Evaluation and management of patients with chronic thromboembolic pulmonary hypertension - consensus statement from the ISHLT.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence.

Advances in targeted therapy for chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by unresolved thrombi in the pulmonary arteries and microvasculopathy in nonoccluded areas. If left untreated, progressive pulmonary hypertension will induce right heart failure and, finally, death. Currently, pulmonary endarterectomy (PEA) remains the only method that has the potential to cure CTEPH. Unfortunately, up to 40% of patients are ineligible for this procedure for various reasons. In recent years, refined balloon pulmonary angioplasty (BPA) has become an alternative option for inoperable CTEPH patients, and it may be another curative treatment in the future, particularly in combination with prior PEA. Nevertheless, 23% of patients still suffer from persistent PH after BPA. Given that CTEPH shares many similarities with idiopathic pulmonary arterial hypertension (PAH), targeted drugs developed for PAH are also attractive options for CTEPH, especially for inoperable or persistent/recurrent CTEPH patients. To date, riociguat, macitentan, and subcutaneous treprostinil are the only drugs proven by randomized control trials to be capable of improving the exercise capacity (6-min walking distance) of CTEPH patients. In this review, we summarize the achievements and unresolved problems of PAH-targeted therapy for CTEPH over the last decade.

Evaluation of the Clinical Utility of Transesophageal Echocardiography and Invasive Monitoring to Assess Right Ventricular Function During and After Pulmonary Endarterectomy.

OBJECTIVE: Patients undergoing pulmonary endarterectomy (PEA) have impaired right ventricular function. The authors sought to assess the clinical utility of commonly used perioperative echocardiographic and right heart catheter measurements in patients undergoing PEA. DESIGN: A single-center prospective observational study. SETTING: The study was conducted in a quaternary care cardiac surgical center in the United Kingdom. PARTICIPANTS: Patients undergoing PEA between April 2015 and January 2016. INTERVENTIONS: Thermodilution cardiac index and echocardiography variables were measured at 3 time points: before sternotomy (T1), after pericardial incision (T2), and after sternal closure (T3). Six-month follow-up echocardiography and 6-minute walk (6-MWT) test were performed. MEASUREMENTS AND MAIN RESULTS: Fifty patients were recruited and complete data sets were available for 41 patients. Tricuspid annular plane systolic excursion declined after pericardial incision and cardiopulmonary bypass (T1: 15 ± 4 mm, T2: 13 ± 4 mm, T3: 7 ± 2 mm; p < 0.0001), returning to baseline 6 months postoperatively. Cardiac index (T1: 2.5 ± 0.7 L/min/m2, T2: 2.6 ± 0.6 L/min/m2, T3: 2.3 ± 0.5 L/min/m2; p = 0.07) and right ventricular fractional area change (T1: 36 ± 11%, T2: 40 ± 12%, T3: 40 ± 9%; p = 0.12) were preserved perioperatively. 6-MWT improved from baseline (294 ± 111 m) to follow-up (357 ± 107 m) (p < 0.001). Pulmonary vascular resistance at T3 correlated moderately with follow-up 6-MWT (R = -0.60). CONCLUSIONS: In patients undergoing PEA, invasive measurements and echocardiography assessment of right ventricular function are not interchangeable. Tricuspid annular plane systolic excursion is not a reliable measure of right ventricular function perioperatively. Pulmonary vascular resistance shows moderate correlation with postoperative functional capacity.

Endovascular treatment of the common femoral artery in the Vascular Quality Initiative.

OBJECTIVE: Endovascular interventions of the common (CFA) and deep (DFA) femoral arteries are becoming more common. However, there is very little published data for guidance. Our objective was to analyze practice patterns and outcomes from these interventions. METHODS: The Vascular Quality Initiative (2010-2015) was queried for all endovascular interventions of the CFA and DFA. Cases that were emergent or for acute limb ischemia were excluded. Those with isolated CFA with or without DFA treatment were analyzed. RESULTS: There were 1014 patients that had either an isolated CFA intervention (946) with or without a DFA intervention (68). Average age of this isolated cohort was 67.4 ± 10.8 years, and 59% were male. Indications were claudication (67%), rest pain (16.3%), and tissue loss (16.7%). Periprocedural complications were access site hematoma (5.2%), arterial dissection (2.9%), distal embolization (0.7%), access site stenosis/occlusion (0.5%), and arterial perforation (0.6%). Thirty-day mortality was 1.6%. Survival was 92.9% at 1 year and 87.2% at 3 years. Amputation-free survival, freedom from loss of patency or death, and reintervention-free survival were 93.5%, 83%, and 87.5% at 1 year, respectively, by Kaplan-Meier analysis. Multivariable predictors of mortality were tissue loss, chronic obstructive pulmonary disease (COPD), end-stage renal disease, urgent case, and age, whereas aspirin use and non-Caucasian race were protective. Tissue loss, rest pain, COPD, end-stage renal disease, stent use, nonambulatory status, and female sex were predictive of major amputation whereas aspirin use, P2Y12 antagonist use, statin use, and initial technical success were protective. Tissue loss, case urgency and nonambulatory status predicted patency loss or death. Tissue loss, COPD, stent use, and history of prior bypass predicted reintervention. CONCLUSIONS: Endovascular interventions of the CFA/DFA have a low rate of periprocedural morbidity and mortality. One-year patency is lower than historically observed for CFA endarterectomy. Stent use is associated with reinterventions and amputation. Longer-term analysis is needed to better assess durability.

