Treatment Of Heart Failure Patients Research Articles

A multi-constituent model for assessing the effect of impeller shroud on the thrombosis potential of a centrifugal blood pump.

Centrifugal blood pumps can be used for treating heart failure patients. However, pump thrombosis has remained one of the complications that trouble clinical treatment. This study analyzed the effect of impeller shroud on the thrombosis risk of the blood pump, and predicted areas prone to thrombosis. Multi-constituent transport equations were presented, considering mechanical activation and biochemical activation. It was found that activated platelets concentration can increase with shear stress and adenosine diphosphate(ADP) concentration increasing, and the highest risk of thrombosis inside the blood pump was under extracorporeal membrane oxygenation (ECMO) mode. Under the same condition, ADP concentration and thrombosis index of semi-shroud impeller can increase by 7.3% and 7.2% compared to the closed-shroud impeller. The main reason for the increase in thrombosis risk was owing to elevated scalar shear stress and more coagulation promoting factor-ADP released. The regions with higher thrombosis potential were in the center hole, top and bottom clearance. As a novelty, the findings revealed that impeller shroud can influence mechanical and biochemical activation factors. It is useful for identifying potential risk regions of thrombus formation based on relative comparisons.

Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure.

Optimization of the highly potent and selective, yet metabolically unstable and poorly soluble hRXFP1 agonist AZ7976 led to the identification of the clinical candidate, AZD5462. Assessment of RXFP1-dependent cell signaling demonstrated that AZD5462 activates a highly similar panel of downstream pathways as relaxin H2 but does not modulate relaxin H2-mediated cAMP second messenger responsiveness. The therapeutic potential of AZD5462 was assessed in a translatable cynomolgus monkey heart failure model. Following 8 weeks of treatment with AZD5462, robust improvements in functional cardiac parameters including LVEF were observed at weeks 9, 13, and 17 without changes in heart rate or mean arterial blood pressure. AZD5462 was well tolerated in both rat and cynomolgus monkey and has successfully completed phase I studies in healthy volunteers. In summary, AZD5462 is a small molecule pharmacological mimetic of relaxin H2 signaling at RXFP1 and holds promise as a potential therapeutic approach to treat heart failure patients.

Adherence to heart failure treatment in patients with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is characterized by left ventricular (LV) dysfunction developing towards the end of pregnancy or in the first months postpartum. Although about 60% of women with PPCM (the majority of which are prescribed evidence based heart failure [HF] medications) show LV recovery within 6 to 12months, others remain with persistently impaired LV function. Poor adherence to medical therapy represents a major cause of avoidable hospitalizations, disability, and death in other cardiovascular conditions. In this study, we aimed to determine drug adherence to HF therapy among women with PPCM and to identify possible associations between drug adherence and LV recovery, functional status and psychological well-being. In this single-centre, prospective, observational study, we included 36 consecutive women with PPCM. Adherence to HF treatment was assessed by (i) verifying the collection of pharmacy refills and (ii) using liquid chromatography high-resolution mass spectrometry (LC-HRMS). Participants were thereby classified as 'adherent' (i.e. all prescribed HF drugs were detectable by LC-HRMS), 'partially adherent' (i.e. at least one prescribed drug detectable) or 'non-adherent' (i.e. none of the prescribed drugs detectable). Health state index scores were assessed by EQ-5D-5L and HADS-A/D (for anxiety/depression). Patients' median age was 32.4years (IQR 27.6-36.1). At the adherence visit (which occurred at a median of 16months [IQR 5-45] after PPCM diagnosis), prescription included beta-blockers (77.8%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (75%), mineralocorticoid receptor antagonists (47.2%) and loop diuretics (95.2%). Less than two thirds of patients (63.9%) collected all their pharmacy refills in the 6months prior to adherence visit. According to LC-HRMS, 23.5% participants were classified as adherent, 53.0% as partially adherent, and 23.5% as non-adherent. Adherence was associated with significantly lower LVEDD at follow-up (47mm [IQR 46-52), vs. 56mm [IQR 49-64] with partial adherence, and 62mm [IQR 55-64] with non-adherence, P=0.022), and higher LVEF at follow-up (60% [IQR 41-65]), vs. partially adherence (46% [IQR 34-50]) and non-adherence (41.0% [IQR 29-47], P=014). Adherent patients had a lower overall EQ- 5D score (5.5 [IQR 5-7.5], vs. 6 [IQR 5-7] in partially adherent, and 10 [IQR 8-15] in non-adherent patients, P=0.032) suggestive of a better self-rated health status. Adherence to HF therapy was associated with favourable LV reverse remodelling in PPCM and better self-rated health status. Our study highlights the importance of drug adherence for functional recovery. Drug adherence should be an important component of patient communication and specific interventions in PPCM.

