68. Minimally Invasive Cardiac Surgery- Clinical Scenarios

Daniel Ragheb MD, Michael Tong MD
Cleveland Clinic Foundation
November 20th, 2024

Abbreviations and Definitions

BPA – Balloon pulmonary angioplasty
CTED – Chronic thromboembolic disease
CTEPH – Chronic thromboembolic pulmonary hypertension
CTPE – Computed tomography pulmonary embolism
mPAP – Mean pulmonary artery pressure
PCWP – Pulmonary capillary wedge pressure
PE – Pulmonary embolism
PH – Pulmonary hypertension
PTE – Pulmonary thromboendarterectomy
PVR – Pulmonary vascular resistance
RHC – Right heart catheterization
V/Q – Ventilation/perfusion
UCSD – University of San Diego
vWF – von Willebrand Factor
WU – Wood Units

Indications and Guidelines for Management

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension (PH) caused by chronic pulmonary embolisms (PE).1 These embolisms clot within the pulmonary vasculature, ultimately leading to an increase in pulmonary pressure. It is estimated that around 3% of patients with PE will develop CTEPH. CTEPH is classified under group 4 of the PH disorders by the World Health Organization, and is considered one of the rarer forms of PH.2

PH can generally be diagnosed by right heart catheterization (RHC), in which mean pulmonary artery pressure (mPAP) will be >20-25 mmHg. PH can be further defined as pre-capillary, post-capillary, or mixed. This further delineates the etiology of the hypertension: pre-capillary will be proximal to the capillaries in the pulmonary arterial system, post-capillary will be distal to the capillaries in the pulmonary venous system, and mixed will involve both pathologies. CTEPH is a pre-capillary disease, resulting in a pulmonary capillary wedge pressure (PCWP) ≤15 mmHg and a pulmonary vascular resistance (PVR) ≥3 Wood Units (WU) on RHC.3 In addition, some patients may have chronic thromboembolic disease without PH and are classified as chronic thromboembolic disease (CTED).

The diagnostic algorithm will be discussed in depth below, but briefly, patients with concerning signs, symptoms, or history should undergo an echocardiogram and a ventilation/perfusion (V/Q) scan. CTEPH is ruled out in patients without V/Q mismatch. In patients with V/Q mismatch, however, computed tomography pulmonary embolism (CTPE) and RHC can then determine the degree of PH and the location of the lesions. In patients with V/Q mismatch but negative CTPE, a pulmonary angiography with lateral views can assess for distal disease.

The treatment of choice in those with operable CTEPH is surgery. Surgery entails pulmonary endarterectomy (PTE), which can be curative.4,5 The surgery involves a highly skilled surgeon placing a patient in circulatory arrest and extracting the thrombotic disease from the pulmonary artery. Balloon pulmonary angioplasty (BPA) and medical therapies may be useful adjuncts or alternatives.

Diagnosis

CTEPH should be suspected, and its presence interrogated, in any patient presenting with PH and those with residual symptoms following PE.6 Additionally, those with dyspnea on exertion, limited exercise capacity, hemoptysis, edema, or right heart dysfunction should have CTEPH as part of their differential diagnoses. Suspicion should be similarly high in patients with risk factors, which include acute PE (especially recurrent and unprovoked), hematologic hypercoagulable pathology, such as elevated Factor VII or von Willebrand Factor (vWF), antiphospholipid antibodies, and lupus, and associated comorbidities including splenectomy, chronic inflammatory disease, malignancy, ventriculo-atrial shunts, pacemaker leads, and chronic indwelling catheters.7 Other patients might raise concern for CTEPH following an abnormal echocardiogram, which would show signs of RV pressure overload, such as RV dilation, depressed systolic function, and abnormal septal bowing.8,9

Patients should undergo an echocardiogram if one has not yet been completed. Then, all individuals should receive a V/Q scan, which provides a spatial representation of pulmonary regions that are ventilated and perfused, essentially showing where air and blood are reaching. A mismatch, such as a region of normal ventilation but limited perfusion, might demonstrate the presence of CTEPH. Those with a normal V/Q scan can confidently be assumed not to have CTEPH, but a positive V/Q scan raises concern and requires additional testing. 8-10

Once CTEPH is suspected, following a positive V/Q scan, a CTPE scan can both help confirm the diagnosis and assist in future operative planning.11 Once the diagnosis of CTEPH is made, the patient should be referred to a CTEPH center for multidisciplinary discussion on the treatment approach. RHC is also essential as it can define PH, pre-capillary disease, and at this point, should be done to determine the degree of PH. In patients with an unclear link between symptoms and hemodynamics, an invasive cardiopulmonary exercise test may be helpful to establish the link. Interpretation of PVR in the context of disease burden is especially important, as it can assist in both prognostication and surgical candidacy. Pulmonary angiography is historically considered the gold standard in diagnosis and is universally performed in some centers.12 However, we have found that in patients with concordant V/Q and CTPE results, without distal disease, pulmonary angiography is not necessary. In those with discordant results or concern for more distal disease, pulmonary angiography with cone beam CT is necessary to identify distal segmental disease where the resolution of CTPE is suboptimal. It is similarly important for those undergoing BPA, which will be discussed in depth later in this chapter.

