Inflammation and cardiovascular events in individuals with and without chronic kidney disease.

Inflammation and chronic kidney disease predict cardiovascular events. Here we evaluated markers of inflammation including fibrinogen, albumin and white blood cell count in individuals with and without stages 3-4 chronic kidney disease to assess inflammation as a risk factor for adverse events, the synergy between inflammation and chronic kidney disease, and the prognostic ability of these inflammatory markers relative to that of C-reactive protein. Using Atherosclerosis Risk in Communities and Cardiovascular Health Study data, inflammation was defined by worst quartile of at least 2 of these 3 markers. In Cox regression models, inflammation was assessed as a risk factor for a composite of cardiac events, stroke and mortality as well as components of this composite. Among 20 413 patients, inflammation was identified in 3594 and chronic kidney disease in 1649. In multivariable analyses, both inflammation and chronic kidney disease predicted all outcomes, but their interaction was non-significant. In 5597 patients with C-reactive protein levels, inflammation and elevated C-reactive protein had similar hazard ratios. When focusing only on individuals with the worst quartile of white cell count and albumin, results remained consistent.

A computer-based Markov decision analysis of the management of symptomatic bifascicular block: the threshold probability for pacing.

This review illustrates the use of computer-based Markov models to estimate cost-effectiveness and prognosis in a complex problem in clinical cardiology. Decision analysis and cost-effectiveness analysis were used to assess whether to implant a permanent cardiac pacemaker, treat with drugs, perform electrophysiologic studies or observe patients who have two clinical features--syncope and bifascicular block--that may or may not be causally related. Using a Markov process model, a computer program simulated the prognosis of five cohorts of such patients--one treated conservatively, one given empiric antiarrhythmic drug therapy, one receiving a pacemaker, one treated with empiric drugs and pacing and one tested with electrophysiologic studies. On the basis of data from published reports and expert opinion, quality-adjusted life expectancy was calculated by summing the average time a member of each cohort would survive with and without symptoms for each initial treatment choice. The costs were estimated from 1985 hospital charges. For patients with normal left ventricular function, electrophysiologic testing provides a benefit of 14 quality-adjusted months of life over observation, at an additional cost of $24,200. Empiric pacing would add 2.5 additional months, at a further cost of $14,300. In patients with poor left ventricular function, empiric drug therapy offers 1.5 additional quality-adjusted months over observation, at a cost of $6,900. Electrophysiologic testing provides a further 16.5 months at an additional cost of $16,900. These results hold when the relation between symptoms and arrhythmia is not firmly established. Varying the probabilities of underlying ventricular tachyarrhythmias, bradyarrhythmic conduction defects or noncardiac causes of syncope affects the cost-effectiveness relative to the alternative treatments.

Plasma homocyst(e)ine levels in men with premature coronary artery disease.

Plasma homocyst(e)ine (that is, the sum of free and bound homocysteine and its oxidized forms, homocystine and homocysteine-cysteine mixed disulfide) levels were determined in 170 men (mean age +/- SD 50 +/- 7 years) with premature coronary artery disease diagnosed at coronary angiography and in 255 control subjects clinically free of coronary artery disease (mean age 49 +/- 6 years). Patients with coronary artery disease had a higher homocyst(e)ine level than control subjects (13.66 +/- 6.44 versus 10.93 +/- 4.92 nmol/ml, p less than 0.001). High density lipoprotein (HDL) cholesterol levels were lower (32 +/- 10 versus 46 +/- 13 mg/dl, p less than 0.001) and triglycerides levels were higher (193 +/- 103 versus 136 +/- 106 mg/dl, p less than 0.001) in the coronary disease group. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels were not significantly different between patients with coronary disease and control subjects. The presence of hypertension, smoking or diabetes mellitus did not significantly alter homocyst(e)ine levels in the patient or the control group. Patients who were not taking a beta-adrenergic blocking drug (n = 70) had a nonsignificantly higher homocyst(e)ine level than did patients taking this class of drugs (n = 100) (14.67 +/- 8.92 versus 12.95 +/- 3.77 nmol/ml, p = 0.087). By design, none of the control subjects were taking a beta-blocker. No significant correlations were observed between homocyst(e)ine and age, serum cholesterol, LDL cholesterol, HDL cholesterol or triglyceride levels. It is concluded that an elevated plasma homocyst(e)ine level is an independent risk factor for the development of premature coronary atherosclerosis in men.