Guideline directed medical therapy induced nephrotoxicity in HFrEF patients; an insight to its mechanism

Guideline Directed Medical Therapy (GDMT) has been the standard pharmacotherapy for the treatment of Heart Failure patients with reduced Ejection Fraction (HFrEF) recommended by the European Society of Cardiology (ESC). However, patients on GDMT are likely to possess nephrotoxicity as an adverse effect. We utilized multiple system biology tools like ADVER-Pred, gene enrichment analysis, molecular docking, molecular dynamic simulations, and MMPBSA analysis to predict a possible molecular mechanism of how selected combinations of GDMT may cause nephrotoxicity. As per the ACC/AHA/ESC guidelines, we categorized the drugs as category 1 including β-blockers (BB), angiotensin receptor blockers (ARB), and sodium-glucose cotransporter-2 inhibitors (SGLT2I), category 2 includes BB’s, SGLT2I, and angiotensin receptor-neprilysin inhibitors (ARNI), and category 3 includes BB’s, SGLT2I, and angiotensin-converting enzyme (ACE) inhibitors. Enrichment analysis predicted category 2 drugs to possess the highest number of proteins to be involved in the development of nephrotoxicity i.e. 79.41%. The targets HBA1, CBR1, ATG5, and SLC6A3 were the top hub genes with an edge count of 7 followed by GPX1 with an edge count of 6. Molecular docking studies revealed candesartan-SLC6A3 to possess the highest binding affinity of −10.2 kcal/mol. In addition, simulation studies displayed empagliflozin-CBR1 to possess the highest stability followed by candesartan-ATG5. A combination of β-blockers, ARBs, and SGLT2I are predicted to likely possess nephrotoxicity which may be due to the modulation of HBA1, CBR1, ATG5, and GPX1. In conclusion, candesartan and empagliflozin are most likely to cause nephrotoxicity via the modulation of HBA1, CBR1, ATG5, and GPX1. Communicated by Ramaswamy H. Sarma

Latest pharmaceutical approaches across the spectrum of heart failure.

Despite major advances in prevention and medical therapy, heart failure (HF) remains associatedwith high morbidity and mortality, especially in older and frailer patients. Therefore, acomplete, guideline-based treatment is essential, even in HF patients with conditionstraditionally associated with a problematic initiation and escalation of the medical HFtherapy, such as chronic kidney disease and arterial hypotension, as the potential adverse effects areovercome by the overall decrease of the absolute risk. Furthermore, since the latestdata suggest that the benefit of a combined medical therapy (MRA, ARNI, SGLT2i,beta-blocker) may extend up to a LVEF of 65%, further trials on these subgroups ofpatients (HFmrEF, HFpEF) are needed to re-evaluate the guideline-directed medicaltherapy across the HF spectrum. In particular, the use of SGLT2i was recentlyextended to HFpEF patients, as evidenced by the DELIVER and EMPEROR-preservedtrials. Moreover, the indication for other conservative treatments in HF patients, suchas the intravenous iron supplementation, was accordingly strengthened in the latestguidelines. Finally, the possible implementation of newer substances, such as finerenone, in guideline-directed medical practice for HF is anticipated with great interest.

Artificial Intelligence in Heart Failure: Friend or Foe?

