bluuebunny/crossref_metadata_2025 huggingface dataset:
Can further benefit be achieved by adding flosequinan to patients with congestive heart failure who remain symptomatic on diuretic, digoxin, and an angiotensin converting enzyme inhibitor? Results of the flosequinan-ACE inhibitor trial (FACET).
Authors: Massie B M , Berk M R , Brozena S C , Elkayam U , Plehn J F , Kukin M L , Packer M , Murphy B E , Neuberg G W , Steingart R M
Published: June 2012

BACKGROUND

Angiotensin converting enzyme inhibitors, diuretics, and digoxin are each effective in treating congestive heart failure, but many patients remain symptom-limited on all three medications. This trial was designed to determine whether the addition of oral flosequinan, a new direct-acting arterial and venous vasodilator with possible dose-dependent positive inotropic effects, improves exercise tolerance and quality of life in such patients.

METHODS AND RESULTS

In a randomized, double-blind multicenter trial, 322 patients with predominantly New York Heart Association class II or III congestive heart failure and left ventricular ejection fractions of 35% or less, who were stabilized on a diuretic, angiotensin converting enzyme inhibitor, and digoxin, were treated with 100 mg flosequinan once daily, 75 mg flosequinan twice daily, or matching placebo. Efficacy was evaluated with serial measurements of treadmill exercise time, responses to the Minnesota Living With Heart Failure Questionnaire (LWHF), and clinical assessments during a baseline phase and a 16-week treatment period. After 16 weeks, 100 mg flosequinan once daily produced a significant increment in median exercise time (64 seconds at 16 weeks) compared with placebo (5 seconds), whereas the higher-dose flosequinan group did not show a statistically significant increase. Flosequinan (100 mg once daily) also improved the overall LWHF score significantly compared with placebo; both active therapies decreased the physical component, but 75 mg flosequinan twice daily was associated with a trend toward worsening of the emotional component. Most clinical assessments tended to improve on active therapy.

CONCLUSIONS

These results indicate that additional symptomatic benefit can be attained by adding flosequinan to a therapeutic regimen already including a converting enzyme inhibitor. Because in the future most patients will fall into this category, flosequinan is a potential adjunctive agent in the management of severe congestive heart failure. However, because recent evidence indicates that the flosequinan dose studied in the present trial has an adverse effect on survival, the benefit-to-risk ratio must be assessed in individual patients.
Contrast echocardiography for evaluation of left ventricular flow dynamics using densitometric analysis.
Authors: Mizushige K , DeMaria A N , Toyama Y , Morita H , Senda S , Matsuo H
Published: June 2012

BACKGROUND

Few data exist regarding intraventricular flow patterns in the presence of left ventricular dysfunction. Therefore, we examined the relation between intracavitary left ventricular flow dynamics and the presence of ventricular contractile abnormalities using videodensitometric analysis of transpulmonary contrast echocardiography.

METHODS AND RESULTS

Two-dimensional echocardiography was performed before, during, and after intravenous injection of sonicated albumin in 8 normal subjects, 22 patients with infarction, and 6 patients with dilated cardiomyopathy. Time-intensity curves were recorded, and disappearance half-times (in cardiac cycles) were measured for regions of interest at the mitral orifice (Ta) and mid-left ventricular cavity (Tb). We observed contrast enhancement of the left ventricular cavity in 28 of 36 patients. Ta and Tb were identical (19 beats) in all normal patients, but Tb was greater than Ta (19 versus 22 beats, P < .001) in patients with dyssynergy. Patients with dyssynergy were divided in three groups: group A, in whom Tb-Ta < or = 3; group B, in whom Tb-Ta > or = 4; and group C, which was composed of patients without contrast enhancement. Left ventricular end-diastolic dimension was similar in normal patients (46.1 mm) and group A patients (50.3 mm) but was less in each cohort than in groups B (58.7 mm) and C (64.1 mm) (all P < .01). Significant correlation was observed between Tb-Ta and both ejection fraction (r = -.67, P < .001) and wall motion index (r = .62, P < .001).

CONCLUSIONS

Clearance of contrast from the mid-left ventricular cavity is prolonged in patients with left ventricular dysfunction. This prolongation may be related to increased left ventricular diastolic volume, impaired intracavitary mixing, or paradoxical systolic flow. Delayed left ventricular contrast washout may have implications regarding the formation of left ventricular thrombi.
Regional entrainment of atrial fibrillation studied by high-resolution mapping in open-chest dogs.
Authors: Kirchhof C , Chorro F , Scheffer G J , Brugada J , Konings K , Zetelaki Z , Allessie M
Published: June 2012

BACKGROUND

It recently has been demonstrated that during atrial fibrillation, a short and variable excitable gap exists, allowing regional control of atrial fibrillation by local stimulation. In the present study, we visualized the process of excitation during regional entrainment of atrial fibrillation by rapid pacing.

