomization. PTCA was successful in 38 of 42 patients (88%) but resulted in non-Q wave MI due to acute closure of the treated site in three of 42 (9.5%). There was no difference in 6-week resting ejection fraction or increase in ejection fraction with exercise between the two groups (47 +/- 12% and 6 +/- 8%, respectively, in the PTCA group; 49 +/- 10% and 5 +/- 9% in the no-PTCA group; p = NS for both.) There were no deaths in either group. Actuarial 12-month infarct-free survival was 97.8% in the no-PTCA group and 90.5% in the PTCA group (p = 0.07).

CONCLUSIONS

There was no functional or clinical benefit from routine late PTCA after MI treated with thrombolytic therapy in this relatively low-risk cohort of patients. These data strongly suggest that patients with an uncomplicated MI after thrombolytic therapy, even if they have a "significant" residual stenosis of the infarct vessel, should be treated medically if they are without evidence of ischemia on stress testing before hospital discharge.
Radiofrequency catheter ablation of left lateral accessory pathways via the coronary sinus.
Authors: Haissaguerre M , Gaita F , Fischer B , Egloff P , Lemetayer P , Warin J F
Published: June 2012

BACKGROUND

The purpose of this study was to describe a new technique for catheter ablation of left lateral accessory pathways (APs) by radiofrequency energy applied at the epicardium through the coronary sinus wall using a unipolar configuration.

METHODS AND RESULTS

In an overall group of 212 patients with left lateral APs, multiple endocardial ablation attempts of the AP were unsuccessful in eight patients. The mean +/- SD cumulative duration of previous attempts was 12 +/- 9 hours, using DC shocks and/or radiofrequency energy applied both at the atrial and/or ventricular AP insertions. Epicardial AP insertion was determined by bipolar and unipolar unfiltered distal electrograms by scanning the coronary sinus with a steerable 6F or 7F catheter with a 4-mm distal electrode. The local atrial to ventricular electrogram amplitude ratio was 0.3-1.6. At the ablation site, the catheter tip was slightly deflected toward the annulus to increase both the ventricular component of electrograms and contact with the epicardium. In four patients, epicardial electrogram timings were earlier than endocardial ones. The AP was ablated in seven of the eight patients with 20-30 W applied for 10-60 seconds. No complications occurred except a marked nonspecific pain during radiofrequency energy application; however, the catheter remained adherent to the coronary sinus wall, and its withdrawal was performed during a new radiofrequency application to decrease the risk of coronary sinus rupture. After ablation, echocardiograms, coronary artery angiograms, and levophase coronary sinus angiograms showed no abnormality in all patients except two who had a probable mural thrombus in the coronary sinus. AP conduction remained abolished for 1-10 months of follow-up in seven patients.

CONCLUSIONS

Radiofrequency catheter ablation of left lateral APs can be achieved effectively and relatively safely via the mid or distal coronary sinus when endocardial approaches are unsuccessful.
Clinical outcomes after the arterial switch operation for transposition. Patient, support, procedural, and institutional risk factors. Congenital Heart Surgeons Society.
Authors: Kirklin J W , Blackstone E H , Tchervenkov C I , Castaneda A R
Published: June 2012

BACKGROUND

As the probability increases that the arterial switch operation is optimal treatment for transposition, detailed information about outcomes and the circumstances in which they are suboptimal becomes important.

METHODS AND RESULTS

A multi-institutional prospective study with annual detailed follow-up included 513 neonates with simple transposition or transposition and ventricular septal defect entering for diagnosis and treatment at < 15 days of age and undergoing an arterial switch repair. The 1-month and 1- and 5-year survivals were 84%, 82%, and 82%, respectively. The hazard function for death had a rapidly declining single phase that approached zero by 12 months after surgery. Among the eight patients who died > or = 3 months after the operation, four had severe ventricular dysfunction, probably related to imperfect coronary arterial transfer. Coexisting single ventricular septal defect was not a risk factor for death. Origin of the left main coronary artery or only the left anterior descending or the circumflex artery from the right posterior sinus (sinus 2) was a risk factor that was even stronger when an intramural course was present; multiplicity of ventricular septal defects was a risk factor. Longer global myocardial ischemic time and total circulatory arrest time were risk factors. Certain institutions were shown to be risk factors for death; the results in some improved with increasing experience, in some they did not, and in some they worsened.

CONCLUSIONS

Good early and intermediate-term clinical outcomes can be obtained in neonates with simple transposition and transposition and ventricular septal defect by use of the arterial switch operation. Certain coronary artery patterns and certain institutions lessen the goodness of outcome.
Transcatheter closure of patent foramen ovale after presumed paradoxical embolism.
Authors: Bridges N D , Hellenbrand W , Latson L , Filiano J , Newburger J W , Lock J E
Published: June 2012

BACKGROUND

Many have proposed a relation between presence of a patent foramen ovale, with or without atrial septal aneurysm, and cryptogenic stroke. The effect of foramen ovale closure on the risk for subsequent strokes is unknown.

