Angiotensin Receptor Blocker-neprilysin Inhibitor Research Articles

Differences in provider approach to initiating and titrating guideline directed medical therapy in heart failure with reduced ejection fraction

BackgroundDespite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking.MethodsA survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4–5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest.ResultsCardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07–3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18–4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01–3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48–4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine.ConclusionsOur results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.

Abstract 16214: Prescription of Teratogenic Medications for Reproductive-Age Women With Heart Failure With Reduced Ejection Fraction in a Safety-Net Health System

Introduction: Angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), angiotensin receptor blocker-neprilysin inhibitors (ARNI), and mineralocorticoid receptor antagonists (MRA) have been proven to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF); however, they have known teratogenic effects. It is uncertain how often reproductive-age women are prescribed these medications and whether they are prescribed contraception. Methods: We included all patients in our health system with documented left ventricular ejection fraction ≤45% within the past 2 years. Patients were excluded from the present study if they had a creatinine ≥2.0 mg/dl (women) or ≥2.5 mg/dl (men), as these are contraindications to MRA. Individuals were stratified into reproductive-age women (age ≤45), women age &gt;45, and men (any age). Contraception prescription was queried via chart review for all reproductive-age women. Rates of ACEi/ARB/ARNI, and MRA, were then compared across 4 subgroups. Results: Of 3,003 patients who met the inclusion criteria, 130 were women ≤45y, 709 were women &gt; 45y, and 2164 were men. Among the 81/130 (62%) reproductive-aged women not prescribed contraception, 78% had an active prescription for either an ACEi, ARB, or ARNI and 56% had an active MRA prescription (Figure). Comparing reproductive-age women not on contraception with all other groups, the ACEi/ARB/ARNI prescription rates were 78% vs. 78% (p = 0.36) and the MRA prescription rates were 56% vs 49% (p = 0.16). Conclusions: In a large safety net health system, most reproductive-aged women with HFrEF, were not prescribed contraception, yet they were commonly prescribed teratogenic heart failure medications. This is an important safety concern that should be addressed at the health system level.

Comparative cardiovascular outcomes of novel drugs as an addition to conventional triple therapy for heart failure with reduced ejection fraction (HFrEF): a network meta-analysis of randomised controlled trials

BackgroundCurrently, there is no head-to-head comparison of novel pharmacological treatments for heart failure with reduced ejection fraction (HFrEF). A network meta-analysis aimed to compare effects of both conventional and alternative...

New Therapeutics for Heart Failure: Focusing on cGMP Signaling.

Current drugs for treating heart failure (HF), for example, angiotensin II receptor blockers and β-blockers, possess specific target molecules involved in the regulation of the cardiac circulatory system. However, most clinically approved drugs are effective in the treatment of HF with reduced ejection fraction (HFrEF). Novel drug classes, including angiotensin receptor blocker/neprilysin inhibitor (ARNI), sodium-glucose co-transporter-2 (SGLT2) inhibitor, hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, soluble guanylyl cyclase (sGC) stimulator/activator, and cardiac myosin activator, have recently been introduced for HF intervention based on their proposed novel mechanisms. SGLT2 inhibitors have been shown to be effective not only for HFrEF but also for HF with preserved ejection fraction (HFpEF). In the myocardium, excess cyclic adenosine monophosphate (cAMP) stimulation has detrimental effects on HFrEF, whereas cyclic guanosine monophosphate (cGMP) signaling inhibits cAMP-mediated responses. Thus, molecules participating in cGMP signaling are promising targets of novel drugs for HF. In this review, we summarize molecular pathways of cGMP signaling and clinical trials of emerging drug classes targeting cGMP signaling in the treatment of HF.

