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Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66) [Display omitted] [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) as a risk of stroke in patients with atrial fibrillation (AF) mainly referred to patients with left ventricular systolic dysfunction. Whether this should include patients with preserved ejection fraction is debatable. The study aimed to investigate the variation in stroke risk of AF patients with heart failure with preserved ejection fraction (HFpEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF) for enhancing risk assessment and subsequent management strategies. In a longitudinal study using the National Taiwan University Hospital integrated Medical Database, 8358 patients with AF were observed for 10 years (mean follow-up, 3.76 years). The study evaluated the risk of ischemic stroke in patients with differing ejection fractions and CHA 2 DS 2 -VASc score, further using Cox models adjusted for risk factors of AF-related stroke. Patients with HFpEF and HFmrEF had a higher mean CHA 2 DS 2 -VASc score compared with patients with HFrEF (4.30 ± 1.729 vs 4.15 ± 1.736 vs 3.73 ± 1.712; P <.001) and higher risk of stroke during follow-up (hazard ratio [HR], 1.40 [1.161–1.688; P <.001] for HFmrEF; HR, 1.184 [1.075–1.303; P =.001] for HFpEF vs no CHF) after multivariate adjustment). In patients with lower CHA 2 DS 2 -VASc score (0–4), presence of any type of CHF increased ischemic stroke risk (HFrEF HR, 1.568 [1.189–2.068; P =.001]; HFmrEF HR, 1.890 [1.372–2.603; P <.001]; HFpEF HR, 1.800 [1.526–2.123; P <.001] vs no CHF). After multivariate adjustment, HFpEF and HFmrEF showed a similar risk of stroke in AF patients. Therefore, it is important to extend the criteria for C in the CHA 2 DS 2 -VASc score to include patients with HFpEF and HFmrEF. In patients with fewer concomitant stroke risk factors, the presence of any subtype of CHF increases risk for ischemic stroke. [Display omitted] [ABSTRACT FROM AUTHOR]

• Clinical settings influence stroke prediction scores in HFrEF with sinus rhythm. • Rivaroxaban is associated with a reduced stroke risk in HFrEF with sinus rhythm and high D-dimer. • The predictive value of stroke risk score should be evaluated further. Patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d -dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban. Stroke risk and treatment effect were computed across risk score and plasma d -dimer tertiles. Risk score was available in 58% of the COMMANDER-HF population (n = 2928). Over a median follow-up of 512 days (range 342–747 days), 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index = 0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P -interaction =.67). Among patients in whom the risk score was estimated, d -dimer was available in 2343 (80%). d -dimer had an acceptable discrimination performance for stroke prediction (C-index = 0.66) and higher plasma d -dimer concentrations were associated with higher rates of stroke (ie, tertile 3 vs tertile 1, hazard ratio 3.65, 95% confidence interval 1.59–8.39, P =.002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by d -dimer levels (ie, >515 ng/mL, hazard ratio 0.42, 95% confidence interval 0.18–0.95, P -interaction =.074), without any safety concerns. In our analysis, plasma d -dimer concentrations performed better than a previously described 3-variable risk score for stroke prediction in patients with heart failure with reduced ejection fraction, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma d -dimer concentration identified patients who might benefit most from rivaroxaban. [ABSTRACT FROM AUTHOR]

• Electrocardiographic changes might differentiate hospitalized heart failure patients with reduced and preserved left ventricular ejection fraction during acute decompensated heart failure. • Common characteristics of HFrEF were men, comorbidities of coronary artery diseases and diabetes mellitus, higher BNP/Pro-BNP, wide QRS, and left bundle branch block on ECG. • Those with HFpEF were older and more likely to have a history of atrial fibrillation, valvular heart diseases, hypertension, chronic obstructive pulmonary, and atrial fibrillation on ECG. An ECG might be a prognostic tool to estimate left ventricular ejection fraction. Electrocardiographic (ECG) changes in heart failure with reduced, mildly reduced, and preserved ejection fractions can be critical in clinical assessment while waiting to perform echocardiograms or when it is unavailable. This integrative review aimed to identify ECG characteristics among hospitalized patients demonstrating three types of heart failure during acute decompensation. We searched an electronic database of PubMed, Web of Science, EMBASE, Scopus, Google Scholar, and ClinicalTrials.gov using medical subject headings (MeSH) terms and keywords. Sixteen studies were synthesized and reported. Heart failure with reduced ejection fraction (HFrEF) was more common in men, comorbid with coronary artery diseases and diabetes mellitus, higher BNP/Pro-BNP, wide QRS, and left bundle branch block on ECG. On average, clients with heart failure with preserved ejection fraction (HFpEF) were older and more likely to have a history of atrial fibrillation, valvular heart diseases, hypertension, chronic obstructive pulmonary, and atrial fibrillation (AF) on ECG. Patients with mildly reduced (HFmrEF) were more similar to HFpEF in older patients, comorbid with hypertension, AF and valvular diseases, and AF on ECG. ECG characteristics might be related to left ventricular ejection fraction. Demographics, BNP/Pro-BNP, and ECG changes might help differentiate different heart failure types. Therefore, ECG might be a prognostic tool while caring for heart failure patients when highly skilled resources are unavailable. These identified ECG characteristics help generate research hypotheses and warrant validation in future research. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is associated with both mortality and a significant decline in health status. Interatrial shunting is increasingly being investigated as a novel therapeutic option. The ALT FLOW Early Feasibility Study was designed to evaluate the safety of the Edwards left atrial to coronary sinus APTURE Transcatheter Shunt System in patients with symptomatic HF. A total of 18 centers enrolled patients with symptomatic HF with a pulmonary capillary wedge pressure >15 mm Hg at rest or 25 mm Hg during exercise. Between May 2018 and September 2022, 87 patients underwent attempted APTURE shunt implantation. Mean age was 71 years, and 53% were male. At baseline, mean left ventricular ejection fraction was 59% with 90% of the patients being in NYHA functional class III. Device success was achieved in 78 patients (90%), with no device occlusions or associated adverse events identified after implantation. The primary safety outcome occurred in only 2 patients (2.3%) at 30 days. At 6 months, health status improved: 67% of participants achieved NYHA functional class I to II status, with a 23-point improvement (P < 0.0001; 95% CI: 17-29 points) in the Kansas City Cardiomyopathy Questionnaire overall summary score. Also at 6 months, 20-W exercise pulmonary capillary wedge pressure was 7 mm Hg lower (P < 0.0001; 95% CI: −11 to −4 mm Hg) without change in right atrial pressure or other right heart function indices. In this single-arm experience, the APTURE Transcatheter Shunt System in patients with symptomatic HF was observed to be safe and resulted in reduction in pulmonary capillary wedge pressure and clinically meaningful improvements in HF symptoms and quality of life indices. [Display omitted] [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is common, but there are limited data to guide selection of rate control medications (RCM). Reasons for selection are multivariable, and the impact on outcomes is unknown. We investigated prescribing patterns of RCM among patients with AF. Using a nationwide database, we identified 135,927 patients with AF. We stratified by baseline presence of heart failure with reduced ejection fraction (HFrEF) and examined prescription rates of RCM as a function of clinical variables. We also evaluated associations with clinical outcomes. Beta blockers (BB) were most commonly prescribed (44.6%), then calcium channel blockers (CCB) (14.0%) and digoxin (8.6%). Patients prescribed BB were more likely male (45.6% vs 43.4%, p < 0.0001), patients prescribed CCB were less likely male (12.0% vs 16.3%, p < 0.0001). There were higher rates of HF hospitalization (HFH) among females and those with Medicaid. Randomized trials are needed to define optimal choice of RCM. [ABSTRACT FROM AUTHOR]

