Heart failure (HF) is a frequent and severe condition. It is estimated that one in four patients will die within a year following hospitalization for acute decompensation, with significant variations across age strata. A recent study reported that the 1-year mortality following hospitalization for HF was 9%, 14%, and 18% for patients under 55, between 55–64, and 65–74 years, respectively.¹ Higher values are found when older and unselected patients are included.²

Another rather recent worrisome finding is the increase in the incidence of HF among younger individuals due to a rise in ischaemic heart disease, especially among men aged 36–50 years in Europe.³ Although younger than 50 years, this population will experience a 25% readmission rate for HF, and 75% for all causes with a mortality exceeding 10% at 2 years.³ Consistent data show an increasing incidence of cardiogenic shock following myocardial infarction among the young, along with an associated increase in mortality from ischaemic cardiogenic shock within this same demographic.⁴ Moreover, epidemiological data confirm that mortality due to HF among young individuals is generally on the rise in North America, even as the availability of treatments and devices continues to increase.⁵ This subgroup of young patients who develop acute coronary syndrome followed by severe cardiac dysfunction and HF is an obvious target for treatment with long-term mechanical circulatory support (MCS) and heart transplantation.

The treatment for HF with reduced ejection fraction relies on four therapeutic classes including beta-blockers, renin–angiotensin system inhibitors, mineralocorticoid receptor antagonists (MRAs), and sodium–glucose cotransporter 2 inhibitors (SGLT2i), each with a class I recommendation.⁶ Meta-analyses of randomized clinical trials demonstrate that the implementation of these four classes could reduce all-cause mortality by 61%, with an estimated increase in survival of 5 years for a patient who would be 70 years old.⁷ However, tolerance of HF treatments is poor, with discontinuation rates ranging from 23% (SGLT2i) to 42% (MRAs) at 1 year according to a multinational observational study.⁸ This intolerance is a sign of advanced HF, and the more risk factors patients have, the higher the likelihood of treatment intolerance becomes.⁹ In these populations with advanced disease, significant myocardial fibrosis makes hormonal therapies ineffective and intolerable, necessitating invasive mechanical therapies based on Laplace's law to reduce left ventricular intraluminal pressure.¹⁰

For selected patients suffering from advanced HF, transplantation is recommended as class I, and long-term MCS are recommended as class IIa for bridge to decision or transplantation or as destination therapies in the 2021 European Society of Cardiology (ESC) HF guidelines and as class I in the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines.^{6, 11} These recommendations are supported by the excellent long-term results of the latest generations of centrifugal pumps, with a survival rate of over 56% at 5 years in randomized trials and registries, corresponding to an absolute 22% reduction in all-cause mortality at 5 years between axial and centrifugal pumps.^{12, 13} With the number of heart transplants per country limited by the availability of grafts, optimizing the care of patients with advanced HF primarily relies on the implementation of long-term MCS. However, data evaluating the evolution of practices in Europe are scarce.

To assess the implementation of left ventricular assist devices (LVADs) following the 2021 ESC HF guidelines⁶ and the dissemination of long-term results from the MOMENTUM 3 trial,¹³ we analysed market data reflecting the sales of long-term MCS systems across various countries from 2018 to 2023. These data serve as a reliable proxy for MCS implantation rates. Our focus was on European nations that reported a minimum of 30 MCS implantations in 2018. It is worth noting that over 98% of implanted MCS devices were LVADs.

We observed an eight-fold variation in LVAD use per capita across European countries ranging from 1.1 to 8.7 implantations per million inhabitants (IPMI) in the United Kingdom (UK) and Germany, respectively (Figure 1). Countries can be schematically divided into three groups according to the rate of implantations: (1) high-implantation countries including Germany and the Czech Republic with rates between 7 and 8 IPMI; (2) intermediate-rate countries between 4 and 6 IPMI including the Netherlands, Austria, Belgium, and Switzerland; and (3) low-implantation countries with rates between 1 and 3 IPMI including Poland, Italy, Sweden, France, and the UK. The number of implantations does not appear to be explained solely by device reimbursement (online supplementary Table Appendix S1.). Indeed, although LVADs are fully reimbursed in countries with high implantation rates, we note that some countries with full reimbursement implant very few (France and Italy, for example).

