Echocardiographic and biochemical evaluation of the development and progression of carcinoid heart disease.

OBJECTIVES: To study the applicability of a newly developed echocardiographic scoring system in the assessment of carcinoid valvular heart disease. BACKGROUND: We investigated prospectively the development, progression and regression of carcinoid valvular heart disease in patients with carcinoid syndrome by serial echocardiography, correlating these features with urinary 5-HIAA levels and clinical data collected during therapy with somatostatin analog. METHODS: Twenty-three patients with carcinoid syndrome underwent serial echocardiographic examinations. An echocardiographic carcinoid valvular heart disease (CVHD) % score was determined from points assigned for tricuspid and pulmonary valve structure and function. RESULTS: Fifteen patients had no CVHD at study entry (group 1), while 8 patients had findings of CVHD (group 2). Five patients in group q developed new CVHD (1B), while one demonstrated progression of CVHD (2B). The remaining patients did not develop (1A) or had no progression of CVHD (2B). Despite major declines in 5-HIAA levels during therapy in most patients, CVHD did not regress. There were significantly lower levels of median baseline 5-HIAA (98.8 vs. 256 mg/24 h), posttreatment 5-HIAA (50.3 vs. 324 mg/24 h) and posttreatment 5-HIAA time integral (37.3 vs. 192 g/24 h* days) in group A vs. B (p < 0.05). However, only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD by multiple step-wise regression analysis (p < 0.005), with a threshold observed in the 100 mg/24 h range. CONCLUSIONS: We designed a new echocardiographic scoring system to evaluate CVHD. Correlating echocardiographic scores with biochemical and clinical markers showed that only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD. This study strengthens the association between serotonin secretion and CVHD, as well as introducing a new technique for serial follow-up of these patients.

Mechanical characteristics of tachycardia-induced left-ventricular failure as evaluated in isolated dog hearts.

Left ventricles of control dog hearts and dog hearts failing due to chronic tachycardia were examined in vivo by echocardiography for systolic function and size, then subsequently studied with an isolated-heart system (artificial perfusion, artificial loading). During 3 weeks of tachycardia (250 bt/min), area ejection fraction fell by 58%, while end-diastolic transverse area increased by 56% (measurements at 120 bt/min). Judging from post-perfusion left-ventricular weights, the dilation occurred with no hypertrophy, raising the question whether the failure model may be associated with anabolic dysfunction. End-diastolic pressure-volume (P-V) relations occurred at higher volumes in failing chambers than in controls, and this was marked by increases in two indices of chamber size (candidate reference volumes): the volume resulting in a diastolic stress of 16 g/cm2, and the volume at which the nearly straight, low-stiffness segment of the end-diastolic P-V relation meets the upward bending, high-stiffness segment. Developed P-V relations of failing chambers were shifted to higher volumes and to lower pressures, the lower pressures being due more to reduced stress-developing ability (contractility) than to reduced wall/cavity ratio (pressure/stress ratio). On average, shortening ability (normalized difference between reference volume and extrapolated volume-axis intercept, i.e., apparent ejection fraction from reference volume in absence of afterload) was not different from that of controls. Isovolumic pressure waves of the failing and dilated chambers were of almost normal duration and shape, extending further the range of conditions where isovolumic pressure can be predicted by fitting a model isovolumic wave function to the isovolumic phases of ejecting beats.

Initiation of ventricular extrasystoles by myocardial stretch in chronically dilated and failing canine left ventricle.

BACKGROUND: Stretch-induced arrhythmias (SIAs) can be elicited in normal canine left ventricles by transient diastolic dilatation. Since clinically important ventricular arrhythmias arise most commonly in failing and dilated ventricles, we hypothesized that the arrhythmogenic effect of transient diastolic stretch would be enhanced in chronically dilated failing canine hearts. METHODS AND RESULTS: Heart failure was induced in seven dogs by right ventricular pacing at 250 min-1 for 20.2 +/- 1.6 days. Left ventricular (LV) mechanical properties were measured in vivo with serial echocardiograms in these seven dogs with the dogs awake and tranquilized to confirm the development of LV dilation and failure. By the third week of pacing, average short-axis area ejection fraction decreased by 64.3% (P < .001) as end-diastolic and end-systolic diameters increased by 25.9% and 50.7%, respectively (P < .001). After heart failure was established, the hearts were harvested and in vitro data were obtained as an isolated, blood-perfused ventricle preparation. A computerized servo pump system connected to an LV intracavitary balloon was used to measure and control LV volume. Results were compared with in vitro data obtained from eight ventricles not subjected to pacing (controls). LV contractility, quantitated in vitro as the slope of the peak isovolumic pressure-volume relation (Emax) normalized to LV cavity size, was much lower in the heart failure group than in controls (182 +/- 18 versus 365 +/- 38 mm Hg, P < .001). In all isolated hearts, SIAs were induced using an electromechanical stimulation protocol in which eight paced beats at 2 Hz were followed by a transient increase in LV volume during early diastole. Prestretch volume (Vi) was selected to yield end-diastolic pressures of 4 to 8 mm Hg in all hearts. The fractional increase in LV volume (delta V) that produced SIAs 50% of the time (delta V 50/Vi) was smaller in failing hearts than in controls (0.78 +/- 0.04 versus 1.18 +/- 0.17, P = .009), indicating an increased sensitivity to SIAs in the failing hearts. Although ventricular pairs were occasionally induced in both groups, the great majority of the arrhythmias induced in both groups were single extrasystoles, and nonsustained runs of ventricular tachycardia were never elicited in either group. LV end-diastolic and peak stretch pressures were similar in the two groups, but LV end-diastolic wall stress was higher by 35.7% (P = .029) in the dilated failing ventricles because LV hypertrophy, which tends to normalize wall stress as the heart dilates, did not occur during the 3 weeks of pacing. For stretch stimuli of comparable arrhythmogenic effectiveness, peak LV wall stress during stretch was similar in the two groups, whereas the fractional increase in volume was significantly smaller in the heart failure group, indicating impaired viscoelastic properties in the failing ventricles. In five control ventricles, acute exposure to 0.5 mumol/L dobutamine increased ventricular sensitivity to the induction of SIAs, as shown by a decrease in delta V50/Vi from 1.27 +/- 0.16 to 1.06 +/- 0.11 (P = .04). CONCLUSIONS: Altered mechanical properties and/or neurohumoral adaptations associated with chronic dilation and failure predispose the ventricle to induction of ventricular extrasystoles by transient LV diastolic stretch.

Vancomycin entry into lung lymph in sheep.

The distribution of antibiotics into target tissues is a crucial factor in therapeutic efficacy. To estimate the availability of systemically administered vancomycin to the interstitial fluid in the lung, we have used a sheep model with a chronic pulmonary lymph fistula to collect simultaneously series of plasma and pulmonary lymph specimens during a 6-h period after an intravenous dose of vancomycin (7 mg/kg). After a minor delay in transit from blood to lymph, vancomycin was completely distributed to pulmonary lymph with a ratio of free drug in lymph to free drug in plasma of 0.9. This suggests that vancomycin is an excellent choice for treating pulmonary infections by susceptible organisms.