bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Interrupting Precordial Compressions on the Calculated Probability of Defibrillation Success During Out-of-Hospital Cardiac Arrest
Authors: Eftestøl Trygve , Sunde Kjetil , Steen Petter Andreas
Published: July 2002

Background

—

Cardiopulmonary resuscitation (CPR) creates artifacts on the ECG and, with automated defibrillators, a pause in CPR is mandatory during rhythm analysis. The rate of return of spontaneous circulation (ROSC) is reduced with increased duration of this hands-off interval in rats. We analyzed whether similar hands-off intervals in humans with ventricular fibrillation causes changes in the ECG predicting a lower probability of ROSC.

Methods and Results

—

The probability of ROSC after a shock was continually determined from ECG signal characteristics for up to 20 seconds of 634 such hands-off intervals in patients with ventricular fibrillation. In hands-off intervals with an initially high (40% to 100%) or median (25% to 40%) probability for ROSC, the probability was gradually reduced with time to a median of 8% to 11% after 20 seconds (
P
<0.001). In episodes with a low initial probability (0% to 25%; median, 5%), there was no further reduction with time.

Conclusions

—

The interval between discontinuation of chest compressions and delivery of a shock should be kept as short as possible.
Survival After Coronary Revascularization in the Elderly
Authors: Graham Michelle M. , Ghali William A. , Faris Peter D. , Galbraith P. Diane , Norris Colleen M. , Knudtson Merril L.
Published: July 2002

Background

—

Elderly patients with ischemic heart disease are increasingly referred for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). However, reports of poor outcomes in the elderly have led to questions about the benefit of these strategies. We studied survival by prescribed treatment (CABG, PCI, or medical therapy) for patients in 3 age categories: <70 years, 70 to 79 years, and ≥80 years of age.

Methods and Results

—

The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) is a clinical data collection and outcome monitoring initiative capturing all patients undergoing cardiac catheterization and revascularization in the province of Alberta, Canada, since 1995. Characteristics and long-term outcomes of a cohort of >6000 elderly patients with ischemic heart disease were compared with younger patients. In 15 392 patients >70 years of age, 4-year adjusted actuarial survival rates for CABG, PCI, and medical therapy were 95.0%, 93.8%, and 90.5%, respectively. In 5198 patients 70 to 79 years of age, survival rates were 87.3%, 83.9%, and 79.1%, respectively. In 983 patients ≥80 years of age, survival was 77.4% for CABG, 71.6% for PCI, and 60.3% for medical therapy. Absolute risk differences in comparison to medical therapy for CABG (17.0%) and PCI (11.3%) were greater for patients ≥80 years of age than for younger patients.

Conclusions

—

Elderly patients paradoxically have greater absolute risk reductions associated with surgical or percutaneous revascularization than do younger patients. The combination of these results with a recent randomized trial suggests that the benefits of aggressive revascularization therapies may extend to subsets of patients in older age groups.
Oral Sildenafil Is an Effective and Specific Pulmonary Vasodilator in Patients With Pulmonary Arterial Hypertension
Authors: Michelakis Evangelos , Tymchak Wayne , Lien Dale , Webster Linda , Hashimoto Kyoko , Archer Stephen
Published: July 2002

Background

—

The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO.

Methods and Results

—

We studied 13 consecutive patients (mean±SEM, 44±2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (−19±5%) and sildenafil (−27±3%), whereas sildenafil+iNO was more effective than iNO alone (−32±5%,
P
<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17±5% and 17±4%, respectively), whereas iNO did not (−0.2±2.0%,
P
<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15±6 versus −9±7%,
P
<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (
P
<0.0001).

Conclusions

—

A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.
Sensitivity to Apoptosis Signal, Clearance Rate, and Ultrastructure of Fas Ligand-Induced Apoptosis in In Vivo Adult Cardiac Cells
Authors: Hayakawa Kenji , Takemura Genzou , Koda Masahiko , Kawase Yukinori , Maruyama Rumi , Li Yiwen , Minatoguchi Shinya , Fujiwara Takako , Fujiwara Hisayoshi
Published: July 2002

Background

—

Sensitivity to apoptotic signals, the clearance rate of apoptosis, and the apoptotic ultrastructure have not been studied in cells of the in vivo adult heart.

Methods and Results

—

To minimize the systemic influence, soluble Fas ligand was injected directly into in vivo rat hearts and livers (as the control) at concentrations of 0, 0.5, 2, and 5 μg/mL (groups C, F0.5, F2, and F5). Apoptotic cardiomyocytes and apoptotic noncardiomyocytes of the heart were identified with similar incidences only in F5. Their incidences peaked at 12 hours after injection (2.0±0.09% in cardiomyocytes) and diminished markedly 24 hours later. Caspase-3 was activated only in F5. Boc-Asp-fmk, a pancaspase inhibitor, inhibited apoptosis, suggesting that the apoptosis sensitivity was regulated upstream of caspase-3. Apoptotic noncardiomyocytes showed typical ultrastructure. In addition to the typical ultrastructure, such as cellular shrinkage, chromatin condensation, and apoptotic bodies, however, apoptotic cardiomyocytes showed unique features: doughnut-like, but not half-moon– or crescent-like, chromatin condensation; frequent plasma membrane rupture even during the early stage; condensed mitochondria with wrinkled cristae inside; the appearance of cytoplasmic lipid-like droplets; and myofibrillar derangement. In the livers, typical apoptosis was induced in hepatocytes and nonhepatocytes of the liver even in the F0.5 group, which were cleared 24 hours later.