Sacubitril/valsartan mitigates cardiac remodeling, systolic dysfunction, and preserves mitochondrial quality in a rat model of mitral regurgitation

Sacubitril/valsartan (SAC/VAL), an angiotensin receptor blocker-neprilysin inhibitor, has been widely used to treat several types of heart failure. Nevertheless, the effects of drugs in mitral regurgitation patients, from the molecular level to therapeutic effects, remain unclear. This study investigates the roles of SAC/VAL on cardiac function, mitochondrial quality, autophagy, mitophagy, and natriuretic peptides in a rat model of chronic mitral regurgitation. Male Sprague–Dawley rats underwent MR induction (n = 16) and sham surgeries (n = 8). Four weeks post-surgery confirmed MR rats were randomly divided into MR (n = 8) and SAC/VAL (n = 8) groups. The SAC/VAL group was administered SAC/VAL, whereas the MR and the sham rats received vehicle via oral gavage daily for 8 weeks. Cardiac geometry, function, and myocardial fibrosis were assessed by echocardiography and histopathology. Spectrophotometry and real-time PCR were performed to assess the pharmacological effects on mitochondrial quality, autophagy, mitophagy, and natriuretic peptides. MR rats demonstrated significant left heart dilation and left ventricular systolic dysfunction compared with the sham group, which could be significantly improved by SAC/VAL. In addition, SAC/VAL significantly reduced myocardial cardiac remodeling and fibrosis in MR rats. SAC/VAL improved the mitochondrial quality by attenuating mitochondrial reactive oxygen species production and mitochondrial depolarization compared with the MR group. Also, the upregulation of autophagy-related, mitophagy-related, and natriuretic peptide system gene expression in MR rats was attenuated by SAC/VAL treatment. In conclusion, this study demonstrated that SAC/VAL treatment could provide numerous beneficial effects in MR conditions, suggesting that this drug may be an effective treatment for MR.

Sex-specific differences in the efficacy of heart failure therapies: a meta-analysis of 84,818 patients.

Women have been historically underrepresented in clinical trials of heart failure (HF). We aimed to assess for sex differences in patient characteristics and the efficacy of guideline-directed medical therapy (GDMT) in HF. Systematic literature search for randomized controlled trials (RCTs) of GDMT reporting cardiovascular outcomes by sex in patients with HF. The primary outcome was the composite of cardiovascular death and hospitalization for HF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using inverse variance weighting and random effects meta-analysis. Twenty-six RCTs totaling 84,818 participants (27% women) were included. Women with HF were older, had higher New York Heart Association (NYHA) class, more hypertension and obesity, and higher mean left ventricular ejection fraction compared to men. There was evidence for most GDMT in reducing the primary outcome in women with HF with reduced ejection fraction (HFrEF) (angiotensin-converting enzyme inhibitors/angiotensin-receptor blocker [RR 0.86, 95% CI 0.75-0.97], angiotensin-receptor blocker/neprilysin inhibitor (ARNI) [RR 0.77, 95% CI 0.62-0.94], beta-blocker [RR 0.67, 95% CI 0.51-0.89], ivabradine [RR 0.74, 95% CI 0.60-0.91], and sodium-glucose cotransporter-2 (SGLT2) inhibitors [RR 0.66, 95% CI 0.54-0.81]) and a non-significant trend for benefit with mineralocorticoid-receptor-antagonist (MRA) [RR 0.77, 95% CI 0.52-1.16]). Compared to men with HFrEF, GDMT reduced the primary outcome in women to a similar degree across all drug classes (ratio of RR 1.05, 95% CI 0.96-1.14). Despite differences in baseline characteristics and an underrepresentation of women in HF clinical trials, GDMT are as efficacious in women as compared to men in reducing cardiovascular events in HF.

Outcomes of Heart Failure with Reduced Ejection Fraction Patients Receiving Sacubitril/Valsartan in Real-World Practice

Objective: To describe clinical outcomes and NT-pro-brain natriuretic peptide (NT-proBNP) level of patients with chronic heart failure with reduced ejection fraction (HFrEF) receiving sacubitril/valsartan (Sac/Val) in real world setting. Materials and Methods: The present research was a single-center, retrospective, non-interventional study in adult patients with HFrEF that received Sac/Val at Bhumibol Adulyadej Hospital. Data were extracted from the hospital’s database and electronic medical records. All patients fulfilling the inclusion criteria were identified and included into the present study. The present study was approved by the Ethics Committees of Bhumibol Adulyadej Hospital. Results: During the two years of the present study, two patients died from cardiovascularly (CV) death. The New York Heart Association (NYHA) class was changed from baseline to 12-month (2.0±0.4) and 24-month (1.8±0.1), p&lt;0.001. Left ventricular ejection fraction (LVEF) was significantly inclined at 24-month compared to baseline. The rate of heart failure and related hospitalization within one year declined from baseline at 19 visits/year to 12-month at 6 visits/year, and 24-month at 5 visits/year. The mean of NT-proBNP level was significantly reduced from baseline at 2,802.3±3,106.7 to 12-month at 2,203.8±4,051.1, and 24-month at 1,157.6±1,069.9 (p=0.03). Total hospitalization due to any cause was decreased from baseline at 26 visits/year to 12-month at 24 visits/year, and 24-month at 12 visits/year. Numbers of emergency room visit, ICU/CCU admission, length of stay for admission, and direct medical cost of heart failure (HF) treatment were diminished from baseline. Conclusion: Sac/Val can reduce hospitalized HF and level of NT-proBNP. Its efficiency in Thai patients with HFrEF was similar to real world data. Keywords: Heart Failure with reduced ejection fraction, Sacubitril/Valsartan, Angiotensin receptor blocker/neprilysin inhibitor (ARNI)