METHODS AND RESULTS

Transcatheter closure of a patent foramen ovale was undertaken in 36 patients with known right-to-left atrial shunting and presumed paradoxical emboli (31 strokes, 25 transient neurological events, four systemic arterial emboli, and two brain abscesses). Individual patients had between one and four such events. None had a left heart or carotid source of embolism; 31 of 35 had no known risk factors for stroke. Events occurred in 12 patients while they were taking warfarin. At cardiac catheterization, patent foramina ovalia were significantly larger than predicted for age in 67% of the patients. Implantation of a double-umbrella device in the patent foramen ovale was achieved in all without serious procedural complications. Of 34 who have returned for follow-up, one has a residual atrial communication that may be clinically important, five had trivial leaks, and 28 have complete closure. There have been no strokes during a mean follow-up of 8.4 months.

CONCLUSIONS

Transcatheter closure of a patent foramen ovale can be accomplished with little morbidity and may reduce the risk of recurrence. Further investigations directed toward identifying the population at risk and assessing the effect of intervention are warranted.
Parallel cardiac and vascular adaptation in hypertension.
Authors: Roman M J , Saba P S , Pini R , Spitzer M , Pickering T G , Rosen S , Alderman M H , Devereux R B
Published: June 2012

BACKGROUND

Although vascular damage in the noncoronary circulation is a major cause of complications in hypertension, relatively little is known of the in vivo geometry and function of the arterial circulation in patients with uncomplicated hypertension or of their relation to left ventricular hypertrophy, a marker of enhanced risk of cardiovascular complications.

METHODS AND RESULTS

Wall thickness and internal diameter of the common carotid artery and the presence of atherosclerosis within the extracranial carotid arteries were determined by ultrasound in 43 asymptomatic hypertensive patients and 43 normotensive subjects matched for sex, age, and body size. Vascular stiffness was estimated from simultaneous superimposed carotid pressure waveforms obtained with an external solid-state transducer. Left ventricular size and function were determined echocardiographically. Compared with normal subjects, hypertensive patients had greater left ventricular absolute and relative wall thicknesses, left ventricular mass, and carotid absolute and relative wall thicknesses (p < 0.005). Carotid intimal-medial thickness exceeded the 95th percentile of normal values in 28% of hypertensive patients (p < 0.01). Carotid atherosclerosis was equally prevalent within the two blood pressure groups and was associated with older age, larger left ventricular and carotid wall thicknesses, and carotid diameter. Despite similar carotid pulse pressures, vascular stiffness was significantly increased in the hypertensive patients. Among the population as a whole, significant relations existed between cardiac and vascular wall thicknesses and internal dimensions. In multivariate analyses, these relations were statistically independent of age and blood pressure.

CONCLUSIONS

The present study documents the presence of geometric and functional changes within the common carotid artery in uncomplicated hypertension that parallel findings within the left ventricle. The potential contribution of these changes to the cardiovascular complications of hypertension, particularly in the setting of left ventricular hypertrophy, is unknown.
Myocardial cell hypertrophy after myocardial infarction with reperfusion in dogs.
Authors: Kambayashi M , Miura T , Oh B H , Murata K , Rockman H A , Parra G , Ross J
Published: June 2012

BACKGROUND

The potential role of myocardial cell hypertrophy in the ischemic zone in the mechanism of late recovery of regional contractile function after myocardial infarction followed by reperfusion has not been examined.

METHODS AND RESULTS

Eight chronically instrumented, conscious dogs were subjected to 90-120 minutes of circumflex coronary artery occlusion followed by reperfusion. The thickness and function of the anterior (AT) and posterior (PT) walls was measured by ultrasonic gauges at control, during occlusion, and after reperfusion. After 3 weeks, cross-sectional areas of surviving cells were determined from subepicardial (epi), midwall (mid), and subendocardial (endo) regions in six dogs and compared with those from six animals without infarction, including three sham-operated control dogs. PT systolic wall thickening showed dyskinesia during occlusion but recovered after reperfusion to 48% of control at 1 week and 67% at 3 weeks. End-diastolic thickness of the PT wall increased markedly after reperfusion, but AT and PT walls were only slightly thicker (p = NS) than in control dogs at 3 weeks. Cross-sectional areas of reperfused dogs in the infarct region averaged 279 (PTepi), 291 (PTmid), and 317 microns 2 (PTendo) and were significantly larger than in control animals (237 [PTepi], 241 [PTmid], and 233 microns 2 [PTendo]). PT cell areas were significantly larger than AT cells, ENDO cell areas were larger than EPI cells (both p < 0.05), and ENDO cells of the AT wall were larger than those of noninfarcted dogs (p < 0.05).

