bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.
Authors: Hii J T , Wyse D G , Gillis A M , Duff H J , Solylo M A , Mitchell L B 
Published: June 2012

BACKGROUND
Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times.

METHODS AND RESULTS
Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy.

CONCLUSIONS
An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.
Pharmacokinetics and pharmacodynamics of intravenous diltiazem in patients with atrial fibrillation or atrial flutter.
Authors: Dias V C , Weir S J , Ellenbogen K A 
Published: June 2012

BACKGROUND
Diltiazem, a calcium channel blocker, has been shown to be safe and effective in the treatment of patients in atrial fibrillation and/or atrial flutter. However, there have been no pharmacokinetic/pharmacodynamic studies of diltiazem in these patients.

METHODS AND RESULTS
The pharmacokinetics and pharmacodynamics of intravenous diltiazem were determined in 32 patients with atrial fibrillation or atrial flutter (mean +/- SD age, 66 +/- 7 years; mean baseline heart rate, 131 +/- 10 beats per minute) after 20 mg or 20 mg followed by 25-mg bolus doses and a 10 and 15 mg/hr infusion for 24 hours. After the 10 and 15 mg/hr infusions of diltiazem, mean +/- SD elimination half-life was 6.8 +/- 1.8 and 6.9 +/- 1.5 hours, volume of distribution was 411 +/- 151.8 and 299 +/- 70.8 I, and systemic clearance was 42 +/- 12.4 and 31 +/- 8.3 l/hr, respectively. Percentages of the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem to diltiazem were < 15% and < 10%, respectively. Thirty of 32 patients maintained response throughout the 24-hour infusion of diltiazem. Using a sigmoidal Emax pharmacodynamic model, a strong relation (mean +/- SD r2, 0.78 +/- 0.2) was observed between plasma diltiazem concentration and percent heart rate reduction. Mean +/- SD Emax (maximum percent reduction in heart rate from baseline) and EC50 (plasma diltiazem concentration that achieves half Emax) were 52 +/- 17% and 110 +/- 84 ng/ml, respectively. The model predicts that mean plasma diltiazem concentration of 79, 172, and 294 ng/ml are required to produce a 20%, 30%, and 40% reduction in heart rate, respectively. A relation between plasma diltiazem concentration and percent change in systolic blood pressure (SBP) or diastolic blood pressure (DBP) from baseline was not observed (mean +/- SD r2, SBP/DBP: 0.35 +/- 0.24/0.36 +/- 0.2). There were no untoward side effects observed.

CONCLUSIONS
First, the pharmacokinetics of diltiazem in patients with atrial fibrillation or atrial flutter is nonlinear with an apparent dose-dependent decrease in systemic clearance with increasing infusion rate. Second, using a sigmoidal Emax model, there is a strong relation between plasma diltiazem concentration and percent heart rate reduction. Third, the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem are low and are not expected to contribute significantly to the pharmacodynamics of intravenous diltiazem in these patients.
Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease.
Authors: Bernardi L , Ricordi L , Lazzari P , Soldá P , Calciati A , Ferrari M R , Vandea I , Finardi G , Fratino P 
Published: June 2012

BACKGROUND
Diabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease.

METHODS AND RESULTS
To assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44 +/- 2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.18-0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95 +/- 0.12 In-msec2 versus 6.73 +/- 0.11, p < 0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11 +/- 0.18 In-msec2 versus 6.52 +/- 0.14, p < 0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects.

CONCLUSIONS
Diabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present.
Mitral valve replacement with and without chordal preservation in patients with chronic mitral regurgitation. Mechanisms for differences in postoperative ejection performance.
Authors: Rozich J D , Carabello B A , Usher B W , Kratz J M , Bell A E , Zile M R 
Published: June 2012

BACKGROUND
Standard mitral valve replacement (MVR) in patients with chronic mitral regurgitation consistently results in a decrease in postoperative left ventricular (LV) ejection performance. This fall in ejection performance has been attributed, at least in part, to unfavorable loading conditions imposed by the elimination of the low-impedance pathway for LV emptying into the left atrium. In contrast to standard MVR in which the chordae tendineae are severed, however, MVR with chordal preservation (MVR-CP) does not usually decrease LV ejection performance despite similar removal of the low-impedance pathway. The purpose of the present study was to define the mechanisms responsible for this discordance in postoperative ejection performance between MVR with and without chordal preservation.