The Treatment of Heart Failure in Patients with Chronic Kidney Disease: Doubts and New Developments from the Last ESC Guidelines.

Patients with heart failure (HF) and associated chronic kidney disease (CKD) are a population less represented in clinical trials; additionally, subjects with more severe estimated glomerular filtration rate reduction are often excluded from large studies. In this setting, most of the data come from post hoc analyses and retrospective studies. Accordingly, in patients with advanced CKD, there are no specific studies evaluating the long-term effects of the traditional drugs commonly administered in HF. Current concerns may affect the practical approach to the traditional treatment, and in this setting, physicians are often reluctant to administer and titrate some agents acting on the renin angiotensin aldosterone system and the sympathetic activity. Therefore, the extensive application in different HF subtypes with wide associated conditions and different renal dysfunction etiologies remains a subject of debate. The role of novel drugs, such as angiotensin receptor blocker neprilysin inhibitors and sodium glucose linked transporters 2 inhibitors seems to offer a new perspective in patients with CKD. Due to its protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. In this review, we discussed the largest trials reporting data on subjects with HF and associated CKD, while suggesting a practical stepwise algorithm to avoid renal and cardiac complications.

Abstract EP28: SO CLOSE YET SO FAR : HOW WELL ARE WE DOING WITH GDMT FOR HEART FAILURE WITH REDUCED EJECTION FRACTION - A COMMUNITY HOSPITAL ANALYSIS

Background: The use of maximum tolerated doses of guideline directed medical therapy (GDMT) for patient with heart failure with reduced ejection fraction (HFrEF) has been suboptimal in routine clinical practice. In particular, the rate of adoption of the angiotensin receptor blocker-neprilysin inhibitor (ARNI) has lagged. In this study, we aim to evaluate the use of optimal GDMT and the effect of ARNI on heart failure related re-admission (HFRR) in a real life setting from a single center community hospital. Method: Retrospective chart review was conducted in patients who were admitted to our hospital system for HFrEF between December 2019-January 2021. Data was collected for patient demographics, comorbidities, admission and discharge medications, length of stay and rate of 30-day HFRR. Results: 357 patients were included in the analysis. 92.7% were discharged on beta blockers, 50% were discharged on ACE-I/ARB, 6.4% were discharged on ARNI and 47.75% were discharged on MRAs. The target doses of each were only achieved in 7.3%, 27%, 100% and &lt;1% respectively. 43% patients were not discharged on either ACE-I/ARB/ARNI. Patients discharged on ARNI had numerically lower rates of chronic kidney disease &gt; stage 3, and lower BNP levels than those discharged on ACE-I/ARB. HFRR was lower in patient discharged on ARNI vs ACE-I/ARB (4.17% vs 16%), although this was not statistically significant due to low sample volume (p = 0.20). Conclusion: Our study shows that the rate of adoption of GDMT, especially ARNI, in hospitalized HFrEF patients in clinical practice lags significantly behind from that reported in clinical trials. Although there was no statistical significance achieved in comparison due to small sample size, we see a trend of decreased heart failure readmission in patients discharged on ARNI. The wide gap of adoption of GDMT in the real world remains a challenge, and adversely impacts patient outcomes.