METHODS AND RESULTS

In six open-chest dogs, the excitation of the left atrial free wall was mapped using a spoon-shaped mapping electrode (248 points). Episodes of atrial fibrillation were induced by burst pacing (50 Hz, 2 seconds). During atrial fibrillation, the electrograms showed rapid irregular activity with a median cycle length of 98 +/- 16 ms (mean +/- SD, n = 6). Rapid pacing in the center of the mapping electrode at intervals slightly shorter or longer than the median atrial fibrillation interval resulted in regional capture of atrial fibrillation. The window of entrainment was 16 +/- 5 ms. Mapping of atrial fibrillation showed that the left atrium was activated by fibrillatory wavelets coming from different directions. During entrainment, a relatively large area with a diameter of about 4 cm was activated by uniform wave fronts propagating away from the site of stimulation. The area of entrainment was limited by intra-atrial conduction block and by collision with fibrillation waves. Regional control of atrial fibrillation was lost by pacing either too slowly or too rapidly. In the first case, retrograde invasion of the area of entrainment by fibrillatory waves resulted in depolarization of the pacing site prior to the stimulus. Pacing too rapidly caused acceleration of atrial fibrillation by induction of local intra-atrial reentry circuits with a revolution time shorter than the pacing interval.

CONCLUSIONS

During atrial fibrillation, an area with a diameter of about 4 cm can be entrained by local pacing. The resulting reduction in fibrillating tissue mass was not sufficient to terminate atrial fibrillation. Extension of the area of entrainment was limited by intra-atrial conduction block, whereas entrainment at a too high rate resulted in acceleration of atrial fibrillation by induction of local microreentry.
Right ventricular-vascular interaction in congestive heart failure. Importance of low-frequency impedance.
Authors: Kussmaul W G , Altschuler J A , Matthai W H , Laskey W K
Published: June 2012

BACKGROUND

Vasodilator agents are widely used in congestive heart failure. These agents may have important effects on the pulsatile aspects of right ventricular hydraulic load.

METHODS AND RESULTS

Fifteen patients with severe congestive heart failure were studied during cardiac catheterization by use of high-fidelity pressure transducers and a catheter-mounted flow velocity probe. Three graded doses of nitroprusside were infused as pulmonary artery (PA) pressure and flow were continuously recorded. From Fourier transforms of signal-averaged waves, PA impedance, hydraulic power, and wave reflection indices were derived. At the highest dose of nitroprusside (66 +/- 41 micrograms/min), cardiac output was significantly improved, whereas PA mean and wedge pressure, resistance, impedance at the first harmonic, characteristic impedance, and wave reflection amplitude were all reduced. At the dose (32 +/- 20 micrograms/min) at which cardiac output first showed improvement, only PA mean pressure and first-harmonic impedance were significantly reduced. Hydraulic power cost per unit of forward flow was also lowered at this dose, despite lack of significant change in pulmonary vascular resistance. At the lowest dose of nitroprusside (11 +/- 4 micrograms/min), six patients experienced a decrease in stroke volume, whereas the other nine were either unchanged (n = 1) or showed an increase (n = 8). Multiple regression revealed that only the change in first-harmonic impedance correlated with this effect, increasing when stroke volume decreased and decreasing when stroke volume increased (P = .02). The change in first-harmonic impedance at this dose appeared to be caused by alterations in the amplitude of PA wave reflections. At higher doses, changes in mean PA pressure (but not in pulmonary vascular resistance) correlated with changes in stroke volume.

CONCLUSIONS

Nitroprusside vasodilation at low doses alters PA hemodynamics in congestive heart failure primarily through changes in low-frequency impedance. In some patients, this effect is associated with decreased stroke output. At higher doses, favorable alterations in resistance, low- and high-frequency impedance, and wave reflections all contribute to increased forward flow and decreased power requirement per unit forward flow. These findings show that ventricular-vascular interaction is importantly affected by pulmonary vasodilation and that appreciation of pulsatile properties is required to understand the effects of pulmonary vasodilation on cardiac output.
Influence of implantable cardioverter-defibrillators on the long-term prognosis of survivors of out-of-hospital cardiac arrest.
Authors: Powell A C , Fuchs T , Finkelstein D M , Garan H , Cannom D S , McGovern B A , Kelly E , Vlahakes G J , Torchiana D F , Ruskin J N
Published: June 2012

BACKGROUND

Survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction are at high risk for recurrent cardiac arrest and sudden cardiac death. The impact of the implantable cardioverter-defibrillator on long-term prognosis in these patients is uncertain.

METHODS AND RESULTS

Three hundred thirty-one survivors of out-of-hospital cardiac arrest (age, 56 +/- 13.7 years) underwent electrophysiologically guided therapy. Implantable defibrillators were placed in 150 patients (45.3%), and 181 patients (54.7%) received pharmacological and/or surgical therapy alone. Left ventricular ejection fraction was 35.2 +/- 16.6% in defibrillator recipients and 45.3 +/- 18.2% in nondefibrillator patients. Median patient follow-up was 24 months in the defibrillator group and 46 months in the nondefibrillator group. In a proportional hazards model, the independent predictors of total cardiac mortality were left ventricular ejection fraction of less than 0.40 (relative risk, 4.55; 95% confidence interval, 2.44 to 8.33; P = .0001), absence of an implantable defibrillator (relative risk, 2.70; confidence interval, 1.41 to 5.00; P = .017), and persistence of inducible sustained ventricular tachycardia (relative risk, 1.84; 95% confidence interval, 0.97 to 3.49; P = .045). The 1- and 5-year probabilities of survival free of cardiac mortality in patients with left ventricular ejection fraction of less than 0.40 were 94.3% and 69.6% with a defibrillator and 82.1% and 45.3% without a defibrillator, respectively. For patients with left ventricular ejection fraction of 0.40 or more, the 1- and 5-year probabilities of survival free of cardiac mortality were 97.7% and 94.6% with a defibrillator and 95.4% and 86.9% without a defibrillator, respectively.

