bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators.
Authors: Rutherford J D , Pfeffer M A , Moyé L A , Davis B R , Flaker G C , Kowey P R , Lamas G A , Miller H S , Packer M , Rouleau J L
Published: June 2012

BACKGROUND

In the Survival and Ventricular Enlargement (SAVE) trial, recurrent myocardial infarction (MI) was the most important predictor of a poor outcome and conferred a sevenfold increase in risk of death. The purpose of this study was to determine the predictors of recurrent MI in study participants and to examine the influence of the angiotensin-converting enzyme inhibitor captopril on this and other myocardial ischemic events.

METHODS AND RESULTS

The 2231 patients had survived the acute phase of MI (3 to 16 days) and had a radionuclide ventricular ejection fraction < or = 40%. Patients were randomly assigned to receive double-blind treatment with either placebo or captopril and were followed for an average of 42 months. The influence of captopril on recurrent MI, cardiac revascularization procedures, and hospitalization with unstable angina was examined. The likelihood of recurrent MI was greater in patients with an MI or functional disability before the index infarction and higher systolic pressure (all P < .001) but was not influenced by baseline left ventricular ejection fraction. Therapy with captopril reduced the risk of development of recurrent MI by 25% (95% confidence intervals, 5% to 40%; P = .015) and the risk of death after recurrent MI by 32% (95% confidence intervals, 4% to 51%; P = .029). Captopril-assigned patients were also less likely to require cardiac revascularization procedures (P = .010), but hospitalization for unstable angina was unaltered. When all three of these major coronary ischemic events were considered together, captopril therapy reduced the risk (14% risk reduction; 95% confidence intervals, 0% to 26%; P = .047).

CONCLUSIONS

In post-MI patients with asymptomatic left ventricular dysfunction, long-term administration of captopril reduced recurrence of MI and the need for cardiac revascularization but had no influence on the rate of hospitalization with a discharge diagnosis of unstable angina. The finding that the recurrence of MI was independent of left ventricular ejection fraction suggests that captopril could be useful in preventing recurrent MI in patients with more preserved left ventricular function. The need for cardiac revascularization was reduced in patients receiving long-term captopril therapy, suggesting either an anti-ischemic effect or the ability of the angiotensin-converting enzyme inhibitor to modify the atherosclerotic process in survivors of MI.
Morphological and quantitative angiographic analyses of progression of coronary stenoses. A comparison of Q-wave and non-Q-wave myocardial infarction.
Authors: Dacanay S , Kennedy H L , Uretz E , Parrillo J E , Klein L W
Published: June 2012

BACKGROUND

The purpose of this study was to determine differences in coronary stenosis severity and morphology and time course of progression between Q-wave and non-Q-wave myocardial infarction (MI).

METHODS AND RESULTS

We studied 32 patients with new Q-wave MI and 38 patients with new non-Q-wave MI who underwent coronary angiography both before and after MI without interval revascularization procedures. Quantitative coronary angiographic analysis was performed by the caliper method, and morphological analysis of coronary angiograms was obtained before and soon after acute MI. Before infarction, the stenosis severity at the site of future MI was worse in Q-wave (44 +/- 25%) versus non-Q-wave (23 +/- 35%) MI patients (P < .01). Eccentric and irregular plaques were more common in Q-wave MI patients (18 of 32, 56%, versus 5 of 38, 13%; P < .001). Non-Q-wave MI patients were more frequently found to have significant collaterals after MI compared with Q-wave MI patients (18 of 38, 47%, versus 1 of 32, 3%; P < .001) despite no difference in post-MI stenosis severity. Analysis according to time interval after pre-MI angiography showed that 9 of 11 patients (82%) with Q-wave MI < 18 months later had a stenosis of > or = 50% versus 7 of 21 (33%) with an interval > 18 months (P < .05). By comparison, non-Q-wave MI patients tended to fall into two categories regardless of time of progression: Either minimal or no stenosis (< 20%) or else a severe stenosis (> 70%) was typically present.

CONCLUSIONS

The atheromatous plaque substrate is different in Q-wave and non-Q-wave MI. Non-Q-wave MI occurs typically at a site shown by pre-MI angiography to involve either minimal luminal narrowing or a severe stenosis before MI, which is usually nonulcerated. By comparison, Q-wave MI follows a moderate stenosis in which the plaque is eccentric and ulcerated. Such differences culminate in differences in thrombus lability and collateral development and consequently in different clinical profiles.
Independent control of skin and muscle sympathetic nerve activity in patients with heart failure.
Authors: Middlekauff H R , Hamilton M A , Stevenson L W , Mark A L
Published: June 2012

BACKGROUND

Sympathetic excitation characterizes heart failure, but the underlying mechanisms remain unknown. Abnormal baroreflex restraint of sympathetic neural outflow has been proposed, since baroreflexes are known to be abnormal in heart failure. The purpose of this study was to determine if sympathetic activation in humans with heart failure is limited to regions governed by the baroreflexes or is generalized to other regions free from baroreflex control.

METHODS AND RESULTS

We report the first direct recordings of skin sympathetic nerve activity (free from baroreflex control) in humans with heart failure and compare simultaneous skin and muscle (baroreflex-dependent) sympathetic peroneal nerve activity in six patients with severe heart failure (mean left ventricular ejection fraction, 0.19 +/- 0.06) and in six age-matched normal control subjects. Although muscle sympathetic nerve activity was markedly increased in heart failure patients (heart failure versus controls, 69 +/- 3 versus 21 +/- 2 bursts per minute; P < .001), skin sympathetic nerve activity was not increased (heart failure versus controls, 12 +/- 1 versus 15 +/- 1 bursts per minute; P = NS).

