bluuebunny/crossref_metadata_2025 huggingface dataset:
Active skeletal muscle mass and cardiopulmonary reserve. Failure to attain peak aerobic capacity during maximal bicycle exercise in patients with severe congestive heart failure.
Authors: Jondeau G , Katz S D , Zohman L , Goldberger M , McCarthy M , Bourdarias J P , LeJemtel T H
Published: June 2012

BACKGROUND

In addition to depressed cardiac reserve, peripheral factors may contribute to limit maximal exercise capacity in patients with congestive heart failure (CHF). To investigate the role of reduced active skeletal muscle mass, peak oxygen uptake (VO2, milligrams per kilogram per minute) was determined during maximal symptom-limited exercise involving the lower limbs (LL) alone and the lower limbs and upper limbs (LL+UL) combined in patients with CHF and in normal subjects of similar age and sex.

METHODS AND RESULTS

LL bicycle exercise was performed upright with a ramp protocol and continuous expired gas analysis. When respiratory exchange ratio (RER) reached 1.0, UL exercise was initiated at constant load with the use of a cranking device positioned at shoulder level. LL exercise alone and combined LL+UL exercise were performed on separate days in randomized order by 24 patients with CHF and seven normal subjects. In patients with CHF, peak VO2 was greater during combined LL+UL exercise than during LL exercise alone, i.e., 15.8 +/- 0.8 versus 14.2 +/- 0.9 ml.kg-1.min-1 (p < 0.001), whereas in normal subjects, maximal VO2 was similar during the two tests, i.e., 26.7 versus 26.2 ml.kg-1.min-1 (NS). The increase in peak VO2 during combined LL+UL exercise relative to LL exercise alone was almost exclusively observed in patients with peak VO2 < 15 ml.kg-1.min-1 (mean increase, 21.7 +/- 4.1%). Peak VO2 during combined LL and UL exercise did not increase relative to LL exercise alone in patients with peak VO2 > 15 ml.kg-1.min-1 and in normal subjects of similar age and sex, i.e., 0.1 +/- 4.0% and 2.0 +/- 2.3% respectively.

CONCLUSIONS

In contrast to normal subjects and patients with moderate CHF, patients with severe CHF do not exhaust their cardiopulmonary reserve during symptom-limited maximal LL exercise on a bicycle.
Intravascular ultrasound evaluation of the effect of rotational atherectomy in obstructive atherosclerotic coronary artery disease.
Authors: Mintz G S , Potkin B N , Keren G , Satler L F , Pichard A D , Kent K M , Popma J J , Leon M B
Published: June 2012

BACKGROUND

High-speed rotational atherectomy uses a diamond-coated, elliptical burr to abrade occlusive atherosclerosis, especially noncompliant calcified plaque.

METHODS AND RESULTS

Intravascular ultrasound (IVUS) was used to analyze 28 patients after atherectomy. Arteries treated and imaged were left main (three), left anterior descending (12), left circumflex (five), right coronary (seven), and saphenous vein graft (one). Twenty patients had adjunct balloon angioplasty. Twenty-two (79%) target lesions were calcified; the intimal arc of calcium was 160 +/- 126 degrees (range, 0-360 degrees). After atherectomy, the intima-lumen interface was unusually distinct and circular. The lumen was larger than the largest burr used for both stand-alone (1.19 +/- 0.19-fold the largest burr size) and adjunct balloon procedures (1.30 +/- 0.15-fold the largest burr). Three-dimensional reconstruction of the ultrasound images showed a smooth lumen, especially in calcified plaque. Deviations from cylindrical geometry occurred only in areas of soft plaque or superficial tissue disruption of calcified plaque. Five patients were studied before and after rotational atherectomy. IVUS showed an increase in lumen size, a decrease in plaque-plus-media area and in arc of target lesion calcification, and no change in target lesion external elastic membrane cross-sectional area.

CONCLUSIONS

Rotational atherectomy causes atheroablation with only moderate evidence of barotrauma in heavily calcified arteries, even after adjunct balloon angioplasty. The lumen is cylindrical, especially in areas of calcified plaque, and somewhat larger than the largest burr tip used.
A randomized comparison of external and internal cardioversion of chronic atrial fibrillation.
Authors: Lévy S , Lauribe P , Dolla E , Kou W , Kadish A , Calkins H , Pagannelli F , Moyal C , Bremondy M , Schork A
Published: June 2012

BACKGROUND

Delivery of shocks within the right atrium has been reported to be more effective than conventional external shocks in converting atrial fibrillation (AF), but these two cardioversion techniques have never been compared prospectively. The purpose of this study was to compare the efficacies of external and internal cardioversion in patients with chronic AF unresponsive to prior attempts at electrical and/or pharmacological cardioversion. Low-dose amiodarone was used in all patients after cardioversion to suppress recurrences of AF.

