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Initial results on visualization of coronary artery stents at multiple heart rates on a moving heart phantom using 64-MDCT.

OBJECTIVE: Evaluation of the image quality of coronary artery stents at various heart rates using Multi Detector Computed Tomography (MDCT). METHODS: Nine different coronary stents were attached to a moving heart phantom and scanned using a 64-MDCT with a rotation time of 330 milliseconds (ms). The heart rate of the phantom was varied between 0 and 115 beats per minute (bpm). Two independent methods were used to investigate image quality. After reconstruction the average Houndsfield Unit (HU) value in the stent lumen was measured in the longitudinal and the cross-sectional plane. The stent images were then presented to two radiologists. The radiologists were asked to rank the images from good to bad based on lumen visibility and overall image quality. A second ranking was obtained using the CT density values. Finally two rankings were compared. RESULTS: Compared to the value for air, the HU-values measured in the lumen increased by 50 to 700 HU. Average slope value in the longitudinal plane was 1.7 +/- 0.6 HU/bpm, and the average slope value in the cross-sectional plane was 1.7 +/- 0.8 HU/bpm. This shows increased attenuation with increasing heart rate and thus a negative correlation between image quality and heart rate in both planes for all stents. The ranking acquired from the radiologists resembled the measured results as they also showed a negative correlation between the two variables. Using the results of the CT density measurements an analysis was done on multi-segment reconstruction (MSR). CONCLUSION: A negative correlation between the heart rate and image quality of coronary stents was found by two independent methods. MSR showed no benefit for image quality in this study.

Air↗

Spectral composition of heart sounds before and after mechanical heart valve implantation using a modified forward-backward Prony's method.

This paper investigates the impact of the lung-thorax and heart-valve system on the overall spectral composition of the externally recorded heart sounds. The study concentrates in the case of the first and the second heart sounds for normal patients and patients before and after implantation of a mechanical valve in the mitral or aortic position. The analysis is performed using a modified forward-backward overdetermined Prony's method (MFBPM) which uses a forward-backward mean filter and a modified procedure for estimating the position of the signal poles. In terms of the normalized cross-correlation coefficient, this method has an average modeling accuracy of 99.62% for representing the first and second heart sounds and an average least square time-domain error of 0.43%. Results obtained from 40 subjects show that the condition of the native mitral or aortic valve affects mostly the distribution of the amplitudes of the spectral components, whereas the number of the spectral components or their respective relative energy remains more or less unchanged. It has been found that the amplitudes of frequency components in the range 120-250 Hz are more affected by abnormalities of native mitral valves. Furthermore, in the case of the second heart sound the region 250-400 Hz has been found to be more affected by abnormalities in the aortic valve. It has also been found that the mechanical prosthetic heart valve affects mostly the spectrum beyond 400 Hz. A clear difference has been observed in the frequency spectrum above 400 Hz between both normally and abnormally functioning native valves and normally functioning mechanical valves. Preliminary results in some malfunctioning cases of mechanical prosthesis suggest that spectral components beyond 400 Hz can be used to monitor the condition of these prostheses.

Adult↗

Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation.

Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.

Adult↗

Interaction between direct sympathetic and vagus nerve stimulation on heart rate in the isolated rabbit heart.

The interaction between the effects of vagus nerve stimulation (VS) and sympathetic stimulation (SS) on intrinsic heart rate was studied in the novel innervated isolated rabbit heart preparation. The effects of background VS, at different frequencies--2 Hz (low), 5 Hz (medium), 7 Hz (high)--on the chronotropic effects of different frequencies of SS--2 Hz (low), 5 Hz (medium), 10 Hz (high)--were studied. The experiments were repeated in the reverse direction studying the effects of different levels of background SS on the chronotropic effects of different levels of VS. Background VS reduced the overall positive chronotropic effect of SS at steady state in a frequency dependent manner and the rate of increase in heart rate during low and medium SS (but not high SS) was slowed in the presence of background VS. These results suggest that pre- and postjunctional mechanisms may be involved in the sympatho-vagal interaction on heart rate. On the other hand, the chronotropic effect of VS was enhanced in the presence of background SS. Vagal stimulation appears to play a dominant role over sympathetic stimulation in chronotropic effects on the isolated heart. The innervated isolated heart preparation is a valuable model to study the complex mechanisms underlying the interaction between sympathetic and parasympathetic stimulation on cardiac function.

