bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiofrequency catheter ablation of sustained intra-atrial reentrant tachycardia in adult patients. Identification of electrophysiological characteristics and endocardial mapping techniques.
Authors: Chen S A , Chiang C E , Yang C J , Cheng C C , Wu T J , Wang S P , Chiang B N , Chang M S
Published: June 2012

BACKGROUND

Information about electrophysiological characteristics and radiofrequency ablation of intra-atrial reentrant tachycardia has not been reported before. We proposed that induction and termination of intra-atrial reentrant tachycardia by atrial extrastimuli or rapid atrial pacing and resetting the response pattern by atrial extrastimuli during intra-atrial reentrant tachycardia could ensure the mechanism of reentry and that the earliest site of endocardial activation and concealed entrainment pace mapping with the shortest stimulus-P wave interval could localize a critical area responsible for intra-atrial reentrant tachycardia and radiofrequency ablation.

METHODS AND RESULTS

Seven patients with refractory atrial tachycardia were referred for electrophysiological studies and radiofrequency ablation. Electrophysiological studies and endocardial mapping found (1) 10 atrial foci with atrial tachycardia cycle length of 406 +/- 41 ms; (2) atrial tachycardia had induction and termination by atrial extrastimuli (8 of 10) or rapid atrial pacing (10 of 10); (3) atrial tachycardia had increasing (6 of 10) or mixed (flat and increasing, 4 of 10) resetting response pattern, with resetting interval of 57 +/- 13 ms (14 +/- 4% of atrial tachycardia cycle length); (4) exit sites of atrial tachycardia in right atrial free wall (6 of 10), right atrial septum (3 of 10), and midposterior left atrium (1 of 10); and (5) earliest activation site had timing relative to P wave by -37 +/- 7 ms, and concealed entrainment pace mapping had shortest stimulus-P interval 23 +/- 3 ms. By the endocardial activation pace-mapping technique, radiofrequency energy (8 +/- 1 pulses, 31 +/- 3 W, 101 +/- 11 seconds) successfully eliminated the 10 atrial foci without recurrence (follow-up, 16 +/- 5 months).

CONCLUSIONS

Mechanism of intra-atrial reentrant tachycardia could be confirmed by the electrophysiological characteristics, and radiofrequency ablation energy delivered to a critical area in the atrial reentrant circuit is safe and effective for the treatment of intra-atrial reentrant tachycardia.
Implantation and intermediate-term follow-up of stents in congenital heart disease.
Authors: O'Laughlin M P , Slack M C , Grifka R G , Perry S B , Lock J E , Mullins C E
Published: June 2012

BACKGROUND

Balloon-expandable stents (Johnson and Johnson Interventional Systems) have been in use for congenital heart disease since late 1989. They have made possible treatment in previously untreatable branch pulmonary artery stenoses and systemic venous stenosis. The purpose of this report is to detail the results and intermediate-term follow-up of stents used for treatment of congenital heart disease.

METHODS AND RESULTS

Eighty-five patients underwent placement of 121 stents in Houston and Boston. Fifty-eight patients had stents put in pulmonary arteries, nine had stents in conduits or outflow tracts, and 21 had stents in venous stenoses or narrowed Fontan anastomoses. (Three patients had stents in two locations.) These stent procedures resulted in gradient reduction from 55.2 +/- 33.3 to 14.2 +/- 13.5 mm Hg in pulmonary arteries, from 41.4 +/- 26.0 to 20.7 +/- 17.0 mm Hg in conduits or outflow tracts, and from 9.8 +/- 6.9 to 2.4 +/- 3.1 mm Hg in venous stenoses or Fontan anastomoses. Diameter of narrowings increased from 4.6 +/- 2.3 to 11.3 +/- 3.2 mm in the pulmonary artery, from 8.8 +/- 3.6 to 12.7 +/- 2.6 in conduits, and from 3.8 +/- 2.9 to 11.3 +/- 2.8 in venous stenoses. Follow-up has shown stent fracture in one patient, restenosis in one, and sudden death in one. Recatheterization has been done in 38 patients an average of 8.6 months after stent installation. Compared with immediately postimplant data, there was no significant change in luminal diameter or pressure gradient. Redilation was performed in 14 patients (17 stents) 1 week to 24 months after implantation (mean, 10.2 months), with a small but significant increase in stenosis diameter.

CONCLUSIONS

We conclude that stent treatment of vascular stenoses in congenital heart disease retains efficacy at medium-term follow-up and offers a much-improved outlook for patients with these lesions.
Growth of the aortic anastomosis, annulus, and root after the arterial switch procedure performed in infancy.
Authors: Hourihan M , Colan S D , Wernovsky G , Maheswari U , Mayer J E , Sanders S P
Published: June 2012

BACKGROUND

We investigated the size and growth potential of the neoaortic root and aortic anastomosis after the arterial switch operation (ASO) for D-transposition of the great arteries (D-TGA) performed in infants. Circumferential suture lines connecting the great arteries and extensive surgery on the arterial roots to transplant the coronary arteries are essential parts of the ASO. However, little is known about the growth of the aortic anastomosis, the neoaortic root, and the neoaortic annulus after the ASO performed in infancy.

