Author + information
- Received January 11, 1988
- Revision received May 3, 1988
- Accepted May 13, 1988
- Published online October 1, 1988.
- Daniel Kulick, MD, FACC,
- Arie Roth, MD,
- Nancy McIntosh, RN,
- Shahbudin H. Rahimtoola, MB, FRCP, FACC and
- Uri Elkayam, MD, FACC∗
- ↵∗Address for reprints: Uri Elkayam, MD, Section of Cardiology, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033.
Oral isosorbide dinitrate bas been widely used to lower elevated left ventricular filling pressure in patients with chronic heart failure. Although the recommended dose of this drug is 40 mg every 6 h, failure to respond to this dose has been observed in many patients with heart failure. In the present study the incidence of resistance to isosorbide dinitrate was evaluated and an attempt was made to identify baseline hemodynamic predictors for this phenomenon in 50 patitents with severe chronic heart failure due to left ventricular systolic dysfunction (mean left ventricular ejection fraction 0.23 ± 0.08).
Twenty-seven (54%) of the 50 patients responded to 40 mg of isosorbide dinitrate (>20% decrease in mean pulmonary artery wedge pressure sustained ≥ 1h) and 23 patients (46%) failed to respond. Nonresponders to 40 mg of isosorbide dinitrate had a significantly higher baseline right atrial pressure than did responders (14 ± 5 versus 10 ± 6 mm Hg, p < 0.02). In addition, all 7 patients with a baseline right atrial pressure of < 7 mm Hg and 12 of 14 patients with a baseline right atrial pressure < 10 mm Hg responded to 40 mg. No significant differences were noted between responders and nonresponders in any other baseline hemodynamic or clinical variables, or in peak isosorbide dinitrate serum levels (32 ± 19 ng/ml in nonresponders versus 44 ± 36 ng/ml in responders). Of the 23 nonresponders to 40 mg, 22 received a higher dose (80 to 120 mg). Ten (45%) of these patients demonstrated the desired hemodynamic response whereas 12 (55%) failed to respond to even a 120 mg dose.
It is concluded that resistance to oral isosorbide dinitrate is common in patients with severe, chronic heart failure. Response to the commonly used dose of 40 mg is seen in all patients with normal right atrial pressure. In patients with elevated right atrial pressure, hemodynamic response is unpredictable and only half of such patients respond to 40 mg whereas about a quarter of them require a higher dose (80 to 120 mg). The other quarter of patients do not respond even to 120 mg and may have to be treated with other vasodilating agents.
- Received January 11, 1988.
- Revision received May 3, 1988.
- Accepted May 13, 1988.