Showing papers on "Myocardial infarction complications published in 2019"

Low-Dose Methotrexate for the Prevention of Atherosclerotic Events

Abstract: Background Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1β, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. Methods We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revas...

Hospital-Level Disparities in the Outcomes of Acute Myocardial Infarction With Cardiogenic Shock.

Abstract: There are limited data on hospital-level disparities in cardiogenic shock complicating acute myocardial infarction (AMI-CS). A retrospective cohort of adult admissions from the National Inpatient Sample database during 2000 to 2014, with primary diagnosis of AMI and concomitant CS were identified. Interhospital transfers were excluded. Hospitals were classified into rural, urban nonteaching and urban teaching (location and teaching status) and small, medium and large (bedsize). The primary endpoint was in-hospital mortality and secondary endpoints included use of early coronary angiography, percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS). Multivariable regression was used to adjust for potential confounding. During 2000 to 2014, 362,065 AMI-CS admissions met the inclusion criteria, of which 92% and 69% respectively were admitted to urban and large hospitals. Admissions to urban and large hospitals were more frequently male, younger, with lower co-morbidity, and higher illness severity. There was a steady increase in early coronary angiography, PCI and MCS across the various hospital categories. Admission to an urban nonteaching hospital (adjusted odds ratio [aOR] 0.81; 95% confidence interval [CI] 0.78 to 0.84], p

Real-life use of left ventricular circulatory support with Impella in cardiogenic shock after acute myocardial infarction: 12 years AMC experience:

Abstract: Aims:Mortality in cardiogenic shock patients remains high. Short-term mechanical circulatory support with Impella can be used to support the circulation in these patients, but data from randomised ...

Risk factors for acute kidney injury in patients with acute myocardial infarction.

Abstract: Background: Acute kidney injury (AKI) is a serious and fatal complication of acute myocardial infarction (AMI). It has high shortand long-term mortality rates and a poor prognosis but is potentially preventable. However, the current incidence, risk factors, and outcomes of AKI in the Chinese population are not well understood and would serve the first step to identify high-risk patients who could receive preventative care. Methods: The medical data of 1124 hospitalized patients diagnosed with AMI from October 2013 to September 2015 were reviewed. AKI was defined according to the 2012 Kidney Disease Improving Global Outcomes criteria. All the patients were divided into either the AKI group or the non-AKI group. A univariate comparison analysis was performed to identify possible risk factors associated with AKI. A multiple logistic regression analysis was used to identify the independent risk factors for AKI in patients with AMI. Results: Overall, the incidence of AKI was 26.0%. The mortality rate of the AKI group was 20.5%, and the mortality rate of the non-AKI group was 0.6% (P 60 years old) (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02–1.05, P = 0.000), hypertension (OR 2.51, 95% CI 1.62–3.87, P = 0.000), chronic kidney disease (OR 3.52, 95% CI 2.01–6.16, P = 0.000), Killip class ≥3 (OR 5.22, 95% CI 3.07–8.87, P = 0.000), extensive anterior myocardial infarction (OR 3.02, 95% CI 1.85–4.93, P = 0.000), use of furosemide (OR 1.02, 95% CI 1.02–1.03, P = 0.000), non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (OR 1.58, 95% CI 1.04–2.40, P = 0.032). These factors provided an accurate tool to identify patients at high risk of developing AKI. Conclusions: Approximately 26.0% of patients undergoing AMI developed AKI, and the development of AKI was strongly correlated with in-hospital mortality. The risk factors for AKI in patients with AMI were determined to help identify high-risk patients and make appropriate clinical decisions. Key words: Acute myocardial infarction; Acute kidney injury; Risk factor

Comparison of the Hemodynamic Response to Intra-Aortic Balloon Counterpulsation in Patients With Cardiogenic Shock Resulting from Acute Myocardial Infarction Versus Acute Decompensated Heart Failure.

