Heart Failure In Clinical Practice Research Articles

Ginsenoside Rb1 ameliorates heart failure through DUSP-1-TMBIM-6-mediated mitochondrial quality control and gut flora interactions

BackgroundThere is currently no specific therapeutic drug available for heart failure in clinical practice. Numerous studies have validated the efficacy of Ginsenoside Rb1, an active component found in various herbal remedies used for heart failure treatment, in effectively ameliorating myocardial ischemia. However, the precise mechanism of action and molecular targets of Ginsenoside Rb1 remain unclear. PurposeThis study aims to explore the molecular mechanisms through which Ginsenoside Rb1 synergistically modulates the gut flora and mitochondrial quality control network in heart failure by targeting the DUSP-1-TMBIM-6-VDAC1 axis. Study designThis study utilized DUSP-1/VDAC1 knockout (DUSP-1-/-/VDAC1-/-) and DUSP-1/VDAC1 transgenic (DUSP-1+/+/VDAC1+/+) mouse models of heart failure, established through Transverse Aortic Constriction (TAC) surgery and genetic modification techniques. The mice were subsequently subjected to treatment with Ginsenoside Rb1. MethodsA series of follow-up multi-omics analyses were conducted, including assessments of intestinal flora, gene transcription sequencing, single-cell databases, and molecular biology assays of primary cardiomyocytes, to investigate the mechanism of action of Ginsenoside Rb1. ResultsGinsenoside Rb1 was found to have multiple regulatory mechanisms on mitochondria. Notably, DUSP-1 was discovered to be a crucial molecular target of Ginsenoside Rb1, controlling both intestinal flora and mitochondrial function. The regulatory effects of DUSP-1 on inflammation and mitochondrial quality control were mediated by changes in TMBIM-6 and VDAC1. Furthermore, NLRP3-mediated inflammatory responses were found to interact with mitochondrial quality control, exacerbating myocardial injury under stress conditions. Ginsenoside Rb1 modulated the DUSP-1-TMBIM-6-VDAC1 axis, inhibited the release of pro-inflammatory factors, altered the structural composition of the gut flora, and protected impaired heart function. These effects indirectly influenced the crosstalk between inflammation, mitochondria, and gut flora. ConclusionThe DUSP-1-TMBIM-6-VDAC1 axis, an upstream pathway regulated by Ginsenoside Rb1, is a profound mechanism through which Ginsenoside Rb1 improves cardiac function in heart failure by modulating inflammation, mitochondria, and gut flora.

SGLT2i IN THE REAL WORLD: DATA FROM THE PONTE (bridge) HF PROJECT (PDTA FOR INTEGRATED TERRITORY HOSPITAL FOLLOW-UP OF PATIENTS WITH HEART FAILURE)

Abstract Background Over the last few years, treatment with sodium glucose cotransporter 2 inhibitors (SGLT2i) dapaglifozin and empaglifozin was shown to reduce the combined risk of cardiovascular death and/or hospitalization for heart failure (HF) among patients with heart failure with reduced ejection fraction. Subsequent RCTs have demonstrated similar reduction in the combined endpoint also in patients with left ventricular ejection fraction (LVEF) >40%. Nevertheless, real world data on the current state of implementation of SGLT2i therapy in HF clinical practice are scarce. The aim of the study was therefore to evaluate the impact of SGLT2i treatment in a real world population of HF patients. Methods 527 consecutive patients with HF, treated with SGLT2i and with 6 months of follow-up already enrolled in the PONTE (PDTA FOR THE INTEGRATED FOLLOW-UP IN THE HOSPITAL TERRITORY OF THE PATIENT WITH HEART FAILURE) HF project, a care model implemented in Puglia region (Italy) based on hospital-territory integration aimed at the optimized management of patient with HF after hospitalization, were considered for the study. Demographic, clinical, laboratory and instrumental characteristics, changes in NYHA class, creatinine, NT-proBNP, medications, LVEF after initiation of therapy with SGLT2i were evaluated. Results The 527 enrolled patients (mean age of 67,40 years, 75% hypertensive, 39% diabetic, 51% ischemic heart disease, 52% with ICD, 35% with atrial fibrillation) were in NYHA class I in 3,2% of cases, class II in 56,6%, class III in 38,5%, class IV in 1,7%. Mean LVEF was 34,20% (63% of patients had LVEF <35%), NT-proBNP 2606,86 pg/ml, creatinine 1,19 mg/dl. 95,1% of patients was on treatment with beta-blockers, 52,7% with ACE inhibitors, 55,1% with ARNI. After a follow-up of 6 months, a reduction of patients in NYHA classes III+IV from 40,2 to 19,0% as well as an increase in patients in classes I+II from 59,8 to 81,0% (NYHA I increasing from 3,2 to 14,6%) were observed. Furthermore, mean LVEF increased from 34,20 to 37,68% and patients taking loop diuretics reduced from 83,9 to 77,4%. Creatinine remained stable (1,19 vs 1,21 mg/dl), while NT-proBNP lowered from 2606,86 to 1603,32 pg/ml. Conclusions Our real world data on SGLT2i in HF patients seem to confirm the efficacy of this class of drugs in a short term follow-up, with a positive effect on symptoms (improvement in NYHA class and fewer patients taking loop diuretics), NT-proBNP and LVEF.

