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Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated
Insights
Positive inotropic therapy in dilated cardiomyopathy (DCM) is limited by poor contractile response and increased afterload. Inadequate hypertrophy in DCM patients significantly impairs dobutamine
Area of Science:
- Cardiology
- Cardiovascular Physiology
- Pharmacology
Background:
- Dilated cardiomyopathy (DCM) presents heterogeneous hemodynamic responses to positive inotropic therapy.
- Left ventricular (LV) response to inotropes is influenced by contractile function and compensatory mechanisms.
Purpose of the Study:
- To assess LV geometry, loading conditions, and contractile state in nonischemic DCM patients.
- To compare hemodynamic responses to dobutamine between DCM subgroups with appropriate and inadequate hypertrophy.
- To investigate the relationship between LV afterload and contractility in DCM.
Main Methods:
- Simultaneous high-fidelity pressure measurements and echocardiography in 13 DCM patients and 9 healthy controls.
- DCM patients categorized into 'appropriate' (n=5) and 'inadequate' (n=8) hypertrophy groups based on LV end-diastolic wall thickness-to-dimension ratio.
- Assessment of LV afterload (circumferential end-systolic wall stress, sigma es) and contractility (rate-corrected mean velocity of fiber shortening, Vcfc) at baseline and during dobutamine infusion.
Main Results:
- Baseline LV afterload was significantly higher in both DCM groups compared to normal subjects.
- Dobutamine decreased LV afterload in normal subjects and group 1 (appropriate hypertrophy) but increased it in group 2 (inadequate hypertrophy).
- Baseline contractility was reduced in both DCM groups (61% of normal in group 1, 44% in group 2).
- Contractile response to dobutamine was attenuated in DCM patients (52% of normal in group 1, 22% in group 2).
Conclusions:
- Positive inotropic therapy with dobutamine in DCM is hampered by reduced contractile reserve and elevated LV afterload.
- Inadequate hypertrophy in DCM patients is associated with a blunted contractile response and detrimental afterload augmentation during dobutamine administration.
- LV afterload is a critical determinant of LV contractility in DCM patients.
Abstract:
Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a wide disparity in the hemodynamic responses to positive inotropic therapy. In addition, the response of the failing left ventricle to positive inotropic agents reflects the net interaction of multiple factors, including the magnitude of contractile abnormality and compensatory mechanisms. In the current study, left ventricular geometry, loading conditions, and contractile state were assessed in 13 patients with nonischemic DCM with the use of simultaneous high-fidelity pressure measurements and echocardiographic recordings. Comparisons were made with echocardiographic and calibrated carotid pulse data acquired in nine age-matched normal subjects. The patients with DCM were divided according to the left ventricular end-diastolic wall thickness-to-dimension ratio into groups with "appropriate" hypertrophy (i.e., less than or equal to 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., greater than 2 SDs from mean normal; n = 8; group 2). Age, New York Heart Association functional class, left ventricular wall mass index, and left ventricular end-diastolic pressure and dimension were similar for the DCM groups. Baseline left ventricular afterload (defined as circumferential end-systolic wall stress, sigma es) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the beta-adrenoceptor agonist dobutamine decreased left ventricular afterload by 12% in the normal subjects and by 10% in group 1 patients, while augmenting afterload by 5% in group 2 patients. The latter response occurred despite a 17% fall in systemic vascular resistance. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., sigma es). The resultant sigma es -Vcfc relationship, a sensitive measure of left ventricular contractility, was determined over a wide range of afterload conditions generated by methoxamine (normal subjects) or nitroprusside (DCM). Baseline left ventricular contractile state was 61% of normal for group 1 and 44% of normal for group 2. The contractile response to dobutamine infusion was 52% of normal for group 1 and only 22% of normal for group 2. Thus, positive inotropic therapy with dobutamine in patients with DCM is limited by (1) an attenuated contractile response and (2) elevated left ventricular afterload, which may be augmented further during its administration.(ABSTRACT TRUNCATED AT 250 WORDS)