CONCLUSIONS

The finding that skin sympathetic nerve activity in contrast to muscle sympathetic nerve activity is not increased in heart failure supports the concept that an altered reflex system, such as the baroreflexes, with nonuniform effects on muscle and skin sympathetic nerve activity, underlies sympatho-excitation in heart failure.
Appropriate sensing of ventricular fibrillation after failed shocks in a transvenous cardioverter-defibrillator system.
Authors: Ellis J R , Martin D T , Venditti F J
Published: June 2012

BACKGROUND

Reduction in R-wave amplitude immediately after defibrillation shocks in an integrated shock/sense transvenous cardioverter-defibrillator (TCD) lead system has prompted concerns regarding adequate sensing after failed shocks. We therefore studied redetection characteristics for ventricular fibrillation after unsuccessful defibrillation shocks in a TCD system to determine if these observations have clinical relevance.

METHODS AND RESULTS

Fifty patients with this shock/sense TCD lead system underwent conversion testing of their TCD at several time intervals. There were a total of 142 failed shocks events recorded, including 10, 15, 70, and 47 events at implantation, predischarge, and 2- and 6-month testing, respectively. Initial detection time (IDT) and redetection time (RDT) for ventricular fibrillation were measured from event markers for all unsuccessful defibrillation shocks. To assess the effect of failed shocks on electrogram quality, 54 failed shock episodes were evaluated in 37 of the 50 patients by measuring electrograms during VF before and after shock. Mean RDT for the entire group was 5.3 +/- 3.5 seconds compared with an IDT of 4.5 +/- 3.3 seconds (P = NS). There were no significant differences between IDT and RDT at implantation or any follow-up testing period, despite a significant decline in R-wave amplitude from 8.1 +/- 3.5 to 6.8 +/- 2.8 mV (P < .0001) measured 3 to 6 seconds after shock delivery. Analysis of 8 individuals with any extended RDT (> or = 10 seconds) showed no significant differences in clinical or implantation characteristics when compared with 42 individuals without extended RDT.

CONCLUSIONS

In this integrated shock/sense TCD lead system, unsuccessful shock delivery has no significant effect on redetection of ventricular fibrillation at device implantation or up to 6 months of follow-up, despite an observed reduction in postshock R-wave amplitude. Therefore, the reported reduction in electrogram quality after a shock is of no practical importance because sensing of ventricular fibrillation does not appear to be compromised in this particular TCD system. Whether this applies to other implantable cardioverter-defibrillator pulse generators and lead systems with different sensing characteristics requires further evaluation.
Effect of capacitor size and pathway resistance on defibrillation threshold for implantable defibrillators.
Authors: Swerdlow C D , Kass R M , Chen P S , Hwang C , Raissi S
Published: June 2012

BACKGROUND

The time constant of truncated exponential pulses used with implantable defibrillators is determined by the output capacitor size and defibrillation pathway resistance. The optimal capacitor size is unknown.

METHODS AND RESULTS

This study compared defibrillation threshold (DFT) for standard 120-microF capacitors (DFT120) and smaller 60-microF capacitors (DFT60) at implantation of cardioverter-defibrillators in 67 patients using epicardial electrodes (15 patients) or one of four transvenous electrode configurations (52 patients). Paired comparisons of DFT60 and DFT120 were made for 44 defibrillation pathways using monophasic pulses and for 53 pathways using biphasic pulses. Truncated exponential pulses with 65% tilt were used. Pooled data from all electrode configurations showed a significant inverse correlation between pathway resistance and the ratio of stored energy DFT60 to DFT120 (monophasic pulses: r = .75, P = .0001; biphasic pulses: r = .68, P = .0001). Data from all electrode configurations formed a continuum with 120-microF capacitors superior for low-resistance pathways and 60-microF capacitors superior for high-resistance pathways. For pathways with resistance < or = 40 omega, the modest advantage of 120-microF capacitors applied primarily to pathways with low DFTs: 8.2 +/- 6.1 versus 9.6 +/- 5.4 J (P = .001) for monophasic pulses and 4.1 +/- 2.8 versus 5.1 +/- 3.1 J (P < .02) for biphasic pulses. The greater advantage of 60-microF capacitors for pathways with resistance > or = 61 omega applied to pathways with higher DFTs: 12.4 +/- 4.3 versus 23.1 +/- 6.4 J (P = .0001) for monophasic pulses and 8.5 +/- 4.9 versus 12.5 +/- 6.4 J (P = .0001) for biphasic pulses. For pathways using monophasic 120-microF pulses versus 95% for 60-microF pulses. Similarly, the DFT was < or = 10 J for 48% of pathways using biphasic 120-microF capacitors versus 83% for 60-microF pulses.

