摘要:

Background—Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation (IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock.Methods and Results—We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998. The hospitals were divided into tertiles (low–, intermediate–, and high–IABP volume hospitals) according to the number of IABPs performed at the given hospital per year. The median number of IABPs performed per hospital per year was 3.4, 12.7, and 37.4 IABPs at low-, intermediate-, and high-volume hospitals, respectively. Of those patients who underwent IABP, there were only minor differences in baseline patient characteristics between the 3 groups. Crude mortality rate decreased with increasing IABP volume: 65.4%, lowest volume tertile; 54.1%, intermediate volume tertile; and 50.6%, highest volume tertile (Pfor trend <0.001). This mortality difference represented 150 fewer deaths per 1000 patients treated at the high IABP hospitals. In the multivariate analysis, high hospital IABP volume for patients with acute myocardial infarction was associated with lower mortality (OR=0.71, 95% CI=0.56 to 0.90), independent of baseline patient characteristics, hospital factors, treatment, and procedures such as PTCA.Conclusions—Among the myocardial infarction patients with cardiogenic shock who underwent IABP placement, mortality rate was significantly lower at high–IABP volume hospitals compared with low–IABP volume hospitals.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Abnormal heart rate turbulence (HRT) is associated with an increased risk of mortality in the chronic phase of myocardial infarction (MI) in the prethrombolytic and thrombolytic eras. However, the impact of direct percutaneous coronary intervention (PCI) on HRT in the acute phase of MI and its association to the epicardial infarct-related arterial flow has not been examined.Methods and Results—We investigated HRT in 126 patients undergoing direct PCI for a first MI. Turbulence onset and turbulence slope were determined before reperfusion, during the initial 2 hours after reperfusion, and during hours 6 to 24 after reperfusion. HRT significantly improved after PCI. There were no significant differences in baseline clinical characteristics between Thrombolysis in Myocardial Infarction Trial classification (TIMI) 2 (n=28) and TIMI 3 (n=98) flow. After PCI, turbulence slope increased (13.2±11 to 18.1±12 ms/beat,P<0.001) and turbulence onset decreased (−0.008±0.04% to −0.023±0.04%,P<0.01) in patients with TIMI 3 flow after PCI, whereas there were no significant alterations of turbulence slope (12.2±10 to 12.8±6.5 ms/beat) and turbulence onset (−0.009±0.05% to −0.003±0.03%) in patients with TIMI 2 flow.Conclusions—The improvement of HRT after successful reperfusion is a previously unreported effect of direct PCI for acute MI, reflecting rapid restoration of baroreceptor response. The persistent impairment of HRT after PCI in patients with TIMI 2 flow indicates a sustained blunted baroreflex response and may reflect a more severe microvascular dysfunction.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—A prolonged QT interval is associated with a risk for life-threatening events. However, little is known about prognostic implications of the reverse—a short QT interval. Several members of 2 different families were referred for syncope, palpitations, and resuscitated cardiac arrest in the presence of a positive family history for sudden cardiac death. Autopsy did not reveal any structural heart disease. All patients had a constantly and uniformly short QT interval at ECG.Methods and Results—Six patients from both families were submitted to extensive noninvasive and invasive work-up, including serial resting ECGs, echocardiogram, cardiac MRI, exercise testing, Holter ECG, and signal-averaged ECG. Four of 6 patients underwent electrophysiological evaluation including programmed ventricular stimulation. In all subjects, a structural heart disease was excluded. At baseline ECG, all patients exhibited a QT interval ≤280 ms (QTc ≤300 ms). During electrophysiological study, short atrial and ventricular refractory periods were documented in all and increased ventricular vulnerability to fibrillation in 3 of 4 patients.Conclusions—The short QT syndrome is characterized by familial sudden death, short refractory periods, and inducible ventricular fibrillation. It is important to recognize this ECG pattern because it is related to a high risk of sudden death in young, otherwise healthy subjects.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that &agr;-adrenergic–blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol.Methods and Results—Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip −3.5 U for carvedilol versus −1.2 U for metoprolol and −2.2 U for placebo,P=0.15; cold pressor test 3.1±8.9 U for carvedilol versus 9.0±2.7 U for metoprolol and 8.2±5.8 U for placebo,P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups.Conclusions—Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by &agr;-adrenergic blockade.