CONCLUSIONS

In survivors of out-of-hospital cardiac arrest, the implantable defibrillator is associated with a reduction in cardiac mortality, particularly in patients with impaired left ventricular function.
Transcatheter occlusion of patent ductus arteriosus with adjustable buttoned device. Initial clinical experience.
Authors: Rao P S , Sideris E B , Haddad J , Rey C , Hausdorf G , Wilson A D , Smith P A , Chopra P S
Published: June 2012

BACKGROUND

Several devices are available for transcatheter occlusion of patent ductus arteriosus. Most of these devices either require complicated intracardiac maneuvering, have not been tried in humans, or need a large-sized sheath for implantation of the device.

METHODS AND RESULTS

During a 26-month period ending November 1992, 14 patients underwent transcatheter closure of patent ductus arteriosus with an adjustable buttoned device delivered via a 7F sheath under an institutional review board-approved custom-made device protocol. The children were 15 months to 8 years of age with weight range of 7.2 to 19 kg. The patent ductus arteriosus measured from 2 to 7.5 mm (median, 3 mm) at the narrowest diameter and was conical, short, or tubular. They were occluded with devices measuring 15 to 20 mm. The ratio of pulmonary to systemic flow decreased (P < .01) from 1.9 +/- 0.6 (mean +/- SD; range, 1.3 to 3.2) to 1.05 +/- 0.1 (1 to 1.3). Continuous murmur of patent ductus arteriosus disappeared in all except 1 patient. Small residual shunts were detected by color Doppler studies in 4 of 14 patients (29%). All patients were followed for 1 to 24 months (mean, 6 +/- 7 months). The device was intact in all patients, and no breakage of the wires was noted. No shunts were seen in 12 of 14 patients (86%), and minute residual shunts were seen in 2 children. No major complications were encountered.

CONCLUSIONS

It is concluded that transcatheter closure of patent ductus arteriosus with the adjustable buttoned device is feasible and effective and can be accomplished via small 7F sheaths; a 7F sheath is adequate for all ductal sizes; and the adjustable length of the loop accommodated all types of patent ductus arteriosus. Clinical trials on a larger number of patients are warranted.
Left ventricular diastolic Doppler characteristics in beta-thalassemia major.
Authors: Kremastinos D T , Tsiapras D P , Tsetsos G A , Rentoukas E I , Vretou H P , Toutouzas P K
Published: June 2012

BACKGROUND

Diastolic left ventricular function expressed by diastolic Doppler characteristics of the left ventricle has never been properly investigated.

METHODS AND RESULTS

Left ventricular inflow and pulmonary vein flow patterns were assessed by Doppler echocardiography in 88 beta-thalassemia major patients with normal left ventricular systolic function; 34 were young (age, 15.1 +/- 3.2 years) and 54 were adults (age, 25.1 +/- 3.6 years). The findings were compared with those obtained from 22 young (age, 13.8 +/- 2.4 years) and 24 adult (age, 25.3 +/- 4.1 years) normal individuals. In both groups of patients, peak flow velocities in early (E) and late (A) diastole were higher than in the control subjects (young E: P < .01; adult E: P < .001; young A: P < .05; adult A: P < .05), whereas no difference was found in the E/A ratio, deceleration time, or isovolumic relaxation time. Pulmonary vein systolic (S) and diastolic (D) velocities were also higher in beta-thalassemia major patients compared with the control subjects (young S: P < .05; adult S: P < .05; young D: P < .05; adult D: P < .05). Restrictive left ventricular abnormalities were only found in 7 patients who were among the oldest beta-thalassemia major population of the adult group (P < .01) with highly elevated mean serum ferritin. In comparison to the remaining adult patients, interventricular septum and left ventricular posterior wall thickness were increased (P < .01 and P < .01, respectively). The left atrium and right ventricle were dilated (P < .05 and P < .01, respectively).

CONCLUSIONS

Doppler diastolic indexes in beta-thalassemia major patients with normal left ventricular systolic function are similar to those seen in conditions with an increased preload, probably because of chronic anemia. Only severe iron loading and deposition in the myocardium leads to the restrictive abnormalities of left ventricular filling.
On-line assessment of left atrial area and function by echocardiographic automatic boundary detection.
Authors: Waggoner A D , Barzilai B , Miller J G , Pérez J E
Published: June 2012

BACKGROUND

Direct assessment of left atrial (LA) function has not been previously performed by noninvasive techniques; rather, LA function has been evaluated only indirectly via the analysis of transmitral flow velocity by Doppler. The recent development of real-time two-dimensional echocardiographic automatic boundary detection suggests that LA dimensions can be measured instantaneously to provide on-line assessment of its systolic and diastolic functions.

METHODS AND RESULTS

We performed echocardiographic assessment of LA dimensions and function with automatic boundary detection in 45 patients by using the apical four-chamber view. Thirty-seven patients had structural or functional cardiac abnormalities, 35 patients were in sinus rhythm, and 10 patients had atrial fibrillation. Moderate to severe mitral regurgitation (MR) was noted in 16 patients. We also studied 10 control subjects to assess normal values of LA cavity area and indexes of function. From the instantaneously derived LA area, we derived indexes of systolic atrial expansion and diastolic atrial emptying. There were excellent correlations between the on-line-derived LA areas and those measured off line from videotaped images of conventional echocardiography (r = .91 for end-diastolic and .93 for end-systolic areas; SEE, 4.0 and 3.8 cm2, respectively). Patients in atrial fibrillation had depressed diastolic emptying index (0.17 +/- 0.05) compared with those in sinus rhythm (0.28 +/- 0.12; P < .02). Furthermore, patients with chronic MR exhibited larger LA cavity areas and depressed systolic and diastolic LA function as compared with those without MR. In addition, the Doppler-determined mitral E/A ratio was related to the ratio of early diastolic-to-late diastolic change in LA cavity area (r = .79; SEE 0.6; n = 35).