Animals↗

ATP depletion and mitochondrial functional loss during ischemia in slow and fast heart-rate hearts.

In the present study, isolated dog and rat hearts were perfused in the Langendorff mode with Krebs bicarbonate buffer in the absence and presence of 10(-5) M oligomycin. The perfusion protocols employed allowed tissue pH to drop during subsequent ischemic incubations essentially as it would in blood-perfused hearts. Tissue pH, ATP, lactate, and mitochondrial respiratory function were measured during the course of subsequent zero-flow ischemic incubations. The adenosinetriphosphatase (ATPase) activities attributable to both mitochondrial and nonmitochondrial ATPases in sonicated heart homogenates and the actomyosin ATPase in isolated cardiac myofibrils were measured in both species. Consistent with earlier results with a different model in which tissue pH was buffered during the ischemic incubations [W. Rouslin, J. L. Erickson, and R. J. Solaro. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H503-H508, 1986], the inhibition of the mitochondrial ATPase in situ by oligomycin markedly slowed both tissue ATP depletion and the loss of mitochondrial function during ischemia in the dog. However, oligomycin had only a very small and transient effect on ATP depletion and mitochondrial function in the rat. This was apparently so because of the fivefold higher rate of glycolytic ATP production as well as the nearly threefold higher total nonmitochondrial ATPase activity of ischemic rat compared with ischemic dog heart. These results suggest that although the inhibition of the mitochondrial ATPase makes a major contribution to ATP conservation in ischemic dog heart, it makes only a very small contribution in rat.

Adenosine Triphosphatases↗

Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial.

BACKGROUND: Preclinical and preliminary clinical data have suggested that tumor necrosis factor-alpha (TNFalpha) may play a role in the evolution and progression of heart failure and that inhibition of TNFalpha may favorably modify the course of the disease. We evaluated the efficacy and safety of infliximab, a chimeric monoclonal antibody to TNFalpha, in patients with moderate-to-severe heart failure. METHODS AND RESULTS: One hundred fifty patients with stable New York Heart Association class III or IV heart failure and left ventricular ejection fraction <or=35% were randomly assigned to receive placebo (n=49), infliximab 5 mg/kg (n=50), or infliximab 10 mg/kg (n=51) at 0, 2, and 6 weeks after randomization and were followed-up prospectively for 28 weeks. Neither dose of infliximab improved clinical status at 14 weeks, the primary endpoint of the study, despite suppression of inflammatory markers (C-reactive protein and interleukin-6) and a modest increase in ejection fraction in the patients receiving 5 mg/kg (P=0.013). Furthermore, after 28 weeks, 13, 10, and 20 patients were hospitalized for any reason in the placebo, 5 mg/kg infliximab, and 10 mg/kg infliximab groups, respectively. The combined risk of death from any cause or hospitalization for heart failure through 28 weeks was increased in the patients randomized to 10 mg/kg infliximab (hazard ratio 2.84, 95% confidence interval 1.01 to 7.97; nominal P=0.043). CONCLUSIONS: Short-term TNFalpha antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.

Antibodies, Monoclonal↗

Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial.

BACKGROUND: beta-Blockade-induced benefit in heart failure (HF) could be related to baseline heart rate and treatment-induced heart rate reduction, but no such relationships have been demonstrated. METHODS AND RESULTS: In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate analysis of CIBIS II showed that in addition to beta-blocker treatment, BHR and HRC were both significantly related to survival and hospitalization for worsening HF, the lowest BHR and the greatest HRC being associated with best survival and reduction of hospital admissions. No interaction between the 3 variables was observed, meaning that on one hand, HRC-related improvement in survival was similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit over placebo for survival was observed to a similar extent at any level of both BHR and HRC. Bisoprolol reduced mortality in patients with sinus rhythm (relative risk 0.58, P:<0.001) but not in patients with atrial fibrillation (relative risk 1.16, P:=NS). A similar result was observed for cardiovascular mortality and hospitalization for HF worsening. CONCLUSIONS: BHR and HRC are significantly related to prognosis in heart failure. beta-Blockade with bisoprolol further improves survival at any level of BHR and HRC and to a similar extent. The benefit of bisoprolol is questionable, however, in patients with atrial fibrillation.