Cost-effectiveness of systematic screening and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with heart failure with preserved ejection fraction (HFpEF) in United States

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure in clinical practice. 99mTc-pyrophosphate scintigraphy (PYP-scan) improves the accuracy of ATTR-CM detection, enabling timely initiation of tafamidis, a drug that slows the progression of ATTR-CM and lowers the risk of adverse cardiac events. PYP-scans, serum free light-chain (FLC) test and immunofixation electrophoresis (IFE) are critical components of a systematic screening. We assessed the cost-effectiveness of universal systematic screening (USS) compared to standard-of-care (SoC) selected clinical referrals for the systematic screening in patients aged 60 years or older with heart failure with preserved ejection fraction (HFpEF) and ventricular wall thickness of at least 12 mm. MethodsTwo screening strategies, USS versus SoC screening for ATTR-CM were compared in a model-based assessment. Treatment decisions were based upon the accuracy of each screening strategy, which was followed by Markov state transitions across New York Heart Association (NYHA) functional classes and death. Model inputs were identified from a literature review. We calculated lifetime cost in 2022 US dollars and quality adjusted life-years (QALYs) of each strategy. The primary outcome was the incremental cost-effectiveness ratio (ICER). ResultsThe USS was associated with a significant increase in lifetime costs ($124,380 vs. $70,412) and modest improvement in QALYs (4.42 QALYs vs 4.36 QALYs). The ICER for the USS was $919,509 per QALY gained. ICER was sensitive to the age at the time of ATTR-CM diagnosis, true prevalence rate of ATTR-CM, and daily cost of tafamidis. ConclusionsOwing to the high cost of treatment with tafamidis, USS along with PYP scan for ATTR-CM in older HFpEF patients with ventricular wall thickening is unlikely to become a cost-effective strategy at a liberal WTP threshold.

Effects of melatonin on cardiac metabolic reprogramming in doxorubicin-induced heart failure rats: A metabolomics study for potential therapeutic targets.

Using mass spectrometry-based targeted metabolomics, we aimed to determine the pattern of cardiac metabolic reprogramming and energetics in doxorubicin-induced heart failure. More importantly, we aimed to identify the potential effects of melatonin on cardiac metabolic reprogramming and energetics in doxorubicin-induced heart failure. Male Wistar rats (n = 18) were randomly divided into three groups (n = 6/group) to receive either (1) normal saline solution as a control, (2) 3 mg/kg/day of doxorubicin on Days 0, 4, 8, 15, 22, and 29, or (3) 3 mg/kg/day of doxorubicin on Days 0, 4, 8, 15, 22, and 29 plus 10 mg/kg/day of melatonin on Days 0-29. On Day 30, echocardiography was carried out and heart rate variability was analyzed for the evaluation of cardiac function. The rats were euthanized on the following day to enable the collection of ventricular cardiac tissue. Compared to the control group, the hearts of rats treated with doxorubicin alone exhibited impaired cardiac function, increased glucose and ketone body utilization, decreased fat utilization, decreased succinate oxidation, and decreased production of adenosine triphosphate. The cotreatment with melatonin could restore cardiac function, glucose and ketone body utilization, and adenosine triphosphate production in the heart. Interestingly, the cotreatment with melatonin led to an increase in cardiac fatty acid oxidation, branched-chain amino acid catabolism, and anaplerosis. All of these findings highlighted the potential efficacy of melatonin with regard to cardiac metabolic reprogramming and energetics. Our findings also suggested that melatonin could be considered as an adjunctive treatment for doxorubicin-induced heart failure in clinical practice.

