bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Capture by Atrial Pacing in Spontaneous Chronic Atrial Fibrillation
Authors: Pandozi Claudio , Bianconi Leopoldo , Villani Mauro , Castro Antonio , Altamura Giuliano , Toscano Salvatore , Jesi Anna P. , Gentilucci Giuseppe , Ammirati Fabrizio , Bianco Francesco Lo , Santini Massimo
Published: June 2012

Background
Atrial fibrillation (AF) is considered to be maintained by multiple reentrant circuits without or with a very short excitable gap. However, the possibility of local atrial capture has been shown recently in experimental AF or induced AF in humans.

Methods and Results
This study was undertaken to evaluate the feasibility of atrial capture—suggestive of an excitable gap—in spontaneous chronic AF. Decremental pacing was performed in 47 right atrial sites in 14 patients with chronic AF, not taking antiarrhythmic drugs. A Franz catheter (for pacing and monophasic action potential recording) and a recording quadripolar catheter positioned about 10 mm apart were used. Local capture was achieved in 41 (87.2%) sites for a total of 100 captures. In 71 episodes the capture was lost within 15 seconds, while in the remaining 29, pacing was stopped after 15 seconds of stable capture. The AF types immediately before capture were type 1 in 83 and type 2 in 17 episodes. Type 3 AF was never captured. Pacing cycle at capture was 175.7±20.9 ms. The baseline atrial interval (FF) was 185.4±24.5, significantly longer than the FF recorded during pacing immediately before capture (176.0±19.8 ms) (
P
<.02).

Conclusions
During spontaneous chronic AF in humans, (1) local capture by atrial pacing is possible up to at least 15 mm from the pacing site, (2) regional entrainment is possible during type 1 and type 2 AF but not type 3 AF, and (3) pacing before capture accelerates AF, probably by transient or local capture. These findings suggest that an excitable gap is present in chronic AF, therefore supporting the hypothesis that leading circle reentry is not the unique electrophysiological mechanism maintaining the arrhythmia.
Three-dimensional Mapping of the Initiation of Nonsustained Ventricular Tachycardia in the Human Heart
Authors: Chung Mina K. , Pogwizd Steven M. , Miller Dave P. , Cain Michael E.
Published: June 2012

Background
Elucidation of the electrophysiological mechanisms of nonsustained ventricular tachycardia (VT) in humans is required to define the relationship between nonsustained VT and sustained VT. This goal requires, at least in part, analysis of transmural ventricular activation in patients with both sustained and nonsustained VTs.

Methods and Results
We analyzed three-dimensional intraoperative cardiac maps of extrastimuli and beats during 44 nonsustained VTs and the initiating beats of 6 sustained VTs from six patients with healed myocardial infarcts who were undergoing arrhythmia surgery. The coupling interval, total activation time, and diastolic interval of each extrastimulus and beat of nonsustained VT were compared with counterparts during sustained VT. Sites activated last during extrastimuli initiating nonsustained or sustained VTs occurred in the same region, and activation times were comparable. However, the site of earliest activation during the initial or subsequent beats of nonsustained VT was discordant from the site activated earliest during the first and subsequent beats of sustained VT in 74% of cases. The mean variance in coupling interval, but not total activation time or diastolic interval, was significantly greater for VT that terminated before the 10th cycle than for VT that sustained. When analyzed from the last extrastimulus up to the fifth VT cycle, the standard deviation of the coupling interval, but not of the total activation time, was greater for nonsustained than for sustained VTs. Electrode density was sufficient to define an arrhythmia mechanism for 36 beats of nonsustained VT. Twenty-one (58%) initiated in the subendocardium, midmyocardium, or epicardium by a macroreentrant mechanism, and 15 (42%) initiated in the subendocardium by a focal mechanism.

Conclusions
Compared with sustained VT, nonsustained VT initiates at discordant sites, is characterized by oscillations in coupling interval but not in total activation time, and initiates by either a macroreentrant or a focal mechanism.
Complex Electrophysiological Characteristics in Atrioventricular Nodal Reentrant Tachycardia With Continuous Atrioventricular Node Function Curves
Authors: Tai Ching-Tai , Chen Shih-Ann , Chiang Chern-En , Lee Shih-Huang , Wen Zu-Chi , Chiou Chuen-Wang , Ueng Kwo-Chang , Chen Yi-Jen , Yu Wen-Chung , Huang Jin-Long , Chang Mau-Song
Published: June 2012

Background
Although typical atrioventricular nodal reentrant tachycardia (AVNRT) with discontinuous AV node function curves has been well studied, there has been a lack of any significant information about AVNRT without evidence of dual AV nodal pathway physiology during atrial extrastimulus testing or atrial pacing.

Methods and Results
Group 1 included 9 patients with continuous curves during atrial extrastimulus testing but without a jump (≥50 ms) of the atrial–His bundle (AH) interval during incremental atrial pacing. The maximal AH interval during atrial pacing (266±61 versus 168±27 ms,
P
=.007) or extrastimulus testing (290±60 versus 176±18 ms,
P
=.005) shortened significantly after ablation. Antegrade and retrograde AV node properties were similar before and after ablation. Group 2 included 14 patients with continuous curves and a jump of the AH interval during incremental atrial pacing. The atrial pacing cycle length with 1:1 AV conduction and effective refractory period (ERP) of the antegrade AV node increased significantly, whereas the maximal AH interval during atrial pacing (358±70 versus 203±28 ms,
P
=.001) or extrastimulus testing (338±75 versus 196±34 ms,
P
=.002) shortened significantly after ablation. Group 3 included 24 patients with discontinuous curves. The maximal AH interval during atrial pacing or extrastimulus testing and the ERP of the antegrade fast AV node shortened, whereas the ERP of the antegrade AV node increased significantly after ablation. The maximal AH interval before ablation, extent of decrease in maximal AH interval after ablation, ERP of the retrograde AV node before ablation, and tachycardia cycle length were significantly shorter in group 1 than groups 2 and 3.