METHODS AND RESULTS

One hundred twelve patients with AF of at least 1 month in duration were randomly assigned to undergo external cardioversion with 300-360-J shocks or internal cardioversion with 200-300-J shocks delivered through a standard electrode catheter within the right atrium. The patients were treated with amiodarone (200 mg/day 5-7 days/week) for 1 month before electrical cardioversion and afterward if the cardioversion was successful. The patients were evaluated at regular intervals during 1 year of follow-up. The efficacy of internal cardioversion was significantly greater than that of external cardioversion (91% versus 67%, p = 0.002). The only variable that was associated with the outcome of cardioversion was body weight. Among patients in whom sinus rhythm was restored, AF recurred as often after internal and external cardioversion; at 1 year of follow-up, 37% of patients in whom external or internal cardioversion had been effective were still in sinus rhythm. Patients who had undergone an attempt at electrical cardioversion before entry into this study were less likely to remain in sinus rhythm after cardioversion. The only complications of cardioversion were one instance of cerebral thromboembolism after external cardioversion and one instance of transient pulmonary edema after internal cardioversion. Therapy with amiodarone was discontinued because of an adverse drug effect in only three patients.

CONCLUSIONS

Internal cardioversion is more effective than external cardioversion in restoring sinus rhythm and is as safe as external cardioversion in patients with chronic AF. The recurrence rate of AF is the same after both types of cardioversion. If conventional electrical cardioversion is ineffective, internal cardioversion should be attempted. The combination of low-dose amiodarone and external or internal cardioversion may result in maintaining sinus rhythm long-term in patients with refractory AF.
Temperature monitoring during radiofrequency catheter ablation of accessory pathways.
Authors: Langberg J J , Calkins H , el-Atassi R , Borganelli M , Leon A , Kalbfleisch S J , Morady F
Published: June 2012

BACKGROUND

Animal studies have suggested that the temperature of the electrode-tissue interface during radiofrequency catheter ablation accurately predicts lesion size. The purpose of the current study was to evaluate the utility of continuous temperature monitoring during radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

METHODS AND RESULTS

Twenty patients with manifest preexcitation were included in the study. The ablation catheter was positioned on the ventricular side of the mitral annulus for left-sided accessory pathways and on the atrial side of the tricuspid annulus for right-sided and septal accessory pathways. A thermistor imbedded in the distal electrode of the ablation catheter allowed continuous temperature monitoring during each energy application. To define the relation between power and temperature, radiofrequency current was applied several times at each site using outputs of 20, 30, 40, and 50 W. The accessory pathways were successfully ablated in each of the 20 patients. Because of marked variability in the efficiency of heating between sites, power output did not predict temperature. However, at any given site, there was a positive dose-response relation between power and temperature. Radiofrequency energy applications on the atrial side of the tricuspid annulus produced lower temperatures than did applications on the ventricular side of the mitral annulus (49 +/- 7 versus 60 +/- 16 degrees C, p = 0.0001). Transient block in the accessory pathways occurred at a mean of 50 +/- 8 degrees C, whereas permanent block was seen at a mean of 62 +/- 15 degrees C (p = 0.0001). Less than half of the applications at outputs < or = 40 W produced temperatures adequate to interrupt accessory pathway conduction. An abrupt rise in impedance caused by coagulum formation occurred only at temperatures between 95 and 100 degrees C.

CONCLUSIONS

Temperature monitoring may facilitate radiofrequency catheter ablation of accessory pathways. By adjusting power output to ensure that adequate but not excessive temperatures have been achieved, a rise in impedance can be avoided and the total number of energy applications and procedure duration may be reduced.
Tobacco use and urinary excretion of thromboxane A2 and prostacyclin metabolites in women stratified by age.
Authors: Rångemark C , Benthin G , Granström E F , Persson L , Winell S , Wennmalm A
Published: June 2012

BACKGROUND

Activated platelets have been implicated in both acute thrombus formation and atherogenesis. Because smoking is a risk factor for cardiovascular disease in men and women and male smokers have biochemical evidence of increased platelet activation, we found it of interest to study whether smoking augments platelet activity in women as well.

METHODS AND RESULTS

Data on smoking habits and a urinary sample were obtained from 125 healthy female nonsmokers and an equal number of smokers, stratified by age in five groups from 18 to 59 years old. Urinary samples were analyzed with gas chromatography/mass spectrometry for the 2,3-dinormetabolites of thromboxane A2 (Tx-M), reflecting platelet activity, and prostacyclin (PGI-M), representing platelet/vessel wall interaction. Urinary Tx-M in smokers was higher than in nonsmokers (p < 0.001), increasing with the number of cigarettes smoked per day and with age. In nonsmokers, there was no difference in Tx-M between the age groups. Urinary PGI-M in smokers was higher than that in nonsmokers (p < 0.001) and decreased with age in nonsmokers but not in smokers. There was no difference in Tx-M between previous smokers and lifelong nonsmokers.

CONCLUSIONS

The elevated Tx-M in women who smoke cigarettes indicates an increased platelet activity that is dependent on smoking intensity. In parallel, PGI-M is augmented, suggesting that platelet/vessel wall interaction is stimulated. Quitting smoking is an effective means to restore platelet function. We propose that the observed increase in platelet activity in women who smoke cigarettes may be related to subsequent development of cardiovascular disease and that quitting smoking should be considered a high-priority medical target also in this sex.
Diagnosis and management of right ventricle-dependent coronary circulation in pulmonary atresia with intact ventricular septum.
Authors: Giglia T M , Mandell V S , Connor A R , Mayer J E , Lock J E
Published: June 2012

BACKGROUND

Coronary artery anomalies including 1) right ventricle (RV)-to-coronary artery fistulas, 2) coronary artery stenoses, and 3) coronary occlusions occur in patients with pulmonary atresia with intact ventricular septum (PA-IVS). In some, a large part of the coronary blood supply may depend on the RV. This RV-dependent coronary circulation may determine survival after right ventricular decompression (RVD): RVD may cause RV "steal" in the presence of fistulas alone and ischemia, coronary isolation, or myocardial infarction in the presence of coronary stenoses.

