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Balloon angioplasty and stent placement for pulmonary arterial stenoses in children are well-established therapies. In contrast, management of isolated peripheral pulmonary arterial stenoses in adults remains relatively unexplored. Four women (ages 18-63 years) with multiple discrete intralobar pulmonary arterial stenoses were treated with balloon angioplasty. Initially, 4-5 stenoses were dilated in each patient. The mean minimum diameter of the stenoses increased from 1.3 to 3.1 mm (P < 0.001), and the mean ratio of right ventricular to aortic systolic pressure decreased from 0.92 to 0.62 (P < 0.05). Each patient had marked symptomatic improvement. However, three patients developed recurrence of symptoms 4-24 months after angioplasty, and two had angiographic evidence of restenosis at previously dilated sites. These restenoses were treated with repeat angioplasty or stent implantation (three stents in each patient). One of these two patients developed near-occlusive restenosis of the stents and had successful bilateral lung transplantation. The other patient had a third catheterization with successful implantation of three additional stents. The third patient with recurrent symptoms died 2 years later, without further intervention. Transcutaneous catheter therapy for multiple intralobar pulmonary arterial stenoses in adults is highly successful acutely, but restenosis is common within several months. For some patients, balloon angioplasty and stent implantation may provide definitive management, while for others these procedures may serve as a bridge to lung transplantation.

Chronic thromboembolic obstruction of the major pulmonary arteries is an underrecognized sequela of acute pulmonary embolism. Depending on the burden and location of thrombus, as well as on the duration of vessel obstruction, chronic thromboembolic disease may lead to pulmonary hypertension and cor pulmonale. Chronic thromboembolic disease affects an estimated 500 to 2500 patients each year in the United States, roughly 0.1 to 0.5 percent of patients who survive acute pulmonary embolism. Consequently, while this disease is uncommon, chronic thromboembolic pulmonary hypertension (CTEPH) is not rare, and should be considered in patients with unexplained dyspnea, as it is potentially correctible with pulmonary thromboendarterectomy.1

Five physicians addressed important issues in the diagnosis and management of patients with pulmonary thromboembolic disease. The roundtable discussion was moderated by Victor F. Tapson, MD, Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, and included William Auger, MD, Professor of Clinical Medicine, University of California, San Diego, Medical Center, San Diego, California; Peter Fedullo, MD, Clinical Professor of Medicine, University of California, San Diego, Medical Center; Eckhard Mayer, MD, Professor of Thoracic Surgery, Department of Cardio-Thoracic Surgery, University Hospital, Mainz, Germany; and Christopher McGregor, MD, Professor of Surgery, Consultant in Cardio-Thoracic Surgery, and Director of the Mayo Clinic William J von Liebig Transplant Center, Rochester, Minnesota.

In their 1993 report, Moser and Bloor [1] described an array of microvascular “pulmonary hypertensive” lesions in patients with operable chronic thromboembolic disease. Although it was concluded that these findings in any one patient did not “preclude a positive haemodynamic and clinical result”, these early observations became the foundation of our current understanding of the evolution of pulmonary hypertension and right heart failure, following the establishment of proximal vessel, occlusive organised thromboembolic disease [2, 3]. Despite the significance and role of the microcirculation in chronic thromboembolic pulmonary hypertension (CTEPH), our understanding of the histopathology remains rather rudimentary [4] and previously confined to descriptions of the precapillary pulmonary …

Patients with pulmonary hypertension due to chronic thromboembolic disease benefit from pulmonary thromboendarterectomy. A subset of these patients present with concomitant coronary or valvular disease.From July 1990 to July 2000, 90 patients (68 males, 22 females, mean age 68 years) with pulmonary vascular resistance (PVR) ranging from 297 to 2261 dynes x sec x cm(-5) underwent pulmonary thromboendarterectomy in conjunction with coronary bypass grafting (59 patients), coronary artery bypass grafting/foramen ovale closure (24 patients), tricuspid annuloplasty (3 patients), mitral valve repair (2 patients), and aortic valve replacement (2 patients). The perioperative and hemodynamic outcomes of these patients were compared with the cohort of 1,100 isolated pulmonary thromboendarterectomies performed at our institution during this time.Overall perioperative survival (93.3%; 84 of 90 patients) and mean diminution in PVR (521 dynes x sec x cm(-5)) for patients undergoing combined operations were similar to those undergoing pulmonary thromboendarterectomy alone (94.2% survival; 1034 of 1100 patients; 547 dynes x sec x cm(-5) mean PVR reduction). Although patients undergoing combined operations were older (mean age 68 vs 50 years, p0.0001), had longer hospital stays (median 14 vs 9 days), and had worse left ventricular function (mean preoperative cardiac output 3.1 vs 4.4, p0.0001), there was no difference in cross-clamp time, resolution of tricuspid regurgitation, or postoperative systolic function between these two groups.Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension may be performed safely in conjunction with other cardiac operations. Older patients evaluated for pulmonary thromboendarterectomy should be screened for concomitant coronary and valvular disease.

