bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Molecular Weight Heparin After Mechanical Heart Valve Replacement
Authors: Montalescot Gilles , Polle Valérie , Collet Jean P. , Leprince Pascal , Bellanger Agnès , Gandjbakhch Iradj , Thomas Daniel
Published: June 2012

Background
—Patients with mechanical heart valves require life-long anticoagulation. We report here the first large and comparative series of consecutive patients anticoagulated with low molecular weight heparin (LMWH) after mechanical heart valve replacement.

Methods and Results
—In this comparative, nonrandomized study, 208 consecutive patients who underwent a single or double heart valve replacement with mechanical prostheses were anticoagulated subcutaneously with unfractionated heparin (UH) in the first period (n=106) and LMWH in the second phase (n=102) of the study. Baseline characteristics were similar in the 2 groups. The mean durations of UH and LMWH treatments were 13.6±0.5 and 14.1±0.6 days, respectively (not significant). On the second day of treatment, 87% of patients treated with LMWH had an anti-Xa activity within the range of efficacy (0.5 to 1 IU/mL), but only 9% of UH-treated patients had an activated partial-thromboplastin time value within the therapeutic range (1.5 to 2.5 times control,
P
<0.0001 between the 2 groups). On the last day of prescription, all LMWH-treated patients had anti-Xa activity above 0.5 IU/mL, but 19% were above 1 IU/mL. In the UH group, 27% of patients had an activated partial-thromboplastin time above 1.5 times control, but 62% were overanticoagulated. Two major bleedings occurred in each group, and one stroke occurred in the UH group.

Conclusions
—In this first comparative study, anticoagulation with LMWHs after mechanical heart valve replacement appears feasible, provides adequate biological anticoagulation, and compares favorably with UH anticoagulation. Randomized studies are now needed to further evaluate this new therapeutic approach.
Aspirin Use Is Low Among United States Outpatients With Coronary Artery Disease
Authors: Stafford Randall S.
Published: June 2012

Background
—The goal of the present study was to assess national trends and patterns of aspirin use among outpatients with coronary artery disease. Although there is strong evidence that the use of aspirin reduces the risk of death and recurrent events in patients with coronary artery disease, current national patterns of aspirin use are unknown.

Methods and Results
—We used data from the 1980 to 1996 National Ambulatory Medical Care Surveys. These surveys provide a nationally representative sample of physician activities during patient visits to physician offices. We evaluated the report of aspirin as a new or continuing medication in 10 942 visits to cardiologists and primary care physicians by patients with coronary artery disease. We evaluated trends in the use of aspirin for 1980 to 1996 and used logistic regression to identify independent predictors of aspirin use for 1993 to 1996. Aspirin use in outpatient visits by persons with coronary artery disease without reported contraindications increased from 5.0% in 1980 to 26.2% in 1996. Large increases occurred in the early 1990s. Independent predictors of aspirin use in 1993 to 1996 were male patient gender (29% versus 21% for females), patient age of <80 years (28% versus 17% for age of ≥80 years), and presence of hyperlipidemia (45% versus 24% for patients without hyperlipidemia; all comparisons
P
<0.001). Cardiologists (37%) were more likely to report aspirin use than were internists (20%), family physicians (18%), or general practitioners (11%;
P
<0.001). These effects persisted after we controlled for potential confounders with the use of logistic regression.

Conclusions
—Although aspirin use in patients with coronary artery disease has increased dramatically, it remains suboptimum. Low rates of aspirin use and variations in use suggest a need to better translate clinical recommendations into practice.
Myocardial Infarction in Treated Hypertensive Patients
Authors: Alderman Michael H. , Cohen Hillel W. , Madhavan Shantha
Published: June 2012

Background
—Despite the impressive decline in coronary heart disease death rates, a mortality differential between blacks and whites persists. Our study objective was to determine whether excess mortality among well-controlled hypertensive black men compared with whites is due to differences in disease incidence or in case fatality.

Methods and Results
—Of 3382 male subjects (1266 blacks and 2116 whites) enrolled between 1973 and 1996 and followed up through 1997 in a work-site hypertension control program, 2343 were followed up until 60 years of age, and 1884 were followed up until >60 years of age (either continuing after 60 years [n=845] or beginning treatment at ≥60 years [n=1039]), with a mean follow-up of 5.2 and 5.5 years, respectively. During follow-up, 186 myocardial infarction (MI) events (including 31 revascularizations) occurred, with 63 in patients <60 years and 123 in patients ≥60 years of age. Age-adjusted MI incidence was nearly twice as high for whites as blacks in younger (6.3 versus 3.4/1000 person-years) and older (14.1 versus 7.5 person-years) subjects. In contrast, the age-adjusted case fatality rate was 3-fold higher for younger blacks than for whites (37.8% versus 12.2%). In older patients, case fatality did not differ significantly between blacks and whites (37.6% versus 50.3%). In separate Cox regression analyses, among younger blacks but not younger whites, history of diabetes and smoking were significantly associated with both incidence and fatality.