METHODS AND RESULTS

Eighty-two patients with PA-IVS who presented between January 1979 and January 1990 were reviewed; 26 (32%) had RV-to-coronary artery fistulas. Of these 26, 23 had adequate preoperative coronary angiograms for analysis. RVD was achieved in 16. Seven of 16 had fistulas only; each survived RVD. Six of 16 had stenosis of a single coronary artery [left anterior descending coronary artery (LAD), four; right coronary artery (RCA), two]; four of six survived RVD. Three of 16 had stenoses and/or occlusion of both the RCA and LAD; all three died shortly after RVD of acute left ventricular dysfunction.

CONCLUSIONS

1) Potential RV steal alone does not preclude successful RVD. 2) Fistulas with stenoses to a single coronary artery may not preclude successful RVD. 3) RVD appears to be contraindicated in the presence of stenoses and/or occlusion involving both the right and left coronary systems. Nonsurvival after RVD seems to depend on the amount of the left ventricular myocardium at risk, i.e., that which is distal to coronary artery stenoses, especially when involvement of both coronary arteries limits effective collateralization. Precise definition of coronary arterial anatomy is mandatory in neonates with PA-IVS.
Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits. A quantitative angiographic and histopathological study.
Authors: Gimple L W , Gertz S D , Haber H L , Ragosta M , Powers E R , Roberts W C , Sarembock I J
Published: June 2012

BACKGROUND

Heparin is known to have antithrombotic, anticoagulant, and antiproliferative effects. We hypothesized that chronic subcutaneous and/or direct intramural administration of heparin would reduce restenosis and inhibit plaque growth after balloon angioplasty.

METHODS AND RESULTS

Focal atherosclerosis was induced bilaterally in the femoral arteries of 59 rabbits by air desiccation intimal injury and a 2% cholesterol diet. After angioplasty, the rabbits were assigned to one of four treatment groups. Control arteries (n = 21) received no additional heparin. A second group of 20 arteries was treated with a porous balloon that delivered heparin (1,500 units) directly into the arterial wall. A third group (n = 29) received subcutaneous heparin (350 units.kg-1.day-1) for 28 days, and a fourth group (n = 23) was treated with subcutaneous and intramural heparin. Quantitative angiography showed a modest reduction in restenosis (defined as the change in minimal luminal diameter from immediately after angioplasty to 28 days) with subcutaneous heparin compared with control arteries (0.32 +/- 0.18 versus 0.58 +/- 0.34 mm, p < 0.01); however, luminal diameter was not improved at 28 days compared with before angioplasty. Intramural delivery of heparin by the porous balloon catheter was confirmed by use of fluoresceinated heparin in one animal. Angiographic restenosis was not reduced in arteries treated with intramural heparin versus controls (0.61 +/- 0.54 versus 0.58 +/- 0.34 mm, p = NS). Blinded planimetric analysis of histological sections showed no differences in luminal cross-sectional area narrowing by atherosclerotic plaque, in plaque area, or in plaque/media ratio at 28 days among the four treatment groups.

CONCLUSIONS

Chronic subcutaneous heparin after balloon angioplasty results in a modest reduction in angiographic restenosis in this model; however, the absolute luminal diameter is not improved compared with before angioplasty, and plaque area and percent luminal narrowing by plaque were not different among the four treatment groups. Heparin can be delivered into an atherosclerotic plaque by a porous balloon, but this treatment does not reduce restenosis after angioplasty in this model.
Differential effects of captopril and enalapril on tissue renin-angiotensin systems in experimental heart failure.
Authors: Hirsch A T , Talsness C E , Smith A D , Schunkert H , Ingelfinger J R , Dzau V J
Published: June 2012

BACKGROUND

Angiotensin converting enzyme (ACE) inhibitor therapy elicits beneficial responses from patients with heart failure. We hypothesized that a major site of action of these drugs is tissue ACE and that ACE inhibitors might differ in their ability to inhibit tissue ACE. To test this hypothesis, we assessed the effects of captopril and enalapril on blood pressure and renal function and on serum and tissue ACE activities in sham-operated rats and rats with heart failure induced by coronary artery ligation.

