bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic determinants in hypertrophic cardiomyopathy. Prospective evaluation of a therapeutic strategy based on clinical, Holter, hemodynamic, and electrophysiological findings.
Authors: Fananapazir L , Chang A C , Epstein S E , McAreavey D
Published: June 2012

BACKGROUND

Patients with hypertrophic cardiomyopathy (HCM) frequently have arrhythmias and hemodynamic abnormalities and are prone to sudden death and syncope. An important need exists for improved risk stratification and definition of appropriate investigation and therapy.

METHODS AND RESULTS

The relation of 31 clinical, Holter, cardiac catheterization, and electrophysiological (EP) variables to subsequent cardiac events in 230 HCM patients was examined by multivariate analysis. Studies were for cardiac arrest (n = 32), syncope (n = 80), presyncope (n = 52), ventricular tachycardia (VT) on Holter (n = 36), a strong family history of sudden death (n = 9), and palpitations (n = 21). Nonsustained VT on Holter was present in 115 patients (50%). Sustained ventricular arrhythmia was induced in 82 patients (36%). Seventeen cardiac events (eight sudden deaths, one cardiac arrest, and eight syncope with defibrillator discharges) occurred during a follow-up of 28 +/- 19 months. The 1-year and 5-year event-free rates were 99% and 79%, respectively. Two variables were significant independent predictors of subsequent events: sustained ventricular arrhythmia induced at EP study (beta, 3.5; p = 0.002) and a history of cardiac arrest or syncope (beta, 2.9; p less than 0.05). Only two of 66 patients without symptoms of impaired consciousness had a cardiac event (3-year event-free rate, 97%). In contrast, nonsustained VT on Holter was associated with a worse prognosis only in patients with symptoms of impaired consciousness: 11 of 79 symptomatic patients with VT on Holter (14%) had events versus only four of 85 symptomatic patients without VT on Holter (5%) (p = 0.057). Notably, none of 51 patients without symptoms of impaired consciousness in whom VT was not induced at EP study had a cardiac event.

CONCLUSIONS

In HCM, VT on Holter is of benign prognostic significance in the absence of symptoms of impaired consciousness and inducible VT, and sustained VT induced at EP study, especially when associated with cardiac arrest or syncope, identifies a subgroup at high risk for subsequent cardiac events.
Declining incidence of ventricular fibrillation in myocardial infarction. Implications for the prophylactic use of lidocaine.
Authors: Antman E M , Berlin J A
Published: June 2012

BACKGROUND

The purposes of the present investigation were 1) to track the incidence of primary ventricular fibrillation (VF) in the control and lidocaine-treated groups in the randomized control trials (RCTs) of lidocaine prophylaxis against primary VF in acute myocardial infarction, with particular emphasis on the time frame of the randomized trial, and 2) to estimate the number of patients who must receive lidocaine currently to prevent one episode of VF.

METHODS AND RESULTS

The following variables from RCTs published between 1969 and 1988 were entered into logistic regression models to predict the percent of patients developing VF: year of publication of the RCT, method of data analysis used in the RCT, route and technique of lidocaine administration, duration of monitoring for VF, and exclusion criteria before randomization (congestive heart failure/cardiogenic shock, ventricular tachycardia/VF, or bradycardia/atrioventricular block). Year of publication was a significant predictor of VF in both the control and lidocaine groups (p less than or equal to 0.002) even after adjusting for other covariates. Based on a univariate logistic regression model with year as the predictor variable, it was estimated that the incidence of primary VF in the control group fell from 4.51% in 1970 to 0.35% in 1990 and from 4.32% down to 0.11% for the lidocaine group over the same time period. Thus, about 400 patients would currently need prophylaxis with lidocaine to prevent one episode of VF.

CONCLUSIONS

Present estimates of the risk:benefit ratio of lidocaine prophylaxis should consider the low risk of VF in control patients and the large number who need lidocaine prophylaxis to prevent one episode of VF. When added to the previously reported trend toward excess mortality in lidocaine-treated patients, these data argue against the routine prophylactic use of lidocaine in patients with acute myocardial infarction.
Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction.
Authors: Horner S M
Published: June 2012

BACKGROUND

To ascertain the effect of the intravenous administration of magnesium in acute myocardial infarction on the frequency of arrhythmias and mortality, a meta-analysis of randomized controlled trials was performed.

METHODS AND RESULTS

The study included 930 patients with acute myocardial infarction admitted to primary referral hospitals. Administration of magnesium in acute myocardial infarction was associated with a 49% reduction in ventricular tachycardia and fibrillation. The incidence of cardiac arrest was reduced by 58%. The frequency of supraventricular tachycardias was also lower. Overall, there was a 54% reduction in mortality.

CONCLUSIONS

Intravenous magnesium is a safe and effective method of reducing the frequency of arrhythmias and mortality in acute myocardial infarction.
Influence of dietary fat, apolipoprotein E phenotype, and sex on plasma lipoprotein levels.
Authors: Cobb M M , Teitlebaum H , Risch N , Jekel J , Ostfeld A
Published: June 2012

BACKGROUND

The "Western" diet, sex, and apolipoprotein (Apo) E polymorphism have been implicated as codeterminants of lipid levels.