Development of a telemedicine group educational program for patients with heart failure: A delphi study

AimsEvidence regarding the most effective and feasible videoconferencing group educational program for patients with heart failure is still equivocal. This study aimed to reach consensus about the structure, acceptability, and feasibility of videoconferencing for people with heart failure in Jordan that improves access to healthcare and clinical outcomes. MethodsThere were two Delphi survey studies of three rounds each. Delphi one survey involved 32 healthcare staff, experienced in heart failure clinical practice and telehealth, to obtain a consensus of opinion on a proposed group videoconferencing program for patients with heart failure. Delphi two involved seven staff of the information technology center, experienced in videoconferencing and using supporting applications, to obtain their consensus on the current capabilities of the healthcare system and patients about information technology. Descriptive statistics were used for each item to determine whether consensus was achieved or not. Items that received 80% disagreement or 80% agreement of participants were not presented for re-rating in the third round, while the items that scored varying degrees of agreement were presented for experts for re-rating. ResultsIn Delphi one a group of items reached consensus regarding structure, factors influencing, and effectiveness of the videoconferencing program. In Delphi two, the findings indicated that videoconferencing modality is applicable and feasible in Jordan. ConclusionThis is the first study that addresses the equivocal evidence for the design and implementation of heart failure videoconferencing programs. The framework of the current proposed program can be utilized as a guideline to test or develop a future videoconference program.

Sacubitril/valsartan use patterns among older adults with heart failure in clinical practice: a population-based cohort study of >25 000 Medicare beneficiaries.

Sacubitril/valsartan is strongly supported in guidelines for the management of heart failure, but suboptimal adherence and treatment non-persistence may limit the population-level benefit that this therapy might otherwise offer. We identified a cohort of Medicare beneficiaries (2014-2017) initiating sacubitril/valsartan after ≥6months of continuous enrolment. We assessed adherence as the proportion of days covered (PDC) and proportion of patients non-persistent (having no prescription available) at 180 days after initiation. We fit a multivariable negative binomial model with a count of adherent days to evaluate independent factors associated with of sacubitril/valsartan adherence. Among 27 063 new sacubitril/valsartan users, most (n=17 663, 65%) were prescribed low-dose at 24 mg/26 mg and most (n=19 984, 74%) were switched from prior angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) rather than being RASi treatment naïve. Median 180-day PDC was 86% (25th-75th percentiles 58-98%). Black patients, those with high comorbid disease burden (≥8 comorbidities), and patients with recent hospitalization within 30 days had fewer adherent days, while those treated with preceding ACEi/ARB had more adherent days. Thirty-four percent of patients did not have an active sacubitril/valsartan prescription at day 180. Among these, few had preceding dose down-titrations (6% among patients on 49 mg/51 mg and 9% among patients on 97 mg/103 mg) and 68% did not have a subsequent ACEi/ARB prescription. Among patients who remained persistent, dose up-titrations occurred in 29% of patients who started on 24 mg/26 mg and 27% of patients on 49 mg/51 mg. Overall adherence to sacubitril/valsartan among Medicare beneficiaries is acceptable, but is lower in Black patients, those with higher comorbidities or those who started therapy after recent hospitalization. While broad implementation of guideline-directed medical therapy is a key priority, additional focused efforts to improve adherence early after hospitalization and among at-risk patients are needed in parallel.

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting

BackgroundGated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. MethodsThis is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. Results276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland–Altman plots demonstrated good agreement. ConclusionsThe presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.

Use of a mobile application for remote monitoring of patients with chronic heart failure in clinical practice