Conclusions
—In these treated male hypertensive patients with good blood pressure control (139.6/85.7 mm Hg), young blacks, despite a lower MI incidence, had higher MI mortality than did their white counterparts. Their higher case fatality rate was associated with fewer coronary artery revascularizations and a higher prevalence of diabetes and smoking.
Clinical Outcomes After Ablation and Pacing Therapy for Atrial Fibrillation
Authors: Wood Mark A. , Brown-Mahoney Chris , Kay G. Neal , Ellenbogen Kenneth A.
Published: June 2012

Background
—Radiofrequency ablation of the atrioventricular node and permanent pacing are used for symptomatic relief in patients with medically refractory atrial fibrillation. In this study, meta-analysis was used to clarify clinical outcomes and survival after ablation and pacing therapy using data from the published literature.

Methods and Results
—We used 21 studies with a total of 1181 patients in the meta-analysis. All patients had medically refractory atrial tachyarrhythmias, primarily atrial fibrillation (97%). Nineteen measures of clinical outcome, encompassing quality of life, ventricular function, exercise duration, and healthcare use, were derived from the studies. The meta-analysis demonstrated significant improvement after ablation and pacing therapy in all outcome measures except fractional shortening, which demonstrated a trend toward improvement (
P
=0.08). Ejection fraction did show significant improvement (
P
<0.001). The calculated 1-year total and sudden death mortality rates after ablation and pacing therapy were 6.3% and 2.0%, respectively.

Conclusions
—Ablation and pacing therapy improves a broad range of clinical outcomes for patients with medically refractory atrial fibrillation. The calculated 1-year mortality rates after this therapy are low and comparable with medical therapy.
Peak Oxygen Uptake Better Predicts Outcome Than Submaximal Respiratory Data in Heart Transplant Candidates
Authors: Pardaens Karel , Van Cleemput Johan , Vanhaecke Johan , Fagard Robert H.
Published: June 2012

Background
—Many studies have focused on the prognostic power of peak oxygen uptake (V̇
o
2
) in patients with chronic heart failure, but maximal exercise testing is not without risk. The purpose of the present study was, therefore, to assess the prognostic significance of the steepness of changes in ventilation and carbon dioxide output (V̇
co
2
) during submaximal exercise in comparison with V̇
o
2
.

Methods and Results
—The study population consisted of 284 adult heart transplant candidates who performed a graded maximal bicycle ergometer test with respiratory gas analysis. Using the respiratory data up to a gas exchange ratio of 1.0, 3 submaximal slopes were calculated in each patient. During follow-up (median, 1.33 years), 57 patients died and 149 had ≥1 cardiovascular event. When using Cox proportional hazards analysis, both peak V̇
o
2
and submaximal respiratory slopes predicted outcome before and after accounting for age, sex, and body mass index. However, whereas the prognostic power of peak V̇
o
2
was independent of submaximal respiratory data, the prognostic significance of the slopes was lost after controlling for peak V̇
o
2
. Stepwise regression analysis even selected peak V̇
o
2
as an independent prognostic index among the following factors: cause of heart failure, ejection fraction, pulmonary vascular resistance, natremia, and the forced expiratory volume in 1 s.

Conclusions
—Respiratory data during submaximal exercise are significant predictors of outcome in patients with chronic heart failure, but their prognostic power is inferior to that of peak V̇
o
2
. However, these data may be useful when maximal exercise is contraindicated or not achievable.
Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation
Authors: Jayachandran J. Vijay , Sih Haris J. , Winkle Wendy , Zipes Douglas P. , Hutchins Gary D. , Olgin Jeffrey E.
Published: June 2012

Background
—Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation.

Methods and Results
—Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals (
P
=0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals (
P
=0.01). The coefficient of variation of HED retention was also greater in paced animals (
P
=0.05) and was greater in the right atrium than in the left atrium (
P
=0.004). Epicardial activation maps of AF were obtained in the paced animals at baseline and with autonomic manipulation. Mean AF cycle length was longer in the right atrium (109.2±5 ms) than in the left atrium (85.8±5.5 ms) at baseline (
P
=0.005). AF cycle length did not vary significantly from baseline (97.6±13.4 ms) with stellate stimulation (100.5±6 ms) but lengthened with propranolol (107.5±6.1 ms,
P
=0.03).

Conclusions
—Rapid rates of AF produce a heterogeneous increase in atrial sympathetic innervation. These changes parallel disparate effects of rapid pacing–induced AF on atrial electrophysiology.
Losartan and Its Metabolite E3174 Modify Cardiac Delayed Rectifier K
+
Currents
Authors: Caballero Ricardo , Delpón Eva , Valenzuela Carmen , Longobardo Mónica , Tamargo Juan
Published: June 2012

Background
—The effects of type 1 angiotensin II receptor antagonist losartan and its metabolite E3174 on transmembrane action potentials, hKv1.5, HERG, and
I
Ks
currents were analyzed.

