bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of endothelin in the maintenance of blood pressure in conscious rats with chronic heart failure. Acute effects of the endothelin receptor antagonist Ro 47-0203 (bosentan).
Authors: Teerlink J R , Löffler B M , Hess P , Maire J P , Clozel M , Clozel J P 
Published: June 2012

BACKGROUND
Endothelin (ET) is a potent vasoconstrictor, and its concentration is increased in patients with heart failure. The purpose of this study was to investigate the role of endothelin in heart failure by use of a rat model.

METHODS AND RESULTS
Experiments were performed on rats at 1 through 16 weeks after sham operation or coronary artery ligation. Rats with left ventricular end-diastolic pressures > 15 mm Hg were considered to have chronic heart failure (CHF), while the others were considered to have uncomplicated myocardial infarction (MI). There were increased ET-1 concentrations in CHF rats at weeks 1 to 16 (Sham, 20 +/- 0.5 pg/mL, n = 45; CHF, 31 +/- 2 pg/mL, n = 50; P < .001) and transient increases in ET-3 concentrations at week 1 in both the MI and CHF groups. There were no significant increases in big ET-1 concentrations, suggesting an increased conversion of ET-1 from big ET-1 in the CHF group. At weeks 2 through 8, oral administration of the mixed (ETA and ETB) endothelin receptor antagonist bosentan significantly decreased mean arterial pressure in conscious CHF rats, an effect that increased over time. Furthermore, bosentan had an additive effect to the angiotensin-converting enzyme inhibitor cilazapril.

CONCLUSIONS
Endothelin plays a role in the maintenance of blood pressure in CHF rats, as evidenced by the significant reduction in mean arterial pressure after oral administration of bosentan. Therefore, endothelin antagonists may be useful therapeutic agents in the treatment of CHF.
Prognosis of patients with left ventricular dysfunction, with and without viable myocardium after myocardial infarction. Relative efficacy of medical therapy and revascularization.
Authors: Lee K S , Marwick T H , Cook S A , Go R T , Fix J S , James K B , Sapp S K , MacIntyre W J , Thomas J D 
Published: June 2012

BACKGROUND
The uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG-) myocardium. Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined. The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcome.

METHODS AND RESULTS
One hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging. After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients were followed clinically for 17 +/- 9 months. Four groups were defined: patients with FDG+ dysfunctional myocardium who were revascularized (n = 49) or treated medically (n = 21) and those with FDG- segments who were revascularized (n = 19) or treated medically (n = 40). The groups of patients with FDG+ or FDG- findings, with and without revascularization, did not differ with respect to known determinants of postinfarction prognosis: age, left ventricular ejection fraction, or the prevalence of multivessel disease. Nonfatal ischemic events occurred in 48% of medically treated FDG+ patients compared with 8% of revascularized patients with FDG+ tissue (P < .001) and 5% of patients with FDG- myocardium (P < .001). Thirteen patients died from cardiac causes; 11 (85%) had a left ventricular ejection fraction of < 30%, and these patients were evenly distributed between FDG+ and FDG- groups. Using Cox's proportional hazards model, only the presence of FDG+ myocardium (odds ratio, 12.9; P < .001) and the absence of revascularization (odds ratio, 5.8; P = .002) independently predicted ischemic events, while only age (P = .02) and ejection fraction (P < .001) but not the presence of viable myocardium were predictive of death.

CONCLUSIONS
Residual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized. Despite this association, age and left ventricular dysfunction remained the strongest predictors of cardiac death after myocardial infarction in these patients with a spectrum of left ventricular dysfunction.
Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study. Studio Trapidil versus Aspirin nella Restenosi Coronarica.
Authors: Maresta A , Balducelli M , Cantini L , Casari A , Chioin R , Fabbri M , Fontanelli A , Monici Preti P A , Repetto S , De Servi S 
Published: June 2012

BACKGROUND
Trapidil is an antiplatelet drug with specific platelet-derived growth factor antagonism and antiproliferative effects in the rat and rabbit models after balloon angioplasty.

METHODS AND RESULTS
The Studio Trapidil versus Aspirin nella Restenosi Coronarica (STARC) is a multicentric, randomized, double-blind trial to assess the effects of trapidil in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either trapidil 100 mg TID or aspirin at the same dosage at least 3 days before angioplasty and for 6 months thereafter. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed with manual calipers. Of the initial 384 patients recruited, 254 were evaluable for restenosis analysis (128 trapidil, 126 aspirin). Restenosis, defined as a loss of initial percent gain after PTCA of at least 50% (primary end point), occurred in 24.2% of the trapidil group and 39.7% of the aspirin group (P < .01). A similar result was obtained when restenosis per vessel was considered (trapidil, 23.3%; aspirin, 36.9%; P = .018). Clinical events at follow-up were similar in the two groups except that recurrent angina was significantly more frequent in the aspirin group, 43.7% versus 25.8% in the trapidil group (P < .01). Trapidil was well tolerated: only 6 patients had to discontinue the drug because of side effects, which was not different from the aspirin group.