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Information is limited regarding the rates of progression to congestive heart failure (CHF) and death in individuals with asymptomatic left ventricular systolic dysfunction (ALVD). We sought to characterize the natural history of ALVD, by studying unselected individuals with this condition in the community.Methods and Results—We studied 4257 participants (1860 men) from the Framingham Study who underwent routine echocardiography. The prevalence of ALVD (visually estimated ejection fraction [EF]≤50% without a history of CHF) was 6.0% in men and 0.8% in women. During up to 12 years of follow-up, rates of CHF among subjects with normal left ventricular systolic function (EF >50%, n=4128) and ALVD (n=129) were 0.7 and 5.8 per 100 person-years, respectively. After adjustment for cardiovascular disease risk factors, ALVD was associated with a hazards ratio (HR) for CHF of 4.7 (95% CI 2.7 to 8.1), compared with individuals without ALVD. An elevated risk of CHF after ALVD was observed even in individuals without prior myocardial infarction or valvular disease, with an adjusted HR of 6.5 (CI 3.1 to 13.5). Mild ALVD (EF 40% to 50%, n=78) and moderate-to-severe ALVD (EF <40%, n=51) were associated with adjusted HRs for CHF of 3.3 (CI 1.7 to 6.6) and 7.8 (CI 3.9 to 15.6), respectively. ALVD was also associated with an increased mortality risk (adjusted HR 1.6, CI 1.1 to 2.4). The median survival of ALVD subjects was 7.1 years.Conclusion—Individuals with ALVD in the community are at high risk of CHF and death, even when only mild impairment of EF is present. Additional studies are needed to define optimal therapy for mild ALVD.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—The prosthesis used for aortic valve replacement (AVR) can be too small in relation to body size, thus causing valve prosthesis-patient mismatch (PPM) and abnormally high transvalvular pressure gradients. This study examined if there is a relation between PPM and short-term mortality after operation.Methods and Results—The indexed valve effective orifice area (EOA) was estimated for each type and size of prosthesis being implanted in 1266 consecutive patients and used to define PPM as not clinically significant if >0.85 cm2/m2, as moderate if >0.65 cm2/m2and ≤0.85 cm2/m2, and as severe if ≤0.65 cm2/m2; it was correlated with 30-day mortality and compared with other relevant variables. Moderate or severe PPM was present in 38% of patients. Thirty-day mortality was 4.6% (58/1266 patients) and the strongest independent predictors in multivariate analysis were left ventricular ejection fraction <40% (P=0.007), infectious endocarditis (P=0.002), emergent/salvage operation (P=0.002), cardiopulmonary bypass time >120 minutes (P=0.001), and PPM (P=0.003). Relative risk of mortality was increased 2.1-fold (95% confidence interval, 1.2 to 3.7) in patients with moderate PPM and 11.4-fold (4.4 to 29.5) in those with severe PPM. Moreover, risk of mortality for every category of PPM was higher in patients with a left ventricular ejection fraction <40% as compared with ≥40% (nonsignificant PPM, 2.7 versus 1.0; moderate PPM, 7.1 versus 1.8; severe PPM, 77.1 versus 11.3).Conclusion—PPM is a strong and independent predictor of short-term mortality among patients undergoing AVR, and its impact is related both to its degree of severity and the status of left ventricular function. In contrast to other risk factors, moderate-severe PPM can be largely avoided with the use of a prospective strategy at the time of operation.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—The adenosine diphosphate (ADP) receptor P2Y12plays a pivotal role in platelet aggregation, as demonstrated by the benefit conferred by its blockade in patients with cardiovascular disease. Some studies have shown interindividual differences in ADP-induced platelet aggregation responses ex vivo, but the mechanisms underlying this variability are unknown.Methods and Results—We examined ADP-induced platelet aggregation responses in 98 healthy volunteers, and we identified 2 phenotypic groups of subjects with high and low responsiveness to 2 &mgr;mol/L ADP. This prompted us to screen the recently identified Gi-coupled ADP receptor geneP2Y12for sequence variations. Among the 5 frequent polymorphisms thus identified, 4 were in total linkage disequilibrium, determining haplotypes H1 and H2, with respective allelic frequencies of 0.86 and 0.14. The number of H2 alleles was associated with the maximal aggregation response to ADP in the overall study population (P=0.007). Downregulation of the platelet cAMP concentration by ADP was more marked in 10 selected H2 carriers than in 10 noncarriers.Conclusions—In healthy subjects, ADP-induced platelet aggregation is associated with a haplotype of the P2Y12receptor gene. Given the crucial role of the P2Y12receptor in platelet functions, carriers of the H2 haplotype may have an increased risk of atherothrombosis and/or a lesser clinical response to drugs inhibiting platelet function.