Matteo Pagnesi, Mauro Riccardi, Francesco Maisano, Julia Grapsa, Vassilis Barberis, Magdy Abdelhamid, Elena-Laura Antohi, Henrike Arfsten, Nicole Karam, Denisa Muraru, Karl-Philipp Rommel, Anna Sannino, Wilfried Mullens, Marianna Adamo, Marco Metra
Atrial functional mitral regurgitation (AFMR) is an increasingly recognized subtype of mitral regurgitation, characterized by left atrial remodelling and mitral annular dilation in the absence of primary mitral valve disease or left ventricular dysfunction. Closely linked to chronic atrial fibrillation and heart failure with preserved ejection fraction, AFMR is associated with poor clinical outcomes and represents a growing therapeutic challenge. This expert opinion paper summarizes current evidence on the epidemiology, pathophysiology, diagnosis and management strategies, including medical therapy and emerging data supporting surgical and transcatheter interventions in selected patients. However, data from prospective controlled clinical trials are still lacking. Future research is needed to refine patient selection, long-term outcomes and to support evidence-based recommendations for this increasingly prevalent condition.
{"title":"Epidemiology, pathophysiology, diagnosis and management of atrial functional mitral regurgitation: An expert opinion paper","authors":"Matteo Pagnesi, Mauro Riccardi, Francesco Maisano, Julia Grapsa, Vassilis Barberis, Magdy Abdelhamid, Elena-Laura Antohi, Henrike Arfsten, Nicole Karam, Denisa Muraru, Karl-Philipp Rommel, Anna Sannino, Wilfried Mullens, Marianna Adamo, Marco Metra","doi":"10.1002/ehf2.15405","DOIUrl":"10.1002/ehf2.15405","url":null,"abstract":"<p>Atrial functional mitral regurgitation (AFMR) is an increasingly recognized subtype of mitral regurgitation, characterized by left atrial remodelling and mitral annular dilation in the absence of primary mitral valve disease or left ventricular dysfunction. Closely linked to chronic atrial fibrillation and heart failure with preserved ejection fraction, AFMR is associated with poor clinical outcomes and represents a growing therapeutic challenge. This expert opinion paper summarizes current evidence on the epidemiology, pathophysiology, diagnosis and management strategies, including medical therapy and emerging data supporting surgical and transcatheter interventions in selected patients. However, data from prospective controlled clinical trials are still lacking. Future research is needed to refine patient selection, long-term outcomes and to support evidence-based recommendations for this increasingly prevalent condition.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"3788-3805"},"PeriodicalIF":3.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Knigge, Marcelo B. Bastos, Bastian Schmack, Liam Schana, Oren Malchin, Ali S. Merzah, Aron F. Popov, Alexander Weymann, Arjang Ruhparwar, Felix Schumacher, Günes Dogan, Jan D. Schmitto
Aims
Non-pharmacological therapies for acute decompensated heart failure (HF) and cardiogenic shock have evolved considerably in recent decades. Short-term mechanical circulatory support (MCS) devices can be used as circulatory backup. While nearly all available devices use continuous flow, evidence indicates that pulsatile flow can be more effective. This study presents the first experimental use of a novel counter-pulsatile left ventricular (LV) assist device (LVAD) with a primary focus on assessing its feasibility and effectiveness.
Methods
The pulsatile ventricular assist platform (pVAP) was applied in six porcine models of acute ischaemic HF with the inlet in the left atrium and the outlet in the aorta. HF was induced through stepwise ligation of the left anterior descending artery and its diagonal branches. The pVAP functioned driven by a conventional IABP console while LV pressure–volume (PV) loops and standard haemodynamics with the device OFF and ON were recorded. Absolute values and percent variations were compared using Mann–Whitney's U test and Wilcoxon's sign-rank test.
Results
The device's output flow is frequency dependent, with an output flow of 2.64 ± 0.22 L/min at 80 bpm. Activation reduced the EDV [132 (90–145) vs. 118 (83–130) mL, P < 0.05], EDP 9 (6–10) vs. 6 (5–9) mmHg, P < 0.001], native cardiac output [CON, 3.64 (2.88–6.71) vs. 1.67 (1.24–2.48) L/min, P < 0.001] and myocardial oxygen consumption [pressure–volume area * heart rate (PVA*HR), 4592 (2944–9272) vs. 2901 (1915–4437) mJ, P < 0.001]. Contractility decreased, with right-shifting the end-systolic PV relationship (ESPVR) while ESP and forward cardiac output COF were constant. The mean arterial pressure increased [54 (48–60) vs. 49 (42–55) mmHg, P < 0.001] and mPAP decreased [10 (8–11) to 9 (7–10) mmHg, P < 0.01]. The PV loop shifted left and downward. No changes occurred in the passive-elastic properties of the LV in diastole.
Conclusions
The pVAP reduced the LV mechanical load while increasing systemic pressures and reducing pulmonary pressures. Its functionality as an LVAD is characterised by consistent and predictable performance. Further research is necessary to elucidate the physiological and clinical impact of the device in animals and, subsequently, in humans.