METHODS AND RESULTS

During short-term (1-week) treatment, captopril (200 mg.kg-1.day-1) and enalapril (25 mg.kg-1.day-1) elicited equipotent effects on blood pressure and inhibition of serum ACE activity (85%). The effects of long-term treatment (47 days) were then studied beginning 45 +/- 5 days after coronary ligation in four treatment groups: sham-operated, vehicle (n = 14); heart failure, vehicle (n = 10); heart failure, captopril (n = 8); and heart failure, enalapril rats (n = 7). During long-term treatment, captopril and enalapril caused comparable falls of 12-18 mm Hg in blood pressure (p < 0.01 compared with vehicle treatment). There was no change in urine volume or sodium or potassium excretion in vehicle- or captopril-treated heart failure rats; in contrast, enalapril-treated heart failure rats demonstrated 83% and 10% increases in urine volume and daily sodium excretion, respectively, compared with vehicle-treated rats (both p < or = 0.01). No significant changes in blood urea nitrogen or creatinine were observed with either treatment. Enalapril but not captopril elicited a significant decrease in serum and lung ACE activities. Captopril but not enalapril inhibited aortic ACE activity. Both agents caused a comparable inhibition of renal ACE activity. The magnitude of inhibition of renal ACE activity but not serum and vascular (aortic) ACE activities correlated with the long-term blood pressure response. Enalapril but not captopril normalized renal angiotensinogen expression; the magnitude of this effect correlated with the increase in daily urinary sodium excretion (r = -0.43; p < or = 0.005).

CONCLUSIONS

These data suggest that chronic treatment with these two agents elicits differential effects on tissue ACE activities and renal angiotensinogen regulation. The differential renal effects of these agents may be important in the treatment of heart failure.
Interposed abdominal compression-cardiopulmonary resuscitation and resuscitation outcome during asystole and electromechanical dissociation.
Authors: Sack J B , Kesselbrenner M B , Jarrad A
Published: June 2012

BACKGROUND

Coronary perfusion pressure has been shown to be a significant determinant of return of spontaneous circulation from cardiac arrest during asystole and electromechanical dissociation. The addition of interposed abdominal compression to otherwise standard cardiopulmonary resuscitation (CPR) increases coronary perfusion pressure in animal and human models.

METHODS AND RESULTS

Accordingly, we conducted a randomized prospective study of 143 consecutive patients experiencing cardiac arrest in a large university-affiliated teaching hospital in whom the initial arrest rhythm was asystole or electromechanical dissociation. Patients were randomized to receive either interposed abdominal compression-CPR or standard CPR. The two end points studied were return of spontaneous circulation and 24-hour survival. In addition, we studied the complications associated with interposed abdominal compression-CPR. Sixty-nine men and 74 women with a mean age of 64 years (range, 19-97 years) were studied. The overall rate of return of spontaneous circulation was 38%. Return of spontaneous circulation was significantly greater in the group receiving interposed abdominal compression-CPR compared with the group receiving standard CPR (49% versus 28%, p = 0.01). At 24 hours, there was a significantly greater number of patients alive in the experimental group than in the control group (33% versus 13%, p = 0.009). We found no complication directly related to the procedure of interposed abdominal compression in a small subset of patients who died and underwent necropsy.

CONCLUSIONS

We conclude that the addition of interposed abdominal compression may be a useful adjunct to otherwise standard CPR that can improve resuscitation outcome of patients experiencing in-hospital cardiac arrest from asystole and electromechanical dissociation.
31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure.
Authors: Neubauer S , Krahe T , Schindler R , Horn M , Hillenbrand H , Entzeroth C , Mader H , Kromer E P , Riegger G A , Lackner K
Published: June 2012

BACKGROUND

The purpose of this work was to further define the value of cardiac 31P magnetic resonance (MR) spectroscopy for patients with coronary artery disease and dilated cardiomyopathy.

METHODS AND RESULTS

Blood-corrected and T1-corrected 31P MR spectra of anteroseptal myocardium were obtained at rest using image-selected in vivo spectroscopy localization, a selected volume of 85 +/- 12 cm3, and a field strength of 1.5 T. Nineteen volunteers had a creatine phosphate (CP)/ATP ratio of 1.95 +/- 0.45 (mean +/- SD) and a PDE/ATP ratio of 1.06 +/- 0.53; in four patients with left anterior descending coronary artery (LAD) stenosis, six patients with chronic anterior wall infarction, and four patients with chronic posterior wall infarction, CP/ATP and phosphodiester (PDE)/ATP ratios did not differ from those in volunteers. Twenty-five measurements of 19 patients with dilated cardiomyopathy yielded a CP/ATP of 1.78 +/- 0.51 and a PDE/ATP of 0.98 +/- 0.56 (p = NS versus volunteers). When these patients were grouped according to the severity of heart failure, however, CP/ATP was 1.94 +/- 0.43 in mild (p = NS versus volunteers) and 1.44 +/- 0.52 in severe DCM (p < 0.05), respectively. No correlation was found between CP/ATP and left ventricular ejection fraction or fractional shortening, but correlation of CP/ATP with the New York Heart Association (NYHA) class was significant (r = 0.60, p < 0.005). Six patients with dilated cardiomyopathy were studied repeatedly before and after 12 +/- 6 weeks of drug treatment leading to clinical recompensation with improvement of the NYHA status by 0.8 +/- 0.3 classes. Concomitantly, CP/ATP increased from 1.51 +/- 0.32 to 2.15 +/- 0.27 (p < 0.01), whereas PDE/ATP did not change significantly.

