Cardiovascular autonomic neuropathy contributes to left ventricular diastolic dysfunction in subjects with Type 2 diabetes and impaired glucose tolerance undergoing coronary angiography.

AIMS: Left ventricular diastolic dysfunction is considered a precursor of diabetic cardiomyopathy, while diabetic cardiovascular autonomic neuropathy is associated with an increased risk of mortality. This study aimed to evaluate the association between left ventricular diastolic dysfunction and cardiovascular autonomic neuropathy, both diagnosed according to the current guidelines. METHODS: We evaluated 145 patients referred for an elective coronary angiography, 52 of whom had Type 2 diabetes and 48 had impaired glucose tolerance, while 45 subjects had normal glucose tolerance. Cardiovascular autonomic neuropathy was diagnosed using autonomic function tests, while left ventricular diastolic dysfunction was verified by tissue Doppler imaging echocardiography. RESULTS: Cardiovascular autonomic neuropathy was diagnosed in 15 (28.8%) patients with Type 2 diabetes and in six (12.5%) individuals with impaired glucose tolerance. The rates of left ventricular diastolic dysfunction were 81 and 33% in patients with and without cardiovascular autonomic neuropathy, respectively (P < 0.001). In the cardiovascular autonomic neuropathy group (n = 21), early diastolic relaxation velocity (Em) was significantly reduced (5.4 ± 0.9 vs. 7.3 ± 2.1 cm/s; P < 0.001) and the E/Em ratio was significantly higher (13.6 ± 4.6 vs. 10.3 ± 3.4 cm/s, P < 0.001) as compared with the group without cardiovascular autonomic neuropathy (n = 79). These findings remained significant after adjustment for age, sex, coronary artery disease, hypertension and HbA(1c) . A severe form of left ventricular diastolic dysfunction was observed in 33 and 15% of patients with and without cardiovascular autonomic neuropathy, respectively (P = 0.001). CONCLUSION: Cardiovascular autonomic neuropathy is associated with a higher prevalence and a more severe form of left ventricular diastolic dysfunction in patients with diabetes or impaired glucose tolerance undergoing coronary angiography. Because both cardiovascular autonomic neuropathy and left ventricular diastolic dysfunction are associated with increased cardiovascular morbidity and mortality, screening for patients with left ventricular diastolic dysfunction and cardiovascular autonomic neuropathy with diabetes or impaired glucose tolerance may identify those at high risk.

Existence of the Frank-Starling mechanism in the failing human heart. Investigations on the organ, tissue, and sarcomere levels.

BACKGROUND: The Frank-Starling mechanism is one of the most important physiological principles for regulation of contractile performance. We therefore studied the question of whether this mechanism may be absent or attenuated in end-stage failing human left ventricular myocardium. METHODS AND RESULTS: Different methodological approaches were used to analyze the effects of this mechanism on the organ, tissue, and sarcomere levels: (1) In excised human whole left ventricles (2 donor hearts, 5 failing hearts), diastolic and systolic pressure-volume relationships were obtained. (2) In isolated muscle strip preparations from the left ventricular wall of donor hearts (n = 14) and failing hearts from patients with idiopathic dilated cardiomyopathy (n = 21) and ischemic cardiomyopathy (n = 11), peak developed force was measured at different muscle lengths of the preparation. (3) Skinned fiber preparations were obtained from failing right and left ventricles (n = 12). In all three studies, we clearly observed the existence of the Frank-Starling mechanism: (1) In isolated failing human left ventricles, peak developed isometric pressure is increased when the preload is elevated. (2) Peak developed tension is increased by approximately 50% to 70% (P < .01) in left ventricular preparations of failing and nonfailing ventricles when the muscles are stretched from 90% to 100% optimum length. (3) An increase in sarcomere length leads to a sensitization of contractile proteins of ventricular skinned fiber preparations from failing human hearts. At 1.9-microns sarcomere length, the EC50 value was 5.56 +/- 0.06, and at 2.3 microns it was 5.70 +/- 0.05 (P < .01; n = 7). CONCLUSIONS: The Frank-Starling mechanism is maintained in end-stage failing human hearts, whereas significant alterations of diastolic myocardial distensibility are evident in chronic heart failure.