Importance of Pulmonary Embolism Anatomy in Ventilatory Distress and Haemodynamics

Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality worldwide, with an annual incidence estimated at 39–115/100,000, causing around 300,000 deaths annually in the US alone. It ranks third among cardiovascular mortality causes and is the leading cause of death in hospitalised patients.^1–5 PE presents with a broad spectrum of clinical symptoms, ranging from mild dyspnoea to life-threatening haemodynamic collapse.⁶ Commonly used guidelines and risk stratification tools such as the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, Simplified/Pulmonary Embolism Severity Index (simplified Pulmonary Embolism Severity Index/Pulmonary Embolism Severity Index ([sPESI/PESI]), the Bova Score and the Pulmonary Embolism Response Team (PERT) algorithm categorise PE into high, intermediate-high, intermediate-low, and low risk based on haemodynamic status, clinical presentation, right ventricular (RV) dysfunction on imaging, and elevated cardiac troponin levels (Table 1).^4,5,7,8

However, while standard risk stratification focuses on systemic markers, the anatomical burden of PE (i.e. the size and location of emboli) remains a critical factor in clinical management (Table 2).^9–11 The distribution of emboli within the pulmonary vasculature critically affects both respiratory function and circulatory dynamics, playing a pivotal role in determining day-to-day clinical outcomes.^12–15 Central emboli, typically located in the main pulmonary arteries, significantly raise mean pulmonary artery pressure (mPAP), disrupt gas exchange, and lead to hypoxaemia and respiratory distress.¹⁶ Clot burden also plays a crucial role in the severity of the ventilation–perfusion (V/Q) mismatch in patients with PE. As more areas of lung parenchyma become ventilated but insufficiently perfused, the clinical impact of the V/Q mismatch intensifies.¹⁷

The anatomical characteristics of PE determine the degree of respiratory dysfunction and influence the haemodynamic burden. Pulmonary hypertension (PH) typically occurs when more than 30% of the pulmonary vascular bed is occluded, resulting in elevated mPAP and pulmonary vascular resistance (PVR).^18–21 In severe cases, the RV is unable to overcome the elevated mPAP and PVR, leading to RV dilation, reduced contractility, RV failure and death.^22,23 Therefore, understanding the anatomical distribution of PE is essential for accurately assessing the severity of the haemodynamic insult and guiding treatment. Central PE often requires immediate intervention, particularly in the case of haemodynamic instability, in which timely thrombolysis, endovascular therapies or surgical embolectomy can mitigate respiratory and circulatory collapse.^14,24,25

Despite advances in the diagnostic assessment and management of PE, accurate prediction of clinical deterioration and outcomes remains challenging. Current risk stratification is primarily based on ESC guidelines; however, these classifications often group patients into broad categories that, in many cases, exhibit significant heterogeneity, particularly regarding clinical outcomes and the risk of haemodynamic deterioration.⁴ Consequently, recent studies increasingly support the need for a more refined and detailed risk stratification model.²⁶ Therefore, this review examines the critical role that PE anatomy plays in ventilatory distress and haemodynamic dysfunction. By evaluating the anatomical distribution of emboli, we aim to clarify how these factors influence gas exchange and RV function. Understanding the anatomical burden is vital for improving risk stratification and tailoring therapeutic strategies in cases in which early intervention is necessary.

Pulmonary Embolism Anatomy

Pulmonary Vascular Anatomy Relevant to Pulmonary Embolism

The pulmonary vasculature is a complex branching network originating as the pulmonary trunk from the RV, and then dividing into the main right and left pulmonary arteries. These arteries progressively branch into lobar, segmental and subsegmental arteries. Each lung is composed of approximately 20 bronchopulmonary segments, 10 in the right lung and seven in the left, with subsegmental arteries further subdividing into smaller vessels (Figure 1 ).²⁷ Lower lobe segments, which constitute approximately 60% of the lung parenchyma, have a more significant clinical, ventilatory and haemodynamic impact when involved in a PE compared with the upper lobes, which comprise 40% of the lung’s volume.²⁷