The steady growth and prevalence of chronic heart failure (CHF) leads to an increase in mortality, repeated hospitalizations and disability of the population. More than half of rehospitalizations are due to poor adherence to therapy, the impossibility of timely observation by a doctor, and inadequate patient education in the basics of self-control and self-help during and after discharge. In order to improve the quality of life of patients with CHF, reduce the frequency of readmissions and mortality, it is necessary to create programs to optimize outpatient care with the possibility of monitoring clinical indicators and timely correction of therapy, which can be done using digital technologies — mHealth. The ubiquity of mobile phones and portable gadgets is thought to make the introduction of remote monitoring software more affordable and cost effective. Thus, the purpose of the review is to collect and analyze the available literature data on the use of mobile technology programs for non-invasive remote monitoring of patients with CHF. Thus, studies investigating the impact of remote monitoring on the course of CHF have included widely varying patient cohorts using dissimilar devices with different support packages. Of course, the heterogeneity of both the sample and the methods used led to the inconsistency of the data obtained, the inability to compare and evaluate the results in full. Along with this, the inability to directly compare different methods of remote monitoring of patients with CHF determines the impossibility of choosing the most effective of them, which, in turn, dictates the need for standardization of methods according to, including the healthcare system in each individual country. Overall, mHealth applications offer a potentially cost-effective solution with continued access to symptom monitoring, encouraging patient engagement in self-care and self-monitoring, and improved outcomes over standard practice. While there is considerable evidence for the effectiveness of remote monitoring programs, many areas of uncertainty remain, and mobile phone interventions require further careful evaluation. Although the available data is insufficient to confirm the impact of mobile phone monitoring, it is clear that the potential is enormous.

Patients with a Combination of Atrial Fibrillation and Chronic Heart Failure in Clinical Practice: Comorbidities, Drug Treatment and Outcomes

Aim. To assess in clinical practice the structure of multimorbidity, cardiovascular pharmacotherapy and outcomes in patients with a combination of atrial fibrillation (AF) and chronic heart failure (CHF) based on prospective registries of patients with cardiovascular diseases (CVD).Materials and Methods. The data of 3795 patients with atrial fibrillation (AF) were analyzed within the registries RECVASA (Ryazan), RECVASA FP (Moscow, Kursk, Tula, Yaroslavl), REGION-PO and REGION-LD (Ryazan), REGION-Moscow, REGATA (Ryazan). The comparison groups consisted of 3016 (79.5%) patients with AF in combination with CHF and 779 (29.5%) patients with AF without CHF. The duration of prospective observation is from 2 to 6 years.Results. Patients with a combination of AF and CHF (n=3016, age was 72.0±10.3 years; 41.8% of men) compared with patients with AF without CHF (n=779, age was 70.3±12.0 years; 43.5% of men) had a higher risk of thromboembolic complications (CHA2DS2-VASc – 4.68±1.59 and 3.10±1.50; p<0.001) and hemorrhagic complications (HAS-BLED – 1.59±0.77 and 1.33±0.76; p<0.05). Patients with a combination of AF and CHF significantly more often (p<0.001) than in the absence of CHF were diagnosed with arterial hypertension (93.9% and 83.8%), coronary heart disease (87.9% and 53,5%), myocardial infarction (28.4% and 14.0%), diabetes mellitus (22.4% and 7.7%), chronic kidney disease (24.8% and 16.2%), as well as respiratory diseases (20.1% and 15.3%; p=0.002). Patients with AF in the presence of CHF, compared with patients without CHF, were more often diagnosed with a permanent form of arrhythmia (49.3% and 32.9%; p<0.001) and less often paroxysmal (22.5% and 46.2%; p<0.001) form of arrhythmia. Ejection fraction ≤40% (9.3% and 1.2%; p<0.001), heart rate ≥90/min (23.7% and 19.3%; p=0.008) and blood pressure ≥140/90 mm Hg (59.9% and 52.2%; p<0.001) were recorded with AF in the presence of CHF more often than in the absence of CHF. The frequency of proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF (64.9%) than in the absence of it (56.1%), but anticoagulants were prescribed less frequently when AF and CHF were combined (38.8% and 49, 0%; p<0.001). The frequency of unreasonable prescription of antiplatelet agents instead of anticoagulants was 52.5% and 33.3% (p<0.001) in the combination of AF, CHF and coronary heart disease, as well as in the combination of AF with coronary heart disease but without CHF. Patients with AF and CHF during the observation period compared with those without CHF had higher mortality from all causes (37.6% and 30.3%; p=0.001), the frequency of non-fatal cerebral stroke (8.2% and 5.4%; p=0.032) and myocardial infarction (4.7% and 2.5%; p=0.036), hospitalizations for CVD (22.8% and 15.5%; p<0.001).Conclusion. Patients with a combination of AF and CHF, compared with the group of patients with AF without CHF, were older, had a higher risk of thromboembolic and hemorrhagic complications, they were more often diagnosed with other concomitant cardiovascular and chronic noncardiac diseases, decreased left ventricular ejection fraction, tachysystole, failure to achieve the target blood pressure level in the presence of arterial hypertension. The frequency of prescribing proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF, while the frequency of prescribing anticoagulants was less. The incidence of mortality from all causes, the development of non-fatal myocardial infarction and cerebral stroke, as well as the incidence of hospitalizations for CVDs were higher in AF associated with CHF.