METHODS AND RESULTS

Serial echocardiograms on 50 patients with D-TGA who underwent ASO in infancy at our institution were reviewed, and the size of the aortic anastomosis, the neoaortic root, and the neoaortic annulus were compared with similar structures in a group of 312 control subjects. Before surgery, the native pulmonary root (future neoaortic root) was 1.59 SD larger (P < .001) and the native pulmonary annulus (future neoaortic annulus) was 1.4 SD larger (P < .001) in infants with D-TGA than the aortic root and annulus of control patients. At a mean of 22 months (12 months to 6 1/2 years) after surgery, the diameter of the aorta at the anastomosis was 0.45 SD smaller than the ascending aorta of control subjects (P < .001). The neoaortic root was 2.9 SD larger (P < .001) and the neoaortic annulus was 1.6 SD larger (P < .001) than the comparable structures in the control population. Most important, growth of the aortic anastomosis was commensurate with somatic growth, but the dilation of the neoaortic root appeared to be progressive over time. The neoaortic root was significantly more dilated in patients with a history of pulmonary artery banding (P < .001) and in patients with neoaortic regurgitation (P < .001). The presence of a ventricular septal defect was not significantly related to postoperative neoaortic root size.

CONCLUSIONS

This study underlies the importance of continued acquisition and examination of the data regarding the long-term outcome of the arterial switch operation performed in infancy.
Echocardiographic follow-up of atrial septal defect after catheter closure by double-umbrella device.
Authors: Boutin C , Musewe N N , Smallhorn J F , Dyck J D , Kobayashi T , Benson L N
Published: June 2012

BACKGROUND

Transcatheter device occlusion of atrial septal defects is an attractive approach, but its efficacy and place in patient management remain to be determined.

METHODS AND RESULTS

To evaluate the medium-term results of atrial septal defect device occlusion and factors influencing residual shunting, transesophageal and transthoracic echocardiograms of 49 patients were reviewed. Transesophageal echocardiograms on 48 patients immediately following surgical closure revealed residual shunting in 2% compared with 91% after device occlusion; this proportion decreased to 53% after a mean follow-up of 10 months. The actuarial analysis suggests a progressive resolution of shunting with time. One patient had residual shunting by transesophageal echocardiography immediately after surgical closure compared with 29 after a mean follow-up of 10 months after device occlusion. Residual shunting was not influenced by (1) dimension, location, or position with relation to the device as assessed by transesophageal echocardiography; (2) location of the defect; or (3) device size relative to the stretched dimension of the defect. In 15 patients, a poor correlation existed between transesophageal and transthoracic echocardiographic findings. Variability in serial transthoracic echocardiographic findings was observed in 14. Right ventricular dimension, heart size, and presence of a murmur at follow-up did not correlate with the presence or size of residual shunting after device occlusion.

CONCLUSIONS

These results suggest that ongoing spontaneous resolution of residual shunting occurs after device insertion. Factors related to the defect or device could not predict eventual resolution of residual shunting. Transthoracic echocardiography in the follow-up of these patients may not be reliable in determining presence of residual shunting.
Amiodarone and post-MI patients.
Authors: Nademanee K , Singh B N , Stevenson W G , Weiss J N
Published: June 2012

Amiodarone is a viable drug for preventing sudden cardiac death, particularly during the first year after MI. If larger trials confirm the aforementioned prospective trials of Ceremuzynski et al, Cairns et al, and the BASIS trial, the efficacy of amiodarone would outweigh the risk of its side effects during the first year after MI. Based on the long-term observation from the BASIS trial, the duration of amiodarone therapy need not be more than 1 year--which, as we have learned, is when these post-MI patients would benefit most from the drug. It is also likely that the effects of amiodarone would complement those of aspirin and angiotensin converting enzyme inhibitors. The SAVE, CONSENSUS II, and SOLVD trials demonstrated that captopril and enalapril did not reduce the mortality rate during the first year after MI, nor did they reduce the sudden cardiac death rate. Their beneficial effects became evident only during the second year and thereafter. Unlike other antiarrhythmic agents of various classes, amiodarone possesses antiarrhythmic properties but does not exert deleterious effects on ventricular function. More studies are needed to determine if the benefit of amiodarone could be enhanced by combination therapy (eg, angiotensin converting enzyme inhibitors, aspirin, or beta-blockers). Whether amiodarone will provide the same protection for patients who have poor left ventricular function or congestive heart failure is not known. The European and VA cooperative studies should help answer this question. If it turns out that amiodarone is beneficial, one must then determine whether higher doses of the drug will offer more protection, and, if so, if that greater protection would be offset by increased toxicity. How much amiodarone should be given to offer the most protection with the least risk? Another intriguing research question is this: If we treat patients with amiodarone for more than 1 year, would the drug continue to improve the mortality rate in subsequent years? Other studies are needed in patients at very high risk of sudden cardiac death (ie, those who have a low ejection fraction and high-density VPDs). A study comparing amiodarone and sotalol in high-risk patients for sudden cardiac death is also needed. These clinical studies should be carried out with basic science research investigating the actions of amiodarone at the molecular and cellular level in order to give us a better understanding of how the drug works.
Natriuretic peptide system in human heart failure.
Authors: Wei C M , Heublein D M , Perrella M A , Lerman A , Rodeheffer R J , McGregor C G , Edwards W D , Schaff H V , Burnett J C
Published: June 2012

BACKGROUND

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are a family of structurally related peptides that participate in the integrated control of renal and cardiovascular function. Previous studies suggest a functional role for these hormonal peptides in cardiorenal regulation in congestive heart failure (CHF).