Abstract: The intra-aortic balloon pump (IABP) neither benefits nor harms patients with acute myocardial infarction (AMI) with cardiogenic shock (CS) but may stabilize those with chronic heart failure who decompensate into CS. We sought to compare its hemodynamic effects in these 2 populations. We performed a retrospective analysis of the hemodynamic effects of IABP for AMI or acute decompensated heart failure (ADHF) patients with hemodynamic evidence of CS. The primary outcome was cardiac output (CO) change following insertion. In total, 205 patients were treated for CS resulting from AMI (73; 35.6%) or ADHF (132; 64.4%). At baseline, both cohorts had significant hemodynamic compromise with mean arterial pressure 75.6 ± 12.3 mm Hg, CO 3.02 ± 0.84 L/min, and cardiac power index 0.26 ± 0.06 W/m2; these parameters were nearly identical between groups though ADHF-CS patients had a higher pre-IABP mean pulmonary artery (PA) pressure than AMI-CS patients. After IABP insertion, ADHF-CS patients had moderate CO augmentation whereas AMI-CS experienced almost no improvement (0.58 ± 0.79 L/min vs 0.12 ± 1.00 L/min; p = 0.0009). Intracardiac filling pressures were reduced by similar amounts in both cohorts. Systemic vascular resistance was reduced in patients with ADHF-CS but not in those with AMI-CS. In conclusion, following IABP insertion, ADHF-CS patients experience roughly a 5-fold greater CO augmentation compared with AMI-CS patients. Pre-IABP PA pressure differences and differential systemic vascular resistance reduction may explain these results and shed light on recent evidence supporting IABP use in ADHF-CS and curbing it in AMI-CS.

Excessive Neutrophil Extracellular Trap Formation Aggravates Acute Myocardial Infarction Injury in Apolipoprotein E Deficiency Mice via the ROS-Dependent Pathway.

Abstract: Genetically human apolipoprotein E (APOE) e32 is associated with a decreased risk of ischemic heart disease. ApoE deficiency in mice impairs infarct healing after myocardial infarction (MI). After the ischemic injury, a large number of neutrophils are firstly recruited into the infarct zone and then degrade dead material and promote reparative phase transformation. The role of ApoE in inflammation response in the early stage of MI remains largely unclear. In this study, we investigated the effect of ApoE deficiency on neutrophils’ function and myocardial injury after myocardial infarction. By left coronary artery ligation in ApoE-/- and wild-type (WT) mice, we observed increased infarct size and neutrophil infiltration in ApoE-/- mice. Within the infarct zone, more neutrophil extracellular traps (NETs) were observed in ApoE-/- mice, while increased ex vivo NET formation was detected in ApoE-/- mouse-derived neutrophils through the NADPH oxidase-ROS-dependent pathway. Suppressing overproduced NETs reduced myocardial injury in ApoE-/- mice after ligation. In general, our findings reveal a critical role of apolipoprotein E in regulating Ly6G+ neutrophil activation and NET formation, resulting in limiting myocardial injury after myocardial infarction. In such a process, apolipoprotein E regulates NET formation via the ROS-MAPK-MSK1 pathway.

Factors Associated With Excess Myocardial Infarction Risk in HIV-Infected Adults: A Systematic Review and Meta-analysis.

Abstract: Objectives:To estimate the pooled relative risk (RR) of incident acute myocardial infarction (AMI) among HIV-infected adults compared with HIV-uninfected controls and explore the contribution of traditional and HIV-related risk factors.Background:Understanding AMI risk and associated risk factors in

Multidisciplinary teams for cardiogenic shock.

Abstract: hypoperfusion due to a primary cardiac problem associated with high mortality and morbidity in the contemporary era [1, 2]. More than 80% of all CS cases in the modern era are due to acute myocardial infarction (AMI) [1, 2]. Despite rapid advancements in the field of interventional cardiology and percutaneous coronary interventions (PCI), AMI-CS continues to be associated with high mortality in excess of 30-40% [3-5]. However, despite shorter door-to-balloon times and greater use of coronary angiography and PCI in recent years, there appears to be minimal incremental mortality benefit in this population [1]. AMI-CS follows a ‘hemometabolic’ cascade, wherein the initial hemodynamic Editorial

LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model.

Abstract: Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of 1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.

Inhibition of inflammation by minocycline improves heart failure and depression-like behaviour in rats after myocardial infarction.