Conclusions
In AVNRT with continuous AV node function curves, dual AV nodal pathway physiology may or may not be demonstrated during atrial pacing. Significant shortening of the maximal AH interval during atrial pacing after radiofrequency ablation suggests successful elimination of AVNRT.
Leisure-Time Physical Activity but Not Work-Related Physical Activity Is Associated With Decreased Plasma Viscosity
Authors: Koenig Wolfgang , Sund Malte , Do¨ring Angela , Ernst Edzard
Published: June 2012

Background
Regular leisure-time physical activity (LTPA) is inversely associated with coronary heart disease (CHD). This has been mainly explained by its impact on traditional CHD risk factors, but more recently it was also shown to lower fibrinogen, which largely determines plasma viscosity. No data on the effect of work activity (WA) on plasma viscosity have been published.

Methods and Results
We studied the relationship between self-reported LTPA or WA and plasma viscosity as well as other CHD risk factors in 3522 men and women age 25 to 64 years. Physical activity was assessed by questionnaire. LTPA was inversely associated with plasma viscosity in both sexes. The unadjusted mean differences in plasma viscosity in men between no activity and the highest activity were 0.024 mPa·s (95% confidence interval [CI], 0.016 to 0.032 mPa·s,
P
<.001) during winter and 0.024 mPa·s (95% CI, 0.016 to 0.031 mPa·s,
P
<.001) during summer. After adjustment for age, cholesterol, smoking, blood pressure, body mass index, and years of education, mean differences decreased but still remained substantial and statistically significant (0.010 mPa·s; 95% CI, 0.003 to 0.018 mPa·s [
P
=.009] for winter activity; and 0.010 mPa·s; 95% CI, 0.002 to 0.017 mPa·s [
P
=.011] for summer activity). Similar results were found in women. WA showed no appreciable association with plasma viscosity after controlling for the covariates.

Conclusions
LTPA is inversely associated with plasma viscosity, independent of other risk factors, whereas WA shows no material effect in men and women. Decreased plasma viscosity may represent one mechanism through which LTPA confers a decrease of CHD risk.
Improved Outcome of Elderly Patients (≥75 Years of Age) With Acute Myocardial Infarction From 1981-1983 to 1992-1994 in Israel
Authors: Gottlieb Shmuel , Goldbourt Uri , Boyko Valentina , Barbash Gabriel , Mandelzweig Lori , Reicher-Reiss Henrietta , Stern Shlomo , Behar Solomon
Published: June 2012

Background
The number of elderly patients experiencing acute myocardial infarction (AMI) is growing rapidly, and their hospital mortality rate remains high, although mortality after AMI declined in the 1990s with the introduction of new therapeutic modalities.

Methods and Results
We compared the management, in-hospital complications, and 30-day and 1-year mortality rates in two cohorts of elderly (≥75 years of age) AMI patients in the coronary care units in Israel before and after the reperfusion era. The first cohort of 789 consecutive patients was from the Secondary Prevention Reinfarction Israel Nifedipine Trial registry in 1981-1983; the second 366 patients came from two prospective nationwide surveys in 1992 and 1994. Reperfusion therapies were not used in 1981-1983 but were used in 1992-1994. The 30-day mortality rate declined from 38% in 1981-1983 to 27% in 1992-1994 (odds ratio, 0.49; 95% confidence interval [CI], 0.34 to 0.71), and the cumulative 1-year mortality rate declined from 52% to 38% (hazard ratio [HR], 0.62; 95% CI, 0.50 to 0.76). In the 1992-1994 cohort, the decline in mortality was most marked in patients reperfused by thrombolysis and/or percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery but was also evident in nonreperfused patients: cumulative 1-year mortality rate was 29% in the former (HR, 0.45; 95% CI, 0.31 to 0.67) and 42% in the latter (HR, 0.60; 95% CI, 0.46 to 0.78).

Conclusions
During the last decade, elderly (≥75 years) AMI patients experienced fewer in-hospital complications and lower 30-day and 1-year mortality rates, which declined ≈30%, most markedly in reperfused patients. The favorable outcome in 1992-1994 was related to changes in patient management. Reperfusion therapy is therefore also advocated in elderly AMI patients, unless specific contraindications are present.
Physiological Effects of Adenoviral Gene Transfer of Sarcoplasmic Reticulum Calcium ATPase in Isolated Rat Myocytes
Authors: Hajjar Roger J. , Kang Jing X. , Gwathmey Judith K. , Rosenzweig Anthony
Published: June 2012

Background
In myocardial cells, relaxation is governed primarily by the sarcoplasmic reticulum (SR) Ca
2+
-ATPase transporting enzyme, which regulates Ca
2+
sequestration into the SR. Human and experimental cardiomyopathies are associated with reduced SR Ca
2+
-ATPase activity.