METHODS AND RESULTS
Echocardiography and sphygmomanometer blood pressures were obtained in 15 patients with pure chronic mitral regurgitation before and 7-10 days after mitral valve surgery. These measurements were used to calculate ventricular volume, wall stress, and ejection fraction. Seven patients underwent MVR with chordal transection (MVR-CT), and eight patients underwent MVR-CP. MVR-CT resulted in no postoperative change in LV end-diastolic volume, a significant increase in LV end-systolic volume, a significant increase in end-systolic stress, from 89 +/- 9 to 111 +/- 12 g/cm2 (p < 0.05), and a significant decrease in ejection fraction, from 0.60 +/- 0.02 to 36 +/- 0.02 (p < 0.05). In contrast, patients who underwent MVR-CP had a significant decrease in LV end-diastolic and end-systolic volumes. End-systolic wall stress actually fell from 95 +/- 6 to 66 +/- 6 g/cm2 (p < 0.05), and ejection fraction was unchanged (0.63 +/- 0.01 before and 0.61 +/- 0.02 after mitral valve surgery) instead of reduced.

CONCLUSIONS
MVR-CT resulted in a decrease in ejection performance caused in part by an increase in end-systolic stress, which in turn increased end-systolic volume. Conversely, MVR-CP resulted in a smaller LV size, allowing a reduced end-systolic stress and preservation of ejection performance despite closure of the low-impedance left atrial ejection pathway.
Preservation of atrioventricular nodal conduction during radiofrequency current catheter ablation of midseptal accessory pathways.
Authors: Kuck K H , Schlüter M , Gürsoy S 
Published: June 2012

BACKGROUND
Septal accessory atrioventricular (AV) pathways may be located in close vicinity of the His bundle-AV nodal conduction system. Attempts at surgical or electrical interruption of these pathways may therefore result in impairment of normal AV conduction. This study focuses on a subset of septal pathways with an atrial insertion located inside the triangle of Koch. In this study, they were called "midseptal."

METHODS AND RESULTS
Six patients with a midseptal accessory pathway (mean +/- SD age, 40 +/- 12 years; five with Wolff-Parkinson-White syndrome and one with a concealed accessory pathway) underwent attempts at ablation of their pathway using 500-kHz radiofrequency current applied to the atrial insertion of the accessory connection. Guided by the recording of accessory pathway activation potentials, the ablation catheter was positioned in all patients in an area bounded anteriorly by the tip electrode of the His bundle catheter and posteriorly by the coronary sinus ostium. All pathways were successfully ablated without the induction of complete heart block. First-degree AV conduction block occurred in one patient in whom a concealed accessory connection was located closer to the AV node than to the coronary sinus ostium.

CONCLUSIONS
Radiofrequency current catheter ablation may be used effectively for midseptal accessory pathways and should be preferred in experienced centers as a safe alternative to surgical therapy.
Cross-bridge dynamics in human ventricular myocardium. Regulation of contractility in the failing heart.
Authors: Hajjar R J , Gwathmey J K 
Published: June 2012

BACKGROUND
To investigate whether altered cross-bridge kinetics contribute to the contractile abnormalities observed in heart failure, we determined the mechanical properties of cardiac muscles from control and myopathic hearts.

METHODS AND RESULTS
Muscle fibers from normal (n = 5) and dilated cardiomyopathy (n = 6) hearts were obtained and chemically skinned with saponin. The muscles were then maximally activated at saturating calcium concentrations. Unloaded shortening velocities (V0) were determined in both groups. V0 in control was 0.72 +/- 0.09 Lmax/sec, whereas in myopathic muscles, V0 was 0.41 +/- 0.06 Lmax/sec at 22 degrees C. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. The dynamic stiffness of the muscles was calculated from the ratio of force response amplitude to length oscillation amplitude. At low frequencies (< 0.2 Hz) the stiffness was constant but was larger in myopathic muscles. In the range of 0.2-1 Hz, there was a drop in the magnitude of dynamic stiffness to approximately one quarter of the low-frequency baseline. This range reflects cross-bridge turnover kinetics. In control muscles, the frequency of minimum stiffness was 0.78 +/- 0.06 Hz, whereas it was 0.42 +/- 0.07 Hz in myopathic muscles. At higher frequencies, the dynamic stiffness increased and reached a plateau at 30 Hz. There were no differences in the plateau reached between control and myopathic muscles.