CONCLUSIONS

Instantaneous LA cavity area measurement by echocardiographic automatic boundary detection is accurate and feasible in patients with diverse cardiac disorders. Patients with atrial fibrillation had a depressed diastolic emptying index and those with significant mitral regurgitation had depressed systolic expansion index as well. LA functional indexes in both systole and diastole can be derived providing an approach for quantitative evaluations of left atrial-left ventricular interactions based on geometric assessment noninvasively.
Effect of endothelin-1 on neutrophil adhesion to endothelial cells and perfused heart.
Authors: López Farré A , Riesco A , Espinosa G , Digiuni E , Cernadas M R , Alvarez V , Montón M , Rivas F , Gallego M J , Egido J
Published: June 2012

BACKGROUND

Based on recent evidence showing that endothelin-1 stimulates several activation mechanisms on neutrophils, the aim of the present study was to analyze the effects of endothelin-1 on neutrophil adhesion to endothelial cells and neutrophil accumulation in the heart.

METHODS AND RESULTS

The experiments included (1) adhesion of 51Cr-labeled human neutrophils to bovine endothelial cells in culture both in the presence and absence of monoclonal antibodies against the alpha- and beta-subunits of integrins; (2) surface expression of the alpha- and beta-integrin antigens; (3) accumulation of 51Cr-labeled neutrophils on the isolated perfused rabbit heart; (4) in vivo accumulation of autologous neutrophils in the heart, as assessed by myeloperoxidase activity. Endothelin-1 stimulated neutrophil adhesion to endothelial cells (increase of 1 x 10(5) +/- 1 x 10(4) neutrophils per well). The endothelin-1-induced adhesion was blocked (83 +/- 6%) by the anti-CD18 antibody TS1/18 and by several anti-alpha-subunit antibodies. The expression of CD18 and CD11b on the neutrophil surface was also increased by endothelin-1. Endothelin-1 enhanced neutrophil accumulation in the isolated rabbit heart by 4.2 times throughout a TS1/18-inhibitable mechanism. Myeloperoxidase activity increased by 4.2 times in hearts infused in vivo with endothelin-1.

CONCLUSIONS

Endothelin-1 stimulates neutrophil adhesion to endothelial cells by an effect on the expression of adhesive molecules on the neutrophil surface. Endothelin-1 stimulates neutrophil accumulation in vivo and in vitro in the heart. Antibodies against the integrin complex block the endothelin-1-dependent neutrophil adhesion. These findings have potential importance in the pathophysiology of endothelin-1-increased states.
Pinacidil-induced electrical heterogeneity and extrasystolic activity in canine ventricular tissues. Does activation of ATP-regulated potassium current promote phase 2 reentry?
Authors: Di Diego J M , Antzelevitch C
Published: June 2012

BACKGROUND

Pinacidil is known to augment a time-independent outward current in cardiac tissues by activating the ATP-regulated potassium channels. Activation of this current, IK-ATP, is thought to be responsible for increased potassium permeability in ischemia. The contribution of IK-ATP activation to arrhythmogenesis and the role of activation of this current in suppression of arrhythmias are areas of great interest and debate. Because electrical depression attending myocardial ischemia is more accentuated in ventricular epicardium than in endocardium, we endeavored to contrast the effects of pinacidil-induced IK-ATP activation on the electrophysiology of canine ventricular epicardium and endocardium.

METHODS AND RESULTS

Standard microelectrode techniques were used. Pinacidil (1 to 5 mumol/L) produced a marked dispersion of repolarization and refractoriness in isolated canine ventricular epicardium as well as between epicardium and endocardium. In endocardium, pinacidil abbreviated action potential duration (APD90) and refractoriness by 8.0 +/- 2.3%. In epicardium, the effects of pinacidil were nonhomogeneous. At some sites, pinacidil induced an all-or-none repolarization at the end of phase 1 of the action potential, resulting in 55.5 +/- 8.7% abbreviation of APD90 and refractoriness. Adjacent to these were sites at which the dome was maintained with only minor changes in APD and refractoriness. Extrasystolic activity displaying features of reentry was observed in isolated sheets of epicardium (63.2%) after exposure to pinacidil (1 to 5 mumol/L) but never in its absence. Dispersion of repolarization and ectopic activity was most readily induced in epicardium by a slowing of the stimulation rate in the presence of pinacidil. Electrical homogeneity was restored and arrhythmias abolished after washout of pinacidil or addition of either a transient outward current blocker, 4-aminopyridine, or a blocker of the ATP-regulated potassium channels, glybenclamide.