Pulmonary thromboendartectomy (PTE) for chronic thromboembolic pulmonary hypertension may be complicated by reperfusion lung injury. This has previously been demonstrated to be neutrophil-mediated. We postulated that blocking selectin-mediated adhesion of neutrophils to the endothelium with Cylexin (CY-1503) would prevent reperfusion lung injury in this patient population. In this double-blind, randomized, placebo-controlled, parallel study, 26 patients received Cylexin the day of surgery and 25 received placebo. Significantly fewer patients in the treated group (31%) compared with the placebo group (60%) developed lung injury (p = 0.036). However, the average number of days of mechanical ventilation, days in the intensive care unit (ICU) and hospital, as well as mortality were not significantly different between the treatment groups. Those with reperfusion lung injury had significantly elevated percent neutrophils, total protein, and soluble P-selectin in bronchoalveolar lavage fluid compared with those without lung injury. We conclude that reperfusion lung injury after PTE is a high-permeability lung injury and its incidence can be reduced by the administration of Cylexin on the day of surgery.

We sought to identify imaging features that help predict surgical success in patients undergoing thromboendarterectomy.Thirty-nine consecutive patients who underwent pulmonary angiography and thromboendarterectomy during 1995 and 1996 were included. Thirty-four underwent helical CT angiography. Measurements of postoperative pulmonary vascular resistance were compared with preoperative imaging features and preoperative pulmonary vascular resistance.The best imaging indicators of a relatively high postoperative pulmonary vascular resistance were the extent of small vessel disease identified on CT angiograms as segments with abnormal perfusion but normal segmental arteries (p = 0.005) and the extent of central disease (p = 0.015). Combined with preoperative pulmonary vascular resistance, these features had a strong correlation with postoperative outcome (p = 0.0005). Segmental arterial disease seen on both conventional angiography and CT angiography correlated poorly with surgical outcome.In patients with chronic thromboembolic pulmonary hypertension, CT angiographic evidence of extensive central vessel disease and limited small vessel involvement indicates a favorable surgical outcome.

Obstruction of major pulmonary vessels with organized thromboemboli is a rare sequelae of acute pulmonary embolic disease. Depending on the extent and duration of vascular occlusion, patients experiencing this unusual disorder may develop significant pulmonary hypertension and cor pulmonale. If left untreated, the ultimate clinical outcome is right heart failure and death. Over the past several decades, the description of this clinical entity has evolved from an autopsy curiosity to a recognized cause of chronic pulmonary hypertension. Also, during this same time period, surgical capabilities have greatly advanced, providing these patients a potentially life-saving remedy for this debilitating form of pulmonary vascular disease. This article provides a historical perspective for our current understanding of major vessel chronic thromboembolic pulmonary hypertension as a distinct clinical disorder. It also chronicles the developments in surgical techniques that have made thromboendarterectomy of the pulmonary arterial bed a reality.

Pulmonary thromboendarterectomy (PTE) surgery is an effective treatment for the majority of patients with chronic thromboembolic pulmonary hypertension (CTEPH), with an acceptable mortality rate. The immediate outcome after PTE has repeatedly shown a dramatic decline in pulmonary vascular resistance, echocardiographic evidence of reduced right heart pressure, and increased perfusion on lung scan. Prospective long-term follow-up studies (1 to 4 years post-PTE) have found most patients to be in New York Heart Association class I or II, with significantly improved quality of life and ability to walk, climb stairs, return to work, and perform household tasks. Disease-related symptoms and hospitalizations and/or emergency room visits have also been significantly reduced. These findings indicate an improved functional status and longer life expectancy can be achieved after PTE.

The postoperative course of the patient undergoing pulmonary thromboendarterectomy poses a unique series of challenges in terms of ventilatory care and hemodynamic management. Experience, cooperation, and interaction are necessary among the various disciplines providing care for these patients during the preoperative, operative, and postoperative phases of care. The purpose of this article is to share the approach necessary for the optimal postoperative care of the patient undergoing thromboendarterectomy, to present the theoretical justification for this care, and to delineate the areas of uncertainty that still exist.