Methods and Results
To modify intracellular calcium mobilization, we created a recombinant adenovirus designed to overexpress the cardiac SR Ca
2+
-ATPase (SERCA2a) under the control of the Rous sarcoma virus (RSV). In neonatal rat myocytes, Ad.RSV.SERCA2a increased the expression of SERCA2a in a concentration-dependent and time-dependent fashion. Enhancement of SR Ca
2+
-ATPase activity was even greater than increases in SERCA2a protein content in cells infected with Ad.RSV.SERCA2a for 48 hours at a multiplicity of infection (MOI) from 0.1 to 10.0 pfu/cell. Intracellular calcium transients measured in the neonatal cells infected with Ad.RSV.SERCA2a were characterized by an abbreviation of the relaxation phase, an increase in peak [Ca
2+
]
i
release, and a decrease in resting [Ca
2+
]
i
levels. Ad.RSV.SERCA2a also enhanced the contraction of the myocardial cells as detected by shortening measurements.

Conclusions
We found that adenovirus-mediated gene transfer of SR Ca
2+
-ATPase can modify intracellular calcium handling and shortening in myocardial cells. Such vectors should be useful in examining the role of reduced SERCA2a activity in the pathophysiology of heart failure and in developing strategies for gene therapy.
Continuous Subcutaneous Angiopeptin Treatment Significantly Reduces Neointimal Hyperplasia in a Porcine Coronary In-Stent Restenosis Model
Authors: Hong Mun K. , Kent Kenneth M. , Mehran Roxana , Mintz Gary S. , Tio Fermin O. , Foegh Marie , Wong S. Chiu , Cathapermal Seedabarum S. , Leon Martin B.
Published: June 2012

Background
In-stent restenosis results primarily from neointimal hyperplasia. This study evaluated the efficacy and the optimal mode of administration of angiopeptin, a somatostatin analogue with antiproliferative activity, in a porcine coronary in-stent restenosis model.

Methods and Results
Forty pigs were randomly assigned to one of four groups (n=10 per group): (1) controls receiving saline infusion at the site of stent implantation via a local delivery catheter, (2) local treatment group receiving one-time treatment (200 μg angiopeptin) at the site of stent placement, (3) systemic treatment group receiving continuous angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 μg/kg total dose), and (4) combined local and systemic treatment group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery diameters, 1.3:1) was implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal percent diameter stenosis), intravascular ultrasound (total in-stent neointimal volume), and histology (maximal area stenosis). Systemic treatment produced the least neointimal hyperplasia and significantly reduced in-stent restenosis compared with the control group by all end points, despite similar degrees of injury. Angiography showed 25±17% versus 50±17% diameter stenosis in the systemic angiopeptin group versus the control group (
P
<.0001), intravascular ultrasound revealed 23±10 versus 58±27 mm
3
neointimal volume in the systemic angiopeptin versus control group (
P
=.0002), and histology showed 41±16% versus 69±18% area stenosis (
P
=.0016) in the systemic angiopeptin versus control group. Plasma angiopeptin levels revealed rapid clearance (within 6 hours) after local therapy, whereas the levels persisted for up to 2 weeks in the systemic group.

Conclusions
This study shows that continuous subcutaneous treatment with angiopeptin after stent implantation significantly reduces in-stent restenosis by inhibiting neointimal hyperplasia.
Skeletal Muscle Ventricles, Left Ventricular Apex-to-Aorta Configuration
Authors: Greer Kevin A. , Lu Huiping , Spanta Ali D. , Hammond Robert L. , Stephenson Larry W.
Published: June 2012

Background
Skeletal muscle ventricles (SMVs) have been used in animals in a variety of configurations to provide circulatory assistance. Long-term survival and function have been demonstrated. Our laboratory recently obtained promising short-term hemodynamic data in a left ventricular apex-to-aorta model.

Methods and Results
SMVs were constructed from the left latissimus dorsi muscle in five adult mongrel dogs. After a 3-week period of vascular delay and 5 to 7 weeks of electrical conditioning, valved conduits were used to connect the left ventricular apex to the SMV and the SMV to the descending aorta. The SMV was then stimulated to contract during cardiac diastole. Initial measurements showed a significant increase in the mean femoral diastolic pressure (62±6 versus 51±5 mm Hg,
P
<.05). There was also a decrease in the left ventricular tension-time index (11.5±2.5 versus 14.6±2.1 mm Hg·s,
P
<.05), indicating a decrease in the work requirement of the left ventricle. During SMV stimulation, the majority of flow (65%) was through the SMV circuit and was associated with reversal of flow in the proximal descending thoracic aorta. The longest-surviving animal survived 76 days, at which time pressure augmentation was still seen (mean femoral diastolic pressure, 63±0.9 versus 50±1.2 mm Hg,
P
<.05).

Conclusions
Survival beyond the acute setting is possible with this model. Diastolic pressure augmentation can be effectively maintained over time.
Regulation of Spontaneous Transient Outward Potassium Currents in Human Coronary Arteries
Authors: Bychkov Rostislav , Gollasch Maik , Ried Christian , Luft Friedrich C. , Haller Hermann
Published: June 2012

Background
Spontaneous transient outward potassium currents (STOCs) induce myogenic relaxation in small cerebral vessels. We found STOCs in human coronary artery vascular smooth muscle cells (VSMCs) and studied their regulation.