Heart failure (HF) often occurs in patients who have more than one comorbidity, with resultant polypharmacy. Medication errors may occur, along with adverse interactions between medicines. This highlights the importance of the pharmacist as part of the multidisciplinary team in the management of HF. Many advances have been made in the way in which heart failure is classified, diagnosed, managed and treated. The body of knowledge is ever-expanding, and hence the need for frequent review of treatment guidelines in light of the data emerging from ongoing research. This article focuses on elucidating some of the current strategies to manage and treat this condition. Certain associated pathological conditions and modalities are therefore beyond the scope of this article and the reader is advised to consult the the latest international guidelines for more detailed explanations of advanced treatment strategies, the cardiomyopathies, congenital heart defects, acute cardiac failure, and heart failure within the context of myocardial infarction, cardiac valve replacement surgery, coronary artery revascularisation and other specialised examples. [ABSTRACT FROM AUTHOR]

Background: With an ageing population and multimorbidity on the rise, polypharmacy is also increasing. Polypharmacy is common in patients with heart failure, possibly due to the application of evidence‐based therapy to improve prognosis and symptoms. Objectives: To identify potentially inappropriate medications according to Beers criteria and the STOPP screening tool;To assess if the recommendations generated from applying these tools could have potentially unintended harmful outcomes in the context of a heart failure diagnosis. Method: Medications for 30 patients, aged ≥75 years with an existing diagnosis of reduced ejection fraction (HFrEF) were extracted from the National Heart Failure Database. Patient medications were reviewed at the point of admission and recommendations documented and reviewed. Results: Patients were prescribed an average of 11 medicines. Beers criteria generated 22 recommendations, of which 27% (6) could have potential detrimental effects on patient outcomes. STOPP screening generated 54 recommendations of which 65% (35) were considered to have potentially unintended harmful consequences in patients with heart failure. Conclusions: Both guidelines for the review of potentially inappropriate medicines generated recommendations that could have potentially detrimental effects on heart failure management when considering patients with HFrEF. [ABSTRACT FROM AUTHOR]

Morbid obesity (MO) is an increasingly common condition in patients with heart failure with reduced ejection fraction (HFrEF). Although substantial weight loss in morbidly obese patients has proved to slow the progression of heart failure, parallel alteration of ejection fraction (EF) and New York Heart Association (NYHA) functional class along with post-bariatric surgery weight loss is yet to be determined. This systematic review aimed to measure the effect of bariatric weight loss on EF and NYHA functional class in patients with HFrEF. A systematic literature review was performed in Medline/PubMed to identify studies in patients with MO and pre-existing HFrEF, who underwent bariatric surgery. A total of 11 studies encompassing 136 patients with HFrEF undergoing bariatric surgery for MO were included. Six studies provided patient-level data on 37 cases. Patients lost an average body mass index (BMI) of 12.9 ± 4.2 kg/m2 (5.1 to 23 kg/m2) after an average follow up of 22.43 ± 18.6 months (2–89 mo). There was a direct correlation between BMI loss and EF improvement (r = 0.61, P <.0001), but not between BMI loss and NYHA functional class changes (r = 0.17, P =.4). Weight loss induced by bariatric surgery results in parallel EF increase in patients with MO and HFrEF. However, current data does not indicate a parallel improvement of clinical symptoms (NYHA functional class) along with such an increase in EF in this population of patients. - Weight loss induced by bariatric surgery result in parallel increase in ejection fraction (EF) in morbidly obese patients with heart failure with reduced ejection fraction (HFrEF). - There is not sufficient data in the literature to support rapid improvement of clinical symptoms in and NYHA functional class parallel with improvement increasing EF. [ABSTRACT FROM AUTHOR]

