We thank Flower et al. for their thoughtful response [1] to our article examining right ventricular (RV) dysfunction in ventilated patients with COVID-19 [2]. We agree that the definition of RV dysfunction is critical when examining this important topic and will be one of the main determinants of prevalence. Furthermore, as they point out, there is no widely accepted definition of RV dysfunction, a situation where we agree that consensus would benefit the researcher and the clinician alike. The term is often used to describe abnormal echocardiographic or biomarker findings where cardiac output is preserved, a setting of ‘pre-’ RV failure. Counterintuitively, RV failure is perhaps easier to define but more difficult to diagnose clinically; RV failure is ‘a complex clinical syndrome characterised by insufficient delivery of blood from the RV in the setting of elevated systemic venous pressure at rest or exercise’ [3]. This definition is not dependent on any single imaging parameter and relies on the integration of imaging along with the clinical findings of systemic hypoperfusion and congestion.

In the article by Sanfilippo et al., we recognise the importance of the PRICES statement for conducting and reporting of critical care echocardiography studies [4]. As part of our a priori protocol for secondary analyses [5], all imaging performed was transferred to a central ‘echo lab’ where additional quantitative methods of assessing RV function, such as tricuspid annular plane systolic excursion, pulsed Doppler S wave and fractional area change, along with speckle tracked strain assessment were performed (an article reporting these data is in submission). While these quantitative methods of interrogating RV function are important study endpoints and help provide insight into mechanisms, as discussed in our article, the primary outcome of the study was intentionally pragmatic, rather than quantitative. Our focus was on providing an endpoint that could be delivered by critical care clinicians at the bedside; these clinicians are the people who are making real-time management decisions regarding these critically ill patients.

We also appreciate the considered response by Zawadka et al. [6]. The study by Huang et al. is one of the largest critical care echo studies in patients with COVID-19 and contributes significantly to our knowledge regarding this patient population, but the results are not directly comparable with our study [7]. It was retrospective, meaning imaging was performed as per clinical necessity (often at times of haemodynamic instability) and not on every patient, risking significant selection bias and limiting its generalisation. Our study reports results on 24% of all ventilated patients with COVID-19 admitted to participating ICUs during the study period, where imaging was performed per-protocol, regardless of clinical necessity. Furthermore, Huang et al.’s study was also performed on a mixed cohort of patients requiring, or not requiring, mechanical ventilation. The higher prevalence of septal flattening (or paradoxical septal motion as described by Huang et al.) may be as a result of the retrospective nature of that study. However, Huang et al.’s study is commendable for providing data on quantitative RV size in the majority (76.4%) of participants. This quantitative assessment may account for the lower prevalence of severe RV dilatation seen in their cohort. As highlighted by Zawadka et al., RV size is often over-estimated by visual assessment, meaning that the prevalence of true severe RV dilatation (if assessed quantitatively) in our study may be lower.

Although a wide range of expertise with echocardiography is highlighted in our study, the majority (82%) had either focused critical care echocardiography mentor status or British Society of Echocardiography accreditation. Echocardiography reporting in our study comes from clinicians who regularly perform focused echo assessment in their clinical practice and who are treating and making real-time management decisions based on their results. We thought that any definition of RV dysfunction needed to be sufficiently pragmatic [8] to empower these clinicians to make the diagnosis. Although lower than seen in some previous reports, we feel our estimate is robust, and that the prevalence of 6% is in keeping with previous work in ventilated patients with acute respiratory distress syndrome by Mekontso Dessap et al. where severe acute cor pulmonale (the definition used in our study) was present in 7% and, as in our study, was associated with mortality [9]. When reporting an alternative definition of RV dysfunction (our online Supporting Information), severe RV dilatation and/or septal flattening, the prevalence of RV dysfunction of was higher at 30%. This prevalence is perhaps more in keeping with other studies, but importantly was not associated with survival in this cohort. As Flower et al. suggest, this definition may include the ‘less sick’. Although the definition of RV dysfunction used undoubtedly impacts on prevalence, other aspects of study design are also important. More than 50% of the studies in the meta-analysis by Corica et al. [10] are retrospective, which can be susceptible to ascertainment bias with a reliance on clinically indicated echocardiograms (often performed at times of haemodynamic instability) leading to higher observed rates of RV dysfunction.

We agree that the endpoint of ‘radiologically confirmed’ or ‘clinically suspected’ pulmonary thromboembolism (PTE) is not perfect. As described in our article, the association described is at high risk of type-2 error and should be treated as exploratory only. Design of the study was that the radiologically confirmed or clinically suspected PTE was in the period before their study echocardiogram. This part of the case report form asked for the presence of confirmed or suspected PTE in the period from hospital admission to 08:00 on the day of their study echocardiogram. This finding should not, therefore, have been influenced by their subsequent study echocardiogram. Despite this, there will have been patients who had additional imaging prior to COVID-RV enrolment, as clinically indicated, which may have influenced clinicians to perform (or not perform) investigations for PTE.

The fact that most imaging societies recommend the use of more than one parameter for assessment of RV function reflects there being no single measure that will accurately reflect ‘RV dysfunction’. The future is likely to include the integration of dynamic and non-dynamic imaging parameters, biomarkers and clinical findings to highlight patients with ‘RV dysfunction’ or at risk of RV failure, allowing interventions to be targeted at those most likely to benefit. However, RV dysfunction or failure is defined, to maximally benefit these patients, its diagnosis must be deliverable at the bedside.