Methods and Results
—Guinea pig ventricular action potentials were recorded with microelectrode techniques and hKv1.5 and HERG currents with the whole-cell patch-clamp technique.
I
Ks
was recorded in guinea pig ventricular myocytes with the perforated-nystatin-patch configuration. Losartan and E3174 transiently increased the hKv1.5 current by 8.0±1.4% and 7.4±1.6%, respectively. Thereafter, they produced a voltage-dependent block, E3174 being more potent than losartan (
P
<0.05) for this effect. Losartan decreased HERG currents elicited at 0 mV (23.3±4.8%), whereas E3174 increased the current (30.5±6.2%). Both drugs shifted the midpoint of the activation curve of HERG channels to more negative potentials. In ventricular myocytes, losartan and E3174 inhibited the
I
Ks
(18.4±3.2% and 6.5±0.7%, respectively). Losartan-induced block was voltage-independent, whereas E3174 shifted the midpoint of the activation curve to more negative potentials. Losartan lengthened the duration of the action potentials at both 50% and 90% of repolarization, whereas E3174 slowed only the final phase of the repolarization process.

Conclusions
—These results demonstrated that at therapeutic concentrations, both losartan and E3174 modified the cardiac delayed rectifier hKv1.5, HERG, and Ks currents.
Radiolabeled Native Low-Density Lipoprotein Injected Into Patients With Carotid Stenosis Accumulates in Macrophages of Atherosclerotic Plaque
Authors: Iuliano L. , Mauriello A. , Sbarigia E. , Spagnoli L. G. , Violi F.
Published: June 2012

Background
—Accumulation of LDL within the arterial wall appears to play a crucial role in the initiation and progression of atherosclerotic plaque. The dynamic sequence of this event has not been fully elucidated in humans.

Methods and Results
—In 7 patients with previous transient ischemic attack or stroke and critical (>70%) carotid stenosis, autologous native [
125
I]-labeled LDL or [
125
I]-labeled human serum albumin were injected 24 to 72 hours before endarterectomy. Carotid specimens obtained at endarterectomy were analyzed by autoradiography and immunohistochemistry. Autoradiographic study showed that LDL was localized prevalently in the foam cells of atherosclerotic plaques, whereas the accumulation in the lipid core was negligible. Immunohistochemistry revealed that foam cells that had accumulated radiolabeled LDL were mostly CD68 positive, whereas a small number were α-actin positive. No accumulation of the radiotracer was detected in atherosclerotic plaques after injection of radiolabeled human serum albumin. In 3 patients treated for 4 weeks with vitamin E (900 mg/d), an almost complete suppression of radiolabeled LDL uptake by macrophages was observed.

Conclusions
—This study shows that circulating LDL rapidly accumulates in human atherosclerotic plaque. The prevalent accumulation of LDL by macrophages provides strong support to the hypothesis that these cells play a crucial role in the pathogenesis of atherosclerosis.
Enoximone Echocardiography for Predicting Recovery of Left Ventricular Dysfunction After Revascularization
Authors: Lu Chunzeng , Carlino Mauro , Fragasso Gabriele , Maisano Francesco , Margonato Alberto , Cappelletti Alberto , Chierchia Sergio L.
Published: June 2012

Background
—The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated.

Methods and Results
—Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 μg · kg
−1
· min
−1
) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by ≥1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%,
P
<0.01) and negative predictive value (90% versus 84%,
P
<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (
P
<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine.

Conclusions
—Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations.
Pulmonary Vein Morphology in Patients With Paroxysmal Atrial Fibrillation Initiated by Ectopic Beats Originating From the Pulmonary Veins
Authors: Lin Wei-Shiang , Prakash V. S. , Tai Ching-Tai , Hsieh Ming-Hsiung , Tsai Chin-Feng , Yu Wen-Chung , Lin Yung-Kuo , Ding Yu-An , Chang Mau-Song , Chen Shih-Ann
Published: June 2012

Background
—Successful ablation of ectopic beats originating from the pulmonary veins (PV) could eliminate paroxysmal atrial fibrillation (PAF). However, information about the structure of the PV in patients with PAF that is initiated by PV ectopic beats has not been reported.

Methods and Results
—We studied the morphology of the PVs and measured their diameters in 3 groups of patients. Group I included 52 patients (aged 66±14 years; 44 men) with focal atrial fibrillation (AF) from the PVs. Group II included 8 patients (aged 50±10 years; 3 men) with focal AF from the superior vena cava or cristal terminalis. Group III included 23 control patients (aged 55±16 years; 17 men). Of the control patients, 11 had AV node and 12 had AV reentrant tachycardia. After an atrial transseptal procedure, selective PV angiography using a biplane system with a right anterior oblique view of 30 degrees, a left anterior oblique view of 60 degrees, and a cranial angle of 20 degrees was performed. The ostial and proximal portions of the right and left superior PVs (RSPV and LSPV) were significantly dilated in group I patients compared with those in groups II and III. Furthermore, the ostia of the RSPV and LSPV were significantly dilated in group II compared with group III patients. However, the mean diameters of the inferior PVs were similar between the 3 groups. Comparisons of the individual PV diameters among the 3 subgroups of group I (which was divided according to where the ectopic focus was located) showed nonselective dilatation of the PV.