CONCLUSIONS

Cardiac high-energy phosphate metabolism at rest is normal in LAD stenosis and chronic myocardial infarction in the absence of heart failure. The CP/ATP ratio has low specificity for the diagnosis of dilated cardiomyopathy. However, CP/ATP correlated with the clinical severity of heart failure and may improve during clinical recompensation.
Myocardial uptake of 111In monoclonal antimyosin Fab in detecting doxorubicin cardiotoxicity in rats. Morphological and hemodynamic findings.
Authors: Hiroe M , Ohta Y , Fujita N , Nagata M , Toyozaki T , Kusakabe K , Sekiguchi M , Marumo F
Published: June 2012

BACKGROUND

The therapeutic value of doxorubicin (DOX) is limited by its cardiotoxicity, which is dose dependent. To improve the detection of such myocardial damage, this study was designed to determine whether the 111In antimyosin antibody Fab could serve as a marker for cardiotoxicity in treated versus control rats on the basis of comparative morphological and hemodynamic findings.

METHODS AND RESULTS

DOX was administered by intravenous injection to rats at a dose of 3 mg.kg-1.week-1 for 5 weeks. Three weeks after the final injection, an intravenous dose of 111In antimyosin, 740 kBq (20 microCi), was administered, and tissue distribution of the radioisotope (percent kilogram dose per gram) was assessed in 48 hours. Myocardial uptake of radioactivity by both ventricles was more prominent in the DOX-treated rats than in control rats (p < 0.001). The heart-to-blood and heart-to-lung uptake ratios were markedly higher in the treated rats than in controls (p < 0.001). As the severity of the myocardial damage increased, there was a progressive increase in myocardial uptake. There was a strong correlation between the severity of myocardial damage and the ventricular end-diastolic pressure (r = 0.84 and r = 0.83 in the left and right ventricles, respectively). On microscopic immunoautoradiography of the DOX-treated heart, there was a specific immunolocalization of the radiotracer in the injured myocytes but no radioactivity in the control myocytes.

CONCLUSIONS

111In antimyosin antibody appears to be a useful immunoradiotracer in detecting cardiac damage induced by DOX administration and in assessing the severity of cardiotoxicity. These data reinforce the clinical observation that myocardial imaging using 111In antimyosin Fab is able to provide information to guide the course of patients receiving DOX treatment.
Use-dependent prolongation of ventricular tachycardia cycle length by type I antiarrhythmic drugs in humans.
Authors: Kidwell G A , Greenspon A J , Greenberg R M , Volosin K J
Published: June 2012

BACKGROUND

Type I antiarrhythmic drugs block the cardiac sodium channel in a use-dependent fashion. This use-dependent behavior causes increased drug binding and consequently increased sodium channel blockade at faster stimulation rates. Importantly, the kinetics of drug association and dissociation from the sodium channel differ for each type I antiarrhythmic drug.

METHODS AND RESULTS

Thirty-five patients receiving type I antiarrhythmic drugs for the treatment of sustained monomorphic ventricular tachycardia (VT) were studied before and after drug therapy. A total of 41 drug studies were performed (lidocaine, n = 10; procainamide, n = 16; flecainide, n = 15). Sustained monomorphic VT of an identical electrocardiographic morphology was induced during the control and follow-up drug studies. During the control study, there was no significant change in the VT cycle length over time. Compared with control, significant prolongation of the onset VT cycle length was observed after treatment with procainamide and flecainide (increase of 52 +/- 24 and 80 +/- 49 msec, respectively) but not after treatment with lidocaine (increase of 8 +/- 37 msec). Additional drug-induced prolongation of the VT cycle length occurred during a 40-second observation period. This secondary "use-dependent" cycle length prolongation contributed significantly to the steady-state VT cycle length during treatment with flecainide (increase of 82 +/- 34 msec; p < 0.0001). Although a use-dependent increase in VT cycle length was observed with procainamide and lidocaine, the increase was not statistically significant (increase of 12 +/- 15 and 8 +/- 8 msec, respectively). The estimated time constants for the onset of use-dependent VT cycle length prolongation were distinctly different for the three drugs. Flecainide's prolongation of the VT cycle length occurred slowly, with an estimated time constant of 12.5 +/- 5.0 seconds. In contrast, the time course of VT cycle length prolongation was rapid during treatment with lidocaine and intermediate during treatment with procainamide (time constants of 0.52 +/- 0.51 and 4.0 +/- 1.3 seconds, respectively).

CONCLUSIONS

Use-dependent prolongation of VT cycle length during treatment with type I antiarrhythmic drugs was observed in humans. This effect was clinically significant during treatment with flecainide (i.e., the use-dependent slowing of the heart rate improved the hemodynamic tolerance of the arrhythmia). Finally, the estimated time constants for the use-dependent prolongation of VT cycle length by the three test drugs are similar to their reported in vitro time constants for use-dependent sodium channel blockade.
Indobufen in the prevention of thromboembolic complications in patients with heart disease. A randomized, placebo-controlled, double-blind study.
Authors: Fornaro G , Rossi P , Mantica P G , Caccia M E , Aralda D , Lavezzari M , Pamparana F , Milanesi G
Published: June 2012

BACKGROUND

The purpose of this randomized, double-blind study was to evaluate the efficacy of indobufen, a reversible inhibitor of platelet cyclooxygenase, in the prevention of embolic events of cardiac origin.