METHODS AND RESULTS

The present studies were performed in normal subjects (n = 6) and in patients with mild (New York Heart Association [NYHA] class I to II, n = 20) and severe (NYHA class III to IV, n = 20) CHF by use of radioimmunoassay and immunohistochemical staining (IHCS). Plasma ANP was significantly increased in both mild and severe CHF compared with normal subjects. In contrast, plasma BNP was only moderately increased in the severe CHF group, and plasma CNP concentration was unchanged in CHF compared with normal subjects. Atrial tissue concentrations of the natriuretic peptides did not parallel circulating concentrations. ANP predominated in normal atrial tissue, but BNP predominated in CHF. In ventricular tissue, IHCS staining was present for all three peptides in normal ventricular myocardium and was markedly enhanced in CHF.

CONCLUSIONS

These studies support a differential regulation of ANP, BNP, and CNP circulating concentrations and tissue activity in human CHF.
Inhibition of experimental neointimal hyperplasia and thrombosis depends on the type of vascular injury and the site of drug administration.
Authors: Rogers C , Karnovsky M J , Edelman E R
Published: June 2012

BACKGROUND

Heparin inhibits vascular smooth muscle cell proliferation in tissue culture and limits neointimal hyperplasia after experimental arterial injury but has been ineffective in reducing clinical restenosis. We examined how this discrepancy might reflect suboptimal drug-tissue interactions and/or differences in the vascular response to injury.

METHODS AND RESULTS

Intravenous infusion was compared with local administration of heparin to injured rabbit iliac arteries either from drug-impregnated polymeric controlled release matrices in the perivascular space or from drug-releasing endovascular stents. Occlusive thrombosis, seen in 42% of control stent-bearing arteries, and partial thrombosis were virtually eliminated by heparin delivery from any route. Intimal area 14 days after balloon withdrawal denudation alone was reduced to an equal extent by continuous systemic heparin or by perivascular heparin for the first 3 days. In contrast, endovascular stents produced more exuberant neointimal hyperplasia, the inhibition of which required continuous rather than only early heparin administration. Neither perivascular delivery limited to the first 3 days nor stent-based delivery reduced neointimal hyperplasia as effectively.

CONCLUSIONS

The antiproliferative and antithrombotic effects of heparin differ markedly, depending on the type of arterial injury and the mode of drug administration. Different forms of injury may require different therapies, and complications of arterial intervention such as excessive neointimal hyperplasia and thrombosis may demand alternate therapeutic regimens. Duration, dose, and site of delivery rather than frank resistance to therapy may explain why experimentally effective antiproliferative and antithrombotic agents fail clinically.
Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts.
Authors: Peters N S , Green C R , Poole-Wilson P A , Severs N J
Published: June 2012

BACKGROUND

Gap junctions are a determinant of myocardial conduction. Disturbances of gap-junctional content may account for abnormalities of impulse propagation, contributing to the arrhythmic tendency and mechanical inefficiency of ischemic and hypertrophied myocardium. The aim of this study was to characterize gap junction organization in normal human ventricular myocardium and to establish whether abnormalities exist in myocardium of chronically ischemic and hypertrophied hearts.

METHODS AND RESULTS

Cardiac gap-junctional connexin43 antibodies and confocal microscopy were used in a quantitative immunohistochemical study of surgical myocardial samples to explore the structural basis of electromechanical ventricular dysfunction in chronic ischemic and hypertrophic heart diseases. Normal adult human left ventricular myocardium had a gap-junctional surface area of 0.0051 micron2/micron3 myocyte volume; gap junctions were confined to intercalated disks, of which there was a mean of 11.6 per cell. The right ventricle showed similar gap junction surface area. Left ventricular myocardium from ischemic hearts (distant from any fibrotic scarring), despite normal numbers of intercalated disks per cell, had a reduced gap junction surface area (0.0027 micron2/micron3; P = .02), as did hypertrophied myocardium (0.0031 micron2/micron3; P = .05). The cardiac myocytes in the pathological tissues were larger than normal, and estimated gap-junctional content per cell was reduced in ischemic ventricle (P = .02) compared with normal.

CONCLUSIONS

Gap junctions in normal adult human working ventricular myocardium occupy an area of 0.0051 micron2/micron3 myocyte volume. This surface area is reduced in ventricular myocardium from hearts subject to chronic hypertrophy and ischemia, despite a normal number of intercellular abutments, and this alteration may contribute to abnormal impulse propagation in these hearts.
Regional blood flow, oxidative metabolism, and glucose utilization in patients with recent myocardial infarction.
Authors: Czernin J , Porenta G , Brunken R , Krivokapich J , Chen K , Bennett R , Hage A , Fung C , Tillisch J , Phelps M E
Published: June 2012

BACKGROUND

Metabolic imaging with positron emission tomography (PET) can detect tissue viability in clinical infarct regions. With appropriate tracer kinetic models and serial PET imaging, regional myocardial blood flow and rates of metabolism can now be quantified in patients with recent myocardial infarctions.

METHODS AND RESULTS

Serial PET imaging with [13N]ammonia, [11C]acetate, and 18F-deoxyglucose was performed in 22 patients with recent infarctions to measure regional blood flow (in milliliters per gram per minute), glucose metabolism (in micromoles per gram per minute), and oxidative metabolism (in clearance rate per minute). Hypoperfused clinical infarct regions were classified as "PET mismatch" if 18F was increased relative to 13N activity or "PET match" if 13N and 18F activities were reduced concordantly. Blood flows differed significantly between normal, mismatch, and match segments (0.83 +/- 0.20, 0.57 +/- 0.20, and 0.32 +/- 0.12 mL.g-1.min-1, respectively). The relation between oxidative metabolism and blood flow was piecewise linear and differed significantly between PET mismatch and PET match. Oxidative metabolism was less severely reduced than blood flow in mismatch regions but but reduced in proportion to blood flow in match regions. There was considerable overlap of blood flows between both types of PET segments.