Conclusions
—Nonspecific dilatation of the ostia and proximal portion of superior PVs were found in patients with PAF initiated by ectopic beats from the superior PVs.
Transthoracic Cardioversion of Atrial Fibrillation
Authors: Mittal Suneet , Ayati Shervin , Stein Kenneth M. , Schwartzman David , Cavlovich Doris , Tchou Patrick J. , Markowitz Steven M. , Slotwiner David J. , Scheiner Marc A. , Lerman Bruce B.
Published: June 2012

Background
—Clinical studies have shown that biphasic shocks are more effective than monophasic shocks for ventricular defibrillation. The purpose of this study was to compare the efficacy of a rectilinear biphasic waveform with a standard damped sine wave monophasic waveform for the transthoracic cardioversion of atrial fibrillation.

Methods and Results
—In this prospective, randomized, multicenter trial, patients undergoing transthoracic cardioversion of atrial fibrillation were randomized to receive either damped sine wave monophasic or rectilinear biphasic shocks. Patients randomized to the monophasic protocol (n=77) received sequential shocks of 100, 200, 300, and 360 J. Patients randomized to the biphasic protocol (n=88) received sequential shocks of 70, 120, 150, and 170 J. First-shock efficacy with the 70-J biphasic waveform (60 of 88 patients, 68%) was significantly greater than that with the 100-J monophasic waveform (16 of 77 patients, 21%,
P
<0.0001), and it was achieved with 50% less delivered current (11±1 versus 22±4 A,
P
<0.0001). Similarly, the cumulative efficacy with the biphasic waveform (83 of 88 patients, 94%) was significantly greater than that with the monophasic waveform (61 of 77 patients, 79%;
P
=0.005). The following 3 variables were independently associated with successful cardioversion: use of a biphasic waveform (relative risk, 4.2; 95% confidence intervals, 1.3 to 13.9;
P
=0.02), transthoracic impedance (relative risk, 0.64 per 10-Ω increase in impedance; 95% confidence intervals, 0.46 to 0.90;
P
=0.005), and duration of atrial fibrillation (relative risk, 0.97 per 30 days of atrial fibrillation; 95% confidence intervals, 0.96 to 0.99;
P
=0.02).

Conclusions
—For transthoracic cardioversion of atrial fibrillation, rectilinear biphasic shocks have greater efficacy (and require less energy) than damped sine wave monophasic shocks.
Canadian Implantable Defibrillator Study (CIDS)
Authors: Connolly Stuart J. , Gent Michael , Roberts Robin S. , Dorian Paul , Roy Denis , Sheldon Robert S. , Mitchell L. Brent , Green Martin S. , Klein George J. , O’Brien Bernard
Published: June 2012

Background
—Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone.

Methods and Results
—A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone. The primary outcome measure was all-cause mortality, and the secondary outcome was arrhythmic death. A total of 328 patients were randomized to receive an ICD. A thoracotomy was done in 33, no ICD was implanted in 18, and the rest had a nonthoracotomy ICD. All 331 patients randomized to amiodarone received it initially. At 5 years, 85.4% of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day, 28.1% of ICD patients were also receiving amiodarone, and 21.4% of amiodarone patients had received an ICD. A nonsignificant reduction in the risk of death was observed with the ICD, from 10.2% per year to 8.3% per year (19.7% relative risk reduction; 95% confidence interval, −7.7% to 40%;
P
=0.142). A nonsignificant reduction in the risk of arrhythmic death was observed, from 4.5% per year to 3.0% per year (32.8% relative risk reduction; 95% confidence interval, −7.2% to 57.8%;
P
=0.094).

Conclusions
—A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone; this reduction did not reach statistical significance.
Direct In Vivo Evidence Demonstrating Neointimal Migration of Adventitial Fibroblasts After Balloon Injury of Rat Carotid Arteries
Authors: Li Guohong , Chen Shi-Juan , Oparil Suzanne , Chen Yiu-Fai , Thompson John A.
Published: June 2012

Background
—Clinical and experimental evidence suggest that the adventitia participates in the response to endoluminal vascular injury. The current study used a direct approach to test the hypothesis that, after balloon injury of the rat carotid artery, adventitial fibroblasts migrate in a luminal direction and contribute to neointima formation.

Methods and Results
—Primary syngeneic adventitial fibroblasts were stably transduced with retroviral particles coordinating expression of β-galactosidase (LacZ) and introduced into the adventitia of right carotid arteries of rats immediately after balloon injury. At defined times after injury and fibroblast implantation, rats were euthanized, and arterial tissue was examined for detection of LacZ mRNA (reverse transcription polymerase chain reaction), DNA (polymerase chain reaction), and in situ enzymatic activity. LacZ expression was detected in the media 5 days postinjury and in both media and neointima at 7, 10, and 14 days postinjury. LacZ was undetectable in injured vessels that had not been seeded with transduced fibroblasts and was restricted to the adventitia in seeded vessels that were not injured.

Conclusions
—These observations provide direct demonstration of adventitial fibroblast migration into neointima of arteries after endoluminal injury.
Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques
Authors: Schieffer Bernhard , Schieffer Elisabeth , Hilfiker-Kleiner Denise , Hilfiker Andres , Kovanen Petri T. , Kaartinen Maija , Nussberger Jörg , Harringer Wolfgang , Drexler Helmut
Published: June 2012

Background
—Patients with an activated renin-angiotensin system (RAS) or genetic alterations of the RAS are at increased risk of myocardial infarction (MI). Administration of ACE inhibitors reduces the risk of MI, and acute coronary syndromes are associated with increased interleukin 6 (IL-6) serum levels. Accordingly, the present study evaluated the expression of angiotensin II (Ang II) in human coronary atherosclerotic plaques and its influence on IL-6 expression in patients with coronary artery disease.