METHODS AND RESULTS

In a retrospective analysis, we evaluated the combined impact of dietary fat, sex, and Apo E phenotype on lipoprotein levels in 67 subjects fed two contrasting, metabolically controlled diets: one a "Western" diet, with a low polyunsaturated to saturated (P:S) fatty acid ratio and the other a "therapeutic" diet, with a high P:S ratio. The high P:S diet compared with P:S diet exerted a far stronger predictive influence on lipoprotein concentrations than Apo E phenotype, sex, or the latter two factors combined. Apo E phenotype alone was associated with a stepwise increase in low density lipoprotein cholesterol (LDL-C), such that 3/2 less than 3/3 less than 4/3 on either the low or the high P:S diets. On the low P:S diet only, sex was shown to be a significant predictor of high density lipoprotein cholesterol (HDL-C) levels, with women greater than men, and the associated LDL/HDL ratio with men greater than women. On the high P:S diet, women displayed a dramatic fall in HDL-C, effectively raising the LDL/HDL ratio to equivalency with men and obliterating the sex influence seen with the low P:S diet. Controlled for dietary fat, Apo E and sex exerted independent, additive effects on lipoprotein levels on the low P:S diet only. Only the Apo E phenotype remained predictive on the high P:S diet.

CONCLUSIONS

Women of the Apo E 3/2 phenotype stand to benefit the least from a high P:S diet because of reduction in the more "protective" HDL-C, whereas men of the 4/3 phenotype showed the greatest improvement in the LDL/HDL ratio.
Lipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group.
Authors: Ettinger W H , Wahl P W , Kuller L H , Bush T L , Tracy R P , Manolio T A , Borhani N O , Wong N D , O'Leary D H
Published: June 2012

BACKGROUND

Cardiovascular disease is the leading cause of death and disability in older people. There is little information about the distributions of risk factors in older populations. This article describes the distribution and correlates of lipoprotein lipids in people greater than or equal to 65 years old.

METHODS AND RESULTS

Lipoprotein lipid concentrations were measured in 2,106 men (M) and 2,732 women (F) who were participants in the Cardiovascular Health Study, a population-based epidemiological study. Distributions of lipids by age and sex and bivariate and multivariate relations among lipids and other variables were determined in cross-sectional analyses. Mean concentrations of lipids were cholesterol: M, 5.20 +/- 0.93 mmol/l (201 +/- 36 mg/dl) and F, 5.81 +/- 0.98 mmol/l (225 +/- 38 mg/dl); triglyceride (TG): M, 1.58 +/- 0.85 mmol/l (140 +/- 75 mg/dl) and F, 1.57 +/- 0.78 mmol/l (139 +/- 69 mg/dl); high density lipoprotein cholesterol (HDL-C): M, 1.23 +/- 0.33 mmol/l (48 +/- 16 mg/dl), and F, 1.53 +/- 0.41 mmol/l (59 +/- 16 mg/dl); low density lipoprotein cholesterol (LDL-C): M, 3.27 +/- 0.85 mmol/l (127 +/- 33 mg/dl) and F, 3.57 +/- 0.93 mmol/l (138 +/- 36 mg/dl). The total cholesterol to HDL-C ratios were M, 4.49 +/- 1.29 and F, 4.05 +/- 1.22. TG, total cholesterol, and LDL-C concentrations were lower with increasing age, the last more evident in men than in women. TG concentration was positively associated with obesity (in women), central fat patterning, glucose intolerance, use of beta-blockers (in men), and use of estrogens (in women) and negatively associated with age, renal function, alcohol use, and socioeconomic status. In general, HDL-C had opposite relations with these variables, except that estrogen use was associated with higher HDL-C concentrations. LDL-C concentration was associated with far fewer variables than the other lipids but was negatively associated with age in men and women and positively correlated with obesity and central fat patterning and negatively correlated with renal function and estrogen use in women. There were no differences in total cholesterol and LDL-C concentrations among participants with and without prevalent coronary heart disease and stroke, but TG concentration was higher and HDL-C lower in men with both coronary heart disease and stroke and in women with coronary heart disease.

CONCLUSIONS

Cholesterol and cholesterol/HDL-C ratio were lower and HDL-C higher than previously reported values in older people, suggesting that lipid risk profiles may be improving in older Americans. TG and HDL-C concentrations, and to a lesser extent LDL-C, were associated with potentially important modifiable factors such as obesity, glucose intolerance, renal function, and medication use.
Rate-dependent effects of diltiazem on human atrioventricular nodal properties.
Authors: Talajic M , Lemery R , Roy D , Villemaire C , Cartier R , Coutu B , Nattel S
Published: June 2012

BACKGROUND

Tachycardia enhances the channel-blocking effects of antiarrhythmic drugs. In contrast to the extensive data regarding the rate-dependent effects of sodium channel blockers in humans, little is known about the frequency-dependent effects of calcium channel blockers on human atrioventricular (AV) nodal properties. Accordingly, the purpose of this study was to evaluate the importance of heart rate in modulating the electrophysiological effects of diltiazem in humans.