Warfarin anticoagulation and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction.

OBJECTIVES: We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction. BACKGROUND: Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial. METHODS: We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome. RESULTS: On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology. CONCLUSIONS: In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.

OBJECTIVES: We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction. BACKGROUND: Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction. METHODS: We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction. RESULTS: Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently. CONCLUSIONS: Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.

Comparison of left and right ventricular end-systolic pressure-volume relations in congestive heart failure.

A hemodynamic-radionuclide study was performed to compare the relations between end-systolic pressure and volume in the left and right ventricles in 10 patients with biventricular failure, and to correlate the end-systolic pressure-volume slope with baseline variables of systolic function. During nitroprusside or nitroglycerin infusion, or a combination of both, linear relations were found between end-systolic pressure and volume for both ventricles. In 9 of 10 patients, the end-systolic pressure-volume slope was greater for the left ventricle (mean +/- SD 1.12 +/- 0.36 mm Hg X m2/ml) than for the right ventricle (0.46 +/- 0.27 mm Hg X m2/ml) (p less than 0.001). In all 10 patients, the volume-axis intercept of the pressure-volume relation was greater for the left ventricle (82 +/- 66 ml/m2) than for the right ventricle (2 +/- 30 ml/m2) (p less than 0.005). Right ventricular pressure-volume slope correlated weakly with baseline right ventricular ejection fraction (r = 0.69, p less than 0.05), strongly with the baseline right ventricular end-systolic pressure-volume ratio (r = 0.89) and inversely with baseline right ventricular end-systolic volume (r = -0.86). In conclusion, 1) in patients with severe biventricular failure, changes in systolic pressure influence end-systolic volume more strongly in the right than in the left ventricle. 2) For the right ventricle, the slope of the end-systolic pressure-volume relation is directly related to rest indexes of systolic function. 3) The greater the end-systolic volume at rest, the greater the predicted improvement in right ventricular emptying for any vasodilator-induced reduction in pulmonary artery end-systolic pressure.

The excimer laser: gross, light microscopic and ultrastructural analysis of potential advantages for use in laser therapy of cardiovascular disease.

Excimer lasers are pulsed gas lasers that use a mixture of a rare gas and halogen as the active medium to generate pulses of short wavelength, high energy ultraviolet light. A krypton-fluoride gas mixture was used to achieve an excimer emission at a wavelength of 248 nm. A total of 30 atherosclerotic coronary artery segments were irradiated over a range of pulse energies (250 to 750 mJ), repetition rates (2 to 25 Hz), average powers (1.9 to 18.8 watts) and cumulative exposures (3 to 12 seconds). In no case was there gross, light microscopic or ultrastructural evidence of the pathologic injury typically associated with continuous wave laser irradiation of coronary artery segments. Similar results were achieved after excimer laser irradiation of 30 samples of myocardium. Excimer irradiation of calcified aortic valve leaflets accomplished focal debridement without pathologic tissue injury; when total debridement was attempted, however, gross charring was observed. The paucity of pathologic alterations observed after excimer irradiation of cardiovascular tissue may prove beneficial in precisely controlling laser ablation of pathologic tissue without injury to the surrounding normal tissue. Clinical application of excimer laser irradiation requires resolution of several issues, including the development of suitable fiber optics and laser coupling, evaluation of potential ultraviolet toxicity, and demonstration that ultraviolet light can be transmitted through a blood-filled system.

Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial.

OBJECTIVES: This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction. BACKGROUND: APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown. METHODS: We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome. RESULTS: APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users. CONCLUSIONS: In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.

