Right Ventricular Function During Exercise After Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension.

Background Pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension improves resting hemodynamics and right ventricular (RV) function. Because exercise tolerance frequently remains impaired, RV function may not have completely normalized after PEA. Therefore, we performed a detailed invasive hemodynamic study to investigate the effect of PEA on RV function during exercise. Methods and Results In this prospective study, all consenting patients with chronic thromboembolic pulmonary hypertension eligible for surgery and able to perform cycle ergometry underwent cardiac magnetic resonance imaging, a maximal cardiopulmonary exercise test, and a submaximal invasive cardiopulmonary exercise test before and 6 months after PEA. Hemodynamic assessment and analysis of RV pressure curves using the single-beat method was used to determine load-independent RV contractility (end systolic elastance), RV afterload (arterial elastance), RV-arterial coupling (end systolic elastance-arterial elastance), and stroke volume both at rest and during exercise. RV rest-to-exercise responses were compared before and after PEA using 2-way repeated-measures analysis of variance with Bonferroni post hoc correction. A total of 19 patients with chronic thromboembolic pulmonary hypertension completed the entire study protocol. Resting hemodynamics improved significantly after PEA. The RV exertional stroke volume response improved 6 months after PEA (79±32 at rest versus 102±28 mL during exercise; P<0.01). Although RV afterload (arterial elastance) increased during exercise, RV contractility (end systolic elastance) did not change during exercise either before (0.43 [0.32-0.58] mm Hg/mL versus 0.45 [0.22-0.65] mm Hg/mL; P=0.6) or after PEA (0.32 [0.23-0.40] mm Hg/mL versus 0.28 [0.19-0.44] mm Hg/mL; P=0.7). In addition, mean pulmonary artery pressure-cardiac output and end systolic elastance-arterial elastance slopes remained unchanged after PEA. Conclusions The exertional RV stroke volume response improves significantly after PEA for chronic thromboembolic pulmonary hypertension despite a persistently abnormal afterload and absence of an RV contractile reserve. This may suggest that at mildly elevated pulmonary pressures, stroke volume is less dependent on RV contractility and afterload and is primarily determined by venous return and conduit function.

A modified perfusion protocol for pulmonary endarterectomy in a patient with a hematologic malignancy treated with a tyrosine kinase inhibitor.

Tyrosine kinase inhibitors (TKI) are known to be highly effective in the treatment of various cancers with kinase-domain mutations such as chronic myelogenous leukemia. However, they have important side effects such as increased vascular permeability and pulmonary hypertension. In patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest, these side effects may exacerbate postoperative complications such as reperfusion edema and persistent pulmonary hypertension. We report on a simple modification of the perfusion strategy to increase intravascular oncotic pressure by retrograde autologous priming and the addition of packed cells and albumin in a patient treated with a TKI.

Anticoagulation management during pulmonary endarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest.

INTRODUCTION: Pulmonary endarterectomy requires cardiopulmonary bypass and deep hypothermic circulatory arrest, which may prolong the activated clotting time. We investigated whether activated clotting time-guided anticoagulation under these circumstances suppresses hemostatic activation. METHODS: Individual heparin sensitivity was determined by the heparin dose-response test, and anticoagulation was monitored by the activated clotting time and heparin concentration. Perioperative hemostasis was evaluated by thromboelastometry, platelet aggregation, and several plasma coagulation markers. RESULTS: Eighteen patients were included in this study. During cooling, tube-based activated clotting time increased from 719 (95% confidence interval = 566-872 seconds) to 1,273 (95% confidence interval = 1,136-1,410 seconds; p < 0.01) and the cartridge-based activated clotting time increased from 693 (95% confidence interval = 590-796 seconds) to 883 (95% confidence interval = 806-960 seconds; p < 0.01), while thrombin-antithrombin showed an eightfold increase. The heparin concentration showed a slightly declining trend during cardiopulmonary bypass. After protamine administration (protamine-to-heparin bolus ratio of 0.82 (0.71-0.90)), more than half of the patients showed an intrinsically activated coagulation test and intrinsically activated coagulation test without heparin effect clotting time >240 seconds. Platelet aggregation through activation of the P2Y12 (adenosine diphosphate test) and thrombin receptor (thrombin receptor activating peptide-6 test) decreased (both -33%) and PF4 levels almost doubled (from 48 (95% confidence interval = 42-53 ng/mL) to 77 (95% confidence interval = 71-82 ng/mL); p < 0.01) between weaning from cardiopulmonary bypass and 3 minutes after protamine administration. CONCLUSION: This study shows a wide variation in individual heparin sensitivity in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest. Although activated clotting time-guided anticoagulation management may underestimate the level of anticoagulation and consequently result in a less profound inhibition of hemostatic activation, this study lacked power to detect adverse outcomes.