目的：近几十年来，急性失代偿性心力衰竭（HF）和心源性休克的非药物治疗已经有了很大的发展。短期机械循环支持（MCS）装置可作为循环备份。虽然几乎所有可用的设备都使用连续流，但有证据表明脉动流可能更有效。本研究提出了一种新型反搏动左心室辅助装置（LVAD）的首次实验应用，主要侧重于评估其可行性和有效性。方法：采用脉动式心室辅助平台（pVAP）对6只左心房进、主动脉出的猪急性缺血性心力衰竭模型进行治疗。采用结扎左前降支及其斜支的方法诱导心衰。pVAP由传统的IABP控制台驱动，同时记录左室压力-体积（PV）环和标准血流动力学。使用Mann-Whitney's U检验和Wilcoxon's sign-rank检验比较绝对值和百分比变化。结果：该装置的输出流量与频率有关，在80 bpm时输出流量为2.64±0.22 L/min。激活降低EDV [132 (90-145) vs. 118 (83-130) mL, P N, 3.64 (2.88-6.71) vs. 1.67 (1.24-2.48) L/min， P F不变。平均动脉压升高[54 (48-60)vs. 49 (42-55) mmHg， P结论：pVAP降低左室机械负荷，同时增加全身压和降低肺压。其功能作为LVAD的特点是一致和可预测的性能。需要进一步的研究来阐明该装置在动物身上以及随后在人类身上的生理和临床影响。
{"title":"First evaluation of a novel pulsatile LVAD: Feasibility and haemodynamic impact in acute heart failure","authors":"Sara Knigge, Marcelo B. Bastos, Bastian Schmack, Liam Schana, Oren Malchin, Ali S. Merzah, Aron F. Popov, Alexander Weymann, Arjang Ruhparwar, Felix Schumacher, Günes Dogan, Jan D. Schmitto","doi":"10.1002/ehf2.15410","DOIUrl":"10.1002/ehf2.15410","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Non-pharmacological therapies for acute decompensated heart failure (HF) and cardiogenic shock have evolved considerably in recent decades. Short-term mechanical circulatory support (MCS) devices can be used as circulatory backup. While nearly all available devices use continuous flow, evidence indicates that pulsatile flow can be more effective. This study presents the first experimental use of a novel counter-pulsatile left ventricular (LV) assist device (LVAD) with a primary focus on assessing its feasibility and effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The pulsatile ventricular assist platform (pVAP) was applied in six porcine models of acute ischaemic HF with the inlet in the left atrium and the outlet in the aorta. HF was induced through stepwise ligation of the left anterior descending artery and its diagonal branches. The pVAP functioned driven by a conventional IABP console while LV pressure–volume (PV) loops and standard haemodynamics with the device OFF and ON were recorded. Absolute values and percent variations were compared using Mann–Whitney's <i>U</i> test and Wilcoxon's sign-rank test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The device's output flow is frequency dependent, with an output flow of 2.64 ± 0.22 L/min at 80 bpm. Activation reduced the EDV [132 (90–145) vs. 118 (83–130) mL, <i>P</i> < 0.05], EDP 9 (6–10) vs. 6 (5–9) mmHg, <i>P</i> < 0.001], native cardiac output [CO<sub>N</sub>, 3.64 (2.88–6.71) vs. 1.67 (1.24–2.48) L/min, <i>P</i> < 0.001] and myocardial oxygen consumption [pressure–volume area * heart rate (PVA*HR), 4592 (2944–9272) vs. 2901 (1915–4437) mJ, <i>P</i> < 0.001]. Contractility decreased, with right-shifting the end-systolic PV relationship (ESPVR) while ESP and forward cardiac output CO<sub>F</sub> were constant. The mean arterial pressure increased [54 (48–60) vs. 49 (42–55) mmHg, <i>P</i> < 0.001] and mPAP decreased [10 (8–11) to 9 (7–10) mmHg, <i>P</i> < 0.01]. The PV loop shifted left and downward. No changes occurred in the passive-elastic properties of the LV in diastole.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The pVAP reduced the LV mechanical load while increasing systemic pressures and reducing pulmonary pressures. Its functionality as an LVAD is characterised by consistent and predictable performance. Further research is necessary to elucidate the physiological and clinical impact of the device in animals and, subsequently, in humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4171-4183"},"PeriodicalIF":3.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart failure (HF) is a multifactorial and pathophysiological complex syndrome, involving not only neurohormonal activation but also oxidative stress, chronic low-grade inflammation, and metabolic derangements. Central to the cellular defence against oxidative damage is nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that orchestrates antioxidant and cytoprotective responses. Preclinical in vitro and in vivo studies reveal that Nrf2 signalling is consistently impaired in HF, contributing to the progression of myocardial dysfunction. The loss of Nrf2 activity intersects a complex network of pathological processes involving neurohormonal activation, ischaemia–reperfusion injury, and sustained inflammation, exacerbating cardiac functional decline. Nrf2 deficiency diminishes resilience to clinical conditions such as hypertension, diabetic cardiomyopathy, and cancer therapy-related cardiotoxicity, favouring the transition from initial cardiac dysfunction to overt HF. Initial evidence supports the therapeutic potential of Nrf2 modulation. Lifestyle interventions such as exercise training, various natural compounds, and established cardiovascular agents (e.g. sodium-glucose cotransporter-2 inhibitors) have been shown to restore Nrf2 activity. This review analyses the emerging role of Nrf2 as both a key player in HF pathogenesis and a promising therapeutic target, highlighting available evidence across HF phenotypes and addressing the controversies surrounding its pharmacological modulation.
{"title":"The emerging role of Nrf2 in heart failure: From cardioprotection to therapeutic approaches","authors":"Emiliano Fiori, Sergio Davinelli, Armando Ferrera, Alessandro Medoro, Carlo Barsali, Allegra Battistoni, Maurizio Volterrani, Massimo Volpe, Luciano Saso, Speranza Rubattu","doi":"10.1002/ehf2.15406","DOIUrl":"10.1002/ehf2.15406","url":null,"abstract":"<p>Heart failure (HF) is a multifactorial and pathophysiological complex syndrome, involving not only neurohormonal activation but also oxidative stress, chronic low-grade inflammation, and metabolic derangements. Central to the cellular defence against oxidative damage is nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that orchestrates antioxidant and cytoprotective responses. Preclinical in vitro and in vivo studies reveal that Nrf2 signalling is consistently impaired in HF, contributing to the progression of myocardial dysfunction. The loss of Nrf2 activity intersects a complex network of pathological processes involving neurohormonal activation, ischaemia–reperfusion injury, and sustained inflammation, exacerbating cardiac functional decline. Nrf2 deficiency diminishes resilience to clinical conditions such as hypertension, diabetic cardiomyopathy, and cancer therapy-related cardiotoxicity, favouring the transition from initial cardiac dysfunction to overt HF. Initial evidence supports the therapeutic potential of Nrf2 modulation. Lifestyle interventions such as exercise training, various natural compounds, and established cardiovascular agents (e.g. sodium-glucose cotransporter-2 inhibitors) have been shown to restore Nrf2 activity. This review analyses the emerging role of Nrf2 as both a key player in HF pathogenesis and a promising therapeutic target, highlighting available evidence across HF phenotypes and addressing the controversies surrounding its pharmacological modulation.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4000-4020"},"PeriodicalIF":3.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cecilia Miu-Ching Chan, Polly Wai-Chi Li, Derek Pok-Him Lee, Esmond Yan-Hang Fong, Ivy Sin-Yee Ng, Samantha Ki-Man Chiu, Clara Woon-Shan Fok, Frederick Kin-Wa Li, Shirley Ka-Wai Lee, Karen K. Y. Ho, Wilson Y. S. Leung, Cathy Cheuk-Sum Chan, Cindy Yiu-Ning Tsang, Michael Kang-Yin Lee
Aims
Despite therapeutic advancements, the prognosis of heart failure (HF) remains poor, with high rates of mortality and readmission, particularly following a HF exacerbation. This study aimed to evaluate the effects of a nurse-coordinated multidisciplinary comprehensive HF management programme on HF patients.