Methods and Results
K
+
currents were recorded in human coronary VSMCs by current- and voltage-clamp techniques. STOCs were recorded in the presence of 200 μmol/L Cd
2+
and 10 μmol/L verapamil, which block voltage-dependent Ca
2+
channels. STOCs were inhibited by iberiotoxin (100 nmol/L), a selective blocker of Ca
2+
-activated potassium channels (BK
Ca
), and disappeared in a Ca
2+
-free bath. Iberiotoxin depolarized the VSMCs within 20 minutes from −44±7 to −18±5 mV (n=17). The Ca
2+
ionophore A23187 increased intracellular Ca
2+
and stimulated whole-cell BK
Ca
current. Depletion of Ca
2+
from the sarcoplasmic reticulum with caffeine (4 mmol/L) abolished STOCs for several minutes. Ryanodine (50 μmol/L) transiently stimulated STOCs but then completely inhibited STOCs within 10 minutes. The firing frequency of STOCs was directly correlated with intracellular Na
+
concentrations from 0 to 24 mmol/L. Lowering intracellular Na
+
to zero abolished STOCs. We next gave monensin (30 μmol/L) to increase intracellular Na
+
. This maneuver resulted in an increase in whole-cell current fluctuations and STOCs. Monensin-induced STOCs were abolished by either lowering extracellular Ca
2+
to zero or chelating Ca
2+
intracellularly with BAPTA-AM (30 μmol/L).

Conclusions
STOCs resulted from BK
Ca
activity and were dependent on extracellular Ca
2+
but not significantly on voltage-dependent Ca
2+
channels. STOCs were dependent on intracellular Na
+
and intracellular calcium store refilling state. We suggest that Ca
2+
entry into the cell through reverse-mode Na
+
/Ca
2+
exchange determines calcium store refilling, which in turn regulates STOC generation in human coronary VSMCs.
Reduced Coronary Flow Reserve During Exercise in Cardiac Transplant Recipients
Authors: Vassalli Giuseppe , Gallino Augusto , Kiowski Wolfgang , Jiang Zhihua , Turina Marko , Hess Otto M.
Published: June 2012

Background
Coronary flow reserve (CFR) is reduced in a majority of patients after heart transplantation (HTx). Pharmacological interventions, however, provide only limited information on CFR under physiological conditions. Thus, CFR during exercise was evaluated in the present study.

Methods and Results
Coronary angiography was performed at rest and during supine bicycle exercise in 35 patients early (2 to 3 months; n=10) or late (1 to 6 years; mean, 2.5 years; n=25) after HTx and in 8 controls (C). CFR was determined by parametric imaging after administration of 10 mg intracoronary papaverine, during exercise, and after 1.6 mg sublingual nitroglycerin. Epicardial coronary artery size was measured by quantitative coronary angiography. CFR after papaverine was normal early (3.6±0.5 versus C, 3.6±0.7;
P
=NS) and late (3.8±1.3;
P
=NS) after HTx. During exercise, CFR was normal early (3.1±0.6 versus C, 3.9±0.9;
P
=NS) but decreased late (2.3±0.6;
P
<.01) after HTx. The increase in coronary cross-sectional area during exercise was also diminished late after HTx (14±10% versus C, 22±10%;
P
<.05). Both exercise-induced CFR (
r
=−.39,
P
<.05) and coronary vasodilation (
r
=−.44,
P
<.01) were inversely correlated with time after HTx.

Conclusions
CFR during exercise is normal early but reduced late after HTx, whereas CFR after papaverine administration is maintained. This difference between physiological and pharmacological vasodilation suggests progressive endothelial dysfunction after HTx.
Fetoscopic and Open Transumbilical Fetal Cardiac Catheterization in Sheep
Authors: Kohl Thomas , Szabo Zoltan , Suda Kenji , Petrossian Edwin , Ko Eitetsu , Kececioglu Deniz , Moore Philip , Silverman Norman H. , Harrison Michael R. , Chou Tony M. , Hanley Frank L.
Published: June 2012

Background
Shortening the prenatal disease course of severe aortic and pulmonary stenoses by balloon valvuloplasty may diminish their postnatal expression. The purpose of this study in fetal sheep was to assess the feasibility of fetoscopic and open transumbilical fetal cardiac catheterization guided by fetal transesophageal echocardiography to provide alternative approaches for human fetal cardiac intervention.

Methods and Results
We studied a total of nine fetal sheep (95 to 103 days of gestation; term=145 to 150 days) and performed transumbilical fetal cardiac catheterization by a minimally invasive fetoscopic (n=6) or an open fetal surgical approach (n=3). Monitored by fetal transesophageal echocardiography, with an 8F or 10F, 10-MHz intravascular ultrasound catheter we placed guidewires and interventional catheters via the umbilical arterial route into the fetal heart. In three of the fetuses, we created supravalvar pulmonary artery stenosis by open fetal cardiac surgery. After fetal and maternal recovery, we exteriorized these fetuses and performed open transumbilical fetal cardiac catheterization with successful pulmonary arterial angioplasty in two. Three fetuses survived fetoscopic transumbilical catheterization for 1 or 2 days and died most likely of blood loss after sheath dislodgment (n=1) or removal (n=2). By securing the sheath insertion site with a suture, we prevented sheath dislodgment and minimized bleeding during sheath removal in three fetuses. These fetuses then survived fetoscopic transumbilical fetal cardiac catheterization for 1 to 2 weeks before being killed.

Conclusions
This study in fetal sheep demonstrates that fetoscopic and open transumbilical fetal cardiac catheterization are feasible and, guided by fetal transesophageal echocardiography, provide potential alternative approaches for human fetal cardiac intervention.
Antithrombotic Potency of Hirudin Is Increased in Nonhuman Primates by Fibrin Targeting
Authors: Bode Christoph , Hanson Stephen R. , Schmedtje John F. , Haber Edgar , Mehwald Petra , Kelly Andrew B. , Harker Laurence A. , Runge Marschall S.
Published: June 2012

Background
Inhibition of thrombin by either the indirect thrombin inhibitor heparin or by more potent direct thrombin inhibitors such as hirudin reduces thrombus formation after arterial injury. The present study was designed to determine if a fibrin-specific thrombin inhibitor could, by local thrombin inhibition, prevent thrombosis more effectively.