METHODS AND RESULTS

Electrophysiological studies were performed in 25 patients. Sinus node, atrial, and AV nodal function were evaluated at multiple atrial rates under control conditions and after administration of one of three intravenous doses of diltiazem designed to produce low, intermediate, and high stable plasma concentrations (designated doses 1, 2, and 3, respectively). Results were analyzed in terms of the longest and shortest cycle lengths obtainable in each patient under control and drug conditions. Plasma concentrations of diltiazem were stable and averaged 43 +/- 4, 73 +/- 6, and 136 +/- 11 ng/ml for doses 1, 2, and 3, respectively. Sinus node recovery time, intra-atrial conduction time, atrial effective refractory period, and HV interval were unaffected by diltiazem infusion. Effects of diltiazem were limited to changes in AV nodal parameters. Stable, dose-dependent increases in Wenckebach cycle length were observed after all three doses of diltiazem (increases of 54 +/- 13, 84 +/- 18, and 174 +/- 33 msec for doses 1, 2, and 3, respectively). Small nonsignificant increases in AH interval and atrioventricular effective refractory period (AVERP) were observed after dose 1 of diltiazem. At long cycle lengths, diltiazem caused modest increases in AH interval (3 +/- 4 and 25 +/- 8 msec for doses 2 and 3, respectively) and AVERP (36 +/- 12 and 70 +/- 25 msec). Drug effects were far greater at short cycle lengths (45 +/- 17 msec, 58 +/- 12 msec for AH interval and 80 +/- 24 msec, 163 +/- 41 msec for AVERP; p less than 0.05 versus values at long cycle lengths). At rapid rates, effects of diltiazem on AVERP substantially exceeded those on AV conduction, a result that could account for the beneficial effects of diltiazem during paroxysmal AV reentrant tachycardia by decreasing the excitable gap.

CONCLUSIONS

Depressant effects of diltiazem on human AV nodal function are highly dependent on atrial rate; the rate-dependent actions on AV nodal refractoriness probably contribute to beneficial effects of diltiazem in patients with supraventricular arrhythmias.
Dipyridamole potentiates the myocardial infarct size-limiting effect of ischemic preconditioning.
Authors: Miura T , Ogawa T , Iwamoto T , Shimamoto K , Iimura O
Published: June 2012

BACKGROUND

Recent studies implicated a key role for adenosine (ADO) receptor activation in the enhancement of ischemic tolerance by ischemic preconditioning. In this study, we aimed to test the hypothesis that dipyridamole, an ADO transport inhibitor, enhances the preconditioning effect.

METHODS AND RESULTS

Six groups of rabbits underwent 30-minute coronary occlusion and 72-hour reperfusion. Infarct size (IS) and the area-at-risk (AR) were determined by histology and by use of fluorescent particles, respectively. IS expressed as the percentage of AR (%IS/AR) was 46.5 +/- 3.4% (n = 13) in control rabbits. Preconditioning with 2-minute ischemia tended to limit %IS/AR (%IS/AR, 35.5 +/- 3.5%, n = 9), and that possible protection was abolished by pretreatment with 10 mg/kg 8-phenyltheophylline (8-PT), an ADO receptor antagonist (%IS/AR, 43.9 +/- 5.8%, n = 9). Administration of dipyridamole (0.25 mg/kg) before the 2-minute preconditioning markedly limited %IS/AR to 13.8 +/- 2.6% (n = 12), indicating the potentiation of the preconditioning effect by this agent. Furthermore, this enhancement of preconditioning effect by dipyridamole treatment was significantly attenuated by 8-PT (%IS/AR, 27.6 +/- 2.1%, n = 11). Dipyridamole given before the 30-minute ischemia, without preconditioning, did not reduce %IS/AR (55.3 +/- 5.2%, n = 7), and a previous study from this laboratory had demonstrated that the present dose of 8-PT alone did not modify IS in the rabbit.

CONCLUSIONS

Dipyridamole significantly potentiated the IS-limiting effect of preconditioning. This finding strongly supports the hypothesis that stimulation of ADO receptors by endogenous ADO, which builds up during preconditioning ischemia, mediates the increased ischemic tolerance afforded by preconditioning.
Long-term predictors of subsequent cardiovascular events with coronary artery disease and 'desirable' levels of plasma total cholesterol.
Authors: Miller M , Seidler A , Kwiterovich P O , Pearson T A
Published: June 2012

BACKGROUND

Patients with coronary artery disease (CAD) are at considerable risk for subsequent cardiovascular events. Although hyperlipidemia accentuates the risk, predictors of subsequent events with CAD and desirable total cholesterol (TC) (less than 5.2 mmol/l) have not been assessed.

METHODS AND RESULTS

A survival analysis was performed in a subset of 740 consecutive patients who underwent diagnostic coronary arteriography between 1977 and 1978. Eight-three men and 24 women with angiographically documented CAD and desirable TC were followed for subsequent cardiovascular events, including myocardial infarction and cardiovascular death. Over a 13-year period, 75% of CAD subjects with reduced high density lipoprotein cholesterol (HDL-C) (less than 0.9 mmol/l) developed a subsequent cardiovascular event compared with 45% of those with HDL-C greater than or equal to 0.9 mmol/l (p = 0.002). A Kaplan-Meier analysis revealed significantly greater survival from cardiovascular end points in patients with baseline levels of HDL-C greater than or equal to 0.9 mmol/l (p = 0.005). After 11 variables were tested, an age-adjusted Cox proportional-hazards model identified two pairs of independent predictors of subsequent cardiovascular events: they were a left ventricular ejection fraction (LVEF) less than 35% (relative risk [RR], 6.5; 95% confidence interval [CI], 2.8, 15.3; p less than 0.001) and reduced HDL-C (RR, 2.0; 95% CI, 1.2, 3.3; p = 0.01) in the first model and LVEF less than 35% (RR, 6.5; 95% CI, 2.7, 15.6; p less than 0.001) and TC:HDL ratio greater than or equal to 5.5 (RR, 1.9; 95% CI, 1.1, 3.1; p = 0.02) in the second model.