Conclusions

—

Compared with liver cells, cardiomyocytes as well as noncardiomyocytes of the heart are more resistant against the apoptotic signal, but the clearance is similarly rapid (within 24 hours). The ultrastructure of apoptotic cardiomyocytes is unique. These findings provide new insights into the dynamics of cell death in the heart.
Transcatheter Closure of Interatrial Communications for Secondary Prevention of Paradoxical Embolism
Authors: Bruch Leonhard , Parsi Anne , Grad Marc Oliver , Rux Sascha , Burmeister Telse , Krebs Heike , Kleber Franz Xaver
Published: July 2002

Background
—

Patients with a patent foramen ovale (PFO) after cerebral, coronary, or systemic embolic events of presumed paradoxical origin are at risk for recurrent thromboembolism. We report our single-center experience of interventional closure of interatrial communications for secondary prevention of presumed paradoxical embolism.

Methods and Results
—

Since 1997, percutaneous closure of interatrial communications was performed at our institution in 66 patients (mean age 47.8±12.7 years; 31 males) with a PFO or an atrial septal defect and at least 1 documented presumed paradoxical thromboembolic event. Fifty-eight patients had cerebral embolism, 10 had coronary embolism, and 3 had peripheral embolism. Several patients experienced multilocal arterial embolism. Fifty-four patients had a PFO, 33 of them with an atrial septal aneurysm, and 12 had an atrial septal defect. The implantation procedure was successful and without complication in all patients. After 3 months, only 2 patients showed a residual shunt, which disappeared in both cases after 12 months. In 112.2 patient-years of follow-up (range, 5 weeks to 3.5 years), we have not seen any recurrent thromboembolic event.

Conclusions
—

Interventional closure of interatrial communications is a safe and effective therapeutic option for the secondary prevention of presumed paradoxical embolism. To further evaluate this strategy, randomized trials comparing interventional closure with anticoagulation have been initiated by us and others.
Assessment of Diastolic Function With Doppler Tissue Imaging to Predict Genotype in Preclinical Hypertrophic Cardiomyopathy
Authors: Ho Carolyn Y. , Sweitzer Nancy K. , McDonough Barbara , Maron Barry J. , Casey Susan A. , Seidman J.G. , Seidman Christine E. , Solomon Scott D.
Published: July 2002

Background

—

Unexplained left ventricular hypertrophy (LVH) is considered diagnostic of hypertrophic cardiomyopathy (HCM) but fails to identify all genetically affected individuals. Altered diastolic function has been hypothesized to represent an earlier manifestation of HCM before the development of LVH; however, data regarding the clinical utility of imaging techniques that assess this parameter are limited.

Methods and Results

—

Echocardiographic studies including Doppler tissue imaging (DTI) were performed in a genotyped HCM population with β-myosin heavy chain (β -MHC) mutations. Genotype (+) individuals with LVH (G+/LVH+; n=18) and genotype (+) individuals without LVH (G+/LVH−; n=18) were compared with normal control subjects (n=36). Left ventricular ejection fraction (EF) was significantly higher in both genotype (+) groups (75±5% and 71±6%, respectively, versus 64± 5% in control subjects;
P
<0.0001). Mean early diastolic myocardial velocities (Ea) were significantly lower in both genotype (+) subgroups, irrespective of LVH (
P
<0.02). However, there was substantial overlap in Ea velocities between the G+/LVH− and control groups. An Ea velocity of ≤13.5 cm/s had 86% specificity and 75% sensitivity for identifying genotype-positive subjects. The combination of EF ≥68% and Ea velocity <15 cm/s was 100% specific and 44% sensitive in predicting affected genotype.

Conclusions

—

Abnormalities of diastolic function assessed by Doppler tissue imaging precede the development of LVH in individuals with HCM caused by β -MHC mutations. Although Ea velocity alone was not sufficiently sensitive as a sole diagnostic criterion, the combination of Ea velocity and EF was highly predictive of affected genotype in individuals without overt manifestations of HCM.
Cytosolic Heat Shock Protein 60, Apoptosis, and Myocardial Injury
Authors: Kirchhoff S.R. , Gupta S. , Knowlton A.A.
Published: July 2002

Background
—

Heat shock proteins (HSPs) are well known for their ability to “protect” the structure and function of native macromolecules, particularly as they traffic across membranes. Considering the role of key mitochondrial proteins in apoptosis and the known antiapoptotic effects of HSP27 and HSP72, we postulated that HSP60, primarily a mitochondrial protein, also exerts an antiapoptotic effect.

Methods and Results
—

To test this hypothesis, we used an antisense phosphorothioate oligonucleotide to effect a 50% reduction in the levels of HSP60 in cardiac myocytes, a cell type that has abundant mitochondria. The induced decrease in HSP60 precipitated apoptosis, as manifested by the release of cytochrome c, activation of caspase 3, and induction of DNA fragmentation. Antisense treatment was associated with an increase in bax and a decrease in bcl-2 secondary to increased synthesis of bax and degradation of bcl-2. A control oligonucleotide had no effect on these measurements. We further demonstrated that cytosolic HSP60 forms a macromolecular complex with bax and bak in vitro suggesting that complex formation with HSP60 may block the ability of bax and bak to effect apoptosis in vivo. Lastly, we show that as cytosolic (nonmitochondrial) HSP60 decreases, a small unbound fraction of bax appears and that the amount of bax associated with the mitochondria and cell membranes increases.