CONCLUSIONS
Because myopathic hearts have a markedly diminished energy reserve, the slowing of the cross-bridge cycling rate plays an important adaptational role in the observed contractility changes in human heart failure. Although the potential to generate maximal Ca(2+)-activated force is similar in normal and myopathic hearts, alterations in contractile protein composition could explain the diminished cross-bridge cycling rate in failing hearts.
Restenosis after placement of Palmaz-Schatz stents in native coronary arteries. Initial results of a multicenter experience.
Authors: Ellis S G , Savage M , Fischman D , Baim D S , Leon M , Goldberg S , Hirshfeld J W , Cleman M W , Teirstein P S , Walker C 
Published: June 2012

BACKGROUND
Several metallic intracoronary stents are currently undergoing preliminary evaluation to ascertain potential benefit as means to reduce the 30-40% incidence of restenosis after balloon angioplasty.

METHODS AND RESULTS
To determine the incidence and correlates of restenosis after placement of Palmaz-Schatz stents in native coronary arteries in the first group of patients selected for this procedure, clinical and quantitative angiographic data from 206 consecutive patients (221 stenoses) with successful stent placement (diameter stenosis < 50%) were analyzed. Six patients (2.9%) had thrombosis-mediated stent closure within 1 month after stent placement and were excluded from long-term angiographic follow-up. One hundred eighty-one (91%) of the remaining 200 patients had angiography at 5.8 +/- 2.1 months. Patients with and without follow-up did not differ in any baseline characteristic; in particular, history of restenosis at the site stented (73% versus 65%), placement of multiple overlapping stents (17% versus 20%), and mean poststent diameter stenosis (16 +/- 12% versus 14 +/- 12%). The overall incidence of restenosis (diameter stenosis > or = 50% at follow-up) in this group at high risk for restenosis was 36% (95% confidence interval, 29-43%) on a per-stenosis basis. The incidence of restenosis when a single stent was placed was 30% (95% confidence interval, 23-37%). Risk was dependent upon a history of restenosis (present versus absent 36% versus 16%, p = 0.02) and upon whether or not a poststent stenosis < or = 0% was achieved (6% versus 33%, p = 0.02). When multiple overlapping stents were placed, restenosis occurred at 64% of sites, and placement of multiple stents was discouraged during the later phases of this study as these results became apparent.

CONCLUSIONS
Although multiple stents appear to yield a poor long-term result, placement of single stents may offer a benefit compared with standard coronary angioplasty, particularly if an excellent angiographic result can be obtained in patients without prior restenosis. Further randomized trials in such patients are needed.
Development and characterization of a cloned rat pulmonary arterial smooth muscle cell line that maintains differentiated properties through multiple subcultures.
Authors: Rothman A , Kulik T J , Taubman M B , Berk B C , Smith C W , Nadal-Ginard B 
Published: June 2012

BACKGROUND
Pulmonary hypertension is associated with abnormal pulmonary arterial contractility and growth. The mechanisms for these abnormalities are largely unknown. To study these processes, we sought to develop an in vitro system. Even though cultured aortic and pulmonary artery smooth muscle cells (SMCs) have been of considerable value in studying smooth muscle biology, one drawback of this system has been that these cells often lose differentiated properties in an unpredictable manner when they are passaged in culture. In addition, there appear to be significant differences in physiological and pathological responses between the systemic and pulmonary circulations, many of which could be directly related to the smooth muscle. We therefore established a cloned population of rat pulmonary arterial SMCs (PASMCs) that maintain differentiated properties through multiple subcultures.

METHODS AND RESULTS
PASMCs were obtained initially by enzymatic dissociation from pulmonary arteries of adult Sprague-Dawley rats. From these cells, clones were isolated. The cloned cells retained expression of functional surface receptors for angiotensin II, norepinephrine, and alpha-thrombin and high levels of the smooth muscle isoforms of alpha-actin, myosin heavy chain, myosin regulatory light chain, and alpha-tropomyosin mRNAs even after multiple passages. The cells could also be transfected and processed exogenous transcripts in a smooth muscle-specific fashion.

CONCLUSIONS
These cloned PASMCs retain many differentiated characteristics and should be valuable for future studies of pulmonary vascular smooth muscle cell biology.
Quantification of regional myocardial perfusion with generator-produced 62Cu-PTSM and positron emission tomography.
Authors: Herrero P , Markham J , Weinheimer C J , Anderson C J , Welch M J , Green M A , Bergmann S R 
Published: June 2012

BACKGROUND
Noninvasive assessment of regional myocardial perfusion at rest and after stress is important for the objective evaluation of the effects of coronary artery disease and its response to therapy. Centers that do not have cyclotrons rely on generator-produced radioisotopes for assessment of regional myocardial perfusion with positron emission tomography (PET). The aim of the present study was to develop and implement an approach to quantify regional myocardial perfusion using copper(II) pyruvaldehyde bis-(N4-thiosemicarbazone) (PTSM) labeled with the generator-produced, positron-emitting radionuclide 62Cu (t1/2 = 9.7 minutes).