CONCLUSIONS

Our data suggest that the activation of IK-ATP can produce a marked dispersion of repolarization and refractoriness in epicardium as well as between epicardium and endocardium, leading to the development of extrasystolic activity via a mechanism that we have called phase 2 reentry. The available data also suggest that blockade of the transient outward current and/or the ATP-regulated potassium channels may be useful antiarrhythmic interventions under ischemic or "ATP depleted" conditions.
Angiotensin I and II exert inotropic effects in atrial but not in ventricular human myocardium. An in vitro study under physiological experimental conditions.
Authors: Holubarsch C , Hasenfuss G , Schmidt-Schweda S , Knorr A , Pieske B , Ruf T , Fasol R , Just H
Published: June 2012

BACKGROUND

The renin-angiotensin system with its renal-humoral and local myocardial components plays an important role in the development and progression of chronic heart failure. Whereas angiotensin receptors have been found in atrial and ventricular myocardium of different species including humans, its influence on myocardial contractility is not yet defined in human failing myocardium and especially in human nonfailing myocardium.

METHODS AND RESULTS

We measured force development of right atrial and right and left ventricular myocardial preparations of patients with a variety of cardiac diseases. To evaluate the physiological effects of angiotensin, experimental temperature and stimulation rates were 37 degrees C and 60 beats per minute, respectively. Angiotensin I and II increased peak developed force in atrial myocardial preparations obtained from patients without heart failure in a concentration-dependent manner. At optimal concentrations, peak developed force is increased from 10.2 +/- 1.8 to 12.3 +/- 1.9 mN/mm2 by angiotensin I (P < .05) and from 15.4 +/- 2.1 to 20.5 +/- 3.3 mN/mm2 by angiotensin II (P < .05). This effect was not influenced by pretreatment with propranolol (10(-6) mol/L) and prazosin (10(-5) mol/L) but was completely blocked by saralasin (10(-6) mol/L). The positive inotropic effect of angiotensin I could be blocked by enalaprilate (10(-5) mol/L). Neither angiotensin I nor angiotensin II had any effect in preparations of the left ventricle from patients with idiopathic dilated cardiomyopathy, mitral valve stenosis, and incompetence or in patients with no significant heart disease. Additionally, no effect could be seen when angiotensin II was applied to right ventricular preparations from infants undergoing reconstructive heart surgery for tetralogy of Fallot.

CONCLUSIONS

Angiotensin I and II exert positive inotropic effects via angiotensin receptors in atrial preparations but not in right or left ventricular preparations. Furthermore, the existence of a local myocardial angiotensin converting enzyme with functional importance is shown.
Effects of active compression-decompression resuscitation on myocardial and cerebral blood flow in pigs.
Authors: Lindner K H , Pfenninger E G , Lurie K G , Schürmann W , Lindner I M , Ahnefeld F W
Published: June 2012

BACKGROUND

This study was designed to assess the effects of a modified cardiopulmonary resuscitation (CPR) technique that consists of both active compression and active decompression of the chest (ACD CPR) versus standard CPR (STD CPR) on myocardial and cerebral blood flow during ventricular fibrillation both before and after epinephrine administration.

METHODS AND RESULTS

During a 30-second period of ventricular fibrillation cardiac arrest, 14 pigs were randomized to receive either STD CPR (n = 7) or ACD CPR (n = 7). Both STD and ACD CPR were performed using an automated pneumatic piston device applied midsternum, designed to provide either active chest compression (1.5 to 2.0 in.) and decompression or only active compression of the chest at 80 compressions per minute and 50% duty cycle. Using radiolabeled microspheres, median total myocardial blood flow after 5 minutes of ventricular fibrillation was 14 (7 to 30, minimum to maximum) STD CPR versus 30 (9 to 46) mL.min-1 x 100 g-1 with ACD CPR (P < .05). Median cerebral blood flow was 15 (10 to 26) mL.min-1 x 100 g-1 with STD CPR and 30 (21 to 39) with ACD CPR (P < .01). When comparing STD with ACD CPR, aortic systolic (62 mm Hg [48 to 70] vs 80 [59 to 86]) and diastolic (22 [18 to 28] vs 28 [21 to 36]) pressures, calculated coronary systolic (30 [22 to 36] vs 49 [37 to 56]) and diastolic (18 [16 to 23] vs 26 [21 to 31]) perfusion pressures, end-tidal CO2 (1.4% [0.8 to 1.8] vs 2.1 (1.8 to 2.4]), cerebral O2 delivery (3.1 mL.min-1 x 100 g-1 [1.5 to 4.5] vs 5.3 [3.8 to 7.5]), and cerebral perfusion pressure (14 mm Hg [4 to 22] vs 26 [6 to 34]) were all significantly higher with ACD CPR: To compare these parameters before and after vasopressor therapy, a bolus of high-dose epinephrine (0.2 mg/kg) was given to all animals after 5 minutes of ventricular fibrillation. Organ blood flow and calculated perfusion pressures increased significantly in both the STD and ACD groups after epinephrine. The differences observed between STD and ACD CPR before epinephrine were diminished 90 seconds after epinephrine but were again statistically significant when assessed 5 minutes later, once the acute effects of epinephrine had decreased. No difference in short-term resuscitation success was found between the two groups.

CONCLUSIONS

We conclude that ACD CPR significantly increases myocardial and cerebral blood flow during cardiac arrest in the absence of vasopressor therapy compared with STD CPR:
Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factors related to long-term angiographic outcome. Coronary Artery Restenosis Prevention on Repeated Thromboxane Antagonism (CARPORT) Study Group.
Authors: Rensing B J , Hermans W R , Vos J , Tijssen J G , Rutch W , Danchin N , Heyndrickx G R , Mast E G , Wijns W , Serruys P W
Published: June 2012

BACKGROUND

The renarrowing process after successful percutaneous transluminal coronary angioplasty (PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The aim of the present study was to find independent patient-related, lesion-related, and procedure-related risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen diameter. This population could then constitute the target population for pharmacological intervention studies.