CONCLUSIONS

In comparison with conventional 120-microF capacitors, 60-microF capacitors had clinically insignificant higher DFTs for low-resistance pathways and clinically important lower DFTs for high-resistance pathways. Optimal capacitance is inversely related to pathway resistance for clinical defibrillation pathways and waveforms.
Initial contact and subsequent adhesion of human neutrophils or monocytes to human aortic endothelial cells releases an endothelial intracellular calcium store.
Authors: Ziegelstein R C , Corda S , Pili R , Passaniti A , Lefer D , Zweier J L , Fraticelli A , Capogrossi M C
Published: June 2012

BACKGROUND

Increases in both leukocyte and endothelial cytosolic free [Ca2+] may be involved in intercellular adhesion by regulating the affinity of surface adhesion molecules or by facilitating transendothelial leukocyte migration. The purpose of this study was to examine the effect of initial contact and subsequent adhesion of human neutrophils or monocytes on human aortic endothelial [Ca2+].

METHODS AND RESULTS

Endothelial monolayers were loaded with the fluorescent Ca2+ indicator indo 1 and exposed to isolated human peripheral blood neutrophils or to a cultured human monocyte cell line. A rapid, fourfold to fivefold increase in endothelial cytosolic [Ca2+] occurred within seconds of leukocyte contact. No increase in endothelial [Ca2+] occurred on contact of 18.25-microns inert microspheres, isolated red blood cells, or suspensions of cultured human aortic endothelial cells. In experiments performed on monolayers grown in 1-mm2 capillary flow tubes, the increase in endothelial cytosolic [Ca2+] on initial leukocyte contact was found to be related to the subsequent resistance to leukocyte detachment during exposure to arterial levels of shear stress (13.4 dyne.cm-2). The increase in endothelial cytosolic [Ca2+] during leukocyte contact was not inhibited in Ca(2+)-free buffer but was abolished by prior depletion of an endoplasmic reticulum Ca2+ store by thapsigargin. Pretreatment of neutrophils with R15.7, a specific monoclonal antibody to the adhesion protein CD-18, inhibited the increase in endothelial cytosolic [Ca2+] on neutrophil contact.

CONCLUSIONS

Initial contact leading to subsequent adhesion of human leukocytes to human aortic endothelial cells releases an endothelial intracellular Ca2+ store. This may, in part, be mediated by specific adhesion proteins and may in turn regulate the affinity of surface adhesion molecules or facilitate transendothelial migration of leukocytes.
Local delivery of an antithrombin inhibits platelet-dependent thrombosis.
Authors: Scott N A , Nunes G L , King S B , Harker L A , Hanson S R
Published: June 2012

BACKGROUND

Platelet-dependent thrombosis can be effectively inhibited by intravenous administration of direct thrombin antagonists. However, an increased propensity for abnormal bleeding has been associated with systemic administration of these agents. The goal of this study was to determine whether local delivery of a potent thrombin inhibitor, D-Phe-L-Pro-L-Arg chloromethyl ketone (PPACK), could inhibit platelet-dependent thrombosis without altering systemic hemostatic function.

METHODS AND RESULTS

Thrombus formation was measured by quantitative imaging of 111In-labeled platelet deposition on segments of thrombogenic vascular graft interposed in arteriovenous shunts in a porcine model. Intravenous administration of PPACK inhibited platelet deposition at a dose of 12.5 micrograms/kg per minute, which was associated with significant prolongations of both template bleeding times and activated partial thromboplastin times. By contrast, local infusion of PPACK at a dose of 0.02 micrograms/kg per minute (ie, a 600-fold smaller dose) into the fluid boundary layer at the interface between flowing blood and the thrombogenic segment produced equivalent inhibition of platelet deposition without prolonging either the bleeding time or the activated partial thromboplastin time. In addition, static exposure of a mural thrombus to solutions of PPACK at concentrations > or = 2.5 mg/mL for 15 minutes produced sustained inhibition of platelet-dependent thrombosis with no change in hemostatic measurements.

CONCLUSIONS

These results indicate that local delivery of the direct antithrombin PPACK, by either boundary layer infusion or static application techniques, effectively inhibits platelet-dependent thrombosis at doses that are several orders of magnitude less than the systemic dose required for an equivalent antithrombotic effect. In contrast to the systemic administration of PPACK, local delivery produced maximal inhibition of thrombosis without alterations in hemostasis.
Characterization of the excitable gap in a functionally determined reentrant circuit. Studies in the sterile pericarditis model of atrial flutter.
Authors: Niwano S , Ortiz J , Abe H , Gonzalez X , Rudy Y , Waldo A L
Published: June 2012

BACKGROUND

Single premature beats were introduced in the reentrant circuit during stable atrial flutter in the canine sterile pericarditis model to test the hypotheses that (1) despite the fact that the reentrant circuit is functionally determined, there is a fully excitable gap; (2) the excitable gap in the reentrant circuit is not uniform; and (3) inhomogeneities of conduction in the reentrant circuit explain the effects of premature beats.

METHODS AND RESULTS

A multiplexing system was used to record 190 unipolar electrograms from the right atrial free wall during 18 atrial flutter episodes in 9 dogs. In all 18 episodes, premature stimuli captured the atrial flutter reentrant circuit. At the longest coupling intervals, the return cycle at the site closest to the pacing site did not prolong. As the coupling interval of the premature stimulus decreased, the return cycle then progressively increased, associated with changes in conduction in the reentrant circuit that were not uniform. The result was that coupling intervals associated with introduction of the premature beat also were not constant. The mean duration of the total (ie, fully plus partially) excitable gap was 12 +/- 4 ms in areas of slow conduction, and it was always shorter than the total excitable gap in other areas (22 +/- 6 ms, P < .001). The mean duration of the fully excitable gap based on analysis of the return cycle was 4 +/- 1 ms in the reentrant circuit. In 13 of 18 atrial flutter episodes, a premature stimulus terminated atrial flutter by causing block of the orthodromic wave front of the premature beat in an area of slow conduction. The mean coupling interval that caused orthodromic block was 113 +/- 5 ms (recorded at the site just proximal to the area of block), and it was always longer than the delivered stimulus coupling interval at the pacing site (96 +/- 8 ms, P < .001).