Background: Clinical congestion is associated with adverse outcomes in patients with heart failure. The pathophysiological mediators of this association remain uncertain.Methods and Results: We prospectively enrolled a cohort of patients with heart failure and reduced left ventricular ejection fraction and performed a detailed clinical examination followed on the same day by an invasive right heart catheterization and blood sampling for biomarkers. High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured. A clinical congestion score was calculated based on jugular venous pressure (cm H20 <10 = 0, 10-14 = 1, >14 = 2 points), bendopnea (0 vs 1), a third heart sound (0 vs 1), or peripheral edema (0-2). Congestion was categorized into tiers as absent (0 points), mild (1 point), or moderate to severe (≥ 2 points). We tested for associations of high-sensitivity troponin T, NT-proBNP, and elevated ventricular filling pressures with clinical congestion in both univariate and multivariable analyses. Of 153 participants, 65 (42%) had absent, 35 mild (23%), and 53 (35%) had moderate to severe clinical congestion. Congestion tier was associated with higher NT-proBNP and hs-troponin levels, and the right atrial pressure and pulmonary capillary wedge pressure (P < .001 for each). Increased congestion tier was also associated with the coexistent presence of elevated troponin T (≥52 ng/L), NT-proBNP (≥1000 pg/mL), and pulmonary capillary wedge pressure (≥22 mm Hg). Specifically, 78% of those with absent clinical congestion had 0 to 1 of these findings, whereas 75% of those with moderate-severe congestion had 2 or all 3 of these abnormalities (P < .001). An elevated hs-troponin was associated with mild or greater clinical congestion (odds ratio 3, 95% confidence interval 1.2-7.5, P = .02) in multivariable analysis adjusting for potential confounders including the right atrial pressure, pulmonary capillary wedge pressure, and NT-proBNP levels.Conclusions: Clinical congestion is a phenotype in which there is a high coexistent presence of elevated ventricular filling pressures, elevated natriuretic peptide levels, and subclinical myocardial injury. An elevated troponin was associated with clinical congestion in multivariable models that adjusted for ventricular filling pressures and natriuretic peptide levels. These data strengthen the evidence base for an association of elevated troponin with clinical congestion, suggesting that subclinical myocardial injury may be an important contributor to the pathophysiology of the congested state. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to evaluate the relationship between three-dimensional echocardiography (3DE)-determined myocardial contraction fraction (MCF) and functional capacity in heart failure with reduced ejection fraction (HFrEF) patients. The MCF is a volumetric index of myocardial function, defined as stroke volume ratio to myocardial volume (MV). Functional capacity was evaluated by a 6-min walk test (6MWT), and health-related quality of life (HRQOL) was assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). In view of cardiac remodeling, we hypothesized that MCF would be superior to left ventricular ejection fraction (LVEF) in predicting functional capacity in HFrEF patients. Methods: The study was conducted on thirty HFrEF patients with an LVEF of no more than 40% with NYHA functional class I-III. Each patient performed, on the same day, the MLHFQ, 6MWT (to calculate the 6-min walk distance "6MWD"), and an ECG gated echocardiographic study including 3DE-determined MCF. MV was calculated as 3DE determined LV mass divided by the specific gravity of the myocardium. Results: Our results showed that MCF is inversely correlated with the Minnesota score (r = ¡0.6, p < 0.001) and positively correlated with 6MWD (r = 0.65, p < 0.001). However, no significant relationship existed between LVEF and MLHFQ score or 6MWD. In a multivariate model, MCF was shown to be an independent echocardiographic predictor (besides pulmonary artery systolic pressure) of 6MWD; however, LVEF failed to offer such potential. Conclusion: Among various echocardiographic parameters, MCF can be considered a volumetric index superior to LVEF in predicting functional capacity in HFrEF patients. [ABSTRACT FROM AUTHOR]

Background: Soluble guanylate cyclase (sGC) stimulators are a novel class of medications with emerging role in heart failure (HF). The aim of this study is to evaluate the efficacy and safety of oral sGC stimulators in patients with HF with reduced and preserved ejection fraction (HFrEF and HFpEF) by pooling data from all available randomized control trials (RCT).Methods: A comprehensive search of electronic databases from 2000-2020 was performed. Seven RCTs, three HFrEF and four HFpEF studies, were identified. The follow-up duration ranged from 1 month to a median of 10.8 months. A random-effects meta-analysis was conducted to summarize the studies.Results: The study population included 7190 patients: 5707 HFrEF and 1483 HFpEF patients. In HFrEF, oral sGC stimulators reduced the composite incidence of HF hospitalization and cardiovascular death (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97; I2 = 0%), primarily driven by lower HF hospitalization (HR 0.88, 95% CI 0.78-0.99; I2 = 0%). There was no significant reduction in all-cause death in HFrEF (HR 0.95, 95% CI 0.83-1.09; I2 = 0%). In HFpEF, there were no improvements in Kansas City Cardiomyopathy Questionnaire clinical summary scores (mean difference 0.81, 95% CI -2.16-3.77; I2 = 72%) or 6-minute walk distance (mean difference 3.34 meters, 95% CI -7.86-14.54; I2 = 28%). There was no difference in all-cause mortality in HFpEF (HR 1.94, 95% CI 0.92-4.09; I2 = 0%). Overall, oral sGC stimulators had low medication-related serious adverse events.Conclusion: Oral sGC stimulators are well tolerated in HF and reduce the incidence of HF hospitalization but not cardiovascular death among patients with HFrEF. However, there are no apparent benefits in HFpEF. [ABSTRACT FROM AUTHOR]

