[Update of the ESC guidelines 2018 on cardiovascular diseases during pregnancy : Most important facts]. / Update 2018 der ESC-Leitlinie zu kardiovaskulären Erkrankungen in der Schwangerschaft : Die wichtigsten Fakten.

Heart diseases are the most common cause of maternal death during pregnancy in Western countries. The current ESC guidelines 2018 for the management of cardiovascular diseases during pregnancy is a guide for any physician facing the challenge of caring for pregnant women with cardiovascular diseases. Among the new concepts compared to 2011, are recommendations to classify maternal risk due to the modified World Health Organization (mWHO) classification, introduction of the pregnancy heart team, guidance on assisted reproductive therapy, specific recommendations on anticoagulation for low-dose and high-dose requirements of vitamin K antagonists and the potential use of bromocriptine in peripartum cardiomyopathy. The Food and Drug Administration (FDA) categories A-D and X should no longer be used. Therefore, the table of drugs was completed with detailed information from animal and human studies on maternal and fetal risks. The new findings on specific heart diseases are presented in detail in the respective chapters.

[New pharmacologic therapies for chronic heart failure]. / Neue medikamentöse Therapieansätze bei chronischer Herzinsuffizienz.

Heart failure is a disease with a high prevalence and incidence. New therapeutic approaches are needed to prevent the onset of heart failure and to reduce the high morbidity and mortality associated with this disease. An optimized therapy of arterial hypertension in patients with risk factors and the use of the SGLT2 inhibitor empagliflozin in type 2 diabetics are proven strategies to prevent heart failure. The therapeutic options in heart failure with preserved ejection fraction are still insufficient. In heart failure with reduced ejection fraction sacubitril/valsartan, the first approved angiotensin receptor-neprilysin inhibitor, is superior to an angiotensin converting enzyme (ACE) inhibitor. Whether digitalis affects the prognosis in heart failure remains unclear; however, serum concentration should be targeted at the lower therapeutic range. Iron supplementation in heart failure with reduced systolic function and iron deficiency improves symptoms and quality of life.

Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction.

BACKGROUND: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) attenuate angiotensin II-induced cellular signaling. Because angiotensin II is involved in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of statin treatment in an experimental model of chronic heart failure after MI. METHODS AND RESULTS: Rats with extensive MI were treated with placebo or cerivastatin (0.3 mg/kg per day) as a dietary supplement or via gavage for 11 weeks starting on the 7th postoperative day. Infarct size and cholesterol levels were similar among all groups. LV cavity area, an index of LV dilatation, was reduced in MI rats on cerivastatin compared with placebo. LV end-diastolic pressure was increased in MI rats on placebo (24.1+/-4.1 mm Hg versus sham: 5.1+/-0.3 mm Hg; P<0.01), and it was significantly reduced by cerivastatin treatment (13.7+/-2.7 mm Hg; P<0.05 versus placebo). Cerivastatin partially normalized LV dP/dt(max) and dP/dt(min), indices of LV systolic and diastolic function, which were significantly reduced in MI rats on placebo. Improvement of LV function by cerivastatin was accompanied by a reduced expression of collagen type I and beta-myosin heavy chain. LV endothelial nitric oxide synthase was increased, whereas the nitrotyrosine protein level was decreased in MI rats by cerivastatin treatment. CONCLUSIONS: Cerivastatin improved LV remodeling and function in rats with heart failure. This effect was associated with an attenuated LV expression of fetal myosin heavy chain isoenzymes and collagen I. Statin treatment may retard the progression of chronic heart failure.

Prevention of endothelial dysfunction in heart failure by vitamin E: attenuation of vascular superoxide anion formation and increase in soluble guanylyl cyclase expression.

OBJECTIVES: Enhanced vascular superoxide anion generation contributes to endothelial dysfunction in heart failure. However, the effect of long-term treatment with the antioxidant vitamin E is unknown. METHODS AND RESULTS: Relaxant responses were determined in aortic rings from Wistar rats with heart failure 12 weeks after myocardial infarction (MI) and compared with responses in tissues from sham-operated animals. From the seventh post-operative day, rats were given either a standard chow or a chow enriched in vitamin E (approximate intake 100 mg/day). In rings from rats with heart failure, acetylcholine-induced relaxation was attenuated (maximum relaxation, R(max) 54 +/- 3%) when compared with rings from sham-operated animals (79 +/- 3%, n=12, P < 0.01), while endothelium-independent relaxation elicited by sodium-nitroprusside was unchanged. Aortic superoxide generation was significantly enhanced in rats with heart failure. Vitamin E supplementation significantly improved acetylcholine-induced relaxation in rats with heart failure (R(max) 75 +/- 4%, P < 0.01) and led to a leftward shift in sodium-nitroprusside-induced relaxation curve. Aortic expression of the beta(1)-subunit of soluble guanylyl cyclase was significantly enhanced by vitamin E supplementation. In addition, the elevated vascular superoxide formation was normalised by vitamin E. CONCLUSIONS: These results demonstrate that dietary supplementation with the antioxidant vitamin E restores normal endothelial function, reduces vascular superoxide anion formation and increases the expression of the soluble guanylyl cyclase in rats with heart failure.

Isometric contraction induces the Ca2+-independent activation of the endothelial nitric oxide synthase.

Shear stress and tyrosine phosphatase inhibitors have been shown to activate the endothelial NO synthase (eNOS) in a Ca2+/calmodulin-independent manner. We report here that isometric contraction of rabbit aorta activates eNOS by a pharmacologically identical pathway. Endothelium-intact aortic rings were precontracted under isometric conditions up to 60% of the maximal phenylephrine-induced tone. The NO synthase inhibitor NGnitro-L-arginine (L-NA) and the soluble guanylyl cyclase inhibitor NS 2028 induced an additional contraction, the amplitude of which depended on the level of precontraction. The maximal production of NO by isometrically contracted aortic rings (as estimated by the increase in cGMP in detector smooth muscle cells in a superfusion bioassay) was observed during the initial phase of isometric contraction and was greater than that detected following the application of acetylcholine. The supplementary L-NA-induced increase in vascular tone was inhibited by the nonselective kinase inhibitor staurosporine and the tyrosine kinase inhibitors erbstatin A and herbimycin A. Another tyrosine kinase inhibitor, genistein, the calmodulin antagonist calmidazolium, and the selective protein kinase C inhibitor, Ro 31-8220, had no effect. Coincident with the enhanced NO formation during isometric contraction was an increase in the tyrosine phosphorylation of endothelial proteins, which also correlated with the level of precontraction. Thus, isometric contraction activates eNOS via a Ca2+-independent, tyrosine kinase inhibitor-sensitive pathway and, like shear stress, seems to be an independent determinant of mechanically induced NO formation.