Hydrogen gas inhalation ameliorates cardiac remodelling and fibrosis by regulating NLRP3 inflammasome in myocardial infarction rats.

It is noteworthy that prolonged cardiac structural changes and excessive fibrosis caused by myocardial infarction (MI) seriously interfere with the treatment of heart failure in clinical practice. Currently, there are no effective and practical means of either prevention or treatment. Thus, novel therapeutic approaches are critical for the long‐term quality of life of individuals with myocardial ischaemia. Herein, we aimed to explore the protective effect of H2, a novel gas signal molecule with anti‐oxidative stress and anti‐inflammatory effects, on cardiac remodelling and fibrosis in MI rats, and to explore its possible mechanism. First, we successfully established MI model rats, which were then exposed to H2 inhalation with 2% concentration for 28 days (3 hours/day). The results showed that hydrogen gas can significantly improve cardiac function and reduce the area of cardiac fibrosis. In vitro experiments further proved that H2 can reduce the hypoxia‐induced damage to cardiomyocytes and alleviate angiotensin II‐induced migration and activation of cardiac fibroblasts. In conclusion, herein, we illustrated for the first time that inhalation of H2 ameliorates myocardial infarction‐induced cardiac remodelling and fibrosis in MI rats and exert its protective effect mainly through inhibiting NLRP3‐mediated pyroptosis.

Quantifying the Impact of Atrial Fibrillation on Heart Failure–Related Patient-Reported Outcomes in the Utah mEVAL Program

BackgroundAtrial fibrillation (AF) frequently complicates heart failure (HF), and each is associated with lower overall health-related quality of life. We aimed to quantify the incremental burden of AF on the health-related quality of life of patients with HF in clinical practice. Methods and ResultsWe used data from the Utah mEVAL program to analyze patient-reported outcomes (PROs) among patients with HF with and without AF. The primary outcome was the HF-specific Kansas City Cardiomyopathy Questionnaire, with generic PROs as secondary outcomes. Among 1707 patients with HF, 36% had AF (n = 616). Those with HF and AF were older (mean age 69 years vs 58 years, P < .001), more likely to have prior stroke (29% vs 17%, P < .001) and ischemic cardiomyopathy (28% vs 23%, P = .01), but had similar ejection fractions (mean 44% each, P = .6). After adjustment, and compared with HF alone, HF with AF was associated with worse Kansas City Cardiomyopathy Questionnaire scores (adjusted mean difference –3.45, 95% confidence interval [CI] –6.24 to –0.65), and worse Patient-Reported Outcomes Measurement Information System physical function scores (adjusted mean difference –1.63, 95% CI –2.59 to –0.67). The difference in visual analog scale general health was borderline (adjusted mean difference –2.01, 95% CI –4.51 to 0.49), and Patient-Reported Outcomes Measurement Information System depression scores were similar (adjusted mean difference 0.54, 95% CI –0.48 to 1.57). ConclusionsAF complicates nearly one-third of HF cases, and patients with HF and AF are substantially older and sicker. After adjustment, AF was independently associated with worse disease-specific and overall health-related quality of life than HF alone. Whether maintaining sinus rhythm can improve the HF-related health status of patients with HF in clinical practice should be explored further.

Representation of Women Physicians in Heart Failure Clinical Practice.

Women have been integral in the development of advanced heart failure (HF) and transplantation as a clinical subspecialty of cardiovascular medicine. However, women remain underrepresented in leadership positions, senior academic ranks and as researchers in HF. In recent years, there have been accelerating efforts to examine sex differences in the clinical and research domains of HF. The purpose of this review is to discuss the representation of women in HF training programmes and clinical practice, the demographics of HF clinicians compared with other cardiology subspecialties, the persistent sex disparities in HF practice and research environments and potential strategies to promote equity and inclusion for women in the field.