Methods and results
This retrospective cohort study involved patients admitted for acute HF exacerbation at a regional hospital in Hong Kong. We established two patient cohorts: the control cohort, recruited between January and December 2021, received standard care, while the programme cohort, recruited from October 2022 to December 2023, participated in a comprehensive programme. This programme included multidisciplinary ward rounds, early initiation of guideline-directed medical therapy (GDMT), discharge education, post-discharge transitional care and cardiac rehabilitation. The primary outcome was the composite endpoint of all-cause mortality and HF-related readmission at 6 months. Secondary endpoints included HF-related readmission and all-cause mortality. We also assessed patient satisfaction and health-related quality of life (HRQoL) in the programme cohort. The study included 732 patients, 24.0% female, 81.6% with HFrEF, mean age of 67.9 ± 13.2 years. After matching for age, sex and type of HF, 366 patients were allocated to each cohort. The programme cohort demonstrated significantly lower rates of the composite endpoint [12.0% vs. 38.0%, adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI) = 0.19–0.37, P < 0.001]) and HF-related readmissions (10.1% vs. 25.4%, aHR = 0.36, 95% CI = 0.24–0.52, P < 0.001) compared with the control cohort. All-cause mortality was also significantly reduced (4.4% vs. 18.3%, aHR = 0.22, 95% CI = 0.13–0.38, P < 0.001). Improvements in HRQoL and high patient satisfaction were noted in the programme cohort.
Conclusions
The nurse-coordinated comprehensive HF management programme significantly reduced readmissions and mortality, with consistent benefits across different subgroups. Further research is needed to confirm these benefits and explore mechanisms.
目的：尽管治疗取得了进步，但心力衰竭（HF）的预后仍然很差，死亡率和再入院率很高，特别是在心力衰竭加重后。本研究旨在评估护士协调的多学科综合心衰管理方案对心衰患者的影响。方法和结果：这项回顾性队列研究纳入了香港一家地区医院收治的急性心衰加重患者。我们建立了两个患者队列：对照队列，于2021年1月至12月招募，接受标准治疗，而方案队列，于2022年10月至2023年12月招募，参加了一个综合方案。该方案包括多学科查房、早期开始指导医疗治疗、出院教育、出院后过渡性护理和心脏康复。主要终点是6个月时全因死亡率和hf相关再入院的综合终点。次要终点包括hf相关的再入院和全因死亡率。我们还评估了项目队列中患者满意度和健康相关生活质量（HRQoL）。研究纳入732例患者，女性占24.0%，HFrEF占81.6%，平均年龄67.9±13.2岁。在匹配年龄、性别和HF类型后，每个队列分配366例患者。方案队列显示复合终点率显著降低[12.0% vs. 38.0%，校正风险比(aHR) = 0.26, 95%置信区间(CI) = 0.19-0.37， P]结论：护士协调的心衰综合管理方案显著降低了再住院率和死亡率，不同亚组的获益一致。需要进一步的研究来证实这些益处并探索其机制。
{"title":"Nurse-coordinated multidisciplinary comprehensive heart failure management programme: A propensity-matched trial","authors":"Cecilia Miu-Ching Chan, Polly Wai-Chi Li, Derek Pok-Him Lee, Esmond Yan-Hang Fong, Ivy Sin-Yee Ng, Samantha Ki-Man Chiu, Clara Woon-Shan Fok, Frederick Kin-Wa Li, Shirley Ka-Wai Lee, Karen K. Y. Ho, Wilson Y. S. Leung, Cathy Cheuk-Sum Chan, Cindy Yiu-Ning Tsang, Michael Kang-Yin Lee","doi":"10.1002/ehf2.15418","DOIUrl":"10.1002/ehf2.15418","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Despite therapeutic advancements, the prognosis of heart failure (HF) remains poor, with high rates of mortality and readmission, particularly following a HF exacerbation. This study aimed to evaluate the effects of a nurse-coordinated multidisciplinary comprehensive HF management programme on HF patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>This retrospective cohort study involved patients admitted for acute HF exacerbation at a regional hospital in Hong Kong. We established two patient cohorts: the control cohort, recruited between January and December 2021, received standard care, while the programme cohort, recruited from October 2022 to December 2023, participated in a comprehensive programme. This programme included multidisciplinary ward rounds, early initiation of guideline-directed medical therapy (GDMT), discharge education, post-discharge transitional care and cardiac rehabilitation. The primary outcome was the composite endpoint of all-cause mortality and HF-related readmission at 6 months. Secondary endpoints included HF-related readmission and all-cause mortality. We also assessed patient satisfaction and health-related quality of life (HRQoL) in the programme cohort. The study included 732 patients, 24.0% female, 81.6% with HFrEF, mean age of 67.9 ± 13.2 years. After matching for age, sex and type of HF, 366 patients were allocated to each cohort. The programme cohort demonstrated significantly lower rates of the composite endpoint [12.0% vs. 38.0%, adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI) = 0.19–0.37, <i>P</i> < 0.001]) and HF-related readmissions (10.1% vs. 25.4%, aHR = 0.36, 95% CI = 0.24–0.52, <i>P</i> < 0.001) compared with the control cohort. All-cause mortality was also significantly reduced (4.4% vs. 18.3%, aHR = 0.22, 95% CI = 0.13–0.38, <i>P</i> < 0.001). Improvements in HRQoL and high patient satisfaction were noted in the programme cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The nurse-coordinated comprehensive HF management programme significantly reduced readmissions and mortality, with consistent benefits across different subgroups. Further research is needed to confirm these benefits and explore mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4160-4170"},"PeriodicalIF":3.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Smruti Desai, Smit Paghdar, Jose Ruiz, Ji-Min Jang, Sharan Malkani, Daniel S. Yip, Juan Leoni, Jose Nativi, Basar Sareyyupoglu, Kevin Landolfo, Si Pham, Parag Patel, Rohan Goswami