The trend in the number of implantations between 2018 and 2023, including the period of the COVID-19 pandemic, exhibited significant variations across countries. The COVID period was associated with a reduction in the number of implantations in the majority of European countries.¹⁴ Focusing on Germany and France, which led in implant numbers in 2018, there was a general downward trend in implantations from 2018 to 2022. However, Germany experienced a reversal, concluding with a modest reduction of 13%, in contrast to France, where the decline persisted, culminating in a 42% decrease.

Countries were divided into three groups according to the change in implantation rate over the 2018–2023 period: (1) countries with a significant decrease, experiencing more than a 25% reduction in activity including France (−42%), the UK (−40%), Sweden (−31%), and Switzerland (−29%); (2) stable countries with a change of <25% including Germany (−13%), Belgium (−9%), Austria (−4%), and Italy (8%); and (3) countries with a significant increase (>25%) including the Netherlands (27%), Poland (67%), the Czech Republic (105%), and Spain (122%). The change in the number of implantations between 2018 and 2023 appears to be independent of a country's implantation rate, with countries exhibiting intermediate implantation rates demonstrating all three possible trends in evolution. It is important to acknowledge that a low baseline implantation rate results in greater variability in percentage calculations.

These data highlight the significant disparity in the rate of LVAD implantation in Europe, the highly variable impact of the COVID-19 pandemic on implantation activity, and a very variable evolutionary trend from one country to another between 2018 and 2023. A presentation of the LVAD per millions of inhabitants/HF prevalence ratio would be useful to describe LVAD utilization, but reliable data on the prevalence of HF in Europe are limited by the absence of a universal definition of HF before 2021 and the unavailability of reliable national statistics or registries.^{15, 16}

The estimated median survival of patients on intravenous inotropes being less than 1 year, and the median survival of ambulatory patients with advanced HF being less than 2 years, the use of LVAD in these patients is justified in order to improve survival outcomes.¹⁰ In the context of a stable number of heart transplants and a persistent shortage of grafts in Europe, the lack of global implementation of LVAD or even a significant reduction in the number of implantations in some countries raises questions.

Several factors may account for this inertia: (i) improvement in pharmacological therapies; (ii) insufficient and late referral; (iii) gaps in the evidence of efficacy of MCS in ambulatory advanced HF patients; (iv) changes in the criteria for heart graft allocation, placing LVAD recipients at a disadvantage; and (v) insufficient acceptance of LVAD by patients and medical teams.

The improvement in HF therapies is real and constant. However, the increase in mortality among young patients and the residual mortality reaching 10% and 20% within a year following hospitalization makes this hypothesis unlikely to explain the lack of implementation.

The challenges of referral, likely exacerbated by the COVID crisis, are a probable explanation for our results. Special attention to the structuring of the network, and the education of patients and cardiologists to the definition of advanced HF, is necessary to improve referral and the number of patients who could benefit from LVAD.

As emphasized in the latest HF guidelines,⁶ the optimal timing for MCS implantation in non-inotrope-dependent advanced HF patients is a subject of debate. Randomized studies are currently underway to specify the place of an earlier LVAD implantation in ambulatory advanced HF patients (AMBU-VAD trial, NCT04768322).

Given the favourable survival of patients supported by LVAD, graft allocation systems in France and in the United States have reduced access to transplantation for patients with supports.^{17, 18} This was associated with a significant decrease in the number of patients implanted with an LVAD before listing or after registration,¹⁹ without reducing mortality on the list nor improving the post-transplant prognosis of isolated heart grafts.²⁰ It appears necessary to better define the role of LVAD in the treatment of advanced HF to increase the overall survival of patients. Unfortunately, we currently lack information on the relative use of LVADs according to different strategies (bridge to transplant/recovery/candidacy or destination therapy) by country in Europe.

The acceptability of the device by patients and cardiologists remains probably one of the obstacles to its use. Although the new generation of LVADs has significantly reduced the risk of thromboembolic complications, improving survival and prognosis, the persistence of the percutaneous power cable makes acceptance difficult and is associated with a continued risk of infection.

In conclusion, despite the increase in HF mortality among young people and the improvement in MCS, we do not assist to an increase in their use and a decrease in implantations is even observed in most countries. Structuring the network, educating practitioners on referral criteria, and redefining the place of LVADs in access to transplantation are necessary to reduce mortality among young patients suffering from advanced HF.

Conflict of interest: G.B. has received personal fees from Abbott, AstraZeneca, Boehringer Ingelheim and Novartis, outside the submitted work. All other authors have nothing to disclose.