CONCLUSIONS

Low HDL-C (or high TC:HDL-C) is strongly predictive of subsequent cardiovascular events in subjects with CAD, despite desirable TC. As such, identification of this potentially modifiable risk factor should be actively pursued in this high-risk subgroup.
Endogenous nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries.
Authors: Yao S K , Ober J C , Krishnaswami A , Ferguson J J , Anderson H V , Golino P , Buja L M , Willerson J T
Published: June 2012

BACKGROUND

This study was designed to test the hypothesis that endogenously produced nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries of mongrel dogs.

METHODS AND RESULTS

NG-Monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation, was administered at 5 mg/kg to 15 dogs after the left anterior descending coronary artery was mechanically injured and narrowed by external constrictors and to nine dogs before endothelial injury of the femoral artery and after injury and moderate arterial constriction. Treatment with L-NMMA resulted in cyclic flow variations (as detected by external Doppler flow probes) in the left anterior descending artery of seven of 15 dogs and in the femoral artery of four of nine dogs after endothelial injury. L-Arginine, the precursor for nitric oxide synthesis, was administered at 60 mg/kg and abolished cyclic flow variations in each of the 11 dogs. D-Arginine did not change the L-NMMA-induced cyclic flow variations. Saline infusion did not induce or change cyclic flow variations in any of the animals. Acetylcholine (1, 10, and 100 micrograms/min; n = 9) was administered in the femoral artery of nine additional dogs before and after endothelial injury in moderately stenosed femoral arteries. Acetylcholine did not induce cyclic flow variations in any animal; however, it did increase the severity of cyclic flow variations that developed in severely stenosed arteries. The diameter of the femoral artery was measured by intravascular ultrasound imaging. L-NMMA caused vasoconstriction of normal arteries, but no change was detected in endothelium-injured arteries. In contrast, L-arginine caused vasodilation of normal arteries, but, again, no change was noted in endothelium-injured arteries. Acetylcholine dilated normal femoral arteries but constricted arteries with endothelial injury. In both in vitro and ex vivo platelet studies, L-NMMA enhanced platelet aggregation, whereas L-arginine significantly reduced platelet aggregation. D-Arginine and acetylcholine showed no effect on platelet aggregation.

CONCLUSIONS

Promotion of nitric oxide production decreases platelet aggregation and may eliminate cyclic flow variations, whereas a reduction in nitric oxide formation enhances platelet aggregation and may induce cyclic flow variations. Acetylcholine causes vasoconstriction at the femoral arterial site of endothelial injury and may increase the severity of cyclic flow variations.
Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.
Authors: Brunken R C , Mody F V , Hawkins R A , Nienaber C , Phelps M E , Schelbert H R
Published: June 2012

BACKGROUND

Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects.

METHODS AND RESULTS

On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest-redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score > or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores < or = 1.4) to 15% (scores > 2.6). For partially reversible defects, only 53% with scores < 2.0 and one of two with scores > or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00).

CONCLUSIONS

In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less-pronounced reductions in segmental 201Tl activity.
QT intervals at heart rates from 50 to 120 beats per minute during 24-hour electrocardiographic recordings in 100 healthy men. Effects of atenolol.
Authors: Viitasalo M , Karjalainen J
Published: June 2012

BACKGROUND

Conflicting reports about changes in QT intervals suggest that QT values should be compared at similar heart rates.

METHODS AND RESULTS

Relations between QT and RR intervals were determined after measurement of QT values by Holter recording at heart rates of 50, 60, 70, 80, 90, 100, 110, and 120 beats per minute in 100 healthy young men. Fifteen men underwent a second recording during acute treatment with the beta-blocking agent atenolol. At heart rates between 80 and 120 beats per minute, the QT interval was significantly longer (from 9 to 16 msec), and at a heart rate of 50 beats per minute significantly shorter (26 msec), than values calculated from Bazett's formula. Sleep prolonged QT values by 18 msec at a heart rate of 60 beats per minute and by 21 msec at a heart rate of 50 beats per minute compared with the waking state. Atenolol lengthened QT intervals significantly (by 11-14 msec) at heart rates between 90 and 110 beats per minute and shortened them (by 12 msec) at a heart rate of 60 beats per minute. During sleep, QT intervals were the same before and after atenolol.