Background: The role of oral vasodilators in the management of acute decompensated heart failure (ADHF) is not clearly defined. We evaluated the use of captopril vs hydralazine-isosorbide dinitrate (H-ISDN) in the transition from sodium nitroprusside (SNP) in patients with ADHF.Methods and Results: A retrospective chart review was performed of 369 consecutive adult patients in the intensive care unit with ADHF and reduced ejection fraction, who received either a captopril or an H-ISDN protocol to transition from SNP. Captopril patients were matched 1:2 to H-ISDN patients, based on serum creatinine and race (Black vs non-Black). Baseline demographics, serum chemistry and use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) were similar in both groups. Time to SNP discontinuation (46.9 vs 40.4 hours, P = 0.11) and length of hospital stay (9.86 vs 7.99 days, P = 0.064) were similar in both groups. Length of hospital stay in the intensive care unit was statistically shorter in the H-ISDN group (4.11 vs 3.96 days, P = 0.038). Fewer H-ISDN protocol patients were discharged on ACEis/ARBs (82.9 % vs 69.9%, P = 0.003) despite similar kidney function at time of discharge (serum creatinine 1.1 vs 1.2, P = 0.113). No difference was observed in rates of readmission (40.7% vs 50%, P = 0.09) or mortality (16.3% vs 17.5 %, P = 0.77) at 1 year postdischarge.Conclusion: Similar inpatient and 1-year outcomes were observed between patients using H-ISDN vs ACEi when transitioning from SNP, even though fewer H-ISDN protocol patients were discharged taking ACEis/ARBs despite similar kidney function. [ABSTRACT FROM AUTHOR]

Cardiac glucose oxidation is decreased in heart failure with reduced ejection fraction (HFrEF), contributing to a decrease in myocardial ATP production. In contrast, circulating ketones and cardiac ketone oxidation are increased in HFrEF. Since ketones compete with glucose as a fuel source, we aimed to determine whether increasing ketone concentration both chronically with the SGLT2 inhibitor, dapagliflozin, or acutely in the perfusate has detrimental effects on cardiac glucose oxidation in HFrEF, and what effect this has on cardiac ATP production. 8-week-old male C57BL6/N mice underwent sham or transverse aortic constriction (TAC) surgery to induce HFrEF over 3 weeks, after which TAC mice were randomized to treatment with either vehicle or the SGLT2 inhibitor, dapagliflozin (DAPA), for 4 weeks (raises blood ketones). Cardiac function was assessed by echocardiography. Cardiac energy metabolism was measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, and either 0.2 mM or 0.6 mM β-hydroxybutyrate (βOHB). TAC hearts had significantly decreased %EF compared to sham hearts, with no effect of DAPA. Glucose oxidation was significantly decreased in TAC hearts compared to sham hearts and did not decrease further in TAC hearts treated with high βOHB or in TAC DAPA hearts, despite βOHB oxidation rates increasing in both TAC vehicle and TAC DAPA hearts at high βOHB concentrations. Rather, increasing βOHB supply to the heart selectively decreased fatty acid oxidation rates. DAPA significantly increased ATP production at both βOHB concentrations by increasing the contribution of glucose oxidation to ATP production. Therefore, increasing ketone concentration increases energy supply and ATP production in HFrEF without further impairing glucose oxidation. [Display omitted] • Increased ketone concentration increases energy supply and fuel production in HFrEF. • Glucose oxidation is not further impaired with higher ketone concentrations. • ATP production is higher from increased contribution of glucose oxidation. • Cardiac efficiency is not increased. [ABSTRACT FROM AUTHOR]

Despite decades of stagnant research with regards to heart failure (HF) management, several blockbuster trials have recently revolutionized therapy and provided a new range of therapeutic options all acting on different disease pathways not only for reduc. [ABSTRACT FROM AUTHOR]

Almost three-quarters of all heart failure patients who are older than 65 have heart failure with preserved ejection fraction (HFpEF). The proportion and hospitalization rate of patients with HFpEF are increasing steadily relative to patients in whom heart failure occurs as result of reduced ejection fraction. The predominance of the HFpEF phenotype most likely is explained by the prevalence of medical conditions associated with an aging population. A multitude of age-related, medical, and lifestyle risk factors for HFpEF have been identified as potential causes for the sustained low-grade proinflammatory state that accelerates disease progression. Profound left ventricular (LV) systolic and diastolic stiffening, elevated LV filling pressures, reduced arterial compliance, left atrial hypertension, pulmonary venous congestion, and microvascular dysfunction characterize HFpEF, but pulmonary arterial hypertension, right ventricular dilation and dysfunction, and atrial fibrillation also frequently occur. These cardiovascular features make patients with HFpEF exquisitely sensitive to the development of hypotension in response to acute declines in LV preload or afterload that may occur during or after surgery. With the exception of symptom mitigation, lifestyle modifications, and rigorous control of comorbid conditions, few long-term treatment options exist for these unfortunate individuals. Patients with HFpEF present for surgery on a regular basis, and anesthesiologists need to be familiar with this heterogeneous and complex clinical syndrome to provide successful care. In this article, the authors review the diagnosis, pathophysiology, and treatment of HFpEF and also discuss its perioperative implications. [ABSTRACT FROM AUTHOR]