心力衰竭 （HF） 是一种常见且严重的疾病。据估计，四分之一的患者将在因急性失代偿住院后一年内死亡，不同年龄层之间存在显着差异。最近的一项研究报告称，55 岁以下、55-64 岁和 65-74 岁患者因 HF 住院后的 1 年死亡率分别为 9%、14% 和 18%。¹ 当包括老年患者和未选择的患者时，会发现更高的值。^{阿拉伯数字}

另一个相当近期令人担忧的发现是，由于缺血性心脏病的增加，年轻人的 HF 发病率增加，尤其是在欧洲 36-50 岁的男性中。³ 尽管年龄小于 50 岁，但该人群的 HF 再入院率为 25%，全因再入院率为 75%，2 年死亡率超过 10%。³ 一致的数据显示，年轻人心肌梗死后心源性休克的发生率增加，同时在同一人群中缺血性心源性休克的死亡率也相应增加。⁴ 此外，流行病学数据证实，尽管治疗方法和设备的可用性持续增加，但北美年轻人因 HF 导致的死亡率普遍呈上升趋势。⁵ 这组年轻患者先发展为急性冠脉综合征，随后出现严重心功能不全和 HF，是长期机械循环支持 （MCS） 和心脏移植治疗的明显靶点。

射血分数降低的 HF 的治疗依赖于四种治疗类别，包括 β 受体阻滞剂、肾素-血管紧张素系统抑制剂、盐皮质激素受体拮抗剂 （MRA） 和钠-葡萄糖协同转运蛋白 2 抑制剂 （SGLT2i），每种都有 I 类推荐。⁶ 随机临床试验的荟萃分析表明，实施这四类可以将全因死亡率降低 61%，估计 70 岁患者的生存期可增加 5 年。⁷ 然而，HF 治疗的耐受性较差，根据一项多国观察性研究，1 年时停药率从 23% （SGLT2i） 到 42% （MRAs） 不等。⁸ 这种不耐受是晚期 HF 的征兆，患者的风险因素越多，治疗不耐受的可能性就越高。⁹ 在这些晚期疾病人群中，严重的心肌纤维化使激素治疗无效且无法耐受，需要基于拉普拉斯定律的侵入性机械疗法来降低左心室腔内压。¹⁰

对于某些患有晚期 HF 的患者，建议将移植作为 I 级，将长期 MCS 推荐作为 IIa 级，用于决策或移植的过渡，或在 2021 年欧洲心脏病学会 （ESC） HF 指南中作为目的地治疗，在 2022 年美国心脏协会/美国心脏病学会/美国心力衰竭学会指南中作为 I 级。^6、11这些建议得到了最新一代离心泵的出色长期结果的支持，在随机试验和注册中，5 年生存率超过 56%，相当于轴流泵和离心泵之间 5 年全因死亡率绝对降低 22%。^12、13由于每个国家的心脏移植数量受到移植物可用性的限制，优化晚期 HF 患者的护理主要依赖于长期 MCS 的实施。然而，评估欧洲实践演变的数据很少。

为了评估按照 2021 年 ESC HF 指南⁶ 实施左心室辅助装置 （LVAD） 的情况以及 MOMENTUM 3 试验长期结果的传播，¹³ 我们分析了反映 2018 年至 2023 年各国长期 MCS 系统销售情况的市场数据。这些数据是 MCS 植入率的可靠代表。我们的重点是 2018 年报告了至少 30 例 MCS 植入的欧洲国家。值得注意的是，超过 98% 的植入式 MCS 设备是 LVAD。

我们观察到欧洲国家的人均 LVAD 使用量存在 8 倍的变化，在英国 （UK） 和德国，分别为每百万居民 1.1 至 8.7 次植入 （IPMI） （图 1）。根据植入率，国家可以示意性地分为三组：（1） 高植入率国家，包括德国和捷克共和国，IPMI 率在 7 到 8 之间;（2） IPMI 在 4 到 6 之间的中等费率国家，包括荷兰、奥地利、比利时和瑞士;（3） IPMI 率在 1 到 3 之间的低植入率国家，包括波兰、意大利、瑞典、法国和英国。植入次数似乎并不能仅用器械报销来解释（在线补充表附录 S1）。事实上，尽管 LVAD 在植入率高的国家可以全额报销，但我们注意到一些全额报销植入的国家很少（例如法国和意大利）。