METHODS AND RESULTS

One hundred ninety-six patients with heart disease and at risk for cardiogenic embolism (90 with atrial fibrillation and 106 in sinus rhythm) were randomly assigned to receive indobufen (100 mg b.i.d.) or placebo. All patients were reexamined every 3 months for the duration of the study. The primary study end points were cerebral ischemic attack (stroke and transient ischemic attack), systemic embolism, pulmonary embolism, and fatal myocardial infarction. The median duration of treatment was 854 days in the indobufen group and 865 days in the placebo group. The frequencies of primary end points (fatal and nonfatal) were 6.1% and 17.3%, respectively, in the indobufen and placebo groups (p < 0.05) for a reduction of 65% in the risk of a primary event (indobufen/placebo relative risk, 0.35; 95% confidence limits, 0.14-0.89). Adverse drug reactions, mostly gastrointestinal or hemostasis disorders, occurred in 9.2% of indobufen-treated patients.

CONCLUSIONS

The results of the study indicate that indobufen may reduce the risk of ischemic events in patients with heart disease associated with an increased risk of embolism.
8-Methoxypsoralen and longwave ultraviolet irradiation are a novel antiproliferative combination for vascular smooth muscle.
Authors: March K L , Patton B L , Wilensky R L , Hathaway D R
Published: June 2012

BACKGROUND

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Although the effects of arterial exposure to high-energy radiation sources such as laser have been investigated in detail, the effects on vascular cells of low-intensity radiant energy in combination with photoactive agents have not been extensively characterized. Psoralens are photoactive agents that are known to be well tolerated when used in conjunction with local exposure to ultraviolet light in the A band (UVA) for the treatment of various dermatologic proliferative disorders.

METHODS AND RESULTS

We have investigated the effects of psoralen/UVA (PUVA) exposure on the proliferation of bovine aortic smooth muscle cells. Proliferation and viability were assessed over a 14-day period by trypan blue exclusion counts. Cell cycle effects were evaluated by thymidine incorporation and flow cytometry with DNA quantitation after addition of serum or platelet-derived growth factor B-chain (PDGF-BB) to subconfluent cells synchronized by serum withdrawal. No effect was observed after exposure to 8-methoxypsoralen (8-MOP) at concentrations up to 10 microM or UVA irradiation at energies up to 2.5 J/cm2. Longwave ultraviolet light and 8-MOP were found to behave synergistically as potent inhibitors of DNA synthesis in bovine aortic smooth muscle cells with the EC50 in combination ranging from 7 microM at 0.35 J/cm2 to 0.2 microM at 2.1 J/cm2. Similar antiproliferative effects were obtained by an inverse variation of dose and energy delivered. After serum stimulation, inhibition of DNA synthesis was found with either an immediate or delayed (16-hour) application of PUVA. This effect was independent of subsequent 8-MOP washout. Flow cytometry of cells treated with PUVA at several times after serum stimulation demonstrated for each time point a block in further cell cycle progression for cells in all phases of the cell cycle. Evaluation of [125I]-labeled PDGF and epidermal growth factor (EGF) binding revealed no effect of PUVA on the apparent number or affinity of PDGF binding sites present but did reveal a dose-dependent inhibition by PUVA of EGF binding. This inhibition of EGF binding occurred increasingly at higher PUVA doses than the cell cycle inhibition and accordingly did not appear to represent a critical mechanism for the antiproliferative effect. Cell counting after a single exposure to PUVA (1 microM, 1.5 J/cm2) revealed complete stasis of cell proliferation over a 28-day period without recurrent exposure. No increase in trypan-positive cells was noted over this period.

CONCLUSIONS

PUVA treatment represents a novel method for locally inhibiting proliferation of vascular smooth muscle cells without producing cytolysis.
Myocardial electrical impedance mapping of ischemic sheep hearts and healing aneurysms.
Authors: Fallert M A , Mirotznik M S , Downing S W , Savage E B , Foster K R , Josephson M E , Bogen D K
Published: June 2012

BACKGROUND

This study was designed to examine the bulk electrical properties of myocardium and their variation with the evolution of infarction after coronary occlusion. These properties may be useful in distinguishing between normal, ischemic, and infarcted tissue on the basis of electrophysiological parameters.

METHODS AND RESULTS

The electrical impedance of myocardial tissue was studied in a sheep model of infarction. The animal model involved a one-stage ligation of the left anterior descending and second diagonal arteries at a point 40% of the distance from the apex to the base. By use of a four-electrode probe, an epicardial mapping system was developed that allowed for cardiac cycle gated and signal-averaged measurements. Subthreshold current (15 microA) was injected through two of the electrodes at frequencies of 1, 5, and 15 kHz and the induced potential measured with the other two electrodes. Epicardial maps of the left ventricle were obtained during acute infarction and at 1-, 2-, and 6-week intervals after occlusion. Results showed the average specific impedance of the myocardium before infarction to be 158 +/- 26 omega-cm independent of location on the epicardium. By 60 minutes after coronary occlusion, the specific impedance had increased by 199% (p < 0.005, n = 9); it remained elevated for up to 4 hours. One week after infarction, the specific impedance decreased to 59% of the control value (p < 0.025, n = 8). Six weeks after occlusion, the specific impedance remained low at 57% of that of the noninfarcted tissue (p < 0.005, n = 9). The phase angle of the complex impedance was also measured and revealed similar changes. The hydroxyproline content of the tissue was assayed to assess infarct healing.