我们感谢 Flower 等人。感谢他们对我们的文章进行了周到的回应 [ 1 ]，该文章检查了 COVID-19 通气患者的右心室 (RV) 功能障碍 [ 2 ]。我们同意 RV 功能障碍的定义在研究这一重要主题时至关重要，并将成为患病率的主要决定因素之一。此外，正如他们所指出的，RV 功能障碍没有被广泛接受的定义，在这种情况下，我们同意共识将使研究人员和临床医生都受益。该术语通常用于描述异常的超声心动图或生物标志物发现，其中心输出量被保留，“预”RV 衰竭的设置。与直觉相反，RV 衰竭可能更容易定义，但临床诊断更难。RV 故障是 '一种复杂的临床综合征，其特点是在休息或运动时全身静脉压升高的情况下，从 RV 供血不足” [ 3 ]。该定义不依赖于任何单一的成像参数，而是依赖于成像与全身性低灌注和充血的临床发现的整合。

在 Sanfilippo 等人的文章中，我们认识到 PRICES 声明对于开展和报告重症监护超声心动图研究 [ 4 ] 的重要性。作为我们用于二次分析的先验协议的一部分 [ 5]，所有进行的成像都转移到中央“回声实验室”，在那里进行了评估 RV 功能的其他定量方法，例如三尖瓣环平面收缩偏移、脉冲多普勒 S 波和分数面积变化，以及散斑跟踪应变评估（报告这些数据的文章正在提交中）。虽然这些询问 RV 功能的定量方法是重要的研究终点，并有助于深入了解机制，正如我们在文章中所讨论的，但该研究的主要结果是有意实用的，而不是定量的。我们的重点是提供一个可由重症监护临床医生在床边提供的终点；这些临床医生是为这些危重病人做出实时管理决策的人。

我们也感谢 Zawadka 等人的深思熟虑的回应。[ 6 ]。Huang等人的研究。是对 COVID-19 患者进行的最大的重症监护回声研究之一，对我们对这一患者群体的了解做出了重大贡献，但结果与我们的研究无法直接比较 [ 7]。它是回顾性的，这意味着成像是根据临床需要（通常在血流动力学不稳定时）进行的，而不是对每一位患者进行，存在显着的选择偏倚并限制其推广。我们的研究报告了在研究期间入住参与 ICU 的所有 COVID-19 通气患者中 24% 的结果，无论临床必要性如何，都按照方案进行成像。此外，Huang 等人的研究还针对需要或不需要机械通气的患者的混合队列进行。室间隔变平（或 Huang 等人描述的自相矛盾的室间隔运动）的较高患病率可能是该研究的回顾性结果。然而，Huang 等人的研究值得称道，因为它提供了大多数 (76.4%) 参与者的定量 RV 大小数据。这种定量评估可能解释了在他们的队列中看到的严重 RV 扩张的较低患病率。正如 Zawadka 等人强调的那样，视觉评估通常会高估 RV 大小，这意味着我们研究中真正严重的 RV 扩张（如果进行定量评估）的患病率可能较低。

尽管我们的研究强调了超声心动图的广泛专业知识，但大多数 (82%) 要么具有重点重症监护超声心动图导师身份或英国超声心动图学会认证。我们研究中的超声心动图报告来自临床医生，他们在临床实践中定期进行有针对性的回声评估，并根据他们的结果进行治疗和做出实时管理决策。我们认为 RV 功能障碍的任何定义都需要足够实用 [ 8] 使这些临床医生能够做出诊断。虽然低于之前的一些报告，但我们认为我们的估计是稳健的，并且 6% 的患病率与 Mekontso Dessap 等人之前对急性呼吸窘迫综合征通气患者的研究一致。其中严重急性肺心病（我们研究中使用的定义）占 7%，并且与我们的研究一样，与死亡率相关 [ 9]。当报告 RV 功能障碍的另一种定义（我们的在线支持信息）、严重的 RV 扩张和/或室间隔变平时，RV 功能障碍的患病率高达 30%。这种患病率可能更符合其他研究，但重要的是与该队列的生存率无关。作为花等人。建议，这个定义可能包括“少病”。尽管 RV 功能障碍的定义无疑会影响患病率，但研究设计的其他方面也很重要。Corica 等人的荟萃分析中超过 50% 的研究。[ 10] 是回顾性的，由于依赖临床指示的超声心动图（通常在血流动力学不稳定时进行），容易受到确定偏倚的影响，从而导致观察到的 RV 功能障碍率更高。

我们同意“放射学证实”或“临床疑似”的终点肺血栓栓塞症（PTE）并不完美。如我们的文章所述，所描述的关联存在 2 型错误的高风险，应仅视为探索性的。该研究的设计是放射学证实或临床怀疑的 PTE 在他们研究超声心动图之前的时期。病例报告表的这一部分要求在他们研究超声心动图当天从入院到 08:00 期间是否存在确诊或疑似 PTE。因此，这一发现不应受到他们随后研究的超声心动图的影响。尽管如此，仍有一些患者在加入 COVID-RV 之前进行了额外的影像学检查，如临床所示，这可能会影响临床医生对 PTE 进行（或不进行）调查。

大多数影像学会建议使用多个参数来评估 RV 功能这一事实反映了没有单一的测量方法可以准确反映“RV 功能障碍”。未来可能包括动态和非动态成像参数、生物标志物和临床发现的整合，以突出“右室功能障碍”或有右室衰竭风险的患者，从而使干预措施能够针对最有可能受益的患者。然而，为了最大限度地使这些患者受益，必须定义 RV 功能障碍或衰竭，其诊断必须在床边进行。