<div> <section> <h3> Background</h3> <p>Patients with end-stage heart failure and chronic kidney disease requiring dual-organ transplantation (DOT) face significant challenges in utilizing durable mechanical circulatory support due to the risks associated with renal replacement therapies (RRTs) and multi-organ failure. Given the limited options available for long-term support in this patient population, there remains a critical need for alternative strategies to optimize end-organ function and bridge patients safely to transplant. With prolonged waitlist times for DOT, we present our experience with the Impella 5.5 as temporary mechanical circulatory support, demonstrating its potential to provide hemodynamic stability and support as a bridge to transplantation (BTT) in this complex cohort.</p> </section> <section> <h3> Methods</h3> <p>A single-centre retrospective review was completed of all patients listed for single-organ transplantation or DOT between December 2019 and November 2022 at Mayo Clinic in Florida, supported by the Impella 5.5 intended as BTT. The focus of this analysis was patients requiring RRT or listed for heart/kidney transplantation. Data were extracted from the electronic health record at baseline and during their transplant episode of care after institutional review board approval as exempt status for retrospective data collection.</p> </section> <section> <h3> Results</h3> <p>A total of 41 patients were supported with Impella 5.5, intended as BTT. All patients underwent successful transplantation. We focus on the 10 patients with Impella support who underwent DOT. In the DOT group, the median age at transplantation was 63 years (59–66), with nine males and one female. The baseline median ejection fraction was 19% (15–22), with 50% Caucasian and 50% African American and an even split between ischaemic and non-ischaemic aetiology. Median body mass index was 30 kg/m<sup>2</sup> (26–31), and 60% were in blood group O. The median time on the waitlist for DOT patients was 53 days (29–75). Perioperative management of DOT Impella patients demonstrated baseline haemodynamics of RA 11 mmHg (7–16), mean PA 36 mmHg (32–47), PCWP 29 mmHg (21–35), mixed venous saturation (SVO<sub>2</sub>%) 51 (46–61) and Fick CI 2.03 L/min/m<sup>2</sup> (1.66–2.5). Post-Impella placement haemodynamics demonstrated significant improvements in RA pressure to 5 mmHg (4–8), <i>P</i> = 0.02, SVO<sub>2</sub> to 70% (65–72), <i>P</i> = 0.002, and Fick CI to 5.5 (5.2–8), <i>P</i> = 0.03. The average duration of support was 44 days (range 10–94). The median glomerular filtration rate at baseline was 27 mmol/L (16–29). Twenty-four hour urine protein averaged 168 mg
{"title":"Mid-term survival in patients awaiting heart and kidney transplantation with Impella 5.5 support","authors":"Smruti Desai, Smit Paghdar, Jose Ruiz, Ji-Min Jang, Sharan Malkani, Daniel S. Yip, Juan Leoni, Jose Nativi, Basar Sareyyupoglu, Kevin Landolfo, Si Pham, Parag Patel, Rohan Goswami","doi":"10.1002/ehf2.15189","DOIUrl":"10.1002/ehf2.15189","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with end-stage heart failure and chronic kidney disease requiring dual-organ transplantation (DOT) face significant challenges in utilizing durable mechanical circulatory support due to the risks associated with renal replacement therapies (RRTs) and multi-organ failure. Given the limited options available for long-term support in this patient population, there remains a critical need for alternative strategies to optimize end-organ function and bridge patients safely to transplant. With prolonged waitlist times for DOT, we present our experience with the Impella 5.5 as temporary mechanical circulatory support, demonstrating its potential to provide hemodynamic stability and support as a bridge to transplantation (BTT) in this complex cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-centre retrospective review was completed of all patients listed for single-organ transplantation or DOT between December 2019 and November 2022 at Mayo Clinic in Florida, supported by the Impella 5.5 intended as BTT. The focus of this analysis was patients requiring RRT or listed for heart/kidney transplantation. Data were extracted from the electronic health record at baseline and during their transplant episode of care after institutional review board approval as exempt status for retrospective data collection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 41 patients were supported with Impella 5.5, intended as BTT. All patients underwent successful transplantation. We focus on the 10 patients with Impella support who underwent DOT. In the DOT group, the median age at transplantation was 63 years (59–66), with nine males and one female. The baseline median ejection fraction was 19% (15–22), with 50% Caucasian and 50% African American and an even split between ischaemic and non-ischaemic aetiology. Median body mass index was 30 kg/m<sup>2</sup> (26–31), and 60% were in blood group O. The median time on the waitlist for DOT patients was 53 days (29–75). Perioperative management of DOT Impella patients demonstrated baseline haemodynamics of RA 11 mmHg (7–16), mean PA 36 mmHg (32–47), PCWP 29 mmHg (21–35), mixed venous saturation (SVO<sub>2</sub>%) 51 (46–61) and Fick CI 2.03 L/min/m<sup>2</sup> (1.66–2.5). Post-Impella placement haemodynamics demonstrated significant improvements in RA pressure to 5 mmHg (4–8), <i>P</i> = 0.02, SVO<sub>2</sub> to 70% (65–72), <i>P</i> = 0.002, and Fick CI to 5.5 (5.2–8), <i>P</i> = 0.03. The average duration of support was 44 days (range 10–94). The median glomerular filtration rate at baseline was 27 mmol/L (16–29). Twenty-four hour urine protein averaged 168 mg","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4140-4149"},"PeriodicalIF":3.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henry Oluwasefunmi Savage, Jason N. Dungu, Anthony Dimarco, Brian Li, Samantha Langley, Jonathan Kojo Amoah, Paraic Cliffe, Archana Ganapathy, Peter Watters, Patricia Campbell, Nicola Melarkey, Simon Duckett, Sean Davies, Matthew Dewhurst, Karen Hann, Louise Clayton, Rhys Williams, Victoria Ruszala, Teresa Onwere-Tan, Fozia Zahir Ahmed, Ibrahim Arosi, Kimberly Gray, Mark C. Petrie, John G.F. Cleland
Aims
To help avoid therapeutic inertia, we developed a pragmatic treatment score (QUAD Score) for use in daily practice by healthcare professionals managing patients with a left ventricular ejection fraction (LVEF) < 50% and heart failure. We now investigate the association between achieved QUAD scores and 1 year outcomes.