In recent times, there have been notable changes in cardiovascular medicine, propelled by the swift advancements in artificial intelligence (AI). The present work provides an overview of the current applications and challenges of AI in the field of heart failure. It emphasizes the "garbage in, garbage out" issue, where AI systems can produce inaccurate results with skewed data. The discussion covers issues in heart failure diagnostic algorithms, particularly discrepancies between existing models. Concerns about the reliance on the left ventricular ejection fraction (LVEF) for classification and treatment are highlighted, showcasing differences in current scientific perceptions. This review also delves into challenges in implementing AI, including variable considerations and biases in training data. It underscores the limitations of current AI models in real-world scenarios and the difficulty in interpreting their predictions, contributing to limited physician trust in AI-based models. The overarching suggestion is that AI can be a valuable tool in clinicians' hands for treating heart failure patients, as far as existing medical inaccuracies have been addressed before integrating AI into these frameworks.

Prognostic value of serum albumin in heart failure patients with cardiac resynchronization therapy.

Aim: There is a lack of data about the association between admission serum albumin levels and long-term mortality in heart failure (HF) patients with cardiac resynchronization therapy defibrillators (CRT-D). We aim to investigate this connection in HF patients with CRT-D. Methods: The study population consisted of 477 HF patients with CRT-D. The cohort was divided into three groups according to albumin values, and the relationship between these groups and long-term mortality were evaluated. Results: Long-term all-cause mortality (HR: 3.32, 95% CI: 2.12-6.84), appropriate (HR: 4.44, 95% CI: 2.44-8.06) and inappropriate (HR: 2.95, 95% CI: 1.88-6.02) shocks were higher in the low albumin group. Conclusion: Low albumin levels are associated with the long-term mortality and appropriate shock treatment in HF patients with CRT-D.

Cost-effectiveness of empagliflozin in the treatment of Malaysian patients with chronic heart failure and preserved or mildly reduced ejection fraction.

Empagliflozin demonstrates promising clinical benefits in patients with heart failure (HF). While an early study demonstrates that empagliflozin is cost-effective for treating HF patients with reduced ejection fraction (HFrEF) in Malaysia, its cost-effectiveness for HF with ejection fraction (EF)>40% remains unclear. Therefore, the current study aimed to assess the cost-effectiveness of adding empagliflozin to the standard of care (SoC) for HF patients with EF>40% from the perspective of Malaysian healthcare system. Subsequently, the results were consolidated with the findings for HFrEF to evaluate the cost-effectiveness of empagliflozin when used for all HF patients in Malaysia, irrespective of EF. A cost-utility analysis was performed using a validated Markov model, which modelled a cohort of adult patients through health states related to symptom severity and functional impairment, to estimate costs and quality-adjusted life-years (QALYs). The influence of model inputs and assumptions, sensitivity, scenario, and subgroup analyses were explored. All costs were expressed in 2022 Malaysian ringgits (RM). Costs and QALYs were discounted at an annual rate of 3.0% as per local pharmacoeconomic guideline. The base-case incremental cost-effectiveness ratio (ICER) for HF patients with EF>40% was RM 40,454 per QALY gained. At a cost-effectiveness threshold of RM 47,439/QALY gained, empagliflozin was cost-effective in 57% of replications. The model outcomes were sensitive to inputs related to the treatment effect of empagliflozin in reducing HF-related hospitalisation and cardiovascular mortality, and empagliflozin cost. For the overall HF population, the ICER was RM 29,463/QALY gained. The findings suggest that empagliflozin is a cost-effective treatment option for the Malaysian HF population, including those with EF>40%. As such, the intervention warrants consideration by the Malaysian healthcare provider to mitigate the burden of HF and address the unmet needs of the EF>40% population.