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Background: There is a lack of research comparing procedural outcomes of surgical ablation (SA) and catheter ablation (CA) among patients with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation (AF). The main objective was to compare the short‐term procedural outcomes of SA and CA in patients with HFrEF. Methods: We used the national inpatient sample to identify hospitalizations over 18 years with HFrEF hospitalization and AF, and undergoing SA and CA from 2016 to 2017. Furthermore, the clinical outcomes of SA vs CA in AF stratified as nonparoxysmal and paroxysmal were analyzed. Results: A total of 1,770 HFrEF hospitalizations with AF who underwent SA and 1,620 HFrEF hospitalizations with AF who underwent CA were included in the analysis. Hospitalizations with CA had higher baseline comorbidities. The in‐hospital mortality among HFrEF with AF undergoing SA as compared with CA was similar (2.8% vs 1.9%, respectively, adjusted P‐value 0.09). Hospitalizations with SA had a significantly longer length of hospital stay, a higher percentage of postprocedural, and cardiac complications. In HFrEF hospitalizations with nonparoxysmal AF, SA as compared with CA was associated with a higher percentage of in‐hospital mortality (2.4% vs 1%, adjusted P‐value <.05), a longer length of stay, a higher cost of treatment, and a higher percentage of cardiac complications. Conclusion: CA is associated with lower in‐hospital adverse procedural outcomes as compared with SA among HFrEF hospitalizations with AF. Further research with freedom from AF as one of the outcome is needed between two groups for HFrEF. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure with reduced left ventricular ejection fraction (LVEF) (HFrEF) experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased mortality risk. The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure (ANTHEM-HF) trial reported improved heart rate variability (HRV) and heart rate turbulence (HRT) and reduced T-wave alternans (TWA) after 12 months of vagus nerve stimulation (VNS). We investigated whether the benefits of chronic VNS persist in the long term.Methods and Results: Effects of chronic VNS on heart rate, HRV, HRT, TWA, R-wave and T-wave heterogeneity (RWH, TWH), and nonsustained ventricular tachycardia (NSVT) incidence were evaluated in all ANTHEM-HF patients with ambulatory ECG data at 24 and 36 months (n = 25). Autonomic markers improved significantly at 24 and 36 months compared to baseline [heart rate, square root of the mean squared differences of successive normal-to-normal intervals (rMSSD), standard deviation of the normal-to-normal intervals (SDNN), HF-HRV, HRT slope, P < 0.05]. Peak TWA levels remained reduced at 24 and 36 months (P < 0.0001). Reductions in RWH and TWH at 6 and 12 months persisted at 24 and 36 months (P < 0.01). NSVT decreased at 12, 24, and 36 months (P < 0.025). No sudden cardiac deaths, ventricular fibrillation, or sustained ventricular tachycardia occurred.Conclusion: In symptomatic patients with HFrEF, chronic VNS appears to confer wide-ranging, persistent improvements in autonomic tone (HRV), baroreceptor sensitivity (HRT), and cardiac electrical stability (TWA, RWH, TWH). [ABSTRACT FROM AUTHOR]

• MIF rs755622 gene polymorphism is implicated in the pathogenesis of heart failure. • Addition of MIF genotype to the established risk factors may improve HF risk prediction. • The GG genotype of MIF rs755622 gene polymorphism associate with a serious medical condition. • Inhibition of MIF gene could permit the development of new therapy. • MIF rs755622 genotypes differed considerably among patients with HFpEF versus HFrEF. Heart failure (HF) is a serious public health concern resulting in death. An individual predisposition to HF is determined by relationship between genetic and environmental variables. The macrophage migration inhibitory factor (MIF) is a significant mediator that involved in a variety of inflammatory and cardiovascular diseases. To reveal contribution of MIF rs755622 G173C gene variants in the promoter region towards HF pathogenesis and investigate association between recognized genotype and clinical characteristics. We recruited 90 patients with HF, 63 with preserved ejection fraction (HFpEF) and 27 with reduced ejection fraction (HFrEF), and 60 age- and sex- matched controls. MIF rs755622 (G > C) single-nucleotide polymorphism was genotyped by PCR-RFLP method. The GG genotype of MIF rs755622 gene polymorphism was more frequent in HF patients than in controls which increased the risk of HF by about 4.25 times (p <0.05). The distribution of the GG, GC and CC genotypes of MIF were 42%, 21% and 0.0% among HFrEF, and 33.3%, 55.6% and 11.1% among HFpEF respectively. Higher frequency of MIF rs755622 G allele among HFrEF (100%) compared to HFpEF (88.9%) (p = 0.007). MIF-GG genotype variant had significantly lower LVEF. In multivariate analysis, MIF-GG genotype was independent risk predictor among HF (OR 4.6). MIF rs755622 (GG) could be considered as a probable genotypic risk factor for HF, especially in those with HFrEF which increases the possibility that MIF contribute to HF progression. MIF genotype assay may serve as early predictor and help to recognize those at great risk of developing HF. [ABSTRACT FROM AUTHOR]

Heart failure (HF) often occurs in patients who have more than one comorbidity, with resultant polypharmacy. Medication errors may occur, along with adverse interactions between medicines. This highlights the importance of the pharmacist as part of the multidisciplinary team in the management of HF. Many advances have been made in the way in which heart failure is classified, diagnosed, managed and treated. The body of knowledge is ever-expanding and hence the need for frequent review of treatment guidelines in light of the data emerging from ongoing research. This article focuses on elucidating some of the currrent strategies to manage and treat this condition. Certain associated pathological conditions and modalities are therefore beyond the scope of this article and the reader is advised to consult the the latest international guidelines for more detailed explanations of advanced treatment strategies, the cardiomyopathies, congenital heart defects, acute cardiac failure, and heart failure within the context of myocardial infarction, cardiac valve replacement surgery, coronary artery revascularisation and other specialised examples. [ABSTRACT FROM AUTHOR]

