Increased ventricular contractility is not sufficient for effective positive inotropic intervention.

Positive inotropic intervention with dobutamine in patients with congestive heart failure is accompanied by complementary vascular changes, as measured by the aortic input impedance spectrum, that promote the efficient transfer of augmented myocardial contractile power. It is unknown whether this is a nonspecific response to increased ventricular contractility or is a function of the properties of the positive inotropic agent employed. Therefore, the influence of two different positive inotropic interventions, dobutamine and dopamine, on ventricular-vascular coupling was examined in 15 patients with congestive heart failure. Significant reductions in characteristic aortic impedance, wave reflection, and low-frequency impedance moduli were noted with dobutamine and were not seen with dopamine. Consequently, a significantly (P = 0.0008) greater increase in pulsatile, rather than steady-state, power output was noted with dopamine that was reflective of a significantly diminished efficiency of power transfer. Therefore, optimal transfer of increased ventricular contractile power in patients with congestive heart failure requires increases in large vessel compliance and complementary changes in ventriculoarterial coupling.

Determinants of longitudinal changes in spirometric function among swine confinement operators and farmers.

To assess whether working in a swine confinement facility causes an excess or accelerated decline in lung function, we conducted a population-based study to evaluate the determinants of longitudinal changes in airflow in a population of swine confinement operators. Spirometric measures of lung function were compared between swine confinement operators (N = 168) and neighborhood farmer control subjects (N = 127). Study subjects were randomly selected from a cohort of swine confinement operators in eastern Iowa. The control farming population was matched by geographic location, age, and sex to the swine confinement operators. On average, the follow-up time was approximately 2 yr, with a range of follow-up between 56 and 1,900 d. Although swine confinement operators and neighborhood farmers had similar demographic characteristics (age, gender, racial background, smoking history, and atopy status), swine confinement operators tended to have less farming experience and were more extensively followed (more measures of lung function and longer periods of observation) than the neighborhood farmer control group. Swine confinement operators were also exposed to higher environmental dust concentrations and other irritants than the farmer control subjects. Interestingly, the cross-sectional data indicated that swine confinement operators tended to have slightly lower measures of airflow and greater workshift declines in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and mid-expiratory flow (FEF25-75) than the neighborhood farmer control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinal changes in lung function among asbestos-exposed workers.

To prospectively identify the determinants of persistent or accelerated loss of lung function among workers occupationally exposed to asbestos and assess the relative contribution of cigarette smoking, asbestos-induced pleural fibrosis, and specific findings from bronchoalveolar lavage and high resolution CT scans, we examined the determinants of lung function changes in 117 subjects occupationally exposed to asbestos for at least 1 yr in a high exposure setting. A minimum of 20 yr was required between the first exposure to asbestos and entry into the study. Baseline studies included an independent assessment of dyspnea, lung volumes, diffusing capacity of carbon monoxide (DLCO), a chest radiograph, a high resolution CT (HRCT) scan, and bronchoalveolar lavage (BAL). Subjects were observed for an average of 2 yr (range, 0.5 to 4.0 yr), and lung function was measured on at least two separate occasions (mean, 4.1 separate tests). During the period of observation, there was an average 1.5% decrease in the TLC and a 2.5% decrease in the DLCO. In this longitudinal data set, after controlling for age, height, pack-years of cigarette smoking, and follow-up time, persistently lower measures of TLC were independently related to moderate to severe dyspnea (p = 0.005), diffuse pleural thickening (p = 0.007), and higher concentrations of fibronectin in BAL fluid (p = 0.01). Interstitial lung disease either on the chest radiograph or HRCT scan was not independently associated with persistently lower measures of TLC during the period of observation. However, none of the clinical variables we examined were associated with an accelerated decline in TLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of progression in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive form of lung disease with a median survival of less than 5 yr. To address the progressive nature of this disease process, we investigated the determinants of decrements in lung function in patients with IPF. We prospectively evaluated 39 subjects with IPF. Our study subjects were followed for an average of 2 yr (range, 49 to 1,883 days) and lung function was measured on at least two separate occasions (mean = 9.1 separate tests) during the follow-up period. Since IPF is characterized by reduced lung volume and abnormal gas exchange, our analysis focused on the determinants of total lung capacity (TLC) and diffusing capacity of carbon monoxide (DLCO) during the period of observation. Although, on average, there was a 5.3% increase in the TLC and a 9.8% increase in DLCO between the first and last measure of lung function, 25% of the study population experienced a decline in the TLC and 28% of the study population experienced a decline in the DLCO. Decrements in TLC were independently associated with severe dyspnea (p = 0.01) and treatment with cyclophosphamide (p = 0.03). Decrements in DLCO were significantly and independently associated with more pack-years of cigarette smoking (p = 0.02), moderate (p = 0.03) or severe (p = 0.02) dyspnea, and treatment with cyclophosphamide (p = 0.0002). These findings indicate that several clinical characteristics are independently associated with subsequent declines in TLC and DLCO in patients with IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of survival in idiopathic pulmonary fibrosis.