CONCLUSIONS
Trapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter.
Four-year experience with Palmaz-Schatz stenting in coronary angioplasty complicated by dissection with threatened or present vessel closure.
Authors: Schömig A , Kastrati A , Mudra H , Blasini R , Schühlen H , Klauss V , Richardt G , Neumann F J 
Published: June 2012

BACKGROUND
Abrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) is associated with major adverse events. Different surgical and nonsurgical approaches have been advocated to treat or prevent this complication. This study summarizes our 4-year experience with Palmaz-Schatz stenting for the management of 339 patients with present or threatened occlusion after PTCA.

METHODS AND RESULTS
Stent implantation was attempted in a total of 339 and 4959 patients with PTCA during the study period and was successful in 327 (96.5%). During the follow-up, events like death, myocardial infarction, need for revascularization (bypass surgery and repeat in-stent angioplasty), and major vascular complications were recorded. Angiographic follow-up at 6 months was performed in 89.3% of the eligible patients. As part of an initial policy, stenting was intended as a bridge to nonemergency bypass surgery in 26 patients. In 301 patients for whom stenting was intended as permanent treatment, early clinical course (first 4 weeks) was characterized by a 1.3% cardiac mortality and a 4.0% nonfatal myocardial infarction rate; bypass surgery was necessary in 1%, and 6.3% required early repeat PTCA. Surgical repair for peripheral vascular complications was required in 5.6%, and major bleeding events were encountered in 9%. The incidence of subacute stent closure was 6.9%, with subsequent recanalization successful in 86%; subacute stent closure was predicted by presence of vessel occlusion before stenting and localization of the stent in a vessel other than the right coronary artery. Survival rate at 2 years was 95.4%, survival without myocardial infarction was 91.1%, and event-free survival was 70.7%. Survival at 2 years was lower for patients with stents in bypass vein grafts and with myocardial infarction after stenting. Six-month control angiography revealed a restenosis rate of 29.6%.

CONCLUSIONS
Patients with present or threatened occlusion after PTCA may benefit from Palmaz-Schatz stenting. It is associated with a low mortality and myocardial infarction rate and with a long-term event-free rate comparable to that of uncomplicated PTCA.
Increased coronary perforation in the new device era. Incidence, classification, management, and outcome.
Authors: Ellis S G , Ajluni S , Arnold A Z , Popma J J , Bittl J A , Eigler N L , Cowley M J , Raymond R E , Safian R D , Whitlow P L 
Published: June 2012

BACKGROUND
The incidence of coronary perforation using new percutaneous revascularization techniques may be increased compared with PTCA. Still, perforation is uncommonly reported, and the optimal management and expected outcome remain unknown. The objectives of the study were to determine the incidence of coronary perforation using balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA) and new revascularization techniques and to develop optimal strategies for its management based on classification and outcome.

METHODS AND RESULTS
Eleven sites with frequent use of new revascularization devices and prospective coding of consecutive procedures for coronary perforation during 1990 to 1991 contributed to a perforation registry. Patients with perforation were matched by device with an equal-sized cohort without perforation. Data were collected centrally, and all procedural cineangiograms were reviewed at a core angiographic laboratory. A classification scheme based on angiographic appearance of the perforation (I, extraluminal crater without extravasation; II, pericardial or myocardial blushing; III, perforation > or = 1-mm diameter with contrast streaming; and cavity spilling) was evaluated as a predictor of outcome and as a basis for management. Perforation was observed in 62 of 12,900 procedures reported (0.5%; 95% confidence interval, 0.4% to 0.6%), more commonly with devices intended to remove or ablate tissue (atherectomy, laser) than with PTCA (1.3%, 0.9% to 1.6% versus 0.1%, 0.1% to 0.1%; P < .001). The perforation population was notable for its advanced age (67 +/- 10 years) and high incidence of female sex (46%) (both P < .001 compared with patients without perforation). Perforation could be treated expectantly or with PTCA but without cardiac surgery in 85%, 90%, and 44% of class I, II, and III perforations, respectively. Class I perforations (n = 13, 21%) were associated with death in none, myocardial infarction in none, and tamponade in 8%. The incidences of these adverse events were 0%, 14%, and 13% in class II perforations (n = 31, 50%) and 19%, 50%, and 63% in non-cavity spilling class III perforations, respectively (n = 16, 26%). Two of the 15 instances of cardiac tamponade (13%) were delayed, occurring within 24 hours after dismissal from the catheterization laboratory.

