摘要:

BackgroundExperimental studies have demonstrated that intravenous &bgr;‐blocker administration before coronary artery occlusion significantly reduces myocardial injury. Clinical studies have shown that intracoronary (IC) propranolol administration before percutaneous coronary intervention (PCI) delays myocardial ischemia. The present study tested the hypothesis that IC propranolol treatment protects ischemic myocardium from myocardial damage and reduces the incidence of myocardial infarction (MI) and short‐term adverse outcomes after PCI.Methods and ResultsPatients undergoing PCI (n=150) were randomly assigned in a double‐blind fashion to receive IC propranolol (n=75) or placebo (n=75). Study drug was delivered before first balloon inflation via an intracoronary catheter with the tip distal to the coronary lesion. Biochemical markers were evaluated through the first 24 hours and clinical outcomes to 30 days. Evidence of MI with creatine kinase‐MB elevation after PCI was seen in 36% of placebo and 17% of propranolol patients (P=0.01). Troponin T elevation was seen in 33% of placebo and 13% of propranolol patients (P=0.005). At 30 days, the composite end point of death, postprocedural MI, non‐Q‐wave MI after PCI hospitalization, or urgent target‐lesion revascularization occurred in 40% of placebo versus 18% of propranolol patients (hazard ratio 2.14, 95% CI 1.24 to 3.71,P=0.004).ConclusionsIC administration of propranolol protects the myocardium during PCI, significantly reducing the incidence of MI and improving short‐term clinical outcomes. (Circulation.2003;107:2914‐2919.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundAtrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality.Methods and ResultsWe studied participants in the Framingham Study with new‐onset AF or CHF. Multivariable Cox proportional hazards models with time‐dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person‐years, and the incidence of AF among CHF subjects was 54 per 1000 person‐years. In AF subjects, the subsequent development of CHF was associated with increased mortality (men: HR 2.7; 95% CI, 1.9 to 3.7; women: HR 3.1; 95% CI, 2.2 to 4.2). Similarly, in CHF subjects, later development of AF was associated with increased mortality (men: HR 1.6; 95% CI, 1.2 to 2.1; women: HR 2.7, 95% CI, 2.0 to 3.6). Preexisting CHF adversely affected survival in individuals with AF, but preexisting AF was not associated with adverse survival in those with CHF.ConclusionsIndividuals with AF or CHF who subsequently develop the other condition have a poor prognosis. Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted. (Circulation.2003;107:2920‐2925.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundAtrial fibrillation (AF) is frequently encountered in patients with heart failure (HF) and is also a predictor of morbidity and mortality in this population. Recent experimental studies have shown electrical and structural atrial remodeling with increased fibrosis in animals with HF and have suggested a preventive effect of ACE inhibitors (ACEi) on the development of AF. To verify the hypothesis that ACEi prevent the development of AF in patients with HF, we conducted a retrospective analysis of the patients from the Montreal Heart Institute (MHI) included in the Studies Of Left Ventricular Dysfunction (SOLVD).Methods and ResultsClinical charts were reviewed and serial ECGs interpreted by a single cardiologist blinded to drug allocation. Patients with AF or flutter on the baseline ECG were excluded. Baseline characteristics were obtained from the SOLVD databases. The mean follow‐up was 2.9±1.0 years. Of the 391 patients randomly assigned at MHI, 374 were in sinus rhythm at the time of random assignment, with 186 taking enalapril and 188 taking placebo. Baseline characteristics were similar in the two groups except for a higher incidence of previous myocardial infarction in the enalapril group. Fifty‐five patients had AF during the follow‐up: 10 (5.4%) in the enalapril group and 45 (24%) in the placebo group (P<0.0001). By Cox multivariate analysis, enalapril was the most powerful predictor for risk reduction of AF (hazard ratio, 0.22; 95% CI, 0.11 to 0.44;P<0.0001).ConclusionsTreatment with the ACEi enalapril markedly reduces the risk of development of atrial fibrillation in patients with left ventricular dysfunction. (Circulation.2003;107:2926‐2931.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundDual‐chamber (DDDR) pacing preserves AV synchrony and may reduce heart failure (HF) and atrial fibrillation (AF) compared with ventricular (VVIR) pacing in sinus node dysfunction (SND). However, DDDR pacing often results in prolonged QRS durations (QRSd) as the result of right ventricular stimulation, and ventricular desynchronization may result. The effect of pacing‐induced ventricular desynchronization in patients with normal baseline QRSd is unknown.Methods and ResultsBaseline QRSd was obtained from 12‐lead ECGs before pacemaker implantation in MOST, a 2010‐patient, 6‐year, randomized trial of DDDR versus VVIR pacing in SND. Cumulative percent ventricular paced (Cum%VP) was determined from stored pacemaker data. Baseline QRSd <120 ms was observed in 1339 patients (707 