[Pathobiology, pathology and genetics of pulmonary hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Pathobiologie, Pathologie und Genetik der pulmonalen Hypertonie: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) are also valid for Germany. While the guidelines contain detailed recommendations regarding clinical aspects of pulmonary arterial hypertension (PAH) and other forms of PH, they contain only a relatively short paragraph on novel findings on the pathobiology, pathology, and genetics. However, these are of great importance for our understanding of this complex disease both from a clinical and scientific point of view, and they are essential for the development of novel treatment strategies. To this end, a number of current data are relevant, prompting a detailed commentary to the guidelines, and the consideration of new scientific data. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the pathobiology, pathology and genetics of PH. This article summarizes the results and recommendations of this working group.

[General and supportive therapy of pulmonary arterial hypertension]. / Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.

Oximetría cerebral en endarterectomía pulmonar con parada circulatoria / Cerebral oximetry in pulmonary thromboendarterectomy with circulatory arrest

La tromboendarterectomía pulmonar es un procedimiento infrecuente que precisa parada circulatoria para su realización, por lo que uno de sus principales riesgos son las lesiones neurológicas postoperatorias. La monitorización cerebral intra- y postoperatoria sería, por tanto, conveniente en estos procedimientos para detectar precozmente episodios de hipoperfusión, su intensidad, así como otros episodios postoperatorios de desaturación cerebral que puedan empeorar el pronóstico neurológico (AU)

Pulmonary thromboendarterectomy is an uncommon procedure and should be performed with circulatory arrest. One of the major concerns is the postoperative central neurological injuries. Perioperative brain oxygen monitoring is advisable in this surgical procedure for the early detection of brain hypoperfusion episodes and their intensity as well as any other postoperative episodes that can deteriorate the neurological outcome (AU)

[Thrombo-embolic pulmonary hypertension--do not spoil a chance for effective surgery!]. / Zakrzepowo-zatorowe nadcisnienie plucne--nie marnujmy szansy na skuteczne leczenie operacyjne!

Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary hypertension with persistent pulmonary perfusion defects causes by unresolved thrombi. All symptomatic CTEPH patients with documented pulmonary vascular resistance > 300 dyn*sec*cm(-5) and proximal lesions should be considered for surgical treatment--pulmonary endarterectomy. The role of pharmacological treatment remains controversial and should be restricted to inoperable cases and persistent pulmonary hypertension after pulmonary endarterectomy. Every year about 30 procedures is performed in two specialised centers in Poland with 1 year mortality at 8-9%. Number of procedures done gives the frequency of pulmonary endarterectomy at 0.7/million of population/year. Current data from UK indicate the actual ratio of surgical treatment of CTPH at 2/million/year. The article discusses reasons for CTEPH is underdiagnosed and why rate of surgical therapy in Poland is too low.

The role of surgery when endovascular treatment is considered the first choice therapy for ruptured intracranial aneurysms.

AIM: Nowadays endovascular therapy is more and more considered as first choice treatment for ruptured intracranial aneurysms. The aim of this study was to understand the impact that endovascular treatment (EVT), chosen as first therapeutic strategy, has had in the selection of ruptured intracranial aneurysms submitted to surgery at our Institution and what role neurosurgeons still play in this setting. METHODS: From 1998 to 2002, 272 consecutive patients were treated at the Hospital of Toulouse for ruptured intracranial aneurysms: 222 by embolization and 50 by surgery. The two groups were homogeneous for sex, age and aneurysms multiplicity. RESULTS: The patients of the surgical group had a worst clinical-radiological status at the treatment time than those treated by EVT. Clipping was performed for different reasons: 16% for failure of attempted EVT; 32% for intracranial hematoma requiring surgical evacuation; 30% for aneurysm morphology unsuitable for EVT and 22% for absence of the endovascular operator. Aneurysms of the middle cerebral artery (MCA) represented the main surgical group. The aneurysms judged unsuitable for EVT and addressed to surgery had often a complex morphology representing a challenge also for surgery. Mid-term outcome is significantly better for patients treated by EVT. CONCLUSION: The results show that microsurgery continues to have a role in the treatment of ruptured intracranial aneurysms even when EVT is the first choice. The precarious clinical conditions of the patients submitted to surgery and the frequent complexity of their aneurysms explain their worst outcome. This would advise training dedicated vascular Neurosurgeons to guaranty a high level treatment when EVT is not possible.