CONCLUSION
The incidence of perforation, while low, is increased with new devices. Women and the elderly are at highest risk. The clinical risk after perforation can be classified angiographically, but even low-risk perforations occasionally have poor clinical outcome. Patients should be observed for delayed cardiac tamponade for at least 24 hours.
Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy. Relation to symptoms and prognosis.
Authors: Rihal C S , Nishimura R A , Hatle L K , Bailey K R , Tajik A J 
Published: June 2012

BACKGROUND
Dilated cardiomyopathy is an important cause of morbidity and mortality among patients with congestive heart failure. Hemodynamic and prognostic characterization are critical in guiding selection of medical and surgical therapies.

METHODS AND RESULTS
A cohort of 102 patients with the clinical diagnosis of dilated cardiomyopathy who underwent echocardiographic examination between 1986 and 1990 was identified and followed up through July 1, 1991. Patients with moderate or severe symptoms had lower indices of systolic function and greater left atrial and right ventricular dilation. Mitral inflow Doppler signals were characterized by a restrictive left ventricular filling pattern. In multivariate logistic regression analysis, deceleration time, ejection fraction, and peak E velocity were independently associated with symptom status. Over a mean follow-up of 36 months, 35 patients died. Kaplan-Meier estimated survival at 1, 2, and 4 years was 84%, 73%, and 61%, respectively, and was significantly poorer than that of an age- and sex-matched population. The subgroup with an ejection fraction < 0.25 and deceleration time < 130 milliseconds had a 2-year survival of only 35%. The subgroup with ejection fraction < 0.25 and deceleration time > 130 milliseconds had an intermediate 2-year survival of 72%, whereas patients with an ejection fraction > or = 0.25 had 2-year survivals > or = 95% regardless of deceleration time. In multivariate analysis, ejection fraction and systolic blood pressure were independently predictive of subsequent mortality. Mitral deceleration time was significant in univariate analysis.

CONCLUSIONS
In patients with the clinical diagnosis of dilated cardiomyopathy, markers of diastolic dysfunction correlated strongly with congestive symptoms, whereas variables of systolic function were the strongest predictors of survival. Consideration of both ejection fraction and deceleration time allowed identification of subgroups with divergent long-term prognoses.
Results and efficiency of programmed ventricular stimulation with four extrastimuli compared with one, two, and three extrastimuli.
Authors: Hummel J D , Strickberger S A , Daoud E , Niebauer M , Bakr O , Man K C , Williamson B D , Morady F 
Published: June 2012

BACKGROUND
Conventional programmed ventricular stimulation protocols are inefficient compared with more recently proposed protocols. The purpose of the present study was to determine if additional efficiency could be derived from a 6-step programmed ventricular stimulation protocol that exclusively uses four extrastimuli.

METHODS AND RESULTS
The subjects were 209 consecutive patients with coronary artery disease and documented sustained monomorphic ventricular tachycardia, nonsustained ventricular tachycardia, aborted sudden death, or syncope. These patients underwent 159 electrophysiological tests in the absence of antiarrhythmic drug therapy and 105 electrophysiological tests in the presence of antiarrhythmic therapy. Programmed stimulation was performed with two protocols in random order in each patient. Both protocols used an eight-beat drive train, 4-s intertrain pause, and basic drive cycle lengths of 350, 400, and 600 ms. The 6-step protocol started with coupling intervals of 290, 280, 270, and 260 ms, which were shortened simultaneously in 10-ms steps until S2 was refractory. The 18-step protocol used one, two and three extrastimuli in conventional sequential fashion. The end points were 30 s of sustained monomorphic ventricular tachycardia, two episodes of polymorphic ventricular tachycardia requiring cardioversion, or completion of the protocol at two right ventricular sites. There was no significant difference in the yield of sustained monomorphic ventricular tachycardia using the two protocols, regardless of the clinical presentation or treatment with antiarrhythmic drugs. Polymorphic ventricular tachycardia occurred with the 18-step protocol twice as frequently as with the 6-step protocol (6% versus 3%, P < .001). The duration of the 18-step protocol was significantly longer than that of the 6-step protocol in patients with inducible ventricular tachycardia (5.5 +/- 7 versus 2.3 +/- 2 minutes, P < .001), as well as in patients without inducible ventricular tachycardia (25.4 +/- 7 versus 6.9 +/- 2 minutes, P < .001).

CONCLUSION
A stimulation protocol that exclusively uses four extrastimuli improves the specificity and efficiency of programmed ventricular stimulation without compromising the yield of monomorphic ventricular tachycardia in patients with coronary artery disease.
Nonthoracotomy- versus thoracotomy-implantable defibrillators. Intention-to-treat comparison of clinical outcomes.
Authors: Kleman J M , Castle L W , Kidwell G A , Maloney J D , Morant V A , Trohman R G , Wilkoff B L , McCarthy P M , Pinski S L 
Published: June 2012

BACKGROUND
Nonthoracotomy-implantable cardioverter/defibrillator (ICD) systems may represent a significant advance in the treatment of patients with life-threatening ventricular arrhythmias, but their merits relative to those of the well-established thoracotomy systems remain largely unknown. The objective of this study was to compare the short- and long-term clinical outcomes after attempted ICD implantation via a nonthoracotomy versus thoracotomy approach in similar groups of patients.