Patients with sickle cell disease have been reported to have an increased risk of thromboembolism and pulmonary hypertension. Some of these patients may benefit from pulmonary thromboendarterectomy (PTE), a procedure that requires profound hypothermia, cardiopulmonary bypass, and periods of circulatory arrest, factors that may potentially increase the risk of sickling. Two patients with sickle cell disease (sickle-thalassemia [Hb S/beta+] and Hb SS) presented to the Pulmonary Vascular Center of UCSD Medical Center with significant shortness of breath and limitation of daily activities. Both of these patients were found to have surgically accessible chronic thromboembolic disease with pulmonary hypertension. PTE was performed in both patients using exchange transfusion, with avoidance of anemia, hypoxia, and acidosis. A successful outcome with resolution of pulmonary hypertension was achieved in both cases. To our knowledge this is the first report of patients with sickle cell disease who successfully underwent PTE for chronic thromboembolic pulmonary hypertension.

Background Although studies have found diminished aortic root motion in left ventricular systolic dysfunction, few data exist on aortic root excursion in isolated right ventricular dysfunction due to chronic thromboembolic pulmonary hypertension (CTEPH). Objective We conducted this study to evaluate aortic root excursion in CTEPH. Methods We studied 20 consecutive patients with CTEPH, normal left ventricular ejection fraction and pulmonary capillary wedge pressures, and 10 normal control subjects. Anterior excursion of the aortic root was measured using M-mode echocardiography as the difference between the maximal and minimal anterior distance of the posterior wall of the aortic root at the level of the aortic valve. Results Mean aortic excursion for CTEPH patients was approximately half that of normal controls (0.66 ± 0.25 cm vs. 1.16 ± 0.15 cm, P

The finding of a restrictive pulmonary defect may divert clinicians from considering the diagnosis of chronic thromboembolic pulmonary hypertension because lung volumes are usually normal in this disorder. We have, however, encountered a significant number of these patients with reduced lung volumes. Furthermore, we have observed many patients who have developed parenchymal scars and/or pleural thickening. To determine whether such findings are associated with lung volume restriction, we analyzed patients evaluated at our institution for chronic thromboembolic pulmonary hypertension over a 20-month period in whom thoracic high-resolution CT scans and pulmonary function testing had been performed. Patients with obstructive or restrictive lung disease from another cause were excluded. We compared the presence of lung restriction (total lung capacity below 80% of predicted) with the extent of parenchymal scarring, pleural thickening, and pulmonary artery diameter on CT scans. Of 191 patients evaluated, 51 met criteria for entry. Eleven patients (22%) had lung restriction. Parenchymal scarring was highly associated with lung restriction (p=0.01). Neither pleural thickening (p=0.08) nor pulmonary artery diameter (p=0.80) was associated with lung restriction. Conclusions A significant number of patients with chronic thromboembolic pulmonary hypertension may have restrictive lung defects. The restriction may be due to parenchymal scarring.

Background Inhaled nitric oxide (NO) has been shown to be a selective pulmonary vasodilator in certain patients with primary pulmonary hypertension (PPH). Objectives The purpose of this study was to design and test a system for delivery of NO to awaken, ambulatory patients with PPH and to evaluate this system in the home setting. Methods The ambulatory delivery system consisted of a tank of 80 ppm of NO (balance N 2 ), a modified gas-pulsing device, and nasal cannulas. The pulsing device was set to deliver NO for 0.1 s at the beginning of each inspiration. Results Using this system, eight patients with PPH were studied with pulmonary artery catheters in place. Inhalation of NO led to significant reductions in both mean pulmonary arterial pressure (PAPm) (51±12 to 43±10 mm Hg; p=0.001) and pulmonary vascular resistance (PVR) (790±285 to 620±208 dyne·s·cm −5 ; p=0.01). Three of the eight patients had both greater than 20% and greater than 30% decreases in PAPm and PVR, respectively. No exhaled NO or NO 2 was detectable in any of the eight patients. One patient was discharged home from the hospital on a regimen of inhaled NO. At 9 months, no adverse effects were noted and the system was working well. Conclusions Pulsed delivery of inhaled NO to ambulatory patients with PPH, via nasal prongs, is feasible and, in some patients, leads to significant improvement in pulmonary hypertension. Inhaled 09NO, therefore, may have a role in the long-term treatment of patients with PPH.