Abstract: Rationale Patients with heart failure have an increased incidence of depression. Central and peripheral inflammation play a major role in the pathophysiology of both heart failure and depression. Aim Minocycline is an antibiotic that inhibits microglia activation and release of pro-inflammatory cytokines. We assessed effects of minocycline on extent of heart failure and depression at 2 and 8 weeks post myocardial infarction. Methods/Results Male Wistar rats were randomly divided into 3 groups: (i) sham + vehicle; (ii) MI + vehicle; and (iii) MI + minocycline with n/group of 8, 9 and 9 at 2 weeks, and 10, 16, 8 at weeks, respectively. Oral minocycline (50 mg/kg/day) or vehicle started 2 days before surgery. Depression-like behaviour was assessed with sucrose preference and forced swim tests, and cardiac function with echo and hemodynamics. After myocardial infarction, microglia activation and plasma/brain pro-inflammatory cytokines increased, which were mostly prevented by minocycline. At 8 weeks, cardiac dysfunction was attenuated by minocycline: infarct size (MI + Vehicle 29±1, MI + Min 23±1%), ejection fraction (Sham 80±1, MI + Vehicle 48±2, MI + Min 58±2%) and end diastolic pressure (Sham 3.2±0.3, MI + Vehicle 18.2±1.1, MI + Min 8.5±0.9 mm Hg). Depression-like behaviour was significantly improved by minocycline in sucrose preference test (% Sucrose Intake: Sham 96±1, MI + Vehicle 78±2, MI + Min 87±2) and forced swim test (% Immobile: Sham 40±4, MI + Vehicle 61±3, MI + Min 37±6). Conclusion Rats post myocardial infarction develop systemic inflammation, heart failure and depression-like behaviour that are all attenuated by minocycline. Targeting (neuro) inflammation may represent new therapeutic strategy for patients with heart failure and depression.

Salvage MitraClip in severe secondary mitral regurgitation complicating acute myocardial infarction: data from a multicentre international study.

Abstract: Chronic secondary mitral regurgitation (SMR) is associated with a poor prognosis among patients with heart failure (HF). Although medical therapy is the mainstay of treatment for this condition,1 data obtained from largescale registries2,3 and recent randomized controlled trials suggest that transcatheter edge-to-edge mitral valve repair with the MitraClip device may improve functional capacity and quality of life.4 While the impact of MitraClip implantation on outcomes in chronic severe symptomatic ischaemic SMR has been established,5 there are sparse data regarding patients with severe acute ischaemic SMR who are often not included in registries or randomized trials. The acute onset of severe SMR often causes pulmonary congestion and forward left ventricular failure. Although most patients may clinically improve with appropriate medical therapy, some remain symptomatic and may require urgent mitral valve intervention to allow recovery. We used the national Israeli MitraClip Registry (IMCR), a multicentre retrospective registry, involving nine sites in Israel, which collects data on all patients who underwent MitraClip procedures in Israel since January 2011. Additional data were added from three non-Israeli centres: (i) University Hospital of Zurich, Zurich, Switzerland; (ii) Sunnybrook Health Sciences Centre, Toronto, Canada; and (iii) HYGEIA Hospital, Athens, Greece. Patients were included if they were treated with MitraClip due to SMR within 90 days of myocardial infarction (MI), with no evidence of structural valvular damage (ruptured cord or papillary muscle). All patients remained symptomatic despite optimal medical therapy and were evaluated by a multidisciplinary team and were deemed high risk for surgery and therefore salvage MitraClip procedure was performed to allow stabilization and recovery. We evaluated immediate, 30-day and intermediate term outcomes in these patients. The study complies with the Declaration of Helsinki, the locally appointed ethics committee has approved the research protocol, and informed consent was obtained from all subjects (or their legally authorized representatives). Results are expressed as the mean± standard deviation, or as percentages. Paired ttest was used to compare differences between groups for continuous variables and the chisquare test was used for categorical data. From January 2011 to September 2018, 558 patients were treated with MitraClip system in Israel. Eight patients (1.4%) were identified as being treated for SMR in the

Unresolved issues in left ventricular postischemic remodeling and progression to heart failure.