CONCLUSIONS

In dogs with myocardial infarction followed by reperfusion, the cross-sectional areas of cells in the infarcted PT wall were larger than those in the noninfarcted AT wall, and within both the infarcted and noninfarcted zones, cell areas were larger in the endocardial than the epicardial region. In all regions of the infarcted wall and in the ENDO region of the noninfarcted wall, cell areas were generally larger than those of control dogs without infarction, and the control dogs showed no transmural differences in cell areas. The mechanisms responsible for this significant remodeling of the reperfused infarcted zone, which involves myocardial cellular hypertrophy, are unknown, but it is possible that hypertrophy of surviving regions of the infarcted wall played a role in the late recovery of regional function that accompanied this hypertrophic response.
Critical analysis of the signal-averaged electrocardiogram. Improved identification of late potentials.
Authors: Lander P , Berbari E J , Rajagopalan C V , Vatterott P , Lazzara R
Published: June 2012

BACKGROUND

This study performed a critical analysis of signal-averaging methods. The objective was to optimize detection of late potentials.

METHODS AND RESULTS

We studied two patient populations: a low-arrhythmia-risk group with no evidence of heart disease and a group with clinically documented ventricular tachycardia (VT). Filtered QRS duration (QRSD) and terminal QRS amplitude (RMS40) were measured from the vector magnitude. A QRS duration based on the latest detectable ventricular activity in any of the three individual XYZ leads was also measured. Because of improved signal-to-noise ratio, both individual lead analysis and extended (600-versus 200-beat) averaging yielded significant changes in signal-averaged ECG parameters. Both approaches gave an increased sensitivity for VT identification. Sensitivity, specificity, and accuracy were evaluated as functions of critical values of QRSD and RMS40. RMS measurements in the terminal QRS, ranging from 20 to 100 msec and including RMS40, did not contribute to maximizing sensitivity and were highly correlated with QRSD. Our results from the low-arrhythmia-risk group suggest that age and sex should be considered in the definition of late potentials.

CONCLUSIONS

We propose a VT risk stratification scheme using signal-averaged ECG parameters obtained from both individual lead and vector magnitude analysis. This allows definition of four categories of VT risk derived statistically from the study data. This definition is based on combined measures of sensitivity, specificity, and negative and positive predictive value.
Association of early-onset coronary heart disease in South Asian men with glucose intolerance and hyperinsulinemia.
Authors: McKeigue P M , Ferrie J E , Pierpoint T , Marmot M G
Published: June 2012

BACKGROUND

Rates of coronary heart disease are higher in South Asians (Indians, Pakistanis, and Bangladeshis) settled overseas than in other ethnic groups. We tested the hypothesis that this excess risk results from metabolic disturbances associated with insulin resistance.

METHODS AND RESULTS

There were 1,421 South Asian men and 1,515 European men aged 40-69 years in London examined in the Southall Study. Prevalence of ischemic ECG abnormalities was higher in South Asians than in Europeans (17% versus 12%, p < 0.001), with an excess of major Q waves (Minnesota codes 1-1 or 1-2) in younger South Asian men (p = 0.01 for the age-ethnicity interaction). Major Q waves were strongly associated with glucose intolerance and hyperinsulinemia in younger South Asians; these factors accounted statistically for 73% of major Q waves in those aged 40-54 years. Age-standardized prevalence of a positive history of coronary heart disease was similar in South Asians and Europeans (8.5% versus 8.2%, NS), and positive history without Q waves was not associated with glucose intolerance or hyperinsulinemia in South Asians. Smoking rates and average plasma cholesterol were lower in South Asians than in Europeans; in a logistic model controlling for smoking and cholesterol, the odds ratio for major Q waves in South Asians compared with Europeans was 2.4 (95% CI, 1.5-3.8). Adjusting for glucose intolerance and hyperinsulinemia reduced this ratio to 1.5 (95% CI, 0.9-2.5).

CONCLUSIONS

These results are consistent with the hypothesis that insulin resistance underlies the high coronary risk in South Asian people and strengthen the evidence for a fundamental role of this metabolic pattern in the etiology of coronary heart disease.
Accuracy of exercise 201Tl myocardial scintigraphy in asymptomatic young men.
Authors: Schwartz R S , Jackson W G , Celio P V , Richardson L A , Hickman J R
Published: June 2012

BACKGROUND

Little is known about the diagnostic usefulness of 201Tl scintigraphy for detecting asymptomatic coronary artery disease in apparently healthy men. We thus evaluated planar 201Tl exercise myocardial scintigraphy in 845 asymptomatic male military aircrew undergoing coronary arteriography because of abnormal noninvasive tests suggesting possible myocardial ischemia.

METHODS AND RESULTS

Patients were stratified by prior disease risk into six subgroups using age (< 45 and > or = 45 years) and ratio of total to high density lipoprotein cholesterol (< 4.5, 4.5-6.0, and > 6.0). Significant coronary artery disease (> or = 50% diameter stenosis in any major coronary artery) was present in 143 (16.9% prevalence). Overall sensitivity and specificity of 201Tl scintigraphy adjusted for verification bias were estimated to be 45 +/- 4% and 78 +/- 1%, respectively. These values are lower than corresponding values accepted for clinical populations. Positive and negative predictive values varied across subgroups. A normal thallium scan indicated low risk of disease, but an abnormal test was likely to be a false-positive result. A logistic equation was retrospectively fit to the data for estimating the probability of disease given age, cholesterol ratio, and thallium results. Within each quintile of estimated risk, the average risk did not differ significantly from the observed disease prevalence.