METHODS AND RESULTS

Quantitative angiography was performed on 666 successfully dilated lesions at angioplasty and at 6-month follow-up. Multivariate linear regression analysis was performed to obtain variables with an independent contribution to the prediction of the absolute change in minimal lumen diameter. Diabetes mellitus, duration of angina < 2.3 months, gain in MLD at angioplasty, pre-PTCA MLD, lesion length > or = 6.8 mm, and thrombus after PTCA were independently predictive of change in MLD. Overall prediction of the model was poor, however, percentage-correct classification for a predicted change between -0.1 to -0.4 mm was approximately 10%. Lesions showing no change or regression (change > -0.1 mm) and lesions showing large progression (< or = -0.4 mm) were more predictable (correct classification, 59.5% and 49.7%, respectively).

CONCLUSIONS

Renarrowing after successful PTCA as determined with contrast angiography is a process that cannot be accurately predicted by simple clinical, morphological, and lesion characteristics.
Transcatheter occlusion of patent ductus arteriosus with Gianturco coils.
Authors: Lloyd T R , Fedderly R , Mendelsohn A M , Sandhu S K , Beekman R H
Published: June 2012

BACKGROUND

Transcatheter occlusion with Gianturco coils has been attempted in a small number of patients with tiny (< or = 1.5-mm diameter) patent ductus arteriosus, and preliminary results have been encouraging. The present study extends this method to larger ductus sizes and makes recommendations for proper coil size selection.

METHODS AND RESULTS

Coil occlusion was attempted in 24 consecutive patients with patent ductus arteriosus who did not require other cardiac surgery. Median patient age was 4.2 years (8 months to 30 years), and mean ductus diameter was 1.7 +/- 0.8 mm. Two instances of coil embolization occurred in the first 4 patients, with successful coil retrieval. Based on this experience, we proposed that the coil helical diameter should be twice or more the minimum ductus diameter, with coil length sufficient for three or more loops. With these recommendations, coils were successfully implanted in the subsequent 20 consecutive patients. Of the 22 patients with successful coil implantation, 15 (68%) had no residual shunting, and 7 had trace residual shunting by angiography. The continuous murmur was abolished in all 22 patients. No significant complications occurred, and all patients were discharged within 24 hours of successful coil implantation. No change in the systolic pressure gradient between main and left pulmonary artery or ascending and descending aorta was observed.

CONCLUSIONS

Transcatheter occlusion of patent ductus arteriosus can be safely and effectively achieved in patients with ductus diameters up to 3.3 mm. Coil occlusion does not cause obstruction to flow in the left pulmonary artery or descending aorta. Coils should be selected to provide a helical diameter twice or more the minimum ductus diameter and a length sufficient for three or more loops.
Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes.
Authors: Laakso M , Lehto S , Penttilä I , Pyörälä K
Published: June 2012

BACKGROUND

The aim of this study was to investigate the association of lipoprotein fractions with the future risk of coronary heart disease (CHD) in patients with non-insulin-dependent diabetes (NIDDM).

METHODS AND RESULTS

At baseline, lipoprotein fractions were determined in 313 diabetic patients with NIDDM (153 men and 160 women), and these patients were followed up for 7 years with respect to CHD events (CHD death or all CHD events including CHD death or nonfatal myocardial infarction). Altogether, 56 NIDDM patients (28 men and 28 women) died from CHD and 25 had a nonfatal myocardial infarction (17 men and 8 women) during the follow-up. NIDDM patients having these CHD events during the follow-up had higher levels of total and very-low-density lipoprotein (VLDL) triglycerides and VLDL cholesterol and lower levels of high-density lipoprotein (HDL) and HDL2 cholesterol than those without CHD events. The risk for CHD death was fourfold and for all CHD events, twofold higher among diabetics with low HDL cholesterol (< 0.9 mmol/L) than among diabetics with HDL cholesterol > or = 0.9 mmol/L. High triglyceride level (> 2.3 mmol/L) was associated with a twofold increase in the risk of CHD events. In multiple logistic regression analyses, HDL was inversely associated with CHD events and VLDL triglycerides with CHD events in NIDDM patients with low HDL cholesterol level (< or = 1.12 mmol/L).

CONCLUSIONS

Our 7-year follow-up study gives evidence that low HDL and HDL2 cholesterol, high VLDL cholesterol, and high total and VLDL triglycerides are powerful risk indicators for CHD events in patients with NIDDM:
Insulin resistance is an important determinant of left ventricular mass in the obese.
Authors: Sasson Z , Rasooly Y , Bhesania T , Rasooly I
Published: June 2012

BACKGROUND

Obesity in adults is associated with increased left ventricular (LV) mass. The mechanism for this is unclear, however. We tested the hypothesis that insulin resistance is an important independent contributing factor to LV mass in the healthy obese population.

METHODS AND RESULTS

The study population consisted of 40 normotensive, nondiabetic, otherwise healthy obese subjects with body mass index (BMI) > 25 kg/m2. LV mass was echocardiographically determined according to the Penn convention, using the formula of Devereux and Reichek. Insulin resistance was assessed using indices derived from Intravenous Glucose Tolerance Test (IVGTT): insulin level at baseline, insulin level at 90 minutes of IVGTT (insulin-90), insulin integration over 90 minutes of IVGTT, and rate of glucose disposal (k value). Insulin-90 (r = .61, P = .0001), k value (r = .55, P = .003), insulin integration over 90 minutes (r = .46, P = .003), basal insulin (r = .44, P = .005), and BMI (r = .59, P = .0001) were all strongly correlated with LV mass by univariate analysis. No significant correlation was found with blood pressure or age. In multivariate regression analysis, only insulin-90 and k value correlated significantly with LV mass (P = .03, P = .02, respectively), accounting for 50% of the variance of LV mass, whereas the association with BMI became insignificant (P = .2).