Conclusions
—

These results support a key antiapoptotic role for cytosolic HSP60. To our knowledge, this is the first report suggesting that interactions of HSP60 with bax and/or bak regulate apoptosis.
Polymorphic Reentrant Ventricular Tachycardia in the Isolated Rabbit Heart Studied by High-Density Mapping
Authors: Boersma Lucas , Zetelaki Zoltan , Brugada Josep , Allessie Maurits
Published: July 2002

Background

—

The role of dispersion of refractoriness and reentry for the genesis of polymorphic ventricular tachycardia (VT) has recently become emphasized. We investigated the mechanisms of polymorphic arrhythmias in a 2D preparation confining an area of prolonged refractoriness.

Methods and Results

—

In 16 Langendorff-perfused rabbit hearts, a sheet of left ventricular epicardium was obtained by a cryoprocedure. Enhanced spatial heterogeneity in a refractory period was created by cooling a central region (diameter=12 mm). This markedly prolonged the refractory period (by 36±14 ms) inside but only slightly prolonged it (by 5±11 ms) outside the cooled area (n=6). During a control procedure, programmed stimulation with up to 3 premature stimuli induced an episode of monomorphic VT in only 1 of 10 hearts. During regional cooling, episodes of polymorphic VT with a maximum duration of 35 seconds could be induced in all hearts. High-resolution mapping (229 electrodes) of epicardial activation revealed that polymorphic VT was caused by a functional reentrant circuit located partially within the region of prolonged refractoriness. The reentrant wavefront was continuously shifting along the border of the cooled region, resulting in beat-to-beat changes in the excitation pattern. Spontaneous termination of polymorphic VT occurred either by a shift of the reentrant circuit outside the cooled region or by a block in the central common pathway during figure-of-8 reentry in the region of prolonged refractoriness.

Conclusions

—

A shifting functional reentrant circuit was the underlying mechanism of polymorphic VT in a substrate of enhanced spatial heterogeneity of refractoriness.
Pharmacological Rescue of Human K
+
Channel Long-QT2 Mutations
Authors: Rajamani Sridharan , Anderson Corey L. , Anson Blake D. , January Craig T.
Published: July 2002

Background
—

Defective protein trafficking is a consequence of gene mutations. Human long-QT (LQT) syndrome results from mutations in several genes, including the
human ether-a-go-go-related gene
(HERG), which encodes a delayed rectifier K
+
current. Trafficking-defective mutant HERG protein is a mechanism for reduced delayed rectifier K
+
current in LQT2, and high-affinity HERG channel-blocking drugs can result in pharmacological rescue.

Methods and Results
—

We postulated that drug molecules modified to remove high-affinity HERG block may still stabilize mutant proteins in a conformation required for rescue. We tested terfenadine carboxylate (fexofenadine) and terfenadine, structurally similar drugs with markedly different affinities for HERG block, for rescue of trafficking-defective LQT2 mutations. Terfenadine rescued the N470D mutation but blocked the channels. In contrast, fexofenadine rescued N470D with a half-maximal rescue concentration of 177 nmol/L, which is ≈350-fold lower than the half-maximal channel block concentration. The G601S mutation was also rescued without channel block.

Conclusions
—

Pharmacological rescue can occur without channel block. This could represent a new antiarrhythmic paradigm in the treatment of some trafficking-defective LQT2 mutations.
Sequential Follow-Up Results of Catheter Intervention for Coronary Artery Lesions After Kawasaki Disease
Authors: Ishii Masahiro , Ueno Takafumi , Ikeda Hisao , Iemura Motofumi , Sugimura Tetsu , Furui Jun , Sugahara Yoko , Muta Hiromi , Akagi Teiji , Nomura Yuichi , Homma Tomoki , Yokoi Hiroyoshi , Nobuyoshi Masakiyo , Matsuishi Toyojiro , Kato Hirohisa
Published: July 2002

Background

—

The purpose of this study was to assess the sequential follow-up results of catheter intervention in Kawasaki disease by use of quantitative coronary angiography (QCA) and intravascular ultrasound imaging.

Methods and Results

—

Catheter intervention was performed on 23 stenotic lesions in 22 patients (aged 2 to 24 years). Percutaneous balloon angioplasty (PBA) was performed in 4 patients, stent implantation in 7, percutaneous transluminal coronary rotational ablation (PTCRA) in 10, and a combination of PTCRA with stent implantation in 2. A total of 21 lesions (91%) were successfully dilated by catheter intervention without major or minor complications. One patient immediately underwent coronary artery bypass grafting (CABG) surgery because stent implantation failed to resolve his lesion. At 4 to 6 months after catheter intervention, 2 restenotic lesions (9%) were detected by QCA in 2 patients who had undergone PBA, and these patients subsequently underwent CABG surgery. In 6 months to 3 years after catheter intervention, no patients showed evidence of ischemic findings. At 3 to 4 years after catheter intervention, QCA and intravascular ultrasound studies were performed on 15 lesions in 14 patients. Two restenotic lesions (13%) were detected by QCA in 2 patients. One of the 2 had stent implantation and underwent CABG surgery, and the other had undergone PTCRA and underwent re-PTCRA. Thirteen patients demonstrated no ischemic findings at 3 to 8 years after catheter intervention.

Conclusion

—

Catheter intervention for Kawasaki disease can be accomplished and can be effective in the short term, but the long-term efficacy should be verified by further study.
Neurohormonal Activation and the Chronic Heart Failure Syndrome in Adults With Congenital Heart Disease
Authors: Bolger Aidan P. , Sharma Rakesh , Li Wei , Leenarts Marjolein , Kalra Paul R. , Kemp Michael , Coats Andrew J.S. , Anker Stefan D. , Gatzoulis Michael A.
Published: July 2002

Background

—

Neurohormonal activation characterizes chronic heart failure, relates to outcome, and is a therapeutic target. It is not known whether a similar pattern of neurohormonal activation exists in adults with congenital heart disease and, if so, whether it relates to common measures of disease severity or whether cardiac anatomy is a better discriminant.

