bluuebunny/crossref_metadata_2025 huggingface dataset:
Losartan in Heart Failure
Authors: Crozier Ian , Ikram Hamid , Awan Najam , Cleland John , Stephen Nigel , Dickstein Kenneth , Frey Martin , Young James , Klinger George , Makris Lukas , Rucinska Ewa
Published: June 2012

Background
The aim of the present study was to assess the short- and long-term effects of multiple doses of the angiotensin II receptor antagonist losartan in heart failure.

Methods and Results
A multicenter, placebo-controlled, oral, multidose (2.5, 10, 25, and 50 mg losartan once daily) double-blind comparison in patients with symptomatic heart failure and impaired left ventricular function (ejection fraction <40%). Invasive 24-hour hemodynamic assessment was performed after the first dose and after 12 weeks of treatment. Clinical status and tolerability of treatment with losartan over the 12-week period were also evaluated. One hundred fifty-four patients were enrolled, of which 134 met the protocol criterion of baseline pulmonary capillary wedge pressure ≥13 mm Hg. During short-term administration, systemic vascular resistance (SVR) (largest reduction against placebo of 197 dyne · s
−1
· cm
−5
at 4 hours) and blood pressure fell significantly with 50 mg, lesser decreases were seen with 25 mg, and no discernible effects were seen with 2.5 and 10 mg. After 12 weeks of treatment, similar effects were seen on SVR and blood pressure (maximal fall in SVR against placebo, 318 dyne · s
−1
· cm
−5
at 5 hours with 50 mg). In addition, pulmonary capillary wedge pressure fell with 2.5, 25, and 50 mg (largest reduction against placebo of 6.3 mm Hg at 6 hours with 50 mg), cardiac index rose with 25 and 50 mg, and heart rate was lower with all active treatment groups. Active treatment was well tolerated, and excess cough was not reported.

Conclusions
This study showed that oral losartan administered to patients with symptomatic heart failure resulted in beneficial hemodynamic effects with short-term administration, with additional beneficial hemodynamic effects seen after 12 weeks of therapy. Clear effects were seen with both 25 and 50 mg, with the greatest effect seen with 50 mg.
Fractal Clustering of Ventricular Ectopy Correlates With Sympathetic Tone Preceding Ectopic Beats
Authors: Stein Kenneth M. , Karagounis Labros A. , Anderson Jeffrey L. , Kligfield Paul , Lerman Bruce B.
Published: June 2012

Background
Fractal geometric analysis of ventricular ectopy yields a fractal dimension, which can range from zero to one and is inversely related to clustering of ventricular premature contractions (VPCs). Low values of this fractal dimension, which reflect significantly nonuniform distributions of ventricular ectopy, are found in patients with life-threatening ventricular arrhythmias and predict adverse outcomes in selected patients with congestive heart failure and with mitral regurgitation. However, the physiological mechanism and correlates of the fractal dimension are unknown.

Methods and Results
To explore the physiological correlates of clustered ventricular ectopy, we studied 30 patients with a history of sustained ventricular tachycardia or ventricular fibrillation who had inducible sustained monomorphic ventricular tachycardia during electrophysiological study and also underwent drug-free 24-hour ambulatory ECG. In addition to fractal dimension (determined by use of our previously described algorithm), we measured the mean RR interval (±SD) for all sinus beats preceding a sinus beat and for all sinus beats preceding a single VPC and the mean root-mean-square difference (RMSSD) of all windows of 15 successive RR intervals (excluding ectopic beats) preceding a sinus beat and preceding a single VPC. Based on the directional changes of mean RR (a measure of both sympathetic and parasympathetic tone) and of RMSSD (a measure of parasympathetic tone), each patient’s inferred relative sympathetic tone preceding ventricular ectopy was classified as increased, unchanged, or decreased. If these values changed concordantly, relative sympathetic tone was indeterminate. Fractal dimension did not correlate with the mean RR interval, SD of the RR interval, or RMSSD preceding sinus beats or preceding VPCs (all
P
>.10). In 20 patients, fractal dimension was significantly lower among those with increased relative sympathetic tone (n=14) than those with unchanged or decreased sympathetic tone (n=6,
P
=.008). Ten patients had indeterminate relative sympathetic tone.

Conclusions
Clustering of ventricular ectopy, as measured by the fractal dimension, is observed in patients at increased risk of sudden cardiac death. A low fractal dimension (clustered ventricular ectopy) is related to changes in heart rate and heart rate variability that are consistent with transient increases in cardiac sympathetic tone.
Determinants of Echocardiographic Aortic Root Size
Authors: Vasan Ramachandran S. , Larson Martin G. , Levy Daniel
Published: June 2012

Background
Previous studies that evaluated the determinants of aortic root size have not yielded uniform results. We examined the relations of age, height, weight, body surface area, sex, and blood pressure to echocardiographically determined aortic root size in a population-based cohort.