CONCLUSIONS

Quantification of regional blood flow and substrate metabolism in postinfarction patients revealed alterations in the relation between substrate delivery and consumption demonstrated previously only in invasive animal experiments. The preserved oxidative metabolism in myocardium with PET mismatches may be ascribed to a regional increase in oxygen extraction. Such increase together with preserved glucose utilization may be the prerequisite for survival of ischemically injured myocardium.
Relation of plasma lipoprotein(a) to infarct artery patency in survivors of myocardial infarction.
Authors: Moliterno D J , Lange R A , Meidell R S , Willard J E , Leffert C C , Gerard R D , Boerwinkle E , Hobbs H H , Hillis L D
Published: June 2012

BACKGROUND

In the minutes to days after myocardial infarction, endogenous lysis of an occlusive coronary arterial thrombus occurs in most subjects. Compared with those in whom thrombolysis does not occur, those with antegrade flow in the infarct artery have improved left ventricular performance, less left ventricular dilatation, and improved survival. This study was performed to assess intrinsic hemostasis and fibrinolysis in survivors of myocardial infarction with or without antegrade perfusion of the infarct artery.

METHODS AND RESULTS

In 105 survivors of infarction (75 men, 30 women; age, 30 to 80 years) not given thrombolytic therapy, coronary angiography revealed a patent (group 1, n = 52) or occluded (group 2, n = 53) infarct artery. Plasma concentrations of plasminogen, fibrinogen, tissue plasminogen activator activity, infarct artery. Plasma concentrations of plasminogen, fibrinogen, tissue plasminogen activator activity, plasminogen activator inhibitor activity, cholesterol, triglycerides, and lipoproteins, including lipoprotein(a) (Lp[a]), were measured in blood procured 23 +/- 13 (mean +/- SD) months after infarction. Groups 1 and 2 were similar in age, sex, race, cardioactive medications, infarct artery, extent of coronary artery disease, and left ventricular performance. Of the plasma constituents assayed, the groups were similar except that Lp(a) averaged 18.5 +/- 21.7 mg/dL in group 1 and 49.1 +/- 44.8 mg/dL in group 2 (P < .001). This difference was evident in both Caucasian (n = 65) (P = .009) and African American (n = 40) (P = .01) subjects.

CONCLUSIONS

Survivors of myocardial infarction who failed to recanalize the infarct artery have higher plasma Lp(a) concentrations than those with a patent infarct artery. Lp(a) may inhibit intrinsic fibrinolysis.
Relation of phasic coronary flow velocity profile to clinical and hemodynamic characteristics of patients with aortic valve disease.
Authors: Hongo M , Goto T , Watanabe N , Nakatsuka T , Tanaka M , Kinoshita O , Yamada H , Okubo S , Sekiguchi M
Published: June 2012

BACKGROUND

Our objective was to assess phasic coronary blood flow and velocity characteristics of the proximal portion of the left anterior descending artery and to evaluate their relation to the clinical and hemodynamic manifestations in patients with aortic valve disease.

METHODS AND RESULTS

We examined 26 patients with chronic aortic regurgitation (AR), 12 patients with predominant aortic stenosis (AS), and 11 control subjects using an intravascular Doppler catheter with spectral analysis. Angiographic assessment of AR identified 10 patients with mild regurgitation and 16 with severe regurgitation. The resting systolic coronary flow velocity-time integral (VTI) was significantly higher and the diastolic VTI was slightly but significantly higher in patients with severe regurgitation than in those with mild regurgitation (11.8 +/- 4.2 vs 4.1 +/- 1.1 cm, P < .001; 18.5 +/- 5.8 vs 13.2 +/- 3.2 cm, P < .05) and control subjects (4.0 +/- 1.0 cm, P < .001 and 13.3 +/- 3.6 cm, P < .05), respectively. Patients with AS had a slightly lower resting systolic VTI (3.8 +/- 1.4 cm) and a higher diastolic VTI (14.6 +/- 3.7 cm) than control subjects. Resting coronary blood flow was greater in patients with aortic valve disease than in control subjects. There was a significant correlation between the ratio of the resting systolic to diastolic VTI (S/D ratio) and the ratio of the aortic systolic to diastolic pressure (r = .75, P < .001) in patients with AR. The S/D ratio was inversely correlated with left ventricular systolic pressure (r = -.92, P < .001) and positively correlated with the ratio of the aortic systolic to diastolic pressure (r = .68, P < .05) in patients with AS.

CONCLUSIONS

Our results indicate that hemodynamic changes related to aortic valve disease contribute to alterations in the resting phasic coronary blood flow and velocity profiles observed in these patients.
Streptokinase induces intravascular release of platelet-activating factor in patients with acute myocardial infarction and stimulates its synthesis by cultured human endothelial cells.
Authors: Montrucchio G , Bergerone S , Bussolino F , Alloatti G , Silvestro L , Lupia E , Cravetto A , Di Leo M , Emanuelli G , Camussi G
Published: June 2012

BACKGROUND

Reocclusion of a successfully recanalized infarct-related artery may account for failure of thrombolytic therapy. Evidence suggests that the intravascular activation of platelets may limit the response to this treatment. The aim of the present study was to investigate whether platelet-activating factor (PAF), an ether lipid mediator with multiple potent biological activities, is synthesized during therapy with thrombolytic agents. Two sets of experiments were performed: (1) we extracted and quantified PAF in blood of patients with acute myocardial infarction treated or untreated with streptokinase (SK), and (2) since the endothelium/platelet interaction is thought to be at the basis of vascular reocclusion, we studied whether cultured human endothelial cells synthesize PAF after stimulation with SK or plasmin.