Use of pulsed energy delivery to minimize tissue injury resulting from carbon dioxide laser irradiation of cardiovascular tissues.

The carbon dioxide (CO2) laser has been utilized for preliminary intraoperative cardiovascular applications, including coronary endarterectomy and ventricular endocardiectomy. CO2 lasers used for these applications have been operated in the continuous wave, chopped or pulsed mode at low peak powers. To evaluate the extent of boundary tissue injury, continuous, chopped and pulsed energy delivery of CO2 laser emission was used to bore through 192 5 mm thick myocardial slices in air. Continuous, chopped and pulsed delivery at a peak power of 500 W or less failed to eliminate light microscopic or ultrastructural signs of thermal injury. Only when a high energy CO2 laser (pulse energy 80 to 300 mJ, pulse duration 1 microseconds) was used at a peak power greater than 80 kW were all signs of thermal injury eliminated; furthermore, high peak power prevented thermal injury only when the beam was focused to achieve a peak power density greater than 60 kW/mm2. Under these conditions, pathologic findings were identical to those observed using excimer wavelengths. The results of these experiments indicate that: conventional CO2 lasers fail to minimize boundary tissue injury, elimination of thermal injury during intraoperative laser ablation requires that CO2 laser energy be focused to achieve a peak power density greater than 60 kW/mm2, and elimination of thermal injury can be achieved at a variety of wavelengths, provided that an appropriate energy profile is employed.

Familial lipoprotein disorders and premature coronary artery disease.

Significant risk factors for premature coronary heart disease include: (1) family history, (2) elevated low density lipoprotein (LDL) cholesterol level > or = 160 mg/dl, l, (3) decreased high density lipoprotein (HDL) cholesterol level < 35 mg/dl, l, (4) cigarette smoking, (5) high blood pressure and (6) diabetes mellitus. All of these risk factors are common in patients with premature heart disease. Common familial lipid disorders associated with premature heart disease include familial lipoprotein(a) excess, familial dyslipidemia (elevated triglycerides and decreased HDL cholesterol), familial combined hyperlipidemia (elevations of LDL cholesterol and triglycerides, and often decreased HDL cholesterol), familial hypoapobetalipoproteinemia (elevated apolipoprotein B levels), familial hypoalphalipoproteinemia (low HDL cholesterol levels), and familial hypercholesterolemia (elevated LDL cholesterol levels). All these disorders have been characterized using age and gender specific 90th and 10th percentile values from the normal population. The diagnosis and potential management of these disorders is reviewed.

The MspI restriction fragment length polymorphism 3' to the apolipoprotein A-II gene: relationships with lipids, apolipoproteins, and premature coronary artery disease.

In previous studies, a restriction fragment length polymorphism (RFLP) has been identified using MspI restriction endonuclease in the 3' region of the apo A-II gene. The rare variant site for this MspI (M2) has been reported to be associated with higher levels of HDL cholesterol and apo A-II. We have studied the frequency and lipid associations of this RFLP in a population of 168 coronary artery disease (CAD) male and female patients, who had more than 50% narrowing of one or more arteries prior to age 60 years, as well as 255 aged-matched males and females from the Framingham Offspring Study. We also studied 31 kindreds in which the proband had premature CAD. The frequency of the M2 allele was higher in CAD cases (0.20) than in the controls (0.13) (P less than 0.05). In general, those subjects carrying the M2 allele had lower HDL cholesterol and apo A-I plasma levels; however, this difference was only significant (P less than 0.02 and 0.002, respectively) in females with CAD. No cosegregation of the M2 allele with hypoalphalipoproteinemia was found in 31 kindreds studied. However, in both generations there was a trend for those subjects carrying the M2 allele to have lower HDL cholesterol levels than those carrying the M1 allele. Sequence analysis of the apo A-II gene of subjects homozygous for either the M1 (n = 1) or the M2 allele (n = 2) revealed that this RFLP is due to a T----C single base mutation 528 bp 3' to the apo A-II gene. In the subjects homozygous for the M2 allele no other mutations were found within the coding region of the apo A-II gene that could result in changes in the primary sequence of the protein. These data indicate that the MspI RFLP 3' to the apo A-II gene is somewhat more frequent in the CAD group. However, there was no significant association between this RFLP and any of the parameters examined. In conclusion, this DNA marker lacks the specificity to be clinically useful for CAD risk assessment in the population studied.