A new method using deep transfer learning on ECG to predict the response to cardiac resynchronization therapy

Background: Cardiac resynchronization therapy (CRT) has emerged as an effective treatment for heart failure patients with electrical dyssynchrony. However, accurately predicting which patients will respond to CRT remains a challenge. This study explores the application of deep transfer learning techniques to train a predictive model for CRT response. Methods: In this study, the short-time Fourier transform (STFT) technique was employed to transform ECG signals into two-dimensional images. A transfer learning approach was then applied to the MIT-BIT ECG database to pre-train a convolutional neural network (CNN) model. The model was fine-tuned to extract relevant features from the ECG images and then tested on our dataset of CRT patients to predict their response. Results: Seventy-one CRT patients were enrolled in this study. The transfer learning model achieved an accuracy of 72% in distinguishing responders from non-responders in the local dataset. Furthermore, the model showed good sensitivity (0.78) and specificity (0.79) in identifying CRT responders. The performance of our model outperformed clinic guidelines and traditional machine learning approaches. Conclusion: The utilization of ECG images as input and leveraging the power of transfer learning allows for improved accuracy in identifying CRT responders. This approach offers potential for enhancing patient selection and improving the outcomes of CRT.

Post-implantation CMR imaging to study biventricular pacing effects on the right ventricle in left bundle branch block patients.

Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with left ventricular dysfunction and a left bundle branch block. However, its impact on right ventricular (RV) function remains uncertain. This cardiac magnetic resonance imaging study found that CRT did not improve RV volumes and function, and CRT-off during follow-up had an immediate detrimental effect on the RV, which may suggest potential unfavorable RV remodeling with RV pacing during CRT.

Numerical simulation analysis of multi-scale computational fluid dynamics on hemodynamic parameters modulated by pulsatile working modes for the centrifugal and axial left ventricular assist devices

Continuous flow (CF) left ventricular assist devices (LVAD) operate at a constant speed mode, which could result in increased risk of adverse events due to reduced vascular pulsatility. Consequently, pump speed modulation algorithms have been proposed to augment vascular pulsatility. However, the quantitative local hemodynamic effects on the aorta when the pump is operating with speed modulation using different types of CF-LVADs are still under investigation. The computational fluid dynamics (CFD) study was conducted to quantitatively elucidate the hemodynamic effects on a clinical patient-specific aortic model under different speed patterns of CF-LVADs. Pressure distribution, wall shear stress (WSS), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and velocity were calculated to compare their differences at constant and pulsatile speeds under centrifugal and axial LVAD support. Results showed that pulse pressure on the aorta was significantly larger under pulsatile speed mode than that under constant speed mode for both CF-LVADs, indicating enhanced aorta pulsatility, as well as the higher peak blood flow velocity on some representative slices of aorta. Pulsatile speed modulation enhanced peak WSS compared to constant speed; high TAWSS region appeared near the branch of left common carotid artery and distal aorta regardless of speed modes and CF-LVADs but these regions also had low OSI; RRT was almost the same for all the cases. This study may provide a basis for the scientific and reasonable selection of the pulsatile speed patterns of CF-LVADs for treating heart failure patients.

Home- versus clinic-based exercise intervention in patients with heart failure (EXIT-HF trial): a pragmatic randomized controlled trial

Abstract Background The limited accessibility partially explains the low uptake of cardiac rehabilitation (ExCR) for heart failure (HF). Home-based programs might address those obstacles but few data from randomized trials are available. Purpose To compare the effectiveness of a home-based versus clinic-based ExCR intervention in HF patients. Methods Single-center, single-blind, parallel groups, non-inferiority pragmatic randomized control trial (1:1 and after COVID-19 2:1 home- vs clinic-based). Adult HF patients referred to our cardiac rehabilitation (CR) unit were randomized to either a clinic-based (24 supervised sessions at a CR unit of a tertiary hospital over 12 weeks) or home-based (4 supervised ExT sessions to familiarize with the training protocol and the remaining sessions continued at home) over 12 weeks. Exercise training protocol consisted of a combination of endurance (at 60%-80% of peak oxygen uptake [VO2peak] and resistance training (elastic bands). The primary endpoint was the change in VO2peak at the end of the 12-week program. Secondary outcomes included adherence (>80% of sessions attendance) and change of Minnesota Living with HF Questionnaire (MLHFQ) scores. Results 120 patients (mean age 64±11 years; 64% men) were randomized: 44 to clinic- and to 76 home-based intervention. 41% had an ischemic cardiomyopathy, 27% had an ICD/CRT, the mean LVEF was 36±11% (62% had LVEF <40%), 73% were on NYHA class II, and the median NT-proBNP was 361 [IQR 170-1008] ng/mL. Intervention groups were well balanced, including basal VO2peak that was similar between groups (17.8±4.8 vs 18.1±5.2 mL/min/Kg; p=0.75). Adherence was similar between groups (87.5% vs 82.5%; p=0.50). At week 12, on average, patients increased VO2 peak by 0.9±2.5 mL/min/Kg compared to baseline (p<0.001). No significant differences were found between clinic- and home-based interventions (p=0.25). Consistently, the MLHFQ total score decreased significantly overall (-10.3±1.7 points; p<0.001), with no significant differences between groups (p=0.91). The drop-out rate was 14% and 17% in clinic- and home-based groups, respectively. Conclusions The clinical impact of home-based CR program on peakVO2 and health-related quality of life of HF patients was similar to a standard supervised clinic-based one. Our data support the home-based program as an effective alternative way of delivering CR in HF.