Heart failure is considered to be a common condition in the adult population and is associated with substantial morbidity and mortality rates worldwide. Many advances have been made in the way in which heart failure is classified, diagnosed, managed and treated, and the body of knowledge is ever-expanding. This results in a need for frequent re-review of treatment guidelines and the emerging data from ongoing research. Due to the vastness of the subject matter, however, this article can only focus on the basic essentials to try and elucidate some of the current strategies pertaining to this condition in general. Certain associated pathological conditions and modalities are therefore beyond the scope of this article and the reader is advised to consult the latest international guidelines for more detailed explanations of advanced treatment strategies, the cardiomyopathies, congenital heart defects, acute cardiac failure, and heart failure within the context of myocardial infarction, cardiac valve replacement surgery, coronary artery revascularisation and other specialised examples. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a common clinical condition encountered in various healthcare settings with a vast socioeconomic impact. Recent advancements in pharmacotherapy have led to the evolution of novel therapeutic agents with a decrease in hospitalization and mortality rates in HF with reduced left ventricular ejection fraction (HFrEF). Lately, the introduction of artificial intelligence (AI) to construct decision-making models for the early detection of HF has played a vital role in optimizing cardiovascular disease outcomes. In this review, we examine the newer therapies and evidence behind goal-directed medical therapy (GDMT) for managing HF. We also explore the application of AI and machine learning (ML) in HF, including early diagnosis and risk stratification for HFrEF. [ABSTRACT FROM AUTHOR]

Aims: The ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) has recently emerged as a novel measure of left ventricular (LV) filling pressure. This new measure has demonstrated to have prognostic value superior to E/e'. This study aimed to investigate the prognostic value of E/e'sr in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF) in relation to all-cause mortality.Methods: We retrospectively studied 897 HFrEF (mean age 66 ± 12 years, 73% male, 59% ischemic cardiomyopathy) patients who underwent speckle tracking echocardiography where E/e'sr along with novel and conventional echocardiographic parameters were obtained. The primary endpoint was defined as all-cause mortality.Results: During follow-up (median: 40 months IQR: 22-57), 137 (15.3%) patients died. Both E/e'sr and E/e' were significantly associated with mortality (E/e'sr: HR 1.03 95%CI [1.02-1.04], p<0.001, per 0.10m increase) and (E/e': HR 1.04 95%CI [1.02-1.06], p = 0.001, per 1unit increase). E/e'sr remained an independent predictor in a multivariable model after adjusting for age, gender, mean arterial pressure, heart rate, BMI, total cholesterol, diabetes mellitus, ischemic cardiomyopathy, LVEF, LVIDd, LVMI, LAVI, TAPSE and LV-GLS (HR 1.02 95%CI [1.01-1.03], p = 0.007) whereas E/e' did not (HR 1.01 95%CI [0.98-1.04], p = 0.57). Furthermore, E/e'sr provided incremental prognostic information beyond a model including known risk factors: age, gender, total cholesterol, mean arterial pressure, heart rate, BMI, smoking status and E/e' (Harrell's C-statistics: 0.72 (0.68-0.77) vs 0.70 (0.66-0.75), p = 0.047).Conclusions: In HFrEF patients, E/e'sr provides independent and incremental prognostic information regarding all-cause mortality superior to E/e'. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a risk factor for atrial fibrillation (AF), stroke, and post-stroke disability. However, differing definitions and application of HF-criteria may impact model prediction. We compared the predictive ability of left ventricular ejection fraction (LVEF), a readily available objective echocardiographic index, with clinical HF definitions for functional disability and AF in stroke patients.Methods: We retrospectively analyzed ischemic stroke patients evaluated between January 2013 and May 2015. Outcomes of interest were: (a) 90-day functional disability (modified Rankin score 3-6) and (b) AF. We compared: (1) LVEF (continuous variable), (2) left ventricular systolic dysfunction (LVSD)-categories (absent to severe), (3) clinical history of HF, and (4) HF/LVSD-categories: (i) HF absent without LVSD, (ii) HF absent with LVSD, (iii) HF with preserved ejection fraction (HFpEF), and (iv) HF with reduced ejection fraction (HFrEF). Multivariable logistic regression was used to determine the predictive ability for 90-day disability and AF, respectively.Results: Six hundred eighty five consecutive patients (44.5% female) fulfilled the study criteria and were included. After adjustment, the LVEF was independently associated with 90-day disability (OR .98, 95% CI .96-.99, P = .011) with similar predictive ability (area under the curve [AUC] = .85) to models including the LVSD-categories (AUC = .85), clinically define HF (AUC = .86), and HF/LVSD-categories (AUC = .86). The LVEF, HF, LVSD-, and HF/LVSD-categories were independently associated with AF (P < .01, each) with similar predictive ability (AUC = .74, .74, .73, and .75, respectively).Conclusions: Compared to commonly defined HF definitions, the objectively determined LVEF possesses comparable predictive ability for 90-day disability and AF in stroke patients. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating evidence points at red cell distribution width(RDW) being a marker of poor outcome in heart failure(HF).We sought to investigate the prognostic value of RDW in an Indian population of patients with HF. Methods A total of 210 patients of HF due to LV systolic dysfunction had RDW measured at baseline and were followed up for 1 year. The study endpoint was mortality at 1 year of follow-up. Results The study endpoint was met in 44 patients (20.9%).RDW at baseline was strongly associated with mortality at 1 year(p<0.001). Male sex, DM, NYHA class III/IV and atrial fibrillation(AF) were strong predictors of mortality. Higher RDW was associated with worse NYHA class, ischemic etiology and diabetes mellitus(DM). Conclusion RDW is a simple and cost effective biomarker which has a strong predictive value for mortality in heart failure. [ABSTRACT FROM AUTHOR]