DNA polymorphisms of the apolipoprotein B gene in patients with premature coronary artery disease.

Elevated plasma levels of low density cholesterol and their major apolipoprotein (apo B) are associated with an increased risk of coronary artery disease (CAD). We have examined allele frequencies of restriction fragment length polymorphisms (RFLP) of the apo B gene in 111 male Caucasians with premature CAD (mean age 49 +/- 7 years) and in 122 elderly Caucasian males (mean age, 73 +/- 5 years), free of clinical cardiovascular disease. The rare allele (R1) of the EcoR1 RFLP in exon 29, resulting in an amino acid change (Glu----Lys4154) was seen more frequently in CAD than in controls (0.270 vs 0.207, P less than 0.05). The R1 RFLP and the MspI insertion polymorphisms (MI) within the 3' hypervariable region (HVR) were observed together in 87% and are likely in linkage disequilibrium. The MI RFLP were slightly more frequent in CAD than control (0.239 vs. 0.211, P = 0.08). A second MspI RFLP in exon 26 results in an amino acid change (Arg----Glu3611); the rare allele M2 was seen more frequently in patients than in controls (0.150 vs. 0.057, P less than 0.005). No significant differences in allele frequencies were observed for the Xba1 RFLP in exon 26 (0.500 vs. 0.529, P = ns) or for the PvuII RFLP near the 5' end (P2) (0.105 vs. 0.088, P = ns). No statistically significant differences in lipid, lipoprotein cholesterol or apolipoproteins A-I and B were observed in patients or in controls. Two of the RFLPs examined (R1 and M2) result in changes in amino acid sequence and their allele frequencies are increased in CAD cases when compared with controls. Genetic variability within the apo B gene may thus contribute to cardiovascular risk. The physiological effects of individual mutations within apo B remain to be determined. It is unlikely, however that the single site polymorphisms examined in this study, will impart further information about CAD risk than conventional lipid parameters.

Limb loss due to transvenous endocardial pacemaker therapy.

Although intravenous thrombosis frequently complicates placement of transvenous endocardial leads in patients with permanent pacemakers, clinical manifestations of upper extremity thrombosis are uncommon. Most, including upper extremity edema, cervical venous engorgement, and even superior vena cava syndrome, can be successfully managed with conservative therapy. In the patient described in the present report, clinical manifestations of pacemaker-electrode thrombosis were neither mild nor responsive to conservative therapies: in this patient, pacemaker-electrode thrombosis ultimately required amputation of the right upper extremity. Complications of the magnitude described in this patient emphasize the need for continual review of the indications for pacemaker therapy as understanding of the risk-benefit ratio of this procedure broadens.

Comparison of histamine release effects of ionic and non-ionic radiographic contrast media.

Histamine release may underline the side effects (particularly anaphylactoid) of radiographic contrast media. To study the histamine-releasing properties of radiographic contrast media, this study measured the in vitro release of histamine from human basophils incubated with diatrizoate, a standard ionic radiographic contrast agent, and with iopamidol, a newly developed non-ionic contrast agent. The basophils were separated from blood obtained from 16 patients scheduled for coronary angiography. For both diatrizoate and iopamidol, the concentration of histamine released varied as the concentration of radiographic contrast agent was increased from 0.075 M to 0.50 M. At the higher concentrations tested, the percent of histamine released by iopamidol was about half that released by diatrizoate (p less than 0.05). These data suggest that the use of non-ionic contrast media may involve less patient risk from the histamine-mediated allergic and/or hemodynamic side effects associated with radiographic contrast procedures.