CONCLUSIONS

The method of plotting QT against RR intervals after measurement of QT values at similar stable spontaneous heart rates before and after intervention allows changes in autonomic state and heart rate to be taken into account. By this method, QT values can be compared without distortion effects caused by correction formulas.
Abnormal neuroendocrine responses during exercise in heart transplant recipients.
Authors: Braith R W , Wood C E , Limacher M C , Pollock M L , Lowenthal D T , Phillips M I , Staples E D
Published: June 2012

BACKGROUND

Osmotic and neural factors stimulate neuroendocrine activity during exercise. In contrast to excitatory mechanisms, afferent information from cardiac mechanoreceptors inhibits integrative centers in the hypothalamus and medula oblongata, which serves to buffer neuroendocrine activity. Orthotopic cardiac transplantation results in the loss of afferent information from cardiac mechanoreceptors. Thus, transplantation possibly results in exaggerated neuroendocrine responses when patients are physically active.

METHODS AND RESULTS

We measured the neuroendocrine response to moderate and strenuous exercise performed at the same relative intensity in 11 heart transplant recipients (50 +/- 14 years old) 18 +/- 12 months after transplantation and 11 control subjects matched with respect to sex, age, and body size. Plasma levels of norepinephrine, vasopressin, renin activity, atrial natriuretic peptide, angiotensin II, and aldosterone were measured at rest, during a maximal graded exercise test, and during submaximal exercise at 40% and 70% of peak power output on a cycle ergometer (W). Plasma renin activity and atrial natriuretic peptide were elevated at rest in heart transplant recipients (p < or = 0.05). Heart rate (%HRmax reserve), rating of perceived exertion, and reductions in plasma volume (% delta from rest) at the conclusion of the three exercise conditions did not differ between heart transplant recipients and control (p > or = 0.05). Relative changes in neuroendocrine hormones were similar (p > or = 0.05) in heart transplant recipients and control during exercise at 40% of peak power output. Relative changes in plasma norepinephrine, vasopressin, atrial natriuretic peptide, and plasma renin activity were greater (p < or = 0.05) in heart transplant recipients during exercise at 70% of peak power output and the graded exercise test.

CONCLUSIONS

We interpret these data as a possible indication of ablation of cardiac mechanoreceptor afferents and unopposed neuroendocrine stimulation in heart transplant recipients. Furthermore, chronic neuroendocrine hyperactivity is likely in ambulatory heart transplant recipients. Although cyclosporine nephrotoxicity is implicated in the development of hypertension, our data suggest that chronic neuroendocrine hyperactivity, which alters renal volume regulation, also contributes to the incidence and severity of hypertension in heart transplant recipients.
A prospective study of nutritional factors and hypertension among US men.
Authors: Ascherio A , Rimm E B , Giovannucci E L , Colditz G A , Rosner B , Willett W C , Sacks F , Stampfer M J
Published: June 2012

BACKGROUND

An effect of diet in determining blood pressure is suggested by epidemiological studies, but the role of specific nutrients is still unsettled.

METHODS AND RESULTS

The relation of various nutritional factors with hypertension was examined prospectively among 30,681 predominantly white US male health professionals, 40-75 years old, without diagnosed hypertension. During 4 years of follow-up, 1,248 men reported a diagnosis of hypertension. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary fiber, potassium, and magnesium were each significantly associated with lower risk of hypertension when considered individually and after adjustment for age, relative weight, alcohol consumption, and energy intake. When these nutrients were considered simultaneously, only dietary fiber had an independent inverse association with hypertension. For men with a fiber intake of < 12 g/day, the relative risk of hypertension was 1.57 (95% confidence interval, 1.20-2.05) compared with an intake of > 24 g/day. Calcium was significantly associated with lower risk of hypertension only in lean men. Dietary fiber, potassium, and magnesium were also inversely related to baseline systolic and diastolic blood pressure and to change in blood pressure during the follow-up among men who did not develop hypertension. Calcium was inversely associated with baseline blood pressure but not with change in blood pressure. No significant associations with hypertension were observed for sodium, total fat, or saturated, transunsaturated, and polyunsaturated fatty acids. Fruit fiber but not vegetable or cereal fiber was inversely associated with incidence of hypertension.

CONCLUSIONS

These results support hypotheses that an increased intake of fiber and magnesium may contribute to the prevention of hypertension.
Percutaneous polymeric stents in porcine coronary arteries. Initial experience with polyethylene terephthalate stents.
Authors: Murphy J G , Schwartz R S , Edwards W D , Camrud A R , Vlietstra R E , Holmes D R
Published: June 2012

BACKGROUND

To test the feasibility of percutaneous deployment of intracoronary polymeric stents, a prototype polyethylene terephthalate (PET) stent and a catheter-based delivery system were developed.

METHODS AND RESULTS

Polymeric stents were deployed in the coronary arteries of 11 Yucatan swine: six stents were placed in the left anterior descending coronary artery, four stents were placed in the circumflex artery, and one stent was placed in the right coronary artery. Stent deployment was achieved by withdrawal of an outer delivery sheath, thus allowing the PET stent to self-expand to a preformed configuration. Two animals died during surgery, one during stent placement and the other several hours after implantation due to intracoronary thrombus formation. Two animals were electively sacrificed within 24 hours of stent implant to examine the adequacy of stent deployment within the coronary vessel. The remaining seven animals survived until the termination of the study 4-6 weeks later. Light microscopic examination of the stented vessels showed an extensive neointimal proliferative response with vessel occlusion in all animals who survived initial stent placement. There were two distinct types of histological responses to the PET stent--a chronic foreign body inflammatory response around the stent tines and a neointimal proliferative response in the center of the occluded vessel lumen. The histological response seen in the central area of the vessel was morphologically similar to that seen in patients with restenosis after successful percutaneous transluminal coronary angioplasty, whereas the morphological response seen at the periphery of the stent tine was similar to that exhibited by a chronic foreign body reaction and was not typical of that seen in a restenosis lesion. A ventricular aneurysm also developed in the area of myocardium that was previously supplied by the occluded vessel.