Rationale and Objectives. We evaluated the accuracy of contrast-enhanced magnetic resonance (MR) angiography in demonstrating the findings of chronic pulmonary thromboembolism (CPTE) compared with conventional pulmonary angiography. Methods. We examined 18 patients with CPTE proved by conventional pulmonary angiography and 16 healthy control patients. T1-weighted and single-breathhold, two-dimensional multiplanar spoiled gradient-recalled pulmonary images were obtained after injection of gadopentetate dimeglumine. Images were interpreted independently by two radiologists. Results. All patients with CPTE were identified on MR angiography images by both readers. Sensitivity and specificity for MR angiography in diagnosing abnormal segments were 76% and 95% for reader 1 and 68% and 93% for reader 2, respectively. Sensitivity and specificity for MR angiography in depicting abnormal lobes were 83% and 96% for reader 1 and 82% and 93% for reader 2, respectively. Interobserver agreement was high; kappas for abnormal segments and abnormal lobes were .72 and .84, respectively. The T1-weighted spin-echo images demonstrated a mosaic signal intensity pattern in all patients with CPTE. Conclusion. Contrast-enhanced MR angiography accurately depicts abnormal segments and lobes in occlusive vascular disease and clearly distinguishes between patients with CPTE and those with healthy lungs.

PURPOSE : An increased occurrence of thrombotic events has been described in patients exhibiting a lupus anticoagulant (LA). In patients with chronic, major vessel thromboembolic pulmonary hypertension, not only has there been a relatively high frequency of the LA, but also an unexpected association with heparin-related thrombocytopenia. This retrospective report emphasizes the frequency of this association. PATIENTS AND METHODS : We retrospectively reviewed the medical records of 216 patients admitted to the University of California, San Diego, Medical Center who were being considered for surgical correction of their chronic thromboembolic pulmonary hypertension. For each patient, the following information was sought : presence of an LA, variation in platelet numbers during the preoperative evaluation, and determination of whether an observed thrombocytopenia was related to heparin use. RESULTS : An LA was found in 23 of the 216 patients (10.6%). Of the remaining patients, sufficient platelet data for comparison were available for 68 patients. These 68 patients constituted the control group. Within the LA group, platelet counts during the preoperative evaluation declined to 51.6% ± 16.7% of baseline counts, a highly significant difference (P

Patients on mechanical ventilation are occasionally hard to wean because of fatigue and/or depression. It is difficult to diagnose depression in this population, and treatment with traditional antidepressants has too slow an onset to be useful. Two cases are presented which suggest the possible utility of psychostimulants in this setting.

Studies have shown that left ventricular cardiac power output (CPO) is a measure of global cardiac function and a predictor of cardiogenic shock mortality. The utility of right ventricular (RV) CPO, however, is unclear. Our aim was to investigate RV CPO in patients with chronic thromboembolic

Background We sought to determine the efficacy and safety of perioperative treatment with methylprednisolone on the development of lung injury after pulmonary thromboendarterectomy. Methods This was a randomized, prospective, double-blind, placebo-controlled study of 98 adult patients with chronic thromboembolic pulmonary hypertension who were undergoing pulmonary thromboendarterectomy at a single institution. The patients received either placebo (n = 47) or methylprednisolone (n = 51) (30 mg/kg in the cardiopulmonary bypass prime, 500 mg IV bolus following the final circulatory arrest, and 250 mg IV bolus 36 h after surgery). The primary end point was the presence of lung injury as determined by two independent, blinded physicians using prospectively defined criteria. The secondary end points included ventilator-free, ICU-free, and hospital-free days and selected levels of cytokines in the blood and in BAL fluid. Results The incidence of lung injury was similar in both treatment groups (45% placebo, 41% steroid; P = .72). There were no statistical differences in the secondary clinical end points between treatment groups. Treatment with methylprednisolone, compared with placebo, was associated with a statistically significant reduction in plasma IL-6 and IL-8, a significant increase in plasma IL-10, and a significant reduction in postoperative IL-1ra and IL-6, but not IL-8 in BAL fluid obtained 1 day after surgery. Conclusions Perioperative methylprednisolone does not reduce the incidence of lung injury following pulmonary thromboendarterectomy surgery despite having an antiinflammatory effect on plasma and lavage cytokine levels.