Methods and Results
—Immunohistochemical colocalization of Ang II, ACE, Ang II type 1 (AT
1
) receptor, and IL-6 was examined in coronary arteries from patients with ischemic or dilated cardiomyopathy undergoing heart transplantation (n=12), in atherectomy samples from patients with unstable angina (culprit lesion; n=8), and in ruptured coronary arteries from patients who died of MI (n=13). Synthesis and release of IL-6 was investigated in smooth muscle cells and macrophages after Ang II stimulation. Colocalization of ACE, Ang II, AT
1
receptor, and IL-6 with CD68-positive macrophages was observed at the shoulder region of coronary atherosclerotic plaques and in atherectomy tissue of patients with unstable angina. Ang II was identified in close proximity to the presumed rupture site of human coronary arteries in acute MI. Ang II induced synthesis and release of IL-6 shortly after stimulation in vitro in macrophages and rat smooth muscle cells.

Conclusions
— Ang II, AT
1
receptor, and ACE are expressed at strategic sites of human atherosclerotic coronary arteries, suggesting that Ang II is produced primarily by ACE within coronary plaques. The observation that Ang II induces IL-6 and their colocalization with the AT
1
receptor and ACE is consistent with the notion that the RAS may contribute to inflammatory processes within the vascular wall and to the development of acute coronary syndromes.
Atrial Fibrillation After Coronary Artery Bypass Surgery
Authors: Zaman Azfar G. , Archbold R. Andrew , Helft Gérard , Paul Elizabeth A. , Curzen Nicholas P. , Mills Peter G.
Published: June 2012

Background
—Atrial fibrillation (AF) occurs in 20% to 40% of patients after CABG. Identification of patients vulnerable for arrhythmia will allow targeting of those most likely to benefit from prophylactic therapy. The aim of the present study was to evaluate accuracy of a prospectively defined signal-averaged P-wave duration (SAPD) cutoff and additional preoperative characteristics for the prediction of AF after CABG.

Methods and Results
—Patients undergoing elective isolated CABG were recruited to the present prospective study. SAPD was recorded in all patients. Filtered signals from 3 orthogonal leads were combined in a vector analysis, and total SAPD was measured preoperatively. Postoperative in-hospital AF occurred in 92 (28.2%) of 326 patients. Patients who developed AF were older (65.9 versus 61.7 years of age;
P
<0.0005) and had longer SAPD (158 versus 145 ms;
P
<0.0005) than non-AF patients. Incidence of AF increased in patients ≥75 years of age and increased progressively throughout the range of SAPD. Stepwise logistic regression analysis of preoperative variables identified that SAPD >155 ms (odds ratio, 5.37; 95% CI, 3.10 to 9.30;
P
<0.0005), advanced age (odds ratio, 1.53; 95% CI, 1.26 to 1.86 per 5-year increase in age;
P
<0.0005), and male sex (odds ratio, 2.88; 95% CI, 1.30 to 6.40;
P
<0.01) independently predicted AF. Prospectively defined SAPD >155 ms predicted AF with positive and negative predictive accuracy of 49% and 84%, respectively.

Conclusions
—A combination of prolonged SAPD, advanced age, and male sex identifies patients at high risk for development of AF after CABG.
Vein of Marshall Cannulation for the Analysis of Electrical Activity in Patients With Focal Atrial Fibrillation
Authors: Hwang Chun , Wu Tsu-Juey , Doshi Rahul N. , Peter C. Thomas , Chen Peng-Sheng
Published: June 2012

Background
—Whether or not the muscle bundle within the ligament of Marshall (LOM) can serve as the origin of focal atrial fibrillation (AF) is unknown.

Methods and Results
—A total of 28 consecutive patients with paroxysmal AF underwent balloon-occlusion coronary sinus angiograms to identify the vein of Marshall (VOM). Attempts were then made to advance a 1.5-French electrophysiological catheter into the VOM via the coronary sinus orifice. In 17 of the 28 patients (10 of 17 were men aged 38±15 years), cannulation was successful. Double potentials were registered in 8 of these 17 patients. The first potential corresponded with local left atrial activation. The second potential was shorter and narrower than the first. The sequence of activation in the second potential in the VOM was proximal to distal. In 6 patients with direct VOM recordings, we documented that the origin of AF was in the muscle bundle within the LOM. Radiofrequency catheter ablation aimed at the insertion site of the VOM successfully terminated AF in 4 of these 6 patients.