Biomarkers of Zinc and Copper Status and Associated Factors in Outpatients with Ischemic and Non-Ischemic Heart Failure

Background: Few studies have explored the impact of ischemic and non-ischemic etiologies of heart failure and other factors associated with heart failure on zinc and copper status. This study examined zinc and copper status in 80 outpatients with ischemic (n = 36) and non-ischemic (n = 44) heart failure and associations with biodemographic, clinical, biochemical, and nutritional parameters. Materials: Biomarkers of plasma zinc and copper, copper-zinc ratio, 24-h urinary zinc excretion, ceruloplasmin, and dietary intake of zinc and copper were assessed. Plasma zinc and copper and urinary zinc were measured by inductively coupled plasma mass spectrometry (ICP-MS). Results: Patients with ischemic heart failure showed lower dietary zinc intake and higher dietary copper intake (both p = 0.02). Zinc and copper in plasma, copper-zinc ratio, ceruloplasmin, and 24-h urinary zinc excretion showed no statistical differences between the groups (all p ≥ 0.05). An inverse association was found between age (β =−0.001; p = 0.005) and the use of diuretics (β = -0.047; p = 0.013) and plasma zinc. Copper levels in plasma (β = 0.001; p < 0.001), and albumin (β = 0.090; p<0.001) were directly associated with plasma zinc. A positive association was found between ceruloplasmin (β = 0.011; p < 0.001), gamma-glutamyl transferase (β = 0.001; p < 0.001), albumin (β = 0.077; p = 0.001), and high-sensitivity c-reactive protein (β = 0.001; p = 0.024) and plasma copper. Conclusion: Zinc and copper biomarkers in clinically stable patients with heart failure did not seem to be responsive to the differences in zinc and copper intake observed in this study, regardless of heart failure etiology. The predictors of plasma zinc and copper levels related to oxidative stress and inflammation should be monitored in heart failure clinical practice.

Risk-Based Approach for the Prediction and Prevention of Heart Failure.

Targeted prevention of heart failure (HF) remains a critical need given the high prevalence of HF morbidity and mortality. Similar to risk-based prevention of atherosclerotic cardiovascular disease, optimal HF prevention strategies should include quantification of risk in the individual patient. In this review, we discuss incorporation of a quantitative risk-based approach into the existing HF staging landscape and the clinical opportunity that exists to translate available data on risk estimation to help guide personalized decision making. We first summarize the recent development of key HF risk prediction tools that can be applied broadly at a population level to estimate risk of incident HF. Next, we provide an in-depth description of the clinical utility of biomarkers to personalize risk estimation in select patients at the highest risk of developing HF. We also discuss integration of genomics-enhanced approaches (eg, Titin [TTN]) and other risk-enhancing features to reclassify risk with a precision medicine approach to HF prevention. Although sequential testing is very likely to identify low and high-risk individuals with excellent accuracy, whether or not interventions based on these risk models prevent HF in clinical practice requires prompt attention including randomized placebo-controlled trials of candidate therapies in risk-enriched populations. We conclude with a summary of unanswered questions and gaps in evidence that must be addressed to move the field of HF risk assessment forward.

Novel Echocardiographic Approach to Hemodynamic Phenotypes Predicts Outcome of Patients Hospitalized With Heart Failure.

Although in clinical practice heart failure (HF) patients are classified using left ventricular ejection fraction (LVEF), this categorization is insufficient for prognosis, especially when LVEF is preserved or there is a concomitant right ventricular (RV) dysfunction. We hypothesized that a combined noninvasive evaluation of LV forward flow, filling pressure, and RV function would be better than LVEF in predicting all-cause mortality of hospitalized patients with HF. Transthoracic echocardiographic examinations of 603 patients hospitalized with HF were analyzed. In a subsample of 200 patients with HF, LV stroke volume index, LV filling pressure estimation, tricuspid annular plane systolic excursion, and systolic pulmonary artery pressure were combined to determine 4 hemodynamic profiles: normal flow-normal pressure, normal flow-high pressure, low flow without RV dysfunction, and low flow with RV dysfunction profile. This model was then applied in a validation cohort (n=403). Prognosis worsened from the normal flow-normal pressure profile to the low flow with right ventricular dysfunction profile. At the multivariate survival analysis, the model showed independent high risk-stratification capability (P<0.001), even in subgroups of patients with LVEF < or ≥50% (P=0.011 and P<0.001, respectively) and < or ≥40% (P=0.044 and P<0.001, respectively). LVEF and HF classification based on LVEF did not predict outcome. Echocardiographic-derived profiling of LV forward flow, filling pressure, and RV function allowed categorization of patients hospitalized with HF and predicted all-cause mortality independently of LVEF. This model is based on conventional echocardiography, is easy to apply, and is, therefore, suggested for clinical practice.