Methods
This was a multicentre cohort study in consecutive patients with incident heart failure and LVEF <50%, who completed therapy titration between January 2021 and June 2023. The primary outcome was a composite of first hospitalization for heart failure (HHF) and all-cause mortality at 1 year after final therapy titration, for QUAD scores that were poor (<8), good (8–14) or excellent (15–24).
Results
Data were analysed from 1691 participants, collected from 10 UK centres, of whom 30% were women and 82% were White. Median age, N terminal pro-B-type natriuretic peptide (NTproBNP) and LVEF were 70 (59–78.5) years, 1624 (536–4138) ng/L and 34 (25–38) %, respectively. At the start of therapy titration, only 97 (5%) patients were naïve to any of the four pillars of therapy. After investigator-declared final titration, QUAD scores were excellent in 806 (48%), good in 382 (22%) and poor in 503 (30%) patients. Patients who failed eventually to achieve a good or excellent QUAD score were more often women, older and had poorer renal function and higher plasma NTproBNP (P < 0.01). The median number of days to final therapy titration was longer in those who achieved an excellent QUAD score, [174 (99–290) days,133 (80–232) days and 108 (57–193) days P < 0.01, for excellent, good and poor QUAD groups, respectively. There was wide variation in titration schedules across participating centres and overall, 33% of patients completed therapy titration within 90 days, 63% within 6 months and 88% within 1 year. The primary composite outcome at 1 year for those with poor, good and excellent QUAD scores were respectively 16.9%, 9.4% and 5.6%, (log rank P < 0.01), for mortality were 13.1%, 6.5% and 2.4% (log rank P < 0.001) and for first HHF were 7.7%, 3.9% and 3.2% (log rank P < 0.001).
Conclusions
The QUAD score is a simple tool that can help audit and incentivize uptake of guideline-recommended therapy for HFrEF and prevent treatment inertia. Excellent QUAD scores are associated with better outcomes.
{"title":"A novel treatment score (QUAD score) to promote treatment optimization in heart failure with a reduced ejection fraction","authors":"Henry Oluwasefunmi Savage, Jason N. Dungu, Anthony Dimarco, Brian Li, Samantha Langley, Jonathan Kojo Amoah, Paraic Cliffe, Archana Ganapathy, Peter Watters, Patricia Campbell, Nicola Melarkey, Simon Duckett, Sean Davies, Matthew Dewhurst, Karen Hann, Louise Clayton, Rhys Williams, Victoria Ruszala, Teresa Onwere-Tan, Fozia Zahir Ahmed, Ibrahim Arosi, Kimberly Gray, Mark C. Petrie, John G.F. Cleland","doi":"10.1002/ehf2.15407","DOIUrl":"10.1002/ehf2.15407","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To help avoid therapeutic inertia, we developed a pragmatic treatment score (QUAD Score) for use in daily practice by healthcare professionals managing patients with a left ventricular ejection fraction (LVEF) < 50% and heart failure. We now investigate the association between achieved QUAD scores and 1 year outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a multicentre cohort study in consecutive patients with incident heart failure and LVEF <50%, who completed therapy titration between January 2021 and June 2023. The primary outcome was a composite of first hospitalization for heart failure (HHF) and all-cause mortality at 1 year after final therapy titration, for QUAD scores that were poor (<8), good (8–14) or excellent (15–24).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data were analysed from 1691 participants, collected from 10 UK centres, of whom 30% were women and 82% were White. Median age, N terminal pro-B-type natriuretic peptide (NTproBNP) and LVEF were 70 (59–78.5) years, 1624 (536–4138) ng/L and 34 (25–38) %, respectively. At the start of therapy titration, only 97 (5%) patients were naïve to any of the four pillars of therapy. After investigator-declared final titration, QUAD scores were excellent in 806 (48%), good in 382 (22%) and poor in 503 (30%) patients. Patients who failed eventually to achieve a good or excellent QUAD score were more often women, older and had poorer renal function and higher plasma NTproBNP (<i>P</i> < 0.01). The median number of days to final therapy titration was longer in those who achieved an excellent QUAD score, [174 (99–290) days,133 (80–232) days and 108 (57–193) days <i>P</i> < 0.01, for excellent, good and poor QUAD groups, respectively. There was wide variation in titration schedules across participating centres and overall, 33% of patients completed therapy titration within 90 days, 63% within 6 months and 88% within 1 year. The primary composite outcome at 1 year for those with poor, good and excellent QUAD scores were respectively 16.9%, 9.4% and 5.6%, (log rank <i>P</i> < 0.01), for mortality were 13.1%, 6.5% and 2.4% (log rank <i>P</i> < 0.001) and for first HHF were 7.7%, 3.9% and 3.2% (log rank <i>P</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The QUAD score is a simple tool that can help audit and incentivize uptake of guideline-recommended therapy for HFrEF and prevent treatment inertia. Excellent QUAD scores are associated with better outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4150-4159"},"PeriodicalIF":3.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vitaris Kodogo, Karen Sliwa, Alice M. Jackson, Hasan Al-Farhan, Sorel Goland, Jasper Tromp, Peter van der Meer, Kamilu Karaye, Alexandre Mebazaa, Johann Bauersachs, Liam Bell, Julian Hoevelmann, Charle Viljoen, the EurObservational Research Programme in conjunction with the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy
Aims
The diagnosis of peripartum cardiomyopathy (PPCM) is often delayed due to the absence of disease-specific biomarkers. Recently, serum proteins—QSOX1, adiponectin (ADIPOQ) and ITIH3—have shown potential for improving diagnostic accuracy, especially when used with NT-proBNP. However, the influence of ethnicity on their expression remains unclear. We aimed to assess whether serum biomarker profiles differ among ethnic groups in a multinational PPCM cohort.