CONCLUSIONS

Exercise 201Tl scintigraphy is limited by the frequent occurrence of false-positive tests in detecting asymptomatic, anatomic coronary artery disease in young men in accordance with Bayesian probability theory.
Circadian variations in ischemic threshold and their relation to the occurrence of ischemic episodes.
Authors: Benhorin J , Banai S , Moriel M , Gavish A , Keren A , Stern S , Tzivoni D
Published: June 2012

BACKGROUND

The occurrence of ischemic episodes during daily activity has been reported to exhibit a bimodal circadian distribution, yet its relation to the ischemic threshold (heart rate at 1-mm ST segment depression) has not been explored.

METHODS AND RESULTS

To determine whether the ischemic threshold during daily activity exhibits a circadian pattern that might relate to the frequency of occurrence of ischemic episodes, we studied the time of occurrence and the heart rate at onset of ischemia in 1,371 ischemic episodes recorded in 41 patients with stable coronary disease, positive exercise testing, and repeated ischemic episodes during ambulatory ECG monitoring (AEM). All patients had 7 days of AEM; 23 were off any anti-ischemic therapy, while 18 were on low dose of beta-blockers. The occurrence of ischemic episodes exhibited the typical bimodal circadian distribution with a prominent peak between 7:00 and 11:00 AM and a second less prominent peak between 6:00 and 9:00 PM. The threshold of myocardial ischemia exhibited a different single-peaked circadian distribution; it was lowest between 1:00 and 3:00 AM and highest between 10 AM and 1 PM. Time series analyses indicated a strong hour-by-hour trend of each of the two circadian distributions, whereas the two series cross-correlated maximally at a lag of zero hours (p < 0.01), indicating a complex interplay between myocardial oxygen demand and supply in determining the occurrence of ischemic episodes during daily activity. The morning increase in the frequency of ischemic episodes could not be attributed to a reduced threshold but rather to an increase in demand. The low threshold at night-time might probably indicate that the mechanism of ischemia during these hours is reduced coronary flow due to increased coronary tone. Secondary analyses for several predefined patients' subsets gave similar results. Patients who received low-dose beta-blockers maintained the bimodal circadian distribution of the occurrence of ischemic episodes, whereas the ischemic threshold exhibited a constant pattern with no circadian changes.

CONCLUSIONS

Our results demonstrate that myocardial oxygen demand is a major determinant of daily ischemia, yet changes in the ischemic threshold that probably reflect dynamic changes in coronary tone play also an important role. The relative contribution of increased demand and decreased threshold to the genesis of ischemic episodes during daily activity can be assessed by AEM and may help to optimize medical therapy.
A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989.
Authors: Munger T M , Packer D L , Hammill S C , Feldman B J , Bailey K R , Ballard D J , Holmes D R , Gersh B J
Published: June 2012

BACKGROUND

Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population.

METHODS AND RESULTS

We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis.

CONCLUSIONS

The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.
Adenosine alters glucose use during ischemia and reperfusion in isolated rat hearts.
Authors: Finegan B A , Lopaschuk G D , Coulson C S , Clanachan A S
Published: June 2012

BACKGROUND

Adenosine possesses marked cardioprotective properties, but the mechanisms for this beneficial effect are unclear. The objective of this study was to determine the effect of adenosine given before ischemia or at reperfusion on mechanical function, glucose oxidation, glycolysis, and metabolite levels in isolated, paced (280 beats per minute) working rat hearts.

METHODS AND RESULTS

Hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microU.mL-1 insulin at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Adenosine (100 microM) pretreatment or adenosine (100 microM) at reperfusion markedly increased the recovery of mechanical function (from 44% to 81% and 96%, respectively) after 60 minutes of low-flow ischemia (coronary flow, 0.5 mL.min-1). Glucose oxidation (mumol.min-1 x g dry wt-1) was inhibited during ischemia (from 0.44 +/- 0.04 to 0.12 +/- 0.01), and this was not altered by adenosine (100 microM). During reperfusion, glucose oxidation recovered (to 0.38 +/- 0.02) and adenosine (100 microM), given at reperfusion, further increased glucose oxidation (to 0.52 +/- 0.06). The rate of glycolysis (mumol.min-1 x g dry wt-1), which was unaffected by ischemia per se, was inhibited by adenosine pretreatment (from 4.7 +/- 0.3 to 2.6 +/- 0.3). During reperfusion, glycolysis was also inhibited by adenosine relative to control (3.9 +/- 0.8) either when present during ischemia (2.6 +/- 0.6) or during reperfusion (1.4 +/- 0.4). These effects of adenosine on glucose metabolism reduced the calculated rate of H+ production attributable to glucose metabolism during the ischemic and reperfusion periods. Tissue lactate levels (mumol.g dry wt-1), which increased during ischemia (from 9.3 +/- 1.1 to 87.4 +/- 10.3) and then declined during reperfusion (to 26.2 +/- 3.7), were depressed further by adenosine pretreatment (to 19.7 +/- 4.1) and by adenosine at reperfusion (to 13.6 +/- 2.1). ATP levels (mumol.g dry wt-1), which were depressed by ischemia (from 18.1 +/- 1.1 to 10.6 +/- 1.3) and tended to be further depressed during reperfusion (to 7.1 +/- 0.7), were increased by adenosine pretreatment (to 14.1 +/- 1.2) and by adenosine at reperfusion (to 15.6 +/- 2.4).