Prevalence of risk factors in men with premature coronary artery disease.

The prevalence of modifiable cardiovascular risk factors (systemic hypertension, diabetes mellitus, cigarette smoking, low-density lipoprotein [LDL] cholesterol greater than or equal to 160 mg/dl and high-density lipoprotein [HDL] cholesterol less than 35 mg/dl) was determined in 321 men less than 60 years of age (mean +/- standard deviation 50 +/- 7) with premature coronary artery disease (CAD) documented at coronary angiography. The prevalence of these risk factors was markedly different than in the Framingham Offspring Study population, used here as a comparison group. In the patients with CAD, only 3% had no risk factor (other than male sex), compared with 31% in the Framingham Offspring Study subjects. Most patients with CAD (97%) had greater than or equal to 1 additional risk factor. When the patients with CAD were divided by age groups (40 to 49 years [n = 109], 50 to 59 [n = 191]), no significant differences were observed in the prevalence of risk factors between the young and older patients. The prevalence of systemic hypertension (41 vs 19%, p less than 0.001), diabetes mellitus (12 vs 1.1%, p less than 0.001), cigarette smoking (67 vs 28%, p less than 0.001) and HDL cholesterol less than 35 mg/dl (63 vs 19%, p less than 0.001) was markedly higher in the patients with CAD than in Framingham Offspring Study subjects, whereas the prevalence of LDL cholesterol greater than or equal to 160 mg/dl was not significantly different between patients with CAD and Framingham Offspring Study subjects (26 vs 26%).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic and electrophysiologic effects of pirmenol in ventricular tachycardia.

Twenty patients with ventricular tachycardia refractory to drug treatment underwent electrophysiologic study with pirmenol. Patients ranged in age from 39 to 84 years (mean 61); the presenting arrhythmia was sustained ventricular tachycardia in 15, nonsustained ventricular tachycardia in 3 and ventricular fibrillation in 2. After discontinuation of all antiarrhythmic drugs (for at least 5 half-lives) and assessment of electrocardiographic and electrophysiologic parameters in the drug-free state, patients underwent comprehensive intracardiac electrophysiologic evaluation with intravenous pirmenol (mean dose 195 +/- 46 mg). Programmed ventricular stimulation began at least 30 minutes after pirmenol infusion was started in each patient. There was significant shortening of sinus cycle length in all patients, from 746 +/- 155 to 683 +/- 107 ms (mean +/- standard deviation). In 7 patients in whom ventricular tachycardia could not be induced after intravenous pirmenol, an oral pirmenol regimen was begun. The dosage was 200 or 250 mg (both 3 times/day) in 2 and 5 patients, respectively. Seven hours after the third dose of oral drug was given, these patients underwent repeat electrophysiologic testing. Intravenous and oral pirmenol significantly prolonged the PR, QT, QTc and JT intervals compared with baseline. Intravenous pirmenol also significantly prolonged the QRS interval compared with baseline. Oral pirmenol significantly prolonged the sinus node recovery time compared with intravenous pirmenol. Intravenous pirmenol significantly increased the HV interval compared with control; oral pirmenol did not demonstrate a significant prolongation of the HV interval, but this is due to the smaller number of patients studied while taking oral drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Permanent pacemaker therapy in corrected transposition of the great arteries: analysis of site of lead placement in 40 patients.