CONCLUSIONS

LV mass in the normotensive nondiabetic obese population is strongly associated with, and may be mediated by, the degree of insulin resistance and its associated hyperinsulinemia, independent of BMI and blood pressure.
Coronary vasomotor effects of serotonin in patients with angina. Relation to coronary stenosis morphology.
Authors: Tousoulis D , Davies G , McFadden E , Clarke J , Kaski J C , Maseri A
Published: June 2012

BACKGROUND

Previous experimental studies have shown that the effect of serotonin on a coronary stenosis depends on whether that stenosis is compliant or fixed. However, the relation between coronary stenosis morphology and the response to serotonin in patients with angina is not known.

METHODS AND RESULTS

Using computerized quantitative coronary angiography, we studied the effects of intracoronary infusion of serotonin on 38 coronary stenoses of different morphologies (concentric, eccentric, complicated) in 11 patients with stable angina and 4 with variant angina. In response to the maximum infused concentration of serotonin, 100% of complicated stenoses and 50% of concentric stenoses constricted by > or = 20% (P < .05). The magnitude of constriction was greater at eccentric stenoses (32.08 +/- 4.1%) than concentric stenoses (15.68 +/- 2.8%, P < .05) and greater in complicated stenoses (57.69 +/- 7.6%, P < .05) than eccentric stenoses. At complicated stenoses, the constriction was greater (0.85 +/- 0.16 mm, P < .05) than at the adjacent reference segments (0.42 +/- 0.12 mm). It was similar to the reference segment for both concentric and eccentric stenoses. The constriction at the stenosis was greater for irregular (complicated) lesions than for smooth (concentric and eccentric) lesions in both patients with stable (51.8 +/- 7.3% versus 22.5 +/- 4.1%, P < .001) and those with variant (77 +/- 17% versus 28.2 +/- 8.1%, P < .05) angina. There was a weak correlation (r = .39) of magnitude of constriction with stenosis length but not with baseline stenosis severity (minimum diameter).

CONCLUSIONS

In these patients, the magnitude of the vasoconstrictor response to serotonin at the site of an atheromatous coronary plaque depends on the morphological characteristics of the plaque and is more closely related to irregular contour than stenosis severity or length. This relation suggests that variations in receptor type or density or in the smooth muscle cell response to stimulation may determine the response to locally released serotonin in patients with coronary disease.
Vascular complications after balloon and new device angioplasty.
Authors: Popma J J , Satler L F , Pichard A D , Kent K M , Campbell A , Chuang Y C , Clark C , Merritt A J , Bucher T A , Leon M B
Published: June 2012

BACKGROUND

Despite their potential advantages, new coronary angioplasty devices may be associated with more frequent vascular complications than noted after standard balloon angioplasty, theoretically due to the larger sheaths and prolonged periods of anticoagulation required by some of these devices. This study sought to identify the incidence, predictors, and clinical outcome of vascular complications after new device angioplasty.

METHODS AND RESULTS

The clinical course of 1413 patients was reviewed after balloon or new device angioplasty. Vascular complications were defined as formation of a pseudoaneurysm, arteriovenous fistula, retroperitoneal hematoma, or groin hematoma associated with a > 15-point hematocrit drop or the need for surgical repair. Stepwise logistic regression was used to identify independent predictors for vascular complications. Vascular complications developed after 84 (5.9%) procedures; they occurred more frequently after intracoronary stenting (14.0%) and extraction atherectomy (12.5%) than after balloon angioplasty (3.2%) (odds ratios, 4.86; P < .001, and 4.26, P < .05, respectively). Independent predictors of vascular complications included the use of intraprocedural thrombolytic agents (P < .01), intracoronary stenting (P < .005), or extraction atherectomy (P < .05); high maximum creatinine level (P < .005); low nadir platelet count (P < .001); longer periods of excess anticoagulation (P < .05); and the need for repeat coronary angioplasty (P < .005). Vascular complications were not related to the size of the arterial sheath used.

CONCLUSIONS

Vascular complications developed more frequently after new device angioplasty than after balloon angioplasty, with the risk for vascular complications directly related to the degree of periprocedural anticoagulation.
Evaluation of ketanserin in the prevention of restenosis after percutaneous transluminal coronary angioplasty. A multicenter randomized double-blind placebo-controlled trial.
Authors: Serruys P W , Klein W , Tijssen J P , Rutsch W , Heyndrickx G R , Emanuelsson H , Ball S G , Decoster O , Schroeder E , Liberman H
Published: June 2012

BACKGROUND

Ketanserin is a serotonin S2-receptor antagonist that inhibits the platelet activation and vasoconstriction induced by serotonin and also inhibits the mitogenic effect of serotonin on vascular smooth muscle cells.