Anatomic Suitability for Branched Thoracic Endovascular Repair in Patients with Aortic Arch Pathological Features.

Background Endovascular repair has become a viable alternative for aortic pathological features, including those located within the aortic arch. We investigated the anatomic suitability for branched thoracic endovascular repair in patients previously treated with conventional open surgery for aortic arch pathological features. Methods and Results Patients who underwent open surgery for aortic arch pathological features at our institution between 2000 and 2018 were included. Anatomic suitability was determined by strict compliance with the anatomic criteria within manufacturers' instructions for use for each of the following branched thoracic stent grafts: Relay Plus Double-Branched (Terumo-Aortic), TAG Thoracic Branch Endoprosthesis (W.L. Gore & Associates), Zenith Arch Branched Device (Cook-Medical), and Nexus Stent Graft System (Endospan Ltd/Jotec GmbH). Computed tomography angiography images were analyzed with outer luminal line measurements. A total of 377 patients (mean age, 64±14 years; 64% men) were identified, 153 of whom had suitable computed tomography angiography images for measurements. In total, 59 patients (15.6% of the total cohort and 38.6% of the measured cohort) were eligible for endovascular repair using at least one of the devices. Device suitability was 30.9% for thoracic aneurysms, 4.6% for type A dissections, 62.5% for type B dissections, and 28.6% for other pathological features. Conclusions The anatomic suitability for endovascular repair of all aortic arch pathological features was modest. The highest suitability rates were observed for thoracic aneurysms and for type B dissections, of which repair included part of the aortic arch. We suggest endovascular repair of arch pathological features should be reserved for high-volume centers with experience in endovascular arch repair.

Management of Multiple Secreting Paragangliomas in a Succinate Dehydrogenase Subunit D (SDHD) Variant Carrier.

Management of functional intrathoracic sympathetic paragangliomas in succinate dehydrogenase subunit D (SDHD) mutation carriers is challenging, and there is no uniform guideline for treatment to date. The risks of potential malignant behavior and long-term cardiovascular morbidity have to be weighed against the risks of treatment complications. We report the multidisciplinary and shared decision-making approach that resulted in successful surgical removal of 3 paragangliomas in a SDHD mutation carrier.

[Salvage surgery for locally recurrent lung cancer: options for patients who have been treated with high dose radiotherapy]. / 'Salvage'-chirurgie voor lokaal recidief longcarcinoom.

A combination of chemotherapy and high dose radiotherapy is the cornerstone of the treatment of locally-advanced non-small cell lung cancer (NSCLC). For selected patients with early stage NSCLC, stereotactic body radiation therapy (SBRT, also known as SABR, stereotactic ablative radiotherapy) is a good option. Unfortunately, metastases can occur in patients following these treatments. However, in some patients, the recurrence remains localized to the previous irradiated area, so-called local recurrence. For selected patients with such a recurrence, radical salvage surgery - a treatment modality with curative intent - is an option. In this article we describe two patients with local recurrence after high dose radiotherapy, who were subsequently treated operatively. We also discuss which subset of lung cancer patients should be selected for this type of surgery.

Diagnostic evaluation and treatment strategy in patients with suspected prosthetic heart valve dysfunction: The incremental value of MDCT.

BACKGROUND: In patients with suspected prosthetic heart valve (PHV) dysfunction, routine evaluation echocardiography and fluoroscopy may provide unsatisfactory results for identifying the cause of dysfunction. This study assessed the value of MDCT as a routine, complementary imaging modality in suspected PHV-dysfunction for diagnosing the cause of PHV dysfunction and proposing a treatment strategy. METHODS: Patients with suspected PHV dysfunction were prospectively recruited. All patients underwent routine diagnostic work-up (TTE, TEE ± fluoroscopy) and additional MDCT imaging. An expert panel reviewed all cases and assessed the diagnosis and treatment strategy, first based on routine evaluation only, second with additional MDCT information. RESULTS: Forty-two patients were included with suspected PHV obstruction (n = 30) and PHV regurgitation (n = 12). The addition of MDCT showed incremental value to routine evaluation in 26/30 (87%) cases for detecting the specific cause of PHV obstruction and in 7/12 (58%) regurgitation cases for assessment of complications and surgical planning. The addition of MDCT resulted in treatment strategy change in 8/30 (27%) patients with suspected obstruction and 3/12 (25%) patients with regurgitation. CONCLUSION: In addition to echocardiography and fluoroscopy, MDCT may identify the cause of PHV dysfunction and alter the treatment strategy.

Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension.

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 µM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients.

Baseline MDCT findings after prosthetic heart valve implantation provide important complementary information to echocardiography for follow-up purposes.

OBJECTIVES: Recent studies have proposed additional multidetector-row CT (MDCT) for prosthetic heart valve (PHV) dysfunction. References to discriminate physiological from pathological conditions early after implantation are lacking. We present baseline MDCT findings of PHVs 6 weeks post implantation. METHODS: Patients were prospectively enrolled and TTE was performed according to clinical guidelines. 256-MDCT images were systematically assessed for leaflet excursions, image quality, valve-related artefacts, and pathological and additional findings. RESULTS: Forty-six patients were included comprising 33 mechanical and 16 biological PHVs. Overall, MDCT image quality was good and relevant regions remained reliably assessable despite mild-moderate PHV-artefacts. MDCT detected three unexpected valve-related pathology cases: (1) prominent subprosthetic tissue, (2) pseudoaneurysm and (3) extensive pseudoaneurysms and valve dehiscence. The latter patient required valve surgery to be redone. TTE only showed trace periprosthetic regurgitation, and no abnormalities in the other cases. Additional findings were: tilted aortic PHV position (n = 3), pericardial haematoma (n = 3) and pericardial effusion (n = 3). Periaortic induration was present in 33/40 (83 %) aortic valve patients. CONCLUSIONS: MDCT allowed evaluation of relevant PHV regions in all valves, revealed baseline postsurgical findings and, despite normal TTE findings, detected three cases of unexpected, clinically relevant pathology. KEY POINTS: • Postoperative MDCT presents baseline morphology relevant for prosthetic valve follow-up. • 83 % of patients show periaortic induration 6 weeks after aortic valve replacement. • MDCT detected three cases of clinically relevant pathology not found with TTE. • Valve dehiscence detection by MDCT required redo valve surgery in one patient. • MDCT is a suitable and complementary imaging tool for follow-up purposes.

Feasibility of 3-dimensional video-assisted thoracic surgery (3D-VATS) for pulmonary resection.

BACKGROUND: Two-dimensional video-assisted thoracic surgery (2D-VATS) has gained its position in daily practise. Although very useful, its two-dimensional view has its drawbacks when performing pulmonary resections. We report our first experience with 3-dimensional video-assisted surgery (3D-VATS). Advantages and differences with 2D-VATS and robotic surgery (RS) are discussed. METHODS: To evaluate feasibility, we scheduled patients for surgery by 3D-VATS who would normally be treated with 2D-VATS. The main difference of the equipment in 3D-VATS compared with former VATS equipment, is the flexible camera-tip (100-degrees) and the necessary 3D-glasses. RESULTS: Four patients were successfully operated for anatomic pulmonary resections. On-the-structure dissection was easily performed and with the flexible camera-tip, a perfect view can be obtained, with clear visualisation of important (hilar) structures. These features highly facilitate the surgeon in tissue preparation and recognition of the dissection planes. CONCLUSION: In our opinion, 3D-VATS is superior to 2D-VATS for performing anatomic pulmonary resection and we expect an improvement in terms of operation time and learning curve. Furthermore, it is a valuable alternative for RS at lower costs.

Multidetector-row computed tomography for prosthetic heart valve dysfunction: is concomitant non-invasive coronary angiography possible before redo-surgery?