Allied health professional-physician collaboration to enhance guideline-directed medical therapy of heart failure: expanding therapeutic opportunities

Abstract Background Guideline-directed medical therapy (GDMT) is the cornerstone of treatment for heart failure patients with reduced ejection fraction (HFrEF). Optimization of GDMT at a targeted allied professional medication titration clinic represents a key opportunity to provide greater access to care and further refine patient care models, leading to improvements in clinical outcomes. Purpose To evaluate the effectiveness of an allied health practitioner optimization clinic model in HFrEF as indicated by changes in rates of triple and quadruple GDMT therapy (see associated table). Methods Qualified patients were either: proactively screened from clinic lists, having demonstrated a diagnosis of heart failure, reduced ejection fraction, and not receiving triple or quadruple therapy, or were physician-referred after initial optimization during 2021-2022. Participants subsequently underwent medication review and optimization by an allied health professional, involving introduction, up-titration, down-titration, or withdrawal of medications across relevant medication classes as tolerated. Results 52 (78.8% male) patients with a mean age of 70.3 (11.4) years and mean ejection fraction of 30.1 (6.7) percent underwent medication optimization. Along with HFrEF, all patients exhibited cardio-metabolic multi-morbidity (2-3 cardio-metabolic diagnoses), including hypertension (59.6%), dyslipidemia (71.2%), coronary artery disease (61.5%), atrial fibrillation (42.3%), and type 2 diabetes (21.2%). Pre-optimization prescription rates ranged from: 53.8% for ACEi/ARB, 30.8% for ARNI, 80.8% for beta-blockers, 59.6% for MRA, 40.4% for diuretics, and 13.5% for SGLT2i. Medication review and optimization spanned an average of 2.8 (1-7) meetings, and lead to an average of 1.9 (range 0-4) medication changes. Among 49 patients considered for ARNI optimization, there were 43 (87.7%) successful introductions and progressive dose adjustments, including 12 (27.9%) dose adjustments among those already prescribed. Additional changes involved optimizations in: beta-blockers (5 introductions, 5 dose-changes), MRA (8 introductions, 4 dose-changes, 2 withdrawals), diuretics (1 introduction, 7 dose-changes, 2 withdrawals), and SGLT2i (17 introductions). Collaboration between allied health professionals and physicians in optimization demonstrated significant improvements in rates of triple (42.3% vs 63.5%, P= 0.003) and quadruple (5.8% vs 26.9%, P= 0.001) therapy post-optimization. Discussion A Collaborative approach to medication optimization increased the use of GDMT in ambulatory patients with HFrEF. Collaboration presents both clinicians and health systems with greater opportunities to improve healthcare access, therapeutic inertia, and disease management.Pre-post Changes in GDMT Rates