Abstract: In the past decades, myocardial infarction periacute mortality markedly declined since coronary reperfusion therapy has been adopted. Despite immediate benefits of coronary blood flow restoration, the percentage of new onset heart failure has increased over time suggesting that ischemia can run detrimental consequences beyond the immediate anoxic hit. By accepting to aggregate all types of heart failure regardless of underlying cause, the current practice did not help to shed light on the complex postischemic cardiac biology indicating that heart failure is somewhat unavoidable. In the ischemic sequel, the activated mechanisms aim to repair the infarcted zone and to compensate for the lost myocyte functions, thus allowing the heart to maintain the efficient cardiac output for vital organs. The variety of underlying preexisting conditions, as well as the multifaceted components of cardiac molecular structure, cellular state, and electrophysiological postischemic events pave the way for long-term adverse cardiac remodeling. We focused our attention on multiple factors, which include myocyte loss, hypertrophy, hyperplasia, extracellular matrix changes linked to myocardial fibrosis and scar, metabolic imbalance, as well as immunologic response occurring in the acute myocardial aftermath. Moreover, we reported both current pharmacological strategies and future perspectives that might be useful in clinical practice. Furthermore, we discussed the cardiac magnetic resonance as the most promising noninvasive imaging tool, which could be helpful in identifying the amount of myocardial damage. Despite the redundancy of molecular pathogenic mechanisms making it impossible to estimate the proportionate contributions in generating the heart failure phenotype, a deeper understanding will contribute to more customized patient management.

ASSOCIATION OF RETINAL VEIN OCCLUSION WITH CARDIOVASCULAR EVENTS AND MORTALITY: A Systematic Review and Meta-analysis

Abstract: Purpose:Previous studies examining the association of retinal vein occlusion (RVO) and cardiovascular events have been inconsistent and have mostly focused on stroke and myocardial infarction. The goal of this study is to use meta-analysis to examine the available evidence examining the association

Dual antiplatelet therapy in patients with cirrhosis and acute myocardial infarction - A 13-year nationwide cohort study.

Abstract: Background Patients with cirrhosis and acute myocardial infarction (AMI) present dilemma whether dual antiplatelet therapy (DAPT) should be used. Methods Electronic medical records between 2001–2013 were retrieved from Taiwan National Health Insurance Research Database. Patients were excluded for missing information, age <20 years old, history of AMI, liver transplant, autoimmune disease, coagulopathy, taking DAPT 3 months before index date, follow-up <3 months, anticoagulation user, without DAPT, and events of myocardial infarction (MI), ischemic stroke, major bleeding, and heart failure within 3-month of enrollment. Primary outcomes were 1-year all-cause mortality, recurrent MI, major bleeding, and gastrointestinal bleeding. Results A total of 150,887 patients with AMI retrieved. After exclusion criteria and propensity score-matching, 914 cirrhotic and 3,656 non-cirrhotic patients with AMI on DAPT were studied. During 1-year follow-up, there was significantly increased mortality in cirrhotic patients compared to non-cirrhotic patients (HR = 1.49, 95% CI = 1.28–1.74). There was significantly decreased recurrent MI in cirrhotic patients compared to non-cirrhotic patients (subdistribution HR [SHR] = 0.71, 95% CI = 0.54–0.92). However, non-significantly increased major bleeding (SHR = 1.23, 95% CI = 0.87–1.73) and significantly increased gastrointestinal bleeding (SHR = 1.49, 95% CI = 1.31–1.70). Conclusions In cirrhotic patients with AMI, DAPT offers benefit with decreased recurrent MI at the expense of increased gastrointestinal bleeding.

MitraClip and Tertiary Mitral Regurgitation-Mitral Regurgitation Gets Curiouser and Curiouser.

Abstract: Primary MR In primary MR, an anatomic abnormality in the structure of the valve causes it to leak. Causative mechanisms include fibroelastic deficiency disease, Barlow disease, rheumatic disease, and infective endocarditis. Primary MR is the disease wherein the valve abnormalities cause left ventricular (LV) volume overload, neurohormonal activation, LV damage, and eventual death. Fortunately, timely valve repair can be curative, allowing for restoration of mitral competence, LV function, and longevity.1

Increased Ratio of Circulating T-Helper 1 to T-Helper 2 Cells and Severity of Coronary Artery Disease in Patients with Acute Myocardial Infarction: A Prospective Observational Study.