PE can occur at any level of the pulmonary vascular tree (Figure 2). Approximately 30–40% of PEs involve proximal arteries (main or lobar), often leading to larger vascular obstruction and more significant ventilatory and haemodynamic effects. In healthy individuals, high-risk PE carries an early mortality risk of up to 30%. Most high-risk PEs are central. Within this subset, a twofold increase in early mortality has been reported.²⁶ Among patients with comorbidities such as heart disease or cancer, mortality may rise to 30–50%. Additionally, a high thrombotic burden has been associated with up to a 17-fold increase in mortality.^28,29 Distal emboli, which affect the segmental or subsegmental arteries, account for 60–70% of cases. While distal PEs are less severe in healthy patients, they may have significant clinical implications in those with pre-existing pulmonary or cardiac conditions.^23,24 Segmental and subsegmental PE is associated with a mortality rate of 1–2% if untreated. In patients with significant comorbidities, mortality can rise to 5–20%, especially when the embolism exacerbates existing conditions or when they are in advanced stages of illness.²⁹

Impact of Pulmonary Embolism Anatomical Characteristics on Obstruction and Clinical Presentation

The size and location of a PE almost always correlate directly with clinical severity and the short- and long-term outcomes. Proximal emboli in the main and lobar pulmonary arteries can block up to 50% of pulmonary vascular flow, resulting in severe symptoms almost immediately. Dyspnoea affects approximately 80% of PE patients, while hypoxaemia affects approximately 50% of patients with proximal PE, with oxygen saturation levels often falling below 90%.^30,31 Syncope, particularly after a PE, is a sign of severity and occurs in 10–20% of massive PEs, especially in cases in which emboli occlude more than 40% of the pulmonary vasculature.^6,30,31

Distal PE, affecting segmental and subsegmental branches, leads to smaller perfusion deficits. These emboli typically block less than 20–30% of the pulmonary vasculature, resulting in milder symptoms. Pleuritic chest pain is common in peripheral PE, occurring in approximately 40% of patients.³² However, even small emboli can trigger significant clinical responses in vulnerable populations, particularly patients with pulmonary, cardiovascular or systemic conditions. Distal PEs can still result in severe hypoxaemia and dyspnoea, with oxygen saturation levels dropping by 5–10% from baseline.^30,31

Impact of Pulmonary Embolism Anatomy on Ventilatory Distress

Effect of Pulmonary Embolism on Ventilatory Function

PE impairs ventilatory function by creating alveolar dead space, resulting from ventilated lung regions losing perfusion due to vascular obstruction. This leads to a V/Q mismatch, where ventilation exceeds perfusion in the affected areas.^31,33 Dead space, normally approximately 25% of tidal volume in healthy individuals, can increase to over 50% depending on embolus location and size (Figure 3).^31,33–35 Proximal emboli, involving the main and lobar branches, may obstruct over 40% of the pulmonary vasculature, significantly increasing dead space.³⁶ In contrast, distal emboli, affecting segmental or subsegmental branches, involve smaller areas and thus cause a more localised increase in dead space.³⁶ The extent of the V/Q mismatch and the resulting gas exchange inefficiencies depend on the size and location of the emboli. Proximal emboli lead to pronounced reductions in gas exchange efficiency, with partial pressure of oxygen (PaO₂) levels dropping by 10–20 mmHg, sometimes below 60 mmHg.³⁷ Distal emboli generally have a milder effect, often minimally affecting PaO₂.^33,36

Compensatory hyperventilation typically follows hypoxaemia, significantly when more than 50% of the vasculature is affected. The respiratory rate may rise by 20–30% to compensate for this new-onset hypoxaemia. However, PaO₂ may decline by 5–10% in severe cases.^12,38 Distal emboli may also trigger hyperventilation, although the impact on oxygen saturation is usually less severe. Prolonged hyperventilation, particularly in proximal emboli, can lead to respiratory alkalosis, contributing to respiratory fatigue and increasing the risk of respiratory failure.³⁸ Respiratory fatigue ultimately worsens ventilatory distress and increases the risk of respiratory failure in cases of significant pulmonary compromise.³⁹

Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension in Pulmonary Embolism