Efficacy and Safety of Fuzi Formulae on the Treatment of Heart Failure as Complementary Therapy: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials

Objective Heart failure is a major public health problem worldwide nowadays. However, the morbidity, mortality, and awareness of heart failure are not satisfied as well as the status of current treatments. According to the standard treatment for chronic heart failure (CHFST), Fuzi (the seminal root of Aconitum carmichaelii Debx.) formulae are widely used as a complementary treatment for heart failure in clinical practice for a long time. We are aiming to assess the efficacy and safety of Fuzi formulae (FZF) on the treatment of heart failure according to high-quality randomized controlled trials (RCTs). Methods RCTs in PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database were searched from their inception until June 2019. In addition, the U.S. National Library of Medicine (clinicaltrials.gov) and the Chinese Clinical Trial Registry (http://www.chictr.org.cn) were also searched. We included RCTs that test the efficacy and safety of FZF for the treatment of heart failure, compared with placebo, CHFST, or placebo plus CHFST. The methodological quality of included studies were evaluated by the Cochrane Collaboration's tool for assessing risk of bias. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analysis. The meta-analysis was conducted through RevMan 5.2 software. The GRADE approach was used to assess the quality of the evidence. Results Twelve RCTs with 1490 participants were identified. The studies investigated the efficacy and safety of FZF, such as FZF plus the CHFST vs placebo plus CHFST (n = 4), FZF plus CHFST vs CHFST (n = 6), FZF plus digoxin tablets (DT) plus CHFST vs placebo plus DT plus CHFST (n = 1), and FZF plus placebo plus CHFST vs placebo plus DT plus CHFST (n = 1). Meta-analysis indicated that FZF have additional benefits based on the CHFST in reducing plasma NT-proBNP level, MLHFQ scores, Lee's heart failure scores (LHFs), and composite cardiac events (CCEs). Meanwhile, it also improved the efficacy on TCM symptoms (TCMs), NYHA functional classification (NYHAfc), 6MWD, and LVEF. Adverse events were reported in 6 out of 12 studies without significant statistical difference. However, after assessing the strength of evidence, it was found that only the quality of evidence for CCEs was high, and the others were either moderate or low or very low. So we could not draw confirmative conclusions on its additional benefits except CCEs. Further clinical trials should be well designed to avoid the issues that were identified in this study. Conclusion The efficacy and additional benefits of FZF for CCEs were certain according to the high-quality evidence assessed through GRADE. However, the efficacy and additional benefits for the other outcomes were uncertain judging from current studies. In addition, the safety assessment has a great room for improvement. Thus, further research studies are needed to find more convincing proofs.

P1664Pharmacological treatment patterns in heart failure: a real world cohort study

Abstract Background Although the efficacy and safety of existing therapies of heart failure (HF) have been demonstrated in clinical trials in the last 35 years, little is known about the treatment patterns of HF in clinical practice, especially in France. Objectives To describe the treatment initiation patterns and the subsequent treatment changes among HF patients, in the first year following an incident hospitalisation for HF, in a French real-world setting. Methods A cohort of patients aged 40 years old and older, with an incident hospitalisation for HF between January 1, 2008 and December 31, 2013, was identified in the EGB, a 1/97 permanent random sample of the French nationwide claims database. All patients who died during the index hospitalization or with a period of at least 3 consecutive months with no healthcare dispensing recorded were excluded. All included patients were followed one year. HF drugs of interest were: beta blockers (BB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), aldosterone antagonists (AA), diuretics, digoxin or ivabradine. Drug exposure was assessed quarterly using a Proportion of Days Covered &gt;66% (&gt;60 days out of the 90 days of the quarter covered by the treatment of interest), by considering HF drugs individually or in combination. Drug changes were assessed between each quarter over the first year of follow-up. Results Between 2008 and 2013, 7,387 from the EGB were included in the cohort study. The mean age at baseline was 77.7 years (±12.0 years) and 51.6% were women. During the follow-up, 24.4% of patients died and 20% did not receive any HF treatment. During the first quarter following initial hospitalisation, 42.7% of patients had diuretics, 26.0% had BB, 25.7% had ACEI, 7.4% had ARB, 7.6% had AA, 4.7% had digoxin and 1.3% had ivabradine. the most frequent combination was BB/ACE/ARB (23.4%). These proportions remained globally constant in each quarter of the follow-up. The main change occurred between thee first and the second quarter and concerned 53.1% of the initially untreated patients; by the second quarter, 22.2% of them initiated a BB/ACI/ARB combination, 13% a diuretic alone, 7.4% a BB and 4.9% a BB/ACI/ARB/AA combination. Conclusion This study provides precious information on treatment patterns after an initial hospital admission for HF at a time when new treatments for HF are emerging. Acknowledgement/Funding None