Abstract: BACKGROUND This study aimed to determine the association between CD4-positive T-helper (Th) cell subsets, T-helper 1 (Th1) and T-helper 2 (Th2) in patients with acute myocardial infarction (AMI) and the severity of coronary artery disease (CAD) determined by coronary artery angiography. MATERIAL AND METHODS Three groups of patients with AMI who underwent coronary angiography and percutaneous coronary intervention (PCI) included patients with stable CAD (n=35), ST-segment elevation myocardial infarction (STEMI) (n=30), and non-STEMI (NSTEMI) (n=35), and controls (n=33). Measurement of high-sensitivity cardiac troponin T (hs-cTnT) was performed. The numbers of circulating CD4-positive Th1 and Th2 cells were measured using flow cytometry. Plasma levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS An increase in the Th1 lymphocyte population was associated with more CAD, and an increased Th1/Th2 ratio was found in patients with NSTEMI and STEMI (controls 7.27±2.98; stable CAD 7.58±2.52; NSTEMI 16.62±2.74; and STEMI 22.32±7.35) (P<0.001). The proportion of Th1 cells and the Th1/Th2 ratio increased as the number of affected arteries, the degree of stenosis, and the lesion length increased. At a median follow-up of 18.2 months, patients with CAD and an increased Th1/Th2 ratio had a significant increase in adverse cardiac events compared with patients with a reduced Th1/Th2 ratio (log-rank, P=0.042). CONCLUSIONS An increased ratio of circulating Th1 to Th2 cells in patients with AMI was associated with the severity of CAD determined by angiography.

Theacrine attenuates myocardial fibrosis after myocardial infarction via the SIRT3/β-catenin/PPARγ pathway in estrogen-deficient mice.

Abstract: Objective To investigate the role of theacrine in the protection of ventricular remodeling and chronic heart failure after myocardial infarction in the estrogen-deficient mice. Materials and methods Female C57BL/6 mice aged 8 weeks old were selected and then subjected to bilateral oophorectomy. At 7 days after surgery, the models of the myocardial infarction were established by ligating the anterior descending coronary artery. On the first day after myocardial infarction, Theacrine (20 mg/kg) was administered via gavage for continuous 28 days. Thereafter, the cardiac function in each group of mice was detected via cardiac ultrasonography for small animals at 7, 14, and 28 days after surgery. The mice were sacrificed after 28 days. The infarct size of mice was determined through 2,3,5-triphenyltetrazolium chloride (TTC) and Evan blue double staining assay, while the myocardial fibrosis was assessed via Masson staining assay. The expression levels of collagen-related proteins Collagen I, Collagen III, alpha-smooth muscle actin (α-SMA), and the transforming growth factor-β (TGF-β) were measured by Western blotting (WB). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining assay was applied to evaluate the myocardial apoptosis, and the WB was employed to detect apoptosis-associated proteins. The expression level of silent information regulator 2 homologue 3 (SIRT3) protein was detected by immunohistochemistry, and the expression levels of SIRT3, β-catenin and peroxisome proliferator-activated receptor gamma (PPARγ) protein were measured via WB. Results Compared with those in the Sham group, the ejection fraction (EF) and fractional shortening (FS) in estrogen-deficient mice were significantly lowered, the myocardial fibrosis and myocardial apoptosis were clearly aggravated, and the SIRT3 expression was decreased at 28 days after myocardial infarction. The theacrine could improve the cardiac function after the myocardial infarction in estrogen-deficient mice and relieve both myocardial fibrosis and myocardial apoptosis during chronic remodeling after myocardial infarction in estrogen-deficient mice. After the intervention with theacrine, the estrogen-deficient mice with myocardial infarction had up-regulated SIRT3 and PPARγ levels and a reduced β-catenin level in the heart. Conclusions Theacrine is able to activate SIRT3 and repress myocardial fibrosis and apoptosis after myocardial infarction in ovariectomized mice, thereby improving the cardiac function of ovariectomized mice with myocardial infarction through the possible downstream signal pathway β-catenin/PPARγ.

Understanding the role of echocardiography in remodeling after acute myocardial infarction and development of heart failure with preserved ejection fraction.