METHODS AND RESULTS

PAF was extracted from blood samples immediately after acidification to destroy the acid-labile PAF-acetylhydrolase in 25 patients with acute myocardial infarction treated (group A, n = 14) and untreated (group B, n = 11) with intravenous infusion of SK. PAF was detected in 10 of 14 patients of group A and none of group B. PAF began to be detectable 60 to 90 minutes after SK infusion and disappeared from the circulation within 120 to 180 minutes. Percent variation of platelet count over basal values correlated negatively with the amount of PAF present in the circulation at 90 minutes (r = -.719; P < .001) and at 120 minutes (r = -.652; P < .001). Cultured human umbilical cord vein-derived endothelial cells (ECs) synthesized PAF in a dose-dependent manner in response to SK and plasmin, with a synthesis that peaked at 15 minutes and persisted up to 30 minutes for SK and 2 hours for plasmin. PAF extracted from blood samples or from ECs was quantified by bioassay performed after purification by thin-layer chromatography and high-performance liquid chromatography (HPLC). PAF-bioactive material was characterized as PAF with physicochemical and enzymatic treatments, HPLC-tandem mass spectrometry, and specific PAF-receptor antagonists.

CONCLUSIONS

The observation that PAF was detectable in the blood of patients of group A only after treatment with SK and was not detectable in patients with a comparable infarct not treated with SK (group B) suggested that SK stimulates the synthesis of this mediator either directly or via plasmin generation. Indeed, cultured human ECs synthesize PAF after stimulation with both SK and plasmin. PAF production by ECs may promote platelet activation and interaction of these cells as well as of circulating leukocytes with endothelium. These events may limit the beneficial effects of thrombolytic therapy.
Race and prognosis after myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) phase II trial.
Authors: Taylor H A , Chaitman B R , Rogers W J , Kern M J , Terrin M L , Aguirre F V , Sopko G , McMahon R , Ross R N , Bovill E C
Published: June 2012

BACKGROUND

To better understand the role of race/ethnicity in survival after acute myocardial infarction, we compared clinical and laboratory data, response to thrombolytic therapy, and clinical outcome in 2885 patients participating in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Trial among three groups of patients (2564 whites, 174 blacks, and 147 Hispanics).

METHODS AND RESULTS

Differences were found in baseline characteristics among the three groups including (1) age (mean age for whites, 57.2 years; blacks, 54.8 years; Hispanics, 52.8 years; P < .001), (2) sex (percentage of women for whites, 17.6; blacks, 28.7; Hispanics, 14.3; P < .001), and (3) risk factor prevalence: current smoking (percent for whites, 49.4; blacks, 62.1; Hispanics, 55.1; P < .003), history of hypertension (percent for whites, 36.6; blacks, 55.7; Hispanics, 39.5; P < .001), and diabetes mellitus (percent for whites, 11.9; blacks, 22.4; Hispanics, 19.7; P < .001). Changes in hemostatic factors 5 hours after infusion of recombinant tissue plasminogen activator (rt-PA) revealed a more profound fall in fibrinogen levels in black patients compared with the response seen in Hispanic or white patients (mean change in fibrinogen +/- SD, mg/dL: 151.3 +/- 107.4, 112.2 +/- 97.0, 109.4 +/- 98.6; P < .001, respectively) without more frequent infarct-related artery patency or hemorrhagic complications. Mortality was similar in the white, black, and Hispanic patients through the first year after adjustment for baseline variables.

CONCLUSIONS

TIMI II data yield evidence that (1) corroborates published reports of a high prevalence of classic cardiovascular risk factors among minority patients with acute myocardial infarction, (2) there is a greater decrease in fibrinogen levels 5 hours after the start of rt-PA infusion among black patients than in white and Hispanic patients without evidence of more frequent infarct-related artery patency or hemorrhagic complications, and (3) thrombolytic therapy with appropriate supplemental measures is associated with comparable 1-year mortality in white, black, and Hispanic patients.
Initial experience with a direct antithrombin, Hirulog, in unstable angina. Anticoagulant, antithrombotic, and clinical effects.
Authors: Lidón R M , Théroux P , Juneau M , Adelman B , Maraganore J
Published: June 2012

BACKGROUND

Currently available antithrombotic therapy for unstable angina is unwieldy and occasionally ineffective. This study was designed to investigate the potential of Hirulog, a new synthetic specific antithrombin agent, for the management of this condition.

