Enoximone echocardiography: a novel test to evaluate left ventricular contractile reserve in patients with heart failure on chronic beta-blocker therapy

BACKGROUND: It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. METHODS: We studied 26 patients (21 males and five females) with a mean age of 58 ± 10 years: 11 were not receiving beta-blockers (noBB group); 15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of 1.5 mg/kg. RESULTS: The ejection fraction in the noBB group increased by 9% with dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by 6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic velocities were evaluated by means of tissue Doppler imaging in four basal and four medium level segments. In the noBB group, they increased more with dobutamine than with enoximone in three of the eight segments; no significant differences were found in the BB group. Dobutamine induced non-sustained ventricular tachycardia in three patients and supraventricular tachycardia in one, whereas enoximone did not induce any repetitive arrhythmias. CONCLUSIONS: Enoximone might be preferable to low-dose dobutamine for evaluating left ventricular contractile reserve in chronically beta-blocked heart failure patients as it is slightly more potent and has a better safety profile

Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure

<p>Abstract</p> <p>Introduction</p> <p>Inotropes are associated with adverse outcomes in heart failure (HF), raising concern they may accelerate myocardial injury. Whether biomarkers of myocardial necrosis, inflammation and apoptosis change in response to acute milrinone administration is not well established.</p> <p>Methods</p> <p>Ten patients with severe HF and reduced cardiac output who were to receive milrinone were studied. Blood samples were taken just before initiation of milrinone and after 24 hours of infusion. Dosing was at the discretion of the patient's attending physician (range 0.25–0.5 mcg/kg/min). Plasma measurements of troponin, myoglobin, N-terminal-pro-BNP, interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand were performed at both time points.</p> <p>Results</p> <p>Troponin was elevated at baseline in all patients (mean 0.1259 ± 0.17 ng/ml), but there was no significant change after 24 hours of milrinone (mean 0.1345 ± 0.16 ng/ml, p = 0.44). There were significant improvements in interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand (all p < 0.05) indicative of reduced inflammatory and apoptotic signaling compared to baseline.</p> <p>Conclusion</p> <p>In conclusion, among patients with severe HF and low cardiac output, ongoing myocardial injury is common, and initiation of milrinone did not result in exacerbation of myocardial injury but instead was associated with salutary effects on other biomarkers.</p

Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals

BACKGROUND: The appropriate evaluation of atrial electrical function is only possible by means of invasive electrophysiology techniques, which are expensive and therefore not suitable for widespread use. Mechanical atrial function is mainly determined from atrial volumes and volume-derived indices that are load-dependent, time-consuming and difficult to reproduce because they are observer-dependent. AIMS: To assess the feasibility of tissue velocity echocardiography (TVE) to evaluate atrial electromechanical function in young, healthy volunteers. SUBJECTS AND METHODS: We studied 37 healthy individuals: 28 men and nine women with a mean age of 29 years (range 20–47). Standard two-dimensional (2-D) and Doppler echocardiograms with superimposed TVE images were performed. Standard echocardiographic images were digitized during three consecutive cardiac cycles in cine-loop format for off-line analysis. Several indices of regional atrial electrical and mechanical function were derived from both 2-D and TVE modalities. RESULTS: Some TVE-derived variables indirectly reflected the atrial electrical activation that follows the known activation process as revealed by invasive electrophysiology. Regionally, the atrium shows an upward movement of its walls at the region near the atrio-ventricular ring with a reduction of this movement towards the upper levels of the atrial walls. The atrial mechanical function as assessed by several TVE-derived indices was quite similar in all left atrium (LA) walls. However, all such indices were higher in the right (RA) than the LA. There were no correlations between the 2-D- and TVE-derived variables expressing atrial mechanical function. Values of measurement error and repeatability were good for atrial mechanical function, but only acceptable for atrial electrical function. CONCLUSION: TVE may provide a simple, easy to obtain, reproducible, repeatable and potentially clinically useful tool for quantifying atrial electromechanical function

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research

Decreased vasomotor effect of endothelin on the coronary arteries during angioplasty in hypertensive patients

To investigate if the response of the contralateral artery during coronary angioplasty (PTCA) is different in hypertensive than in normotensive patients and whether this response is related to plasma levels of endothelin-1 (ET-1). We examined the change in ET-1 plasma levels and the reactivity of the left circumflex artery (LCx) during PTCA of the left anterior descending branch in 10 hypertensive and 23 normotensive patients. Peripheral vein blood samples were drawn for ET-1 estimation at baseline, after the end of the first balloon inflation, at the end of PTCA, and 4 h later. Angiograms of the LCx were obtained at baseline and during the 1(st) balloon inflation. The ET-1 level in hypertensives increased from 6.81 +/- 3.76 at baseline to 7.54 +/- 4.76 pmol/l (P = n.s.) at the end of PTCA, while in normotensives it increased from 8.21 +/- 3.73 to 11.56 +/- 5.04 pmol/l (F = 7.48, P = 0.0002) respectively. The LCx distal segment diameter increased from 1.29 to 1.50 mm during balloon inflation in hypertensives, and from 1.44 to 1.53 mm (F = 5.03, P = 0.03) in normotensives. The diameter increase was related to the baseline ET-1 level (r = -0.67, P = 0.005) in the normotensives, but not in the hypertensives. Thus, ET-1 has a weaker vasomotion effect on the coronary vasculature in hypertensives than in normotensives during PTCA