CONCLUSIONS

The effects of adenosine on glucose metabolism that would tend to decrease cellular acidosis and hence, Ca2+ overload, may explain the beneficial effects of adenosine on mechanical function observed in these hearts during reperfusion after ischemia.
Heat-shock response and limitation of tissue necrosis during occlusion/reperfusion in rabbit hearts.
Authors: Currie R W , Tanguay R M , Kingma J G
Published: June 2012

BACKGROUND

Induction of stress proteins, such as heat-shock protein 71 (HSP71), is associated with cardioprotection in isolated ischemic myocardium. We tested this hypothesis in rabbits pretreated with whole-body hyperthermia and then subjected to 30 or 45 minutes of regional coronary occlusion (CO) followed by 3 hours reperfusion (Rep).

METHODS AND RESULTS

Control rabbits did not undergo whole-body hyperthermia; heat-shocked (HS) rabbits were subjected to whole-body hyperthermia at 42 degrees C for 15 minutes. Rabbits were allowed to recover from whole-body hyperthermia for 24 or 40 hours and were then subjected to CO/Rep. Heart rate and arterial blood pressure were recorded during the experiments. Area of necrosis (tetrazolium staining) was normalized to anatomic risk zone size (microsphere autoradiography). In rabbits treated with whole-body hyperthermia and 24 hours of recovery, infarct size was significantly reduced in HS rabbits compared with control rabbits (41.2 +/- 7.8% versus 23.2 +/- 6.6%; p < or = 0.05; mean +/- SD) after 30 minutes of CO and 3 hours of Rep. Risk zone size was similar for the two experimental groups. In rabbits treated with whole-body hyperthermia and 40 hours of recovery, infarct size was similar for control and HS animals with either 30 or 45 minutes of CO (p = NS) and 3 hours of Rep. Risk zone size and area of necrosis were similar for these experimental groups. Biopsies from ischemic and nonischemic myocardium were obtained from rabbits at 24 and 40 hours after heat shock and control rabbits to verify expression of HSP71; expression was determined by Western blot analysis.

CONCLUSIONS

Our findings demonstrate a considerable increase in expression of HSP71 in myocardium from hyperthermia-treated rabbits. Infarct size was significantly reduced after 30 minutes of CO and 3 hours of Rep in hearts at 24 but not 40 hours after heat shock compared with control hearts. We conclude that heat shock-induced cardioprotection is transient and delays the onset of irreversible myocardial injury caused by ischemia.
Prognostic significance of progression of coronary atherosclerosis.
Authors: Waters D , Craven T E , Lespérance J
Published: June 2012

BACKGROUND

Angiographic progression of coronary atherosclerosis is frequently observed in clinical practice and is used as an end point in clinical trials; however, its prognostic significance is unclear.

METHODS AND RESULTS

Progression defined as an increase in diameter stenosis by > or = 15% of at least one coronary lesion was seen in 141 (42%) of 335 patients who underwent repeat coronary arteriography after a 2-year interval as part of clinical trial. Coronary lesions were measured quantitatively from comparable end-diastolic frames selected by a radiologist viewing each pair of films together. During a mean follow-up of 44 +/- 10 months after the second arteriogram, cardiac death occurred in 19 patients (5.7%), cardiac death or nonfatal infarction was seen in 40 cases (11.9%), and 90 patients (26.9%) underwent coronary revascularization. At least one end point event occurred in 112 of the 335 patients. Sixteen of the 19 cardiac deaths were in progressors, a relative risk of 7.3 (95% CI, 2.2-24.7; p < 0.001). The relative risk of cardiac death or nonfatal infarction for progressors was 2.3 (1.3-4.2, p = 0.009) and of any cardiac event was 1.7 (1.3-2.3, p < 0.001). A stepwise multivariable Cox regression model of time to event was used to assess the relative contribution of progression as a predictor of coronary events. Low ejection fraction (p = 0.001), progression (p = 0.001), and hypertension (p = 0.011) were retained as predictors of cardiac death. Angina and the number of diseased vessels were the strongest predictors of revascularization.

CONCLUSIONS

Coronary progression is a strong, independent predictor of future coronary events, particularly cardiac death, and its use as a surrogate end point in clinical trials is justified.
Coronary artery size and dilating capacity in ultradistance runners.
Authors: Haskell W L , Sims C , Myll J , Bortz W M , St Goar F G , Alderman E L
Published: June 2012

BACKGROUND

Increases in coronary artery size and dilating capacity have been observed in some animals after endurance training, and at autopsy, active men appear to have enlarged epicardial coronary arteries. This cross-sectional study was designed to test the hypothesis that highly trained endurance runners have larger epicardial coronary arteries and greater dilating capacity than inactive men.