Methods and results
Eighty-two PPCM patients from seven countries in the EURObservational Research Programme (EORP) provided demographic data and serum samples. Ethnicity was self-reported. Proteomic profiling at diagnosis was performed using DIA-based label-free LC–MS, and data were analysed with Spectronaut v15. Ethnic variation was evaluated through principal component analysis (PCA). Participants had a mean age of 30.5 ± 6.7 years; 75% had no hypertension during pregnancy. Median LVEF was 35% (IQR 27.0–41.1), with no ethnic differences. Middle Eastern women showed more severe LV dilatation. PCA revealed no significant clustering by ethnicity; PC1 and PC2 explained 15.2% and 12.0% of variance, respectively.
Conclusions
QSOX1, ADIPOQ and ITIH3 exhibited consistent expressions across ethnic groups, supporting their use as universal PPCM biomarkers.
{"title":"Ethnic differences in protein biomarkers of peripartum cardiomyopathy: a proteomic study on the EORP cohort","authors":"Vitaris Kodogo, Karen Sliwa, Alice M. Jackson, Hasan Al-Farhan, Sorel Goland, Jasper Tromp, Peter van der Meer, Kamilu Karaye, Alexandre Mebazaa, Johann Bauersachs, Liam Bell, Julian Hoevelmann, Charle Viljoen, the EurObservational Research Programme in conjunction with the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy","doi":"10.1002/ehf2.15419","DOIUrl":"10.1002/ehf2.15419","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The diagnosis of peripartum cardiomyopathy (PPCM) is often delayed due to the absence of disease-specific biomarkers. Recently, serum proteins—QSOX1, adiponectin (ADIPOQ) and ITIH3—have shown potential for improving diagnostic accuracy, especially when used with NT-proBNP. However, the influence of ethnicity on their expression remains unclear. We aimed to assess whether serum biomarker profiles differ among ethnic groups in a multinational PPCM cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Eighty-two PPCM patients from seven countries in the EURObservational Research Programme (EORP) provided demographic data and serum samples. Ethnicity was self-reported. Proteomic profiling at diagnosis was performed using DIA-based label-free LC–MS, and data were analysed with Spectronaut v15. Ethnic variation was evaluated through principal component analysis (PCA). Participants had a mean age of 30.5 ± 6.7 years; 75% had no hypertension during pregnancy. Median LVEF was 35% (IQR 27.0–41.1), with no ethnic differences. Middle Eastern women showed more severe LV dilatation. PCA revealed no significant clustering by ethnicity; PC1 and PC2 explained 15.2% and 12.0% of variance, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>QSOX1, ADIPOQ and ITIH3 exhibited consistent expressions across ethnic groups, supporting their use as universal PPCM biomarkers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4521-4526"},"PeriodicalIF":3.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcin Ufnal, Macarena P. Quintana-Hayashi, Kathleen Connolly, Daniel Pettersen, Zsolt Cselényi, Aurelija Jucaite, Magnus Schou, Andrea Varrone, Melanie Chan, Lars H. Lund
Aims
Renal impairment frequently coexists with heart failure (HF) and is associated with increased risk of poor clinical outcomes. This highlights the urgent need for therapies targeting both cardiac and renal dysfunction. AZD3427, a long-acting recombinant fusion protein and relaxin analogue that selectively activates the relaxin family peptide receptor 1 (RXFP1), showed trends of increased stroke volume and estimated glomerular filtration rate (eGFR) in HF patients (NCT04630067). The hypothesis is that AZD3427 may enhance GFR by expanding the functional renal cortex volume and improving renal perfusion.
Methods and results
The Re-PERFUSE study (NCT06611423) is a Phase 1b, randomised, double-blind, placebo-controlled trial aimed at evaluating the effects of AZD3427 on renal perfusion in patients with HF and reduced ejection fraction (HFrEF) with reduced eGFR. Patients with HF, EF ≤ 40% and an eGFR of 30 to 90 mL/min/1.73 m2, assessed by the CKD-EPI 2021, will receive a single dose of subcutaneous AZD3427 (n = 6) or placebo (n = 6). Intravenous dopamine will serve as a positive control for increased renal blood flow. Positron emission tomography (PET) imaging with [15O]-labelled water will be used to measure renal cortex blood flow pre- and post-treatment, allowing differentiation between global and focal renal blood flow changes and providing insights into potential nephron recruitment and increased filtration membrane area. Safety and tolerability will be assessed through monitoring of adverse events, clinical laboratory tests and vital signs.
Conclusions
This study, alongside other ongoing AZD3427 studies, aims to evaluate the dual effects of AZD3427 in improving both cardiac and renal function. These insights could guide the development of future therapeutic strategies for managing HF and renal impairment.