Methods and Results

—

Concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1), renin, aldosterone, norepinephrine, and epinephrine were determined in 53 adults with congenital heart disease, comprising 4 distinct anatomic subgroups (29 female; 33.5±1.5 years of age; New York Heart Association class 2.0±0.1, mean±SEM) and 15 healthy control subjects (8 female; 32.3±1.3 years of age). Systemic ventricular function was graded by a blinded echocardiographer as normal or mildly, moderately, or severely impaired. Adults with congenital heart disease had elevated levels of ANP (56.6 versus 3.1 pmol/L), BNP (35.8 versus 5.7 pmol/L), ET-1 (2.5 versus 0.7 pmol/L, all
P
<0.0001), renin (147 versus 16.3 pmol/L), norepinephrine (2.2 versus 1.6 pmol/L, both
P
<0.01) and aldosterone (546 versus 337 pmol/L,
P
<0.05). There was a highly significant stepwise increase in ANP, BNP, ET-1, and norepinephrine according to New York Heart Association class and systemic ventricular function, with even asymptomatic patients having evidence of significant neurohormonal activation. In contrast, there was no direct relationship between the 4 anatomic subgroups and any of the neurohormones studied.

Conclusions

—

Neurohormonal activation in adult congenital heart disease bears the hallmarks of chronic heart failure, relating to symptom severity and ventricular dysfunction and not necessarily to anatomic substrate. Neurohormonal antagonism across this large and anatomically diverse population should be considered.
Advanced Coronary and Carotid Arteriopathy in Young Adults With Childhood-Onset Chronic Renal Failure
Authors: Oh Jun , Wunsch Rainer , Turzer Martin , Bahner Malte , Raggi Paolo , Querfeld Uwe , Mehls Otto , Schaefer Franz
Published: July 2002

Background

—

Cardiovascular mortality is excessive in young adults with end-stage renal disease (ESRD). The factors contributing to ESRD-related vascular disease are incompletely understood. Young adults with childhood-onset chronic renal failure (CRF) are uniquely suited for risk factor assessment because of their long-term exposure at an age when vascular pathology in the general population is still minimal.

Methods and Results

—

We used novel noninvasive technologies to screen for coronary and carotid artery disease in 39 patients with ESRD aged 19 to 39 years with childhood-onset CRF presently treated by dialysis or renal transplantation. Coronary artery calcification burden was assessed by CT scan with ECG gating and the intima-media thickness (IMT) of the carotid arteries by high-resolution ultrasound. Coronary artery calcifications were present in 92% of patients; calcium scores exceeded the 95th age- and sex-specific percentiles >10-fold on average. Carotid IMT was significantly increased compared with matched control subjects. Both coronary calcium scores and IMT were associated with cumulative dialysis and ESRD time and the cumulative serum calcium-phosphate product. Coronary calcium scores were strongly correlated with C-reactive protein and
Chlamydia pneumoniae
seropositivity, time-averaged mean serum parathyroid hormone, and plasma homocysteine. C-reactive protein and parathyroid hormone independently predicted coronary calcium accumulation. Smoking, obesity, and HbA1c were correlated with IMT in the control subjects but not in the patients.

Conclusions

—

Young adults with childhood-onset CRF have a high prevalence of arteriopathy associated with indicators of microinflammation, hyperparathyroidism, calcium-phosphate overload, and hyperhomocysteinemia but not traditional atherogenic risk factors. These risk factors persist even after successful renal transplantation.
Mechanism of Inducible Regional Dysfunction During Dipyridamole Stress
Authors: Bin Jian-Ping , Le Elizabeth , Pelberg Robert A. , Coggins Matthew P. , Wei Kevin , Kaul Sanjiv
Published: July 2002

Background

—

We hypothesized that increased myocardial oxygen demand resulting from hypotension and reflex tachycardia unmasking a reduced endocardial myocardial blood flow (MBF) reserve is the mechanism of dipyridamole-induced regional dysfunction in chronic coronary artery disease.

Methods and Results

—

Ameroid constrictors were placed around the proximal coronary arteries and their major branches in 15 dogs to create chronic coronary stenosis. Seven days later, radiolabeled microsphere–derived MBF and 2-dimensional echocardiography–derived percent wall thickening (%WT) were measured at rest and after 0.56 mg/kg dipyridamole. Dipyridamole caused an increase (mean, 21%) in the rate-pressure product secondary to reflex tachycardia resulting from mild systemic hypotension. %WT in myocardial segments with an endocardial MBF reserve (dipyridamole/resting MBF) of 1.5 to 2.5 (n=35) did not change after dipyridamole, whereas it decreased in segments with an endocardial MBF reserve of <1.5 (n=30) and increased in those with an endocardial MBF reserve of ≥2.5 (n=45) (
P
<0.05). Most (80%) segments with endocardial MBF reserve of <1.5 and 14% with an endocardial MBF reserve of 1.5 to 2.5 showed inducible dysfunction after dipyridamole, whereas none of the segments with an endocardial MBF reserve of ≥2.5 showed this finding. A sigmoid relation (
y
=−6.74/[1+exp (19.9 · [
x
−1.84])]+1.35 ·
x
,
r
=0.93,
P
<0.0001) was noted between endocardial MBF reserve and Δ%WT. In contrast, neither the epicardial MBF reserve nor the endocardial/epicardial MBF ratio during hyperemia was associated with inducible regional dysfunction.

Conclusions

—

Increased myocardial oxygen demand resulting from hypotension and reflex tachycardia unmasking a reduced endocardial MBF reserve is the primary mechanism of dipyridamole-induced regional dysfunction in chronic coronary artery disease.
Impaired Carotid Viscoelastic Properties in Women With Polycystic Ovaries
Authors: Lakhani Kalpana , Seifalian Alexander M. , Hardiman Paul
Published: July 2002

Background

—

The purpose of this study was to assess the elastic properties of the carotid arteries in women with polycystic ovarian syndrome, asymptomatic women with polycystic ovaries, and healthy controls.

Methods and Results

—

We recruited the following 60 subjects: 20 symptomatic women with polycystic ovaries attending the reproductive endocrinology clinics, 20 asymptomatic women with polycystic ovaries attending the family planning clinic, and 20 staff volunteers as healthy controls with normal ovaries on transvaginal scan. Compliance and stiffness index were assessed in the common and internal carotid arteries using duplex ultrasound equipped with an echo-locked arterial wall–tracking system. Compliance was significantly lower in the common carotid artery in symptomatic and asymptomatic women with polycystic ovaries than in the controls (10.7, 14.1, and 19.2 %mm Hg
−1
×10
−2
, respectively). The arterial stiffness index was correspondingly increased (12.3, 10.2, and 6.7, respectively). Similar results were obtained in the internal carotid artery for compliance (10.1, 11.0, and 16.9 %mm Hg
−1
×10
−2
, respectively) and stiffness index (14.8, 16.2, and 8.7, respectively).

Conclusions

—

The results of this study provide additional evidence of vascular dysfunction in women with polycystic ovaries and are compatible with the hypothesis that they are at increased risk from coronary artery disease and stroke.
Transforming Growth Factor-β Function Blocking Prevents Myocardial Fibrosis and Diastolic Dysfunction in Pressure-Overloaded Rats
Authors: Kuwahara Fumitaka , Kai Hisashi , Tokuda Keisuke , Kai Mamiko , Takeshita Akira , Egashira Kensuke , Imaizumi Tsutomu
Published: July 2002

Background

—

Excessive myocardial fibrosis impairs cardiac function in hypertensive hearts. Roles of transforming growth factor (TGF)-β in myocardial remodeling and cardiac dysfunction were examined in pressure-overloaded rats.

Methods and Results

—

Pressure overload was induced by a suprarenal aortic constriction in Wistar rats. Fibroblast activation (proliferation and phenotype transition to myofibroblasts) was observed after day 3 and peaked at days 3 to 7. Thereafter, myocyte hypertrophy and myocardial fibrosis developed by day 28. At day 28, echocardiography showed normal left ventricular fractional shortening, but the decreased ratio of early to late filling velocity of the transmitral Doppler velocity and hemodynamic measurement revealed left ventricular end-diastolic pressure elevation, indicating normal systolic but abnormal diastolic function. Myocardial TGF-β mRNA expression was induced after day 3, peaked at day 7, and remained modestly increased at day 28. An anti–TGF-β neutralizing antibody, which was administered intraperitoneally daily from 1 day before operation, inhibited fibroblast activation and subsequently prevented collagen mRNA induction and myocardial fibrosis, but not myocyte hypertrophy. Neutralizing antibody reversed diastolic dysfunction without affecting blood pressure and systolic function.

Conclusions

—

TGF-β plays a causal role in myocardial fibrosis and diastolic dysfunction through fibroblast activation in pressure-overloaded hearts. Our findings may provide an insight into a new therapeutic strategy to prevent myocardial fibrosis and diastolic dysfunction in pressure-overloaded hearts.
Interventions on Prevention of Postoperative Atrial Fibrillation in Patients Undergoing Heart Surgery
Authors: Crystal Eugene , Connolly Stuart J. , Sleik Khaled , Ginger Tracy J. , Yusuf Salim
Published: July 2002

Background

—

Postoperative atrial fibrillation (AF) is a common complication of cardiac surgery and has been associated with increased incidence of other complications and increased hospital length of stay (LOS). Prevention of AF is a reasonable clinical goal, and, consequently, many randomized trials have evaluated the effectiveness of pharmacological and nonpharmacological interventions for prevention of AF. To better understand the role of various prophylactic therapies against postoperative AF, a systematic review of evidence from randomized trials was performed.

Methods and Results

—

Fifty-two randomized trials (controlled by placebo or routine treatment) of β-blockers, sotalol, amiodarone, or pacing were identified by systematic literature search. The 3 drug treatments each prevented AF with the following odds ratios (ORs): β-blockers, 0.39 (95% CI, 0.28 to 0.52); sotalol, 0.35 (95% CI, 0.26 to 0.49); and amiodarone, 0.48 (95% CI, 0.37 to 0.61). Pacing was also effective; for biatrial pacing, the OR was 0.46 (95% CI, 0.30 to 0.71). The influence of pharmacological interventions on LOS was as follows: −0.66 day (95% CI, 2.04 to 0.72) for β-blockers; −0.40 day (95% CI, 0.87 to 0.08) for sotalol; and −0.91 day (95% CI, 1.59 to −0.23) for amiodarone. The influence for biatrial pacing was −1.54 day (95% CI, −2.85 to −0.24). The incidence of stroke was 1.2% in all the treatment groups combined and 1.4% in controls (OR, 0.90; 95% CI, 0.46 to 1.74).

Conclusions

—

β-Blockers, sotalol, and amiodarone all reduce risk of postoperative AF with no marked difference between them. There is evidence that use of these drugs will reduce LOS. Biatrial pacing is a promising new treatment opportunity. There was no evidence that reducing postoperative AF reduces stroke; however, data on stroke are incomplete.
Change in Systolic Left Ventricular Performance After 3 Years of Antihypertensive Treatment
Authors: Wachtell Kristian , Palmieri Vittorio , Olsen Michael H. , Gerdts Eva , Papademetriou Vasilios , Nieminen Markku S. , Smith Gunnar , Dahlöf Björn , Aurigemma Gerard P. , Devereux Richard B.
Published: July 2002

Background

—

We have shown that hypertensive patients with left ventricular (LV) hypertrophy have decreased LV midwall mechanics, but the effect of antihypertensive therapy remains unclear.

Methods and Results

—

Echocardiograms were recorded at baseline in 679 hypertensive patients and ECG LV hypertrophy and repeated yearly during 3 years of blinded treatment to achieve target blood pressures (BPs) of 140/90 mm Hg. On average, BP was reduced from 174±21 to 147±19 over 95±11 to 82±10 mm Hg and LV mass from 234±56 to 194±50 g. Endocardial fractional shortening (FS) decreased slightly, whereas midwall FS increased from 15.4±2.0% to 16.8±2.1% and stress-corrected midwall FS increased from 97±13 to 105±12% (all
P
<0.001). Change in midwall FS was related inversely to change in LV mass (LVM), relative wall thickness (RWT), and diastolic BP and directly to change in Doppler stroke volume (SV, all
P
<0.001). Multivariate analysis showed that change in MWS was independently inversely related to changes in LVM (β=−0.211), RWT (β=−0.334, all
P
<0.001), and diastolic BP (β=−0.088,
P
<0.05) and directly related to SV (β=0.192,
P
<0.001) with control for blinded therapy. Change in stress-corrected midwall shortening was inversely independently associated with changes in LVM (β=−0.153) and RWT (β=−0.562) and directly with changes in SV (β=0.145) and systolic BP (β=0.s221, all
P
<0.001) with control for blinded therapy.

Conclusions

—

Antihypertensive therapy reduced LVM and increased LV midwall shortening and contractility with a small decrease in LV chamber function and significant increase in SV. Change in systolic LV performance was independently associated inversely with change in LVM, RWT, and BP and directly with change in SV.
Smooth Muscle Cells, But Not Myocytes, of Host Origin in Transplanted Human Hearts
Authors: Glaser Ruchira , Lu Min Min , Narula Navneet , Epstein Jonathan A.
Published: July 2002

Background

—

There is increasing evidence to support a role for stem cells in the regeneration and repair of the human cardiovascular system. However, significant controversy still remains about the extent of chimerism present in blood vessels and myocytes of transplanted human hearts.

Methods and Results

—

We investigated the contribution of infiltrating host cells to human cardiac allografts by evaluating the origin of vascular smooth muscle cells and cardiac myocytes in hearts after orthotopic cardiac transplantation. Smooth muscle cells were identified in pathological human coronary artery specimens with antibodies against smooth muscle α-actin. DNA in situ hybridization for the human Y chromosome was then performed on the same samples to identify cells of male origin. Both myocytes and vascular smooth muscle cells were examined for the presence of the Y chromosome in sex-mismatched specimens. In positive control samples, 34.7% of nuclei contained a detectable Y chromosome; in sex-mismatched samples, 2.6% of the smooth muscle cells examined were of host origin. The Y chromosome in myocyte nuclei in male positive controls was detected; however, despite examination of >6000 myocyte nuclei in sex-mismatched specimens, we were unable to detect any nuclei with the clear presence of the Y chromosome.

Conclusions

—

Vascular smooth muscle cells of infiltrating host cell origin can be found in human cardiac allografts. However, unlike prior reports, we found no evidence that chimerism is present in cardiac myocytes.
Use of Irbesartan to Maintain Sinus Rhythm in Patients With Long-Lasting Persistent Atrial Fibrillation
Authors: Madrid Antonio H. , Bueno Manuel G. , Rebollo Jose M.G. , Marín Irene , Peña Gonzalo , Bernal Enrique , Rodriguez Aníbal , Cano Lucas , Cano José M. , Cabeza Pedro , Moro Concepción
Published: July 2002

Background

—

Data from studies of angiotensin-converting enzyme inhibitors provide evidence that the renin-angiotensin-aldosterone system plays a role as a mediator of atrial remodeling in atrial fibrillation. The present study has evaluated the effect of treatment with the angiotensin I type 1 receptor blocker irbesartan on maintaining sinus rhythm after conversion from persistent atrial fibrillation.

Methods and Results

—

To be included in the present study, patients must have had an episode of persistent atrial fibrillation for >7 days. The patients were then randomized and scheduled for electrical cardioversion. Two groups of patients were compared: Group I was treated with amiodarone, and group II was treated with amiodarone plus irbesartan. The primary end point was the length of time to a first recurrence of atrial fibrillation. From a total of 186 patients assessed in the study, 154 were analyzed with the use of intention-to-treat analysis. Seventy-five patients were randomly allocated to group I and 79 to group II. After 2 months of follow-up in the intention-to-treat analysis, the group treated with irbesartan had fewer patients with recurrent atrial fibrillation (Kaplan-Meier analysis, 84.79% versus 63.16%,
P
=0.008). The Kaplan-Meier analysis of time to first recurrence during the follow-up period (median time, 254 days [range, 60 to 710]) also showed that patients treated with irbesartan had a greater probability of remaining free of atrial fibrillation (79.52% versus 55.91%,
P
=0.007).

Conclusions

—

Patients treated with amiodarone plus irbesartan had a lower rate of recurrence of atrial fibrillation than did patients treated with amiodarone alone.
Assessment of Survival in Patients With Primary Pulmonary Hypertension
Authors: Wensel Roland , Opitz Christian F. , Anker Stefan D. , Winkler Jörg , Höffken Gert , Kleber Franz X. , Sharma Rakesh , Hummel Manfred , Hetzer Roland , Ewert Ralf
Published: July 2002

Background

—

Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessment is an important factor in determining medical treatment and lung transplantation. Whether cardiopulmonary exercise testing data predict survival has not been reported previously.

Methods and Results

—

We studied 86 patients with PPH (58 female, age 46±2 years, median NYHA class III) between 1996 and 2001 who were followed up in a tertiary referral center. Right heart catheterization was performed and serum uric acid levels were measured in all patients. Seventy patients were able to undergo exercise testing. At the start of the study, the average pulmonary artery pressure was 60±2 mm Hg, average pulmonary vascular resistance was 1664±81 dyne · s · cm
−5
, average serum uric acid level was 7.5±0.35 mg/dL, and average peak oxygen uptake during exercise (peak V̇
o
2
) was 11.2±0.5 mL · kg
−1
· min
−1
. During follow-up (mean: 567±48 days), 28 patients died and 16 underwent lung transplantation (1-year cumulative event-free survival: 68%; 95% CI 58 to 78). The strongest predictors of impaired survival were low peak V̇
o
2
(
P
<0.0001) and low systolic blood pressure at peak exercise (peak SBP;
P
<0.0001). In a multivariable analysis, serum uric acid levels (all
P
<0.005) and diastolic blood pressure at peak exercise independently predicted survival (
P
<0.05). Patients with peak V̇
o
2
≤10.4 mL · kg
−1
· min
−1
and peak SBP ≤120 mm Hg (ie, 2 risk factors) had poor survival rates at 12 months (23%), whereas patients with 1 or none of these risk factors had better survival rates (79% and 97%, respectively).

Conclusions

—

Peak V̇
o
2
and peak SBP are independent and strong predictors of survival in PPH patients. Hemodynamic parameters, although also accurate predictors, provide no independent prognostic information.
Synthesis of Collagen Is Dysregulated in Cultured Fibroblasts Derived From Skin of Subjects With Varicose Veins as It Is in Venous Smooth Muscle Cells
Authors: Sansilvestri-Morel Patricia , Rupin Alain , Jaisson Stéphane , Fabiani Jean-Noël , Verbeuren Tony J. , Vanhoutte Paul M.
Published: July 2002

Background

—

The dilatation and tortuosity observed in varicose veins provide evidence for progressive venous wall remodeling associated with abnormalities of smooth muscle cells and extracellular matrix. The present study was designed to examine if the phenotypic modulations observed in the venous smooth muscle cells of patients with varicose veins were also present in their dermal fibroblasts.

Methods and Results

—

Collagen type I (collagen I), type III (collagen III), and type V (collagen V) were compared in dermal fibroblasts derived from the skin of control subjects and patients with varicose veins. The synthesis of collagen I, the release of its metabolites, and the expression of its mRNA were increased in fibroblasts from patients with varicose veins, whereas the synthesis of collagen III was decreased but not correlated with a decrease in mRNA expression and in metabolite release. Matrix metalloproteinases (MMP1, 2, 7, 8, 9, and 13) and their inhibitors (TIMP1 and 2) were quantified in both cell types; only the production of proMMP2 was increased in cells derived from patients with varicose veins.

Conclusions

—

These findings suggest that the synthesis of collagen I and III is dysregulated in dermal fibroblasts derived from patients with varicose veins. These results are comparable with those observed in smooth muscle cells derived from varicose veins, thus suggesting a systemic alteration of tissue remodeling in subjects with varicose veins.
Use of the Logical Analysis of Data Method for Assessing Long-Term Mortality Risk After Exercise Electrocardiography
Authors: Lauer Michael S. , Alexe Sorin , Pothier Snader Claire E. , Blackstone Eugene H. , Ishwaran Hemant , Hammer Peter L.
Published: July 2002

Background

—

Logical Analysis of Data is a methodology of mathematical optimization on the basis of the systematic identification of patterns or “syndromes.” In this study, we used Logical Analysis of Data for risk stratification and compared it to regression techniques.

Methods and Results

—

Using a cohort of 9454 patients referred for exercise testing, Logical Analysis of Data was applied to identify syndromes based on 20 variables. High-risk syndromes were patterns of up to 3 findings associated with >5-fold increase in risk of death, whereas low-risk syndromes were associated with >5-fold decrease. Syndromes were derived on a randomly derived training set of 4722 patients and validated in 4732 others. There were 15 high-risk and 26 low-risk syndromes. A risk score was derived based on the proportion of possible high risk and low risk syndromes present. A value ≥0, meaning the same or a greater proportion of high-risk syndromes, was noted in 979 patients (21%) in the validation set and was predictive of 5-year death (11% versus 1%, hazard ratio 8.3, 95% CI 5.9 to 11.6, P<0.0001), accounting for 67% of events. Calibration of expected versus observed death rates based on Logical Analysis of Data and Cox regression showed that both methods performed very well.

Conclusion

—

Using the Logical Analysis of Data method, we identified subsets of patients who had an increased risk and who also accounted for the majority of deaths. Future research is needed to determine how best to use this technique for risk stratification.
Cardiorespiratory Fitness and C-Reactive Protein Among a Tri-Ethnic Sample of Women
Authors: LaMonte Michael J. , Durstine J. Larry , Yanowitz Frank G. , Lim Tobin , DuBose Katrina D. , Davis Paul , Ainsworth Barbara E.
Published: July 2002

Background

—

Elevated C-reactive protein (CRP) is associated with increased coronary heart disease (CHD) risk. Cardiorespiratory fitness (“fitness”) is related with lower CHD risk; however, its relationship with CRP is relatively unknown.

Methods and Results

—

Cross-sectional associations between fitness and plasma CRP were examined among 135 African American (AA), Native American (NA), and Caucasian (CA) women (55±11 year; 28±6 kg/m
2
). Fitness was assessed with a maximal treadmill exercise test. Plasma CRP concentrations were determined with the Dade Behring high-sensitivity immunoassay. Geometric mean CRP levels were 0.43, 0.25, and 0.23 mg/dL, and average maximal MET levels of fitness were 7.2, 9.1, and 10 METs for AA, NA, and CA, respectively. CRP decreased across tertiles of fitness (
P
=0.002), increased across tertiles of BMI (
P
=0.0007), and varied by race (
P
=0.002). After adjustment for covariates, lower CRP (
P
<0.05) was observed across tertiles of fitness among NA and CA, but not AA. Among all women, after adjusting for race and covariates, the odds of high-risk CRP (>0.19 mg/dL) were 0.67 (95% CI=0.19 to 2.4) among fit (>6.5 METs) versus unfit women.

Conclusions

—

The health benefits from enhanced fitness may have an antiinflammatory mechanism.
Serine Protease Activity in M-1 Cortical Collecting Duct Cells
Authors: Liu Lian , Hering-Smith Kathleen S. , Schiro Faith R. , Hamm L. Lee
Published: July 2002

An apical serine protease, channel-activating protease 1 (CAP1), augments sodium transport in A6 cells. Prostasin, a novel serine protease originally purified from seminal fluid, has been proposed to be the mammalian ortholog of CAP1. We have recently found functional evidence for a similar protease activity in the M-1 cortical collecting duct cell line. The purposes of the present studies were to determine whether prostasin (or CAP1) is present in collecting duct cells by use of mouse M-1 cells, to sequence mouse prostasin, and to further characterize the identity of the serine protease activity and additional functional features in M-1 cells. Using mouse expressed sequence tag sequences that are highly homologous to the published human prostasin sequence as templates, reverse transcription–polymerase chain reaction and RACE (rapid amplification of cDNA ends) were used to sequence mouse prostasin mRNA, which shows 99% identical to published mouse CAP1 sequence. A single 1800-bp transcript was found by Northern analysis, and this was not altered by aldosterone. Equivalent short-circuit current (I
eq
), which represents sodium transport in these cells, dropped to 59±3% of control value within 1 hour of incubation with aprotinin, a serine protease inhibitor. Trypsin increased the I
eq
in aprotinin-treated cells to the value of the control group within 5 minutes. Application of aprotinin not only inhibited amiloride sensitive I
eq
but also reduced transepithelial resistance (R
te
) to 43±2%, an effect not expected with simple inhibition of sodium channels. Trypsin partially reversed the effect of aprotinin on R
te
. Another serine protease inhibitor, soybean trypsin inhibitor (STI), decreased I
eq
in M-1 cells. STI inhibited I
eq
gradually over 6 hours, and the inhibition of I
eq
by 2 inhibitors was additive. STI decreased transepithelial resistance much less than did aprotinin. Neither aldosterone nor dexamethasone significantly augmented protease activity or prostasin mRNA levels, and in fact, dexamethasone decreased prostasin mRNA expression. In conclusion, although prostasin is present in M-1 cells and probably augments sodium transport in these cells, serine proteases probably have other effects (eg, resistance) in the collecting duct in addition to effects on sodium channels. Steroids do not alter these effects in M-1 cells. Additional proteases are likely also present in mouse collecting duct cells.
The T-786→C Mutation in Endothelial Nitric Oxide Synthase Is Associated With Hypertension
Authors: Hyndman Matthew E. , Parsons Howard G. , Verma Subodh , Bridge Peter J. , Edworthy Steven , Jones Charlotte , Lonn Eva , Charbonneau Francois , Anderson Todd J.
Published: July 2002

Although the pathogenic mechanisms involved in predisposing individuals to hypertension are not well defined, evidence is accumulating that suggests a strong genetic transmission. Animal studies and some clinical investigations have revealed that aberrant NO production may be an important contributing factor. Indeed, a missense mutation in the endothelial NO gene caused by a Glu298Asp alteration has been strongly associated with essential hypertension, coronary artery spasm, and myocardial infarction. Recently, another point mutation caused by a T-786→C transition in the 5′-flanking region of the endothelial NO synthase gene has been identified and, like the Glu298Asp mutation, is associated with coronary artery spasm. The present study was conducted to determine the effect of the T-786→C point mutation on hypertension. We investigated the interaction between the endothelial NO synthase T-786→C polymorphism and blood pressure in a large (n=705) clinically healthy population. Allele frequencies for the T and C alleles were 62% and 38%, translating into 39%, 46% and 15% of the population having the T/T, T/C, and C/C genotypes, respectively, for the T-786→C point mutation. Subjects with the C/C genotype had significantly higher systolic blood pressures and were 2.16(95% confidence interval, 1.3 to 3.7) more likely to be hypertensive. Therefore, the −786 C/C genotype in NO synthase is a significant contributing factor for increasing the risk of essential hypertension.