METHODS AND RESULTS

The subjects, ages 39-66 years, included 11 male volunteers who had participated in ultradistance running during the past 2 years and 11 physically inactive men who had been referred for arteriography but had no visible coronary artery disease. The internal diameter of the proximal segments of each major epicardial coronary artery was measured before and after nitroglycerin administration using a computer-based quantitative arteriographic analysis system. Measurements also included maximal oxygen uptake, plasma lipoprotein concentrations, body composition, and cardiac mass by echocardiography. Before nitroglycerin, the sum of the cross-sectional areas for the proximal right, left anterior descending, and circumflex arteries was not different for the runners and the inactive men: 22.7 +/- 4.79 versus 21.0 +/- 7.97 mm2 (p = 0.57), respectively. However, the increase in the sum of the cross-sectional area for the proximal right, left anterior descending, and circumflex arteries in response to nitroglycerin was greater for the runners (13.20 +/- 4.76 versus 6.00 +/- 3.02 mm2; p = 0.002). Left ventricular mass index (152 +/- 21 versus 116 +/- 41 g/m2; p < 0.05) but not left ventricular mass (284 +/- 40 versus 246 +/- 91 g; p = 0.22) was significantly greater for the runners. Among the runners, dilating capacity was positively correlated with aerobic capacity and negatively related to adiposity, resting heart rate, and plasma lipoprotein concentrations.

CONCLUSIONS

Highly trained, middle-aged endurance runners demonstrated a significantly greater dilating capacity of their epicardial coronary arteries in response to nitroglycerin compared with inactive men. The causes of this greater dilating capacity and its clinical significance need to be determined.
Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease.
Authors: Linnanmäki E , Leinonen M , Mattila K , Nieminen M S , Valtonen V , Saikku P
Published: June 2012

BACKGROUND

An association of chronic Chlamydia pneumoniae infection to coronary heart disease has been suggested recently. In a recent study, we demonstrated circulating immune complexes containing chlamydial genus-specific lipopolysaccharide in patients with coronary heart disease. The objective of the present study was to investigate whether C. pneumoniae species-specific immune complexes are present in chronic coronary heart disease.

METHODS AND RESULTS

The presence of Chlamydia-specific circulating immune complexes was studied in 46 patients with chronic coronary heart disease and in control subjects. Chlamydial lipopolysaccharide-containing immune complexes were detected with the antigen-specific capture method, and they were present in 41% of patients and 15% of control subjects (p < 0.01). The presence of C. pneumoniae antibodies in circulating immune complexes was studied by testing the specificity of antibodies derived from isolated and dissociated immune complexes by microimmunofluorescence testing and immunoblotting. The C. pneumoniae indexes based on the relative amount of immune complex-derived antibodies and free antibodies were significantly higher among patients compared with control subjects (median, 1/8 versus 1/16; p < 0.001). Immune complex bound antibodies showed specificity for 98-kd and 42-kd proteins of C. pneumoniae.

CONCLUSIONS

The results suggest that the majority of the patients with chronic coronary heart disease have a chronic C. pneumoniae infection in which chlamydial components have an easy access to circulation to form immune complexes with preexisting antibodies. These findings give further evidence for the association of chronic C. pneumoniae infection with coronary heart disease.
Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation.
Authors: Cheng G C , Loree H M , Kamm R D , Fishbein M C , Lee R T
Published: June 2012

BACKGROUND

Although rupture of an atherosclerotic plaque is considered to be the cause of most acute coronary syndromes, the mechanism of plaque rupture is controversial.

METHODS AND RESULTS

To test the hypothesis that plaque rupture occurs at sites of high circumferential stress in the diseased vessel, the distribution of stress was analyzed in 24 coronary artery lesions. Histological specimens from 12 coronary artery lesions that caused lethal myocardial infarction were compared with those from 12 stable control lesions. A finite element model was used to calculate the stress distributions at a mean intraluminal pressure of 110 mm Hg. The maximum circumferential stress in plaques that ruptured was significantly higher than maximum stress in stable specimens (4,091 +/- 1,199 versus 1,444 +/- 485 mm Hg, p < 0.0001). Twelve of 12 ruptured lesions had a total of 31 regions of stress concentration of more than 2,250 mm Hg (mean, 2.6 +/- 1.4 high stress regions per lesion); only one of 12 control lesions had a single stress concentration region of more than 2,250 mm Hg. In seven of 12 lethal lesions (58%), rupture occurred in the region of maximum circumferential stress; in 10 of the 12 lethal lesions (83%), rupture occurred in a region where computed stress was more than 2,250 mm Hg.