CONCLUSIONS

We conclude that in this functionally determined atrial flutter reentrant circuit in the canine sterile pericarditis model, (1) a fully excitable gap is present in at least part of the reentrant circuit; (2) the duration of the excitable gap in the reentrant circuit is shortest in areas of slow conduction; and (3) when a premature beat encounters the partially excitable gap of the reentrant circuit, it results in changes in conduction such that the coupling intervals are not uniform throughout in the reentrant circuit.
Control of rapid ventricular response by radiofrequency catheter modification of the atrioventricular node in patients with medically refractory atrial fibrillation.
Authors: Feld G K , Fleck R P , Fujimura O , Prothro D L , Bahnson T D , Ibarra M
Published: June 2012

BACKGROUND

Pharmacological control of rapid ventricular response to atrial fibrillation may be difficult in some patients. Alternative treatments, including curative surgery or atrioventricular (AV) node ablation with pacemaker implantation, have significant potential morbidity. In view of evidence that dual AV nodal physiology may exist in a significant percentage of the population, even in those without AV nodal reentrant tachycardia, we postulated that control of ventricular response might be achieved by radiofrequency (RF) catheter ablation in the region of the AV nodal slow pathway with its short refractory period.

METHODS AND RESULTS

Ten patients underwent attempted AV node modification using a 4-mm-tipped electrode catheter positioned in the middle or posterior septum, between the His bundle and coronary sinus ostium on the tricuspid valve annulus. RF energy was applied at 16 to 30 W for up to 60 seconds, until average ventricular response fell below 100 beats per minute. Reduction of maximal ventricular response below 120 beats per minute was confirmed with atropine 1 mg IV. If required, additional ablations were performed progressively more posteriorly up to the coronary sinus ostium. Patients with successful AV node modification were discharged off AV node-blocking drugs and followed in the clinic at regular intervals. Twenty-four-hour ambulatory ECG recordings and/or treadmill stress tests were obtained before and after ablation for statistical comparison of maximum ventricular rate. Resting average ventricular rate was determined during electrophysiology study before and after ablation. In 7 of 10 patients (70%), maximum ventricular rate was reduced from a mean of 164 +/- 12 to 123 +/- 16 beats per minute (P < .01) and average ventricular rate from a mean of 128 +/- 11 to 83 +/- 10 beats per minute after ablation. Mean minimum ventricular rate was 54 +/- 11 beats per minute after ablation. These 7 patients have remained symptom free from rapid ventricular response for a mean of 14 +/- 8 months (range, 1 to 22). Three remain off all AV node-blocking drugs, 3 remain on digoxin alone, which was previously ineffective, and 1 remains on a beta-blocker for angina. In the 3 patients who did not respond to AV node modification, complete AV node ablation and permanent pacemaker implantation was performed in 2 and DC cardioversion after amiodarone loading was performed in 1.

CONCLUSIONS

RF catheter modification of AV node conduction is effective in controlling rapid ventricular response to atrial fibrillation in a significant percentage of medically refractory patients. A possible mechanism of RF modification of AV node conduction is AV nodal slow pathway ablation. Large-scale clinical trials will be needed to determine the overall efficacy and safety of this technique.
Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors.
Authors: French B A , Mazur W , Geske R S , Bolli R
Published: June 2012

BACKGROUND

Efficient methods of introducing genes into myocardial cells must be developed before local somatic cell gene therapy can be implemented against myocardial disease. Although adenoviral (Ad5) vectors have been used to target rodent hearts and plasmid DNA has been directly injected into the myocardium of rats and dogs, the amounts of recombinant protein produced by these procedures have not been reported, and adenoviral vectors have not been used in large mammalian hearts.

METHODS AND RESULTS

Replication-deficient recombinant adenoviral vectors carrying either the luciferase or lacZ reporter genes were injected directly into the ventricular myocardium of adult domestic swine for evaluation of reporter gene expression. This procedure did not affect regional myocardial function as assessed by systolic wall thickening using ultrasonic crystals. Luciferase activity was detected 3 days after injection, increased markedly at 7 days, and then declined progressively at 14 and 21 days. Luciferase production was comparable in the right and left ventricular walls and increased with increasing amounts of virus, reaching 61 +/- 21 ng at the highest dose examined (3.6 x 10(9) plaque-forming units). The injection of 200 micrograms of plasmid DNA (pRSVL) produced levels of luciferase comparable to 1.8 x 10(8) plaque-forming units of recombinant Ad5; however, when normalized to the number of genes injected, the adenovirus was 140,000 times more efficient than plasmid DNA. Histochemical analysis of beta-galactosidase activity produced by a second Ad5 vector demonstrated that nearly all (> 95%) of the stained cells were cardiomyocytes and that the percentage of cardiomyocytes infected by the virus could be quite high in microscopic regions adjacent to the needle track (up to 75% in fields of 60 to 70 cells); however, Ad5-infected cells were rarely observed farther than 5 mm from the injection site. Furthermore, the Ad5 vector induced pronounced leukocytic infiltration that was far in excess of that seen after injection of vehicle alone.