Methods and Results
The study sample consisted of 1849 men and 2152 women in the Framingham Heart Study and Framingham Offspring Study who were free of clinically apparent cardiac disease when echocardiography was performed. Aortic root measurements were made by M-mode echocardiography using a leading-edge-to-leading-edge technique. The relations of age, height, weight, body surface area, and blood pressure variables (contemporary and those obtained 8 years before) to aortic root dimension were examined by use of sex-specific correlations and linear regression analyses. Age, height, weight, and sex emerged as the principal determinants of aortic root dimensions in adults (cumulative
R
2
=.2085 in men and .2327 in women). The additional effect of contemporary or previous blood pressure measures was small and revealed direct associations of aortic root dimension with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures. Previous blood pressure measurements did not contribute significantly to prediction of aortic root size once contemporary blood pressure variables entered the models. Results of regression analyses using a sex-pooled data set showed that on average, the aortic root measurement in women was 2.4 mm smaller than that of men of comparable age, height, and weight. Logistic regression was used to assess the likelihood of aortic root enlargement according to blood pressure levels. After adjustment for age, height, and weight, the odds ratio of aortic dilation for a 1-SD increment in systolic pressure was 0.70 (95% CI, 0.52 to 0.95) in men and 0.79 (95% CI, 0.60 to 1.04) in women; the odds ratio for a 1-SD increment in diastolic pressure was 1.22 (95% CI, 0.91 to 1.63) in men and 1.33 (95% CI, 1.01 to 1.73) in women.

Conclusions
Age, height, weight, and sex emerged as the principal determinants of aortic root dimensions. The additional influences of blood pressure measurements were small; direct associations of aortic root dimensions with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures were observed. Additional prospective studies are needed to confirm these observations and to assess the impact of aortic root dimensions on the incidence of hypertension.
Proximal Jet Size by Doppler Color Flow Mapping Predicts Severityof Mitral Regurgitation
Authors: Mele Donato , Vandervoort Pieter , Palacios Igor , Rivera J. Miguel , Dinsmore Robert E. , Schwammenthal Ehud , Marshall Jane E. , Weyman Arthur E. , Levine Robert A.
Published: June 2012

Background
Recent studies have shown that many instrument and physiological factors limit the ability of color Doppler total jet area within the receiving chamber to predict the severity of valvular regurgitation. In contrast, the proximal or initial dimensions of the jet as it emerges from the orifice have been shown to increase directly with orifice size and to correlate well with the severity of aortic insufficiency. Only limited data, however, are available regarding the value of proximal jet size in mitral regurgitation, and it has not been examined in short-axis or transthoracic views. The purpose of the present study, therefore, was to evaluate the relation between proximal jet size and other measures of the severity of mitral regurgitation.

Methods and Results
In 49 patients, the anteroposterior height of the proximal jet as it emerges from the mitral valve was measured in the parasternal long-axis view; proximal jet width and area were measured in the short-axis view at the same level. Results were compared with regurgitant volume and fraction by pulsed Doppler subtraction of aortic and mitral flows in 47 patients without more than trace aortic insufficiency; with angiographic grade determined within 24 hours in 33 catheterized patients; and with angiographic regurgitant fraction in 13 patients who were in normal sinus rhythm and had no significant aortic and tricuspid insufficiency. Proximal jet height, width, and area correlated well with Doppler regurgitant volume and fraction (
r
=.86 to .95; SEE=7.7 to 9.0 mL; 5.9% to 7.3%). Proximal jet size could also be used to distinguish angiographic grades of mitral regurgitation with minimal overlap (
P
<.0001) and correlated well with angiographic regurgitant fraction (
r
=.85 to .91; SEE=4.1% to 5.1%).

Conclusions
Proximal jet size correlates well with established measures of the severity of mitral regurgitation. It is conveniently available with transthoracic clinical scanning and should be useful in the routine evaluation of patients with mitral regurgitation.
Hyperinsulinemic Microalbuminuria
Authors: Kuusisto Johanna , Mykkänen Leena , Pyörälä Kalevi , Laakso Markku
Published: June 2012

Background
Both hyperinsulinemia and microalbuminuria have been shown to increase coronary heart disease (CHD) risk, but the interaction among hyperinsulinemia, microalbuminuria, and the risk for CHD has not been investigated in previous studies.

Methods and Results
The risk of CHD in relation to hyperinsulinemia and microalbuminuria was examined in a cohort of 1069 elderly nondiabetic subjects from Kuopio, east Finland, during 3.5 years of follow-up. The overall incidence of CHD death was 2.8%, and 6.9% of study subjects died of CHD or had a nonfatal myocardial infarction (later referred to as all CHD events). In the highest fasting-insulin quintile (fasting insulin ≥114.0 pmol/L), there was a slightly but insignificantly higher incidence rate of both CHD mortality and all CHD events compared with lower quintiles. The incidence rates of CHD mortality and all CHD events were significantly higher in the highest urinary albumin/creatinine ratio (ACR) quintile (ACR ≥3.22 mg/mmol) compared with lower quintiles (
P
<.05 and
P
<.01, respectively). Hyperinsulinemic microalbuminuria (simultaneous presence of fasting insulin ≥114.0 pmol/L and ACR ≥3.22 mg/mmol) markedly increased the risk of CHD mortality (12.5%,
P
<.001) and all CHD events (18.8%,
P
<.001) compared with normoinsulinemic subjects without microalbuminuria (2.2% and 5.8%, respectively). In univariate logistic regression analyses, hyperinsulinemic microalbuminuria was a strong predictor of both CHD death (odds ratio [OR], 5.93;
P
<.001) and all CHD events (OR, 3.39;
P
=.002). Multivariate logistic regression analyses were also performed, including sex, current smoking, waist-hip ratio, systolic blood pressure, and HDL cholesterol, with insulin, ACR, or both as independent variables. Even after adjustment for these variables, hyperinsulinemic microalbuminuria remained a strong predictor of CHD death (OR, 7.91;
P
<.001) and all CHD events (OR, 2.95;
P
=.014). The group with hyperinsulinemic microalbuminuria was characterized by the most adversely affected risk factor pattern (high triglycerides ≥2.3 mmol/L, low HDL cholesterol ≤0.9 mmol/L in men and ≤1.20 mmol/L in women, and hypertension).