To identify the determinants of survival in patients with idiopathic pulmonary fibrosis (IPF), we performed a survival analysis on 74 subjects with IPF. The study subjects were on average 64 yr of age (range, 25 to 83 yr), 62% were male, and 29% were never smokers. A tissue diagnosis was made in 67 (91%) of our study subjects. These subjects were followed for a mean period of 4 yr (range, 1.4 to 118.8 months) after the onset of pulmonary symptoms. During the period of observation, 41 subjects died (median survival = 28.2 months) and 33 continue to survive (median follow-up period = 60.9 months). A univariate analysis demonstrated that diminished survival was significantly associated with male gender (hazard ratio = 1.98; 95% confidence interval [CI] = 1.01-3.85), a higher FEV1/FVC ratio (hazard ratio = 1.82 [per 10% increase in the FEV1/FVC ratio]; 95% CI = 1.21-2.73), a lower percent predicted FVC (hazard ratio = 0.74; 95% CI = 0.60-0.91), a lower percent predicted total lung capacity (TLC) (hazard ratio = 0.75; 95% CI = 0.60-0.94), a lower percent predicted diffusing capacity of carbon monoxide (DLCO) (hazard ratio = 0.69; 95% CI = 0.53-0.89), a higher ILO profusion category on chest radiograph (hazard ratio = 3.52; 95% CI = 1.58-7.87), and an enhanced release of prostaglandin E2 (PGE2) by cultured alveolar macrophages (hazard ratio = 1.32 [per 10 pm/ml of PGE2]; 95% CI = 1.07-1.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter trial of ionic versus nonionic contrast media for cardiac angiography. The Iohexol Cooperative Study.

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.

Influence of positive inotropic therapy on pulsatile hydraulic load and ventricular-vascular coupling in congestive heart failure.

The aortic input impedance spectrum provides a description of the total hydraulic load imposed on the left ventricle and may be used to assess the coupling of the ventricle to the vasculature. The adaptation of the vasculature to positive inotropic intervention was examined in 10 patients with idiopathic dilated cardiomyopathy to test the hypothesis that increased myocardial contractility is matched by complementary changes in aortic impedance that optimize ventricular-vascular coupling and maximize power transfer to the circulation. High fidelity intravascular recordings of aortic pressure and flow were obtained at baseline study and during infusion of dobutamine to derive the aortic input impedance spectrum. In eight patients in whom increased staged infusion of dobutamine resulted in a significant increase in stroke volume (22.3 +/- 14.5 ml/beat increase over baseline), the significant (p less than 0.05) increase in the maximum of the first derivative left ventricular pressure pulse (dP/dt) was accompanied by significant decreases in characteristic impedance of the aorta (138 +/- 88 to 92 +/- 44 dyne.s.cm-5) wave reflection index (238 +/- 144 to 109 +/- 59 dyne.s.cm-5), and low frequency moduli of impedance. Effective positive inotropic therapy with dobutamine in the setting of congestive heart failure is accompanied by complementary changes in the aortic impedance spectrum, which represent a matching of impedance to the increased contractile state of the ventricle and facilitation of ventricular-vascular coupling.

Prevalence of mitral valve prolapse in primary fibromyalgia: a pilot investigation.

Fifty patients with primary fibromyalgia and a negative cardiovascular symptom history underwent echocardiography to determine the prevalence of mitral valve prolapse (MVP). The mean age of the population was 40 +/- 13 years (14 men, 36 women). Mitral valve prolapse was detected in 75%; 33% with myxomatous mitral valve leaflets. The prevalence of MVP in this population is significantly higher (p less than 0.0001) than in the general population. Primary fibromyalgia and MVP may be part of a more generalized connective tissue abnormality characterized by distinct genetically determined variants.

Pulsus alternans induced by inferior vena caval occlusion in man.

To assess the effect of rapid preload reduction on left ventricular performance in nonischemic cardiomyopathy, 11 patients were studied during inferior vena caval (IVC) balloon occlusion. Five developed sustained pulsus alternans. During pulsus alternans, the strong beats demonstrated systolic performance characteristics similar to baseline values, despite a drop in both left ventricular (LV) end-diastolic diameter (66 +/- 13 to 61 +/- 13 mm; p less than 0.05) and LV end-diastolic pressure (21 +/- 8 to 9 +/- 6 mmHg; p less than 0.05). In contrast, the weak beats demonstrated a reduction in peak systolic pressure (130 +/- 36 to 109 +/- 33 mmHg; p less than 0.02), fractional shortening (20% +/- 4% to 17% +/- 9%; p less than 0.05) and peak positive dP/dt (1,006 +/- 224 to 921 +/- 287 mmHg; p less than 0.05). Measures of diastolic performance (peak negative dP/dt, the time constant of LV relaxation, the length of diastasis, and LV end-diastolic stress) were not different between baseline beats and the strong beats; and only LV end-diastolic stress differed when baseline beats were compared to the weak beats. When the strong beats were compared to the weak beats during induced pulsus alternans, significant differences were observed in peak systolic pressure, peak positive dP/dt, and fractional shortening, but no differences in any measured diastolic parameter was observed. A slight difference was noted in the left ventricular end-diastolic diameters, with the weak beat consistently beginning at a slightly smaller diameter (61 +/- 13; mm vs 59 +/- 13; p less than 0.05). In summary, these data are consistent with an augmentation and deletion of intrinsic contractile forces in association with an alternation in preload on a beat-to-beat basis as best describing left ventricular performance during pulsus alternans.

Safety and efficacy of inferior vena caval occlusion to rapidly alter ventricular loading conditions in idiopathic dilated cardiomyopathy.

To investigate the safety and efficacy of inferior vena caval (IVC) balloon occlusion for preload alteration in humans, 13 patients with dilated cardiomyopathy were studied before and during repeated (total of 78) IVC occlusions. Left and right ventricular (LV and RV) micromanometer pressures were simultaneously measured and M-mode and 2-D echocardiograms were recorded at end expiration. Complications were limited to abdominal discomfort in 2 patients. With IVC occlusion, RV collapse fluoroscopically shifted the heart toward midline and ventricular septal motion was frequently disordered. Significant (p = 0.001) changes occurred in RV and LV systolic peak pressures (from 19 +/- 6 to 12 +/- 5 mm Hg and from 129 +/- 34 to 109 +/- 25 mm Hg, respectively). LV and RV end-diastolic pressures also decreased significantly (from 18 +/- 7 to 6 +/- 6 mm Hg and from 5 +/- 3 to 2 +/- 2 mm Hg, respectively) (both p less than or equal to 0.0055). Similarly, LV end-diastolic diameter decreased 13% (from 61 +/- 11 to 53 +/- 12 mm, p = 0.0002). Mean heart rate did not change significantly (from 76 +/- 19 to 78 +/- 21 beats/min). Thus, IVC balloon occlusion provides a safe method of repeatedly altering loading conditions in humans. This approach allows for acquisition of important information regarding cardiac chamber dynamics while minimizing the effects of reflex mechanisms and avoiding use of pharmacologic agents.