Abstract Objectives This was a first-in-human study to assess the feasibility, safety, and exploratory efficacy of interatrial shunting for treating high-risk heart failure (HF) in patients with reduced and preserved ejection fraction. Methods A single-arm open-label study of patients with New York Heart Association functional class III or IV HF on optimal therapy was performed at 6 centers. The V-Wave shunt, an hourglass-shaped implant containing a 1-way bioprosthetic valve, was implanted by transseptal catheterization. Clinical, functional, echocardiographic, and hemodynamic evaluations were performed at baseline, 3 and 12 months, and annually (clinical follow-up) thereafter (median follow-up 28 months; interquartile range: 21 to 31 months). Results A total of 38 patients were enrolled (30 with HF with reduced ejection fraction and 8 with HF with preserved ejection fraction; mean age 66 ± 9 years; 97% and 3% in New York Heart Association functional classes III and IV, respectively), and the shunt device was successfully implanted in all cases without periprocedural mortality. The rate of major device- or procedure-related complications during the first 12 months was 2.6% (periprocedural cardiac tamponade in 1 patient). At 3- and 12-month follow-up, there were improvements in New York Heart Association functional class (classes I and II in 78% and 60% of patients, respectively), quality of life (improvements ≥5 points in 74% and 73% of patients, respectively), and 6-min walk distance (mean increases of 41 ± 63 m and 28 ± 83 m, respectively) (p < 0.02 for all, data available for 36 patients), without changes in objective measures of left- or right-sided function. All shunts were patent at 3 months, but 5 of 36 (14%) had occluded, and another 13 of 36 (36%) were stenotic at the valve by 12 months. Patients with widely patent shunts had lower long-term rates of death, left ventricular assist device placement or heart transplantation (p = 0.001), and HF hospitalization (p = 0.008), along with a reduction of pulmonary capillary wedge pressure (from 23.3 ± 5.4 mm Hg at baseline to 18.0 ± 4.0 mm Hg at 12 months; p = 0.011). Conclusions Interatrial shunting with the V-Wave system was feasible and safe in patients with HF with reduced and preserved ejection fraction. Improvements in clinical and functional status were observed early and at 12 months despite attenuation of shunt patency in one-half of the patients. Patients with preserved shunt patency tended to maintain clinical benefit during longer term follow-up. Device modification that improves the durability of patency is likely worthwhile before confirmation of these findings in a randomized trial. Graphical abstract [ABSTRACT FROM AUTHOR]

Background: Peak exercise pulmonary oxygen uptake (V̇O2) is a primary marker of prognosis in heart failure (HF). The pathophysiology of impaired peak V̇O2 is unclear in patients. To what extent alveolar airway function affects V̇O2 during cardiopulmonary exercise testing (CPET) has not been fully elucidated. This study aimed to describe how changes in alveolar ventilation (V̇A), volume (VA), and related parameters couple with exercise V̇O2 in HF.Methods and Results: A total of 35 patients with HF (left ventricular ejection fraction 20 ± 6%, age 53 ± 7 y) participated in CPET with breath-to-breath measurements of ventilation and gas exchange. At rest, 20 W, and peak exercise, arterial CO2 tension was measured via radial arterial catheterization and used in alveolar equations to derive V̇A and VA. Resting lung diffusion capacity for carbon monoxide (DLCO) was assessed and indexed to VA for each time point. Resting R2 between V̇O2 and V̇A, VA, DLCO, and DLCO/VA was 0.68, 0.18, 0.20, and 0.07, respectively (all P < .05 except DLCO/VA). 20 W R2 between V̇O2 and V̇A, VA, DLCO, and DLCO/VA was 0.64, 0.32, 0.07, and 0.18 (all P < .05 except DLCO). Peak exercise R2 between V̇O2 and V̇A, VA, DLCO, and DLCO/VA was 0.55, 0.31, 0.34, and 0.06 (all P < .05 except DLCO/VA).Conclusions: These data suggest that alveolar airway function that is not exclusively related to effects caused by localized lung diffusivity affects exercise V̇O2 in moderate-to-severe HF. [ABSTRACT FROM AUTHOR]

Objectives To investigate the different clinical and echocardiographic predictors of evolving PH in patients with heart failure with and without reduced ejection fraction. Methods and Results The study included 153 heart failure patients with reduced ejection fraction (HFrEF) ( n = 89) and preserved ejection fraction (HFpEF) ( n = 64) both of which were subdivided into 2 subgroups according to the presence of PH. All patients were subjected to detailed clinical assessment and full transthoracic echocardiogram. There were significant differences between the 2 HFrEF subgroups regarding systolic BP, presence of diabetes, dyslipidemia, diuretics usage, all LV parameters, LAD, LAV and LAV indexed to BSA, E/A ratio, DT and severity of TR. Using multivariate analysis, the presence of diabetes ( P = 0.04), diuretics usage ( P = 0.04), LAV ( P = 0.007) and TR grade ( P < 0.001) were significant independent predictors for the development of PH among HFrEF patients. There were significant differences between the 2 HFpEF subgroups regarding presence of hypertension, diuretics usage, LAD, LAA, TR severity. Using multivariate analysis, only diuretics usage ( P = 0.02) and TR grade ( P < 0.0001) were significant independent predictors for the development of PH among HFpEF patients. Conclusion Neither the decrease in EF among HFrEF patients nor the DD grade in HFpEF patients act as independent predictor for evolving PH. Common independent predictors for evolving PH in both HFrEF and HFpEF patients are TR grade and use of diuretics. Other independent predictors in HFrEF and not HFpEF patients are the presence of diabetes and increased LAV. [ABSTRACT FROM AUTHOR]