A program to alleviate chronic, major vessel thromboembolic pulmonary hypertension by pulmonary thromboendarterectomy was initiated at this institution in 1970. Multiple evolutionary changes in the diagnostic evaluation, surgical approach, and postoperative management have been implemented over the series of 323 thromboendarterectomies performed through March 1992. A sequence of five surgeons at the University of California at San Diego have performed these procedures, with the last 150 having been performed by one surgeon. We report here the changes in surgical approach developed over the last 150 cases and the results obtained. The operation involves a median sternotomy incision, the institution of cardiopulmonary bypass, and deep hypothermia with circulatory arrest periods. Incisions are made in both pulmonary arteries into the lower lobe branches. Pulmonary thromboendarterectomy is always bilateral, with removal of both organized thrombus and an endarterectomy plane from all involved vessels. The right atrium is routinely explored for atrial septal defects. Current techniques appear to allow more thorough revascularization and shorter circulatory arrest times. The surgical mortality of 8.7% over this span is below that previously reported from this and other institutions. Among survivors, the hemodynamic and functional results have been excellent. Surgically correctable chronic thromboembolic pulmonary hypertension likely remains underdiagnosed. The diagnostic, surgical, and postoperative management evolution provided by the coordinated team involved at this institution has established that pulmonary thromboendarterectomy can be performed with an acceptable risk and good hemodynamic and symptomatic results.

Considerable advances have been made in the diagnostic approach and surgical management of patients afflicted with chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH occurs in a minority of patients following a single or recurrent episode of pulmonary embolism. Although incidence figures 3.1% following a single episode of pulmonary embolism and 13.4% following a recurrent venous thromboembolism have been reported, these figures would appear to substantially overstate the true incidence. Recent series suggest an incidence of 0.8–1.0%, a rate somewhat more consistent with the annual number of patients experiencing pulmonary embolism and the number of pulmonary thromboendarterectomy (PTE) procedures performed in the USA. Given what appears to be a large number of patients with persistent postembolic pulmonary vascular obstruction, it also remains uncertain why only a relatively small number develop pulmonary hypertension and what factors determine the initiation and progression of their disease. Although the overall extent of pulmonary vascular obstruction appears to play a central role in the initiation, there is a growing body of evidence to suggest that the increa­sing pulmonary vascular resistance (PVR) in the majority of patients arises from events in the distal pulmonary vascular bed rather than from central obstruction. That the progression of the pulmonary hypertension is a consequence of this distal arteriopathy is supported by several lines of evidence. What is not subject to debate is that survival without intervention is poor and, as in other forms of pulmonary hypertension, is proportional to the degree of pulmonary hypertension and right ventricular dysfunction at the time of diagnosis.

HEN DISCUSSING heart failure, the left ventricle normally takes center stage, and the right ventricle (RV) can become an afterthought. However, in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH), the RV takes the lead role. These patients can present with increased right ventricular oxygen consumption with a concomitant decrease in right ventricular oxygen supply, placing them at high risk for right ventricular ischemia and failure. Fortunately, after a pulmonary thromboendarterectomy (PTE), rightheart hemodynamics greatly improve in most CTEPH patients, and right ventricular perfusion is no longer an issue. The authors, however, present a case discussing the management of a patient with severe pulmonary hypertension (PH) undergoing a PTE with residual severe PH even after their PTE.

Background Echocardiographic evaluation of left ventricular (LV) strain and strain rate (SR) by 2D speckle tracking may be useful tools to assess chronic thromboembolic pulmonary hypertension (CTEPH) severity as well as response to successful pulmonary thromboendarterectomy (PTE). Methods We evaluated 30 patients with CTEPH before and after PTE using 2D speckle tracking measurements of LV radial and circumferential strain and SR in the short axis, and correlated the data with right heart catheterization (RHC). Results PTE resulted in a decrease in mean PA pressure (44 ± 15 to 29 ± 9 mmHg), decrease in PVR (950 ± 550 to 31 ± 160 [dyne-sec]/cm5), and an increase in cardiac output (3.9 ± 1.0 to 5.0 ± 1.0 L/min, p < 0.001 for all). Circumferential and posterior wall radial strain changed by -11% and +15% respectively (p < 0.001 for both). Circumferential SR and posterior wall radial SR changed by -7% and 6% after PTE. While the increase in posterior wall SR with PTE reached statistical significance (p = 0.04) circumferential SR did not (p = 0.07). In addition, septal radial strain and SR did not change significantly after PTE (p = 0.1 and 0.8 respectively). Linear regression analyses of circumferential and posterior wall radial strain and SR revealed little correlation between strain/SR measurements and PVR, mean PA pressure, or cardiac output. However, change in circumferential strain and change in posterior wall radial strain correlated moderately well with changes in PVR, mean PA pressure and cardiac output (r = 0.69, 0.76, and 0.51 for circumferential strain [p < 0.001 for all] and r = 0.7, 0.7, 0.45 for posterior wall radial strain [p = 0.001, 0.001, and 0.02, respectively]). Conclusions LV circumferential and posterior wall radial strain change after relief of pulmonary arterial obstruction in patients with CTEPH, and these improvements occur rapidly. These changes in LV strain may reflect effects from improved LV diastolic filling, and may be useful non-invasive markers of successful PTE.