A retrospective analysis of 58 pacemaker leads in 40 patients with corrected transposition of the great arteries (CTGA) was made to compare the function of endocardial and epicardial leads. Extensive trabeculations of the normal right ventricle are generally thought to be essential for endocardial pacemaker lead stability. Because the systemic venous ventricle in CTGA lacks an extensive trabecular network, there has been concern that transvenous lead placement may result in a high rate of dislodgement. Epicardial leads have been assumed to be more reliable in these patients. Forty-seven epicardial and 11 endocardial leads were placed in 40 patients with CTGA who required permanent pacemaker therapy for symptomatic bradycardia. Of 13 episodes of epicardial lead malfunction in 158 patient-years, 3 were due to lead fracture and 10 to high thresholds. Surgery was required to correct the lead malfunction in 12 instances and thoracotomy was necessary for new lead placement in 6 patients. During 26.2 patient-years, there were 2 episodes of endocardial lead failure due to a high acute threshold and perforation. There were no instances of endocardial lead dislodgement. No association between type of failure and lead design was noted for either endocardial or epicardial leads. Actuarial analysis of survival revealed no significant differences in reliability between endocardial and epicardial leads. Endocardial lead fixation in the systemic venous ventricle in patients with CTGA is adequate to prevent lead dislodgement and preferable to epicardial lead placement because thoracotomy is avoided.

Enhanced hepatic uptake of thallium-201 in patients with severe narrowing of the right coronary artery.

To assess the hepatic uptake of thallium-201 after exercise treadmill testing and to investigate whether hepatic uptake of thallium-201 may be a useful marker of right coronary artery (RCA) disease, 43 patients were studied: 17 with RCA disease (9 with 1-vessel disease, 8 with multivessel disease including the RCA), 8 with left coronary system disease alone, and 18 with a low probability (< 5%) of coronary disease. All subjects were studied with symptom-limited exercise and redistribution thallium-201 single-photon emission computed tomographic (SPECT) scintigraphy. Two indexes of hepatic uptake were derived: a liver-to-heart ratio after stress, and a stress-to-rest hepatic ratio. The low-probability group had a liver/heart ratio of 0.48 +/- 0.02. In the group with RCA disease alone, liver/heart ratio was 1.29 +/- 0.20 (p < 0.005 vs low-probability group). Patients with multivessel coronary artery disease involving the RCA had a ratio of 1.19 +/- 0.16 (p < 0.005 vs low-probability group), and patients with only left coronary system disease had a liver/heart ratio of 0.87 +/- 0.15 (p < 0.05 vs low-probability group). The stress/rest ratio of the low-probability group was 0.83 +/- 0.04. Patients with RCA disease alone had a stress/rest ratio of 1.49 +/- 0.25 (p < 0.05 vs low-probability group), and patients with multivessel disease involving the RCA had a stress/rest ratio of 1.16 +/- 0.08 (p < 0.005 vs low-probability group).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular inotropic effect of atrial pacing after coronary artery bypass grafting.

The effect of atrial pacing on left ventricular (LV) performance was studied in 19 patients, 24 hours after coronary artery bypass grafting (CABG). LV volumes were calculated from simultaneous radionuclide-thermodilution measurements at rest (heart rate 82 +/- 12 beats/min), 10 minutes after the start of atrial pacing (100 beats/min), and with atrial pacing plus volume loading to return preload toward baseline. Atrial pacing reduced preload as reflected by LV end-diastolic volume index (69 +/- 14 vs 60 +/- 14 ml/m2, mean +/- standard deviation) (p less than 0.0001), but returned to baseline with volume loading. Afterload, as reflected by arterial end-systolic pressure, did not change with atrial pacing (63 +/- 9 at baseline vs 64 +/- 8 mm Hg with pacing, difference not significant). Afterload increased with volume loading (68 +/- 10 mm Hg, p less than 0.025 vs baseline and pacing). LV stroke volume decreased with atrial pacing due to reduced preload, but returned to baseline with volume loading. Cardiac index increased with atrial pacing and increased further with volume loading. Compared with baseline, LV end-systolic volume index was reduced during atrial pacing both before and after volume loading, despite unchanged or augmented afterload. The combination of atrial pacing and volume loading resulted in augmentation of LV stroke work, despite no increase in preload compared with baseline. Thus, after CABG, increased (paced) heart rate augments inotropic state, as indicated by reduced LV end-systolic volume under conditions of unchanged or increased afterload, and elevated LV stroke work without an increase in preload or a decrease in afterload.