An often-overlooked mechanism in PE-induced ventilatory distress is hypoxic pulmonary vasoconstriction (HPV).⁴⁰ In response to reduced PaO₂ due to significant PE, the pulmonary vasculature undergoes vasoconstriction to redirect blood flow to well-ventilated lung regions.^17,40 While this compensatory mechanism can initially improve V/Q mismatch, in the context of PE it leads to a paradoxical worsening of PH.⁴⁰

As HPV increases PVR, the pressure within the pulmonary circulation rises, further complicating gas exchange. This increase in RV afterload may precipitate RV strain, which, in severe cases, may progress to right heart failure. This is particularly relevant in cases of proximal PE, significantly increasing PAP.^40,41 Right heart strain exacerbates the reduced oxygen delivery by decreasing cardiac output, limiting perfusion to non-occluded lung regions. This combination of increased dead space ventilation, PH and reduced cardiac output creates a vicious cycle, worsening both hypoxaemia and respiratory effort.⁴¹

Ventilatory Mechanics in Pulmonary Embolism

PE significantly affects both ventilatory function and the mechanical aspects of breathing when larger vessels are obstructed. Proximal emboli, by occluding main or lobar branches, can dramatically reduce lung compliance by 15–20%.^16,42 This reduction makes the lungs stiffer and more resistant to inflation, increasing the breathing work by 40–60% compared with normal conditions.¹⁶ As a result, more significant respiratory effort is required, leading to respiratory muscle fatigue, further compounding hypoxaemia and dyspnoea, with oxygen saturation (SaO₂) potentially dropping an extra 5–10% in severe cases.^16,42

In addition to the increased effort required, PE impairs gas exchange by causing alveolar collapse and reducing the lung’s overall efficiency.⁴³ This compliance reduction originates from mechanical obstruction and inflammatory changes within lung parenchyma, which may include alveolar oedema.⁴⁴ These changes further compromise the alveolar–capillary barrier, impairing oxygen diffusion and exacerbating hypoxaemia.⁴⁴ Finally, as the lungs stiffen and ventilation becomes increasingly inefficient, the body compensates by increasing the respiratory rate and recruiting accessory muscles. This compensation increases breathing work and, over time, can lead to respiratory muscle fatigue, especially in patients who are critically ill or have pre-existing lung disease. When respiratory muscles can no longer sustain the increased effort, the body’s ability to maintain adequate ventilation declines, leading to progressive hypoxaemia, hypercapnia and, if left untreated, respiratory failure and arrest.

Impact of Pulmonary Embolism Anatomy on Haemodynamics

Haemodynamic Impact Based on Pulmonary Embolism Location and Size

PE anatomical location and extension play a vital role in the severity of haemodynamic disruption.⁴ Proximal PE is associated with more profound haemodynamic consequences than distal emboli in the segmental and subsegmental arteries. A large embolus occludes a major pulmonary artery, significantly reducing the cross-sectional area of the pulmonary vasculature and leading to a steep increase in PVR. This rise in PVR forces the RV to pump against a much higher afterload, resulting in an acute elevation in mPAP.⁴⁵ Under normal physiological conditions, mPAP ranges between 9 and 18 mmHg, but in cases of severe PE, mPAP can exceed 40 mmHg, placing immense strain on the RV.^4,46 Given that the RV is structurally suited for low-pressure work, this sudden and excessive pressure load compromises its ability to maintain effective output, leading to RV dilation and dysfunction.⁴⁷

In a normal physiological state, the RV is well-suited to maintain blood flow through the low-resistance pulmonary vasculature; however, it lacks structural robustness to cope with high afterload over prolonged periods. There is a sharp and significant rise in PVR in a massive PE, in which one or more large pulmonary arteries are obstructed.⁴⁵ Typically, PVR remains below 2 Wood units (WU), but in the presence of a central embolism, it can surge to 8 WU or higher, depending on the degree of vascular obstruction. When more than 30–50% of the pulmonary vascular tree is occluded, the RV must generate significantly higher pressures to maintain blood flow.^45,48 This acute increase in afterload quickly overwhelms the compensatory capacity of the RV, leading to dilation and impaired contractility. As the RV becomes unable to sustain an adequate stroke volume, there is a subsequent drop in cardiac output, precipitating systemic hypotension and potentially leading to RV failure.⁴⁷