METHODS AND RESULTS

A total of 55 patients in the acute phase of unstable angina received intravenous Hirulog according to one of two protocols. In an acute dose-escalating study, 0.02, 0.05, 0.1, 0.25, and 0.5 mg.kg-1 x h-1, each for 30 minutes, were infused in 15 patients. Prolongation of activated partial thromboplastin time (aPTT) (r = .95), fibrinopeptide A inhibition (r = .96), and Hirulog plasma levels (r = .91) correlated closely with the dose infused, with significant changes compared with baseline appearing at doses of 0.25 mg.kg-1 x h-1 and higher. The purposes of the second protocol were to determine whether the anticoagulant and antithrombotic effects of the drug were sustained during a 72-hour infusion and to assess whether such treatment prevented the complications of unstable angina. Based on the initial study, we planned to give a dose of 0.25 mg.kg-1 x h-1 to each patient until 2 patients failed therapy, then successively higher doses until a 95% success rate was achieved or adverse effects intervened, increasing the dose after two failures had occurred at each level. Five patients received the 0.25-mg.kg-1 x h-1 dose and 14 the 0.5-mg.kg-1 x h-1 dose before two failures occurred. Failure was observed in only one of 21 patients at the dose of 1 mg.kg-1 x h-1. aPTT (+/- SEM) levels increased to 62 +/- 5, 76 +/- 2, and 98 +/- 3 seconds at the three doses, with minimal intraindividual variation, and Hirulog plasma levels to 1050, 2100, and 4200 mg/mL, respectively. Fibrinopeptide A plasma levels decreased at all doses but more consistently at the dose of 1 mg.kg-1 x h-1. The overall clinical success rate was 87.5%: 60% (3/5) at the low dose, 86% (12/14) at the intermediate dose, and 95% (20/21) at the high dose. No deaths, myocardial infarctions, or bleeding complications occurred.

CONCLUSIONS

In unstable angina patients, Hirulog infusions quickly and reproducibly yield stable, dose-dependent anticoagulant and antithrombotic effects with a favorable clinical efficacy profile.
Ionic mechanisms of electronic inhibition and concealed conduction in rabbit atrioventricular nodal myocytes.
Authors: Liu Y , Zeng W , Delmar M , Jalife J
Published: June 2012

BACKGROUND

The term "concealed conduction" is used in electrocardiography when a proximal (atrial or ventricular) impulse penetrates the atrioventricular (AV) node but fails to traverse it completely. Its penetration into the node is inferred by its after effects on the propagation of succeeding impulses. Concealed AV nodal conduction is a well-established phenomenon, but its precise cellular and subcellular mechanisms are unknown. It has been suggested that concealed conduction results from a transient impairment of excitability caused by the subthreshold depolarization (ie, electrotonic inhibition) that is elicited downstream of the site of block.

METHODS AND RESULTS

We studied the ionic mechanism of electrotonic inhibition and concealed conduction in single myocytes isolated from the rabbit AV node. Cells were paced using just-threshold current pulses delivered at a constant (basic) cycle length of 1 second. Appropriately timed interpolation of a conditioning pulse of depolarizing but subthreshold current led to failure of the subsequent, previously successful activation. The ability of the subthreshold response to inhibit subsequent excitation was increased when the interval between the conditioning and succeeding pulses was shortened, when the amplitude of the conditioning pulse was increased, or when the inward sodium current was blocked by superfusion with tetrodotoxin (30 microM). Voltage clamp analysis demonstrated that electrotonic inhibition results from partial inactivation of the transient calcium current (ICa.T). Similar results were obtained using a mathematical model (Hodgkin-Huxley type) of the AV nodal myocyte. Additional simulations in a linear array of AV nodal cells showed that when a premature impulse fails to traverse the AV node, the subthreshold depolarization elicited downstream of the site of block may lead to a transient reduction of excitability with consequent delay or block of the succeeding impulse.

CONCLUSIONS

The overall data strongly suggest that some of the electrocardiographic manifestations of concealed AV conduction are the result of electrotonic inhibition of excitability secondary to a transient decrease in ICa.T.
Tetralogy of Fallot with pulmonary atresia. Rehabilitation of diminutive pulmonary arteries.
Authors: Rome J J , Mayer J E , Castaneda A R , Lock J E
Published: June 2012

BACKGROUND

Patients with tetralogy of Fallot, pulmonary atresia, and diminutive pulmonary arteries are a high-risk group for whom there is no consensus on the correct approach to medical management. The purpose of this report is to review a 14-year experience in the treatment of these patients comparing management schemes.

METHODS AND RESULTS

Between January 1978 and August 1988, 91 patients with tetralogy of Fallot and pulmonary atresia had an adequate evaluation of their pulmonary artery anatomy before any surgical management. Forty-eight of these patients had diminutive pulmonary arteries (38 to 104 mm2/m2) supplied by aortopulmonary collaterals and were managed in four different fashions. Of the 9 patients repaired primarily, 7 died early and the two survivors had poor hemodynamic outcome. Of the 9 patients conservatively managed with no intervention before 5 years of age, 4 died and only 1 had a satisfactory hemodynamic result after repair. Of 10 shunted patients, 3 died and 3 had satisfactory repairs. Since 1984, we have rehabilitated pulmonary arteries with (1) right ventricle to pulmonary artery surgical graft, (2) balloon dilation of residual pulmonary artery stenoses and embolization of collaterals, and (3) surgical closure of ventricular septal defect and repair of remaining obstructions. Of 20 patients so managed, 7 died after various stages, but 10 of 20 had complete repairs. All repaired patients with subsystemic right ventricular pressures had at least one successful pulmonary artery dilation.

CONCLUSIONS

A combined catheter-surgery approach begun at an early age in patients with tetralogy of Fallot and pulmonary atresia with diminutive pulmonary arteries appears to enhance the chances of satisfactory complete repair.
Mitral valve repair in rheumatic disease. The flexible solution.
Authors: Bernal J M , Rabasa J M , Vilchez F G , Cagigas J C , Revuelta J M
Published: June 2012

BACKGROUND

Mitral valve repair in rheumatic disease is technically more difficult, and there is little information on the long-term stability of this technique.