OBJECTIVES: Retrospective ECG-gated multidetector-row computed tomography (MDCT) is increasingly used for the assessment of prosthetic heart valve (PHV) dysfunction, but is also hampered by PHV-related artefacts/cardiac arrhythmias. Furthermore, it is performed without nitroglycerine or heart rate correction. The purpose was to determine whether MDCT performed before potential redo-PHV surgery is feasible for concomitant coronary artery stenosis assessment and can replace invasive coronary angiography (CAG). METHODS: PHV patients with CAG and MDCT were identified. Based on medical history, two groups were created: (I) patients with no known coronary artery disease (CAD), (II) patients with known CAD. All images were scored for the presence of significant (>50 %) stenosis. CAG was the reference test. RESULTS: Fifty-one patients were included. In group I (n = 38), MDCT accurately ruled out significant stenosis in 19/38 (50 %) patients, but could not replace CAG in the remaining 19/38 (50 %) patients due to non-diagnostic image quality (n = 16) or significant stenosis (n = 3) detection. In group II (n = 13), MDCT correctly found no patients without significant stenosis, requiring CAG imaging in all. MDCT assessed patency in 16/19 (84 %) grafts and detected a hostile anatomy in two. CONCLUSION: MDCT performed for PHV dysfunction assessment can replace CAG (100 % accurate) in approximately half of patients without previously known CAD. KEY POINTS: • Retrospective MDCT is increasingly used for prosthetic heart valve dysfunction assessment • In case of PHV reoperation, invasive coronary angiography is also required • MDCT can replace CAG in 50 % of patients without coronary artery disease • When conclusive for coronary assessment, MDCT stenosis rule out is highly accurate • Replacing CAG saves associated risks of distant embolization of thrombi or vegetations.

The impact of a new model-based iterative reconstruction algorithm on prosthetic heart valve related artifacts at reduced radiation dose MDCT.

To assess the impact of hybrid iterative reconstruction (IR) and novel model-based iterative reconstruction (IMR) and dose reduction on prosthetic heart valve (PHV) related artifacts and objective image quality. One transcatheter and two mechanical PHVs were embedded in diluted contrast-gel, inserted in an anthropomorphic phantom and imaged stationary with retrospectively ECG-gated computed tomography. Eight acquisitions were obtained of each PHV at 120 kV, 600 mAs (routine), 300 and 150 mAs (reduced dose). Data were reconstructed with filtered back projection (FBP), IR and IMR. Hypodense and hyperdense artifact volumes were quantified using two threshold filters. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Artifact volumes differed significantly between reconstruction algorithms for all PHVs (P < 0.005). Compared to FBP, IR decreased overall hypodense and hyperdense artifact volumes; at 150 mAs by 53 and 20 % (IR) and 67 and 23 % (IMR), respectively and significantly increased SNR and CNR at all doses (P < 0.012). Even at reduced dose, IMR resulted in higher image quality than routine dose FBP and IR. Iterative reconstruction and particularly IMR significantly reduce PHV-related artifacts and improve objective image quality in non-pulsatile conditions, even in reduced-dose images. Also, this study suggests that IMR allows for more radiation dose reduction in comparison to hybrid IR while maintaining high image quality.

Comparison of multidetector-row computed tomography to echocardiography and fluoroscopy for evaluation of patients with mechanical prosthetic valve obstruction.

For evaluation of prosthetic heart valve obstruction echocardiography and fluoroscopy provide primarily functional information but may not unequivocally establish the cause of dysfunction. Our objective was to evaluate whether multidetector-row computed tomographic (MDCT) imaging could detect the morphologic substrate for such functional abnormalities. Thirteen patients with 15 prosthetic valves, in whom prosthetic valve obstruction was suspected from echocardiography or fluoroscopy but no sufficient cause could be found, underwent electrocardiographically gated multidetector-row computed tomography. MDCT data were retrospectively reconstructed at every 10% of the electrocardiographic interval and analyzed using multiplanar reformatting in anatomically adapted planes. MDCT images were evaluated for morphologic prosthetic and periprosthetic abnormalities. Results could be compared to intraoperative findings or autopsy in 7 patients. Multidetector-row computed tomography disclosed a morphologic substrate for obstruction in 8 of 13 patients. MDCT findings compatible with obstruction were confirmed at surgery or autopsy in 6 patients. In a seventh patient, incomplete leaflet closure found with multidetector-row computed tomography was confirmed at surgery. The most commonly identified causes for obstruction were subprosthetic tissue (6 patients) and abnormal anatomic orientation (3 patients). Despite an indication for surgery, 2 patients were not operated on due to recurrent bacteremias and prohibitive co-morbidity. Multidetector-row computed tomography detected leaflet motion restriction in 7 patients compared to 4 by fluoroscopy. Confirmation of leaflet restriction was available in 5 patients. Multidetector-row computed tomography missed a periprosthetic leak. In conclusion, this initial experience demonstrates that multidetector-row computed tomography can identify causes of prosthetic valve obstruction that constitute indications for surgery but are missed at echocardiography or fluoroscopy.