CONCLUSIONS

In this animal model, impedance is a bulk electrical property of tissue that varies with the evolution of myocardial infarction. Impedance mapping revealed significantly different values for normal, ischemic, and infarcted tissue and may prove useful in better defining the electrophysiological characteristics of such tissue.
Long-term outcome of patients with depressed left ventricular function undergoing percutaneous transluminal coronary angioplasty. The NHLBI PTCA Registry.
Authors: Holmes D R , Detre K M , Williams D O , Kent K M , King S B , Yeh W , Steenkiste A
Published: June 2012

BACKGROUND

Coronary revascularization with bypass has been shown to improve survival in patients with coronary artery disease and left ventricular dysfunction. In these patients, use of nonsurgical revascularization with percutaneous transluminal coronary angioplasty (PTCA) is increasing, although their long-term outcome has not been well delineated. The purpose of this investigation was to characterize the outcome of angioplasty in patients with decreased left ventricular function and contrast it with the results in patients with normal left ventricular function.

METHODS AND RESULTS

In the 1985-1986 National Heart, Lung, and Blood Institute's PTCA Registry, of 1,802 patients undergoing PTCA, 244 patients (13.5%) had an ejection fraction of < or = 45% (mean, 39.6 +/- 6.8%). These patients had a higher incidence of prior infarction, a longer and worse history of manifestations of coronary disease, and more extensive coronary artery disease than patients with well-preserved function; 88% and 91%, respectively, had successful dilation of at least one lesion (nonsignificant difference). However, patients with decreased left ventricular function had a decreased frequency of successful dilation of all lesions in which PTCA was attempted (76% versus 84%, p < 0.01). There were no statistically significant differences in in-hospital complications--death occurred in 0.8% and 0.7%, nonfatal myocardial infarction occurred in 4.9% and 4.5%, and emergency surgical revascularization was performed in 4.5% and 3.2%, respectively. Patients were followed for a mean of 4.1 years; during this time, patients with decreased left ventricular function had significantly worse survival and combined event-free survival. Despite this, at 4 years, 87% of the patients with a mean ejection fraction of 39.6% remained alive, and 77% were alive and had not experienced infarction or required bypass.

CONCLUSIONS

PTCA is effective in selected patients with depressed left ventricular function. Initial outcome and risk-benefit ratio are excellent. Successful dilation of at least one vessel was achieved in 88% of patients with depressed left ventricular function and in 91% of patients with more normal left ventricular function. The former group, however, had a decreased incidence of successful dilation in all lesions in which dilation was attempted (76% versus 84%, p < 0.01). There was no significant difference in in-hospital complications between the two groups. During follow-up, patients with decreased left ventricular function had worse event-free survival, although 77% were alive without infarction or bypass grafting at 4 years.
Cigarette smoking is a major risk factor for coronary spasm.
Authors: Sugiishi M , Takatsu F
Published: June 2012

BACKGROUND

Although there have been many studies on the risk factors for coronary artery disease, the etiology of coronary artery spasm has not yet been determined.

METHODS AND RESULTS

After diagnosis by coronary arteriography, various risk factors were compared between two groups of subjects using logistic regression analysis. The vasospasm group included 175 patients with angiographically determined coronary artery spasm but no coronary artery narrowing exceeding 25% of the luminal diameter. The control group comprised 176 subjects with completely normal coronary arteries and a negative response to ergonovine maleate. The adjusted odds ratio and 95% confidence interval for smoking as a risk factor for vasospasm was 2.41 and 1.53-3.82, respectively (p < 0.05). The adjusted odds ratios for total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, diabetes mellitus, and body mass index, calculated by multivariate logistic regression analysis, were not statistically nonsignificant.

CONCLUSIONS

Smoking appears to be a major risk factor for vasospastic angina without significant coronary narrowing. The other risk factors for coronary artery disease may not contribute to coronary vasospasm.
Radiofrequency catheter ablation of ventricular tachycardia in patients with coronary artery disease.
Authors: Morady F , Harvey M , Kalbfleisch S J , el-Atassi R , Calkins H , Langberg J J
Published: June 2012

BACKGROUND

Radiofrequency (RF) ablation of idiopathic ventricular tachycardia (VT) has been demonstrated to be highly efficacious, but the efficacy of RF ablation of VT in patients with coronary artery disease has been unknown. Therefore, the purpose of this study was to determine the feasibility of RF ablation of VT in patients with coronary artery disease.