METHODS AND RESULTS

From January 1975 to December 1990, 327 patients underwent mitral valve repair with the Duran flexible ring annuloplasty for rheumatic valve disease. Mean age was 45.4 +/- 12.6 years (range, 23 to 73 years). The techniques used for valve repair include a Duran flexible ring annuloplasty in all cases, commissurotomy in 272 (83.2%), papillary muscle splitting in 171 (52.3%), and subvalvular apparatus repair in 59 patients (18.0%). One hundred one patients required associated tricuspid valve surgery (30.8%). Hospital mortality was 3.36%, being lower for patients with isolated mitral valve repair (2.7%) than those with mitrotricuspid surgery (4.9%). Mean follow-up was 8.6 years (range, 1 to 17 years) and was 96.5% completed. Thirty-four patients required reoperation for severe mitral insufficiency in 12, mitral restenosis in 18, and aortic valve disease in 4. The actuarial curve free from reoperation for mitral cause at 16 years is 89.9 +/- 3.2%. Late mortality occurred in 42 patients (13.2%). Actuarial survival curve at 16 years is 84.0 +/- 3.2% for isolated mitral valve repair and 64.6 +/- 6.7% for mitrotricuspid patients.

CONCLUSIONS

Mitral valve reconstruction with Duran flexible ring annuloplasty in rheumatic valve disease entails a low hospital mortality with satisfactory long-term clinical results.
Acute effect of percutaneous transvenous mitral commissurotomy on ventilatory and hemodynamic responses to exercise. Pathophysiological basis for early symptomatic improvement.
Authors: Tanabe Y , Suzuki M , Takahashi M , Oshima M , Yamazaki Y , Yamaguchi T , Igarashi Y , Tamura Y , Yamazoe M , Shibata A
Published: June 2012

BACKGROUND

Improvement of exertional dyspnea occurs immediately after percutaneous transvenous mitral commissurotomy (PTMC), but the pathophysiological basis for this early symptomatic improvement has not been elucidated.

METHODS AND RESULTS

Exercise hemodynamic measurement and exercise ventilatory measurement with arterial blood gas analysis were performed in 21 patients aged 50.4 +/- 9.5 years (mean +/- SD) with symptomatic mitral stenosis before and a few days after PTMC. Exercise ventilatory measurement were also performed in 14 normal control subjects aged 48.9 +/- 4.9 years. After PTMC, mitral valve area increased (from 1.0 +/- 0.3 to 1.7 +/- 0.3 cm2, P < .001), mean mitral gradient (from 12.2 +/- 5.2 to 5.2 +/- 2.2 mm Hg, P < .001), and mean left atrial pressure (from 18.7 +/- 6.1 to 12.1 +/- 4.0 mm Hg, P < .001) decreased. All patients experienced significant symptomatic improvement soon after PTMC. Comparison of hemodynamic parameters at the same ergometer work rate showed a significant decrease in pulmonary artery systolic pressure (from 77 +/- 18 to 67 +/- 14 mm Hg, P < .001) and diastolic pressure (from 36 +/- 10 to 28 +/- 7 mm Hg, P < .001) and a significant increase in cardiac output (from 6.4 +/- 1.4 to 8.1 +/- 1.9 L/min, P < .001). Despite the improvement in exercise hemodynamics and symptoms, exercise capacity determined by peak oxygen uptake (from 18.0 +/- 2.9 to 18.6 +/- 3.1 mL.kg-1 x min-1) and anaerobic threshold (from 11.7 +/- 2.4 to 12.0 +/- 2.4 mL.kg-1 x min-1) remained unchanged. Excessive exercise ventilation, as assessed by the slope of the regression line between expired minute ventilation and carbon dioxide output, decreased significantly from 37.2 +/- 6.7 to 33.9 +/- 5.8 (P < .001), but remained significantly higher than that in the normal subjects (27.9 +/- 3.6, P < .01). The ratio of total dead space to tidal volume and total dead space per breath during exercise decreased significantly after PTMC (P < .05). The change in excessive exercise ventilation after PTMC was correlated with the change in dead space to tidal volume ratio (r = .59).

CONCLUSIONS

Significant relief of exertional dyspnea immediately after PTMC is not accompanied by an improvement in exercise capacity. A decrease in excessive ventilation due to a decrease in physiological dead space resulting from hemodynamic improvement partly contributes to the early relief of symptoms after PTMC. However, lung compliance, which was not measured in the present study, may have changed after PTMC. This change may also contribute to the symptomatic improvement.
Bystander cardiopulmonary resuscitation. Is ventilation necessary?
Authors: Berg R A , Kern K B , Sanders A B , Otto C W , Hilwig R W , Ewy G A
Published: June 2012

BACKGROUND

Prompt initiation of bystander cardiopulmonary resuscitation (CPR) improves survival. Basic life support with mouth-to-mouth ventilation and chest compressions is intimidating, difficult to remember, and difficult to perform. Chest compressions alone can be easily taught, easily remembered, easily performed, adequately taught by dispatcher-delivered telephone instruction, and more readily accepted by the public. The principal objective of this study was to evaluate the need for ventilation during CPR in a clinically relevant swine model of prehospital witnessed cardiac arrest.

METHODS AND RESULTS

Thirty seconds after ventricular fibrillation, swine were randomly assigned to 12 minutes of chest compressions plus mechanical ventilation (group A), chest compressions only (group B), or no CPR (group C). Standard advanced cardiac life support was then provided. Animals successfully resuscitated were supported for 2 hours in an intensive care setting, and then observed for 24 hours. All 16 swine in groups A and B were successfully resuscitated and neurologically normal at 24 hours, whereas only 2 of 8 group C animals survived for 24 hours (P < .001, Fisher's exact test). One of the 2 group C survivors was comatose and unresponsive.