Methods and Results
We first studied antithrombotic potency in vitro, comparing fibrin-targeted hirudin (recombinant hirudin covalently linked to the Fab′ fragment of the anti-fibrin monoclonal antibody 59D8) to recombinant hirudin in baboon plasma. Fibrin-targeted hirudin was nine times more effective than recombinant hirudin in inhibiting fibrin deposition on experimental clot surfaces in baboon plasma (
P
<.01). The potency of fibrin-targeted hirudin was then compared with that of recombinant hirudin in a baboon model of thrombus formation.
111
In-labeled platelet deposition was measured in a synthetic graft segment of an extracorporeal arteriovenous shunt in control animals and in animals receiving either fibrin-targeted hirudin or hirudin. In these experiments, fibrin-targeted hirudin was 10-fold more potent than hirudin in inhibiting platelet deposition and thrombus formation (
P
<.05).

Conclusions
These data indicate that targeting a thrombin inhibitor such as hirudin to an epitope present in thrombi results in increased antithrombotic potency.
Acoustic Assessment of the Physical Integrity of Bjo¨rk-Shiley Convexo-Concave Heart Valves
Authors: Dow J.J. , Plemons Terry D. , Scarbrough Kent , Reeder Hugh , Hovenga Mike , Wieting David W. , Chandler James G.
Published: June 2012

Background
Several lines of evidence indicate a two-stage failure mode for the Bjo¨rk-Shiley convexo-concave (C/C) heart valve, in which one of the two outlet strut legs separates from the flange before the other, potentially providing an opportunity to identify and prophylactically replace failure-prone valves. Radiographic single leg separation (SLS) detection, although successful, is subjective and skill intensive, implying a need for both an objective preliminary screen and subsequent corroboration of the radiographic findings.

Methods and Results
We developed a time-windowed, power density analysis of C/C valve closing sounds to detect the vibrational resonance that characterizes the presence of an intact outlet strut in clinically functioning, 29-mm-flange size C/C valves. Recordings from more than 800 patients enrolled in radiographic SLS detection studies were analyzed, and the assessment algorithm was evaluated through a blinded test of 32 study valves for which the true status became known consequent to an autopsy or surgical explantation. Valves were objectively scored on a 0-to-1 scale, with 1 being assuredly intact and scores of <0.50 indicating a probable SLS. All except five valves (incorrectly designated probable SLS) were classified correctly, for a sensitivity of 1.00 (95% confidence interval, 0.79 to 1.00) and a specificity of 0.69 (0.41 to 0.89).

Conclusions
This level of accuracy is sufficient to serve as an effective preliminary screen, potentially allowing a threefold concentration of SLS prevalence among the C/C valves of patients undergoing radiographic assessment. The value of acoustic classification in avoiding unnecessary operations prompted by false-positive radiographs is less certain.
Effects of Aging on Left Ventricular Relaxation in Humans
Authors: Yamakado Tetsu , Takagi Eiji , Okubo Setsuya , Imanaka-Yoshida Kyoko , Tarumi Toshiaki , Nakamura Mamoo , Nakano Takeshi
Published: June 2012

Background
Some experimental studies in animals have shown that myocardial relaxation is prolonged with aging. However, it is not known whether aging alters ventricular isovolumic relaxation in human subjects.

Methods and Results
We analyzed high-fidelity left ventricular pressures, measured by use of a catheter-tipped manometer, and biplane left ventriculograms in 55 normal subjects who underwent diagnostic cardiac catheterization but who were found to have normal cardiac anatomy and function. There were 38 men and 17 women, ranging in age from 20 to 77 years. Left ventricular isovolumic relaxation was assessed by the exponential time constants of isovolumic pressure decay with (Tb) and without (Tw) an asymptote pressure. Left ventricular volume, ejection fraction, and wall thickness or mass were calculated from left ventricular angiograms. Neither of the time constants of left ventricular relaxation correlated with age (Tb:
r
=.001 to .10,
P
=NS; Tw:
r
=.02 to .05,
P
=NS). Left ventricular systolic function (ie, ejection fraction and end-systolic volume index), heart rate, and left ventricular wall thickness or mass, which are major hemodynamic determinants of left ventricular relaxation, were not significantly affected by aging. The multivariate analysis of age and hemodynamic variables against the time constants of left ventricular relaxation also indicated that no significant relation was found between age and left ventricular relaxation.

Conclusions
In the absence of coronary artery disease, systemic hypertension, left ventricular systolic dysfunction, or hypertrophy, left ventricular relaxation assessed by the time constant of isovolumic pressure decay remains essentially unchanged with normal adult aging, at least until the eighth decade.
Role of Myocyte Nitric Oxide in β-Adrenergic Hyporesponsiveness in Heart Failure
Authors: Yamamoto Shimako , Tsutsui Hiroyuki , Tagawa Hirofumi , Saito Keiko , Takahashi Masaru , Tada Hideo , Yamamoto Mitsutaka , Katoh Makoto , Egashira Kensuke , Takeshita Akira
Published: June 2012

Background
The positive inotropic response to β-adrenergic stimulation is attenuated at the isolated myocyte level in heart failure. Nitric oxide (NO) has a negative inotropic effect and attenuates the response to isoproterenol. It has been suggested that NO synthesis is increased in failing myocytes. However, the pathophysiological consequences after induction of NO in myocyte contractility are less clear in the setting of heart failure.

