The rat infarct model is widely used in heart failure research, but few echocardiographic indexes of left ventricular (LV) function are validated in this model. Accordingly, the objective of this study was to validate a 13-segment LV wall motion score index (WMSI) and the myocardial performance index (MPI) in infarcted rats. Twenty-nine male Wistar rats underwent left coronary artery ligation or sham operation and were evaluated with two-dimensional and Doppler flow echocardiography 8 wk later. After echocardiography, invasive indexes were obtained using a high-fidelity catheter. WMSI and MPI were correlated with the invasive and noninvasive measurements of LV function. WMSI and MPI significantly correlated directly with end-diastolic pressure (r=0.72 and 0.42 for WMSI and MPI, respectively) and the time constant of isovolumic relaxation (r=0.68 and 0.48) and inversely with peak rate of rise of LV pressure (+dP/dt; r=-0.68 and -0.50), peak rate of decline in LV pressure (r=-0.57 and -0.44), LV developed pressure (r=-0.58 and -0.42), area fractional shortening (r=-0.85 and -0.53), and cardiac index (r=-0.74 and -0.74). Stepwise linear regression analyses revealed that LV end-diastolic pressure, +dP/dt, area fractional shortening, and cardiac index were independent determinants of WMSI (r=0.994) and that cardiac index and +dP/dt were independent determinants of MPI (r=0.781). We conclude that the 13-segment WMSI and MPI are reproducible and correlate strongly with established echocardiographic and invasive indexes of systolic and diastolic function. These findings support the use of WMSI and MPI as indexes of global LV function in the rat infarction model of heart failure.

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Moderate levels of SBD are associated with impaired conduit and resistance endothelial function in women. Women with SDB may be more vulnerable to early SDB-related cardiovascular disease than are men.

OSA is significantly associated with increased urine albumin excretion, especially among those with more severe disease. These data provide further evidence supporting endothelial dysfunction as a mediating pathway between cardiovascular disease and OSA.

Recently, we showed that compared with the A/J inbred mouse strain, C57BL/6J (B6) mice have an athlete's cardiac phenotype. We postulated that strain differences would result in greater left ventricular (LV) hypertrophy in response to isoproterenol in B6 than A/J mice and tested the hypothesis that a differential response could be explained partly by differences in ␤-adrenergic receptor (␤-AR) density and/or coupling. A/J and B6 mice were randomized to receive daily isoproterenol (100 mg/kg sc) or isovolumic vehicle for 5 days. Animals were studied using echocardiography, tail-cuff blood pressure, histopathology, ␤-AR density and percent high-affinity binding, and basal and stimulated adenylyl cyclase activities. One hundred twenty-eight mice (66 A/J and 62 B6) were studied. Isoproterenol-treated A/J mice demonstrated greater percent increases in echocardiographic LV mass/body weight (97 Ϯ 11 vs. 20 Ϯ 10%, P ϭ 0.001) and in gravimetric heart mass/body weight versus same-strain controls than B6 mice. Histopathology scores (a composite of myocyte hypertrophy, nuclear changes, fibrosis, and calcification) were greater in isoproterenol-treated A/J vs. B6 mice (2.8 Ϯ 0.2 vs.1.9 Ϯ 0.3, P Ͻ 0.05), as was quantitation of myocyte damage (22.3 Ϯ 11.5 vs. 4.3 Ϯ 3.5%). Interstrain differences in basal ␤-AR density, high-affinity binding, and adenylyl cyclase activity were not significant. However, whereas isoproterenol-treated A/J mice showed nonsignificant increases in all ␤-AR activity measures, isoproterenol-treated B6 mice had lower ␤-AR density (57 Ϯ 6 vs. 83 Ϯ 8 fmol/mg, P Ͻ 0.05), percent high-affinity binding (15 Ϯ 2 vs. 26 Ϯ 3%, P Ͻ 0.005), and GTP ϩ isoproterenol-stimulated adenylyl cyclase activity (10 Ϯ 1.1 vs. 5.8 Ϯ 1.5 pmol cAMP ⅐ mg Ϫ1 ⅐ min Ϫ1 ) compared with controls. High-dose, short-term isoproterenol produces greater macro-and microscopic cardiac hypertrophy and injury in A/J than B6 mice. A/J mice, unlike B6 mice, do not experience ␤-AR downregulation or uncoupling in response to isoproterenol. Abnormalities in ␤-adrenergic regulation may contribute to strain-related differences in the vulnerability to isoproterenolinduced cardiac changes. echocardiography; myocyte injury LEFT VENTRICULAR (LV) hypertrophy (LVH) results from the chronic pressure or volume overload of the heart that frequently accompanies conditions such as hypertension, myocardial infarction, and valvular heart disease. LVH is a potent and independent risk factor for cardiovascular morbidity, all-cause mortality, and stroke both in patients with cardiovascular disease and in the population at large (9, 13). However, the propensity for reactive hypertrophy does not appear to be uniformly distributed within the human population. For example, hypertensive African-Americans are almost twice as likely to develop LVH than are Caucasians (2), and one populationbased study (1) of hypertensive siblings suggests that LV mass is more tightly correlated between African-American siblings than their Caucasian counterparts. These observations suggest t...

BackgroundObstructive sleep apnea (OSA) is an independent risk factor for many cardiovascular conditions such as coronary artery disease, myocardial infarction, systemic hypertension, pulmonary hypertension, and stroke. However, the association of OSA with outcomes in patients hospitalized for ST‐elevation myocardial infarction remains controversial.Methods and ResultsWe used the nation‐wide inpatient sample between 2003 and 2011 to identify patients with a primary discharge diagnosis of ST‐elevation myocardial infarction and then used the International Classification of Diseases, Clinical Modification code 327.23 to identify a group of patients with OSA. The primary outcome of interest was in‐hospital mortality, and secondary outcomes were in‐hospital cardiac arrest, length of stay and hospital charges. Our cohort included 1 850 625 patients with ST‐elevation myocardial infarction, of which 1.3% (24 623) had documented OSA. OSA patients were younger and more likely to be male, smokers, and have chronic pulmonary disease, depression, hypertension, known history of coronary artery disease, dyslipidemia, obesity, and renal failure (P<0.001 for all). Patients with OSA had significantly decreased in‐hospital mortality (adjusted odds ratio, 0.78 [95% CI, 0.73–0.84]), longer hospital stay (5.00±4.68 versus 4.85±5.96 days), and incurred greater hospital charges ($79 460.12±70 621.91 versus $62 889.91±69 124.15). There was no difference in incidence of in‐hospital cardiac arrest (adjusted odds ratio, 0.93 [95% CI, 0.84–1.03]) between these 2 groups.Conclusion ST‐elevation myocardial infarction patients with recognized OSA had significantly decreased mortality compared with patients without OSA. Although patients with OSA had longer hospital stays and incurred greater hospital charges, there was no difference in incidence of in‐hospital cardiac arrest.

Abstract-Congestive heart failure (CHF) is a clinical syndrome, which is the result of systolic or diastolic ventricular dysfunction. During CHF, vascular tone is regulated by the interplay of neurohormonal mechanisms and endothelialdependent factors and is characterized by both central and peripheral vasoconstriction as well as a resistance to nitric oxide (NO)-mediated vasodilatation. At the molecular level, vascular tone depends on the level of regulatory myosin light chain phosphorylation, which is determined by the relative activities of myosin light chain kinase and myosin light chain phosphatase (MLCP). The MLCP is a trimeric enzyme with a catalytic, a 20-kDa and a myosin targeting (MYPT1) subunit. Alternative splicing of a 3Ј exon produces leucine zipper positive and negative (LZ ϩ/Ϫ ) MYPT1 isoforms. Expression of a LZ ϩ MYPT1 has been suggested to be required for NO-mediated smooth muscle relaxation. Thus, we hypothesized that the resistance to NO-mediated vasodilatation in CHF could be attributable to a change in the relative expression of LZ ϩ/Ϫ MYPT1 isoforms. To test this hypothesis, left coronary artery ligation was used to induce CHF in rats, and both the dose response relationship of relaxation to 8-Br-cGMP in skinned smooth muscle and the relative expression of LZ ϩ/Ϫ MYPT1 isoforms were determined. In control animals, the expression of the LZ ϩ MYPT1 isoform predominated in both the aorta and iliac artery. In CHF rats, LVEF was reduced to 30Ϯ5% and there was a significant decrease in both the sensitivity to 8-Br-cGMP and expression of the LZ ϩ MYPT1 isoform. These results indicate that CHF is associated with a decrease in the relative expression of the LZ ϩ MYPT1 isoform and the sensitivity to 8-Br-cGMP-mediated smooth muscle relaxation. The data suggest that the resistance to NO-mediated relaxation observed during CHF lies at least in part at the level of the smooth muscle and is a consequence of the decrease in the expression of the LZ ϩ MYPT1 isoform.

Background We sought to determine (1) long‐term outcomes in patients presenting with documented Takotsubo syndrome (TS), (2) whether left ventricular global longitudinal strain (LV‐GLS) provides incremental prognostic value, and (3) prognostic cutoffs of LV ejection fraction (LVEF) and LV‐GLS during an acute TS episode. Methods and Results We studied 650 patients with TS (aged 66±14 years, 88% women) who were diagnosed clinically and angiographically between 2006 and 2018. Baseline LVEF and LV‐GLS (using velocity vector imaging) were recorded. The primary end point was all‐cause mortality. TS triggers were unknown (34%), emotional (16%), physical (41%), and neurologic (10%). Mean LVEF and LV‐GLS were 36±10% and −11.6±0.4%; in addition, 94% patients had LVEF <52%, and 80% had apical ballooning. No patient had obstructive coronary artery disease. At a median of 2.2 years (interquartile range, 0.7–4.4), 175 (27%) had died (9% in‐hospital deaths). Multivariate Cox survival analysis revealed that higher age (hazard ratio [HR], 1.35), male sex (HR, 1.75), lower baseline LVEF (HR, 1.02), worse LV‐GLS (HR, 1.04), neurologic trigger (HR, 2.66), and physical trigger (HR, 2.64) were associated with mortality, whereas aspirin (HR, 0.70) and β‐blockers (HR, 0.73) improved survival (all P <0.049). The addition of LVEF and LV‐GLS to clinical markers (age, sex, cardiogenic shock at presentation, and peak troponin I) significantly increased log‐likelihood ratios: clinical (−521.48), clinical plus LVEF (−511.32, P <0.001), and clinical plus LVEF and LV‐GLS (−500.68, P <0.001). On penalized spline analysis, LVEF of 38% and LV‐GLS of −10% were cutoffs below which survival was significantly worse. Conclusions Patients with TS with a neurologic or physical trigger had significantly worse survival than those without such a trigger, with baseline LVEF and LV‐GLS providing incremental prognostic value.