ABSTRACT
Background: Pulmonary hypertension (PH) is an established risk factor in patients with heart failure (HF). However, right heart catheterisation (RHC) and vasoreactivity testing (VRT) are not routinely recommended in these patients. Methods: The primary objective of the present study was to explore the impact of VRT using sublingual glyceryl trinitrate (GTN) on transplant/ventricular assist device-free survival in HF patients with post-capillary PH. RHC parameters were correlated retrospectively with the primary outcome. Results: The cohort comprised 154 HF patients with post-capillary PH undergoing RHC with GTN-VRT at a tertiary heart failure centre. Multiple parameters were associated with survival. After adjustment for established prognosis-relevant clinical variables from the MAGGIC Score, variables with the most relevant odds ratios (OR) obtained after GTN-VRT were: calculated effective pulmonary arterial (PA) elastance (adjusted OR 2.26, 95%CI 1.30-3.92; p = 0.004), PA compliance (PAC-GTN; adjusted OR 0.45, 95%CI 0.25-0.80; p = 0.006), and total pulmonary resistance (adjusted OR 2.29, 95%CI 1.34-3.93; p = 0.003). Forest plot analysis including these three variables as well as PAC at baseline, delta PAC, and the presence of combined post- and pre-capillary PH revealed prognostic superiority of PAC-GTN, which was confirmed by Kaplan-Meier analysis. Conclusions: In our cohort of symptomatic HF patients with post-capillary PH, improved PAC after administration of GTN was associated with survival independent of established hemodynamic and clinical risk factors. VRT using GTN may be better described as unloading test due to GTN's complex effects on the circulation. This could be used for advanced prognostication and should be investigated in further studies.
ABSTRACT
OBJECTIVE: Patients with left ventricular (LV) diastolic dysfunction are characterized by exertional dyspnoea. Heart rate (HR) reduction by ß-blockers can improve exercise tolerance by prolonging LV filling, but their negative inotropic and lusitropic properties can be detrimental in this disease. We tested the effects of administering ivabradine, a HR-lowering drug without impact on cardiac kinetics that may favorably affect diastolic function. METHODS: Twenty-four patients with coronary artery disease (CAD) and normal LV ejection fraction on chronic ß-blocker therapy were included. NT-proBNP serum levels were determined prior to and after cardiopulmonary exercise. ß-Blockers were then replaced by ivabradine and patients were re-tested after 6 weeks. Patients were initially classified as having a low (E/e' ≤ 8; n = 11) or high (E/e' > 8; n = 13) LV filling index. RESULTS: E/e' significantly decreased during ivabradine therapy in patients with high E/e' (10.7 ± 2.9 vs. 8.9 ± 1.7; p < 0.01), whereas no difference occurred in patients with low E/e' (6.4 ± 0.7 vs. 6.5 ± 1.1; p = ns). With ivabradine, patients with high E/e' had an increased oxygen uptake at the anaerobic threshold (from 10.8 ± 1.4 to 11.8 ± 1.9 ml/min/kg; p < 0.05) and a steeper slope of the initial oxygen pulse curve (from 293 ± 109 to 359 ± 117 µl/beat/kg/W; p < 0.05). Moreover, patients with high E/e' had lower NT-proBNP serum levels at rest (169 ± 207 vs. 126 ± 146 pg/ml; p < 0.05) and after exercise (190 ± 256 vs. 136 ± 162 pg/ml; p < 0.05) during ivabradine therapy. CONCLUSIONS: In patients with CAD and elevated E/e', switching therapy from ß-blockers to ivabradine may cause a reduction in LV filling pressures and an improved stroke volume response to exercise.