Conclusions
Simultaneous occurrence of hyperinsulinemia and microalbuminuria identifies a group of subjects with a highly increased risk for CHD in elderly nondiabetic subjects.
Permanent Pacemaker Selection and Subsequent Survival in Elderly Medicare Pacemaker Recipients
Authors: Lamas Gervasio A. , Pashos Chris L. , Normand Sharon-Lise T. , McNeil Barbara
Published: June 2012

Background
Dual-chamber pacemakers have been in use for more than 15 years. Although they may confer a physiological advantage over single-chamber ventricular pacemakers, they are more expensive and have a generally shorter service life than single-chamber devices. We carried out the present study to identify patient subgroups who were preferentially receiving greater or lesser proportions of dual-chamber devices and to determine whether the selection of different types of pacemakers was associated with differences in mortality.

Methods and Results
We analyzed a 20% random national sample of all Medicare beneficiaries aged 65 years or older who underwent initial placement of a permanent pacemaker and were discharged in 1988, 1989, or 1990 (n=36 312). The minimum follow-up for vital status was 1 year. The relation of pacemaker type to patient and provider characteristics was determined using logistic regression analysis. The relation between pacemaker type and mortality was determined using the Cox proportional hazards method. The proportion of dual-chamber systems that were received increased from 27.2% in 1988 to 37.0% in 1990 (
P
<.001). Dual-chamber pacemaker recipients were younger (
P
<.001) than ventricular pacemaker recipients. Other independent correlates of dual-chamber pacemaker selection included male sex (odds ratio and 95% confidence intervals, 1.18 and 1.12 to 1.24, respectively), atrioventricular block (1.59 and 1.51 to 1.67), congestive heart failure (1.14 and 1.08 to 1.20), atrial fibrillation (0.36 and 0.34 to 0.39), and the presence of a major noncardiac diagnosis (0.86 and 0.83 to 0.89). Nonmedical predictors of dual-chamber pacemaker selection included Medicaid eligibility (0.78 and 0.71 to 0.86), implantation in the western United States (1.19 and 1.10 to 1.29), implantation by a rural provider (0.70 and 0.65 to 0.76), hospitalization in a 500-bed-or-larger hospital (1.20 and 1.13 to 1.28), hospitalization in a private hospital (1.19 and 1.10 to 1.28), or hospitalization in a hospital with a catheterization laboratory (1.47 and 1.38 to 1.56). Dual-chamber pacemaker selection was an independent predictor of survival at 1 year (0.82 and 0.77 to 0.87) and at 2 years (0.82 and 0.77 to 0.87) after controlling for potentially confounding patient-level and hospital-level characteristics.

Conclusions
The present study describes important variations in the clinical practice of cardiac pacing, many of which are not based on clinical characteristics. Furthermore, the selection of a dual-chamber pacemaker is associated with increased survival. These results underscore the need for prospective, outcome-based clinical trials of pacemaker mode selection.
Characterization of Atrioventricular Nodal Behavior and Ventricular Response During Atrial Fibrillation Before and After a Selective Slow-Pathway Ablation
Authors: Blanck Zalmen , Dhala Anwer A. , Sra Jasbir , Deshpande Sanjay S. , Anderson Alfred J. , Akhtar Masood , Jazayeri Mohammad R.
Published: June 2012

Background
The presence of atrioventricular nodal dual-pathway physiology in patients with atrioventricular nodal reentrant tachycardia (AVNRT) provides an opportunity to characterize the effect of a selective slow-pathway ablation on the ventricular rate during atrial fibrillation (AF). This may have important clinical implications for the nonpharmacological management of AF with a rapid ventricular rate.

Methods and Results
Selective radiofrequency catheter ablation of the atrioventricular nodal slow pathway was performed with a stepwise approach in patients with documented sustained AVNRT. The AV nodal conduction properties and refractoriness and the ventricular rate during induced AF were assessed at baseline and under autonomic blockade before and after a selective slow-pathway ablation in 18 patients (mean age, 34±8 years). Sustained AVNRT was induced with a mean cycle length of 339±58 ms. A slow-pathway ablation was successfully achieved with 5±4 applications of radiofrequency energy. The shortest cycle length of 1:1 AV conduction and the AV nodal effective refractory period significantly prolonged after ablation (367±53 versus 403±55 ms,
P
<.0001, and 258±55 versus 292±74 ms,
P
<.05, respectively). Selective slow-pathway ablation significantly prolonged the mean (526±93 versus 612±107 ms,
P
<.0001), the shortest (378±59 versus 423±73 ms,
P
<.0001), and the longest (826±150 versus 969±226 ms,
P
<.01) cycle lengths of the ventricular response to AF. Significant slowing of the ventricular rate during AF occurred in 13 patients (72%), including all eight patients in whom AV nodal dual-pathway physiology was abolished. Five patients did not have a significant change in the ventricular rate during AF; a persistent dual AV nodal pathway physiology was demonstrable in four of these patients. Loss of dual-pathway physiology after ablation had a sensitivity of 77%, specificity of 80%, and positive predictive value of 91% for slowing the ventricular rate during AF.