Adrenergic beta-Antagonists↗

The Seattle Heart Failure Model: prediction of survival in heart failure.

BACKGROUND: Heart failure has an annual mortality rate ranging from 5% to 75%. The purpose of the study was to develop and validate a multivariate risk model to predict 1-, 2-, and 3-year survival in heart failure patients with the use of easily obtainable characteristics relating to clinical status, therapy (pharmacological as well as devices), and laboratory parameters. METHODS AND RESULTS: The Seattle Heart Failure Model was derived in a cohort of 1125 heart failure patients with the use of a multivariate Cox model. For medications and devices not available in the derivation database, hazard ratios were estimated from published literature. The model was prospectively validated in 5 additional cohorts totaling 9942 heart failure patients and 17,307 person-years of follow-up. The accuracy of the model was excellent, with predicted versus actual 1-year survival rates of 73.4% versus 74.3% in the derivation cohort and 90.5% versus 88.5%, 86.5% versus 86.5%, 83.8% versus 83.3%, 90.9% versus 91.0%, and 89.6% versus 86.7% in the 5 validation cohorts. For the lowest score, the 2-year survival was 92.8% compared with 88.7%, 77.8%, 58.1%, 29.5%, and 10.8% for scores of 0, 1, 2, 3, and 4, respectively. The overall receiver operating characteristic area under the curve was 0.729 (95% CI, 0.714 to 0.744). The model also allowed estimation of the benefit of adding medications or devices to an individual patient's therapeutic regimen. CONCLUSIONS: The Seattle Heart Failure Model provides an accurate estimate of 1-, 2-, and 3-year survival with the use of easily obtained clinical, pharmacological, device, and laboratory characteristics.

Adult↗

MesP1 is expressed in the heart precursor cells and required for the formation of a single heart tube.

The Mesp1 gene encodes the basic HLH protein MesP1 which is expressed in the mesodermal cell lineage during early gastrulation. Disruption of the Mesp1 gene leads to aberrant heart morphogenesis, resulting in cardia bifida. In order to study the defects in Mesp1-expressing cells during gastrulation and in the specification of mesodermal cell lineages, we introduced a (beta)-galactosidase gene (lacZ) under the control of the Mesp1 promoter by homologous recombination. The early expression pattern revealed by (beta)-gal staining in heterozygous embryos was almost identical to that observed by whole mount in situ hybridization. However, the (beta)-gal activity was retained longer than the mRNA signal, which enabled us to follow cell migration during gastrulation. In heterozygous embryos, the Mesp1-expressing cells migrated out from the primitive streak and were incorporated into the head mesenchyme and heart field. In contrast, Mesp1-expressing cells in the homozygous deficient embryos stayed in the primitive streak for a longer period of time before departure. The expression of FLK-1, an early marker of endothelial cell precursors including heart precursors, also accumulated abnormally in the posterior region in Mesp1-deficient embryos. In addition, using the Cre-loxP site-specific recombination system, we could determine the lineage of the Mesp1-expressing cells. The first mesodermal cells that ingressed through the primitive streak were incorporated as the mesodermal component of the amnion, and the next mesodermal population mainly contributed to the myocardium of the heart tube but not to the endocardium. These results strongly suggest that MesP1 is expressed in the heart tube precursor cells and is required for mesodermal cells to depart from the primitive streak and to generate a single heart tube.

Animals↗

Non-invasive assessment of the performance of the right heart during dynamic exercise, a study of left-sided heart disease.

A simplified, non-invasive method for assessment of the performance of the right heart during supine leg exercise was described, which necessitated no more than a bicycle "ergometer" for leg exercise, a radiocardiograph for recording cardiac index (CI) and a "water" manometer for measuring cubital venous pressure (VP). Because the use of a cardiac catheter was omitted, right atrial pressure (RA), right ventricular diastolic pressure (RVd) or pulmonary arterial pressure (PA) were not measured. In 11 healthy subjects and 25 patients with primarily left-sided valvular disease and hypertension, the observed shift of CI-VP plot with exercise was similar to the published records of exercise-induced shift of CI-RA plot or CI-RVd plot in normal subjects and the same types of heart disease. With levels of load used in this study, a dividing line separating normal from abnormal elevation of VP during supine leg exercise (deltaVP) could be drawn at deltaVP = 35 mm H2O, because (1) none of the healthy subjects had deltaVP in excess of 35 mm H2O and (2) in these types of heart disease, deltaVP in excess of 35 mm H2O was always associated with a "subnormal" increase in CI (deltaCI less than 0.8 lit. min-1. M-2) with exercise, except in a few cases who appeared, clinically, to be in what may be termed "latent heart failure". Factors probably responsible for an impaired pumping ability of the right heart during exercise in left-sided heart disease were discussed, in relation to deltaVP.