CONCLUSIONS

This study demonstrates for the first time that direct intramyocardial injection of replication-deficient adenovirus can program recombinant gene expression in the cardiomyocytes of a large animal species with relevance to human physiology. The efficiency of adenovirus-mediated gene transfer is far superior to that of plasmid DNA injection, and this method appears to be capable of producing more recombinant protein. However, the cell-mediated immune response to the Ad5 vector and the limited distribution of reporter gene expression suggest that less immunogenic recombinant vectors and more homogeneous administration methods will be required before Ad5 vectors can be successfully used for phenotypic modulation.
Endocarditis risk of the USCI PDA umbrella for transcatheter closure of patent ductus arteriosus.
Authors: Latson L A , McManus B M , Doer C , Kilzer K , Cheatham J P
Published: June 2012

BACKGROUND

The USCI PDA Umbrella is a device to close patent ductus arteriosus (PDA) by a transcatheter technique. Human clinical trials have shown excellent efficacy in reducing or eliminating the PDA shunt, but concerns remain about the risk of infection with this device. The purpose of this study was to evaluate the risk of infection using an animal model.

METHODS AND RESULTS

Susceptibility to developing endocarditis was tested by injecting a single intravenous dose of group L streptococcus. Ten piglets with a closed ductus served as controls. Two of these developed valvular vegetations. PDA was produced in 19 animals by balloon dilation of the ductus. Seven of 7 animals with PDA at the time of bacterial injection developed endarteritis of the ductus and valvular vegetations. A PDA Umbrella was placed in the remaining 12 animals, and bacteria were injected 2 weeks after device implantation. Infection was evident in the PDA Umbrella only in the single animal in which the Umbrella had embolized and been left in the left pulmonary artery. Three of the remaining 11 piglets had a significant residual leak, and all developed infection in the ductus and an additional valve. Similar to the control group, none of the animals with complete (n = 8) or nearly complete (n = 2) closure of the ductus by the PDA Umbrella had infection in or around the ductus, and only 1 had a valvular vegetation.

CONCLUSIONS

In this animal model, presence of a significant PDA shunt (with or without a PDA Umbrella present) results in significantly increased susceptibility to endarteritis and endocarditis. The PDA Umbrella device does not appear to be susceptible to direct infection as early as 2 weeks after implantation if it is properly located in the ductus arteriosus. Animals with no shunt or a trivial shunt are no more susceptible to developing endocarditis 2 weeks after PDA Umbrella implantation than are controls.
Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction.
Authors: Loh E , Stamler J S , Hare J M , Loscalzo J , Colucci W S
Published: June 2012

BACKGROUND

Pulmonary vascular resistance (PVR) is frequently elevated in patients with advanced heart failure. Nitric oxide (NO), which contributes to the activity of endothelium-derived relaxing factor, causes relaxation of pulmonary arteries and veins in vitro. Inhalation of NO gas causes pulmonary vasodilation in patients with primary and secondary forms of pulmonary hypertension.

METHODS AND RESULTS

To test the hypothesis that inhalation of NO gas lowers PVR in patients with heart failure, we studied the hemodynamic effects of a 10-minute inhalation of NO (80 ppm) in 19 patients with New York Heart Association class III (n = 5) and class IV (n = 14) heart failure due to left ventricular (LV) dysfunction. Although inhalation of NO had no effect on pulmonary artery pressures, the PVR decreased by 31 +/- 7% (P < .001) due to a 23 +/- 7% increase (P < .001) in pulmonary artery wedge pressure and despite a 4 +/- 2% (P < .05) decrease in cardiac index. The magnitude of the decrease in PVR with inhaled NO was inversely related (r = -.713; P < .001) to the baseline PVR. Inhaled NO had no effect on heart rate, systemic arterial pressure, systemic vascular resistance, or LV peak +dP/dt or -dP/dt.

CONCLUSIONS

In patients with heart failure due to LV dysfunction, inhalation of NO causes a decrease in the PVR associated with an increase in LV filling pressure. These findings predict that inhaled NO, if used alone at this dose (80 ppm), may have adverse effects in patients with LV failure.
Abnormal diurnal variation of blood pressure, cardiac output, and vascular resistance in cardiac transplant recipients.
Authors: Idema R N , van den Meiracker A H , Balk A H , Bos E , Schalekamp M A , Man in 't Veld A J
Published: June 2012

BACKGROUND

An attenuated or absent nocturnal decline in blood pressure has repeatedly been documented in cardiac transplant recipients. The present study was aimed at investigating the hemodynamic mechanism underlying this abnormality.