Abstract 13017: An Innovative Clinical Decision Support Alert to Increase Utilization of ARNIs Among HFrEF Patients

Introduction: After PARADIGM-HF showed a significant reduction in cardiovascular death and heart failure hospitalizations in patients treated with sacubitril-valsartan, an angiotensin receptor blocker-neprilysin inhibitor, the ACC/AHA/HFSA guidelines for management of HFrEF included a class I recommendation for ARNI therapy in these patients and recommended replacement of ACE-Is/ARBs with ARNI in patients with NYHA class II or III chronic HFrEF. A 2021 update recommends initiation of ARNI over ACEi or ARB when possible. Intervention: At Thomas Jefferson University Hospital, 2,322 unique patients with a history of HFrEF were admitted between January 2019 and August 2020. Of these, 217 were discharged on sacubitril-valsartan - an individual utilization rate of only 9.3%. Working with the electronic medical record (EMR) team, we devised a set of clinical decision support (CDS) alerts to facilitate transition to ARNI in patients with HFrEF. The first alert fires if an ACE-I is ordered, to encourage switching to an ARB for washout. A second alert fires if an ARB is ordered, suggesting ARNI as a therapeutic alternative. Results: Between December 2020 and May 2021, the alert fired 569 times for 143 unique patients. 102 (71%) were discharged on RAAS blockade. Major reasons for no RAAS blockade included hypotension (51%) and AKI/CKD (20%). Of patients who were discharged on RAAS blockade, 17 (16.7%) were discharged on sacubitril-valsartan. During the intervention period, sacubitril-valsartan use on discharge increased from 9.3% to 16.7% for patients with a history of HFrEF. Conclusion: This project demonstrates how an innovative CDS tool within the EMR can increase adherence to guideline directed medical therapies in HFrEF. While not possible to directly implicate this alert with increased ARNI usage, chart review implies that it at least spurred discussion around the topic and triggered follow-up actions to further investigate the feasibility of prescribing them.

The ADDition of DAPAgliflozin to angiotensin receptor blocker-neprilysin inhibitors non-responders in patient with refractory HFrEF

Abstract Objectives We evaluated the efficacy and safety of dapagliflozin, a SGLT2i along with ARNI in refractory HFrEF irrespective of their diabetic status. Methods We performed a prospective, open-label study of symptomatic patients of HFrEF despite of optimal medical management with ARNI between January–June 2020. Despite the maximum tolerated dose of ARNI and other medications in patients the symptoms of heart failure persisted. The initial dose of 5 mg was started and after 4 weeks irrespective of their glycemic control, then the dose was escalated to 10 mg. They were followed for the 6-months after the combination of ARNI and SGLT2i. Results The 104 patients who had HFrEF despite of optical medical management were added dapagliflozin on top of ARNI. The primary endpoint of mean change in Left Ventricular ejection fraction (LVEF) +9.00±0.62 with a significant p value of &amp;lt;0.001. The Mean difference in NYHA class was −2.9±0.057. A study of 104 patients at 6-months follow-up found that 92.6% of patients were in NYHA class I and 7.4% were in NYHA class II. They also reached the HbA1C goal of &amp;lt;7% in the diabetic subgroup. None of them had either symptomatic hypotension, dyselectrolytemia, and elevation of serum creatinine. The drug was well received by most patients (Picture 1). Conclusions Dapagliflozin are not only oral hypoglycaemic agents but can be used in refractory HFrEF despite the use of ARNI. The combination of the ARNI and SGLT2i is well tolerated but we need large, randomized trials to prove this hypothesis (Picture 2). Funding Acknowledgement Type of funding sources: None. Picture 1. Screening and outcomes of patientsPicture 2. Graphical abstract

Effect of 24-hour blood pressure and heart rate on the prognosis of patients with reduced and midrange LVEF.