2018 年至 2023 年期间（包括 COVID-19 大流行期间）植入数量的趋势在各国之间表现出显着差异。COVID 时期与大多数欧洲国家植入数量的减少有关。¹⁴ 以 2018 年种植牙数量领先的德国和法国为例，2018 年至 2022 年种植牙总体呈下降趋势。然而，德国经历了逆转，以 13% 的小幅下降结束，而法国则持续下降，最终下降 42%。

根据 2018-2023 年期间植入率的变化，将国家分为三组：（1） 活动显著减少的国家，活动减少超过 25%，包括法国 （-42%）、英国 （-40%）、瑞典 （-31%） 和瑞士 （-29%）;（2） 变化为 <25% 的稳定国家，包括德国 （-13%）、比利时 （-9%）、奥地利 （-4%） 和意大利 （8%）;（3） 显著增长的国家 （>25%），包括荷兰 （27%）、波兰 （67%）、捷克共和国 （105%） 和西班牙 （122%）。2018 年至 2023 年间植入率的变化似乎与一个国家的植入率无关，国家表现出中等植入率，展示了所有三种可能的进化趋势。重要的是要承认，低基线植入率会导致百分比计算的可变性更大。

这些数据凸显了欧洲 LVAD 植入率的显著差异、COVID-19 大流行对植入活动的高度可变影响，以及 2018 年至 2023 年从一个国家到另一个国家非常可变的进化趋势。每百万居民的 LVAD/HF 患病率的表示有助于描述 LVAD 的利用，但由于 2021 年之前缺乏 HF 的通用定义，并且无法获得可靠的国家统计数据或登记处，因此欧洲 HF 患病率的可靠数据受到限制。^15、16 元

静脉注射正性肌力药物患者的估计中位生存期小于 1 年，晚期 HF 非卧床患者的中位生存期小于 2 年，为了改善生存结局，在这些患者中使用 LVAD 是合理的。¹⁰ 在欧洲心脏移植数量稳定且移植物持续短缺的背景下，缺乏 LVAD 的全球实施，甚至一些国家/地区的植入数量显着减少都引发了问题。

有几个因素可以解释这种惰性：（i） 药物治疗的改善;（ii） 转介不足和延迟;（iii） MCS 对非卧床晚期 HF 患者疗效的证据存在差距;（iv） 心脏移植物分配标准的变化，使 LVAD 接受者处于不利地位;（v） 患者和医疗团队对 LVAD 的接受度不足。

HF 治疗的改善是真实且持续的。然而，年轻患者死亡率的增加以及住院后一年内残余死亡率达到 10% 和 20%，这使得这一假设不太可能解释缺乏实施。

转诊的挑战可能因 COVID 危机而加剧，这可能是我们结果的一个可能解释。特别关注网络的结构，以及对患者和心脏病专家进行晚期 HF 定义的教育，对于改善转诊和可能从 LVAD 中受益的患者数量是必要的。

正如最新的 HF 指南所强调的，⁶ 非促性药物依赖性晚期 HF 患者植入 MCS 的最佳时机是一个争论的话题。目前正在进行随机研究，以指定非卧床晚期 HF 患者中早期 LVAD 植入的位置（AMBU-VAD 试验，NCT04768322）。

鉴于 LVAD 支持的患者生存率良好，法国和美国的移植物分配系统减少了接受支持的患者获得移植的机会。^17、18 元这与上市前或注册后植入 LVAD 的患者数量显著减少有关，¹⁹ 且名单上的死亡率未降低，也未改善离体心脏移植物的移植后预后。²⁰ 似乎有必要更好地定义 LVAD 在晚期 HF 治疗中的作用，以提高患者的总生存期。不幸的是，我们目前缺乏根据欧洲国家/地区不同策略 （移植/恢复/候选或目的地治疗） 的 LVAD 相对使用情况的信息。

患者和心脏病专家对该设备的接受度可能仍然是其使用的障碍之一。尽管新一代 LVAD 显著降低了血栓栓塞并发症的风险，提高了生存率和预后，但经皮电源线的持续存在使接受变得困难，并且与持续的感染风险相关。

总之，尽管年轻人的 HF 死亡率增加且 MCS 有所改善，但我们并没有帮助增加它们的使用，甚至在大多数国家观察到植入率下降。构建网络、对从业者进行转诊标准教育以及重新定义 LVAD 在移植中的地位对于降低晚期 HF 年轻患者的死亡率是必要的。

利益冲突：G.B. 在提交的作品之外收到了 Abbott、AstraZeneca、Boehringer Ingelheim 和 Novartis 的个人费用。所有其他作者都没有什么可披露的。