METHODS AND RESULTS

In 23 cardiac transplant recipients (11 to 36 months after transplantation) and in 23 control subjects matched for age and 24-hour mean arterial pressure, invasive 24-hour ambulatory blood pressure was measured by means of the Oxford technique. Beat-to-beat relative values of stroke volume were determined by means of a pulse-contour method, and relative changes of cardiac output (stroke volume x heart rate) and total peripheral vascular resistance (blood pressure/cardiac output) over the 24-hour period were calculated. The nocturnal decline in blood pressure was 20 +/- 8% (mean +/- SD) in control subjects but only 5 +/- 9% (P < .001) in cardiac transplant recipients. In control subjects, the nocturnal decline in blood pressure was associated with a nocturnal fall in cardiac output of 24 +/- 13%, whereas vascular resistance compared with daytime value did not change. The small nocturnal decline in blood pressure in cardiac transplant recipients was associated with an attenuated nocturnal fall in cardiac output of 14 +/- 12% (P < .05 versus control subjects). In addition, vascular resistance compared with daytime value was increased by 9 +/- 9% (P < .05) during the night. Both in cardiac transplant recipients and in control subjects, the nocturnal changes in blood pressure were correlated with the nocturnal changes in cardiac output but not with the nocturnal changes in total peripheral vascular resistance.

CONCLUSIONS

This study confirms the attenuated nocturnal fall in blood pressure in cardiac transplant recipients. Hemodynamically, this attenuated blood pressure decline is characterized by a reduced nocturnal fall in cardiac output, and it is associated with a nocturnal increase in vascular resistance.
Role of nitric oxide in exercise-induced vasodilation of the forearm.
Authors: Endo T , Imaizumi T , Tagawa T , Shiramoto M , Ando S , Takeshita A
Published: June 2012

BACKGROUND

We wished to determine the role of NO in exercise-induced metabolic forearm vasodilation.

METHODS AND RESULTS

Young healthy volunteers (n = 11) underwent static handgrip exercise (4 to 5 kg, 3 minutes). Forearm blood flow (FBF) measured by strain plethysmography increased from 4.1 +/- 0.7 mL.min-1.100 mL-1 at rest to 9.8 +/- 1.2 mL.min-1.100 mL-1 immediately after exercise and gradually decreased thereafter. Exercise was repeated after intrabrachial artery infusion of NG-monomethyl-L-arginine (L-NMMA) at 4.0 mumol/min for 5 minutes. L-NMMA did not alter blood pressure and heart rate. L-NMMA decreased FBF at rest to 2.9 +/- 0.4 mL.min-1.100 mL-1 (P < .01), peak FBF immediately after exercise to 7.2 +/- 0.7 mL.min-1.100 mL-1 (P < .01), and FBF during the mid to late phase of metabolic vasodilation (P < .01). Calculated oxygen consumption during peak exercise was comparable before and after L-NMMA. Intra-arterially infused L-arginine (10 mg/min, 5 minutes) reversed the inhibitory effect of L-NMMA. To determine the effect of the decrease in resting FBF on exercise-induced hyperemia, we normalized FBF after exercise by resting FBF. The percent increases in FBF after exercise from resting FBF were similar before and after L-NMMA. Furthermore, we examined the effect of intra-arterially infused angiotensin II on FBF at rest and after exercise (n = 7). Angiotensin II decreased FBF at rest from 3.1 +/- 0.3 to 1.8 +/- 0.3 mL.min-1.100 mL-1 (P < .01), peak FBF after exercise from 8.1 +/- 0.5 to 5.6 +/- 0.5 mL.min-1.100 mL-1 (P < .01), and FBF during the mid to late phase of metabolic vasodilation. The effects of L-NMMA and angiotensin II on FBF at rest and exercise were similar.

CONCLUSIONS

Our results suggest that L-NMMA decreased FBF after exercise largely by decreasing resting FBF. These results suggest that NO may not play a significant role in exercise-induced metabolic arteriolar vasodilation in the forearm of healthy humans.
Magnetic resonance and echocardiographic imaging of pulmonary artery size throughout stages of Fontan reconstruction.
Authors: Fogel M A , Donofrio M T , Ramaciotti C , Hubbard A M , Weinberg P M
Published: June 2012

BACKGROUND

Because pulmonary artery size is considered by most investigators to be a major prognosticator of outcome in patients undergoing staged Fontan reconstruction, the objective of the present study was to determine the efficacy of noninvasive measures in determining pulmonary artery size.

METHODS AND RESULTS

This study analyzed the T1-weighted, spin-echo magnetic resonance and echocardiographic images of 36 functional single-ventricle patients throughout stages of Fontan reconstruction (prebidirectional and postbidirectional cavopulmonary anastomosis and after Fontan) and compared them with angiography images at cardiac catheterization. Magnetic resonance imaging had a high degree of agreement with angiography, with the McGoon index agreeing better than the Nakata index and absolute right and left pulmonary diameters. Although echocardiography had fair agreement with angiography, it agreed less well and had a wider standard deviation than magnetic resonance imaging for all indexes and measurements and, based on the prediction interval, would be a poorer prospective measure of pulmonary artery size in this population. In addition, echocardiography was a poorer measure of pulmonary artery size as the size of the vessel increases. Magnetic resonance imaging correctly detected five of five patients with nonconfluent branch pulmonary arteries and six of six patients with stenoses, whereas echocardiography was unable to visualize any of the patients with nonconfluent branch pulmonary arteries with certainty and only two of six (33%) with stenoses.