Aim Optimal combination therapy for chronic heart failure (CHF) currently implies the mandatory use of at least four classes of drugs: renin-angiotensin-aldosterone (RAAS) system inhibitors or angiotensin receptor blocker neprilysin inhibitors (ARNI); beta-adrenoblockers (BAB); mineralocorticoid receptor antagonists; and sodium-glucose cotransporter 2 inhibitors. Furthermore, many of these drugs are able to decrease blood pressure even to hypotension and alleviate tachycardia. This study focused on the relationship of 24-h blood pressure (BP) and heart rate (HR) with the prognosis for CHF patients with sinus rhythm and left ventricular ejection fraction (LV EF) &lt;50 % as well as on suggesting possible variants of safe therapy for CHF depending on the combination of studied factors.Material and methods Effects of clinical data, echocardiographic parameters, 24-h BP, and heart rhythm (data from 24-h BP and ECG monitors) on the prognosis of 155 patients with clinically pronounced CHF, LV EF &lt;50 %, and sinus rhythm who were followed up for 5 years after discharge from the hospital.Results The one-factor analysis showed that the prognosis of CHF patients was statistically significantly influenced by the more severe functional class (FC) III CHF compared to FC II, reduced LV EF (&lt;35 %), a lower 24-h systolic BP (SBP) (&lt;103 mm Hg), the absence of hypotensive episodes in daytime, a low variability of nighttime BP (&lt;7.5 mm Hg), a higher 24-h HR (&gt;71 bpm vs. &lt;60 bpm), the absence of therapy with RAAS inhibitors + BAB, and a lower body weight index. The multi-factor analysis showed that more severe CHF FC, lower LV EF, and the absence of RAAS inhibitors + BAB therapy retained the influence on the prognosis. After eliminating the influencing factor of drug therapy, also a low SBP variability significantly influenced the prognosis. An additional analysis determined the following four groups of CHF patients with reduced heart systolic function according to mean 24-h HR and SBP: the largest group (38.1 % of all patients) with controlled HR (≤69 bpm), preserved SBP (&gt;103 mm Hg), and the lowest death rate of 15.3 %; the group with increased HR (&gt;69 bpm) but preserved SBP (30.3 % of all patients) where the death rate was 44.7 %, which was significantly higher than in the first group; the group with normal HR (≤69 bpm) but reduced SBP (≤103 mm Hg) (16.1 % of patients) where the death rate was 40 %, which was comparable with the second group and significantly worse than in the first group; and the group with both increased HR (&gt;69 bpm) and reduced SBP (≤103 mm Hg) (15.5 % of patients), which resulted in the maximal risk of death (70.8 % of patients with CHF and LV EF &lt;50 %), which was significantly higher than in the three other groups.Conclusion Low SBP (including 24-h SBP with reduced variability in day- and nighttime) in combination with high HR (including by data of Holter monitoring), low LV EF, more severe clinical course of CHF, and the absence of an adequate treatment with neurohormonal modulators (RAAS inhibitors and BAB) significantly increased the risk of death. Isolating four types of FC II-III CHF with sinus rhythm and EF &lt;50% based on the combination of HR and BP identifies patients with an unfavorable prognosis, which will help developing differentiated therapeutic approaches taking into account clinical features.

ADDition of DAPAgliflozin, Sodium-Glucose Cotransporter-2 Inhibitor to Angiotensin Receptor Blocker-Neprilysin Inhibitors Non-Responders in Patient with Refractory Heart Failure with Reduced Ejection Fraction (ADD DAPA trial)

ObjectivesWe evaluated the efficacy and safety of dapagliflozin, a SGLT2i along with ARNI in refractory HFrEF irrespective of their diabetic status. MethodsWe performed a retrospective analysis of 104 symptomatic patients of HFrEF despite of optimal medical management with ARNI between January–June 2020. Despite the optimal GDMT, dapagliflozin, SGLT2i was added inpatients withrefractory heart failure. At 6-months follow-up, the primary outcome was change in left ventricular ejection fraction, and secondary outcomes included changes in NYHA functional class, vital parameters, renal function, potassium levels, and NT-pro BNP levels. ResultsThe primary outcomeat 6-months follow-up was a mean change in left ventricular ejection fraction (LVEF) +9.00 ± 0.62 (p < 0.001). The secondary outcome was a significant improvement (69%) in median NYHA functional class by 2.3 (95% Confidence interval 2.245–2.355) with 92.6% of patients were in NYHA class I and 7.4% were in NYHA class II.Diabetic subgroup reached the HbA1C goal of <7%. None of them had either symptomatic hypotension, hypoglycaemia, dyselectrolaemia, and decline in renal function. The drug was well received by most of the patients. ConclusionsDapagliflozin, an SGLT2i, should be used in symptomatic, refractory HFrEF patients despite the use of ARNI. The combination of ARNI and SGLT2i is well tolerated, but large, randomized trials are needed to prove this hypothesis.