Distal PE typically induces less severe haemodynamic disturbances. While they still contribute to an increase in PVR and mPAP, the overall impact is mitigated by the pulmonary circulation’s ability to redistribute blood flow through unaffected vascular regions.⁴⁹ Consequently, the RV is subject to a more moderate afterload increase, preserving its function to a greater extent than in cases of proximal PE. However, it is important to note that patients with underlying cardiopulmonary disease may have a heightened sensitivity to even small distal emboli.^45,48 In these patients, baseline PVR is already elevated, and their compensatory reserves are limited, meaning that even a small embolic burden can precipitate significant haemodynamic compromise.⁴⁷

Current evidence does not support a direct correlation between anatomical thrombus burden and clinical prognosis in normotensive PE patients. Although central thrombi (particularly saddle emboli) are frequently associated with acute haemodynamic compromise and early adverse events, several studies have demonstrated similar overall mortality rates between saddle and non-saddle PE.^50,51 Moreover, a large multicentre prospective analysis showed that central thrombus localisation alone was not an independent predictor of 30-day mortality in haemodynamically stable patients.⁵² Haemodynamic outcomes thus appear to depend more strongly on factors such as underlying cardiopulmonary reserve, RV dysfunction, and physiological compensation rather than solely on thrombus size or anatomical distribution.⁵³

Haemodynamic Collapse and Hypotensive Shock

Haemodynamic collapse and hypotensive shock are among the most severe complications associated with PE.^45,47 These events occur when the RV can no longer maintain sufficient forward flow into the pulmonary circulation, leading to a marked reduction in cardiac output and systemic perfusion. Hypotensive shock is defined by a drop in systolic blood pressure (SBP) below 90 mmHg or a decrease of 40 mmHg or more from baseline for at least 15 minutes.³¹ This reflects the RV’s inability to cope with the acute rise in afterload caused by the PE, particularly when mPAP exceeds 40 mmHg and PVR surpasses 5 WU.⁴⁵

At this point, the RV’s capacity to generate an adequate stroke volume is severely compromised.^4,47,49 As a result, systemic perfusion fails to meet the body’s metabolic demands, leading to widespread tissue hypoxia and the onset of multi-organ dysfunction. Activation of compensatory neurohormonal mechanisms, such as the sympathetic nervous system and renin–angiotensin–aldosterone system, further exacerbates the shock state by increasing afterload, worsening RV dysfunction.⁵⁴

As RV failure progresses, coronary perfusion to the RV becomes increasingly impaired.⁵⁵ The coronary arteries supplying the RV are largely perfused during systole, unlike those of the left ventricle (LV), which are predominantly perfused during diastole. In the setting of elevated mPAP and RV pressures, coronary flow to the RV is reduced, compounding the effects of myocardial ischaemia. Ischaemic injury to the RV myocardium further impairs contractility, accelerating RV output and systemic perfusion decline. The cycle of ischaemia, RV failure and hypotension becomes difficult to interrupt, often leading to refractory shock and, without intervention, death (Figure 4).⁵⁶

Patients with pre-existing pulmonary conditions, such as chronic obstructive pulmonary disease (COPD) or left-sided PH, exhibit an altered haemodynamic response to PE, often experiencing more pronounced increases in PVR and mPAP. In COPD, chronic hypoxaemia and vascular remodelling contribute to baseline elevations in PVR, limiting the pulmonary circulation’s capacity to adapt to additional thrombotic obstruction. Furthermore, dynamic hyperinflation and increased intrathoracic pressure in COPD patients can impair venous return, exacerbating RV dysfunction during acute PE.⁵⁷ Similarly, in patients with left-sided PH due to heart failure or valvular disease, an already elevated left atrial pressure restricts pulmonary artery compliance, making even minor embolic events more likely to precipitate haemodynamic decompensation.⁵⁸

Normotensive Shock in Pulmonary Embolism

Normotensive shock occurs when patients with PE have RV dysfunction without systemic hypotension. These patients often have proximal emboli in the main or lobar pulmonary arteries and show signs of RV strain, demonstrated as a reduced cardiac output (≤2.2 l/min/m²), despite maintaining an SBP ≥90 mmHg, maintained by compensatory mechanisms.⁵⁹ Biomarkers, such as elevated brain natriuretic peptide or troponin, and imaging findings, such as an increased RV/LV ratio, can confirm RV dysfunction.^53,60,61 The preserved systemic blood pressure in normotensive shock results from compensatory mechanisms that mask the underlying cardiovascular stress.⁵⁹