Conclusions
In patients undergoing a slow-pathway ablation for control of AVNRT, selective slow-pathway ablation may cause a significant decrease in the ventricular rate during AF. These effects are primarily due to the prolongation of AV nodal conduction properties and refractory period of the residual AV nodal transmission system. These findings may have important therapeutic implications for the nonpharmacological treatment of AF, particularly in patients with underlying dual AV nodal physiology.
Papillary Muscle Displacement Causes Systolic Anterior Motion of the Mitral Valve
Authors: Levine Robert A. , Vlahakes Gus J. , Lefebvre Xavier , Guerrero J. Luis , Cape Edward G. , Yoganathan Ajit P. , Weyman Arthur E.
Published: June 2012

Background
Systolic anterior motion (SAM) of the mitral valve in hypertrophic cardiomyopathy (HCM) has generally been explained by a Venturi effect related to septal hypertrophy, causing outflow tract narrowing and high velocities. Patients with HCM, however, also have primary abnormalities of the mitral apparatus, including anterior and inward or central displacement of the papillary muscles, and leaflet elongation. These findings have led to the hypothesis that changes in the mitral apparatus can be a primary cause of SAM by altering the forces acting on the mitral valve and its ability to move in response to them. Despite suggestive observations, however, it has never been prospectively demonstrated that such changes can actually cause SAM.

Methods and Results
To test this hypothesis in vivo, anterior papillary muscle displacement was created in 7 dogs studied by echocardiography, with controlled cardiac output and heart rate. In all 7 dogs, papillary muscle displacement caused SAM, with an outflow tract gradient (33±19 mm Hg) and mitral regurgitation in 6. As in patients with HCM, the mitral valve was displaced anteriorly and the coaptation point shifted toward the insertion of the leaflets, creating longer distal residual leaflets that moved anteriorly.

Conclusions
Primary changes in the mitral apparatus can cause SAM without septal hypertrophy. In this model, SAM appears to be determined by the ability of the leaflets to move anteriorly (papillary muscle displacement causing slack and increased residual leaflet length) and their interposition into the outflow stream by anterior displacement, determining the direction of this motion. Geometric factors observed in HCM and in patients with SAM without HCM can therefore play a primary role in causing SAM.
Splanchnic Venous Pressure–Volume Relation During Experimental Acute Ischemic Heart Failure
Authors: Wang Steven Y. , Manyari Dante E. , Scott-Douglas Nairne , Smiseth Otto A. , Smith Eldon R. , Tyberg John V.
Published: June 2012

Background
Vasodilator drugs have variable effects on veins and arteries. However, direct measurements of their effects on the splanchnic veins, perhaps the most important volume reservoir, have not been reported. We assessed the effect of acute heart failure and the subsequent administration of hydralazine, enalaprilat, and nitroglycerin on the splanchnic venous pressure–volume relation in intact dogs.

Methods and Results
Experimental acute ischemic heart failure was induced in 19 splenectomized dogs by microsphere embolization of the left main coronary artery. Embolization was repeated until left ventricular end-diastolic pressure (LVEDP) reached 20 mm Hg and cardiac output decreased by 50%. The splanchnic vascular pressure–volume relation was determined by radionuclide plethysmography during the control stage, after acute heart failure had been established, and after administration of a vasodilator (hydralazine, enalaprilat, or nitroglycerin) at a dose sufficient to reduce mean aortic pressure by approximately 20%. Induction of acute heart failure was associated with a decrease in the splanchnic vascular volume from 100% to 86±2% and an increase in LVEDP from 6±1 to 21±1 mm Hg (
P
<.001). There was a parallel leftward shift of the splanchnic vascular pressure–volume curve. After the administration of hydralazine, enalaprilat, and nitroglycerin, the splanchnic vascular volumes increased from 86% to 88±3%, 96±3%, and 113±3%, respectively (
P
=NS,
P
<.01, and
P
<.001, respectively, versus heart failure). After drug administration, the LVEDPs were 18±2, 16±1, and 13±1 mm Hg (
P
=NS,
P
<.05, and
P
<.001, respectively, versus heart failure).

Conclusions
Acute heart failure was associated with a parallel leftward shift of the splanchnic venous pressure–volume relation (venoconstriction). Splanchnic (systemic) venoconstriction may in part explain the increased LVEDP during acute heart failure by displacement of blood to the central compartment. Subsequently administered enalaprilat and, to a greater degree, nitroglycerin produced splanchnic venodilation, thereby lowering LVEDP. Hydralazine had no significant effect on the splanchnic veins and only a modest effect on LVEDP. In this model, splanchnic capacitance changes appear to modulate change in left ventricular preload.
Cardiac Involvement in Mitochondrial Diseases
Authors: Anan Ryuichiro , Nakagawa Masanori , Miyata Masaaki , Higuchi Itsuro , Nakao Shoichiro , Suehara Masahito , Osame Mitsuhiro , Tanaka Hiromitsu
Published: June 2012

Background
Mutations of mitochondrial DNA have been demonstrated as causes of human mitochondrial diseases. While these disorders typically involve multiple organs, the effect of mitochondrial mutations on the heart has not been systematically studied.