CONCLUSIONS

Magnetic resonance imaging is a useful, noninvasive tool to determine pulmonary artery size in patients undergoing Fontan reconstruction and is superior to echocardiography. Echocardiography was a fair predictor of pulmonary artery size, but magnetic resonance imaging agreed with angiography better than echocardiography and outperformed echocardiography in diagnosing branch pulmonary artery discontinuity and stenoses. Magnetic resonance imaging may avoid unnecessary cardiac catheterization, especially in older patients, and may obviate the need for jugular or subclavian catheterization in those who have undergone bidirectional cavopulmonary anastomosis.
Diagnosis in adolescents and adults with congenital heart disease. Prospective assessment of individual and combined roles of magnetic resonance imaging and transesophageal echocardiography.
Authors: Hirsch R , Kilner P J , Connelly M S , Redington A N , St John Sutton M G , Somerville J
Published: June 2012

BACKGROUND

The inability to obtain complete diagnoses with transthoracic echocardiography in many adults with congenital heart disease provided the incentive to evaluate prospectively the individual and combined roles of magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) as "second-line" techniques for unresolved diagnostic problems.

METHODS AND RESULTS

Eighty-five patients were studied; 81 had MRI with a 0.5-T magnet to obtain spin-echo images, cine-MRI, and flow-velocity maps. Seventy-nine patients had TEE (37 biplane). A simple score (range, 0 to 1) was used for quantification of the results of MRI and TEE alone, for their comparison (in the 75 patients who had both), and for assessment of their combination. MRI, TEE, or their combination achieved a score of at least 0.75 in 18 of 25 diagnostic categories. A summary of the scores showed that for intracardiac anatomy. MRI scored 0.34, TEE scored 0.71 (P < .0001), and MRI plus TEE scored 0.84 (P < .003); for extracardiac anatomy, MRI scored 0.76, TEE scored 0.23 (P < .0001), and MRI plus TEE scored 0.84 (P = NS); and for hemodynamics and function, MRI scored 0.58, TEE scored 0.41 (P < .05), and MRI plus TEE scored 0.67 (P = NS). Total scores were MRI, 0.52; TEE, 0.50 (P = NS); and MRI plus TEE, 0.80 (P < .0001). MRI and TEE were inadequate for collateral and coronary arteries and pulmonary vascular resistance. Cine-MRI and flow-velocity maps comprised 43% of the MRI scores. Biplane TEE was better than single plane (scores of 0.59 versus 0.42, P < .0001).

CONCLUSIONS

MRI and TEE are important and complementary "second-line" investigations for congenital heart disease. Analysis of their performance in a wide range of diagnostic categories provides guidelines for their judicious application. Where both are available, diagnostic catheterizations are either obviated or simplified.
Plasma thromboxane B2 concentration in pulmonary hypertension associated with congenital heart disease.
Authors: Fuse S , Kamiya T
Published: June 2012

BACKGROUND

We investigated the plasma concentration of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), to assess platelet activation in 78 patients who had pulmonary hypertension associated with congenital heart disease (PH group) and 16 patients with almost normal hemodynamics (control group).

METHODS AND RESULTS

The PH group was divided into two subgroups: pulmonary vascular resistance (Rp) < or = 10 U/m2 (Rp < or = 10 group) and > 10 U/m2 (Rp > 10 group). In addition, the Rp < or = 10 group was divided on the basis of clinical symptoms into groups with dyspnea (dyspnea[+] group) and without dyspnea (dyspnea[-] group). Plasma TXB2 levels were measured by radioimmunoassay. Plasma TXB2 levels in the three groups (control, Rp < or = 10, and Rp > 10) were significantly different (P < .005); the TXB2 levels in the Rp < or = 10 group were significantly higher than the others. Among the Rp < or = 10 patients, the plasma TXB2 levels were significantly higher in the dyspnea(+) group than in the dyspnea(-) group (P < .0001). In addition, the pulmonary-to-systemic flow ratio and pulmonary blood flow divided by body surface area were significantly higher in the dyspnea(+) group than in the dyspnea(-) group (P < .02 and P < .002, respectively).

CONCLUSIONS

These findings suggest that platelet activation led to increased TXA2 release in patients with pulmonary hypertension, especially those with dyspnea and Rp < or = 10. TXA2 release from platelets probably caused constriction of the pulmonary arterioles and the bronchi, thus worsening pulmonary hypertension and dyspnea in these patients. In the patients with high Rp values, it was considered that the number of pulmonary arterioles where platelets could be activated had been reduced.
Anterior septal coronary artery infarction in the canine: a model of ventricular tachycardia with a subendocardial origin. Ablation and activation sequence mapping.
Authors: Tweddell J S , Rokkas C K , Harada A , Pirolo J S , Branham B H , Schuessler R B , Boineau J P , Cox J L
Published: June 2012

BACKGROUND

In humans, chronic ventricular tachycardia (VT) is usually associated with myocardial infarcts that involve the interventricular septum. In an effort to more closely mimic the anatomic substrate that gives rise to chronic VT in humans, we developed a canine model of VT in which the anterior septal coronary artery was ligated. The site of earliest activation, the subsequent activation sequence, and the mechanism of VT associated with the resultant ventricular septal infarct was then evaluated to determine if this model accurately reflected the characteristics of human VT.