Adult↗

Denopamine (beta 1-selective adrenergic receptor agonist) and isoproterenol (non-selective beta-adrenergic receptor agonist) equally increase heart rate and myocardial oxygen consumption in dog heart.

The effects of denopamine (a beta 1-selective adrenergic receptor agonist) and isoproterenol (a non-selective beta-adrenergic receptor agonist) on heart rate, left ventricular contractility, and left ventricular oxygen consumption (VO2) at the same left ventricular volume were compared in excised cross-circulated dog hearts. Denopamine and isoproterenol increased heart rate and VO2 to a comparable extent at a comparably increased contractility. Moreover, the oxygen cost of contractility which quantifies VO2 for excitation-contraction coupling was the same between the two agents. These findings contradict the previously reported smaller increases in heart rate and VO2 by denopamine than by isoproterenol in open-chest dog hearts, which have been mainly attributed to the beta 1-selectivity of denopamine. Our results suggest that in isolated and denervated hearts, the degree of beta 1-selectivity of a beta-agonistic agent does not directly determine the relative potencies of its inotropic and chronotropic effects and the oxygen cost of contractility.

Adrenergic beta-Agonists↗

[The mode of cardiac action of cardiotonic steroids isolated from Toad Cake in perfused working guinea-pig heart and effect of cinobufagin on experimental heart failure].

The effects of bufadienolides (bufalin, bufotalin, cinobufagin, cinobufotalin, gamabufotalin and resibufogenin) isolated from Toad Cake was compared to that of cardenolides (digitoxin and ouabain) on cardiac function in a guinea-pig working heart preparation. All the steroids showed the cardiotonic effect in a concentration-dependent manner, and the minimum threshold concentration was 10(-8) M for bufalin, cinobufagin, gamabufotalin and digitoxin and 10(-7) M for bufotalin, cinobufotalin and ouabain. In addition, the order of maximum efficacy of cardiotonic action was as follows: cinobufagin (3 X 10(-7) M) = ouabain (3 X 10(-7) M) greater than digitoxin (1 X 10(-7) M) = gamabufotalin (3 X 10(-7) M) greater than cinobufotalin (3 X 10(-7) M) greater than bufotalin (1 X 10(-7) M). The effect of cinobufagin was examined on experimentally induced heart failure caused by acute local ischemia through ligation of the left anterior descending coronary artery in perfused guinea-pig heart. Cinobufagin (3 X 10(-7) M) and digitoxin (1 X 10(-7) M) reestablished the coronary flow of perfused guinea-pig heart to 90% and 98% of the level prior to the coronary artery ligation. The cardiac output and left ventricular pressure of perfused heart were increased to the level prior to the acute local ischemia, and the left ventricular work was increased by cinobufagin (3 X 10(-7) M) and digitoxin (1 X 10(-7) M) to 108% and 106%, respectively, of the pre-ligation level. These results indicate that cinobufagin possesses strong cardiotonic action, similar, to digitoxin, in experimentally induced heart failure due to acute local ischemia.

Animals↗

The effect of adrenomedullin, amylin fragment 8-37 and calcitonin gene-related peptide on contractile force, heart rate and coronary perfusion pressure in isolated rat hearts.