Angiotensin-converting enzyme inhibitors, angiotensin-II-receptor antagonists and angiotensin-receptor blocker/neprilysin inhibitor utilization in heart failure patients: Sub-analysis of a nation-wide population-based study in the Czech Republic.

Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018 aimed at angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II-receptor antagonists (ARB) and angiotensin receptor blocker/neprilysin inhibitor (ARNI) use. ACEi and ARBs were generally used in 87.6% of all HF patients in 2012 (n=154 627); 84.5% in 2013 (n=170 861); 83.5% in 2014 (n=186 963); 81.6% in 2015 (n=198 844); 80.1% in 2016 (n=205 793); 78.0% in 2017 (n=212 152) and in 76.7% in 2018 (n=219 235). In a sub-analysis of patients with a medical procedure and/or examination using an I50.x ICD code accounted for in the given year, ACEi and ARBs were generally used in 99.3% in 2012 (n=63 250); 96% in 2013 (n=62 241); 95.2% in 2014 (n=64 414); 93.3% in 2015 (n=65 217); 91.8% in 2016 (n=65 236); 90.1% in 2017 (n=65 761) and in 88.6% in 2018 (n=66 332). In 2018, the majority of patients with HF were prescribed ramipril (n=49 909; 17.5%) and perindopril (n=44 332; 15.5%). The mostly prescribed ARBs in 2018 were telmisartan (n=18 669; 6.5%); losartan (n=13 935; 4.9%) and valsartan (n=4 849; 1.7%). In 24.5% of cases, ACEIs and ARBs were prescribed in a fixed combination with another drug. ARNI became gradually more prescribed from 2018 (n=9 659 in November 2020). In an analysis of ACEIs, ARBs and ARNIs utilization in all patients treated for heart failure in the given year in the whole country, we found a comparable rate of drug prescription in comparison with specific heart failure registries. This indicates a good translation of current standard of care into common clinical practice. Ramipril and perindopril remained the mostly prescribed ACEIs and telmisartan became the mostly prescribed ARB. Since 2018, ARNIs began to be widely prescribed.

Pulmonary vasodilator use in continuous-flow left ventricular assist device management.

Pulmonary hypertension (PH) due to left heart disease is the most common etiology for PH. PH in patients with heart failure with reduced fraction (HFrEF) is associated with reduced functional capacity and increased mortality. PH-HFrEF can be isolated post-capillary or combined pre- and post-capillary PH. Chronic elevation of left-sided filling pressures may lead to reverse remodeling of the pulmonary vasculature with development of precapillary component of PH. Untreated PH in patients with HFrEF results in predominant right heart failure (RHF) with irreversible end-organ dysfunction. Management of PH-HFrEF includes diuretics, vasodilators like angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers or angiotensin-receptor blocker-neprilysin inhibitors, hydralazine and nitrates. There is no role for pulmonary vasodilator use in patients with PH-HFrEF due to increased mortality in clinical trials. In patients with end-stage HFrEF and fixed PH unresponsive to vasodilator challenge, implantation of continuous-flow left ventricular assist device (cfLVAD) results in marked improvement in pulmonary artery pressures within 6 months due to left ventricular (LV) mechanical unloading. The role of pulmonary vasodilators in management of precapillary component of PH after cfLVAD is not well-defined. The purpose of this review is to discuss the pharmacologic management of PH after cfLVAD implantation.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.

BackgroundChronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD.Methods and ResultsWe examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM‐HF (Prospective Comparison of Angiotensin Receptor Blocker–Neprilysin Inhibitor With Angiotensin‐Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non‐COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P<0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P<0.001) and Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (73 versus 81; P<0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta‐blockade (87% versus 94%; P<0.001) and diuretics (85% versus 80%; P<0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13–1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05–1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94–1.30), or all‐cause mortality (HR, 1.14; 95% CI, 0.99–1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05–1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29–1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points.ConclusionsIn PARADIGM‐HF, COPD was associated with lower use of beta‐blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high‐risk subgroup.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01035255.