Determinants and differences of delay in cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is recommended for the treatment of heart failure (HF) patients with reduced ejection fraction and left bundle branch block (LBBB) but is still largely underused which may further deteriorate the HF condition. Studying the impact and factors related to delays in CRT with or without an Implantable cardioverter defibrillator (ICD) is fundamental to enhance CRT implementation in clinical practice. Methods We used a central ECG database together with National patient registries to identify LBBB patients with a QRS duration of more than 150 ms and estimated a class I indication for CRT based on a registered diagnosis of HF and ejection fraction < 35% (baseline date). We compared patient characteristics in those with CRT-D, CRT without defibrillator (CRT-P) and patients with an indication but without CRT. Factors associated with CRT-P or CRT-D were analyzed as well as factors related to delay in CRT utilization. Outcome parameters were HF hospitalization and combined total and CV mortality and the impact of the delay in CRT utilization on outcome was analysed. Results Of 5359 patients with LBBB and QRS > 150ms, 1268 (24%) developed a class I indication for CRT. Of these 31% received a CRT-P, 36% CRT-D and 33% were not implanted. Independent predictors for CRT-P were age > 75 years and for CRT-D ischemic heart failure aetiology, hypertension and male sex. Patients with CRT-D had similar HF hospitalization rate (hazard ratio (HR): 0.95, 95% (CI) 0.80-1.14) as patients with CRT-P. In contrast, patients indicated but not implanted with CRT had a significantly higher prevalence of HF hospitalization (HR: 1.65, CI 1.39-1.96). A delay in CRT use > 365 days (161 patients) from indication (baseline) was associated with increased risk of overall mortality and cardiovascular mortality compared to CRT implantation < 30 days from the indication (HR: 1.64, CI 1.05-2.55 and HR: 1.87, CI 1.10-3.18). Age > 75 years, male sex, paroxysmal atrial fibrillation, diabetes and ischemic heart disease were associated with significant delay in CRT use (>365 days). Conclusion In a large real-world setting, delay in CRT implantation was common and associated with increased mortality. The findings suggest a need for new methods to find and treat HF patients with an indication for CRT.

Abstract 12622: Long Term Use of Adaptive Servo Ventilation Improves and Maintains Cardiac Function in Patients With Heart Failure With Central Sleep Apnea and Prevents Readmission Due to Worsening Heart Failure Compared to Short Term Use

Introduction: Central sleep apnea (CSA) is closely associated with poor prognosis in heart failure (HF) patients. Adaptive servo-ventilation (ASV) was expected as a new treatment for HF patients with CSA. However, the efficacy of ASV is controversial, especially the efficacy of long-term use has remained unclear. Methods: We retrospectively examined all HF patients with CSA treated with ASV seen between May 2008 and November 2022 in our hospital who had not been admitted to the hospital due to worsening HF in the 6 months before initiating ASV therapy. We divided them into 2 groups: (A) non-continues-ASV-treated patients; (B) continues-ASV-treated patients. The outcome was a composite of readmission due to worsening HF and all-cause mortality. Results: During a median follow-up of 10.3 years after leaving the hospital, 11 patients died out of 101 patients. Twenty-two patients (group A) could not continue to use ASV because of its discomfort. Seventy-nine patients (group B) could continue to use the ASV device at night after leaving the hospital over a long period. There were almost no significant differences in the baseline characteristics between the two groups. In group B, during 6-, 12-, and 24-month observations, left ventricular ejection fraction (46.4 +/- 17.9 to 47.1 +/- 15.6, 49.8 +/- 15.8, and 48.2+/- 18.9%, p<0.05 compared with baseline) and brain natriuretic peptide (685.5 +/- 1087.2 to 233.1+/- 362.9, 391.8 +/- 929.0 and 166.9 +/- 195.1 pg/ml, p<0.05 compared with baseline) improved significantly. And there was significantly less readmission by worsening HF than in group A (log-rank P<0.001). However, there were no significant differences in all-cause mortality between the two groups (log-rank P=0.221). Conclusions: This study showed that long-term ASV therapy for more than 10 years reduced readmission by worsening HF with CSA patients compared to short-term use due to improved and maintained cardiac function but did not affect mortality.