Methods and Results
We examined the effects of an NO synthase (NOS) inhibitor on contractile function in myocytes isolated from 11 dogs with rapid pacing–induced heart failure (ejection fraction, 29±2%) and 8 control dogs (ejection fraction, 74±3%). Sarcomere shortening velocity was measured as an index of contractility under four experimental conditions: at baseline, after adding isoproterenol (ISO; 1 nmol/L), after an NOS inhibitor (
N
ϖ
-nitro-
l
-arginine methyl ester [L-NAME], 0.1 nmol/L), and after L-NAME plus ISO. L-NAME alone had no effects on basal sarcomere shortening velocity in either control or heart failure myocytes. However, L-NAME significantly augmented the inotropic response to isoproterenol in heart failure myocytes (107.1±7.3% [ISO alone] versus 140.6±10.7% [ISO plus L-NAME] increase from baseline;
P
<.05) but not in control myocytes (135.5±9.9% [ISO alone] versus 137.1±11.4% [ISO plus L-NAME];
P
=NS). Myocardial NOS activity measured by the conversion of arginine to citrulline was significantly increased in dogs with heart failure compared with that in control dogs.

Conclusions
The increased NO induction in failing myocytes does not alter baseline sarcomere mechanics but attenuates the positive inotropic response to isoproterenol. Thus, myocyte NO plays an important role in the autocrine regulation of the contractile function of myocytes in congestive heart failure.
Simvastatin, an HMG–Coenzyme A Reductase Inhibitor, Improves Endothelial Function Within 1 Month
Authors: O'Driscoll Gerard , Green Danny , Taylor Roger R.
Published: June 2012

Background
Cholesterol-lowering therapy can improve cardiovascular morbidity and mortality in patients with atherosclerosis. Although the mechanisms responsible are unclear, these benefits precede macroscopic changes in the vasculature. Emerging evidence that improvement in endothelial function may occur requires substantiation; in particular, it is unclear how early any such improvement would be detectable after initiation of therapy.

Methods and Results
This randomized, double-blind, placebo-controlled crossover study evaluated the effect of simvastatin (20 mg daily for 4 weeks) on endothelium-dependent and endothelium-independent vasodilation and on the response to the inhibitor of nitric oxide synthesis,
N
G
-monomethyl-
l
-arginine (L-NMMA), in the forearm vasculature of subjects with moderate elevation of total serum cholesterol (6.0 to 10.0 mmol/L) by use of strain-gauge plethysmography. Studies were repeated after 3 more months of open therapy. When the results are expressed as percentage changes in flow in the infused arm relative to the noninfused arm, the vasodilator response to acetylcholine was significantly increased after 4 weeks of treatment with simvastatin (
P
<.0005), and this improvement was further enhanced after 3 months (
P
<.005). Concurrently, simvastatin augmented the vasoconstrictor response to L-NMMA, an effect that was maintained at 3 months (
P
<.0005). The response to the endothelium-independent vasodilator sodium nitroprusside was unaltered.

Conclusions
These observations indicate that within 1 month of treatment with simvastatin, both the stimulated and basal nitric oxide dilator functions of the endothelium are augmented, and the benefits of this HMG–coenzyme A reductase inhibitor persist with continued therapy.
Effect of Rotablator Atherectomy and Adjunctive Balloon Angioplasty on Coronary Blood Flow
Authors: Bowers Terry R. , Stewart Richard E. , O'Neill William W. , Reddy Venu M. , Safian Robert D.
Published: June 2012

Background
The purpose of this study was to assess serial changes in coronary blood flow velocity before and after Rotablator atherectomy and after adjunctive percutaneous transluminal coronary angioplasty (PTCA). Since Rotablator atherectomy results in luminal enlargement by plaque pulverization and distal embolization, improvement in coronary blood flow could be attenuated despite luminal enlargement.

Methods and Results
Intracoronary Doppler blood flow velocity measurements were obtained with a Doppler Flowire. Basal average peak velocity (bAPV), hyperemic APV (hAPV), diastolic/systolic velocity ratio (DSVR), and coronary flow reserve (CFR) were assessed before intervention, after Rotablator, and after adjunctive PTCA. Complete clinical, angiographic, and Doppler data were obtained in 22 patients. There was a small but significant difference (
P
=.02) in resting heart rate and mean arterial pressure before and after Rotablator and after adjunctive PTCA. Minimum lumen diameter increased from 0.8±0.1 to 1.5±0.2 to 2.0±0.1 mm (
P
<.001), corresponding to decreases in diameter stenosis from 72±3% to 41±4% to 36±3% (
P
<.001). Although bAPV, hAPV, and DSVR increased significantly (
P
<.001), CFR remained abnormally low in 19 of 22 patients (despite an increase from baseline to post-PTCA). hAPV >30 cm/s was the best Doppler correlate of angiographic success.

Conclusions
Rotablator atherectomy and adjunctive PTCA significantly improve distal coronary blood flow velocity and DSVR but not CFR. Failure to normalize CFR could be secondary to parallel increases in bAPV and hAPV, “acquired” microvascular disease due to distal microembolization or spasm, and/or angiographically inapparent dissection or residual stenosis. Adjunctive PTCA contributes significantly to the overall physiological benefit of a combined procedure.
Analysis of Abnormal Intra-QRS Potentials
Authors: Lander Paul , Gomis Pedro , Goyal Rajiva , Berbari Edward J. , Caminal Pere , Lazzara Ralph , Steinberg Jonathan S.
Published: June 2012

Background
Using the signal-averaged ECG (SAECG), this study developed a new electrical index for predicting arrhythmic events: abnormal intra-QRS potentials (AIQP).

