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MDL 17,043, when administered intravenously in humans, produces a significant and salutary hemodynamic response. To determine its acute effect when administered orally (3 mg/kg), 10 patients with severe congestive heart failure were studied by right-sided cardiac catheterization for 8 hours. At 4 hours after drug ingestion, there was significant improvement in several hemodynamic measurements. Cardiac index increased 38% over baseline (from 1.9 +/- 0.4 to 2.6 +/- 0.4 liters/min/m2, p less than 0.01), arteriovenous oxygen difference decreased by 30% (from 8.0 +/- 1.4 to 5.6 +/- 1.2 vol%, p less than 0.01), heart rate increased by 8% (from 85 +/- 16 to 92 +/- 16 beats/min, p less than 0.05), stroke volume index increased by 22% (from 23 +/- 5 to 28 +/- 4 ml/beat/m2, p less than 0.05), left ventricular stroke work increased by 24% (from 18 +/- 5 to 22 +/- 5 g-m/m2, p less than 0.01), mean arterial pressure decreased by 10% (from 79 +/- 6 to 71 +/- 9 mm Hg, p less than 0.01), mean right atrial pressure decreased by 40% (from 10 +/- 5 to 6 +/- 4 mm Hg, p less than 0.01), and mean pulmonary artery wedge pressure decreased by 36% (from 22 +/- 5 to 14 +/- 6 mm Hg, p less than 0.01). Cardiac index, arteriovenous oxygen difference, mean arterial pressure, right atrial pressure, and pulmonary artery wedge pressure remained significantly improved at 8 hours. These findings indicate that MDL 17,043 is active when administered orally and produces beneficial hemodynamic effects for as long as 8 hours.

The hemodynamic and hormonal responses to dobutamine alone and with the addition of amrinone were studied in ten patients with severe heart failure. Dobutamine significantly increased heart rate, cardiac index, and stroke volume index and significantly decreased mean right atrial and systemic arterial pressures and systemic and pulmonary vascular resistance. The addition of amrinone further decreased significantly mean right atrial, pulmonary arterial, and pulmonary arterial wedge pressures and systemic vascular resistance, while heart rate rose. The response of the cardiac index was variable, increasing in seven and decreasing in three patients. Plasma renin activity rose significantly with dobutamine and further increased with amrinone. We conclude that in most patients with severe heart failure, amrinone, when combined with dobutamine, improves hemodynamics. The further increase in heart rate, variable effects on the cardiac index, and marked activation of the renin-angiotensin system suggest caution and potential limitations in the use of this combination.

Uncontrolled studies have suggested that the newer oral phosphodiesterase inhibitors milrinone and enoximone acutely improve exercise performance in patients with severe chronic cardiac failure. To determine whether an oral placebo presented as an inotropic agent could acutely enhance exercise capacity, two separate groups of stable heart failure patients were studied by serial exercise testing and respiratory gas exchange analysis. Group 1 had nine patients studied four hours after a single oral dose of placebo, and group 2 had ten patients retested after one to two weeks of placebo therapy. No significant change was seen in the mean exercise time, mean peak oxygen consumption, and the mean oxygen consumption at anaerobic threshold after placebo administration in both group 1 and group 2 patients. Improvements in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold occurred in five patients in group 1 and seven patients in group 2. The improvements exceeded the baseline variability of 10 percent in three group 1 patients. Among group 2 patients, the increase in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold exceeded 10 percent in six, four, and four patients, respectively. Thus, stable chronic heart failure patients can achieve a true baseline exercise capacity. Small improvements in exercise performance seen acutely after oral inotropic drug therapy in individual heart failure patients must be interpreted with caution, as they may be due to a placebo effect.

The absolute intensity of the first (S1), third (S3), and fourth (S4) heart sounds (in mm Hg) and the relative intensity of S4 compared with S1 were measured in 146 normal persons, aged 8 to 91 years, using an infinite time-constant, calibrated pressure mechanocardiograph applied to the chest wall with a loading pressure of 400 mm Hg. The absolute intensity of S1 (r = 0.28) and S3 (r = 0.43) decreases with age, but the absolute intensity of S4 does not increase with age (r = 0.06). Therefore, the relative intensity of S4 compared with S1 increases with age (r = 0.31). This finding may explain the increased frequency of S4 in qualitative phonocardiograms in older persons.

The efficacy of noninvasive indexes for predicting pulmonary artery wedge (PAW) pressure was reviewed in 77 patients with mitral stenosis. M-mode echocardiography and phonocardiography were used to measure the aortic valve closure-mitral valve E-point interval (A2-E) and the electrocardiographic Q wave-mitral valve closure interval (Q-C) close to the time of diagnostic cardiac catheterization. During catheterization, in 65 patients PAW pressure was measured and in 12 left atrial (LA) pressure was measured. The A2-E and Q-C intervals taken alone had only modest correlation with PAW pressure (r = -0.54 and r = 0.46, respectively). The correlation was weakest in patients with atrial fibrillation and best in sinus rhythm when heart rate variation between invasive and noninvasive studies was within +/- 5 beats. Substitution of V-wave pressure for mean PAW pressure and correction for variation in blood pressure improved the A2-E correlation (r = -0.64), as did combining the A2-E and Q-C intervals into a ratio [(Q-C)/(A2-E)] (r = 0.62). However, the best results were obtained in patients where LA pressure was measured directly (r = -0.91 for A2-E), suggesting the PAW pressure is not always an accurate reflection of LA pressure. In conclusion, many factors in addition to LA pressure affect the Q-C and A2-E intervals which, in many situations, decrease their predictive value. However, if used appropriately, these intervals may allow an estimation of PAW pressure.