METHODS AND RESULTS

Seventeen dogs underwent occlusion-reperfusion ventricular septal infarcts. Four to 7 days later, electrophysiological studies were performed. VT was initiated by programmed electrical stimulation and terminated by pacing at a cycle length of 50% to 75% of the VT cycle length. Electrophysiological studies were performed using a 256-channel mapping system. A total of 15 VT morphologies were mapped in 9 animals. Fourteen of 15 morphologies had septal subendocardial sites of earliest activation and 1 had a septal midwall site of earliest activation. VT ablation was performed using a nitrous oxide cryoprobe and confirmed the site of earliest activation by subsequently rendering VT noninducible. Electrophysiological studies demonstrated four distinct VT activation sequences: (1) circular reentrant (n = 7), (2) concentric spread (n = 5), (3) figure-of-eight (n = 2), and (4) septal midwall (n = 1).

CONCLUSIONS

This canine model of ventricular septal infarction produces VTs with sites of earliest activation and activation sequences similar to those in humans. A reentrant mechanism as the basis of these arrhythmias is supported by the following observations: (1) all VT was initiated and terminated with programmed electrical stimulation; (2) VT activation sequences were consistent with reentry; and (3) precise interruption of the sequence terminated the VT and rendered it noninducible.
Transesophageal Echocardiography for the Diagnosis and Management of Nonobstructive Thrombosis of Mechanical Mitral Valve Prosthesis
Authors: Gueret Pascal , Vignon Philippe , Fournier Pierre , Chabernaud Jean-Marc , Gomez Marie , LaCroix Philippe , Bensaid Julien
Published: June 2012

Background
Diagnosis of a mechanical mitral valve prosthesis thrombosis is currently made with transthoracic Doppler echocardiography and occasionally with fluoroscopy. However, identifying a thrombus on a valve prosthesis may be difficult, especially if the thrombus is nonobstructive. To prospectively define the role of transesophageal echocardiography for identification of nonobstructive thrombi, we studied a series of patients in whom the prosthetic valve was considered to function normally on clinical examination and transthoracic echocardiography.

Methods and Results
One hundred fourteen consecutive patients with mechanical mitral valve prosthesis were investigated by both transthoracic echocardiography and transesophageal echocardiography. These examinations were performed for recent systemic emboli (15 patients), fever of unknown etiology (11 patients), routine postoperative evaluation (56 patients), and other reasons (32 patients). Based on transthoracic echo diagnosis, all prostheses were considered normal. Yet, in 20 patients transesophageal echocardiography revealed the presence of a 2- to 15-mm-long mobile thrombus localized on the atrial surface of the prosthesis. When compared with the remaining 94 patients with no visible thrombi, there was no significant difference between the two groups in terms of incidence of atrial fibrillation (65% versus 52%), left atrial size (48±9 versus 51±13 mm), left ventricular end-diastolic diameter (49±10 versus 51±13 mm) and fractional shortening (28±9% versus 31±10%), presence of spontaneous contrast in the left atrium (40% versus 41%), transprosthetic mean pressure gradient (4.0±1.4 versus 3.9±1.5 mm Hg), or the type of prosthesis used. After we discovered a nonobstructive thrombosis, patients were treated with heparin (n=9) or oral anticoagulation (n=11). The presence of a localized thrombus was confirmed in 3 patients who were operated on. In the present study, evolution appeared to depend on thrombus size: of 14 patients exhibiting a small (<5 mm) thrombus, 10 had an uneventful course, whereas 5 of 6 patients with a large (≥5 mm) thrombus developed complications or died.

Conclusions
Transesophageal echocardiography appears to be a reliable method to diagnose thrombi on a mechanical mitral valve prosthesis, even when transthoracic Doppler echocardiographic parameters appear to be normal. Transesophageal echo assessment of thrombus size may be helpful in deciding whether a patient with mitral prosthesis should be treated by anticoagulation, thrombolysis, or valve rereplacement. .
Surgical Therapy for Coronary Artery Disease Among Patients With Combined Coronary Artery and Peripheral Vascular Disease
Authors: Rihal Charanjit S. , Eagle Kim A. , Mickel Mary C. , Foster Eric D. , Sopko George , Gersh Bernard J.
Published: June 2012

Background
Among patients with combined coronary artery and peripheral vascular disease, long-term benefits of surgical therapy compared with medical therapy for coronary artery disease are unknown.

Methods and Results
Using prospectively collected data from the Coronary Artery Surgery Study registry, we performed a retrospective cohort analysis of 1834 patients (mean age, 56 years; 20% women) with both coronary artery and peripheral vascular disease and evaluated their long-term outcomes. Of these patients, 986 received (nonrandomly) coronary artery bypass graft surgery, and 848 were treated medically. Perioperative mortality was 4.2% (2.9% in the absence of peripheral vascular disease;
P
=.02). In a mean follow-up period of 10.4 years, 1100 deaths occurred (80% due to cardiovascular causes). For the surgical group, 4-, 8-, 12-, and 16-year estimated probabilities of survival were 88%, 72%, 55%, and 41%, respectively, and 73%, 57%, 44%, and 34%, respectively, for the medical group (
P
<.0001). Multivariate analysis demonstrated that type of therapy was independently associated with survival (
P
=.0001; χ
2
=15.34). Subgroup analysis suggested that benefits of surgical treatment on survival were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction. Survival free of death or myocardial infarction was also significantly better among the surgical group. Type of therapy was significantly associated with occurrence of late events (
P
=.01; χ
2
=6.55). Subgroup analysis again demonstrated that beneficial effects of surgery were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction.

Conclusions
Surgical treatment provides long-term benefit for certain subgroups of patients with combined coronary artery and peripheral arterial vascular disease.