CONCLUSIONS

These data suggest that concentrations of circumferential tensile stress in the atherosclerotic plaque may play an important role in plaque rupture and myocardial infarction. However, plaque rupture may not always occur at the region of highest stress, suggesting that local variations in plaque material properties contribute to plaque rupture.
Suppression of protein degradation in progressive cardiac hypertrophy of chronic aortic regurgitation.
Authors: Magid N M , Borer J S , Young M S , Wallerson D C , DeMonteiro C
Published: June 2012

BACKGROUND

The heart adapts to the volume overload of aortic regurgitation with dilation and hypertrophy. The development of left ventricular hypertrophy at the protein level is a dynamic process resulting from an imbalance between cardiac protein synthesis and degradation. The objective of the present study was to determine in vivo the relative contributions of cardiac protein synthesis and degradation to the progressive hypertrophy that occurs in response to chronic aortic regurgitation and to compare these with responses earlier in the course of this stress.

METHODS AND RESULTS

Continuous intravenous infusions of [3H]-leucine were administered 3 days and 1 month after surgical induction of aortic regurgitation and sham operation in rabbits. Total cardiac protein and myosin heavy chain fractional synthesis rates were obtained by analysis of plasma and protein hydrolysate data using [14C]-dansyl chloride assays. Left ventricular growth rates were determined from serial echocardiographic and postmortem left ventricular weight and protein concentration measurements; protein degradation rates were determined by subtraction of growth rates from synthesis rates.

CONCLUSIONS

In comparison with sham-operated control rabbits, protein fractional synthesis rates were increased at 3 days but not at 1 month after induction of aortic regurgitation Progressive cardiac hypertrophy occurring at 1 month was caused by a decrease in protein fractional degradation rates. An increase in protein synthesis contributes only to the early phase of hypertrophy caused by acute aortic regurgitation, whereas progressive eccentric hypertrophy in chronic volume overload is due to suppression of protein degradation.
Intraluminal vapor bubble induced by excimer laser pulse causes microsecond arterial dilation and invagination leading to extensive wall damage in the rabbit.
Authors: van Leeuwen T G , Meertens J H , Velema E , Post M J , Borst C
Published: June 2012

BACKGROUND

Previous in vitro studies demonstrated that during excimer laser ablation of aortic tissue in saline, a fast-expanding and imploding vapor bubble is formed. The present in vivo study was designed to demonstrate the formation of a fast-expanding intraluminal bubble in flowing blood and to assess any damage to the adjacent arterial wall.

METHODS AND RESULTS

Excimer laser pulses (one to 10, at 55 mJ/mm2 per pulse) were delivered coaxially in the femoral and iliac arteries of nine normal rabbits. Time-resolved flash photography of dissected arteries in situ demonstrated a 50% diameter increase within 75 microseconds after the laser pulse and a subsequent invagination (150-500 microseconds) that corresponded with the temporal course of the bubble expansion (up to 3.2 mm in diameter) and implosion observed in a hemoglobin solution. One day after laser light delivery, light microscopy (47 arterial segments) showed abrasion of the internal elastic lamina, medial necrosis, and extensive dissection planes filled with red blood cells. The degree (up to 100% medial necrosis) and extent of damage (up to 1.9 mm in length) increased with the number of delivered laser pulses.

CONCLUSIONS

In blood, each excimer laser pulse generated a fast-expanding and imploding vapor bubble. In vivo, the intraluminal vapor bubble produced microsecond dilation and invagination of the adjacent arterial segment, which induced dissections and extensive wall damage far beyond the penetration depth of 308-nm laser light (< 100 microns). This unique pattern of extensive wall damage observed in the rabbit might explain the mechanism of dissection observed in humans and might have an impact on the acute and chronic outcome after excimer laser coronary angioplasty.
Changes in diastolic function during development and correction of chronic LV volume overload produced by mitral regurgitation.
Authors: Zile M R , Tomita M , Ishihara K , Nakano K , Lindroth J , Spinale F , Swindle M , Carabello B A
Published: June 2012

BACKGROUND

Mitral regurgitation (MR) causes an augmentation in left ventricular (LV) diastolic function, increasing early diastolic filling rate and decreasing LV stiffness. Whether these changes in diastolic function persist, return to normal, or become abnormal after mitral valve replacement (MVR) is unknown.

METHODS AND RESULTS

Simultaneous LV echocardiography and catheterization studies were performed in six dogs in the baseline state (baseline), 3 months after creation of MR (chronic MR), and 3 months after MVR. Chronic MR caused LV dilation (end-diastolic dimension increased from 4.5 +/- 0.1 cm in baseline to 5.8 +/- 0.1 cm in chronic MR, p < 0.05) and eccentric LV hypertrophy (LV-to-body weight ratio increased from 3.6 +/- 0.2 g/kg in baseline to 4.9 +/- 0.4 g/kg in chronic MR, p < 0.05). Chronic MR caused an increase in LV early diastolic filling rate (peak rate of increase in minor-axis dimension increased from 11 +/- 1 cm/sec in baseline to 18 +/- 1 cm/sec in chronic MR, p < 0.05), did not change the time constant of myocardial relaxation (tau was 31 +/- 4 msec in baseline and 30 +/- 2 msec in chronic MR), and caused a decrease in the modulus of regional chamber stiffness from 7.7 +/- 1.2 in baseline to 2.4 +/- 0.03 in chronic MR, p < 0.05. MVR caused the resolution of LV dilation (end-diastolic dimension returned to normal [4.8 +/- 0.2 cm]), but three months after MVR, regression of LV hypertrophy was incomplete (LV-to-body weight ratio remained elevated [4.4 +/- 0.5 g/kg]). After MVR, LV early diastolic filling rate (8 +/- 1 cm/sec), the relaxation time constant (31 +/- 2 msec), chamber stiffness (7.1 +/- 1.8), myocardial stiffness (11.2 +/- 3.1), and LV end-diastolic pressure (8 +/- 1 mm Hg) returned to normal.