Abstract: Despite the use of reperfusion therapies in the last decades, acute myocardial infarction further remains one of the most frequent causes of mortality. This is mainly caused by changes in the ventricular architecture leading to ventricular remodeling, followed by progressive development of heart failure. Transthoracic echocardiography is a non-invasive instrument which can provide information about the extent of the ischemic process and its consequences but can also predict the outcomes after myocardial infarction. Although standard echocardiographic parameters are currently used for risk stratification of these patients, they might not truly reflect left ventricular systolic dysfunction in acute myocardial infarct patients, since the detection of subtle changes in the myocardial function is beyond their limits. The aim of this review is to underline the use of advanced echocardiographic parameters in identifying patients at risk for developing post-acute myocardial infarction heart failure and subsequent adverse events. Advanced echocardiographic parameters derived from speckle tracking echocardiography provide a detailed assessment on the global and regional left ventricular deformation. Therefore, speckle tracking echocardiography has a major role in predicting the prognosis of acute myocardial infarction patients and particularly in the development of subsequent heart failure, which might be prevented with early initiation of adequate therapy.

Use of Nitrates and Risk of Cardiovascular Events in Patients With Heart Failure With Preserved Ejection Fraction.

Abstract: Objective To assess the association of nitrate use with cardiovascular events in patients with heart failure with preserved ejection fraction (HFpEF). Patients and Methods Patient data were collected from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist trial, which had been conducted at 233 sites in 6 countries from August 10, 2006, through January 31, 2012. The primary outcome was the occurrence of a major adverse cardiovascular event (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) or heart failure hospitalization. The association between nitrate use and cardiovascular risk was evaluated using Cox proportional hazards analysis. In addition, we verified the results using propensity score–matched patients. Results A total of 3417 patients with HFpEF were evaluated over a mean follow-up of 3.1 years, and 778 experienced a primary outcome event. The risk of primary outcome events was significantly higher in patients taking nitrates than in those not taking nitrates (hazard ratio [HR], 1.21; 95% CI, 1.01-1.46, P=.04). The risk of major adverse cardiovascular events was significantly higher in patients taking nitrates than in those not taking nitrates (HR, 1.32; 95% CI, 1.05-1.66, P=.01). Furthermore, the risk of hospitalization for heart failure was higher in patients taking nitrates (HR, 1.25; 95% CI, 0.99-1.60, P=.06), with propensity score–matched analyses revealing similar findings. In addition, a similar association was observed in various subgroups. Conclusion This study reported that nitrate use in patients with HFpEF was associated with a significantly increased risk of cardiovascular events.

Specific Inhibition of Brain Angiotensin III Formation as a New Strategy for Prevention of Heart Failure After Myocardial Infarction.

Abstract: Aims Inhibition of brain angiotensin III by central infusion of aminopeptidase A (APA) inhibitor firibastat (RB150) inhibits sympathetic hyperactivity and heart failure in rats after myocardial infarction (MI). This study evaluated effectiveness of systemic treatment with firibastat compared with AT1R blocker, losartan. Methods and results MI was induced by ligation of left coronary artery in male Wistar rats. Rats were treated from 1 to 5 weeks after MI in protocol 1 with vehicle, or firibastat at 50 mg/kg/d subcutaneously (s.c.) or 150 mg/kg/d oral, once daily, and in protocol 2, with vehicle, firibastat 150 mg/kg or losartan 50 mg/kg oral twice daily. At 5 weeks, left ventricle function was evaluated by echocardiography and Millar catheter. After MI, rats developed moderate severe heart failure. Both s.c. and oral firibastat inhibited brain APA and attenuated left ventricle dysfunction. Oral firibastat and losartan similarly improved left ventricular end diastolic pressure. However, whereas firibastat improved dP/dtmax, losartan lowered dP/dtmax and left ventricular peak systolic pressure, and increased plasma creatinine by ~50%. On the other hand, losartan more effectively inhibited cardiac fibrosis. Conclusion Inhibition of the brain renin-angiotensin system by oral APA inhibitor is at least as effective as oral AT1R blocker to inhibit cardiac dysfunction after MI but without hypotension or renal dysfunction.