Abstract 14356: Higher Burdon of Premature Ventricular Complexes is Not Uncommon in Stable Well Treated Heart Failure Patients and Relate to Poorer Outcomes

Introduction: While premature ventricular contractions (PVCs) are generally considered benign, recent evidence suggests that even the contractions preceding PVCs are inefficient so that even a moderate burden of PVCs may be associated with loss of contractile efficiency and increased risk of events. It is however unclear what proportion of stable heart failure (HF) patients have a moderate to high burden of PVCs, despite being well-treated. Aim: The aim of this study was to assess the proportion of HF patients that have more than 5% PVCs and whether this higher number is related to worse outcomes. Methods: We retrospectively analyzed electronic medical records from 676 adult patients with either an ejection fraction < 40% or NTproBNP more than 600 pg/ml at the Amsterdam UMC (AMC) who received Holter monitoring between 2014 and 2022. In a second independent cohort from a heart failure registry at Henry Ford Hospital (HFH) in Detroit, Michigan, we retrospectively reviewed all participants with ejection fraction < 40% that had a Holter monitor at any point (n=180). Results: The median baseline age of the Amsterdam UMC patients was 62 and 40% were female. The HFH cohort had a median age of 64 years and 50% were female. Results are summarized in the table. During the follow-up period, significantly more patients died in the group with more than 5% PVCs (p < 0.05 in the Amsterdam UMC cohort). Conclusions: We show in two independent cohorts that around 8-10% of HF patients have a significant burden of PVCs (i.e. >5% of all heartbeats), despite adequate use of beta-blocker therapy. This proportion of PVCs is associated with an increased risk of death over one year. This suggests that in HFrEF patients, PVCs burden more than 5% of heartbeats may not be as harmless as often thought.

Exercise in hypoxia: a model from laboratory to on-field studies.

Clinical outcome and quality of life of patients with chronic heart failure (HF) have greatly improved over the last two decades. These results and the availability of modern lifts allow many cardiac patients to spend leisure time at altitude. Heart failure per se does not impede a safe stay at altitude, but exercise at both simulated and real altitudes is associated with a reduction in performance, which is inversely proportional to HF severity. For example, in normal subjects, the reduction in functional capacity is ∼2% every 1000 m altitude increase, whereas it is 4 and 10% in HF patients with normal or slightly diminished exercise capacity and in HF patients with markedly diminished exercise capacity, respectively. Also, the on-field experience with HF patients at altitude confirms safety and shows overall similar data to that reported at simulated altitude. Even 'optimal' HF treatment in patients spending time at altitude or at hypoxic conditions is likely different from optimal treatment at sea level, particularly with regard to the selectivity of β-blockers. Furthermore, high altitude, both simulated and on-field, represents a stimulating model of hypoxia in HF patients and healthy subjects. Our data suggest that spending time at altitude (<3500 m) can be safe even for HF patients, provided that subjects are free from comorbidities that may directly interfere with the adaptation to altitude and are stable. However, HF patients experience a reduction of exercise capacity directly proportional to HF severity and altitude. Finally, HF patients should be tested for functional capacity and must undergo a specific 'hypoxic-tailored treatment' to avoid pharmacological interference with altitude adaptation mechanisms, particularly with regard to the selectivity of β-blockers.

Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial.

Introduction: There is an increasing interest in using metformin in cardiovascular diseases and its potential new roles. Only two randomized controlled trials investigated the effect of metformin in nondiabetic heart failure (HF) patients. However, none of these studies assess the role of metformin in reducing oxidative stress. We hypothesized that metformin might improve oxidative stress and left ventricular remodeling in nondiabetic HF patients with reduced ejection fraction (HFrEF). Methods and Methods: Seventy HFrEF patients (EF 37% ± 8%; median age 66 years) were randomized to metformin (n = 35) or standard of care (SOC) for HF (n = 35) for 6 months in addition to standard therapy. Outcomes included the difference in the change (Δ) in total antioxidant capacity (TAC) and malondialdehyde (MDA), both assessed colorimetrically and left ventricular mass index (LVMI) assessed through transthoracic echocardiography. Results: Compared with the SOC, metformin treatment increased TAC [Δ = 0.12 mmol/L, confidence intervals (95% CIs): 0.03-0.21; P = 0.007]. TAC increased significantly only in the metformin group (0.90 ± 0.08 mmol/L at baseline vs. 1.04 ± 0.99 mmol/L at 6 months, P < 0.05). Metformin therapy preserved LVMI (Δ = -23 g/m2, 95% CI: -42.91 to -4.92; P = 0.014) and reduced fasting plasma glucose (Δ = -6.16, 95% CI: -12.31 to -0.02, P = 0.047) compared with the SOC. Results did not change after adjusting for baseline values. Changes in MDA left ventricular ejection fraction (LVEF) and blood pressure were not significantly different between groups. Conclusion: Metformin treatment in HF patients with reduced LVEF improved TAC and prevented the increase in LVMI compared with the SOC. These effects of metformin warrant further research in HF patients without diabetes to explore the potential benefits of metformin. Trial Registration Number: This protocol was registered in ClinicalTrials.gov under the number NCT05177588.