The pulmonary angiograms of 250 patients evaluated for chronic thromboembolic pulmonary hypertension were reviewed. Pulmonary thromboendarterectomy was performed in each of these individuals, and the surgical findings were correlated with abnormal angiographic patterns. The pulmonary angiographic findings suggestive of chronic thromboembolic disease included "pouching" defects, webs or bands, intimal irregularities, abrupt vascular narrowing, and complete vascular obstruction. Pouching is reported by the authors to be a previously undescribed angiographic feature of this disease. Carefully obtained and properly interpreted pulmonary angiograms are necessary to confirm the diagnosis of operable chronic thromboembolic disease. Differential diagnostic possibilities should be considered prior to a decision to perform surgical correction.

Background— The currently recommended treatment for chronic thromboembolic pulmonary hypertension is pulmonary thromboendarterectomy (PTE). No convincing evidence for the use of pulmonary hypertensive medical therapy (PHT) exists in operable candidates. We sought to determine the prevalence of the use of PHT on referral for PTE and the effects on pre-PTE hemodynamics and post-PTE outcomes/hemodynamics. Methods and Results— We performed a retrospective analysis of chronic thromboembolic pulmonary hypertension patients referred for PTE during 2005–2007. The prevalence of PHT was determined for all patients referred to our institution. Hemodynamic and outcomes analysis involved only those undergoing PTE. Data included baseline demographics, PHT medication(s), dosage, duration of therapy, and time to referral. Hemodynamic data were acquired from the time of diagnosis, the time of referral visit, and after PTE. Outcomes included intensive care unit, hospital, and ventilator days; bleeding and infection rates; incidence of reperfusion lung injury; and in-hospital mortality. The control group (n=244) was compared with the PHT group (n=111); subgroups included monotherapy with bosentan, sildenafil, or epoprostenol and combination therapy. The prevalence of PHT significantly increased from 19.9% in 2005 to 37% in 2007. There was minimal benefit of treatment with PHT on pre-PTE mean pulmonary artery pressure, but its use was associated with a significant delay in time to referral for PTE. Both groups experienced significant improvements in hemodynamic parameters after PTE. The 2 groups did not differ significantly in any post-PTE outcome. Similar results were obtained for each subgroup. Conclusions— Our results suggest that PHT use has minimal effect on pre-PTE hemodynamics and no effect on post-PTE outcomes/hemodynamics.

The last 4 decades have witnessed dramatic changes in the treatment of patients with pulmonary hypertension. And with the advances in cardiothoracic surgical techniques, selected patients with chronic thromboembolic pulmonary hypertension (CTEPH) are afforded a surgical remedy for their disease. In the vast majority of these patients, surgical endarterectomy of chronic thromboemboli from the pulmonary vascular bed effectively treats even severe pulmonary hypertension, and as a result, the debilitating symptoms of right heart dysfunction. This article reviews the natural history of chronic thromboembolic disease and outline a suggested diagnostic approach to determine whether a patient with chronic thromboembolic disease might be an appropriate surgical candidate. Pulmonary thromboendarterectomy surgery, and the growing information on the use of pharmacotherapy in inoperable CTEPH, are also reviewed.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle α-actin (SM-αA)-positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34+Flk-1+) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34+Flk-1+CD133+cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45+) and collagen-secreting cells (procollagen-1+) were detected in the proximal vascular wall. Some of the CD34+cells in CTEPH cells isolated from proximal regions were also positive for SM-αA. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.