CONCLUSIONS

This study demonstrates that percutaneous deployment of polymeric stents in the coronary arteries is technically feasible. The use of PET polymer was associated with an intense proliferative neointimal response that resulted in complete vessel occlusion. Histological examination of the stented segments of the vessel revealed no evidence that dissection of the vessel wall had occurred at the time of initial stent deployment. Although the PET polymer was of similar quality to that used in the manufacture of balloon angioplasty catheters, a toxic chemical or contaminant effect cannot be completely excluded as the stimulus to intimal proliferation. This finding may have relevance to the selection of materials for use as intravascular devices.
Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures. A comparison of different measures of treatment effect.
Authors: Blankenhorn D H , Selzer R H , Mack W J , Crawford D W , Pogoda J , Lee P L , Shircore A M , Azen S P
Published: June 2012

BACKGROUND

The Cholesterol Lowering Atherosclerosis Study has demonstrated beneficial effect of colestipol/niacin on coronary atherosclerosis using a panel-determined global coronary change score. We now report treatment group comparisons using quantitative coronary angiographic (QCA) measures from all processable segments in 85 of 162 randomly selected baseline/2-year film pairs.

METHODS AND RESULTS

Treatment benefit was established for percent stenosis for either continuous or categorical analyses with regression established regardless of the per-patient scoring procedure. In addition, treatment benefit favoring regression was established in some cases for roughness and for percent involvement, a longitudinal estimate of the percent of coronary surface involved by raised lesions. Benefit on minimum diameter was directly related to whether the segment was proximal to a graft insertion and hemodynamically related to the bypass graft. QCA correlates of panel-determined progression were increases in percent stenosis and numbers of occluded lesions in native arteries and the number of progressing lesions in bypass grafts.

CONCLUSIONS

These results demonstrate that a variety of computer measures can be used as end points in coronary angiographic therapy trials, but change in percent stenosis correlates best with visual panel assessments and best reflects the treatment benefit; when treatment effect sizes are moderate to large, the required sample size of coronary angiographic trials can be reduced when QCA is used.
Effect of baffle fenestration on outcome of the modified Fontan operation.
Authors: Bridges N D , Mayer J E , Lock J E , Jonas R A , Hanley F L , Keane J F , Perry S B , Castaneda A R
Published: June 2012

BACKGROUND

The "fenestrated Fontan" (surgical baffle fenestration followed by transcatheter test occlusion and permanent closure after postoperative recovery) was adopted in an effort to reduce perioperative mortality and morbidity. This study assesses the effect of baffle fenestration on outcome.

METHODS AND RESULTS

Patients having a modified Fontan operation with a cavocaval baffle and cavopulmonary anastomosis were retrospectively selected for study. Those with baffle fenestration (n = 91) were compared with those without baffle fenestration (n = 56) with respect to preoperative risk factors, age, anatomy, surgical date, and presence or absence of a previous bidirectional cavopulmonary anastomosis. Outcome variables were failure (death or take-down) and duration of postoperative pleural effusions and hospitalization. Survival and clinical status after hospital discharge were ascertained. The two groups did not appear to differ with respect to age or anatomic diagnosis. Patients having baffle fenestration were at significantly greater preoperative risk by univariate and multivariate analysis (p < 0.01). Operative failure was low in both groups (11% without and 7% with baffle fenestration, p = NS). Durations of pleural effusions and hospitalization were significantly shorter with baffle fenestration (p < 0.01). Neither date of surgery nor a previous bidirectional cavopulmonary anastomosis appeared to contribute to improved outcome. Patients with baffle fenestration had lower postoperative systemic venous pressure (p < 0.01). There were no late deaths. Functional status in both groups is good (82% in New York Heart Association class I).

CONCLUSIONS

Baffle fenestration is associated with low mortality, significantly less pleural effusion, and significantly shorter hospitalization among high-risk patients having a modified Fontan operation.
Angiotensin converting enzyme inhibition restores cardiac and hormonal responses to volume overload in patients with dilated cardiomyopathy and mild heart failure.
Authors: Volpe M , Tritto C , DeLuca N , Rubattu S , Mele A F , Lembo G , Enea I , deCampora P , Rendina V , Romano M
Published: June 2012

BACKGROUND

Angiotensin converting enzyme (ACE) inhibition exerts a favorable effect on the response to exercise in heart failure. This study was planned to define the influence of ACE inhibition on the adaptation to volume overload.