Conclusions
—(1) It is possible to cannulate and to record electrical potentials from the VOM. (2) The characteristics of the double potentials within the VOM suggest that the second potential is from the muscle bundle (Marshall bundle) within the LOM. (3) The Marshall bundle may be the origin of focal AF in some patients.
Genetic Determinants of Hemostasis Phenotypes in Spanish Families
Authors: Souto Juan Carlos , Almasy Laura , Borrell Montserrat , Garí Merce , Martínez Elisabet , Mateo José , Stone William H. , Blangero John , Fontcuberta Jordi
Published: June 2012

Background
—Recent studies have described genetic mutations that affect the risk of thrombosis as a result of abnormal levels of such hemostatic parameters as protein C, protein S, and the activated protein C resistance ratio. Although these mutations suggest that genes play a part in determining variability in some hemostasis-related phenotypes, the relative importance of genetic influences on these traits has not been evaluated.

Methods and Results
—The relative contributions of genetic and environmental influences to a panel of hemostasis-related phenotypes were assessed in a sample of 397 individuals in 21 extended pedigrees. The effects of measured covariates (sex, age, smoking, and exogenous sex hormones), genes, and environmental variables shared by members of a household were quantified for 27 hemostasis-related measures. All of these phenotypes showed significant genetic contributions, with the majority of heritabilities ranging between 22% and 55% of the residual phenotypic variance after correction for covariate effects. Activated protein C resistance ratio, activated partial thromboplastin time, and Factor XII showed the strongest heritabilities, with 71.3%, 83.0%, and 67.3%, respectively, of the residual phenotypic variation attributable to genetic effects.

Conclusions
—These results clearly demonstrate the importance of genetic factors in determining variation in hemostasis-related phenotypes that are components of the coagulation and fibrinolysis pathways and that have been implicated in risk for thrombosis. The presence of such strong genetic effects suggests that it will be possible to localize previously unknown genes that influence quantitative variation in these hemostasis-related phenotypes that may contribute to risk for thrombosis.
Global Right Atrial Mapping of Human Atrial Flutter: The Presence of Posteromedial (Sinus Venosa Region) Functional Block and Double Potentials
Authors: Friedman Paul A. , Luria David , Fenton Alexis M. , Munger Thomas M. , Jahangir Arshad , Shen Win K. , Rea Robert F. , Stanton Marshall S. , Hammill Stephen C. , Packer Douglas L.
Published: June 2012

Background
—Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter.

Methods and Results
—Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter.

Conclusions
—(1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.
Prospective Study of Potentially Virulent Strains of
Helicobacter pylori
and Coronary Heart Disease in Middle-Aged Men
Authors: Whincup Peter , Danesh John , Walker Mary , Lennon Lucy , Thomson Andrew , Appleby Paul , Hawkey Chris , Atherton John
Published: June 2012

Background
—Studies are needed to test claims that potentially virulent strains of
Helicobacter pylori
are more strongly related to coronary heart disease (CHD) than are other strains.

Methods and Results
—We measured serum IgG antibodies to mixed
H pylori
antigens and separately to the virulence-associated
H pylori
antigen CagA (cytotoxin-associated gene product A) in 505 CHD cases and in 1025 age-matched controls “nested” in a prospective study of 7735 British men (mean duration of follow-up in controls, 16 years). Of the 505 cases, 401 (79%) were seropositive for
H pylori
antibodies compared with 740 (72%) of the 1025 controls, yielding an odds ratio for CHD of 1.55 (95% CI 1.19 to 2.03), which fell to 1.30 (95% CI 0.88 to 1.90) after adjustments were made for standard vascular risk factors and indicators of socioeconomic status. Of the CHD cases, 240 (48%) were seropositive for IgG antibodies to CagA compared with 450 (44%) of the controls. When CagA-seropositive individuals were compared with
H pylori
–seronegative individuals, the odds ratio for CHD was 1.42 (95% CI 1.06 to 1.91), which fell to 1.10 (95% CI 0.71 to 1.71) after adjustments. In an analysis restricted to the 1141 (75%)
H pylori
–seropositive participants, the odds ratio for CHD was 1.0 (95% CI 0.78 to 1.29) in CagA–seropositive men. No strong associations were observed between
H pylori
seropositivity and blood lipids, blood pressure, markers of systemic inflammation, or plasma homocysteine.

Conclusions
—
H pylori
infection is not strongly related to the incidence of CHD in late middle-aged men, and CagA-positive strains appear to be no more strongly related to the disease than other strains. However, further studies are required to confirm or refute the existence of any moderate associations, particularly at younger ages.
Correction of Arterial Structure and Endothelial Dysfunction in Human Essential Hypertension by the Angiotensin Receptor Antagonist Losartan
Authors: Schiffrin Ernesto L. , Park Jeong Bae , Intengan Hope D. , Touyz Rhian M.
Published: June 2012

Background
—Structural and functional alterations of the vasculature may contribute to complications of hypertension. Because angiotensin II may be pivotal in some of these vascular abnormalities, we tested the hypothesis that the angiotensin type 1 (AT
1
) receptor antagonist losartan, in contrast to the β-blocker atenolol, would correct resistance artery abnormalities in patients with essential hypertension.