Context Ventilator-associated pneumonia (VAP) causes substantial morbidity. A silver-coated endotracheal tube has been designed to reduce VAP incidence by preventing bacterial colonization and biofilm formation. Objective To determine whether a silver-coated endotracheal tube would reduce the incidence of microbiologically confirmed VAP. Design, Setting, and Participants Prospective, randomized, single-blind, controlled study conducted in 54 centers in North America. A total of 9417 adult patients (≥18 years) were screened between 2002 and 2006. A total of 2003 patients expected to require mechanical ventilation for 24 hours or longer were randomized. Intervention Patients were assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal tubes, similar except for a silver coating on the experimental tube. Main Outcome Measures Primary outcome was VAP incidence based on quantitative bronchoalveolar lavage fluid culture with 10 4 colony-forming units/mL or greater in patients intubated for 24 hours or longer. Other outcomes were VAP incidence in all intubated patients, time to VAP onset, length of intubation and duration of intensive care unit and hospital stay, mortality, and adverse events. Results Among patients intubated for 24 hours or longer, rates of microbiologically confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI], 3.4%-6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95% CI, 5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%] [P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal tube was associated with delayed occurrence of VAP (P = .005). No statistically significant between-group differences were observed in durations of intubation, intensive care unit stay, and hospital stay; mortality; and frequency and severity of adverse events. Conclusion Patients receiving a silver-coated endotracheal tube had a statistically significant reduction in the incidence of VAP and delayed time to VAP occurrence compared with those receiving a similar, uncoated tube. Trial Registration clinicaltrials.gov Identifier: NCT00148642

Pulmonary thromboendarterectomy is being performed with increasing frequency for incapacitating pulmonary hypertension caused by chronic large-vessel pulmonary embolism. However, patient-related risk factors and procedural complications associated with morbidity and mortality have not been fully defined. From Oct. 1, 1984, to April 10, 1989, we performed pulmonary thromboendarterectomy using deep hypothermia and circulatory arrest in 127 consecutive patients (62.2% male, mean age 50 ± 16 [standard deviation], range 20 to 82 years) in whom the exposure and dissection of the pulmonary arteries and methods for myocardial protection have been standardized. End points for univariate and multivariate analyses of risk factors were reperfusion pulmonary edema leading to respiratory insufficiency as defined by ventilator dependency (≥5 days) (31.5%, 39/124) and hospital mortality (12.6%, 16/127). Multivariate analyses showed that ascites and need for 4 units of blood or more predicted ventilator dependency (p

s S159 W.R. Auger.1 1Division of Pulmonary and Critical Care, University of California, San Diego, La Jolla, CA; 2Division of Cardiothoracic Surgery, University of California, San Diego, La Jolla, CA. Purpose: The definitive treatment for chronic thromboembolic pulmonary hypertension remains a pulmonary endarterectomy (PEA) at an experienced surgical center. Despite this recommendation, many patients with surgically accessible disease are pre-treated with pulmonary arterial hypertension-targeted medications. The effects of such a strategy on post-operative outcomes are not well defined. Methods: We examined all patients who underwent PEA at UCSD from January 2011 through December 2013. Differences in outcomes were compared between patients pre-treated and those who were not using t-tests for continuous variables and chi-square tests for dichotomous variables. Logistic regression was used to determine odds of reperfusion lung injury. Results: Of the 438 patients who underwent surgery during this time period, 43.6% were pre-treated with any PAH medications. There was no significant difference in preoperative PVR between the two groups (671.9 vs. 656.5, untreated vs. pre-treated; p= 0.656), but the mean PA pressure (42.8 vs. 45.7, untreated vs. treated; p= 0.01) and cardiac output (4.35 vs. 4.79, untreated vs. pre-treated; p= 0.001) were higher in the pre-treated group. There were no differences in post-operative mortality (1.6% vs. 1.0%, untreated vs. pre-treated; p= 0.62) or residual pulmonary hypertension (7.3% vs. 11.6%, untreated vs. pre-treated; p= 0.14) between the two groups, but those pre-treated had a higher incidence of reperfusion lung injury (15.7% vs. 27.4%, untreated vs. pre-treated; p= 0.003). Adjusting for age, sex, BMI, preoperative right atrial pressure, cardiac output, mean PA pressure and PVR, the odds a pre-treated patient developed reperfusion lung injury were 2.46 times higher (95% CI: 1.44-4.20) than the odds a untreated patient developed lung injury. Conclusion: There was no difference in post-operative mortality or residual pulmonary hypertension between treated and untreated patients. Pre-treated patients had a higher rate of reperfusion lung injury, a risk that remained after adjusting known risk factors for reperfusion lung injury. These findings need to be corroborated in a prospective, randomized controlled trial of medical therapy before PEA.