Although systemic blood pressure remains normal, patients with normotensive shock may present with subtle signs of systemic hypoperfusion, such as cool extremities, altered mental status or oliguria.⁵⁹ Despite the absence of overt hypotension, the ongoing haemodynamic stress weakens RV function over time. Without timely intervention, RV output may progressively diminish, leading to delayed haemodynamic collapse. Early therapeutic intervention to reduce PVR and support RV function is critical to prevent further deterioration.⁵³

Therapeutic Implications Based on Pulmonary Embolism Anatomy

Therapeutic Strategies Guided by Pulmonary Embolism Anatomy

Large, proximal emboli in the main and lobar arteries pose a significant risk for RV dysfunction and increased mortality.^56,62 Systemic thrombolysis remains the primary treatment for haemodynamically unstable patients, with a 50–60% success rate in restoring haemodynamic stability. Thrombolysis is used in approximately 15% of these cases, with mortality rates as high as 30% without intervention.⁶³ In this context, clinical tools that combine anatomical and physiological parameters are increasingly used to refine risk stratification and treatment decisions. The Composite Shock Score, developed from the FLASH registry, incorporates haemodynamic variables and biomarkers to quantify cardiopulmonary compromise and has shown utility in identifying patients who may benefit from advanced interventions such as mechanical thrombectomy.⁵³ Also, the FLAME study provides insights into the outcomes of high-risk PE patients treated with mechanical thrombectomy compared with alternative therapies. In-hospital mortality was 1.9% in the FlowTriever group, significantly lower than the 29.5% observed in the control group, in which most patients received systemic thrombolysis or anticoagulation alone.⁶⁴ Pebror et al. also evaluated the use of the FlowTriever System to treat intermediate- and high-risk PE in a real-world clinical setting, demonstrating technical success as high as 96.9% with minimal adverse events.⁶⁵ Significant improvements in PAP and heart rate were observed after the procedure.⁶⁵

Optimal patient selection for catheter-directed therapy (CDT) is rapidly evolving with emerging evidence to help guide decision-making. CDT may be a useful treatment for patients unsuitable for systemic thrombosis or those who fail initial treatment.^14,24 CDT is especially useful for preventing RV failure progression in high- and intermediate-risk PE patients, with favourable outcomes in both short-term survival and functional recovery.⁶⁶ Recent clinical evidence supports the efficacy and safety of CDT in selected intermediate- and high-risk PE patients, especially those with significant comorbidities or contraindications to systemic thrombolysis. A contemporary multicentre registry demonstrated that CDT provides effective reperfusion with a favourable safety profile, highlighting its potential role in refining risk stratification and management strategies for these patients.⁶⁷

Distal PEs confined to segmental or subsegmental arteries typically follow a more conservative management approach. Anticoagulation, using low-molecular-weight heparin, direct oral anticoagulants or vitamin K antagonists, is the mainstay of treatment, effectively preventing further clot extension and recurrence.⁴ In isolated subsegmental PEs, particularly in asymptomatic patients with low recurrence risk, conservative observation may suffice, especially without significant comorbidities. Conservative observation is debated in approximately 5–10% of cases, but outcomes are generally favourable when managed appropriately.⁴

Conclusion

The anatomical distribution and burden of PE are crucial factors influencing patient outcomes, but they remain underrepresented in current risk stratification tools. Proximal emboli, located in the main pulmonary arteries, are associated with higher mortality rates and more severe haemodynamic compromise, emphasising the need for aggressive interventions, such as systemic thrombolysis or CDT. In contrast, distal emboli, although generally managed with anticoagulation, can still pose significant risks, particularly in patients with comorbidities. Given the impact of clot burden and location on mortality, there is a strong rationale for expanding indications for mechanical thrombectomy in high-risk patients. A patient-centred, anatomy-guided approach is essential to optimise therapeutic decisions and improve clinical outcomes.