Uric acid is a biomarker for heart failure, but not therapeutic target: result from a comprehensive meta-analysis.

This systematic review and meta-analysis aimed to investigate the association between serum uric acid (SUA) levels and the incidence rate and prognosis of heart failure (HF), as well as the impact of uric acid-lowering treatment on HF patients. PubMed and Embase were searched for original articles reporting on the association between SUA and HF incidence, adverse outcomes, and the effect of uric acid-lowering treatment in HF patients. Data were pooled using random effects or fixed effects models. Univariable meta-regression analysis assessed the influence of study characteristics on research outcomes. Statistical analyses were conducted using RevMan software and STATA software version 15.0. Eleven studies on HF incidence and 24 studies on adverse outcomes in HF patients were included. Higher SUA levels were associated with an increased risk of HF (RR: 1.81, 95% CI: 1.53-2.16), all-cause mortality (RR: 1.44, 95% CI: 1.25-1.66), cardiac death (RR: 1.56, 95% CI: 1.32-1.84), and HF rehospitalization (RR: 2.07, 95% CI: 1.37-3.13) in HF patients. Uric acid-lowering treatment was found to increase all-cause mortality in HF patients (RR: 1.15, 95% CI: 1.05-1.25). Uric acid is an independent predictor of heart failure occurrence and adverse prognosis. Targeting uric acid lowering as a therapeutic intervention does not improve the prognosis of patients with heart failure. It may not be advisable to use traditional urate-lowering drugs in young patients with heart failure, and elderly patients should exercise caution when using them.

Echocardiography-based machine learning algorithm for distinguishing ischemic cardiomyopathy from dilated cardiomyopathy

BackgroundMachine learning (ML) can identify and integrate connections among data and has the potential to predict events. Heart failure is primarily caused by cardiomyopathy, and different etiologies require different treatments. The present study examined the diagnostic value of a ML algorithm that combines echocardiographic data to automatically differentiate ischemic cardiomyopathy (ICM) from dilated cardiomyopathy (DCM).MethodsWe retrospectively collected the echocardiographic data of 200 DCM patients and 199 ICM patients treated in the First Affiliated Hospital of Guangxi Medical University between July 2016 and March 2022. All patients underwent invasive coronary angiography for diagnosis of ICM or DCM. The data were randomly divided into a training set and a test set via 10-fold cross-validation. Four ML algorithms (random forest, logistic regression, neural network, and XGBoost [ML algorithm under gradient boosting framework]) were used to generate a training model for the optimal subset, and the parameters were optimized. Finally, model performance was independently evaluated on the test set, and external validation was performed on 79 patients from another center.ResultsCompared with the logistic regression model (area under the curve [AUC] = 0.925), neural network model (AUC = 0.893), and random forest model (AUC = 0.900), the XGBoost model had the best identification rate, with an average sensitivity of 72% and average specificity of 78%. The average accuracy was 75%, and the AUC of the optimal subset was 0.934. External validation produced an AUC of 0.804, accuracy of 78%, sensitivity of 64% and specificity of 93%.ConclusionsWe demonstrate that utilizing advanced ML algorithms can help to differentiate ICM from DCM and provide appreciable precision for etiological diagnosis and individualized treatment of heart failure patients.