METHODS AND RESULTS

Fifteen consecutive patients with coronary artery disease and a history of myocardial infarction underwent an attempt at RF ablation of 16 hemodynamically stable monomorphic VTs that had been documented clinically on a 12-lead ECG and that had not been successfully managed by pharmacological or device therapy. One VT was incessant, five occurred more than 25 times, and the remainder occurred two to 20 times. An additional four VTs that had not been documented clinically also were targeted for ablation. The mean age of the patients was 68 +/- 7 years (+/- SD), and their mean left ventricular ejection fraction was 0.27 +/- 0.08. The mean cycle length of the 20 VTs targeted for ablation was 438 +/- 82 msec. Ablation sites were selected based on endocardial activation mapping, pace mapping, identification of an isolated mid-diastolic potential, or concealed entrainment. Sixteen of the 20 VTs (80%) were successfully ablated in 11 of 15 patients (73%), using a mean of 4.2 +/- 3 applications of RF energy, and no recurrences of the ablated VTs occurred during 9.1 +/- 3.3 months of follow-up. The mean duration of the ablation procedures was 128 +/- 30 minutes. No complications occurred in any of the patients.

CONCLUSIONS

The results of this study demonstrate that RF ablation of hemodynamically stable VT is feasible as adjunctive therapy in selected patients with coronary artery disease.
Inhaled nitric oxide in congenital heart disease.
Authors: Roberts J D , Lang P , Bigatello L M , Vlahakes G J , Zapol W M
Published: June 2012

BACKGROUND

Congenital heart lesions may be complicated by pulmonary arterial smooth muscle hyperplasia, hypertrophy, and hypertension. We assessed whether inhaling low levels of nitric oxide (NO), an endothelium-derived relaxing factor, would produce selective pulmonary vasodilation in pediatric patients with congenital heart disease and pulmonary hypertension. We also compared the pulmonary vasodilator potencies of inhaled NO and oxygen in these patients.

METHODS AND RESULTS

In 10 sequentially presenting, spontaneously breathing patients, we determined whether inhaling 20-80 ppm by volume of NO at inspired oxygen concentrations (FIO2) of 0.21-0.3 and 0.9 would reduce the pulmonary vascular resistance index (Rp). We then compared breathing oxygen with inhaling NO. Inhaling 80 ppm NO at FIO2 0.21-0.3 reduced mean pulmonary artery pressure from 48 +/- 19 to 40 +/- 14 mm Hg and Rp from 658 +/- 421 to 491 +/- 417 dyne.sec.cm-5.m-2 (mean +/- SD, both p < 0.05). Increasing the FIO2 to 0.9 without adding NO did not reduce mean pulmonary artery pressure but reduced Rp and increased the ratio of pulmonary to systemic blood flow (Qp/Qs), primarily by increasing Qp (p < 0.05). Breathing 80 ppm NO at FIO2 0.9 reduced mean pulmonary artery pressure and Rp to the lowest levels and increased Qp and Qp/Qs (all p < 0.05). While breathing at FIO2 0.9, inhalation of 40 ppm NO reduced Rp (p < 0.05); the maximum reduction of Rp occurred while breathing 80 ppm NO. Inhaling 80 ppm NO at FIO2 0.21-0.9 did not alter mean aortic pressure or systemic vascular resistance. Methemoglobin levels were unchanged by breathing up to 80 ppm NO for 30 minutes.

CONCLUSIONS

Inhaled NO is a potent and selective pulmonary vasodilator in pediatric patients with congenital heart disease complicated by pulmonary artery hypertension. Inhaling low levels of NO may provide an important and safe means for evaluating the pulmonary vasodilatory capacity of patients with congenital heart disease without producing systemic vasodilation.
Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart.
Authors: Ungerer M , Böhm M , Elce J S , Erdmann E , Lohse M J
Published: June 2012

BACKGROUND

In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK).

METHODS AND RESULTS

We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters.

CONCLUSIONS

In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.
Direct comparison of [13N]ammonia and [15O]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres.
Authors: Bol A , Melin J A , Vanoverschelde J L , Baudhuin T , Vogelaers D , De Pauw M , Michel C , Luxen A , Labar D , Cogneau M
Published: June 2012

BACKGROUND

Both [13N]ammonia and [15O]water have been used to quantify myocardial blood flow with positron emission tomography using appropriate tracer kinetic models. A direct comparison of the two tracers with radioactive microspheres has not been performed in the same experimental preparation.

METHODS AND RESULTS

The two tracers have been tested for myocardial blood flow quantification in closed-chest dogs with circumflex coronary stenosis or permanent occlusion at rest and during adenosine-induced hyperemia. [13N]ammonia- and [15O]water-derived myocardial blood flow values have been compared with radiolabeled microspheres. Validation studies consisted of simultaneous measurements of blood flow with positron emission tomography and microspheres over a wide range of flow values. Blood pool and regional tissue activity curves were fitted with a three-compartment model for [13N]ammonia with and without arterial metabolite correction and with a single-tissue-compartment model for [15O]water. A correction for finite-resolution effect before the fit was also applied. In large regions of interest (5 cm3), a good correlation between the microsphere method and [13N]ammonia (with metabolite correction) was obtained (y = 3 + 0.78x, r = 0.94). The correlation with microspheres was slightly better with [15O]water (y = -3 + 0.89x, r = 0.97). Similar correlations were achieved in smaller regions of interest (1 cm3) as well as in akinetic segments and in central infarct regions.

CONCLUSIONS

Positron emission tomography with appropriate tracer kinetic models using [13N]ammonia and [15O]water provides an accurate quantitative method for measuring regional myocardial blood flow over a wide range of flow values in normally contracting or akinetic canine myocardium in the absence and in the presence of infarction.