METHODS AND RESULTS

We studied the hemodynamic, hormonal, and renal responses to acute volume expansion (sodium chloride, 0.9%, 0.25 ml.kg-1.min-1 for 2 hours) in patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (New York Heart Association class I or II, ejection fraction < or = 50%). The patients were studied without any pretreatment (n = 14) or after 1 week of treatment with the oral ACE inhibitor quinapril at a dosage of 10 mg/day (n = 11). Seven patients were studied during constant intravenous infusion with nitroglycerin (0.1 micrograms.kg-1.min-1). The study groups had similar hemodynamic and clinical characteristics and hormonal profile at baseline evaluation. In the untreated patients, volume expansion did not increase left ventricular end-diastolic volume measured by echocardiography and was associated with a reduction in ejection fraction (p < 0.05) and with a paradoxical increase in forearm vascular resistance (p < 0.05) estimated by plethysmography. In addition, plasma atrial natriuretic factor did not change, and plasma norepinephrine was increased by saline loading. In contrast, in the patients treated with quinapril, volume expansion induced an increase of both left ventricular volumes (p < 0.001) without changing ejection fraction and reduced forearm vascular resistance (p < 0.05). In addition, in this group, plasma atrial natriuretic factor levels increased (p < 0.05) and plasma norepinephrine did not change during volume overload. During nitroglycerin infusion, volume expansion was associated with peripheral vasodilatation, increases of left ventricular volumes, and no change in ejection fraction. In this group, however, plasma atrial natriuretic factor levels did not change in response to volume overload.

CONCLUSIONS

We conclude that pretreatment with the ACE inhibitor quinapril significantly improves compromised responses to acute isotonic volume overload in patients with dilated cardiomyopathy and mild heart failure. The favorable influence of ACE inhibition on cardiovascular and hormonal responses to volume expansion seems to be related to the cardiac unloading produced by this treatment.
Angiotensin II directly stimulates release of atrial natriuretic factor in isolated rabbit hearts.
Authors: Focaccio A , Volpe M , Ambrosio G , Lembo G , Pannain S , Rubattu S , Enea I , Pignalosa S , Chiariello M
Published: June 2012

BACKGROUND

Previous studies have shown that infusion of angiotensin II (Ang II) increases plasma concentrations of atrial natriuretic factor (ANF) in vivo. This phenomenon has been considered secondary to the effects of Ang II on cardiac and systemic hemodynamics. The present study was designed to assess whether Ang II may exert a direct stimulatory effect on ANF release from the heart independent of changes in hemodynamics.

METHODS AND RESULTS

Isolated rabbit hearts were perfused in the Langendorff mode. Heart rate, coronary flow, and atrial and left ventricular (LV) volumes were kept constant. After stabilization, Ang II was infused intracoronary at increasing doses (10(-11) to 10(-8) M) in nine hearts and at a single dose of 10(-10) M in 10 hearts. Each infusion lasted for 5 minutes and was followed by a 10-minute washout period. Four hearts received vehicle alone for 80 minutes. Ang II induced a dose-dependent increase in coronary perfusion pressure and in LV developed pressure. ANF release, measured by radioimmunoassay on the extracts of the cardiac effluent, also increased during Ang II infusion and returned to the basal values during the 10-minute washout period. In the control group, coronary perfusion pressure, LV developed pressure, and LV end-diastolic pressure did not change appreciably over the observation period, whereas ANF release progressively decreased during perfusion.

CONCLUSIONS

Ang II can directly stimulate cardiac release of ANF in isolated rabbit hearts independently of changes in hemodynamics.
Ischemic preconditioning increases adenosine release and 5'-nucleotidase activity during myocardial ischemia and reperfusion in dogs. Implications for myocardial salvage.
Authors: Kitakaze M , Hori M , Takashima S , Sato H , Inoue M , Kamada T
Published: June 2012

BACKGROUND

Adenosine has been reported to mediate the necrosis-limiting effects of ischemic preconditioning; however, it is unclear how this mediation occurs. The present study was undertaken to test the hypothesis that ischemic preconditioning increases 5'-nucleotidase activity and adenosine release during sustained ischemia and subsequent reperfusion.

METHODS AND RESULTS

After thoracotomy, the left anterior descending coronary artery was cannulated and perfused with blood redirected from the left carotid artery in 32 dogs. Ischemic preconditioning was produced by four cycles in which the coronary artery was occluded and then reperfused for 5 minutes each. After the last cycle of ischemia and reperfusion, the coronary artery was occluded for 40 minutes. This was followed by 120 minutes of reperfusion. In the control group, the coronary artery was occluded for 40 minutes and reperfused for 120 minutes without ischemic preconditioning. The plasma adenosine concentration was measured and blood gases were analyzed in coronary arterial and venous blood samples taken during 120 minutes of reperfusion. Myocardial 5'-nucleotidase activity was measured before and at 40 minutes of sustained ischemia with and without ischemic preconditioning. The adenosine concentration in coronary venous blood during reperfusion was significantly higher in preconditioned hearts than in the control hearts: 1 minute after the onset of reperfusion, 546 +/- 57 versus 244 +/- 41 pmol/ml; 10 minutes after, 308 +/- 30 versus 114 +/- 14 pmol/ml; 30 minutes after, 175 +/- 24 versus 82 +/- 16 pmol/ml, respectively (p < 0.01). Ectosolic and cytosolic 5'-nucleotidase activities increased in both endocardial and epicardial myocardium in the ischemia-preconditioned hearts. Furthermore, 40 minutes of ischemia increased 5'-nucleotidase activity in ischemia-preconditioned hearts more than in control hearts.