METHODS AND RESULTS
Regional perfusion was estimated from dynamic PET scans after intravenous administration of 62Cu-PTSM in 21 studies in 13 intact dogs evaluated over a wide range of myocardial flow values. In 15 interventions in nine dogs, regional perfusion was also estimated with H2(15)O. Regional perfusion with 62Cu-PTSM was estimated from dynamic blood and tissue time-activity curves, along with the model parameter k1 (forward rate of transport) and the PET parameter FBM (fraction of blood pool activity observed in tissue), using a two-compartment kinetic model. Arterial blood activity was corrected for red blood cell-associated 62Cu. In 44 comparisons, estimates of regional perfusion with 62Cu-PTSM correlated well with estimates obtained with concomitantly administered radiolabeled microspheres (y = 0.90x +/- 0.15, r = 0.95, p < 0.05) over a flow range from 0.23 to 6.14 ml/g per minute. In five healthy human volunteers evaluated at rest with H2(15)O and 62Cu-PTSM, regional perfusion estimated with 62Cu-PTSM was not significantly different from that obtained with H2(15)O (1.05 +/- 0.36 versus 0.96 +/- 0.28 ml/g per minute). 62Cu-PTSM provided high-quality images of the heart.

CONCLUSIONS
The results of this study demonstrate that quantification of regional myocardial perfusion is feasible using generator-produced 62Cu-PTSM. Since 62Cu-PTSM can be used to estimate perfusion in the brain, kidney, and tumors as well as in the heart, it is an attractive tracer for centers that rely on generator-produced tracers for the evaluation of perfusion with PET.
Significance of smoking in patients receiving thrombolytic therapy for acute myocardial infarction. Experience gleaned from the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.
Authors: Barbash G I , White H D , Modan M , Diaz R , Hampton J R , Heikkila J , Kristinsson A , Moulopoulos S , Paolasso E A , Van der Werf T 
Published: June 2012

BACKGROUND
Despite the fact that smoking is a well-established risk factor for the development of coronary artery disease, some investigators have noted that hospital mortality after acute myocardial infarction is lower in patients who smoke than in nonsmoking patients. To evaluate the association of smoking with mortality during hospitalization after thrombolytic therapy and 6 months afterward, we analyzed the results of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

METHODS AND RESULTS
Patients were divided into three groups: nonsmokers (those who never smoked), ex-smokers, and active smokers. Multivariate and univariate comparisons were made with respect to baseline characteristics and clinical outcome. There were 2,366 nonsmokers, 2,244 ex-smokers, and 3,649 active smokers. The baseline characteristics of nonsmoking patients differed significantly from the ex-smokers and active smokers. The nonsmoking group included more women than the ex-smokers or active smokers (45% versus 10.6% and 17.6%, respectively), was older (67 +/- 10 years versus 64 +/- 10 years and 58 +/- 11 years), had a higher rate of diabetes mellitus (16.3% versus 11.1% and 7.5%), and had a worse Killip class at admission. Nonsmoking patients and ex-smokers experienced more in-hospital reinfarction than active smokers (4.7% and 5% versus 2.7%, p < 0.0001, respectively). Nonsmokers experienced more in-hospital shock than the ex-smokers or active smokers (9.2% versus 6.4% and 5.8%, p < 0.0001), stroke (1.9% versus 1.8% and 0.8%, p < 0.0001), and bleeding (7.2% versus 6.5% and 4.4%, p < 0.0001). They also experienced a higher in-hospital and 6-month mortality (12.8% and 17.6%) than ex-smokers (8.2% and 12.1%) or active smokers (5.4% and 7.8%) (p < 0.0001). A multivariate analysis accounting for all baseline characteristics demonstrated a significant association between nonsmoking and increased hospital mortality, with an odds ratio of 1.42 (confidence limits, 1.15-1.72). Among active smokers, there was a nonsignificant trend for mortality rates to decrease with increasing numbers of cigarettes smoked per day.

CONCLUSIONS
This retrospective analysis indicates that smokers receiving thrombolytic therapy after acute myocardial infarction have significantly better hospital and 6-month outcome than nonsmokers or ex-smokers. However, smokers sustained their infarction at a significantly earlier age than nonsmokers, and strenuous efforts should continue to be made to decrease the incidence of new and continued smoking.