Recent efforts have seen major advances in elucidating the mechanisms underlying pulmonary arterial hypertension. However, chronic thromboembolic pulmonary hypertension (CTEPH) often has been excluded from these studies. Consequently, whereas the clinical, radiographic, and hemodynamic characteristics of CTEPH have been well described, there remains a deficit in our understanding of the cellular, molecular, and genetic mechanisms underlying CTEPH. Furthermore, although prior venous thromboembolism may act as the inciting event, it is still unclear what predisposes some patients to develop CTEPH. CTEPH has two major pathogenic components. The first is the primary obstruction of central pulmonary arteries by accumulation of thrombotic material. The second is characterized by severe pulmonary vascular remodeling, similar to that seen in idiopathic pulmonary arterial hypertension. Other articles in this series describe the pathological, surgical, and therapeutic aspects of CTEPH. Here, we review the potential molecular and cellular mechanisms that may contribute to the pathogenesis of CTEPH.

Objective: The purpose of this study was to evaluate the accuracy and precision of a novel algorithm that evaluates cardiac output by using arterial pressure waveform characteristics. Design: Prospective, observational study comparing the cardiac output values of intermittent thermodilution, continuous thermodilution, and continuous arterial pressure wave assessment. Setting: The intensive care unit in a tertiary care university hospital. Participants: Fifty postoperative cardiac surgical patients, within the first 12 hours after surgery. Interventions: All patients received a pulmonary artery catheter (PAC) and at least 1 systemic arterial pressure catheter. The data from the arterial catheter were processed by using a new arterial pressure cardiac output (APCO) algorithm. The data from the PAC (continuous and intermittent assessments) were collected for comparison with the APCO. Measurements: Two hundred ninety-five cardiac output measurements using intermittent thermodilution (ICO), continuous thermodilution (CCO), and arterial pressure-based output (APCO) were obtained during various times during the first 12 postoperative hours. The measurements of each method at each time point were compared by using Bland-Altman analysis. Results: The mean cardiac output ranged from 2.77 to 9.60 L/min. APCO, compared with ICO, revealed a bias of 0.55 L/min and precision of 0.98 L/min. APCO, compared with CCO, revealed a bias of 0.06 L/min and precision of 1.06 L/min. The APCO agreement between femoral and radial arterial catheters was close; the bias was −0.15 L/min, and the precision was 0.56 L/min. Conclusions: This novel arterial pressure cardiac output algorithm provides cardiac output assessments that agree satisfactorily for clinical purposes with intermittent and continuous thermodilution techniques in postoperative cardiac surgical patients. Further study is required for other patient populations and clinical situations.

The purpose of this study was to investigate the cause of abnormal left ventricular (LV) Doppler diastolic filling characteristics in chronic thromboembolic pulmonary hypertension (CTEPH).In CTEPH, LV diastolic function often appears abnormal. It is unclear whether this "impaired relaxation" (EA) filling pattern is caused by septal hypertrophy, right ventricular (RV) enlargement and LV chamber distortion, or low LV preload and underfilling.We studied 61 patients with an EA transmitral pattern and CTEPH who underwent pulmonary thromboendarterectomy (PTE). We compared the results of pre- and postoperative transthoracic echocardiography and right heart catheterization measurements.After PTE, mitral E velocity increased (from 54 +/- 16 cm/s to 81 +/- 20 cm/s, p0.001), whereas A velocity decreased (77 +/- 22 cm/s to 71 +/- 20 cm/s, p0.001). E/A ratio normalized (0.72 +/- 0.16 cm/s to 1.22 +/- 0.40 cm/s, p0.001). Pulmonary venous systolic and diastolic velocities both increased (57 +/- 13 cm/s to 68 +/- 16 cm/s and 39 +/- 15 cm/s to 70 +/- 21 cm/s, respectively, p0.001 for both). Diastolic velocity of the septal mitral annulus (E(m)) did not change after PTE (8.0 +/- 3.1 cm/s to 8.1 +/- 2.0 cm/s, p = ns), whereas the velocity of the lateral mitral annulus increased (9.3 +/- 3.2 cm/s to 11.8 +/- 3.1 cm/s, p0.001). Mean pulmonary capillary wedge pressure increased from 9.3 +/- 3.2 mm Hg to 10.6 +/- 3.8 mm Hg (p = 0.035). Despite these marked changes in LV inflow, M-mode measurements of LV septal and posterior wall thickness were normal before PTE and did not change after surgery (septal: 10 +/- 2 mm vs. 10 +/- 1 mm; posterior: 10 +/- 2 mm vs. 10 +/- 1 mm; p = NS for both comparisons).The results of this study strongly suggest that the impaired relaxation pattern observed in patients with CTEPH is not solely the result of geometric effects of RV enlargement and LV chamber distortion but is caused in large part by low LV preload and relative underfilling.