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Low birth weight predisposes to later coronary disease. To further elucidate the mechanisms behind this association and their timing, vascular endothelial function—a key factor in early pathophysiology of atherosclerosis—was studied in 54 infants born either before the third trimester or at term.Methods and Results—All subjects were studied at 3 months of postnatal age. A laser-Doppler technique was used to measure skin perfusion before and after transdermal iontophoresis of acetylcholine (ACh; an endothelium-dependent vasodilator). In infants born at term (n=19; birth weight range: 2230 to 4205 g), maximum perfusion after ACh was 109±8 perfusion units (PU, mean±SEM) in normal–birth weight controls compared with 56±13 PU among those who had been small for gestational age at birth (P<0.01). In infants born preterm (n=35; birth weight range, 722 to 1868 g), ACh induced similar perfusion responses among subjects appropriate for gestational age (113±16 PU) and in those small for gestational age at birth (109±19 PU).Conclusions—Impairment in human endothelial function associated with low birth weight occurs or emerges late in pregnancy. Very preterm birth attenuates this association. Different gene–environment interactions in the third trimester may contribute to this finding.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Tumor necrosis factor (TNF) is initially synthesized as a 26-kDa transmembrane protein that is enzymatically cleaved by TNF-&agr; converting enzyme (TACE) to generate a 17-kDa form of “secreted” TNF. Whereas the effects of secreted TNF in the heart have been characterized extensively, the effects of transmembrane TNF in the heart are unknown.Methods and Results—We generated lines of transgenic mice with cardiac-restricted overexpression of a noncleavable, transmembrane form of TNF. We next treated a previously generated transgenic line of mice with cardiac-restricted expression of cleavable TNF (referred to as MHCsTNF mice) with a TACE inhibitor (DPC-IDR1) to determine whether TACE inhibition would prevent the transition from concentric hypertrophy to left ventricular (LV) dilation that occurs in this line of transgenic mice. Two of the founder lines did not have a demonstrable phenotype (M-41 and M-45), whereas a third line developed a concentric hypertrophic cardiac phenotype (M-48). Characterization of the M-48 line at 6 weeks of age showed that this line developed concentric hypertrophy, with an increase in myocyte cross-sectional area and reexpression of the fetal gene program. Four weeks of TACE inhibition abrogated the LV dilation in the MHCsTNF mice and resulted in an increase in LV wall thickness and increased myocyte cross-sectional area, thus mimicking the effects observed in the mice with noncleavable, transmembrane TNF.Conclusions—These studies show that transmembrane TNF is biologically active and provokes a concentric hypertrophic cardiac phenotype, thus suggesting that posttranslational processing (ie, secretion) of TNF is responsible for the dilated cardiomyopathic phenotype in mice with targeted, cardiac-restricted overexpression of TNF.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Delivery and tracking of endomyocardial stem cells are limited by the inability to image transplanted cells noninvasively in the beating heart. We hypothesized that mesenchymal stem cells (MSCs) could be labeled with a iron fluorophore particle (IFP) to provide MRI contrast in vivo to assess immediate and long-term localization.Methods and Results—MSCs were isolated from swine. Short-term incubation of MSCs with IFP resulted in dose-dependent and efficient labeling. Labeled cells remained viable for multiple passages and retained in vitro proliferation and differentiation capacity. Labeled MSCs (104to 106cells/150 &mgr;L) were injected percutaneously into normal and freshly infarcted myocardium in swine. One, 3, and 1 animals underwent serial cardiac MRI (1.5T) for 4, 8, and 21 days, respectively. MRI contrast properties were measured both in vivo and in vitro for cells embedded in agar. Injection sites containing as few as 105MSCs could be detected and contained intact IFP-bearing MSCs on histology.Conclusions—IFP labeling of MSCs imparts useful MRI contrast, enabling ready detection in the beating heart on a conventional cardiac MR scanner after transplantation into normal and infarcted myocardium. The dual-labeled MSCs can be identified at locations corresponding to injection sites, both ex vivo using fluorescence microscopy and in vivo using susceptibility contrast on MRI. This technology may permit effective in vivo study of stem cell retention, engraftment, and migration.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID