Best of heart failure

39 contemporary clinical practice (featuring drugs) who can be titrated to target beta- be in the range of 20 to 40% [ 31 ]. Hyperpolarization-activated c nucleotide-gated channel inh Hyperpolarization-activated cyclic nuc channels play important roles both in t neuronal excitability. HCN channels o tion voltage, permeate to potassium and an inward current, which is modulated adenosine monophosphate (cAMP). In thologies, dysfunctional HCN channels to be a direct cause of rhythm disorder of-function in atrial fibrillation, ventric failure might help enhance ectopic elect mote arrhythmogenesis [ 32 ]. Novel compounds with enhanced selec channel isoforms are being studied as p new drug development. Ivabradine is t inhibitor being clinically approved in 20 chronic stable angina pectoris and HF. Iv HR-reducing drug that works only in si inhibiting the so-called funny current (I through the blockade of the I f channel (Fi The current across the I f channel is a um current, and the I f channel is activate and regulated by direct binding of cAM rectly modulates the HCN channel by in of channel opening during diastole; in t depolarization slope becomes steeper an Fig. 1 The mechanism of action of ivabradine. Ivabradine within SA node selectively blocks the HCN channel, inhibits the If current, slows diastolic depolarization, and lowers heart rate. HCN channel hyperpolarization-activated cyclic nucleotide-gated; If current inward flow of positively charged ions that initiates the spontaneous diastolic depolarization phase, modulating heart rate; SA node sinoatrial node Heart Fail Rev (2018) 23:517 – 525 recommended to be in reach the target 97/10 should not be given c to risk for angioedema, stopped for 36 h bef patients with eGFR < impairment, the starti daily and ARNI is not hepatic impairment [ 3 With the results of t ommendations have b HF Guidelines. First, ACE inhibitors or an strategy of RAS inhibit or ARB or ARNI. T strategy of inhibition of evidence: A), or A (level of evidence: B – beta-blockers and aldo is recommended for p morbidity and mortalit In the 2017 Focuse with chronic symptom tolerate an ACE inhibit recommended to furth 36 •• ]. In those patie switched to ARNI fro to note that ARNI sho with ACE inhibitors or inhibitor due to angio should not be administ edema [ 1 •• ]. In the stu inhibition, blacks and angioedema [ 35 ]. It is be educated about rec ma and to alert health scription of ACE inhi In a phase II trial i served ejection fractio greater extent than di tolerated [ 39 ]. The eff compe sated HF, in a IV symptoms, or in p time and is being teste Ivabradine Ivabradine is a specifi channel. If ion channel in spontaneously activ node, the AV node, an is a mixed Na/K curre at voltages in the dia 39 Page 4 of 9 the interaction of genetics and the environment [ 6 ]. In patients with HF, increased sympathetic activity is associated with a positive chronotropic stimulation leading to accelerated rest- ing HR [ 7 ]. Indeed, resting HR is a major determinant of myocardial oxygen demand, coronary blood flow, and overall myocardial performance. It acts along with myocardial wall stress and LV contractility [ 8 , 9 ]. It is well known that coronary arterial perfusion mainly occurs during isovolumetric relaxation, especially in the left coronary artery: for this reason, a reduction in diastole dura- tion reduces myocardial perfusion time. Coronary blood flow decreases at higher HR values physiologically, but the full amount of flow per minute rises as a result of metabolic vaso- dilatation of coronary resistance vessels. Indeed, an increase in HR in the presence of stable coronary artery stenosis causes an imbalance between myocardial oxygen requirement and perfusion, enhances coronary shear stress, and can also pre- dispose to arrhythmias [ 10 , 11 ]. This mechanism, in synergy with β 2 -adrenergic-mediated vasodilatation, adjusts the quan- tity of blood supply depending on the level of myocardial oxygen consumption when tachycardia reduces the diastolic time available for coronary perfusion [ 10 , 11 ]. Resting HR is known to predict longevity and cardiovascular diseases, and current evidence suggests that it is also an important marker of outcome in cardiovascular disease, including HF [ 12 ]. Increased HR has been associated with reduced myocardial function, progressive mechanical dyssynchrony, and reduced inotropy [ 13 – 16 ]. Chronic elevations in HR cause a reversible syndrome of LV dysfunction known as tachycardia-mediated cardiomyopathy, and even pacing at progressively increased but non-tachycardic rates are associated with worsening LV function and depressed exercise capacity [ 17 ]. Part of the ability of the HR to predict risk is related to the forces driving it, namely, neurohormonal activation, which is also associated with increased mortality. However, there is substantial evidence that high HR is a mediator and not simply a marker of risk, a phenomenon that has been also observed in illnesses outside of cardiology, for example in cancer [ 18 ]. Teodorescu et al. performed a study to evaluate the relation- ship between HR, LV systolic dysfunction (LVSD), HR- modulating drugs, and sudden cardiac death (SCD) in the community by using a case-control approach [ 19 ]. Mean rest- ing HR was significantly higher among 378 SCD cases com- pared to that among 378 controls from the Oregon Sudden Unexpected Death Study (7.5 beats per minute (bpm differ- ence; p < 0.0001). HR was a significant determinant of SCD after adjustment for significant co-morbidities and medica- tions (odds ratio for 10 bpm increase 1.26; 95% confidence interval 1.14 – 1.38; p < 0.0001). After considering LVSD, resting HR was slightly attenuated but remained significantly associated with SCD ( p = 0.005). Contrary to expectations, the significant relationship between increased resting HR and SCD persisted even after adjustment for LVSD and HR- modulating drugs [ 19 ]. In patients with coronary artery dis- ease (CAD) and left ventricular dysfunction, a heart rate of 70 bpm or higher was associated with a 34% increased risk of cardiovascular death and a 53% increase in admission to hos- pital for heart failure compared with heart rate lower than 70 bpm [ 20 ]. The association between HR and survival has also been observed among 1520 patients discharged after an e isod of acute HF, in which the highest stratum of HR (> 80 bpm) was associated with a 41% increase in th risk of death versus the first quartile (HR, 1.41; 95% CI, 1.08 – 1.84) [ 21 ]. The association of increased HR with morbidity and mortality out- comes was well documented in ma y other studies [ 14 , 22 – 27 ]. These data suggest that for patients with HF, ig residual HR indicates high residual risk and an opportunity for treatment. Therapies that reduce HR in patients in sinus rhythm, such as beta-blockers, improve outcomes in HF, and the extent of HR reduction predicts the magnitude of this benefit. However, these medicines also have effects on c n- tractility, remodeling, autonomic tone, and arrhythmia burden that importantly contribute to their benefit. Besides, pati nts who were receiving beta-blockers but had the highest HR were at highest risk, indicating that t ere are patients resistant to beta-blocker therapy and that t ese patients are t even higher risk [ 28 ]. There are data indicating improper HR control in HF pa- tients resulting from both: resistance to t erapy and unaware- ness of and adherence to guidelines for HR control among physicians. Pourdjabbar et al. perfor ed a retrospective art review of 300 patients being followed in a heart function clinic for a minimum of 1 year to identify the prevalence of su opti- mal HR control among real-life patients and to identify the potential role for further HR reducing therapy. I this analysis, over one third (36.5%) of analyzed patients had suboptimal HR control, of which 75% had sinus rhythm, in spite of a very high usage of beta-blocker use (~ 95% on a beta-blocker and over 25% at target doses) and other available guideline recommend- ed agents [ 29 ]. The survey of HR in pati nt with HF in Sweden (HR-HF survey) was an investigator-initiated, prospective, multicenter, observational longitudinal study designed to inves- tigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guideli es for HR control among physicians who focus on the contributing role of beta-blockers. The 734 patients with HF enrolled i to the registry had a mean HR of 68 ± 12 bpm (37.2% of the patients had a HR > 70 bpm). The authors concluded that sub- optimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision-making rather than to the use of beta-blockers. Their results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care [ 30 ]. However, the proportion of patients in 518 Heart Fail Rev (2018) 23:517 – 525