CTEPH Mimickers

There are several CTEPH mimickers, which can complicate diagnosis if the clinical team is not aware and vigilant of their possibility. These include pulmonary vasculitis, pulmonary artery sarcoma, in situ thrombosis in the presence of primary PH, Eisenmenger, sarcoidosis, pulmonary vein stenosis, and fibrosing mediastinitis.13

Pulmonary vasculitis should be especially investigated if other symptoms of vasculitis are present, including stroke, limb claudication, and visual defects. In interrogation, many radiographic differences will be observed, including the presence of pulmonary aneurysm, transmural arterial calcification, and the absence of intramural thrombus. Similarly, in situ thrombosis in the presence of PH is a common mimicker among those with congenital heart disease, and can show central pulmonary artery thrombus on imaging.

On the other hand, like CTEPH, sarcoidosis is a disease that often shows mismatched perfusion defects on a V/Q scan, as well as narrowed vasculature on imaging. Importantly, however, sarcoidosis will present with symptoms within other organ systems and will not demonstrate any filling defects in the pulmonary arteries. Lastly, fibrosing mediastinitis, a disease in which diffuse proliferation of fibrous tissue in the mediastinum will compress surrounding structures, is particularly common in areas where histoplasmosis is endemic and will also show mismatched perfusion defects on V/Q scan. Other imaging modalities will reveal these patients to have heavy hilar calcification or even airway narrowing, which can help differentiate it from CTEPH.

Pulmonary vein stenosis secondary to ablation for atrial fibrillation, pulmonary veno-occlusive disease, and malignancy are additional diseases that may mimic CTEPH, and thus, all patients with suspected CTEPH require an in-depth history and physical in addition to the previously mentioned imaging.

Patients with a CTEPH mimicker who are offered PTE make up a disproportionately high percentage of PTE mortality, as the surgery is unlikely to be of any benefit. The mitigation of this misdiagnosis is one of the main benefits of multidisciplinary team evaluation and decision making before treatment strategies are offered.

Classification

It is worth briefly reviewing how varying degrees of CTEPH are categorized. Additional factors that may make a patient a higher risk candidate will also be discussed. There are two prevalent systems for categorization: the original Jamieson classification14 and the more updated level classification by UCSD in 201615 (Table 1). It is critical to understand that the level of disease and the subsequent classification can only be truly confirmed intraoperatively, as the extent of disease surgically extracted can often differ from what is radiographically visualized.

Table 1: CTEPH Classification, as suggested by UCSD and Jamieson.

Level/Type UCSD Criteria Jamieson Classification
0 No surgical evidence for chronic thromboembolic disease N/A
I Obstruction involves one of the main pulmonary arteries Fresh thrombus in main lobar arteries
IC Obstruction involves one of the main pulmonary arteries; the entire artery is obstructed, resulting in complete nonperfusion of the entire lung N/A
II Obstruction involves lobar branches Intimal thickening and fibrosis proximal to segmental arteries
III Obstruction involves segmental branches Disease within distal segmental arteries only
IV Obstruction only begins at the subsegmental level Distal arteriolar vasculopathy without visible thromboembolic disease

Risk Stratification

When considering patients for surgery, there are three critical factors to consider. First, the disease must be surgically accessible. Especially distal clots may not be reachable during surgery and may not be able to be removed. However, endarterectomy of only proximal disease, while leaving distal clot, is not effective and will not improve patient outcomes. What might be viewed as “too distal” will differ from center to center, yet again reinforcing the fact that these patients must be seen at a center of excellence.

Second, the degree of PVR greatly impacts the surgical risk of the patient. Those with greater PVR have more difficulty coming off pump if the complete disease burden isn’t relieved intraoperatively, and these patients have higher mortality. Although there is no explicit cutoff for PVR during pre-operative prognostication,16 patients with higher PVR may have a higher risk profile. Patients with lower PVR (<6) and a good surgical extraction will do the best. Patients with lower PVR but who have inadequate surgical extraction may not improve with surgery; however, these patients should still be able to separate from cardiopulmonary bypass and return to the same level of health. On the other hand, patients with higher PVR (>10) and who have good surgical extraction will do well. However, patients with both higher PVR and an inadequate surgical extraction will struggle to come off bypass and ultimately will have the highest mortality. Therefore, it is in these patients with higher PVR and poor or unclear disease extractability who may benefit from medical management first to lower their PVR and ultimately lower their risk of surgery.