CONCLUSIONS

Ischemic preconditioning increases adenosine release and 5'-nucleotidase activity during sustained ischemia and subsequent reperfusion.
Effects of subendocardial ablation on anodal supernormal excitation and ventricular vulnerability in open-chest dogs.
Authors: Chen P S , Wolf P L , Cha Y M , Peters B B , Topham S L
Published: June 2012

BACKGROUND

In Langendorff-perfused hearts and in hearts on cardiopulmonary bypass, chemical ablation of the subendocardium of both ventricles decreases ventricular vulnerability to fibrillation. It was hypothesized that the effects of ablation are a result of the elimination of the subendocardial Purkinje fiber network. This hypothesis has been supported by recent observations that the supernormal excitability that is demonstrable in the Purkinje fibers is associated with arrhythmogenesis.

METHODS AND RESULTS

We tested this hypothesis on 10 open-chest dogs by evaluating the strength-interval curves of anodal and cathodal stimulation with the assistance of computerized mapping techniques. The ventricular fibrillation threshold was also determined. The same test was then performed after chemical ablation of the subendocardium of either the right ventricle (six dogs) or both ventricles (four dogs). Anodal supernormality was consistently demonstrated in all the dogs studied both before and after subendocardial ablation. The ventricular fibrillation thresholds were 23 +/- 5 mA both before and after right ventricular subendocardial ablation (p = NS). The ventricular fibrillation thresholds before and after biventricular subendocardial ablation were 25 +/- 3 and 22 +/- 10 mA, respectively (p = NS).

CONCLUSIONS

We conclude that 1) subendocardial ablation does not decrease ventricular vulnerability when the heart is in situ and is not on cardiopulmonary bypass and 2) anodal supernormal excitability can be demonstrated in ventricles without a subendocardial Purkinje fiber network.
Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function.
Authors: Shivalkar B , Van Loon J , Wieland W , Tjandra-Maga T B , Borgers M , Plets C , Flameng W
Published: June 2012

BACKGROUND

Studies done in potential donors for heart transplantation and in experimental animals have suggested that brain death can have major histopathological and functional effects on the myocardium.

METHODS AND RESULTS

We developed experimental models of brain death using dogs to study the hemodynamic and catecholamine changes, the extent of myocardial structural damage, and the recovery potential of donor hearts obtained from brain-dead donors. Brain death was caused by increasing the intracranial pressure (ICP) suddenly or gradually by injecting saline in an epidural Foley catheter. In a first series of experiments, dogs given a sudden rise in ICP (n = 5) showed a hyperdynamic response and a 1,000-fold increase in the level of epinephrine after brain death. Histology revealed 93 +/- 2% of the myocardium to be severely ischemic. Dogs given a gradual rise in ICP (n = 6) showed a lesser hyperdynamic response, almost 200-fold increase in the level of epinephrine after brain death, and mild ischemic damage to the myocardium (23 +/- 1%). In a second series, hearts obtained from brain-dead and non-brain-dead donors were transplanted in recipients, and the weaning and recovery potential were studied. All four recipients with hearts from non-brain-dead donors were weaned with good functional recovery. Also, all four recipients with hearts from brain-dead dogs given a gradual rise in ICP were weaned with only moderate functional recovery. However, only two of four recipients with hearts from donors given a sudden rise in ICP were weaned and showed poor functional recovery.

CONCLUSIONS

Our results indicate that a sudden rise in ICP can cause irreversible myocardial damage.
Vascular injury induces angiotensinogen gene expression in the media and neointima.
Authors: Rakugi H , Jacob H J , Krieger J E , Ingelfinger J R , Pratt R E
Published: June 2012

BACKGROUND

Angiotensin II promotes growth of vascular smooth muscle cells in vitro via the autocrine production of growth factors such as platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-beta. Furthermore, experimental studies have demonstrated that angiotensin infusion can enhance smooth muscle proliferation after balloon injury in vivo. Consistent with this, angiotensin converting enzyme inhibitors have been shown to prevent myointimal proliferation. The origin of vascular angiotensin that participate in this process is of interest. We have demonstrated the presence of angiotensinogen messenger RNA (mRNA) in the adventitial and medial layers of the rat aorta and have speculated that local angiotensinogen production may play an important role during myointimal proliferation. To provide further evidence toward this hypothesis, we compared the localization and expression of angiotensinogen mRNA in control and balloon injured vessels using in situ hybridization.

METHODS AND RESULTS

Abdominal aorta of Sprague-Dawley rats were studied before or after injury with a balloon catheter. Neointimal hyperplasia developed as documented morphologically by a progressive increase in the ratio of neointimal to medial thickness from 0.17 at 1 week to 1.17 at 6 weeks after injury. Angiotensinogen mRNA was detected clearly in the adventitia and media of control and injured aorta. However, at 1 week after injury, the medial-to-adventitial angiotensinogen mRNA ratio was higher in the injured aorta, suggesting increased gene expression in the media compared with control. Of potential importance, angiotensinogen mRNA was also detected in the neointima of the injured aorta, and this was also highest at 1 week after injury.

CONCLUSIONS

These data are consistent with the hypothesis that balloon injury leads to activation of the vascular renin-angiotensin system, which may participate in the myointimal proliferation.