Methods and Results
We studied 173 patients followed after myocardial infarction for a mean duration of 14±7 months. Sixteen arrhythmic events occurred, defined as sudden cardiac death, documented sustained ventricular tachycardia, or nonfatal cardiac arrest. Noninvasive indices of arrhythmia risk were measured, including AIQP, conventional SAECG, Holter, and left ventricular ejection fraction (LVEF). Abnormal intra-QRS potentials were defined as abnormal signals occurring anywhere within the QRS period. They were estimated with a lead-specific, parametric modeling method that removed the smooth, predictable part of the QRS. AIQPs are characterized by the remaining transient, unpredictable component of the QRS and manifest as low-amplitude notches and slurs. A combined XYZ-lead AIQP index exhibited higher specificity (95%) and predictive value (PV) (+PV, 47%; −PV, 94%) than the conventional SAECG in combination with Holter and LVEF (specificity, 89%; +PV, 25%; −PV, 93%).

Conclusions
AIQP improved specificity and predictive value, compared with conventional tests, for prediction of arrhythmic events. AIQP emerged as the best noninvasive univariate predictor of arrhythmic events after myocardial infarction in this study. A review of several other reports shows that AIQP in the present study outperformed the conventional predictive indices reported in those other data sets.
Effects of Long-term Infusion of Prostacyclin (Epoprostenol) on Echocardiographic Measures of Right Ventricular Structure and Function in Primary Pulmonary Hypertension
Authors: Hinderliter Alan L. , Willis Park W. , Barst Robyn J. , Rich Stuart , Rubin Lewis J. , Badesch David B. , Groves Bertron M. , McGoon Michael D. , Tapson Victor F. , Bourge Robert C. , Brundage Bruce H. , Koerner Spencer K. , Langleben David , Keller Cesar A. , Murali Srinivas , Uretsky Barry F. , Koch Gary , Li Shu , Clayton Linda M. , Jöbsis Maria M. , Blackburn Shelmer D. , Crow James W. , Long Walker A.
Published: June 2012

Background
Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationships of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy.

Methods and Results
The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n=41) or conventional therapy alone (n=40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity.

Conclusions
The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.
Programming of Implantable Cardioverter-Defibrillators on the Basis of the Upper Limit of Vulnerability
Authors: Swerdlow Charles D. , Peter C. Thomas , Kass Robert M. , Gang Eli S. , Mandel William J. , Hwang Chun , Martin David J. , Chen Peng-Sheng
Published: June 2012

Background
A patient-specific measure of defibrillation efficacy that requires a minimum number of ventricular fibrillation (VF) episodes would be valuable for programming implantable cardioverter-defibrillators (ICDs). The upper limit of vulnerability (ULV) is the weakest shock strength at or above which VF is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. It correlates with the defibrillation threshold (DFT) and can be determined with a single episode of VF. The objective of this study was to test the hypothesis that ICDs programmed on the basis of the ULV convert spontaneous ICD-detected VF reliably.

Methods and Results
We studied 100 consecutive patients at ICD implantation and during follow-up of 20±7 months. At implantation, the ULV and DFT were determined, and the ICD system was tested at a shock strength equal to the ULV+3 J. During follow-up, the strength of the first shock was programmed to the ULV+5 J for arrhythmias detected in the VF zone (cycle length <292±17 ms). We reviewed stored detection intervals and electrograms from spontaneous episodes of ICD-detected VF to determine the success rate for appropriate first shocks. The programmed first-shock strength was 17.5±5.2 J. During follow-up, there were 120 appropriate first shocks in 37 patients. The arrhythmia was rapid monomorphic ventricular tachycardia (VT) in 70% of episodes (31 patients), VF in 11% (13 patients), polymorphic VT in 1%, and unclassified in 17% (15 patients). The first shock was successful in 119 of 120 episodes (99%; 95% CI, 93% to 100%). One unclassified episode required two shocks. No patient had syncope associated with an ICD shock or arrhythmic death.

Conclusions
ICD shocks can be programmed on the basis of the ULV, a measurement made in regular rhythm, without a direct measure of defibrillation efficacy.
Bradykinin Mediation of Ca
2+
-Activated K
+
Channels Regulates Coronary Blood Flow in Ischemic Myocardium
Authors: Node Koichi , Kitakaze Masafumi , Kosaka Hiroaki , Minamino Tetsuo , Hori Masatsugu
Published: June 2012

Background
Endothelium-dependent hyperpolarizing factor relaxes vascular smooth muscles by opening the Ca
2+
-activated K
+
(K
Ca
) channels. The role of the opening of K
Ca
channels in coronary vasodilation during myocardial ischemia was investigated.

Methods and Results
The left anterior descending coronary arteries of open-chest dogs were perfused with blood through an extracorporeal bypass tube from the carotid artery. Intracoronary administration of bradykinin increased coronary blood flow (CBF) in dogs treated with
N
G
-nitro-
l
-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; this effect was completely inhibited by the K
Ca
channel blocker iberiotoxin. In dogs treated with L-NAME, the bypass tube was occluded to reduce CBF to one third of the baseline value, after which coronary perfusion pressure was maintained constant. Intracoronary administration of iberiotoxin for 20 minutes further decreased CBF (from 33±2 to 19±2 mL·100 g
−1
·min
−1
,
P
<.01), fractional shortening, and lactate extraction ratio during coronary hypoperfusion. Bradykinin was released, and the bradykinin receptor antagonist HOE-140 blocked the effects of iberiotoxin on coronary hemodynamic and metabolic parameters during myocardial ischemia. Although the combination of L-NAME and the adenosine receptor antagonist 8-sulfophenyltheophylline reduced reactive hyperemic flow after 20 seconds of coronary occlusion, the additional presence of iberiotoxin resulted in a further decrease in this parameter.