The effect of human adrenomedullin, human amylin fragment 8-37 (amylin 8-37) and rat calcitonin gene-related peptide (CGRP) on contractile force, heart rate and coronary perfusion pressure has been investigated in the isolated perfused rat hearts. Adrenomedullin (2x10(-10), 2x10(-9) and 2x10(-8) M) produced a significant decrease in contractile force and perfusion pressure, but only the peptide caused a decline in heart rate at the highest dose. Amylin (10(-9), 10(-8) and 10(-7) M) significantly increased and then decreased contractile force. Two doses of amylin (10(-8) and 10(-7) M) induced a significant increase in heart rate, however amylin did not change perfusion pressure in all the doses used. Rat alpha CGRP (10(-8), 10(-7) and 10(-6) M) evoked a slight decline in contractile force following a significant increase in contractile force induced by the peptide. CGRP in all the doses raised heart rate and lowered perfusion pressure. Our results suggest that adrenomedullin has negative inotropic, negative chronotropic and coronary vasodilator actions. Amylin produces a biphasic inotropic effect and evokes a positive chronotropy. CGRP causes positive inotropic, positive chronotropic and vasodilatory effects in isolated rat hearts.

Adrenomedullin↗

Circadian rhythm of blood pressure and heart rate in cardiopathic patients before and after heart transplantation.

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitorings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation, the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.

Adult↗

[Heart function and clinical observations of patients with severe congestive heart failure treated with milrinone].

To evaluate the clinical effects of milrinone in patients with severe heart failure, heart function and clinical observations were performed on 25 patients with severe congestive heart failure treated with domestic intravenous milrinone for 15 days. Results showed that the total response rate to milrinone was 96% while 60% of them had significant improvement. Heart function and diameter of left atrial, left ventricle, and right ventricle were measured by pulsed Doppler and M-mode echocardiographg before and after the treatment. The systolic function of the left ventricle (such as SV, CO, EF, FS, IVST, PLVWT) was significantly improved. The diastolic function of the left ventricle (such as E peak, A peak, IRT) was also improved. Diameter of left atrial, left ventricle, and right ventricle was significantly reduced. The heart rate and blood pressure remained unchanged. No obvious side-effect was found in our observation. The domestic intravenous milrinone is a drug of choice for the management of patients with severe congestive heart failure.

Adult↗

[Is heart rate reduction beneficial to patients with heart insufficiency? Focus on beta-blockade].

The aim of this review was to assess the effect of pharmacological reduction of the heart rate on prognosis in patients with chronic heart failure. Although a high heart rate is associated with a reduced life expectancy and causes a number of unwanted pathophysiological effects on the failing heart, there is no documentation that the beneficial effect of beta-blockers or other heart failure agents on survival is mediated through a reduction in heart rate.

Adrenergic beta-Antagonists↗

[Refractory heart failure. Myocardial revascularization as alternative to heart transplantation].

Coronary artery disease is the most common cause of heart failure in the western world. Due to shortage of donors, heart transplantation is not a realistic treatment for the great majority of patients with heart failure, while surgical revascularization is a valuable alternative in selected patients. Several variables have to be taken into account in order to appropriately identify patients with severe left ventricular dysfunction who are likely to benefit from myocardial revascularization. The recovery of cardiac function can be expected only in patients with sufficiently large areas of hibernating myocardium, particularly when the contractile reserve is documented. The anatomy of the coronary arteries should be suitable for coronary bypass grafting and provide a good run-off. Patients with an excessively dilated heart, with signs and symptoms of right heart failure and significant pulmonary hypertension are not candidates for myocardial revascularization. An appropriate surgical strategy, also including the reduction of the left ventricular volume and/or the correction of mitral insufficiency if needed, is the key factor for a successful revascularization procedure in patients with coronary artery disease and heart failure as the predominant symptom.

Heart Failure↗

[Return of circadian blood pressure and heart rate changes in patients with heart transplants].

A loss of the circadian rhythm pattern of blood pressure (BP) and heart rate, as well as the development of hypertension have been found after heart transplantation (Htx). To study whether a return of this rhythm occurs in the long-term after Htx, we used 24-h ambulatory monitoring to study 62 patients 5 days to 6.5 years after Htx. Patients were divided into two groups (Group 1: less than 6 months after Htx (n = 30), Group 2: 6 months or more after Htx (n = 32)). Group 2 had a higher BP and heart rate, as well as a significantly higher difference between systolic day and systolic night BP than group 1. There was also a significantly higher difference in heart rate between day and night values in group 2. The return of the circadian rhythm pattern in the longer term after heart transplantation may result from partial reinnervation of the heart, although other neurohumoral factors or concomitant medication may play a role.

Adrenergic beta-Agonists↗