Successful Surgical Intervention in Severe Chronic Thromboembolic Pulmonary Hypertension

doi:10.1378/chest.64.1.29

Chest

Volume 64, Issue 1, July 1973, Pages 29-35

https://doi.org/10.1378/chest.64.1.29 Get rights and content

A 69-year-old man, in whom extensive embolic obstruction of the pulmonary arteries had likely been present for ten years, and who exhibited marked pulmonary hypertension and compromise of right ventricular function, was submitted to thromboendarterectomy. The course after surgery included extensive hemorrhagic infiltration of the reperfused lung zones (predicted before operation), which required special management. Four months after surgery, reduction in pulmonary vascular resistance of almost 50 percent was demonstrated. The patient is improved and maintains normal activity more than two years after surgery. The patient demonstrates that, despite several negative features before operation, successful thromboendarterectomy is possible, if recent technical and conceptual advances are applied in a coordinated manner during all phases of management.

Section snippets

CASE REPORT

The patient, a 67-year-old white man, was admitted to the University Hospital of San Diego County July 9, 1970. His history dated to 1943 when “aching in the calves” during exercise first occurred, and bilateral varicose veins were noted. Over the next 11 years, he had multiple bilateral episodes of superficial phlebitis, for which he was treated with several sodium morrhuate injections.

In 1954 he had an episode of sudden, severe dyspnea with a diagnosis of a “slight heart attack.” Thereafter,

DISCUSSION

The diagnosis and management of this patient included application of a variety of recent conceptual and technical advances. Furthermore, careful planning and interdisciplinary coordination marked each phase of his course. Four such phases are of interest: presurgical; surgical; hospital postsurgical course; outpatient, postsurgical course.

ACKNOWLEDGMENT

The authors wish to acknowledge the assistance of Dr. Richard Kahler of the Scripps Clinic and Research Foundation and of the many other physicians and allied health personnel who participated greatly in the diagnosis and management of this patient.

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Cited by (107)

Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study
2024, The Lancet Respiratory Medicine
Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar.
The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II–IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm⁵ and a walk distance of 150–450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292.
Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 71·5% of baseline in the macitentan group and to 87·6% in the placebo group (geometric means ratio 0·81, 95% CI 0·70–0·95, p=0·0098). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]).
In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated.
Actelion Pharmaceuticals Ltd.
Distribution of thrombus predicts severe reperfusion pulmonary edema after pulmonary endarterectomy
2023, Asian Journal of Surgery
Patients underwent pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to investigate the effect of thrombus distribution on the occurrence of severe reperfusion pulmonary edema (RPE) and identify specific parameters for predicting severe RPE.
Patients with CTEPH who underwent PEA surgery were retrospectively analyzed. The thrombus in pulmonary arteries were evaluated through computed tomography pulmonary angiography. Based on presence of prolonged artificial ventilation, extracorporeal membrane oxygenation required, or perioperative death due to RPE, the patients were divided into the severe RPE and without severe RPE groups.
Among the 77 patients (29 women), 16 (20.8%) patients developed severe RPE. The right major pulmonary artery (RPA) (0.64[0.58, 0.73] vs 0.58[0.49, 0.64]; p = 0.008) and pulmonary artery trunk (PAT) thrombus ratios (0.48[0.44, 0.61] vs 0.42[0.39, 0.50]; p = 0.009) (the PAT ratio is expressed as the sum of the right middle lobe clot burden and right lower lobe clot burden divided by the total clot burden multiplied by 100) of the severe RPE group was significantly higher than that of the without severe RPE group. Receiver operator characteristics curve identified a PAT ratio of 43.4% as the threshold with areas under the curve = 0.71(95%CI 0.582; 0.841) for the development of severe RPE (sensitivity 0.875, specificity 0.541). The logistic regression analysis demonstrated that age, period from symptom onset to PEA, NT-pro BNP, preoperative mPAP, preoperative PVR, RPA ratio, and PAT ratio were associated with the development of severe RPE. Multivariable logistic regression analysis revealed PAT ratio (odds ratio = 10.2; 95% confidence interval 1.87, 55.53, P = 0.007) and period from symptom onset to PEA (OR = 1.01; 95% CI = 1.00–1.02, P = 0.015) as independent risk factors for the development of severe RPE.
The thrombus distribution could be a key factor in the severity of RPE. PAT ratio and medical history could predict the development of severe RPE.
Angiopoietin 2 and hsCRP are associated with pulmonary hemodynamics and long-term mortality respectively in CTEPH—Results from a prospective discovery and validation biomarker study
2023, Journal of Heart and Lung Transplantation
Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed disease of uncertain etiology. Altered endothelial homeostasis, defective angiogenesis and inflammation are implicated. Angiopoietin 2 (Ang2) impairs acute thrombus resolution and is associated with vasculopathy in idiopathic pulmonary arterial hypertension.
We assessed circulating proteins associated with these processes in serum from patients with CTEPH (n = 71) before and after pulmonary endarterectomy (PEA), chronic thromboembolic pulmonary disease without pulmonary hypertension (CTEPD, n = 9) and healthy controls (n = 20) using Luminex multiplex arrays. Comparisons between groups were made using multivariable rank regression models. Ang2 and high-sensitivity C-reactive protein (hsCRP) were measured in a larger validation dataset (CTEPH = 277, CTEPD = 26). Cox proportional hazards models were used to identify markers predictive of survival.
In CTEPH patients, Ang2, interleukin (IL) 8, tumor necrosis factor α, and hsCRP were elevated compared to controls, while vascular endothelial growth factor (VEGF) c was lower (p < 0.05). Ang2 fell post-PEA (p < 0.05) and was associated with both pre- and post-PEA pulmonary hemodynamic variables and functional assessments (p < 0.05). In the validation dataset, Ang2 was significantly higher in CTEPH compared to CTEPD. Pre-operative hsCRP was an independent predictor of mortality.
We hypothesize that CTEPH patients have significant distal micro-vasculopathy and consequently high circulating Ang2. Patients with CTEPD without pulmonary hypertension have no discernible distal micro-vasculopathy and therefore have low circulating Ang2. This suggests Ang2 may be critical to CTEPH disease pathogenesis (impaired thrombus organization and disease severity).
“It Will Work”: The Story of Nina Starr Braunwald and the First Successful Mitral Valve Replacement
2021, Annals of Thoracic Surgery
Cardiothoracic surgery is a clinical and scientific discipline that has evolved enormously over the last decades. Cardiac problems that were historically death sentences can now be addressed with approaches that only continue to improve. In the late 1950s, while cardiothoracic surgery was still a nascent field, Nina Starr Braunwald emerged as a pioneer for this exponential improvement. As the first woman cardiac surgeon in an era in which general surgery and surgical specialties were dominated by men, Dr Braunwald not only made revolutionary contributions to cardiothoracic surgery, but also did so while balancing roles as a dedicated mother and supportive partner.
History and Current Status of Cardiac Anesthesia in Singapore
2019, Journal of Cardiothoracic and Vascular Anesthesia
Singapore is a small Southeast Asian island city-state located at the tip of the Malay peninsula with a population of 5.61 million people. It was a former British colony that went on to become a part of Malaysia before gaining independence in 1965. Since then, Singapore has developed tremendously from a small fishing village into the region's medical hub. This article will explore the roots of cardiac anesthesia in Singapore and how it has developed into a subspecialty today.
Extracorporeal Membrane Oxygenation in Pulmonary Endarterectomy Patients
2019, Journal of Cardiothoracic and Vascular Anesthesia
To investigate short-term outcomes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) presenting for pulmonary endarterectomy (PEA) and requiring extracorporeal membrane oxygenation (ECMO) during the perioperative period.
Retrospective observational case series involving patients who underwent PEA for CTEPH, with focus on a subpopulation requiring perioperative ECMO support.
Single academic tertiary center.
Patients who underwent PEA for CTEPH between January 1997 and December 2015 and required ECMO support.
PEA for CTEPH with ECMO support at any time during the perioperative period.
A total of 150 patients underwent PEA for CEPTH during the study period. Of the 150 patients, 14 (9.3%) required ECMO support and (43%) survived, were discharged, and were alive at the time of the review. A total of 8 (57%) ECMO patients died during hospitalization. Although indications and type of support changed in some patients during their hospital course, the majority of patients required venovenous ECMO support for hypoxia (N = 9) versus venoarterial ECMO for hemodynamic support (N = 5) as initial indication. The mean length of stay among survivors was 42.2 ± 22 days. Severe RV dysfunction was present preoperatively among 6 patients in the nonsurvivors group (75%) and 2 in the survivors group (33%). The overall mean duration of ECMO support was 7.3 ± 5.3 days (8.3 ± 7.3 days among survivors and 6.5 ± 3.5 days among nonsurvivors). Four patients died while on ECMO.
Although still associated with high morbidity and mortality, ECMO appears to be an important treatment adjunct providing additional time for healing and recovery of cardiopulmonary function in patients who develop severe hypoxemia or right ventricular failure after PEA.

View all citing articles on Scopus

: Supported in part by grants from the John A. Hartford Foundation, Inc., and the National Heart and Lung Institute (HL14169).

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Chest

Successful Surgical Intervention in Severe Chronic Thromboembolic Pulmonary Hypertension

Section snippets

CASE REPORT

DISCUSSION

ACKNOWLEDGMENT

J Thorac Cardiovasc Surg

Am J Med

Am J Med

Am J Med

A survey of the current status of pulmonary embolectomy for massive pulmonary embolism

Circulation (Suppl 1)

Limitations in the feasibility of pulmonary embolectomy

Circulation

Rapid resolution of pulmonary thromboemboli in man

JAMA

Observations on the fate of large pulmonary emboli

Am J Roentgenol, Radium Ther Nucl Med

Experimental pulmonary embolism with serum-induced thrombi

Am J Pathol

Chronic unilateral pulmonary artery thrombosis: Successful thromboendarterectomy with thirty-month follow-up

N Engl J Med