Methods and Results
—Nineteen untreated patients with mild essential hypertension (47±2 years, range 30 to 65 years; 57% male) were randomly assigned in double-blind fashion to losartan or atenolol treatment for 1 year. Nine age/sex-matched normotensive subjects were also studied. Both treatments reduced blood pressure to a comparable degree (losartan, from 149±4.1/101±1.6 to 128±3.6/86±2.2 mm Hg,
P
<0.01; atenolol, from 150±4.0/99±1.2 to 130±3.2/84±1.4 mm Hg,
P
<0.01). Resistance arteries (luminal diameter 150 to 350 μm) dissected from gluteal subcutaneous biopsies were studied on a pressurized myograph. After 1 year of treatment, the ratio of the media width to lumen diameter of arteries from losartan-treated patients was significantly reduced (from 8.4±0.4% to 6.7±0.3%,
P
<0.01). Arteries from atenolol-treated patients exhibited no significant change (from 8.3±0.3% to 8.8±0.5% after treatment). Endothelium-dependent relaxation (acetylcholine-induced) was normalized by losartan (from 82.1±4.9% to 94.7±1.1%,
P
<0.01) but not by atenolol (from 80.4±2.7% to 81.7±4.6%). Endothelium-independent relaxation (by sodium nitroprusside) was unchanged after treatment.

Conclusions
—The AT
1
antagonist losartan corrected the altered structure and endothelial dysfunction of resistance arteries from patients with essential hypertension, whereas the β-blocker atenolol had no effect.
Adventitial Mast Cells Connect With Sensory Nerve Fibers in Atherosclerotic Coronary Arteries
Authors: Laine Petri , Naukkarinen Anita , Heikkilä Lasse , Penttilä Antti , Kovanen Petri T.
Published: June 2012

Background
—The number of activated mast cells is increased in the adventitia of coronary segments with plaque rupture and in spastic atherosclerotic coronary segments. Neurogenic activation of mast cells has been demonstrated previously in other tissues. Here we identified and quantified contacts between mast cells and nerves in the adventitia of normal and atherosclerotic coronary segments.

Methods and Results
—Normal (types 0 or I) and atherosclerotic (lesion types II, III, and IV) coronary segments from 22 unselected autopsy cases were stained for mast cells and sensory nerves by a histochemical double-labeling method. Contacts between mast cells and sensory nerves were quantified morphometrically and also identified by confocal microscopy. Coronary arteries obtained during heart transplantation were stained for the neuropeptides capable of stimulating mast cells, ie, substance P and calcitonin gene–related peptide. In the adventitia of atherosclerotic coronary segments with type IV lesions, the numbers of mast cells and mast cell-nerve contacts (104±15 mast cells/mm
2
and 30±5 nerve contacts/mm
2
; mean±SEM) were significantly greater than in segments with type III lesions (79±12 [
P
<0.001] and 24±6 [
P
<0.001]), those with type II lesions (54±4 [
P
<0.001] and 12±2 [
P
<0.001]), or those with normal intima (31±3 [
P
<0.001] and 4±1 [
P
<0.001]). The nerve fibers connected with mast cells contained both substance P and calcitonin gene–related peptide, which identified them as sensory nerves.

Conclusions
—Neurogenic stimulation of mast cells in the adventitia of coronary arteries may release vasoactive compounds, such as histamine and leukotrienes, which can contribute to the complex neurohormonal response that leads to abnormal coronary vasoconstriction.
Coronary Artery Imaging in Grown Up Congenital Heart Disease
Authors: Taylor Andrew M. , Thorne Sara A. , Rubens Michael B. , Jhooti Permi , Keegan Jennifer , Gatehouse Peter D. , Wiesmann Frank , Grothues Frank , Somerville Jane , Pennell Dudley J.
Published: June 2012

Background
—There is a high incidence of anomalous coronary arteries in subjects with congenital heart disease. These abnormalities can be responsible for myocardial ischemia and sudden death or be damaged during surgical intervention. It can be difficult to define the proximal course of anomalous coronary arteries with the use of conventional x-ray coronary angiography. Magnetic resonance coronary angiography (MRCA) has been shown to be useful in the assessment of the 3-dimensional relationship between the coronary arteries and the great vessels in subjects with normal cardiac morphology but has not been used in patients with congenital heart disease.

Methods and Results
—Twenty-five adults with various congenital heart abnormalities were studied. X-ray coronary angiography and respiratory-gated MRCA were performed in all subjects. Coronary artery origin and proximal course were assessed for each imaging modality by separate, blinded investigators. Images were then compared, and a consensus diagnosis was reached. With the consensus readings for both magnetic resonance and x-ray coronary angiography, it was possible to identify the origin and course of the proximal coronary arteries in all 25 subjects: 16 with coronary anomalies and 9 with normal coronary arteries. Respiratory-gated MRCA had an accuracy of 92%, a sensitivity of 88%, and a specificity of 100% for the detection of abnormal coronary arteries. The MRCA results were more likely to agree with the consensus for definition of the proximal course of the coronary arteries (
P
<0.02).