DDDR, 632 VVIR). Cum%VP was greater in DDDR versus VVIR (90% versus 58%,P=0.001). Cox models demonstrated that the time‐dependent covariate Cum%VP was a strong predictor of HF hospitalization in DDDR (hazard ratio [HR], 2.99 [95% CI, 1.15 to 7.75] for Cum%VP >40%) and VVIR (HR 2.56 [95% CI, 1.48 to 4.43] for Cum%VP >80%). The risk of AF increased linearly with Cum%VP from 0% to 85% in both groups (DDDR, HR 1.36 [95% CI, 1.09, 1.69]; VVIR, HR 1.21 [95% CI 1.02, 1.43], for each 25% increase in Cum%VP). Model results were unaffected by adjustment for known baseline predictors of HF hospitalization and AF.ConclusionsVentricular desynchronization imposed by ventricular pacing even when AV synchrony is preserved increases the risk of HF hospitalization and AF in SND with normal baseline QRSd.(Circulation. 2003;107:2932‐2937.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundThe importance of pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) is increasingly recognized, but little is known regarding its underlying mechanisms. This phase‐contrast cine magnetic resonance (PC MR) study was performed to evaluate the relative contribution of each lung to total regurgitant volume.Methods and ResultsTwenty‐two patients with significant PR underwent a PC MR 3 to 16 years after repair of TOF. Regurgitant fraction of the main pulmonary artery was 39±10%. Regurgitant fraction of the left pulmonary artery (LPA; 46±18%) was greater than that of the right pulmonary artery (34±16%;P=0.002). The average contribution of the LPA to the total regurgitant flow volume was 54±19%, whereas its average contribution to the total forward flow volume was 44±13% (P=0.002). In 4 patients, regurgitant flow in the LPA accounted for 75% to 100% of the total regurgitant flow. There was a linear relationship between regurgitant fraction and fraction of the regurgitant flow duration in the main pulmonary artery (P<0.001) and right pulmonary artery (P=0.001) but not in the LPA (P=0.129).ConclusionsPR after repair of TOF is commonly associated with differential regurgitation in the branch pulmonary arteries, which is usually greater in the LPA. Although the cause of this disparity requires further investigation, those patients with a significant unilateral contribution to total PR may be amenable to localized techniques to reduce regurgitation. (Circulation.2003;107:2938‐2943.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundLoss‐of‐function mutations in the ATP‐binding cassette (ABCA)‐1 gene locus are the underlying cause for familial hypoalphalipoproteinemia, providing a human isolated low‐HDL model. In these familial hypoalphalipoproteinemia subjects, we evaluated the impact of isolated low HDL on endothelial function and the vascular effects of an acute increase in HDL.Methods and ResultsIn 9 ABCA1 heterozygotes and 9 control subjects, vascular function was assessed by venous occlusion plethysmography. Forearm blood flow responses to the endothelium‐dependent and ‐independent vasodilators serotonin (5HT) and sodium nitroprusside, respectively, and the inhibitor of nitric oxide synthaseNG‐monomethyl‐Larginine (L‐NMMA) were measured. Dose‐response curves were repeated after systemic infusion of apolipoprotein A‐I/phosphatidylcholine (apoA‐I/PC) disks. At baseline, ABCA1 heterozygotes had decreased HDL levels (0.4±0.2 mmol/L;P<0.05), and their forearm blood flow responses to both 5HT (maximum, 49.0±10.4%) and L‐NMMA (maximum, ‐22.8±22.9%) were blunted compared with control subjects (bothP≤0.005). Infusion of apoA‐I/PC disks increased plasma HDL to 1.3±0.4 mmol/L in ABCA1 heterozygotes, which resulted in complete restoration of vasomotor responses to both 5HT and L‐NMMA (bothP≤0.001). Endothelium‐independent vasodilation remained unaltered throughout the protocol.ConclusionsIn ABCA1 heterozygotes, isolated low HDL is associated with endothelial dysfunction, attested to by impaired basal and stimulated NO bioactivity. Strikingly, both parameters were completely restored after a single, rapid infusion of apoA‐I/PC. These findings indicate that in addition to its long‐term role within reverse cholesterol transport, HDL per se also exerts direct beneficial effects on the arterial wall.(Circulation. 2003;107:2944‐2948.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundNorepinephrine transporter (NET) inhibition increases the responsiveness to vasoactive medications and attenuates the response to sympathetic stimuli. The phenomenon may be a result of impaired regulation of sympathetic vasomotor tone.Methods and ResultsWe studied the effects of the selective NET blocker reboxetine and placebo on baroreflex control of heart rate (HR) and sympathetic traffic in a randomized, double‐blind, crossover manner in healthy subjects. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1 hour before testing. ECGs were measured for HR, brachial and finger blood pressure (BP), and muscle sympathetic nerve activity (MSNA). Sympathetic and parasympathetic baroreflex slopes were determined by use of incremental phenylephrine and nitroprusside infusions. The dose to reach BP changes of 12.5 mm Hg was significantly lower during NET inhibition (0.25 versus 0.64 &mgr;g • kg‐1• min‐1phenylephrine and 0.40 versus 1.10 &mgr;g • kg‐1• min‐1nitroprusside,P<0.01). Baroreflex control of HR was similar (16 ms/mm Hg with placebo versus 14 ms/mm Hg with reboxetine) but reset to higher BP values. MSNA and sympathetically mediated low‐frequency BP oscillations were profoundly reduced at baseline and failed to increase sufficiently during nitroprusside infusion. Reboxetine attenuated BP and MSNA responses to cold pressor testing.ConclusionsNET inhibition profoundly and selectively reduces baroreflex control of sympathetic vasomotor tone and attenuates the responsiveness to sympathetic stimuli. The reduction in baroreflex buffering increases the sensitivity to vasoactive medications. Therefore, our findings represent a novel mechanism for drug interactions. (Circulation.2003; 107:2949‐2954.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundHepatocyte growth factor/scatter factor (HGF/SF) can sufficiently and independently induce pathophysiological angiogenesis. However, the treatment strategies have mostly been unsuccessful. The present study is the first to evaluate the possible targeting of downstream signals for the inhibition of HGF/SF‐induced angiogenesis.Methods and ResultsIn a multichannel scratch assay with human endothelial cells (ECs), HGF/SF induced a strong and prolonged activation of MAPK and cell proliferation that was inhibited by PD98059 and LY294002/wortmannin, selective inhibitors of MAPK and PI3K signaling modules, respectively. Western blotting demonstrated a temporal relation between the activation of the two pathways. Chemical inhibition of the PI3K and MAPK signals inhibited HGF/SF‐induced chemoinvasion of ECs in vitro and blocked the HGF/SF‐induced neovascularization into a polymer scaffold in vivo, as quantified by vessel counts and the clearance of radioactive133Xe.ConclusionsThese data indicate that MEK and PI3K inhibitors represent a promising approach to the clinical management of pathological conditions characterized by overt HGF/SF‐induced angiogenesis. (Circulation. 2003;107: 2955‐2961.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundIt has been hypothesized that because of its rapid heart rate, the intact murine heart functions near maximal contractility in the basal state. If this hypothesis is correct, then the fast and slow components of myocardial length‐dependent activation should be blunted compared with larger mammals.Methods and ResultsMice (n=24) were anesthetized, and via an open chest, LV pressure‐volume relationships were determined by a dual‐frequency conductance catheter system. Baseline pressure‐volume relationships were determined during transient occlusion of the inferior vena cava, and repeat measurements were made after 1 (n=10) and 7 (n=21) minutes of sustained aortic occlusion. Control experiments were performed in a subset of mice (n=3). For baseline to 1 minute, an increase in afterload (maximal pressure 95±9 to 126±7 mm Hg;P<0.001) and effective arterial elastance (5.9±3.1 to 9.2±3.9 mm Hg/μl;P<0.001) resulted in an increase in end‐diastolic volume (31±8 to 35±9 μL;P<0.001). The result was maintenance of stroke volume (17±6 to 15±6;P=NS) owing to an increase in contractility (leftward shift in V100[the volume of end‐systolic elastance at 100 mm Hg], 24±9 to 16±5 μL;P<0.001). No additional augmentation of systolic function was found at 7 minutes.ConclusionsThis study demonstrates that the fast phase of length‐dependent activation is intact but not the slow phase, consistent with murine myocardium functioning near maximal contractility in the basal state. (Circulation.2003;107: 2962‐2968.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundWe hypothesize that 2 tendon‐like anterior basal stay chords, which remain taut during the entire cardiac cycle, limit the motion of the anterior mitral leaflet.Methods and ResultsSonomicrometric crystals were implanted in 6 sheep at the insertion of stay chords at anterior mitral leaflet (S1 and S2), papillary muscle tips, fibrous trigones, mitral annulus, and the tip of the anterior leaflet (AL). Distances between crystals were recorded before and after section of stay chords. During the cardiac cycle, the angle &agr; between mitral annulus and AL changed by +54.2±12.4 degrees; the angles between mitral annulus and S1 (&bgr;1) changed by +25.7±14.6 degrees, and between mitral annulus and S2 (&bgr;2) by +20.4±7.8 degrees. During diastole, AL twice crossed the virtual plane formed by the stay chords: during E‐wave by a maximum of 6.5 mm (mean, 2.5±2.2 mm) and during A‐wave by a maximum of 3.2 mm (mean, 1.7±0.9 mm). After section of both stay chords, total anterior mitral leaflet motion increased as follows: AL, +6.9±3.4 degrees; S1, +13.1±4.4 degrees; and S2, +30.9±11.7 degrees (P<0.05).ConclusionsAlthough the lateral movement of anterior mitral leaflet is limited by stay chords, the midportion moves unimpaired toward the septum, like a sail, between the 2 stay chords during diastole. A diastolic left ventricular‐inflow and systolic left ventricular‐outflow funnel mechanism is created. Stay chord section increased lateral anterior mitral leaflet movement. (Circulation. 2003;107:2969‐2974.)

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID