bluuebunny/crossref_metadata_2025 huggingface dataset:
Relations of Left Ventricular Mass to Fat-Free and Adipose Body Mass
Authors: Bella Jonathan N. , Devereux Richard B. , Roman Mary J. , O’Grady Michael J. , Welty Thomas K. , Lee Elisa T. , Fabsitz Richard R. , Howard Barbara V.
Published: June 2012

Background
—It is unclear whether increased left ventricular (LV) mass in overweight individuals is related to their adiposity or to greater fat-free mass (FFM).

Methods and Results
—We compared echocardiographic LV mass to FFM and adipose body mass by bioelectric impedance and to anthropometric measurements in 3107 American Indian participants in the Strong Heart Study. In men and women, the relations of LV mass and FFM (
r
=0.37 and 0.38,
P
<0.001) were closer (
P
<0.05 to <0.001) than they were with adipose mass, waist/hip ratio, body mass index, systolic blood pressure, height, or height
2.7
. Regression analyses showed that in men LV mass had the strongest independent relation with FFM, followed by systolic blood pressure and age (all
P
<0.001); in women, LV mass was related to FFM more strongly than it was to systolic blood pressure, age (all
P
<0.001), and diabetes (
P
=0.012). Adipose mass had no independent relation to LV mass. When waist/hip ratio or body mass index were substituted for adipose mass, LV mass was independently related to FFM (
P
<0.001) and body mass index (
P
=0.02) but not to waist/hip ratio in men and was independently related to FFM and waist/hip ratio (both
P
<0.001) but not to body mass index in women. Using 97.5 percentile gender-specific partitions for LV mass/FFM in reference individuals, we found that LV hypertrophy occurred in 20.8% of Strong Heart Study participants with hypertension, overweight , or diabetes compared with 10.5% and 16.7% by LV mass indexed for body surface area or height
2.7
.

Conclusions
—LV mass is more strongly related to FFM than to adipose mass, waist/hip ratio, body mass index, or height-based surrogates for lean body weight; LV mass/FFM criteria may increase sensitivity to detect LV hypertrophy.
Measurement of Atherosclerotic Carotid Plaque Size In Vivo Using High Resolution Magnetic Resonance Imaging
Authors: Yuan Chun , Beach Kirk W. , Smith Llewellyn Hillyer , Hatsukami Thomas S.
Published: June 2012

Background
—Current imaging modalities, such as contrast angiography, accurately determine the degree of luminal narrowing but provide no direct information on plaque size. Magnetic resonance imaging (MRI), however, has potential for noninvasively determining arterial wall area (WA). This study was conducted to determine the accuracy of in vivo MRI for measuring the cross-sectional maximum wall area (MaxWA) of atherosclerotic carotid arteries in a group of patients undergoing carotid endarterectomy.

Methods and Results
—Fourteen patients scheduled for carotid endarterectomy underwent preoperative carotid MRI using a custom-made phased-array coil. The plaques were excised en bloc and scanned using similar imaging parameters. MaxWA measurements from the ex vivo MRI were used as the reference standard and compared with MaxWA measurements from the corresponding in vivo MR study. Agreement between the in vivo and ex vivo measurement was analyzed using the Bland-Altman method. The paired in vivo and ex vivo MaxWA measurements strongly agreed: the mean difference (in vivo minus ex vivo) in MaxWA was 13.1±6.5 mm

2

for T1-weighted (T1W) imaging (mean MaxWA in vivo=94.7 mm
2
, ex vivo=81.6 mm
2
) and 14.1±11.7 mm

2

for proton density–weighted (PDW) imaging (mean MaxWA in vivo=93.4 mm
2
, ex vivo=79.3 mm
2
). Intraobserver and interobserver variability was small, with intraclass correlation coefficients ranging from 0.90 to 0.98.

Conclusions
—MRI is highly accurate for in vivo measurement of artery WA in atherosclerotic carotid lesions. This imaging technique has potential application monitoring lesion size in studies examining plaque progression and/or regression.
Regular Physical Exercise Corrects Endothelial Dysfunction and Improves Exercise Capacity in Patients With Chronic Heart Failure
Authors: Hambrecht Rainer , Fiehn Eduard , Weigl Claudia , Gielen Stephan , Hamann Caroline , Kaiser Ralf , Yu Jiangtao , Adams Volker , Niebauer Josef , Schuler Gerhard
Published: June 2012

Background
—The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF.

Methods and Results
—Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24±4%) or a control group (n=10, LVEF 23±3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endothelium-independent vasodilation remained unaltered (271% versus 281%,
P
=NS). Peripheral blood flow improved significantly in response to 90 μg/min acetylcholine by 203% (from 152±79 to 461±104 mL/min,
P
<0.05 versus control group) and the inhibiting effect of L-NMMA increased by 174% (from −46±25 to −126±19 mL/min,
P
<0.05 versus control group). Peak oxygen uptake increased by 26% (
P
<0.01 versus control group). The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow (r=0.64,
P
<0.005).

Conclusions
—Regular physical exercise improves both basal endothelial nitric oxide (NO) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF. The correction of endothelium dysfunction is associated with a significant increase in exercise capacity.
Atrial Natriuretic Peptide Has Different Effects on Contractility and Intracellular pH in Normal and Hypertrophied Myocytes From Pressure-Overloaded Hearts
Authors: Tajima Minori , Bartunek Jozef , Weinberg Ellen O. , Ito Nobuhiko , Lorell Beverly H.
Published: June 2012

Background
—Atrial natriuretic peptide (ANP) depresses contractility in left ventricular myocytes. Its expression is upregulated in pressure-overloaded hypertrophied hearts; however, the effects of ANP on contractility in hypertrophied myocytes are not known. Our aims were (1) to examine the cellular mechanisms of this depression in contractility in normal myocytes and (2) to test the hypothesis that the effects of ANP on contractility differ in hypertrophied myocytes from rats with ascending aortic stenosis.

Methods and Results
—We measured the myocyte shortening as an index of contractility, [Ca
2+
]
i
with fluo 3, and pH
i
with seminaphthorhodafluor-1 (SNARF-1). In normal control myocytes (n=26), ANP caused a concentration-dependent depression of contractility and reduction in pH
i
. In the presence of 10
−6
mol/L ANP, fractional cell shortening was 78±5% of baseline (
P
<0.05) and pH
i
was reduced by 0.16±0.04 U from baseline (
P
<0.01) without changes in [Ca
2+
]
i
. The magnitude of the depression of contraction caused by ANP was similar to that caused by intracellular acidification induced by an NH
4
Cl pulse. The effects of ANP on contractility and pH
i
were prevented in the presence of 5-(
N
-ethyl-
N
-isopropyl)-amiloride (EIPA), which inhibits the Na
+
/H
+
exchanger. In hypertrophied myocytes (n=23), ANP did not depress either myocyte contractility or pH
i
at concentrations of either 10
−8
, 10
−7
, or 10
−6
mol/L. ANP caused no change in pH
i
or the [Ca
2+
]
i
transient in hypertrophied myocytes. The cGMP level was increased and Na
+
/H
+
exchanger mRNA levels were normal in left ventricles from aortic stenosis rats compared with controls.

Conclusions
—ANP directly depresses contractility in normal myocytes via intracellular acidification, which decreases myofilament [Ca
2+
]
i
sensitivity. In contrast, ANP causes no effects on contractility and pH
i
in hypertrophied myocytes, suggesting a suppression in the coupling of the ANP-cGMP intracellular signaling pathway to the Na
+
/H
+
exchanger.
Modulated Dispersion Explains Changes in Arrhythmia Vulnerability During Premature Stimulation of the Heart
Authors: Laurita Kenneth R. , Girouard Steven D. , Akar Fadi G. , Rosenbaum David S.
Published: June 2012

Background
—Previously, we have shown that a premature stimulus can significantly modulate spatial gradients of ventricular repolarization (ie, modulated dispersion), which result from heterogeneous electrophysiological properties between cells. The role modulated dispersion may play in determining electrical instability in the heart is unknown.

Methods and Results
—To determine if premature stimulus–induced changes in repolarization are a mechanism that governs susceptibility to cardiac arrhythmias, optical action potentials were recorded simultaneously from 128 ventricular sites (1 cm
2
) in 8 Langendorff-perfused guinea pig hearts. After baseline pacing (S
1
), a single premature stimulus (S
2
) was introduced over a range of S
1
S
2
coupling intervals. Arrhythmia vulnerability after each premature stimulus was determined by measurement of a modified ventricular fibrillation threshold (VFT) during the T wave of each S
2
beat (ie, S
2
-VFT). As the S
1
S
2
interval was shortened to an intermediate value, spatial gradients of repolarization and vulnerability to fibrillation decreased by 51±9% (mean±SEM) and 73±45%, respectively, compared with baseline levels. As the S
1
S
2
interval was further shortened, repolarization gradients increased above baseline levels by 54±30%, which was paralleled by a corresponding increase (37±8%) in vulnerability.

Conclusions
—These data demonstrate that modulation of repolarization gradients by a single premature stimulus significantly influences vulnerability to ventricular fibrillation. This may represent a novel mechanism for the formation of arrhythmogenic substrates during premature stimulation of the heart.
Localization of a Gene Responsible for Arrhythmogenic Right Ventricular Dysplasia to Chromosome 3p23
Authors: Ahmad Ferhaan , Li Duanxiang , Karibe Akihiko , Gonzalez Oscar , Tapscott Terry , Hill Rita , Weilbaecher Donald , Blackie Peter , Furey Michael , Gardner Martin , Bachinski Linda L. , Roberts Robert
Published: June 2012

Background
—Arrhythmogenic right ventricular dysplasia (ARVD), a familial cardiomyopathy occurring with a prevalence of 1 in 5000, is characterized by replacement of myocytes with fatty and fibrous tissue. Clinical manifestations include structural and functional abnormalities of the right ventricle and arrhythmias, leading to a sudden death rate of 2.5% per year. Four loci have been mapped, but no gene has been identified as yet.

Methods and Results
—We identified a large family of >200 members with ARVD segregating as an autosomal dominant trait affecting 10 living individuals. The diagnosis of ARVD was based on international diagnostic criteria including history, physical examination, ECG, echocardiogram, right ventricular angiogram, endomyocardial biopsy, and 24-hour ambulatory ECG. Blood was collected for DNA from 149 family members. Analysis of 257 polymorphic microsatellite markers by genetic linkage excluded previously known loci for ARVD and identified a novel locus at 3p23. Analysis of an additional 20 markers further defined the region. A peak logarithm of the odds score of 6.91 was obtained with marker D3S3613 at θ=0% recombination. Haplotype analysis identified a shared region between markers D3S3610 and D3S3659 of 9.3 cM.

Conclusions
—A novel locus for ARVD has been mapped to 3p23 and the region narrowed to 9.3 cM. Identification of the gene will allow genetic screening and a specific diagnosis for a disease with protean nonspecific findings. It should also provide insight fundamental to understanding cardiac chamber–specific gene expression and/or the mechanism of myocyte apoptosis observed in this disease.
Correlation of Factor VIIa Values With Factor VII Gene Polymorphism, Fasting and Postprandial Triglyceride Levels, and Subclinical Carotid Atherosclerosis
Authors: Ghaddar Habib M. , Folsom Aaron R. , Aleksic Nena , Hearne Leonard B. , Chambless Lloyd E. , Morrissey James H. , Wu Kenneth K.
Published: June 2012

Background
—Factor VII plays a pivotal role in coagulation. Factor VIIc levels were reported to be a risk factor for fatal coronary heart disease (CHD). Factor VIIc and VIIag levels were noted to be positively associated with plasma triglyceride (TG) levels and influenced by a VII gene polymorphism. The purpose of this study is to determine whether these associations are related to activated factor VII (factor VIIa).

Methods and Results
—Fasting and 3.5-hour postprandial samples from 216 cases with subclinical atherosclerosis and 341 matched controls selected from the ARIC cohort were assayed for levels of factors VIIa, VIIc, and VIIag and TG, and factor VII codon 353 gene polymorphism. The level of factor VIIa was higher in
Arg/Arg
than in
Arg/Gln+Gln/Gln
genotypes, and the difference was in accord with that of factors VIIag and VIIc. However, the factor VIIa difference was statistically insignificant. Factor VIIa values were not correlated with fasting or 3.5-hour postprandial TG levels, nor were they associated with subclinical atherosclerosis.

Conclusions
—Factor VIIa levels, like factor VIIag and VIIc levels, are influenced by factor VII gene codon 353 polymorphism. However, unlike factor VIIag or VIIc, factor VIIa is not influenced by TG levels; none of these is associated with subclinical atherosclerosis.
Clinical Outcomes of Therapeutic Agents That Block the Platelet Glycoprotein IIb/IIIa Integrin in Ischemic Heart Disease
Authors: Kong David F. , Califf Robert M. , Miller Dave P. , Moliterno David J. , White Harvey D. , Harrington Robert A. , Tcheng James E. , Lincoff A. Michael , Hasselblad Vic , Topol Eric J.
Published: June 2012

Background
—Several platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been evaluated in clinical trials. We conducted a systematic overview (meta-analysis) to assess the effect of these compounds on death, myocardial infarction (MI), and revascularization.

Methods and Results
—ORs were calculated for 16 randomized, controlled trials of GP IIb/IIIa inhibitors. An empirical Bayesian random-effects model combined the outcomes of 32 135 patients. There was a significant mortality reduction by GP IIb/IIIa inhibitors at 48 to 96 hours, with an OR of 0.70 (95% CI, 0.51 to 0.96;
P
<0.03), equivalent to a reduction of 1 death per 1000 patients treated. Mortality benefits at 30 days (OR, 0.87; 95% CI, 0.74 to 1.02;
P
=0.08) and 6 months (OR, 0.97; 95% CI, 0.86 to 1.10;
P
=0.67) were not statistically significant. For the combined end point of death or MI, there was a highly significant (
P
<0.001) benefit for GP IIb/IIIa inhibitors at each time point. The 30-day OR was 0.76 (95% CI, 0.66 to 0.87), or 20 fewer events per 1000 patients treated. For the composite end point of death, MI, or revascularization, there was also a highly significant (
P
<0.001) benefit for GP IIb/IIIa inhibitors. At 30 days, the OR was 0.77 (95% CI, 0.68 to 0.86), or 30 fewer events per 1000 patients treated. The risk differences for death, death or MI, and composite outcomes were similar at 6 months, indicating a sustained absolute improvement. Similar benefit was seen when trials were subgrouped by therapeutic indication (percutaneous intervention versus acute coronary syndromes).

Conclusions
—Application of this new therapeutic class to clinical practice promises substantial benefit for both indications.
Prognostic Value of Treadmill Exercise Testing
Authors: Roger Veronique L. , Jacobsen Steven J. , Pellikka Patricia A. , Miller Todd D. , Bailey Kent R. , Gersh Bernard J.
Published: June 2012

Background
—The prognostic value of treadmill exercise testing (TMET) has been studied in selected populations. The generalizability of these data to different populations and to women is uncertain.

Methods and Results
—A retrospective, population-based cohort study of all persons (1452 men and 741 women) who underwent TMET in years 1987 to 1989 in Olmsted County, Minnesota, was undertaken. Individuals were followed up for all-cause mortality and cardiac events (cardiac deaths, nonfatal myocardial infarction, or congestive heart failure). Sex-specific analyses were performed to determine whether the predictors of outcome and the magnitude of the associations were similar in both sexes. In men, 77 deaths and 106 cardiac events occurred during 8956 person-years of observation; in women, 46 deaths and 54 cardiac events occurred during 4801 person-years of follow-up. Exercise-induced angina, ECG changes, and workload achieved on the TMET were strongly associated with all-cause mortality and cardiac events in both sexes, and the strength of the association was similar. After adjustment, workload was the only TMET variable associated with outcome. A higher workload was associated with a reduction in the risk of cardiac events and of all-cause mortality; the protective effect of exercise capacity was strong and was similar in both sexes.

Conclusions
—In this population-based cohort, exercise capacity was the TMET variable that exhibited the strongest association with all-cause mortality and cardiac events. This protective effect of exercise capacity was observed in both sexes.
Early Impairment of Renal Hemodynamic Reserve in Patients With Asymptomatic Heart Failure Is Restored by Angiotensin II Antagonism
Authors: Magri Paola , Rao Maria A. E. , Cangianiello Sara , Bellizzi Vincenzo , Russo Rosaria , Mele Alessandro F. , Andreucci Michele , Memoli Bruno , Luca De Nicola  , Volpe Massimo
Published: June 2012

Background
—The early/asymptomatic stages of heart failure (HF) are characterized by sodium retention secondary to derangement of sodium reabsorption at the proximal nephron level. Because this phenomenon is reversed by ACE inhibition, abnormalities of renal sodium handling may depend on intrarenal changes of angiotensin II (AII)/nitric oxide (NO) levels. Renal hemodynamic reserve (ie, the glomerular vasodilatory response to amino acid infusion) has been proposed as a reliable test to assess in vivo AII/NO balance.

Methods and Results
—In this study, the effects of 6 weeks of treatment with 5 mg/d of enalapril or with 50 mg/d of losartan on systemic hemodynamics and renal function were assessed, at baseline and after amino acid infusion (AA), in patients with mild HF (NYHA class I) and in healthy volunteers. Untreated HF patients showed a basal renal function comparable to that of healthy subjects. After AA, glomerular filtration rate and renal plasma flow significantly increased in healthy subjects (+29.0% and +30.4%, respectively), whereas no vasodilatory response was observed in HF. Although they did not affect basal renal hemodynamics, both enalapril and losartan restored a normal response to AA in HF patients. Blood pressure and heart rate were comparable in HF subjects and healthy subjects at baseline and were not modified by either treatment. Left ventricular ejection fraction was depressed in HF but did not change after either drug. Urinary excretions of cGMP and nitrate (indexes of NO activity in the kidney), comparable in healthy subjects and in HF patients, were unchanged by either enalapril or losartan and did not correlate with renal reserve.

Conclusions
—(1) Renal functional reserve is absent in patients with early/asymptomatic HF and normal renal function and (2) both enalapril and losartan restore a normal vasodilatory response to AA in these patients without affecting basal systemic and renal hemodynamics. These data suggest a major role of AII in the development of early abnormalities in patients with HF.
Electrophysiological Characteristics of the Human Atria After Cardioversion of Persistent Atrial Fibrillation
Authors: Pandozi Claudio , Bianconi Leopoldo , Villani Mauro , Gentilucci Giuseppe , Castro Antonio , Altamura Giuliano , Jesi Anna P. , Lamberti Filippo , Ammirati Fabrizio , Santini Massimo
Published: June 2012

Background
—In animal models, induced atrial fibrillation shortens the atrial effective refractory period (ERP) and reverses its physiological adaptation to rate. It is not clear whether this process, known as “electrical remodeling,” occurs in humans.

Methods and Results
—We determined the ERPs, at 5 pacing cycle lengths (300 to 700 ms) and in 5 right atrial sites, after internal cardioversion of chronic atrial fibrillation in 25 patients (14 in pharmacological washout and 11 on amiodarone). The ERPs were 195.5±18.8 ms in the washout and 206.3±17.9 ms in the amiodarone patients (
P
<0.0001). ERPs were closely correlated with the stimulation rates (
r
=0.95 in the washout and
r
=0.94 in the amiodarone group), and slope values indicating a normal (≥0.07) or nearly normal (0.05 to 0.06) adaptation of ERP to rate were found in 77% of the 84 paced sites. The mean ERP was shorter in the lateral wall (198.1±17.9 ms) than in the atrial roof (203.3±21.5 ms) and in the septum (210.5±20.0 ms) (
P
<0.03). After 4 weeks of sinus rhythm, the mean ERP, determined again in 8 patients (4 in wash-out and 4 on amiodarone), was significantly increased compared with the basal study (221.4±21.4 versus 197.8±18.3 ms,
P
<0.0001).

Conclusions
—After cardioversion of chronic atrial fibrillation, (1) atrial ERP adaptation to rate was normal or nearly normal in the majority of the cases, (2) a significant dispersion of refractoriness between different right atrial sites was present, and (3) ERPs were significantly increased after 4 weeks of sinus rhythm in both washout and amiodarone patients.
Preserved Vasodilator Effect of Bradykinin in Dogs With Heart Failure
Authors: Su Jin Bo , Barbe Fabrice , Houel Rémi , Guyene Thanh Tam , Crozatier Bertrand , Hittinger Luc
Published: June 2012

Background
—In heart failure (HF), vasoconstrictor systems are activated and endothelium-derived vasodilation is blunted. Bradykinin, a potent vasodilator, may play an important role in this setting. However, it is not known whether its vasodilator effect is modified in HF.

Methods and Results
—Fourteen chronically instrumented dogs were studied in the control state and in pacing-induced HF (250 bpm for 3 weeks). The dose-dependent decrease in mean aortic pressure (MAP) induced by acetylcholine was significantly blunted in HF. In contrast, in both control and HF, bradykinin infusion caused similar dose-dependent decreases in MAP and increases in cardiac output (CO). This vasodilator effect of exogenous bradykinin was potentiated similarly in both states by enalaprilat, which blocks both angiotensin conversion and bradykinin degradation. For evaluating the role of endogenous bradykinin, the effects of enalaprilat were compared with those of ciprokiren, a pure renin inhibitor. In control, ciprokiren did not produce any effect. Enalaprilat, however, produced a significant decrease in MAP and a significant increase in CO, which were attributed to the inhibition of bradykinin degradation, because these effects were absent after pretreatment with Hoe 140 (a bradykinin B
2
receptor antagonist). In contrast, in HF, vasodilator effects of ciprokiren were observed, but enalaprilat produced larger changes in MAP and CO, and after Hoe 140, the hemodynamic effects of enalaprilat were significantly decreased, showing the effects of endogenous bradykinin, which were similar to those measured in control.

Conclusions
—In this model of HF with a blunted endothelium-derived vasodilation, the vasodilator effects of exogenous and endogenous bradykinin are preserved. These results suggest that bradykinin may play an important role in HF, in which vasoconstriction is present and endothelium-dependent vasodilation is blunted.
Mechanoenergetic Alterations During the Transition From Cardiac Hypertrophy to Failure in Dahl Salt-Sensitive Rats
Authors: Kameyama Tomoki , Chen Zengyi , Bell Stephen P. , VanBuren Peter , Maughan David , LeWinter Martin M.
Published: June 2012

Background
—The time course and mechanisms of altered mechanoenergetics and depressed cross-bridge cycling in hypertrophied and failing myocardium are uncertain.

Methods and Results
—We studied mechanoenergetics in Dahl salt-sensitive (DS) rats fed high-salt diet (HS) for 6 (HS-6) and 12 (HS-12) weeks to produce compensated hypertrophy and failure. The slope of the end-systolic pressure-volume relation (E′
max
) was similar in HS-6 and low-salt controls (LS-6), but reduced in HS-12 compared with controls (LS-12). Efficiency [1/slope of oxygen consumption (V̇
o

2

)–pressure-volume area (PVA) relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (59±16% versus 44±7%,
P
<0.05). Economy [1/slope of the force-time integral (FTI)–V̇
o
2
relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (218±123 versus 74±39×10
3
g · s · mL O
2
−1
· g;
P
<0.05). Compared with controls, myofibrillar ATPase activity was reduced by 24% in HS-6 and 44% in HS-12. V3 Isomyosin was increased in HS-6 (40±12% versus 9±8%;
P
<0.05) and further increased in HS-12 (76±10% versus 22±18%;
P
<0.05). Hypothyroid LS-12 rats had 100% V3 isomyosin, yet efficiency, economy, and ATPase values were intermediate between LS-12 and HS-12. HS-12 rats demonstrated increased troponin T
3
isoform (17±2 versus 23±2%,
P
<0.05). There were no changes in troponin I or tropomyosin isoforms. However, the proportion of phosphorylated troponin T was reduced in HS-12 versus LS-12 hearts (
P
<.001).

Conclusions
—In DS rats, the transition to failure is associated with depressed E′
max
and increased efficiency and economy. These findings are linked to myofibrillar ATPase activity and suggest that mechanisms other than isomyosin switching are important determinants of ventricular energetics. A troponin T isoform switch is one potential mechanism.
Prevention of Aneurysm Development and Rupture by Local Overexpression of Plasminogen Activator Inhibitor-1
Authors: Allaire Eric , Hasenstab David , Kenagy Richard D. , Starcher Barry , Clowes Monika M. , Clowes Alexander W.
Published: June 2012

Background
—Arterial aneurysms exhibit a loss of elastin and an increase in the plasminogen activators urokinase plasminogen activator (u-PA) and tissue plasminogen activator (t-PA). Because u-PA, t-PA, and plasmin have a limited proteolytic activity against elastin, the role of plasminogen activators in the aneurysmal disease is unclear. To investigate this question, we overexpressed plasminogen activator inhibitor-1 (PAI-1), an inhibitor of t-PA and u-PA, in a rat model of aortic aneurysm.

Methods and Results
—Guinea pig–to-rat aortic xenografts were seeded with syngeneic Fischer 344 rat smooth muscle cells retrovirally transduced with the rat PAI-1 gene (LPSN group) or the vector alone (LXSN group). Some grafts were not seeded with cells (NO group). Western blots showed increased PAI-1 in grafts from the LPSN group compared with LXSN and NO groups. All grafts in the NO group (n=8) and 40% in the LXSN group ruptured between days 4 and 14. At 4 weeks in the LXSN group, the remaining unruptured grafts (n=6) were aneurysmal (diameter increase ≥100%), whereas in the LPSN group (n=6) none of the grafts had ruptured or were aneurysmal. Elastin was preserved in the LPSN group. t-PA, the major PA expressed in the model, was decreased in the LPSN group compared with the other groups, as determined by zymography. Quantitative zymography showed decreased levels of two matrix metalloproteinases (MMPs), a 28-kD caseinase, and activated MMP-9 in the LPSN group.

Conclusions
—The blockade of plasminogen activators prevents formation of aneurysms and arterial rupture by inhibiting MMP activation.
Atrial Fibrillation After Radiofrequency Ablation of Type I Atrial Flutter
Authors: Paydak Hakan , Kall John G. , Burke Martin C. , Rubenstein Donald , Kopp Douglas E. , Verdino Ralph J. , Wilber David J.
Published: June 2012

Background
—The occurrence of atrial fibrillation after ablation of type I atrial flutter remains an important clinical problem. To gain further insight into the pathogenesis and significance of postablation atrial fibrillation, we examined the time to onset, determinants, and clinical course of atrial fibrillation after ablation of type I flutter in a large patient cohort.

Methods and Results
—Of 110 consecutive patients with ablation of type I atrial flutter, atrial fibrillation was documented in 28 (25%) during a mean follow-up of 20.1±9.2 months (cumulative probability of 12% at 1 month, 23% at 1 year, and 30% at 2 years). Among 17 clinical and procedural variables, only a history of spontaneous atrial fibrillation (relative risk 3.9, 95% confidence intervals 1.8 to 8.8,
P
=0.001) and left ventricular ejection fraction <50% (relative risk 3.8, 95% confidence intervals 1.7 to 8.5,
P
=0.001) were significant and independent predictors of subsequent atrial fibrillation. The presence of both these characteristics identified a high-risk group with a 74% occurrence of atrial fibrillation. Patients with only 1 of these characteristics were at intermediate risk (20%), and those with neither characteristic were at lowest risk (10%). The determinants and clinical course of atrial fibrillation did not differ between an early (≤1 month) compared with a later onset. Atrial fibrillation was persistent and recurrent, requiring long-term therapy in 18 patients, including 12 of 19 (63%) with prior atrial fibrillation and left ventricular dysfunction.

Conclusions
—Atrial fibrillation after type I flutter ablation is primarily determined by the presence of a preexisting structural and electrophysiological substrate. These data should be considered in planning postablation management. The persistent risk of atrial fibrillation in this population also suggests a potentially important role for atrial fibrillation as a trigger rather than a consequence of type I atrial flutter.
Mechanics of the Single Left Ventricle
Authors: Fogel Mark A. , Weinberg Paul M. , Gupta Krishanu B. , Rychik Jack , Hubbard Anne , Hoffman Eric A. , Haselgrove John
Published: June 2012

Background
—Left ventricular (LV) effects on right ventricular (RV) function are well known. Less is understood about the effect of the RV on systemic LV mechanics. To determine this interaction, we compared systemic LVs with and without an RV mechanically coupled to them.

Methods and Results
—MR myocardial tagging was used to examine 18 subjects with systemic LVs: 10 with functional single LVs (SLV) and 8 normal subjects (NL). Tracking the systolic motion of the intersecting stripes were used to determine regional twist and radial motion. Finite strain analysis was applied to derive principal strains at the atrioventricular valve (AVV) and apical short-axis levels and in 4 anatomic wall regions. Similar
E
1
(circumferential shortening) strain and heterogeneity of strain were noted between SLV and NL except in the septal wall. At the septal wall, NL displayed greater absolute strain (AVV=−0.16±0.02, apex=−0.17±0.02) and less heterogeneity of strain than SLV (AVV=−0.12±0.02, apex=−0.13±0.02). Similar
E
2
(wall thickening) strain and heterogeneity of strain were also noted between SLV and NL except again at the septal wall. At the septal wall, SLV displayed greater absolute
E
2
strain (AVV=0.17±0.08, apex=0.19±0.09) and less heterogeneity of strain than NL (AVV=0.07±0.07, apex=0.05±0.05). SLV twisted significantly less counterclockwise than NL in 6 of 8 wall regions and actually twisted clockwise at the AVV lateral wall. Although there was no significant difference between groups in radial wall motion, the septal and inferior walls of SLV demonstrated significantly less radial motion compared with other SLV walls.

Conclusions
—A major influence of the RV on systemic LV strain and radial motion occurs in the septal wall, whereas absence of the RV causes marked differences in LV twist. These findings may yield clues to the long-term functioning of the SLV and be useful in determining strategies for RV augmentation of LV function.
Activation of gp130 Transduces Hypertrophic Signals via STAT3 in Cardiac Myocytes
Authors: Kunisada Keita , Tone Eiroh , Fujio Yasushi , Matsui Hideo , Yamauchi-Takihara Keiko , Kishimoto Tadamitsu
Published: June 2012

Background
—gp130, a signal transducer of the IL-6–related cytokines, is expressed ubiquitously, including in the heart. The activation of gp130 in cardiac myocytes was reported to induce myocardial hypertrophy. The downstream side of gp130 consists of two distinct pathways in cardiac myocytes, one a Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, the other a mitogen-activated protein kinase (MAPK) pathway. In the present study, we examined whether the JAK/STAT pathway, especially the STAT3-mediated pathway, plays a critical role in gp130-dependent myocardial hypertrophy by transfecting wild-type and mutated-type STAT3 cDNA to cardiac myocytes.

Methods and Results
—We constructed three kinds of replication-defective adenovirus vectors carrying wild-type (AD/WT) or mutated-type (AD/DN) STAT3 cDNA or adenovirus vector itself (AD). Cultured murine cardiac myocytes infected with adenovirus were stimulated with leukemia inhibitory factor (LIF), and the expression of c-
fos
and atrial natriuretic factor (
ANF
) mRNAs and [
3
H]leucine incorporation were examined. There were no significant differences in MAPK activity among the three groups. Compared with AD-transfected cardiac myocytes, induction of c-
fos
and
ANF
mRNAs and protein synthesis after LIF stimulation were significantly augmented in AD/WT-transfected cells. In contrast, induction of c-
fos
and
ANF
mRNA expression and protein synthesis were attenuated after LIF stimulation in cardiac myocytes transfected with AD/DN.

Conclusions
—These results suggest that the STAT3-dependent signaling pathway downstream of gp130 promotes cardiac myocyte hypertrophy under stimulation with LIF.
Induction by Lysophosphatidylcholine, a Major Phospholipid Component of Atherogenic Lipoproteins, of Human Coronary Artery Smooth Muscle Cell Migration
Authors: Kohno Masakazu , Yokokawa Koji , Yasunari Kenichi , Minami Mieko , Kano Hiroaki , Hanehira Takao , Yoshikawa Junichi
Published: June 2012

Background
—The objectives of the present study were (1) to determine whether lysophosphatidylcholine (lyso-PC), a prominent component of oxidatively modified LDL, induces migration of human coronary artery smooth muscle cells (SMCs) and, if so, to clarify the mechanism, and (2) to investigate the possible interactions of lyso-PC and platelet-derived growth factor (PDGF)-BB, endothelin-1 (ET-1), adrenomedullin (AM), or vitamin E on SMC migration by the Boyden’s chamber method.

Methods and Results
—Lyso-PC induced SMC migration in a concentration-dependent manner between 10
−6
and 5×10
−5
mol/L. By contrast, phosphatidylcholine was without significant activity, and lysophosphatidylinositol and lysophosphatidylserine were much less effective than lyso-PC. Lyso-PC increased basic fibroblast growth factor (bFGF) production in a concentration-dependent manner between 10
−6
and 5×10
−5
mol/L in these cells. Furthermore, lyso-PC–induced SMC migration was inhibited by neutralizing antibody to bFGF but not by neutralizing antibody to transforming growth factor-β
1
. Lyso-PC–induced migration was significantly enhanced by PDGF-BB or ET-1 but was clearly inhibited by human AM and vitamin E.

Conclusions
—These results indicate that (1) lyso-PC induces human coronary artery SMC migration at least in part through release of endogenous bFGF and (2) this lyso-PC–induced migration can be further induced by PDGF-BB and ET-1 and can be inhibited by human AM and vitamin E. Lyso-PC may recruit medial SMCs during the process of coronary atherosclerosis in part by releasing bFGF in concert with PDGF-BB or ET-1 in vascular tissues. This lyso-PC–induced SMC migration may be suppressed by AM and vitamin E under certain pathological conditions.
Prospective Study of a Self-Report Type A Scale and Risk of Coronary Heart Disease
Authors: Kawachi Ichiro , Sparrow David , Kubzansky Laura D. , Spiro Avron , Vokonas Pantel S. , Weiss Scott T.
Published: June 2012

Background
—Several methods exist by which to assess type A behavior (TAB). Although the videotaped clinical interview is regarded as the “gold standard,” self-report measures have also proved useful in assessing TAB in large population studies. The purpose of this study was to examine prospectively the relationship of TAB to risk of coronary heart disease (CHD) incidence with the use of the revised Minnesota Multiphasic Personality Inventory (MMPI-2) Type A Scale. To the best of our knowledge, this is the first test of this scale in the context of predicting CHD incidence.

Methods and Results
—The study was performed in the VA Normative Aging Study, an ongoing cohort of older (mean age, 61 years) community-dwelling men. A total of 1305 men who were free of diagnosed CHD in 1986 completed the MMPI-2 Type A Scale. During an average 7.0 years of follow-up, 110 cases of incident CHD occurred. Compared with men in the lowest quartile of type A scores, men in the highest quartile had multivariate adjusted relative risks of 2.86 (95% CI, 1.19 to 6.89;
P
for trend=0.016) for combined CHD death and nonfatal myocardial infarction (MI) and 2.30 (95% CI, 1.32 to 4.01;
P
for trend=0.001) for combined CHD death/nonfatal MI plus angina pectoris. The relationship of TAB to CHD was independent of measures of anger and cynicism.

Conclusions
—The MMPI-2 Type A Scale predicts CHD incidence. Further research is warranted to examine the correlation, if any, between this scale and the videotaped clinical interview.
Which Arterial and Cardiac Parameters Best Predict Left Ventricular Mass?
Authors: Chen Chen-Huan , Ting Chih-Tai , Lin Shing-Jong , Hsu Tsui-Lieh , Ho Shuenn-Jiin , Chou Pesus , Chang Mau-Song , O’Connor Frances , Spurgeon Harold , Lakatta Edward , Yin Frank C. P.
Published: June 2012

Background
—Many cardiovascular and noncardiovascular parameters are thought to be determinants of left ventricular mass (LVM). Complicated interactions necessitate the simultaneous measurement and consideration of each to determine their individual and collective impact on LVM. We undertook such a comprehensive study.

Methods and Results
—The influence of anthropometry, cardiac size and contractility, arterial structure and function, as well as indices of lifestyle, physical activity, and dietary salt intake on LVM (by two-dimensionally guided M-mode echocardiography) was analyzed in 1315 Chinese subjects who were either normotensive or had untreated hypertension. Effects of many cardiac and arterial factors were assessed. In univariate analysis, almost all measured noncardiovascular, cardiac, and arterial variables were significantly correlated with LVM. In multivariate linear regression analyses, when age, sex, body habitus, fasting serum C-peptide level, dietary salt, physical activity, and lifestyle were accounted for, the optimum multivariate linear regression main effects model had an adjusted model
r

2

of 0.740, with 98% of the model variance accounted for by the 5 independent determinants of LVM: stroke volume (49.6%), systolic blood pressure (30.7%), contractility (14.7%), body mass index (1.8%), and aortic root diameter (1.6%). Other proposed arterial indices were significant independent determinants of LVM only when blood pressure was removed from the model and, even then, these indices not only resulted in less powerful prediction but also accounted for only a very small percentage of the total variance of LVM.

Conclusions
—In a large population, we (1) confirmed that age, body habitus, and some indexes of arterial structure and function are independent determinants of LVM; (2) found aortic diameter to be an independent structural determinant of LVM; (3) demonstrated that the effects of the derived measures of arterial function were small and provided no better predictive power than blood pressure alone; and (4) showed that when the best measures of cardiac and vascular load were included, the single most potent predictor was an index of left ventricular size.
RR Interval Dynamics Before Atrial Fibrillation in Patients After Coronary Artery Bypass Graft Surgery
Authors: Hogue Charles W. , Domitrovich Peter P. , Stein Phyllis K. , Despotis George D. , Re Lisa , Schuessler Richard B. , Kleiger Robert E. , Rottman Jeffery N.
Published: June 2012

Background
—Atrial fibrillation/flutter (AF) is a frequent complication of coronary artery bypass graft surgery (CABG) that leads to increased costs and morbidity. We hypothesized that heart rate variability (HRV), an indicator of cardiac sympathovagal balance, is altered before the onset of postoperative AF. Because nonlinear methods of HRV analysis provide information about heart rate dynamics not evident from usual HRV measures, we also hypothesized that approximate entropy (ApEn), a nonlinear measure of HRV, might have predictive value.

Methods and Results
—Analysis of HRV was performed in 3 sequential 20-minute intervals preceding the onset of postoperative AF (24 episodes in 18 patients). These data were compared with corresponding intervals in 18 sex- and age-matched postoperative control subjects who did not develop AF. Patients had left ventricular ejection fractions >45% before surgery and were not receiving β-blockers during ambulatory ECG monitoring after surgery. Logistic regression demonstrated that on the basis of averaged values for the three 20-minute intervals, increased heart rate and decreased ApEn were independently associated with AF. Heart rate dynamics before AF was associated with either lower (n=19) or higher (n=5) RR interval variation by traditional measures of HRV or quantitative Poincaré analysis, suggesting the possibility of divergent autonomic conditions before AF onset.

Conclusions
—In the hour before AF after CABG surgery, higher heart rate and lower heart rate complexity compared with values in control patients were independent predictors of AF. Decreased ApEn occurs in patients with either increased or decreased HRV by traditional measures and may provide a useful tool for risk stratification or investigation of mechanisms.
Role of Echocardiography in Patients Undergoing Elective Cardioversion of Atrial Fibrillation
Authors: Silverman David I. , Manning Warren J.
Published: June 2012

Abstract
—Echocardiography has emerged as a fundamental tool in the evaluation of patients with atrial fibrillation (AF). Transthoracic echocardiography remains a primary tool for the evaluation and management of many patients presenting with their first episode of AF, but it is not adequate for exclusion of atrial thrombi. TEE offers excellent visualization of the atria and accurate identification or exclusion of thrombi. In concert with therapeutic anticoagulation, a TEE-guided approach to early cardioversion appears to have a safety profile similar to that of conventional therapy (1 month of precardioversion warfarin). The TEE-guided approach offers the advantages of simplified anticoagulation management and shorter duration of sustained AF, thereby allowing for a more rapid recovery of atrial mechanical function. Warfarin should be continued for 1 month after cardioversion to allow for more complete recovery of atrial function and for prophylaxis should the patient revert to AF. Cost-effectiveness models demonstrate that TEE-guided cardioversion represents a cost-effective strategy, but only if the transthoracic echocardiogram is omitted. For patients with a thrombus on the initial TEE, follow-up TEE (to document thrombus resolution) is recommended before cardioversion.
Stress-Induced Reversible and Mild-to-Moderate Irreversible Thallium Defects
Authors: Kitsiou Anastasia N. , Srinivasan Gopal , Quyyumi Arshed A. , Summers Ronald M. , Bacharach Stephen L. , Dilsizian Vasken
Published: June 2012

Background
—In patients with coronary artery disease, stress-redistribution-reinjection thallium scintigraphy provides important information regarding myocardial ischemia and viability. Although both reversible and mild-to-moderate irreversible thallium defects retain metabolically active, viable myocardium, we hypothesized that stress-induced reversible thallium defects may better differentiate reversible from irreversible regional left ventricular dysfunction after revascularization.

Methods and Results
—Twenty-four patients with chronic coronary artery disease underwent prerevascularization and postrevascularization exercise-redistribution-reinjection thallium single photon emission CT, gated MRI, and radionuclide angiography. After revascularization, mean left ventricular ejection fraction increased from 30±9% to 37±13% at rest (
P
<0.001). Before revascularization, abnormal contraction at rest was observed in 56 of 110 reversible and 20 of 37 mild-to-moderate irreversible thallium defects (51% and 54%, respectively). After revascularization, regional contraction improved in 44 of 56 reversible compared with 6 of 20 mild-to-moderate irreversible thallium defects (79% and 30%, respectively;
P
<0.001). The final thallium content (maximum tracer uptake on redistribution-reinjection images) was significantly higher in regions with reversible defects that improved than in those that did not improve after revascularization (86±16% versus 66±9%,
P
<0.001). In contrast, final thallium content was similar in regions with mild-to-moderate irreversible defects that improved and in those that did not improve after revascularization (69±9% versus 65±10%,
P
=NS). Furthermore, when asynergic regions were grouped according to the final thallium content, at 60% threshold value, functional recovery was observed in 83% of regions with reversible defects compared with 33% of regions with mild-to-moderate irreversible defects (
P
<0.001).

Conclusions
—These findings suggest that although both reversible and mild-to-moderate irreversible thallium defects after stress retain viable myocardium, the identification of reversible thallium defect on stress in an asynergic region more accurately predicts recovery of function after revascularization. Even at a similar mass of viable myocardial tissue (as reflected by the final thallium content), the presence of inducible ischemia is associated with an increased likelihood of functional recovery.
Mechanisms of Sustained Ventricular Tachycardia in Myotonic Dystrophy
Authors: Merino Jose L. , Carmona Jose R. , Fernández-Lozano Ignacio , Peinado Rafael , Basterra Nuria , Sobrino Jose A.
Published: June 2012

Background
—Ventricular arrhythmias have been documented and linked to the high incidence of sudden death seen in patients with myotonic dystrophy. However, their precise mechanism is unknown, and their definitive therapy remains to be established.

Methods and Results
—We studied 6 consecutive patients with myotonic dystrophy and sustained ventricular tachycardia by means of cardiac electrophysiological testing. Particular attention was paid to establish whether bundle-branch reentry was the tachycardia mechanism, and when such was the case, radiofrequency catheter ablation of either the right or left bundle branch was performed. Clinical tachycardia was inducible in all patients and had a bundle-branch reentrant mechanism. In 1 patient, 2 other morphologies of sustained tachycardia were also inducible, neither of which had ever been clinically documented, and both had a bundle-branch reentrant mechanism. Ventricular tachycardia was no longer inducible after bundle-branch ablation, except for a nonclinically documented and nonsustained ventricular tachycardia in the only patient who had apparent structural heart disease.

Conclusions
—A high clinical suspicion of bundle-branch reentrant tachycardia is justified in patients with myotonic dystrophy who exhibit wide QRS complex tachycardia or tachycardia-related symptoms. Because catheter ablation will easily and effectively abolish bundle-branch reentrant tachycardia, myotonic dystrophy should always be considered in patients with sustained ventricular tachycardia. This is especially true if no apparent heart disease is found.