METHODS AND RESULTS

We conducted a randomized, double blind, placebo-controlled trial to assess the effect of ketanserin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either ketanserin (loading dose, 40 mg 1 hour before PTCA; maintenance dose, 40 mg bid for 6 months) or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6 months were quantitatively analyzed. Six hundred fifty-eight patients were entered into the intention-to-treat analysis. The primary clinical end point of the study was the occurrence between PTCA and 6 months of any one of the following: cardiac death, myocardial infarction, the need for repeat angioplasty, or bypass surgery. It also included the need for revascularization actuated by findings at 6-month follow-up angiography. The primary clinical end point was reached by 92 (28%) patients in the ketanserin group and 104 (32%) in the placebo group (RR, 0.89; 95% CI, 0.70, 1.13; P = .38). Quantitative angiography after PTCA and at follow-up was available in 592 patients (ketanserin, 287; control, 305). The mean difference in minimal lumen diameter between post-PTCA and follow-up angiogram (primary angiographic end point) was 0.27 +/- 0.49 mm in the ketanserin group and 0.24 +/- 0.52 mm in the control group (difference, 0.03 mm; 95% CI, -0.05, 0.11; P = .50).

CONCLUSIONS

Ketanserin at the dose administered in this trial failed to reduce the loss in minimal lumen diameter during follow-up after PTCA and did not significantly improve the clinical outcome.
Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure.
Authors: Gottlieb S S , Dickstein K , Fleck E , Kostis J , Levine T B , LeJemtel T , DeKock M
Published: June 2012

BACKGROUND

Losartan is a new specific angiotensin II receptor antagonist with no agonist properties that provides the opportunity to study the consequences of angiotensin II blockade. The objective of the present study was to evaluate the hemodynamic and neurohormonal response to losartan in patients with congestive heart failure.

METHODS AND RESULTS

After baseline hemodynamic measurements using balloon-tipped pulmonary artery and radial arterial catheters, patients were randomized to receive a single dose of placebo or 5, 10, 25, 75, or 150 mg losartan in a double-blind, sequential fashion. Hemodynamic and neurohormonal parameters were then measured periodically for 24 hours. Losartan caused vasodilation in a dose-dependent manner. By the area-under-the-curve method, the reduction in the mean arterial pressure and systemic vascular resistance grew larger up to a dose of 25 mg, but the higher 75- and 150-mg doses did not produce additional vasodilation. In response to losartan, there were compensatory increases in both angiotensin II concentrations and in plasma renin activity, which were greatest at the highest doses. Aldosterone concentrations were significantly lowered with losartan.

CONCLUSIONS

Blockade of the angiotensin II receptor with the antagonist losartan causes vasodilator and neurohormonal effects in patients with congestive heart failure. The lack of additional vasodilator response with doses of more than 25 mg suggests that neurohormonal activation might limit the efficacy of high dose of losartan.
Why do patients with congestive heart failure tolerate the initiation of beta-blocker therapy?
Authors: Haber H L , Simek C L , Gimple L W , Bergin J D , Subbiah K , Jayaweera A R , Powers E R , Feldman M D
Published: June 2012

BACKGROUND

Despite its negative inotropic effects, the initiation of beta-adrenergic blockade is tolerated by patients with congestive heart failure (CHF). Accordingly, we examined the acute hemodynamic effects of beta-adrenergic blockade on systolic and diastolic left ventricular (LV) function and ventriculo-arterial coupling. In addition, isolated myocardium from patients with CHF shows selective beta 1-receptor downregulation, implying a greater role for the beta 2-receptor in maintaining in vivo LV contractility. As a secondary aim, we hypothesized that nonselective beta-adrenergic blockade would have greater negative inotropic effect than beta 1-blockade in patients with CHF.

METHODS AND RESULTS

Patients with clinical CHF (n = 24) and control patients without CHF (n = 24) were given either the nonselective beta-blocker propranolol or the beta 1-selective blocker metoprolol. LV pressure-volume relations were obtained before and after the administration of intravenous beta-blocker, and measures of LV systolic and diastolic function were examined. Patients with CHF had a deterioration in LV systolic function with a fall in LV systolic pressure (139 +/- 6 to 125 +/- 6 mm Hg), cardiac index (2.56 +/- 0.11 to 2.20 +/- 0.11 mL.min-1 x M-1), dP/dtmax (1173 +/- 63 to 897 +/- 50 mm Hg/s), and end-systolic elastance (0.88 +/- 0.10 to 0.64 +/- 0.10 mm Hg/mL), P < .05 for all. Although there was deterioration of active LV relaxation (isovolumetric relaxation 63 +/- 2 to 73 +/- 3 milliseconds, peak filling rate 543 +/- 33 to 464 +/- 28 mL/s, P < .05 for both), there was no change in passive LV diastolic function (pulmonary capillary wedge, 24 +/- 2 to 24 +/- 1 mm Hg; chamber stiffness, 0.0154 +/- 0.0005 to 0.0163 +/- 0.0005 mL-1, P = NS for both), and a decrease in afterload (arterial elastance 3.85 +/- 0.31 to 3.38 +/- 0.24 mm Hg/mL, P < .05). Control patients had no change in these parameters other than a prolongation of isovolumetric relaxation (48 +/- 1 to 55 +/- 2 milliseconds, P < .05). The effects of propranolol (n = 12) versus metoprolol (n = 12) on these parameters in patients with CHF were similar.

CONCLUSIONS

These data do not support a greater in vivo physiological role of the myocardial beta 2-receptor in CHF. The preservation of passive diastolic function and ventriculo-arterial coupling provide possible explanations of why beta-adrenergic blockade is tolerated by patients with CHF.