CONCLUSIONS

In this swine model of witnessed prehospital cardiac arrest, the survival and neurological outcome data establish that prompt initiation of chest compressions alone appears to be as effective as chest compressions plus ventilation and that both techniques of bystander CPR markedly improve outcome compared with no bystander CPR.
Serotonin-induced coronary spasm in a swine model. A minor role of defective endothelium-derived relaxing factor.
Authors: Fukai T , Egashira K , Hata H , Numaguchi K , Ohara Y , Takahashi T , Tomoike H , Takeshita A
Published: June 2012

BACKGROUND

Coronary spasm may be caused by endothelial dysfunction, vascular smooth muscle hyperreactivity, or both. We aimed to determine the relative role of endothelial dysfunction and vascular smooth muscle hyperreactivity in the pathogenesis of coronary artery spasm in the swine model in vivo.

METHODS AND RESULTS

In Göttingen miniature pigs given a high cholesterol diet, a segment of the left coronary artery was denuded and irradiated with x-ray (total, 30 Gy). Three months after endothelial denudation and irradiation, vasomotor responses of the denuded and control sites to agonists were assessed by quantitative arteriography. Serotonin (10 micrograms/kg) provoked coronary spasm at the denuded site (diameter reduction, 79 +/- 6%) associated with ST elevation but not at the nondenuded control site (21 +/- 6%). Intracoronary infusion of N omega-nitro-L-arginine methyl ester (LNNA, an inhibitor of endothelium-derived nitric oxide) of 1 and 3 mg/kg potentiated constriction evoked with serotonin (1, 3, 10 micrograms/kg) at the control site but did not alter it at the denuded site. However, serotonin-induced constriction after LNNA was still less at the control site (31 +/- 3%) than at the denuded site (80 +/- 5%). Endothelium-dependent vasodilation with substance P (0.1, 1, 10 ng/kg), which was inhibited by LNNA, was less (P < .01) at the denuded site than at the control site, whereas vasodilation with the nitrovasodilator SIN-1 (0.1, 1, 10 ng/kg) was comparable between the two sites. Histological study revealed regenerated endothelial cells and intimal thickening at the denuded site.

CONCLUSIONS

The results suggest that the denuded segment of the coronary artery with regenerated endothelium was associated with defective endothelium-dependent vasodilation mediated by nitric oxide and vascular smooth muscle hyperreactivity to serotonin. However, provocation of coronary spasm with serotonin resulted primarily from vascular smooth muscle hyperreactivity but not by defective nitric oxide production in this swine model.
Hyperbaric oxygen limits infarct size in ischemic rabbit myocardium in vivo.
Authors: Sterling D L , Thornton J D , Swafford A , Gottlieb S F , Bishop S P , Stanley A W , Downey J M
Published: June 2012

BACKGROUND

We explored the ability of increased oxygen pressure to modify necrosis in an open-chest rabbit model of myocardial ischemia and reperfusion.

METHODS AND RESULTS

A branch of the left coronary artery was occluded for 30 minutes followed by 3 hours of reperfusion. Infarction was measured by triphenyl tetrazolium staining and expressed as a percentage of the ischemic zone. Untreated rabbits were ventilated with 100% oxygen at 1 atm absolute. Treatment animals were exposed to hyperbaric oxygen at 2.5 atm absolute. The 1.0-atm control hearts developed 41.5 +/- 4.6% infarction of the ischemic zone. Animals exposed to hyperbaric oxygen during ischemia only, reperfusion only, or ischemia and reperfusion had significantly smaller infarcts with respect to control animals (16.2 +/- 2.9%, 14.5 +/- 3.7%, and 9.8 +/- 2.7%, respectively; P < or = .01), indicating that they had been protected by the procedure. When hyperbaric oxygen was begun 30 minutes after the onset of reperfusion, no protection was seen (35.8 +/- 3.8%).

CONCLUSIONS

We conclude that hyperbaric oxygen limits infarct size in the reperfused rabbit heart and that the effect can be achieved when hyperbaric oxygen is begun at reperfusion.
Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina.
Authors: Théroux P , Waters D , Qiu S , McCans J , de Guise P , Juneau M
Published: June 2012

BACKGROUND

Antiplatelet therapy with aspirin and antithrombotic therapy with heparin both prevent the complications of unstable angina; however, no definitive data exist on the relative clinical efficacy of the two drugs.

METHODS AND RESULTS

Aspirin (325 mg bid) or heparin (5000-U intravenous bolus followed by a perfusion titrated to the APTT) were compared in a double-blind randomized trial of 484 patients in two cohorts enrolled sequentially. The study was initiated at admission to hospital at a mean of 8.3 +/- 7.8 hours after the last episode of pain. End points were assessed 5.7 +/- 3.3 days later, when the decision for long-term management was made. Myocardial infarction occurred in 2 (0.8%) of the 240 patients randomized to heparin and in 9 (3.7%) of the 244 randomized to aspirin (P = .035), an odds ratio of 0.22 and a risk difference of 2.9% (95% confidence limits, 0.3% to 5.6%) with heparin. The only death resulted from a myocardial infarction in an aspirin patient. Survival curves with Cox logistic regression analysis showed that the improvement in survival without myocardial infarction with heparin (P = .035) was independent of other baseline characteristics.

CONCLUSIONS

This study documents that heparin prevents myocardial infarction better than aspirin during the acute phase of unstable angina.