CONCLUSIONS

The enhanced diastolic function seen in chronic MR returned to normal after correction of the chronic volume overload by MVR.
The thyroid and the heart.
Authors: Polikar R , Burger A G , Scherrer U , Nicod P
Published: June 2012

Cardiovascular manifestations are a frequent finding in hyperthyroid and hypothyroid states. In this review, potential mechanisms by which thyroid hormones may exert their cardiovascular effects and pathophysiological consequences of such effects are briefly discussed. Two major concepts have emerged about how thyroid hormones exert their cardiovascular effects. First, there is increasing evidence that thyroid hormones exert direct effects on the myocardium, which are mediated by stimulation of specific nuclear receptors, which in turn leads to specific mRNAs production. Furthermore, there is some evidence that thyroid hormones may also activate extranuclear sites and may directly alter plasma membrane function. Second, thyroid hormones interact with the sympathetic nervous system by altering responsiveness to sympathetic stimulation presumably by modulating adrenergic receptor function and/or density. Pathophysiological consequences of such direct and indirect thyroid hormone effects include increased myocardial contractility and relaxation that may be related to stimulation by T3 of specific myocardial enzymes. However, when left ventricular hypertrophy occurs in association with hyperthyroidism, it may be related to either direct thyroid hormone-induced stimulation of myocardial protein synthesis or to thyrotoxicosis-induced increases in cardiac work load. Although hyperthyroidism generally has little or no effect on mean arterial blood pressure, hypothyroidism is often associated with increases in diastolic blood pressure that are reversible after hormone substitution and may be mediated in part by sympathetic activation. Moreover, there is increasing evidence that thyroid hormones have direct chronotropic effect on the heart that are independent of the sympathetic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Sudden cardiac death. Support for a role of triggering in causation.
Authors: Willich S N , Maclure M , Mittleman M , Arntz H R , Muller J E
Published: June 2012

Epidemiological studies have identified associations between time of day and risk of sudden cardiac death. The marked peak in the occurrence of sudden cardiac death after awakening suggests that the disease is triggered by changes that occur during this time period. Increased sympathetic stimulation is a likely cause of such triggering. In the light of the circadian variation of sudden cardiac death and the evidence linking physical activity or mental stress (both associated with activation of the sympathetic nervous system) to the disease, the role of potential triggering events should be investigated. Controlled studies are needed to determine the relative risk of activities that may trigger sudden cardiac death. Since such studies must rely on witnesses (or resuscitated patients), data quality must be closely scrutinized, and studies using case-control and case-crossover designs are needed. The epidemiological and pathophysiological data reviewed in the present article suggest a number of pathways through which activities may trigger sudden cardiac death. Different extrinsic stimuli may cause similar physiological changes that subsequently lead to acute pathological events, a decrease in the ventricular fibrillation threshold through a direct myocardial effect, or a harmful effect on the conduction system. Myocardial ischemia induced by plaque rupture and thrombosis may lead directly to myocardial electric instability. The presence of chronic structural abnormalities of the myocardial tissue or the conduction system may further lower the threshold for electric instability and ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)
The nitrovasodilators. New ideas about old drugs.
Authors: Harrison D G , Bates J N
Published: June 2012

The nitrovasodilators are a diverse group of pharmacological agents that produce vascular relaxation by releasing nitric oxide. The mechanisms by which these compounds release nitric oxide vary, depending on their chemical structure. Compounds with lower oxidation states of nitrogen such as nitroprusside, nitrosamines, and nitrosothiols release nitric oxide nonenzymatically. In the case of nitroprusside, this involves a one-electron reduction that may occur upon exposure to a variety of reducing agents and tissues such as vascular smooth muscle membranes. In the case of the organic nitrates, which have higher oxidation states of nitrogen, the release of nitric oxide in vascular tissue occurs predominantly by a poorly understood enzymatic process. This interesting property of nitroglycerin is important because it "targets" its effect to vascular tissues that are capable of this enzymatic process. In the case of the coronary circulation, nitroglycerin predominantly dilates the larger coronary arteries while having a minimal effect on coronary resistance vessels < 100 microns in diameter. This prevents the development of coronary steal, which is often encountered with agents that produce intense vasodilation of the coronary resistance vessels. In this review, the mechanisms by which the nitrovasodilators (particularly nitroglycerin) release nitric oxide will be considered, and recent studies of nitroglycerin bioconversion in various-sized coronary vessels will be discussed in detail.