The addition of Dapagliflozin, sodium–glucose cotransporter-2 inhibitor to angiotensin receptor blocker-neprilysin inhibitors non-responders in patient with refractory heart failure with reducedejection fraction

The addition of Dapagliflozin, sodium–glucose cotransporter-2 inhibitor to angiotensin receptor blocker-neprilysin inhibitors non-responders in patient with refractory heart failure with reducedejection fraction

The addition of Dapagliflozin, sodium–glucose cotransporter-2 inhibitor to angiotensin receptorblocker-neprilysin inhibitors non-responders in patient with refractory heart failure with reduced ejection fraction

The addition of Dapagliflozin, sodium–glucose cotransporter-2 inhibitor to angiotensin receptorblocker-neprilysin inhibitors non-responders in patient with refractory heart failure with reduced ejection fraction

Long-Term Effects of Angiotensin Receptor-Neprilysin Inhibitors on Myocardial Function in Chronic Heart Failure Patients with Reduced Ejection Fraction.

Background. We sought to evaluate the long-term effects of angiotensin receptor blocker–neprilysin inhibitor (ARNI) therapy on reverse remodeling of the failing myocardium in HFrEF patients. Methods. We performed a prospective non-randomized longitudinal study on 228 HFrEF patients treated with ARNI at our center. Prior to ARNI introduction all patients received stable doses of ACEI/ARB for at least six months. Clinical, biochemical and echocardiography data were obtained at ARNI introduction and 12-month follow-up. Results At follow-up, we found significant improvements in LVEF (29.7% ± 8% vs. 36.5% ± 9%; p < 0.001), LVOT-VTI (14.8 ± 4.2 cm vs. 17.2 ± 4.2 cm; p < 0.001), TAPSE (1.7 ± 0.5 cm vs. 2.1 ± 0.6 cm; p < 0.001) and LV-EDD (6.5 ± 0.8 cm vs. 6.3 ± 0.9 cm; p = 0.001). NT-proBNP serum levels also decreased significantly (1324 (605, 3281) pg/mL vs. 792 (329, 2022) pg/mL; p = 0.001). A total of 102 (45%) of patients responded favorably to ARNI (ΔLVEF < +5%; Group A) and 126 (55%) patients achieved ΔLVEF ≥ +5% (Group B). The two groups differed significantly in age, heart failure etiology, baseline LVEF and baseline NT-proBNP. On multivariable analysis, nonischemic heart failure, LVEF < 30% and NT-proBNP < 1500 pg/mL emerged as independent correlates of favorable response to ARNI therapy. Conclusion. ARNI therapy appears to improve echocardiographic parameters of left and right ventricular function in HFrEF patients above the effect of pre-existing optimal medical management. These effects may be particularly pronounced in patients with nonischemic heart failure, LVEF < 30% and lower degree of neurohumoral activation.

3-10ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITORS (ARNI) POTENTIALS IN PATIENT WITH HEART FAILURE: A SYSTEMATIC REVIEW

Background: Structural and/or functional cardiac abnormalities that lead to elevated intracardiac pressures with/without reduced output known as heart failure. Progressive establishment of the disease grows concomitantly with the number of cases despite the availability of various therapies. The recent standard recommends the substitution of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs) with angiotensin receptor blocker-neprilysin inhibitors (ARNI) in selected patients. The capacity of ARNI will be analyzed based on the latest clinical trials available. Objective: This study focus on revealing the clinical impact and potentials of ARNI in an attempt to counteract the decreasing capacity of the heart. Method: Literature finding involves four scientific databases, including PubMed, EbscoHost, ProQuest, and Cochrane. The primary search was concluded using certain Medical Subject Heading (MeSH) terms and filters. Two independent authors further analyzed selected interventional articles related to ARNI and heart failure. Relevance studies were reviewed using the Centre for Evidence-based Medicine (CEBM) critical appraisal tool to turn aside bias. The result: Data were collected from patients in three randomized controlled trials within five articles. Four of the reports investigate the use of ARNI compared to enalapril in acute decompensated heart failure (ADHF) and chronic heart failure (CHF). Another study compared ARNI to valsartan only therapy in heart failure patients with reduced ejection fraction (HFrEF). It shows that the use of ARNI contributes to a lower number of hospitalization cases and mortality rates while preventing further progression of heart failure. Conclusion: ARNI has adequate potential to prevent the progression of the disease while the encouragement of future investigation is essential.