Conclusions
The opening of K
Ca
channels in response to endogenous bradykinin contributed to coronary vasodilation and reduced contractile and metabolic dysfunction during myocardial ischemia in open-chest dogs.
Nonselective β-Adrenergic Blockade With Carvedilol Does Not Hinder the Benefits of Exercise Training in Patients With Congestive Heart Failure
Authors: Demopoulos Laura , Yeh Michael , Gentilucci Marco , Testa Marco , Bijou Rachel , Katz Stuart D. , Mancini Donna , Jones Margaret , LeJemtel Thierry H.
Published: June 2012

Background
Long-term β-adrenergic blockade does not appear to be associated with drug-induced training in patients with congestive heart failure (CHF); whether exercise training can increase peak aerobic capacity in patients with CHF who are treated with β-adrenergic blockers is currently unknown.

Methods and Results
We studied 23 patients with CHF who were treated with carvedilol or propranolol in addition to ACE inhibitors, furosemide, and digoxin. Of the patients treated with carvedilol, 8 underwent exercise training and 8 remained sedentary. All 7 patients treated with propranolol underwent exercise training. Peak oxygen consumption (mL·kg
−1
·min
−1
) was serially measured in trained and sedentary patients. Peak reactive hyperemia (mL·min
−1
·100 mL
−1
) was determined in the calf and forearm immediately before and after 12 weeks of training. The peak oxygen consumption of trained patients treated with either carvedilol or propranolol increased from 12.9±1.4 to 16.0±1.6 (
P
<.001) and 12.4±1.0 to 15.7±0.9 (
P
<.001) mL·kg
−1
·min
−1
, respectively, whereas it did not change in the sedentary patients. Peak reactive hyperemia increased significantly in the calves but not the forearms of trained patients.

Conclusions
Long-term, nonselective β-adrenergic blockade with carvedilol or propranolol does not prevent patients with CHF from deriving systemic and regional benefits from physical training.
Estradiol Accelerates Functional Endothelial Recovery After Arterial Injury
Authors: Krasinski Kevin , Spyridopoulos Ioakim , Asahara Takayuki , van der Zee Rien , Isner Jeffrey M. , Losordo Douglas W.
Published: June 2012

Background
The mechanisms of the established atheroprotective effects of estrogen have not been entirely clarified. Recent data suggest that agents that hasten the recovery of the endothelium after denuding injury will deter the development of neointimal lesions. Because estrogen has been shown to exert angiogenic effects in vitro and in vivo, we performed a series of experiments to evaluate whether estrogen was capable of accelerating reendothelialization.

Methods and Results
Ovariectomized Sprague-Dawley rats received estrogen replacement therapy in the form of subcutaneously implanted pellets designed to release 1.5 or 5.0 mg 17β-estradiol over 30 days. Deendothelializing balloon injury was performed 1 week after pellet implantation, and animals were euthanatized after 1 week for evaluation of reendothelialization (Evans blue staining) or 2 weeks for evaluation of reendothelialization and neointimal formation. At both time points, the use of estradiol caused a dose-dependent increase in reendothelialization, which was measured as absolute area and percentage of area that is reendothelialized. Estradiol accelerated functional endothelial recovery, manifested as an increase in nitric oxide production. Neointimal thickening was also shown to be inhibited in a dose-dependent fashion.

Conclusions
Estrogen accelerates functional endothelial recovery after barotraumatic deendothelializing injury. These findings, along with the recent demonstration of estrogen receptor expression by endothelial cells, suggest that the antiatherogenic action of estrogen may be mediated in part through direct effects on endothelial cells.
Contribution of Inadequate Arterial Remodeling to the Development of Focal Coronary Artery Stenoses
Authors: Mintz Gary S. , Kent Kenneth M. , Pichard Augusto D. , Satler Lowell F. , Popma Jeffrey J. , Leon Martin B.
Published: June 2012

Background
Adaptive remodeling occurs to compensate for the accumulation of atherosclerotic plaque. Lumen reduction depends on the relative rates of plaque deposition and adaptive remodeling responses. Intravascular ultrasound permits detailed, high-quality, cross-sectional imaging of the coronary arteries in vivo.

Methods and Results
Preintervention intravascular ultrasound was used to study 603 focal, new, nonostial significant coronary artery stenoses in patients with chronic stable angina. Measurements of the target lesion of the external elastic membrane (EEM), lumen, and plaque plus media (P&M; P&M=EEM−Lumen) cross-sectional areas (CSAs) were compared with a proximal reference segment (most normal-looking cross section within 10 mm proximal to the lesion but distal to any side branch). Inadequate remodeling was defined as lesion/reference EEM CSA that exceeded the upper limits of normal arterial tapering (lesion/reference EEM CSA ratio ≤0.78 or a 21% reduction in EEM CSA per 10-mm length). Overall, the lesion/reference EEM CSA ratio was 1.00±0.22; 15% of lesions had inadequate remodeling, and 37% of the 603 lesions had less plaque than expected. This represented a lesion-specific response. The only predictor of inadequate remodeling was the arc of superficial lesion calcium.

Conclusions
Inadequate remodeling is present in at least 15% of chronic, focal, new coronary arterial stenoses in patients with stable angina. The magnitude of arterial remodeling appears to be a lesion-specific response.