Hipertensão pulmonar na doença tromboembólica crônica / Pulmonary hypertension in chronic thromboembolic disease

Hipertensão pulmonar crônica tromboembólica é observada em até 3,8 por cento dos pacientes que sobreviveram a embolia pulmonar aguda. O desenvolvimento da técnica da tromboendarterectomia possibilitou a melhora significativa da sobrevida dos pacientes portadores de hipertensão pulmonar tromboembólica, com resolução do quadro hipertensivo na maioria dos pacientes operados. Nos últimos anos, tornou-se possível a definição de critérios mais claros para a indicação cirúrgica, assim como de marcadores de prognóstico, o que determinou significativa diminuição do risco cirúrgico associado ao procedimento. Atualmente tratamento médico com drogas está sendo feito em pacientes em que a tromboendarterectomia não apresentou bons resultados ou foi contra-indicada.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Ten years experience in Denmark.

OBJECTIVES: To evaluate survival and functional outcome in patients treated by pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension in Denmark. DESIGN: Follow-up of the first 50 patients operated at Aarhus University Hospital, Denmark. RESULTS: Fifty patients underwent PEA in the period from 1994 to mid 2004. Prior to surgery all patients were in World Health Organization (WHO) function class III (n=33) or IV (n=17). The mean pulmonary artery pressure was 50 mmHg (range 25-76), cardiac index 1.8 l min(-1)m(-2) (range 0.8-2.8) and pulmonary vascular resistance 819 dyn s cm(-5) (range 241-3,067). In-hospital mortality was 12/50 (24%). Surgical mortality was highest in the early period. Since year 2000 in-hospital deaths occurred in only 2 among 23 patients (9%). Leading causes of death were persistent pulmonary hypertension and bleeding. Three patients died during long-term follow-up with a median observation time of 3 years. The overall 5 year survival rate was 74%. At 3 months follow-up 90% of the patients (34/38) had improved one or more WHO functional classes and the systolic pulmonary artery pressure estimated by Doppler echocardiography had decreased from 80 mmHg (range 49-115) to 43 mmHg (range 14-95). CONCLUSION: Pulmonary endarterectomy has been successfully implemented in Denmark. The perioperative mortality was reduced over time to 9% during the past 5 years. Functional outcome and long-term survival were excellent stressing the importance of surgical treatment for chronic thromboembolic pulmonary hypertension.

Carotid artery stenosis and endarterectomy.

This article reviews the disease process of carotid artery stenosis, its symptomatology, and prognosis for progression to ischemic stroke. Indications for both medical and surgical treatment are reviewed as is criteria for surgical categorization as specified by the American Heart Association guidelines for carotid endarterectomy. Although diagnostic testing, medical treatment and alternative therapy options of angioplasty, stenting and thrombolysis are presented, a thorough overview of the surgical procedure of carotid endarterectomy is the major focus of discussion, as it remains the "gold standard" of treatment for severe carotid artery stenosis.

Stent angioplasty for cervical carotid artery stenosis in high-risk symptomatic NASCET-ineligible patients.

BACKGROUND AND PURPOSE: Although the North American Symptomatic Carotid Endarterectomy Trial (NASCET) has shown carotid endarterectomy (CEA) to be protective compared with medical therapy alone, its stringent eligibility criteria excluded patients with severe medical, angiographic, and neurological risk factors. We sought to determine the safety and efficacy of stent angioplasty in this high-risk subset for whom the perioperative morbidity and mortality of surgery are elevated. METHODS: Twenty-eight consecutive symptomatic NASCET-ineligible patients (10 female; median age, 72.2 years) underwent microcatheter-based carotid stent angioplasty. Half of the patients had sustained a previous stroke. Classification of surgical risk by Sundt criteria yielded no patients in grade 1, 3 patients in grade 2 (10.7%), 8 in grade 3 (28.6%), and 17 (60.7%) in grade 4. Stratification of stroke risk for medical therapy according to the European Carotid Surgery Trial (ECST) 5-point score showed 8 patients with a score of 3 (28.6%), 12 with 4 (42.8%), and 8 with 5 (28.6%). Follow-up was obtained in all patients at a median of 14 months. RESULTS: The procedure was technically successful in all cases (100%), with immediate stenosis reduction from a mean of 80.3% to 2.7%. There were no periprocedural deaths, 1 major stroke (3.6%), no minor strokes, and 3 transient ischemic attacks (10.7%). In-hospital complications included 2 nonfatal myocardial infarctions, 1 case of acute renal failure, and 1 groin hematoma requiring transfusion. There were 5 deaths during the follow-up period, all beyond 30 days after the procedure: 3 from cardiac causes, 1 from lung cancer, and 1 following unrelated surgery. The patient with major stroke died at 7.8 months during rehabilitation. No surviving patients had further strokes, and all except 1 (95.5%) remained asymptomatic. Anatomic follow-up in 20 patients showed occlusion in 2 (10%) (1 symptomatic, 1 asymptomatic) and intimal hyperplasia in 3 asymptomatic patients (15%). CONCLUSIONS: The clinical results and sustained freedom from symptoms and stroke during the short available follow-up period suggest that stent angioplasty may be useful in the treatment of symptomatic cervical carotid stenosis in high-risk patients despite a notable incidence of restenosis.