METHODS AND RESULTS
Between September 1990 and December 1992, 212 consecutive patients underwent attempted ICD system implantation without concomitant cardiac surgery at a single institution. Approach selection was not randomized but rather was based primarily on hardware availability. Primary comparisons of short- and long-term outcome were performed according to the "intention-to-treat" principle. Implantation was attempted via a nonthoracotomy approach in 120 patients (57%) and via a thoracotomy approach in 92 patients (43%). Prior cardiac surgery was more prevalent in the nonthoracotomy patients; otherwise, groups did not differ significantly in terms of prognostically relevant clinical characteristics. Nonthoracotomy implantation was successful in 101 patients (84%). After crossover to thoracotomy implantation (14 patients), the eventual success rate for ICD system implantation was 96% in the nonthoracotomy group. Thoracotomy implantation was successful in 89 patients (97%). Operative mortality was 3.3% in the nonthoracotomy and 4.3% in the thoracotomy groups (P = .73). Nonthoracotomy group patients were less likely to experience postoperative congestive heart failure (6% versus 16%; P = .02) or supraventricular arrhythmia (6% versus 18%; P = .004) and had significantly shorter postoperative intensive care and total hospitalization. Total hospital costs were significantly lower in the nonthoracotomy group ($32,205 versus $37,265; P = .001). After a follow-up of 16 +/- 9 months, there were 17 deaths in the nonthoracotomy group (none sudden) and 12 deaths in the thoracotomy group (1 sudden). One- and 2-year Kaplan-Meier survival probabilities were .87 (95% CI, .78 to .91) and .80 (95% CI, .68 to .88) in the nonthoracotomy group and .90 (95% CI, .82 to .95) and .87 (95% CI, .77 to .93) in the thoracotomy group (P = .56; log-rank test).

CONCLUSIONS
Nonthoracotomy ICD implantation is associated with reduced surgical morbidity, postoperative hospital care requirement, and hospital costs and has similar efficacy in preventing sudden death relative to the thoracotomy approach. From these nonrandomized data, it appears that a nonthoracotomy approach should be considered preferable in most patients requiring ICD therapy.
Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation.
Authors: Gilligan D M , Panza J A , Kilcoyne C M , Waclawiw M A , Casino P R , Quyyumi A A 
Published: June 2012

BACKGROUND
Endothelium-derived nitric oxide is an important modulator of resting vascular tone in animals and humans. However, the contribution of nitric oxide to exercise-induced vasodilation is unknown.

METHODS AND RESULTS
The effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on exercise-induced vasodilation was studied in 18 healthy subjects (mean +/- SD, 40 +/- 10 years; 10 women). Acetylcholine was used to test the efficacy of L-NMMA in inhibiting stimulation of nitric oxide synthesis and sodium nitroprusside to test the specificity of L-NMMA in inhibiting endothelium-dependent vasodilation. Intermittent handgrip exercise and infusions of acetylcholine and sodium nitroprusside were performed during intra-arterial infusion of 5% dextrose (control) and L-NMMA (4 to 16 mumol/min). Forearm blood flow was determined by strain-gauge plethysmography. Forearm oxygen extraction was measured from arterial and venous oxygen saturations. In a separate study, 10 subjects performed exercise during infusions of 5% dextrose, L-arginine (the substrate for nitric oxide production), and D-arginine (the stereoisomer that is not a substrate for nitric oxide production). L-NMMA reduced exercise blood flow by 7 +/- 13% (P = .04), increased exercise resistance by 18 +/- 20% (P = .02), and increased exercise oxygen extraction by 16 +/- 17% (P < .001). The degree of inhibition of acetylcholine-induced vasodilation with L-NMMA correlated positively with the degree of reduction in exercise blood flow (r = .55, P = .02). The highest dose of L-NMMA (16 mumol/min) produced the greatest effect; exercise blood flow was reduced by 11 +/- 14% (P = .03), and vascular resistance increased by 26 +/- 23% (P = .005). L-NMMA did not affect the forearm vasodilation produced by sodium nitroprusside. Exercise blood flow, resistance, and oxygen extraction were not significantly modified by infusions of either L- or D-arginine.

CONCLUSIONS
Inhibition of nitric oxide synthesis reduces exercise-induced vasodilation in the human forearm, indicating that nitric oxide plays a role in exercise-induced vasodilation. Increased availability of nitric oxide substrate does not enhance exercise-induced vasodilation in healthy subjects. These findings have important implications for disease states in which endothelium-derived nitric oxide production is impaired.