Methods and Results
We studied mitochondrial mutations and cardiac changes in 17 patients with Kearns-Sayre syndrome; ocular myopathy; myoclonus epilepsy with ragged red fibers (MERRF); and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Cardiac involvement was evaluated by chest radiograph, ECG, His-bundle electrogram, and echocardiogram. All 3 patients with Kearns-Sayre syndrome had large deletions of mitochondrial DNA and disturbances in cardiac conduction. ECG abnormalities were found in 2 of 6 patients with ocular myopathy who showed large deletions of mitochondrial DNA. All 3 patients with MERRF had an A-to-G mutation at nucleotide position 8344; 2 had cardiomegaly, asymmetrical septal hypertrophy, and diffuse hypokinesis of the left ventricle. One patient with asymmetrical septal hypertrophy developed dilated cardiomyopathy 2 years later. All 5 patients with MELAS had an A-to-G mutation at nucleotide position 3243, and 2 had symmetrical left ventricular hypertrophy with or without abnormal wall motion.

Conclusions
The clinical features of cardiac involvement in mitochondrial diseases vary in the different subgroups of these disorders. Particular mitochondrial mutations can cause characteristic cardiac abnormalities.
Intermittent Transdermal Nitroglycerin Therapy
Authors: Parker John D. , Parker Andrea B. , Farrell Bernice , Parker John O.
Published: June 2012

Background
Intermittent transdermal nitroglycerin therapy is effective in the treatment of stable angina and prevents the development of tolerance. Previous investigations have suggested that removal of nitroglycerin patches may be associated with a decrease in anginal threshold. This study examines the effect of nitroglycerin patch removal on anginal threshold in a group of patients with stable angina.

Methods and Results
Twelve patients with stable angina were enrolled in a randomized, double-blind, placebo-controlled, crossover study. These patients had reproducible treadmill walking times and were taking no other long-acting antianginal medications or vasodilators. They received 0.8 mg/h transdermal nitroglycerin or wore a matching placebo patch for 5 to 7 days and then crossed over to the other treatment arm of the study. Transdermal nitroglycerin was applied at 8:00
pm
and removed at 8:00
am
each day. On the last day of each treatment period, patients underwent treadmill exercise testing at 8:00
am
(before patch removal) and at 2, 4, and 6 hours after patch removal. The primary end point was the treadmill walking time until moderate angina (P2). Other end points included the treadmill walking time until onset of angina (P1), the amount of ST segment depression at P1 and P2, and treadmill walking time until the development of 1 mm ST depression. Heart rate, systolic blood pressure, and the rate-pressure product were determined at rest before exercise and at P1 and P2. At 8:00
am
P1 and P2 were not significantly affected by active nitroglycerin compared with placebo, indicating the development of tolerance. Removal of the active transdermal nitroglycerin patch was associated with a significant decrease in the time to P1 at 2, 4, and 6 hours after patch removal compared with placebo. There was also a decrease in the time to P2 after active patch removal that was statistically significant compared with placebo at 2 and 4 hours and was of borderline significance at 6 hours. There were no differences in heart rate, blood pressure, or amount of ST segment depression at either P1 or P2 after active compared with placebo patch removal.

Conclusions
In patients with stable angina pectoris, intermittent transdermal nitroglycerin therapy is associated with a decrease in anginal threshold for 4 to 6 hours after patch removal. Although the cause of this phenomenon remains uncertain, it may be due to counterregulatory responses that develop during nitroglycerin patch application.
Influence of Diabetes Mellitus on Early and Late Outcome After Percutaneous Transluminal Coronary Angioplasty
Authors: Stein Bernardo , Weintraub William S. , Gebhart Suzanne S.P. , Cohen-Bernstein Caryn L. , Grosswald Ralph , Liberman Henry A. , Douglas John S. , Morris Douglas C. , King Spencer B.
Published: June 2012

Background
Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized.

Methods and Results
Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics.

Conclusions
Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined.
Circadian Variation in the Efficacy of Tissue-Type Plasminogen Activator
Authors: Kurnik Peter B.
Published: June 2012

Background
The frequency of onset of acute myocardial infarction follows a circadian pattern, with a peak incidence between 6:00
am
and noon. Circadian variations have been defined for platelet aggregation, plasminogen-activator inhibitor, and a number of hemostatic and physiological factors, all of which might predispose toward clotting in the late morning and thrombolysis in the evening. Thus, the hypothesis for this retrospective analysis was that tissue-type plasminogen activator (TPA) has greater efficacy when administered between noon and midnight, as measured by coronary patency 90 minutes after initiation of treatment.

Methods and Results
Seven hundred twenty-eight patients were enrolled in either of two studies in which TPA was administered under a uniform protocol for the treatment of acute myocardial infarction. Of these, 692 patients had qualifying arteriograms that allowed standardized assessment by a core angiographic laboratory of the primary end point of 90-minute patency. TPA has a circadian pattern of efficacy, with greater TIMI grade 3 patency when administered between noon and midnight (
P
<.001). When TPA was given within 2 hours of symptoms (n=127), the total patency was highest and there was a trend (
P
=.055) toward the greatest magnitude difference occurring between
am
and
pm
patency. The onset of myocardial infarction was confirmed to have a marked circadian variation with a peak incidence about 10:00
am
. The peak efficacy of TPA was about 8:00
pm
, representing a phase difference of about 10 hours after peak infarction incidence.

