Abstract 12880: A Clinical Index of Myocardial Afterload Can Replace Wall Stress Calculations

Introduction: Afterload at the myocardial level is a principal determinant of LV chamber and myocardial wall function, generated by interplay of LV pressure, volume, and mass. Quantitation has relied on wall stress indices which require additional measurements and calculations as well as incorrect assumptions. Unfamiliar to most clinicians, they have largely fallen out of use, but the role of myocardial afterload in contemporary heart failure pathophysiology and therapy merits reevaluation given the roles of EF and myocardial strains in prognostic indices and treatment guidelines. Hypothesis: A simple clinical afterload index using variables fundamental to wall stress indices (systolic pressure(mmHg) * LV volume(ml))/LV mass(g)) or PV/M correlates closely with stress indices and relates similarly to LV EF and myocardial strains. Methods: In 277 normals (54% female, mean age 50.9±12.9 yrs) and small cohorts with dilated non-ischemic cardiomyopathy(35), aortic stenosis(12) and cancer chemotherapy(43), each with matched controls, we used CMR LV volumes, mass and brachial systolic pressure during imaging to compare end-systolic PV/M to stress indices and systolic pressure alone using correlations and correlation standard errors(SEs). Results: There were extremely close correlations (r= 0.97-0.99, all p< 0.001) with minimal SEs between PV/M and Arts and Alters stress indices with similar slopes in all groups and in normal subgroups by age and gender. Negative correlations with EF, global strains and strain rates were also present and extremely similar in all groups. But Mirsky’s stress index and brachial pressure performed less well. Conclusions: A simple clinical afterload index correlates closely with wall stress indices and similarly with LV ejection fraction and strains. It can support efficient reassessment of the role of afterload at the myocardial level in research and potentially, in clinical practice.

P5289Myocardial deformation after ST-elevation infarction measured by CMR feature tracking strain

Background Left ventricular (LV) functional assessment is of imminent value after ST-elevation infarction (STEMI). LV longitudinal strain (LS) evaluates ventricular function on a myocardial level. Feature Tracking (FT) assesses strain from cine cardiac magnetic resonance (CMR) images. It is unknown how LV FT Regional LS (RLS) and Global LS (GLS) changes between the sub-acute and chronic phase after STEMI compared to controls and how GLS and RLS are related to culprit vessel (LAD, LCX or RCA) and infarction size (IS). Aims To assess 1) GLS with FT after 2–6 days (sub-acute) and 6 months (chronic phase) after STEMI compared with controls, 2) if GLS changes between sub-acute and chronic phase, and 3) the relationship between GLS and RLS to IS and infarct location. Methods and results Seventy-seven patients underwent CMR 2–6 days and 6 months after STEMI as well as 27 healthy controls. GLS was impaired at the sub-acute (−8.9±2.3%) and chronic phase (−14.3±2.9%) compared to controls (−18.4±2.4%; p<0.001 for both). GLS improved between the sub-acute and chronic phase (p<0.001). GLS correlated to IS (R=0.47 sub-acute; 0.49 chronic, p<0.001). LAD infarctions had lowest GLS and largest IS. RLS was more impaired in the culprit vessel territory compared to remote. RLS in the RCA region was lower for LAD than RCA infarctions. RLS was impaired in all 6 wall-regions in LAD infarctions, while LCX and RCA infarctions had preserved RLS in remote myocardium. Global Longitudinal Strain (GLS) Conclusion GLS is impaired after STEMI and improves, but do not normalize, to the chronic phase. GLS is only moderately correlated to IS, indicating that other factors and co-morbidities are important to determine ventricular function. Even though RLS is most impaired in the affected region, remote regions can be substantially impaired in LAD-infarctions, why it would be difficult to pinpoint the culprit vessel based on RLS.

Dyslipidemias and Microcirculation

Dyslipidemia is widely accepted as one of the major risk factors in cardiovascular disease mainly due to its contribution in the pathogenesis of atherosclerosis in medium-sized and large arteries. However, it has become increasingly accepted that high-cholesterol levels can also adversely affect the microvasculature prior to the development of overt atherosclerosis. Moreover, hypercholesterolemia has shown, in preclinical animal models, to exert detrimental effects beyond the vascular tree leading to larger infarcts and adverse cardiac remodeling post-myocardial infarction. At a functional level, hypercholesterolemia has shown to impair endotheliumdependent vasodilation because on defects on nitric oxide bioavailability. The pathogenic mechanisms underlying microvascular dysfunction involve an enhanced arginase activity, enhanced production of free radicals and the activation, recruitment and accumulation of leukocytes, primarily neutrophils, via their diffusion through postcapillary venules. In turn, recruited inflammatory cells and certain inflammatory mediators enhance platelet adhesion, overall inducing a proinflammatory and prothrombotic phenotype. Within the present review, we aim to discuss the existing evidence regarding the presence of dyslipidemia - particularly high low density lipoprotein-cholesterol levels - and the occurrence of microvascular dysfunction, the mechanism by which high cholesterol levels induce functional alterations in the microvascular bed and, finally comment on the impact of dislipidemia-induced microvascular dysfunction at the myocardial level.

The effect of the level of total sodium deposited in the myocardium on its stiffness

Aim. To determine a relationship between the level of total sodium in the myocardium to its stiffness. Subjects and methods. The investigation enrolled 18 hypertensive patients who had suddenly died; their mean age was 40±10 years; mean waist circumference, 102±12.5 cm; height, 170±7.7 cm; myocardial mass, 319±53 g. Results. The variation in the myocardial level of total sodium averaged 211.7±37.5 (min, 71.5; max, 226.17) mmol/l. The sodium level was ascertained to be affected to the greatest extent by myocardial mass (SS=3615.56; p=0.00029) and age at death (SS=1965.568; p=0.0029), whereas gender and smoking had a considerably lower impact (SS=778.584; p=0.03). A univariate regression analysis showed that there was a relationship between myocardial sodium levels and the thickness of the anterior wall of the left ventricle (β=0.94; p=0.000001; r2=0.88), that of the anterior wall of the right ventricle (β=0.82; p=0.000021; r2=0.66), and that of the interventricular septum (β=0.94; p=0.000001; r2=0.89). The wall thickness of the myocardium was established to depend on its sodium level (SS=21813.89; p=0.000001; r2=0.88): the higher sodium amount in the myocardium, the thicker its walls. The average velocity of acoustic wave propagation was 6.24±0.51 m/sec. A significant correlation was observed between sodium concentrations in the myocardium and its stiffness (β=0.72; p=0.00062; r2=0.49). Conclusion. The level of sodium deposited in the myocardium, which is directly related to dietary sodium intake, is significantly correlated with myocardial stiffness. It can be assumed that the elevated level of sodium deposited in the myocardium is an independent factor that changes the stiffness of the myocardium and appears to influence the development of its diastolic dysfunction.

The apelin-APJ system in the evolution of heart failure

Heart failure is a chronic, progressive disease in which the overexpression of biologically active molecules and neurohomonal activation are the key factors of the evolution and natural history. The apelin-APJ system is a newly discovered molecular pathway and the RAAS counterbalance is its principal effect. The apelin is a potent inotrope, vasodilator and diuretic with crucial cardioprotective effects against angiotensin and aldosterone injuries. Intense and prolonged RAAS induces the downregulation of the apelin and its receptor at myocardial level and cancels their protection. Compared to the vasoactive agents used in the treatment of acute heart failure, exogen apelin has unique intropic and vasodilatory effects without deleterious consequences, being a promising therapeutic option.