Lastly, other medical comorbidities can greatly impact a patient’s surgical risk. Those with older age, a greater degree of frailty, and/or untreatable left heart disease have been shown to have higher mortality.17,19 Additionally, chronic pulmonary disease and functional class IV are also factors in high-risk patients.20

Adjuncts

Medical management is also a part of the therapeutic plan for all CTEPH patients, whether operable or not. Medical therapy includes anticoagulation21,22 and PH medications. At our institution, we provide prophylactic subcutaneous heparin 5000 units twice a day until post-operative day 3, during which therapeutic anticoagulation is initiated.22 Patients will be started on a novel anticoagulant agent unless they were previously on warfarin, in which case they will be bridged with a heparin infusion with a goal international normalized ratio of 2.0 to 3.0. The PH medications include endothelin-1 competitive inhibitors (Bosentan,23 Macitentan24) and vasodilators (Riociguat,25 Epoprostenol,26 Treprostinil27). Three of these have been studied under randomized controlled trials demonstrating improved outcomes, including lower PVR and improved 6-minute walk test: Bosentan in the BENEFIT trial,28 Riociguat in the CHEST-1 trial,25 and Macitentan in the MERIT-1 trial.24 Most patients following surgery will no longer require their preoperative pulmonary vasodilator medications.

Lastly, although transcatheter therapies are not the focus of this chapter, it is important to consider BPA as an adjunct or alternative to surgery. BPA is a minimally invasive technique in which a balloon is expanded in the pulmonary vasculature to open up a previously narrowed area. In patients who are deemed inoperable, BPA has been shown to be as safe as, but less efficacious than, PTE in operable patients.29 Additionally, in those with residual disease following PTE, BPA has been demonstrated to further relieve disease.30 However, BPA has its limitations. It often takes multiple sessions, with some experts planning 4-6 treatments.31 Even then, it can be difficult to utilize BPA in the treatment of flush occlusions.

Conclusion

The decision algorithm and indications for PTE and CTEPH should be as follows: (1) suspicion of PH, (2) initial screening and diagnostic evaluation for CTEPH with echocardiogram and V/Q scan, (3) further testing by CTPE and RHC to confirm and assist surgical planning, (4) consider pulmonary angiography if discordant imaging or distal disease, (5) offer surgical correction if patient is operable, and (6) consideration of medical management and/or transcatheter interventions. In centers that have a high volume, with surgeons who are experienced in the operation, most patients diagnosed with CTEPH should be offered surgical PTE. High-risk patients and those with other possible etiologies of PH comprise the patients who might not be offered or might not elect to undergo surgical therapy (Table 2).

In conclusion, CTEPH is a highly morbid disease with high mortality. However, surgery has repeatedly been demonstrated to be an effective therapeutic option and may be curative in many patients. If a patient has no underlying disease elevating PVR beyond their CTEPH, PTE should be pursued in most patients as long as a skilled surgeon at a high-volume center is available. Medical therapy and BPA are potential adjuncts to surgical therapy and may also be considered in inoperable patients.

Table 2. Summary of Recommendations.

Patient Characteristics Patient Management
Presence of PH, confirmed on imaging with evidence of obstruction on V/Q scan and other modalities. Elevated PVR is explained by obstructive findings. Other comorbidities do not elevate surgical risk. Disease is not too distal for safe endarterectomy Offer surgical PTE
Presence of PH and evidence of CTEPH, but higher than expected elevation in PVR not fully explained by obstructive findings. Other comorbidities are present, such as older age, medical comorbidities, disease too distal for safe endarterectomy Consider non-surgical management Consider transfer to CTEPH/PH center

Expert Commentary

CTEPH is a rare complication of acute PE but is underdiagnosed. Patients identified with CTEPH often have been misdiagnosed for months to years before arriving at the correct diagnosis. Patients with a hypercoagulable condition, history of PE, unexplained PH, or ongoing symptoms should be screened for CTEPH with an echocardiogram and V/Q scan. This should be followed by CTPE and RHC if the screening tests are positive. Patients with discordant V/Q and CTPE should receive a pulmonary angiogram with lateral views (not AP views, which result in overlapping vessels) to confirm the diagnosis. Disease preferentially affects the right lung and the lower lobes.

Patients should then be evaluated by a multidisciplinary team to discuss treatment options, which will preferentially be PTE in patients who have accessible disease and acceptable comorbidities. In many cases, the diagnosis and decision to operate are not obvious and may require an invasive cardiopulmonary exercise test to confirm that the symptoms and physiology match the hemodynamics.

Identification of the correct surgical plane is the most important step of the operation. When the dissection is not deep enough, residual disease will be left behind. Only patients with extraction of the most distal disease will experience an improvement in hemodynamics and, ultimately, the recruitment of lung segments. However, if the dissection plane is too deep, then pulmonary artery injury and the risk of rupture both increase. In patients with distal disease, the plane will often need to start in the proximal intima to reach the distal disease. In high-volume centers, surgical mortality of <2% with PTE is achievable, and distal segmental disease is accessible.

In the past few years, an increasing number of pulmonary vasodilators have become available and are often used preoperatively in this patient population. They may also be used postoperatively in patients with residual disease. Similarly, BPA is a complementary procedure in patients who have distal, inaccessible disease or patients who have residual disease post-PTE. However, BPA often requires multiple sessions. This is due to the inherent limitation of the procedure, given contrast and radiation safety limits. BPA can also prove challenging in patients with totally occluded vessels rather than stenotic vessels. Yet, in some centers, such as those in Japan, patients preferentially receive BPA over PTE. Comparative studies have shown that the safety of BPA is comparable to PTE, but overall reduction in PVR is superior with PTE.

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