• HF – Healthy binary classification. • HFrEF – HFpEF binary classification. Heart failure (HF) cases are increasing day by day. Rapid diagnosis, initiation of treatment, reduction of mortality and prolongation of lifespan are important. Left ventricular ejection fraction (LVEF) is an important determinant of HF, especially in HF with reduced ejection fraction (HFrEF, LVEF ≤ 40 %) and HF with preserved ejection fraction (HFpEF, LVEF ≥ 50 %). LVEF is a measure of the amount of blood pumped out of the ventricle in one heartbeat. HFrEF is easier to diagnose since LVEF ≤ 40%. However, the diagnosis of HFpEF is difficult even for some specialists, since LVEF is 50 % or higher also in a healthy person. LVEF is measured by echocardiography which is an expensive device and requires a specialist. There may be situations where access to the device is limited. Some invasive and laborious blood tests are also used for diagnosing HF. As an alternative diagnostic method, a new machine learning-based diagnostic algorithm was developed for diagnosing HF and its subtypes using photoplethysmography (PPG). PPGs from volunteers were cleaned with digital filters. Then HRVs were derived from PPG and features were extracted from both PPG and HRV. Features were reduced by statistical methods. The classification was done with three different machine learning algorithms. The evaluation was made with 10-fold cross validation and maximum performance parameters: accuracy %87.78, sensitivity 0.87 and specificity 0.94. With this triple classification, it is determined not only whether the individual has an HF, but also which HF is present. [ABSTRACT FROM AUTHOR]

• HF – Healthy binary classification. • HFrEF – HFpEF binary classification. Heart failure (HF) cases are increasing day by day. Rapid diagnosis, initiation of treatment, reduction of mortality and prolongation of lifespan are important. Left ventricular ejection fraction (LVEF) is an important determinant of HF, especially in HF with reduced ejection fraction (HFrEF, LVEF ≤ 40 %) and HF with preserved ejection fraction (HFpEF, LVEF ≥ 50 %). LVEF is a measure of the amount of blood pumped out of the ventricle in one heartbeat. HFrEF is easier to diagnose since LVEF ≤ 40%. However, the diagnosis of HFpEF is difficult even for some specialists, since LVEF is 50 % or higher also in a healthy person. LVEF is measured by echocardiography which is an expensive device and requires a specialist. There may be situations where access to the device is limited. Some invasive and laborious blood tests are also used for diagnosing HF. As an alternative diagnostic method, a new machine learning-based diagnostic algorithm was developed for diagnosing HF and its subtypes using photoplethysmography (PPG). PPGs from volunteers were cleaned with digital filters. Then HRVs were derived from PPG and features were extracted from both PPG and HRV. Features were reduced by statistical methods. The classification was done with three different machine learning algorithms. The evaluation was made with 10-fold cross validation and maximum performance parameters: accuracy %87.78, sensitivity 0.87 and specificity 0.94. With this triple classification, it is determined not only whether the individual has an HF, but also which HF is present. [ABSTRACT FROM AUTHOR]

An effective approach for determining the clinical classification of heart failure (HF) patients is to estimate cardiac hemodynamics during exercise. This approach is strengthened further when measurements including cardiac power are used to describe cardiac hemodynamics. We hypothesize that cardiac power quantifies the hemodynamic and pressure-generating capability of the heart, relating with exercise tolerance better than traditional measurements in HF. [ABSTRACT FROM AUTHOR]

• MCU, EMRE, MICU1 and MICU2 were all detected in non-failing and failing human heart. • Failing hearts have increased MICU1 and MICU2 abundance and MICU1/MCU ratio. • Ejection fraction decrease seems to correlate with the increase in MICU1/MCU ratio. • mtCU composition might contribute to the initiation/progression of HF in humans. Heart failure (HF) is a leading cause of hospitalization and mortality worldwide. Yet, there is still limited knowledge on the underlying molecular mechanisms, because human tissue for research is scarce, and data obtained in animal models is not directly applicable to humans. Thus, studies of human heart specimen are of particular relevance. Mitochondrial Ca2+ handling is an emerging topic in HF progression because its regulation is central to the energy supply of the heart contractions as well as to avoiding mitochondrial Ca2+ overload and the ensuing cell death induction. Notably, animal studies have already linked impaired mitochondrial Ca2+ transport to the initiation/progression of HF. Mitochondrial Ca2+ uptake is mediated by the Ca2+uniporter (mtCU) that consists of the MCU pore under tight control by the Ca2+-sensing MICU1 and MICU2. The MICU1/MCU protein ratio has been validated as a predictor of the mitochondrial Ca2+ uptake phenotype. We here determined for the first time the protein composition of the mtCU in the human heart. The two regulators MICU1 and MICU2, were elevated in the failing human heart versus non-failing controls, while the MCU density was unchanged. Furthermore, the MICU1/MCU ratio was significantly elevated in the failing human hearts, suggesting altered gating of the MCU by MICU1 and MICU2. Based on a small cohort of patients, the decrease in the cardiac contractile function (ejection fraction) seems to correlate with the increase in MICU1/MCU ratio. Our findings therefore indicate a possible role for adaptive/maladaptive changes in the mtCU composition in the initiation/progression of human HF in humans and point to a potential therapeutic target at the level of the MICU1-dependent regulation of the mtCU. [Display omitted] [ABSTRACT FROM AUTHOR]