{"title":"Re-PERFUSE: Phase 1b study of AZD3427, a novel relaxin receptor agonist, on renal perfusion in HFrEF patients","authors":"Marcin Ufnal, Macarena P. Quintana-Hayashi, Kathleen Connolly, Daniel Pettersen, Zsolt Cselényi, Aurelija Jucaite, Magnus Schou, Andrea Varrone, Melanie Chan, Lars H. Lund","doi":"10.1002/ehf2.15412","DOIUrl":"10.1002/ehf2.15412","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Renal impairment frequently coexists with heart failure (HF) and is associated with increased risk of poor clinical outcomes. This highlights the urgent need for therapies targeting both cardiac and renal dysfunction. AZD3427, a long-acting recombinant fusion protein and relaxin analogue that selectively activates the relaxin family peptide receptor 1 (RXFP1), showed trends of increased stroke volume and estimated glomerular filtration rate (eGFR) in HF patients (NCT04630067). The hypothesis is that AZD3427 may enhance GFR by expanding the functional renal cortex volume and improving renal perfusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>The Re-PERFUSE study (NCT06611423) is a Phase 1b, randomised, double-blind, placebo-controlled trial aimed at evaluating the effects of AZD3427 on renal perfusion in patients with HF and reduced ejection fraction (HFrEF) with reduced eGFR. Patients with HF, EF ≤ 40% and an eGFR of 30 to 90 mL/min/1.73 m<sup>2</sup>, assessed by the CKD-EPI 2021, will receive a single dose of subcutaneous AZD3427 (<i>n</i> = 6) or placebo (<i>n</i> = 6). Intravenous dopamine will serve as a positive control for increased renal blood flow. Positron emission tomography (PET) imaging with [<sup>15</sup>O]-labelled water will be used to measure renal cortex blood flow pre- and post-treatment, allowing differentiation between global and focal renal blood flow changes and providing insights into potential nephron recruitment and increased filtration membrane area. Safety and tolerability will be assessed through monitoring of adverse events, clinical laboratory tests and vital signs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study, alongside other ongoing AZD3427 studies, aims to evaluate the dual effects of AZD3427 in improving both cardiac and renal function. These insights could guide the development of future therapeutic strategies for managing HF and renal impairment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4495-4502"},"PeriodicalIF":3.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiahe Wu, Yi Lu, Xinchen Gao, Xiaorong Hu, Zhibing Lu, Chenze Li
Aims
Protein glycosylation regulated by glycosyltransferases is an important type of post-translational modification. The role of the glycosyltransferase genes (GTGs) in heart failure (HF) remains unclear and requires further investigation.
Methods
Differential expression analysis was performed on the transverse aortic constriction (TAC)-related dataset GSE36074 to screen out the differentially expressed GTGs. Enrichment and protein–protein interaction analyses explored their functional mechanisms and interconnections. Pearson correlation analysis revealed the relationship between GTGs and pathological cardiac remodelling. The upstream miRNAs of GTGs were predicted using corresponding online databases, and the downstream target genes were identified by weighted correlation network analysis (WGCNA). Computer virtual screening and molecular docking predicted potential therapeutic drugs. The identified GTGs were validated in vivo, in vitro and in the human HF-related dataset GSE57338.
Results
Twenty-one differentially expressed GTGs were identified, and these genes were significantly up-regulated in the TAC model except for C1galt1, Extl2 and Pigh. Pearson correlation analysis revealed that 11 GTGs were significantly associated with pathological cardiac remodelling. Fifty-six miRNAs and 31 drugs were predicted to target these GTGs. WGCNA indicated that these GTGs were associated with lipid metabolism-related genes and pathways. Up-regulation of B3gnt9, C1galt1, Gcnt1, Gxylt2 and Mgat5b was observed in the TAC model. GXYLT2 is up-regulated and has high disease-predictive value in patients with dilated cardiomyopathy and ischaemic cardiomyopathy. Knockdown of GXYLT2 in human AC16 cardiomyocytes significantly attenuated angiotensin II (AngII)-induced hypertrophy.
Conclusions
Dysregulation of GTG expression may affect TAC-induced HF through metabolic pathways, and GXYLT2 may be a new potential therapeutic target for HF.
{"title":"Pathogenic glycosyltransferase genes and potential therapeutic drugs in pressure overload-induced heart failure","authors":"Jiahe Wu, Yi Lu, Xinchen Gao, Xiaorong Hu, Zhibing Lu, Chenze Li","doi":"10.1002/ehf2.15409","DOIUrl":"10.1002/ehf2.15409","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Protein glycosylation regulated by glycosyltransferases is an important type of post-translational modification. The role of the glycosyltransferase genes (GTGs) in heart failure (HF) remains unclear and requires further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Differential expression analysis was performed on the transverse aortic constriction (TAC)-related dataset GSE36074 to screen out the differentially expressed GTGs. Enrichment and protein–protein interaction analyses explored their functional mechanisms and interconnections. Pearson correlation analysis revealed the relationship between GTGs and pathological cardiac remodelling. The upstream miRNAs of GTGs were predicted using corresponding online databases, and the downstream target genes were identified by weighted correlation network analysis (WGCNA). Computer virtual screening and molecular docking predicted potential therapeutic drugs. The identified GTGs were validated in vivo, in vitro and in the human HF-related dataset GSE57338.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-one differentially expressed GTGs were identified, and these genes were significantly up-regulated in the TAC model except for C1galt1, Extl2 and Pigh. Pearson correlation analysis revealed that 11 GTGs were significantly associated with pathological cardiac remodelling. Fifty-six miRNAs and 31 drugs were predicted to target these GTGs. WGCNA indicated that these GTGs were associated with lipid metabolism-related genes and pathways. Up-regulation of B3gnt9, C1galt1, Gcnt1, Gxylt2 and Mgat5b was observed in the TAC model. GXYLT2 is up-regulated and has high disease-predictive value in patients with dilated cardiomyopathy and ischaemic cardiomyopathy. Knockdown of GXYLT2 in human AC16 cardiomyocytes significantly attenuated angiotensin II (AngII)-induced hypertrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dysregulation of GTG expression may affect TAC-induced HF through metabolic pathways, and GXYLT2 may be a new potential therapeutic target for HF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"4108-4124"},"PeriodicalIF":3.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The study aims to evaluate the effects of exercise-based cardiac rehabilitation (ExCR) on the health-related quality of life (HRQoL) in people with heart failure preserved ejection fraction (HFpEF).
Methods
This study is a systematic review and meta-analysis. Six bibliographic databases (Medline, Embase, Web of Science, Cumulative Index of Nursing and Allied Health Literature, Cochrane CENTRAL and China National Knowledge Infrastructure database) were searched to April 2024 for randomized controlled trials (RCTs), involving adults with HFpEF undertaking ExCR compared with no exercise control. Subgroup and sensitivity analyses were conducted to explore potential sources of statistical heterogeneity.