Conclusions
—For the assessment of anomalous coronary artery anatomy in patients with congenital heart disease, the use of the combination of MRCA with x-ray coronary angiography improves the definition of the proximal coronary artery course. MRCA provides correct spatial relationships, whereas x-ray angiography provides a view of the entire coronary length and its peripheral run-off. Furthermore, respiratory-gated MRCA can be performed without breath holding and with only limited subject cooperation.
Effects of Flecainide in Patients With New
SCN5A
Mutation
Authors: Benhorin J. , Taub R. , Goldmit M. , Kerem B. , Kass R. S. , Windman I. , Medina A.
Published: June 2012

Background
—Mutations in the cardiac sodium channel gene (
SCN5A
) can cause one variant of the congenital long-QT syndrome. The effects of some of these mutations on the α-subunit channel properties can be blocked by type Ib antiarrhythmic drugs. Recently, we have described a new
SCN5A
mutation (
D1790G
) that affects the channel properties in a manner suggesting that sodium blockers of the Ib type will be ineffective in carriers of this mutation. Hence, the ECG effects of flecainide-acetate, a type Ic sodium blocker, were evaluated in carriers of this mutation.

Methods and Results
—Eight asymptomatic mutation carriers and 5 control subjects were studied. Intravenous lidocaine was tested first in only 2 mutation carriers and had no significant effect on any ECG parameter. Flecainide significantly shortened all heart rate–corrected repolarization duration parameters only in carriers and not in control subjects: QT
c
shortened by 9.5% (from 517±45 to 468±36 ms,
P
=0.011), and the S-offset to T-onset interval shortened by 64.7% (from 187±88 to 66±50 ms,
P
=0.0092). Flecainide also normalized the marked baseline repolarization dispersion in most mutation carriers. These effects among carriers were maintained during long-term (9 to 17 months) outpatient flecainide therapy with no adverse effects.

Conclusions
—This report is the first to describe
SCN5A
mutation carriers who significantly responded to flecainide therapy yet did not respond to lidocaine. These results have important implications for long-QT allele–specific therapeutic strategies.
Vascular Superoxide Production and Vasomotor Function in Hypertension Induced by Deoxycorticosterone Acetate–Salt
Authors: Somers Mark J. , Mavromatis Kreton , Galis Zorina S. , Harrison David G.
Published: June 2012

Background
—Angiotensin II–induced hypertension is associated with increased vascular superoxide production, which contributes to hypertension caused by the octapeptide. In cell culture, stretch increases endothelial and vascular smooth muscle production of reactive oxygen species (ROS). In perfused isolated vessels, elevations of pressure can increase vessel angiotensin II production. The effects of low-renin hypertension on vascular ROS production remain unclear. Furthermore, the role of ROS in vascular function and hypertension in low-renin hypertension is undefined.

Methods and Results
—Rats were treated with DOCA and saline drinking water for 3 weeks. Both systolic blood pressure (189±4 versus 126±2 mm Hg) and aortic superoxide production (3972±257 versus 852±287,
P
<0.05) were increased compared with controls. Relaxations of vascular segments to acetylcholine (ACh, 100±2% versus 75±2%,
P
<0.05) and the calcium ionophore A23187 (92±2% versus 72±3%,
P
<0.05) were also impaired in DOCA-salt. Heparin-binding superoxide dismutase (1200 U/d IV for 3 days) had no effect on blood pressure but significantly improved relaxations to ACh and A23187. Losartan (25 mg · kg
−1
· d
−1
PO) for 7 days did not correct the hypertension or endothelium-dependent vessel relaxation in DOCA-salt rats, excluding a role of a local renin/angiotensin II system.

Conclusions
—These findings indicate that increased vascular superoxide production occurs not only in angiotensin II–induced hypertension but also in hypertension known to be associated with low-renin states. Increased superoxide production alters large-vessel endothelium-dependent vascular relaxation but does not modulate blood pressure in low-renin hypertension.
Interferon-γ and Lipopolysaccharide Potentiate Monocyte Tissue Factor Induction by C-Reactive Protein
Authors: Nakagomi Akihiro , Freedman S. Ben , Geczy Carolyn L.
Published: June 2012

Background
—Elevated plasma levels of C-reactive protein (CRP) in population studies and in patients with unstable coronary syndromes are predictive of future adverse events, including cardiac death and myocardial infarction, implicating inflammation in pathogenesis. Although CRP is considered a marker of inflammation, it induces monocyte tissue factor (TF) and may play a prothrombotic role in atherosclerosis and its complications.

Methods and Results
—Peripheral blood mononuclear cells (PBMCs) from 79 healthy men and women aged 26 to 83 years and 21 healthy postmenopausal women taking hormone replacement therapy (HRT) were stimulated with CRP, lipopolysaccharide (LPS), interferon-γ (IFN), or their combination. Levels of CRP in the normal range (1 to 5 μg/mL) increased basal monocyte TF 4- to 6-fold and 40-fold at higher concentrations (25 μg/mL). Coincubation of LPS with CRP produced a greater-than-additive response. IFN did not induce TF but synergized with CRP to approximately double activity. There was a striking positive correlation between age and monocyte TF induction, with a dramatic rise on monocytes from postmenopausal women that was not apparent on cells from women taking HRT.

Conclusions
—Synergy between CRP and inflammatory mediators may play a direct prothrombotic role in the pathogenesis of coronary atherosclerosis and its acute complications by increasing monocyte/macrophage TF. This may contribute to age and sex differences in coronary events and to the protective effects of HRT.