From left ventricular ejection fraction to cardiac hemodynamics: role of echocardiography in evaluating patients with heart failure.

In clinical practice heart failure (HF) patients are generally classified on the basis of left ventricular (LV) ejection fraction. This approach, however, has important limitations. According to the definition of HF as a clinical syndrome that results from any impairment of LV filling or ejection of blood, a more articulated hemodynamic categorization of HF patients taking into account both LV forward flow and filling pressure would be desirable. However, the reliability of hemodynamic measures using echocardiographic techniques, which are the most used in current clinical practice for evaluation of HF patients, needs to be clarified. The aim of this article, therefore, is to verify whether echocardiography has acceptable feasibility, accuracy and reproducibility for the noninvasive evaluation of LV hemodynamics. This evaluation is necessary to progress to a hemodynamic characterization of HF patients that would ultimately overcome the HF classification based on ejection fraction.

Association Between Cardiorespiratory Fitness and Risk of Heart Failure: A Meta-Analysis

Evidence emerges that cardiorespiratory fitness (CRF) might be implicated in the development of heart failure (HF). This meta-analysis aimed to quantify the association between CRF exposed at baseline and HF risk with dose-response analysis and to assess whether CRF changes over time are correlated with alterations in HF risk. Cohort studies that assessed the association between CRF and risk of HF in subjects without baseline HF were included. Study-specific multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Ten studies from 8 articles were included, enrolling 8987 incident HF cases from 154,598 participants. The RR of HF per 1-metabolic equivalent (MET) higher CRF at baseline was 0.82 (95% CI 0.80-0.84) in the overall population. The RRs were similar in men (0.82, 95% CI 0.80-0.85) and women (0.81, 95% CI 0.78-0.84), and remained minorly changed in patients with existing diabetes, hypertension, or cardiovascular disease at entry. No evidence of a nonlinear relationship between CRF at baseline and risk of HF was observed (Pnonlinearity = .18). The RR of HF per 1-MET increase in CRF over time was 0.79 (95% CI 0.67-0.93), and the measurement of CRF provided incremental value to the prediction of HF beyond conventional models. High or increased CRF resulted in reduced risk of HF in a dose-dependent manner, supporting the necessity to increase CRF to prevent HF in clinical practice.

In Vitro Study on the Dynamics of Blood Flow Impelled by an Alternating Current Magnetohydrodynamic Blood Pump.

Artificial hearts are effective devices to treat heart failure in clinical practice and can be divided into two categories: artificial hearts and ventricular assist devices. The goal of this work was to investigate the fluidity and biological changes of in vitro sheep blood using a novel alternating current (AC) magnetohydrodynamic blood pump (central magnetic intensity: 0.9 T, alternating current frequency of the electric motor: 0-80 Hz). Blood samples were collected from five sheep and were divided into two groups: the control group (no exposure to an external magnetic field) and the exposed group (3 h of exposure to an alternating magnetic field). The blood cell counts, changes in blood viscosity, and ultrastructural changes of the blood cells under transmission electron microscopy were investigated. This study demonstrated several findings: (i) Continuous sheep blood flow can be achieved; (ii) The blood cell counts remained unchanged after 3 h of exposure to an alternating magnetic field; (iii) Compared with the control group, the high- and low-shear viscosities of the whole blood from the sheep significantly decreased after 3 h of exposure to an alternating magnetic field (P < 0.05 and P < 0.01, respectively). Plasma viscosity was significantly reduced after exposure to high-intensity alternating magnetic fields (P < 0.001); (iv) The cytoplasm of blood cells (especially erythrocytes) became lighter in color in the exposure group compared to the control group, and "beads-on-string" aggregations of black particles appeared. This work provides detailed and reliable scientific research data for the development of this type of blood pump, which may serve as a transition to the clinical artificial heart.