Conclusions
There is a circadian variation in the ability of TPA to rapidly open coronary arteries, with highest efficacy between noon and midnight. This complements clinical and in vitro knowledge of increased morning thrombosis and is concordant with knowledge of a fibrinolytic profile that is more favorable for evening lysis. This finding has implications for understanding the circadian pathophysiology of myocardial infarction and for its chronotherapy.
Intermittent Transdermal Nitroglycerin Therapy in Angina Pectoris
Authors: Parker John O. , Amies Mark H. , Hawkinson Ron W. , Heilman James M. , Hougham Andrina J. , Vollmer Mark C. , Wilson Richard R.
Published: June 2012

Background
The objectives of this study were to assess the antianginal and anti-ischemic effects of three dose levels of transdermal nitroglycerin patches applied for 12 hours daily for 30 days. The study also assessed the development of tolerance and rebound. Intermittent transdermal nitroglycerin therapy with a patch-free period of 10 to 12 hours each day has documented clinical benefits during the period of patch application, but studies have failed to clearly document prolonged exercise duration for the entire period of patch application. This study was designed to evaluate the efficacy and duration of action of a range of doses of nitroglycerin. The study also permitted the assessment of the maintenance of initial effects, the development of tolerance, and the presence of rebound.

Methods and Results
This study was a multicenter, randomized, double-blind, placebo-controlled parallel design trial with treadmill exercise tests at days 0, 1, 7, 15, and 30. Tests were carried out up to 12 hours after patch application. There was a statistically significant treatment effect with increases in treadmill walking time to moderate angina in each nitroglycerin patch group compared with placebo at various time points up to 12 hours throughout the 30-day study period. Secondary efficacy parameters, including the consistent increase in time to 1-mm ST-segment depression, supported the primary efficacy results. There was no evidence of tolerance or rebound.

Conclusions
Intermittent transdermal nitroglycerin therapy increases exercise duration and maintains anti-ischemic effects for 12 hours after patch application, throughout 30 days of therapy, without significant evidence of nitrate tolerance or rebound phenomena.
Redistribution of Myocardial Blood Flow With Topical Nitroglycerin in Patients With Coronary Artery Disease
Authors: Fallen Ernest L. , Nahmias Claude , Scheffel Anita , Coates Geoff , Beanlands Rob , Garnett E. Stephen
Published: June 2012

Background
Unlike nonselective coronary vasodilators, nitroglycerin (GTN) is said to exert its primary vasodilatory effect on epicardial conductance vessels. Thus, in experimental models of coronary occlusion GTN appears to preferentially direct blood flow to poststenotic zones of ischemia. This phenomenon has, to date, not been tested in humans. Using positron emission tomography we examined the effect of transdermal GTN on global and regional myocardial perfusion in patients with angiographically proven coronary artery disease.

Methods and Results
Myocardial perfusion with [
13
N]ammonia was estimated from dynamic time-activity curves at baseline and 3 hours following application of either a 0.4 mg/h GTN skin patch (n=10) or a placebo patch (n=10) in a double-blind parallel design. From resliced cross-sectional images, regional flow, expressed as [
13
N]ammonia retention, was estimated from 216 myocardial sectors. Ischemia was defined as a significant reduction (>2 SDs from average counts/pixel in maximally perfused zones) in [
13
N]ammonia retention within 10 contiguous myocardial sectors coupled with an increase or no change in counts derived from [
18
F]fluorodeoxyglucose. There was no change in global myocardial blood flow as expressed by [
13
N]ammonia retention following either placebo (0.61±0.14 to 0.62±0.12 min
−1
) or GTN (0.75±0.22 to 0.74±0.19 min
−1
). Conversely, there was a significant increase in the proportion of blood flow to the ischemic zones with GTN (73.9±12.6% to 94.9±17.8%;
P
<.05). No change in the distribution of blood flow to either ischemic or nonischemic zones was observed with placebo. A slight but insignificant decrease in [
13
N]ammonia retention in nonischemic zones was observed with GTN (1.01±0.31 to 0.93±0.26 min
−1
).

Conclusions
This study suggests that under resting conditions topical GTN alters myocardial perfusion by preferentially increasing flow to areas of reduced perfusion with little or no change in global myocardial perfusion in patients whose angina is responsive to GTN.
Coronary Stenting Decreases Restenosis in Lesions With Early Loss in Luminal Diameter 24 Hours After Successful PTCA
Authors: Rodriguez Alfredo E. , Santaera Omar , Larribau Miguel , Fernandez Mario , Sarmiento Ricardo , Baliño Nestor Perez , Newell John B. , Roubin Gary S. , Palacios Igor F.
Published: June 2012

Background
Early loss of minimal luminal diameter (MLD) after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of late restenosis.

Methods and Results
Sixty-six patients (66 lesions) with >0.3 mm MLD loss at 24-hour on-line quantitative coronary angiography were randomized into two groups: 1, Gianturco-Roubin stent (n=33) and 2, Control, who received medical therapy only (n=33). All lesions were suitable for stenting. Baseline demographic, clinical, and angiographic characteristics were similar in the two groups. Restenosis (≥50% stenosis) for the overall group occurred in 32 of 66 patients (48.4%) at 3.6±1-month follow-up angiography. Restenosis was significantly greater in group 2 than in group 1 (75.7% versus 21.2%,
P
<.001). Vascular complications (21.2% versus 0%) and length of hospital stay (7.3±1 versus 2.4±0.5 days,
P
<.01) were higher for the stent group. Although at follow-up there were no differences in mortality or incidence of acute myocardial infarction between the two groups, patients in the control group had a higher incidence of repeat revascularization procedures (73% versus 21%,
P
<.001).