Results
Twelve RCTs recruiting a total of 1005 HFpEF patients with a median of 16 weeks follow-up were included. Four trials defined HFpEF as an ejection fraction of ≥45% and eight trials as ≥50%. Compared with control, ExCR participation was associated with improvements in disease-specific HRQoL as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) [weighted mean difference (WMD): −6.72, 95% confidence interval (Cl): −12.00 to −1.44, P = 0.013] and Kansas City Cardiomyopathy Questionnaire (KCCQ) total scores (WMD: 5.34, 95% CI: 1.75 to 8.93, P < 0.0001) and generic HRQoL assessed by Short-Form 36 and EQ-5D. There was evidence (P ≤ 0.05) of greater improvements in MLHFQ total score with ExCR in trials with shorter exercise duration (<60 min/session), the presence of risk of bias, and larger sample size (>45 patients). Included trials were small and demonstrated substantial clinical and statistical heterogeneity with a range of: (1) population definitions (e.g., definition of HFpEF of ≥45% vs. ≥50%, level and nature of comorbidities), (2) ExCR interventions (e.g., exercise only vs. comprehensive CR programmes, different modes and intensity of exercise, centre- and home-based delivery) and (3) methods of HRQoL assessment (e.g., disease specific vs. generic measure).
Conclusions
This meta-analysis of RCT evidence shows that participation in ExCR provides important gains in HRQoL of people with HFpEF. However, the results should be interpreted with caution given the substantial clinical and statistical heterogeneity. Well reported, fully powered RCTs with longer follow-up are needed to confirm these findings.
目的：本研究旨在评估基于运动的心脏康复（ExCR）对心力衰竭患者保留射血分数（HFpEF）的健康相关生活质量（HRQoL）的影响。方法：本研究采用系统综述和荟萃分析。我们检索了6个文献数据库（Medline、Embase、Web of Science、Nursing and Allied Health Literature Cumulative Index、Cochrane CENTRAL和China National Knowledge Infrastructure数据库），检索了截至2024年4月的随机对照试验（RCTs），涉及HFpEF成人患者进行ExCR与未进行运动控制的对照。进行亚组分析和敏感性分析，以探索统计异质性的潜在来源。结果：纳入了12项随机对照试验，共招募1005例HFpEF患者，中位随访时间为16周。4项试验将HFpEF定义为射血分数≥45%，8项试验定义为≥50%。与对照组相比，通过明尼苏达州心衰患者生活问卷（MLHFQ）[加权平均差（WMD）： -6.72, 95%可信区间（Cl）： -12.00至-1.44,P = 0.013]和堪萨斯城心肌病问卷（KCCQ）总分（WMD: 5.34, 95% CI: 1.75至8.93,P = 45）评估，ExCR参与与疾病特异性HRQoL的改善相关。纳入的试验规模较小，且在临床和统计上具有显著的异质性，其范围包括：(1)人群定义（例如HFpEF≥45% vs≥50%的定义，合并症的水平和性质），(2)ExCR干预措施（例如，仅运动vs综合CR方案，不同的运动模式和强度，以中心和家庭为基础的分娩）以及(3)HRQoL评估方法（例如，疾病特异性vs通用测量）。结论：本荟萃分析的RCT证据显示，参与ExCR可显著提高HFpEF患者的HRQoL。然而，考虑到临床和统计上的巨大异质性，结果应谨慎解释。为了证实这些发现，需要有充分报道的、有较长随访时间的全功率随机对照试验。
{"title":"Cardiac rehabilitation and health-related quality of life in preserved ejection fraction heart failure: A meta-analysis","authors":"Chenyao Ding, Yawen Gao, Rod S. Taylor","doi":"10.1002/ehf2.15404","DOIUrl":"10.1002/ehf2.15404","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The study aims to evaluate the effects of exercise-based cardiac rehabilitation (ExCR) on the health-related quality of life (HRQoL) in people with heart failure preserved ejection fraction (HFpEF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study is a systematic review and meta-analysis. Six bibliographic databases (Medline, Embase, Web of Science, Cumulative Index of Nursing and Allied Health Literature, Cochrane CENTRAL and China National Knowledge Infrastructure database) were searched to April 2024 for randomized controlled trials (RCTs), involving adults with HFpEF undertaking ExCR compared with no exercise control. Subgroup and sensitivity analyses were conducted to explore potential sources of statistical heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve RCTs recruiting a total of 1005 HFpEF patients with a median of 16 weeks follow-up were included. Four trials defined HFpEF as an ejection fraction of ≥45% and eight trials as ≥50%. Compared with control, ExCR participation was associated with improvements in disease-specific HRQoL as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) [weighted mean difference (WMD): −6.72, 95% confidence interval (Cl): −12.00 to −1.44, <i>P</i> = 0.013] and Kansas City Cardiomyopathy Questionnaire (KCCQ) total scores (WMD: 5.34, 95% CI: 1.75 to 8.93, <i>P</i> < 0.0001) and generic HRQoL assessed by Short-Form 36 and EQ-5D. There was evidence (<i>P</i> ≤ 0.05) of greater improvements in MLHFQ total score with ExCR in trials with shorter exercise duration (<60 min/session), the presence of risk of bias, and larger sample size (>45 patients). Included trials were small and demonstrated substantial clinical and statistical heterogeneity with a range of: (1) population definitions (e.g., definition of HFpEF of ≥45% vs. ≥50%, level and nature of comorbidities), (2) ExCR interventions (e.g., exercise only vs. comprehensive CR programmes, different modes and intensity of exercise, centre- and home-based delivery) and (3) methods of HRQoL assessment (e.g., disease specific vs. generic measure).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This meta-analysis of RCT evidence shows that participation in ExCR provides important gains in HRQoL of people with HFpEF. However, the results should be interpreted with caution given the substantial clinical and statistical heterogeneity. Well reported, fully powered RCTs with longer follow-up are needed to confirm these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 6","pages":"3929-3939"},"PeriodicalIF":3.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号