No abstract

Measurement of stroke volume by pulsed Doppler echocardiography has not been validated against a reference method in vivo. We compared Doppler systolic frequency shift integrals with electromagnetic flowmeter stroke volume in seven open-chest dogs. A pulsed Doppler echocardiographic transducer was held on the aortic arch with the sample volume in the ascending aorta. Stroke volume was varied by epinephrine or pentobarbital infusions, fluid administration or inferior vena caval construction. Linear regression analysis of stroke volume vs Doppler systolic frequency shift integrals revealed strong correlations and intercepts close to zero (tau = 0.74-0.096, rho less than 0.001). Minor changes in transducer position did not influence Doppler frequency shift integrals substantially. Therefore, pulsed Doppler echocardiography served as an excellent measurement of stroke volume changes in model. However, serious limitations are presented that may limit its clinical application.

Background. Angiotensin converting enzyme inhibitors, diuretics, and digoxin are each effective in treating congestive heart failure, but many patients remain symptom-limited on all three medications. This trial was designed to determine whether the addition of oral flosequinan, a new direct-acting arterial and venous vasodilator with possible dose-dependent positive inotropic effects, improves exercise tolerance and quality of life in such patients.Methods and Results. In a randomized, double-blind multicenter trial, 322 patients with predominantly

Although atrial synchronous and rate-responsive ventricular pacing have been compared, the importance of maintaining synchronized atrial systole in addition to rate responsiveness has been incompletely defined. That is, the effects of these two pacing modes on cardiac volumes and contractility have not been studied. Accordingly, 16 patients with normal ventricular function were studied while in the upright position and at rest with gated radionuclide ventriculography during both atrial synchronous and ventricular pacing. Twelve of these patients were also studied during low-level upright exercise (300 kilopond-meters). Rest and exercise ventricular pacing heart rates were matched to those recorded with synchronous pacing. Ventricular volumes were determined with a counts-based method. The ejection fraction and peak systolic pressure/end-systolic volume ratio were used as measures of contracility. At rest there were no significant differences in either volumes or contractility between the two pacing modes. However, during exercise to identical heart rates, blood pressures, and workloads, although stroke volume was the same during exercise with atrial synchronous and ventricular pacing (78 + 13 vs 75 12 ml), end-diastolic and end-systolic volumes were lower with ventricular pacing than with atrial synchronous pacing (end-diastolic volume 101 13 vs 113 + 16 ml, p < .001; end-systolic volume 26 ± 4 vs 35 ± 7 ml, p < .001). Stroke volume during ventricular paced exercise was maintained at atrial synchronous pacing levels by means of increased contractility (ejection fraction of 74 4% during ventricular pacing vs 69 5% during atrial synchronous pacing, p = .002; peak systolic pressure/end-systolic volume ratio of 6.51 + 1 during ventricular pacing vs 4.85 + 1 during atrial synchronous pacing, p < .001). Thus, during upright bicycle exercise to workloads corresponding to those of usual daily activities, rate-responsive atrial synchronous pacing results in enhanced ventricular filling and spares contractile reserve when compared with rate-responsive ventricular pacing. Circulation 72, No. 5, 1037No. 5, -1043No. 5, , 1985

#4104 Background: Dose dense (dd) q2wk AC-paclitaxel (P) is superior to q3wk AC-P. Both regimens are associated with a &lt;1% incidence of CHF. In MBC, q3wk nanoparticle albumin-bound paclitaxel (nab-P) is superior to q3wk P and bevacizumab (B) improves progression-free survival when added to P. Based on the MBC data, B may be more effective when targeting minimal residual disease in the adjuvant setting and nab-P may offer superior efficacy with reduced toxicity. However, it is uncertain whether AC plus B increases the risk of CHF. We evaluated the cardiac safety of ddAC-nab-P with concurrent B as adjuvant therapy for BC.&#x2028; Methods: Based upon the accepted cardiac event (CE) rate of approximately 4% in trials with adjuvant trastuzumab, this study was designed with similar monitoring and tolerability thresholds. The primary endpoint is cardiac safety: symptomatic CHF or death from LV dysfunction. Secondary endpoints are toxicity, DFS, OS, and biomarkers for efficacy and toxicity. Eligible pts have resected HER2(-) BC and normal LVEF. B is administered concurrently (10 mg/kg IV q2wk x 8) with chemotherapy (AC at 60/600 mg/m2 q2wk x 4 then nab-P at 260 mg/m2 q2wk x 4) and continues at 15 mg/kg q3wk thereafter for a total one year of B therapy. Pegfilgrastim is administered Day 2 of each chemotherapy cycle. Radiation and endocrine therapy are administered per standard of care. MUGAs are obtained at baseline and mos 2, 6, 9 and 18. Although asymptomatic LVEF declines are not considered CEs, B may be held per protocol and long-term cardiac monitoring initiated. If 3 CEs or &gt; 1 cardiac death from LV dysfunction occur, B + ddAC-nab-P will not be considered safe.&#x2028; Results: The target accrual of 80 pts has been met. Median age is 47y (27-75). As of May 31, 2008, median follow-up is 14 mo (1-21) and 51 pts have completed 1y of planned therapy. No patients have developed symptomatic LV dysfunction at any point during study therapy. Sixteen pts have discontinued treatment due to toxicity: asymptomatic LVEF decline (N=3), hypertension (N=3), wound healing (N=3), headache (N=2), sensory neuropathy (N=2), pain (N=1), hypersensitivity reaction (N=1), and pneumonitis (N=1). Three pts had disease progression, and 8 pts withdrew consent.&#x2028; &#x2028; Conclusions: At the time of this analysis, no symptomatic LV dysfunction has been observed with B + ddAC-nab-P. Follow-up is ongoing. Correlative studies, including analysis of troponin, renin, and circulating endothelial and tumor cells, are underway. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4104.