Conclusions
In patients with successful PTCA but reduced luminal diameter demonstrated by repeat angiography at 24 hours, the Gianturco-Roubin stent appears to reduce angiographic restenosis at follow-up.
Activated Clotting Time as an Appropriate Test to Compare Heparin and Direct Thrombin Inhibitors Such as Hirudin or Ro 46-6240 in Experimental Arterial Thrombosis
Authors: Carteaux Jean Pierre , Gast Alain , Tschopp Thomas B. , Roux Sébastien
Published: June 2012

Background
Specific thrombin inhibitors are considered to be more potent antithrombotics than heparin. However, the relation between the systemic anticoagulation generated by thrombin inhibitors and their antithrombotic effect is not well defined. In a guinea pig carotid thrombosis model, the activated clotting time (ACT), the activated partial thromboplastin time (aPTT), and thrombin-generation tests were evaluated for their ability to predict the arterial antithrombotic effect of direct thrombin inhibitors such as hirudin and Ro 46-6240 compared with heparin.

Methods and Results
Thrombosis of the carotid artery was induced by subendothelial damage in guinea pigs, and the subsequent cyclic flow variations were monitored. The effects of pretreatment with intravenous heparin, hirudin, and Ro 46-6240 were tested. After doubling the baseline aPTT, 1 IU · kg
−1
· min
−1
heparin was inactive, whereas either hirudin or Ro 46-6240 (30 μg · kg
−1
· min
−1
) prevented thrombus formation by 80%. Heparin (10 IU · kg
−1
· min
−1
) induced the same antithrombotic effect but with indefinite aPTT prolongation. However, for similar prolongation of the ACT, the three compounds had equivalent antithrombotic effects. Thrombin generation was predictive of the antithrombotic effect of the thrombin inhibitors but not of heparin.

Conclusions
The arterial antithrombotic effect of direct thrombin inhibitors, when compared with those of heparin, should be evaluated by the ACT and not the aPTT or thrombin-generation assays. For a “therapeutic” aPTT prolongation, thrombin inhibitors induce higher systemic anticoagulation than does heparin and thus might unduly have higher bleeding liability.
Improving Active Compression-Decompression Cardiopulmonary Resuscitation With an Inspiratory Impedance Valve
Authors: Lurie Keith G. , Coffeen Paul , Shultz Jeffrey , McKnite Scott , Detloff Barry , Mulligan Kate
Published: June 2012

Background
Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) has recently been demonstrated to provide significantly more blood flow to vital organs during cardiac arrest. To further enhance the effectiveness of this technique, we tested the hypothesis that intermittent impedance to inspiratory gas exchange during the decompression phase of ACD CPR enhances vital organ blood flow.

Methods and Results
ACD CPR was performed with a pneumatically driven automated compression-decompression device in a porcine model of ventricular fibrillation (VF). Nine pigs were randomized to receive ACD CPR alone, while 8 pigs received ACD CPR plus intermittent impedance to inspiratory gas exchange with a threshold valve set to 40 cm H
2
O. Results comparing 2 minutes of ACD CPR alone versus ACD CPR with the inspiratory impedance threshold valve (ITV) revealed significantly higher mean (±SEM) coronary perfusion pressures (diastolic aortic minus diastolic right atrial pressures) in the ITV (31.0±2.3 mm Hg) group versus with ACD CPR alone (21±3.6 mm Hg) (
P
<.05). Total left ventricular and cerebral blood flows, determined by radiolabeled microspheres, were 0.77±0.095 and 0.47±0.06 mL/min per gram, respectively, with ACD CPR plus the ITV versus 0.45±0.1 and 0.32±0.016 mL/min per gram, respectively, with ACD CPR alone (
P
<.05). Similar improvements in the ITV group were observed after 7 minutes of ACD CPR. After 16 minutes of VF and 13 minutes of ACD CPR, 6 of 8 pigs in the ITV group were successfully resuscitated with less than three successive 150-J shocks, whereas only 2 of 9 pigs with ACD CPR alone were resuscitated with equivalent energy levels (
P
<.02). With up to three additional and successive 200-J shocks, all pigs in the ITV group and 7 of 9 pigs with ACD CPR alone were resuscitated (
P
=.18).

Conclusions
Intermittent impedance to inspiratory flow of respiratory gases during ACD CPR significantly improves coronary perfusion pressures and vital organ blood flow and lowers defibrillation energy requirements in a porcine model of VF.
Cardiac Allograft Vascular Disease
Authors: Deng Mario C. , Bell Steven , Huie Philip , Pinto Fausto , Hunt Sharon A. , Stinson Edward B. , Sibley Richard , Hall Bruce M. , Valantine Hannah A.
Published: June 2012

Background
Cardiac allograft vascular disease is characterized by accelerated and diffuse intimal proliferation involving both the microvasculature and epicardial vessels. Because in vivo documentation of this complication is now possible with intracoronary ultrasound imaging, we can examine the relationship of intimal proliferation to markers of immunity and endothelial activation. We hypothesize that alterations of microvascular cell surface markers likely mirror changes in the epicardial vessels that may be important in the pathophysiology of intimal proliferation.

Methods and Results
Forty-three heart transplant patients were examined by intracoronary ultrasound more than 1 year after transplantation, and these images were analyzed to obtain mean intimal thickness and intimal thickness class (I through IV), calculated from the mean thickness and circumferential involvement. Right ventricular endomyocardial biopsies obtained at the time of intracoronary ultrasound were examined by immunohistochemistry to detect microvascular expression of histocompatibility leukocyte antigen (HLA) classes I and II (HLA ABC, DR, DP, and DQ); endothelial-specific antigen detected by the monoclonal antibody E 1.5; intercellular adhesion molecules (ICAM-1); CD4
+
and CD8
+
lymphocytes and macrophages (CD 14
+
). Microvascular antigen expression was graded 1 through 5 on the basis of the diffuseness of positive staining. The number of each inflammatory cell phenotype present per high-power field was counted. By ANOVA, scores for HLA DR, HLA DQ, and E1.5 expression were lower in intimal thickness classes II, III, and IV compared with class I. This inverse relationship was significant by linear regression analysis of mean intimal thickness. Inflammatory cells were not significantly correlated with intimal thickening. Rejection incidence was higher, and time since transplantation longer, in intimal thickness classes II, III, and IV compared with class I.

Conclusion
Transplant coronary artery intimal proliferation is associated with alteration of microvascular endothelial cell surface markers. These changes in cell surface antigen expression could provide the substrate for coronary artery intimal proliferation and narrowing.
Prediction of ReversibleIschemia After Revascularization
Authors: Tamaki Nagara , Kawamoto Masahide , Tadamura Eiji , Magata Yasuhiro , Yonekura Yoshiharu , Nohara Ryuji , Sasayama Shigetake , Nishimura Kazunobu , Ban Toshihiko , Konishi Junji
Published: June 2012

Background
Accurate noninvasive determination of myocardial viability is of paramount importance for the clinical identification of patients who will benefit most from revascularization. The preserved metabolic activity in the myocardium, as studied with positron emission tomography (PET), has been considered a gold standard for this purpose. However, recent reports show that moderate hypoperfusion or stress-induced ischemia may represent reversible ischemia. The present study was undertaken to compare the value of perfusion and metabolic studies with PET for predicting improvement in wall motion after revascularization.

Methods and Results
Of 61 patients who had regional asynergy and underwent PET before revascularization, 43 patients who had successful revascularization were included in the study. Each patient underwent rest-stress
13
N-ammonia perfusion scans and
18
F-fluorodeoxyglucose (FDG) scan at rest while in a fasting state. Reversible ischemia was considered to be present when the resting perfusion was ≥50% of the peak value, stress-induced hypoperfusion was present, or an increase in FDG uptake was observed. Of 130 asynergy segments, 51 segments had improved wall motion after revascularization. The positive and negative predictive values for improvement in asynergy were 48% and 87% by the rest perfusion study, 63% (
P
=.05 versus the rest value) and 87% by the rest-stress perfusion study, and 76% (
P
<.01 versus the rest value) and 92% by the FDG study.

Conclusions
FDG PET provided the best predictive value for improvement in wall motion after revascularization. On the other hand,
13
N-ammonia PET is useful for predicting nonreversible myocardial scarring when it shows severe hypoperfusion at rest or hypoperfusion without stress-induced ischemia.
Occult and Frequent Transmission of Atherosclerotic Coronary Disease With Cardiac Transplantation
Authors: Tuzcu E. Murat , Hobbs Robert E. , Rincon Gustavo , Bott-Silverman Corinne , De Franco Anthony C. , Robinson Killian , McCarthy Patrick M. , Stewart Robert W. , Guyer Skip , Nissen Steven E.
Published: June 2012

Background
Transplant coronary artery disease is a major cause of morbidity and mortality after cardiac transplantation. However, limited data exist regarding the potential contribution of coronary atherosclerosis in the donor heart to cardiac-allograft vasculopathy.

Methods and Results
We performed quantitative coronary angiography and intravascular ultrasound imaging in 50 of 62 consecutive heart-transplant recipients (40 men, 10 women, mean age, 53±9 years) 4.6±2.6 weeks after transplantation. The donor population consisted of 30 men and 20 women (mean age, 32±12 years). Ultrasound imaging visualized all three coronary arteries in 22 patients, two coronary arteries in 23, and one coronary artery in 5. Ultrasound imaging detected coronary atherosclerosis (intimal thickness ≥0.5 mm) in 28 patients (56%). However, the angiography was abnormal in only 13 patients (26%). The sensitivity and specificity of coronary angiography were 43% and 95%, respectively. With ultrasound, the average atherosclerotic plaque thickness was 1.3±0.6 mm and the cross-sectional area narrowing was 34±16%. Atherosclerotic involvement frequently was focal (85%), eccentric (mean eccentricity index, 87±8), and near arterial bifurcations. Donors of the transplant recipients with coronary atherosclerosis were older than those without atherosclerosis (37±12 versus 25±10 years, P=.001). Maximal intimal thickness correlated with donor age (
r=
.54,
P
=.0001). Multivariate analysis demonstrated that donor age (
P
=.0001), male sex of donor (
P
=.0006), and recipient age (
P
=.03) were independent predictors of atherosclerosis.

Conclusions
Coronary atherosclerosis is frequently but inadvertently transmitted by means of cardiac transplantation from the donor to the recipient. Long-term outcomes of donor-transmitted coronary artery disease will require further evaluation.