The American Heart Association Consensus Statement on guidelines for carotid endarterectomy.

The process by which a multidisciplinary, expert panel arrived at a Consensus Statement concerning indications for carotid endarterectomy was reviewed. It is important to point out that this represents an interpretation of currently available data by the individual members of the Committee as it pertains to 96 specific potential indications for carotid endarterectomy. Clearly, as more data become available, it is likely that there will be changes in the opinion of the Committee members. Therefore, this represents a current status that will require a periodic update.

Controversies in the management of cerebrovascular disease in older patients.

Several ongoing studies are evaluating the optimal management of patients with cerebrovascular disease. The Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin (CASANOVA) study has shown that carotid endarterectomy is not recommended for asymptomatic patients with less than 90% carotid stenosis. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgical Trial (ECST) have demonstrated that endarterectomy should be considered for patients who had recent carotid artery territory ischemic symptoms associated with angiographically defined stenosis of greater than 70%. These and other trials are expected to provide further data regarding management of cerebrovascular disease, including treatment of those patients with moderate (30 to 69%) carotid stenosis. Until that time, treatment decisions must be made on a case-to-case basis.

Concomitant subclavian and carotid artery disease: the need for a combined surgical correction.

To determine the importance of carotid artery disease in patients undergoing revascularization of the proximal subclavian artery for a subclavian steal syndrome, an 18-year experience of 55 patients was reviewed. Concomitant carotid artery disease (> 50% stenosis) was present in 35 patients (Group I: 63.6%). Twenty patients (Group II: 36.4%) had no evidence of hemodynamically significant carotid disease. Twenty-five patients in Group I (Group IA: 71.4%) were treated by endarterectomy (CEA) for all their carotid lesions while one or both carotid lesions were left untreated in 10 patients (Group IB: 28.6%). The actuarial 5-year freedom rate from neurological events was 87.2% in Group IA, 34.9% in Group IB (p < 0.001) and 100% in Group II (Group IB vs. II, p < 0.001; Group IA vs. Group II, p = ns). All untreated carotid lesions had a deleterious effect on the early and late functional results after surgical reconstruction of the subclavian artery. We conclude that the combined correction of subclavian and carotid lesions should be recommended in every case.

Reducing the risk of stroke: identifying patients to refer for carotid endarterectomy.

The most common causes of stroke are two diseases of aging: hypertension and atherosclerosis. Therefore, although stroke may occur at any age, the incidence is highest among the elderly population. Noninvasive efforts to reduce the risk of stroke in the elderly include control of hypertension and diabetes, smoking cessation, low-cholesterol dietary habits, and moderate exercise. Routine low-dose aspirin also provides some protective effect. High-risk patients (with asymptomatic high-grade stenosis, TIAs, or prior stroke) should be considered candidates for carotid endarterectomy in the absence of contraindications to surgery.

South Australian carotid endarterectomy study.

OBJECTIVE: To determine the operative morbidity and mortality of carotid endarterectomy in South Australia. DESIGN: This was a prospective study on consecutive patients already selected independently by their treating clinicians for carotid endarterectomy. Patients were assessed before and after the operation by independent neurologists. SETTING AND PARTICIPANTS: The study involved all patients undergoing carotid endarterectomy in South Australia in public and private hospitals over the 20-months period of the study. All vascular surgeons agreed to participate. INTERVENTION: Two hundred and thirty-nine carotid endarterectomies were performed on 223 patients, always as primary procedures. MAIN OUTCOME MEASURES: Patient characteristics, angiographic findings and indications for surgery were documented before the operation by neurologists who then carried out postoperative assessments and determined neurological status at discharge. Follow-up at six and twelve months was by letter and telephone enquiry to general practitioners or direct to patients. RESULTS: The perioperative death and stroke rate was 6.3% including one stroke after angiography and before endarterectomy. Fourteen patients (5.9%) had strokes after the operation and three died as a result (1.3%). Three patients had reversible ischaemic neurological deficits. In 58 asymptomatic patients, operative morbidity was 3.4%. However, in 42 patients who had had a stroke before the operation, there were seven who had operative complications (16.7%). Neurological complication rates for individual surgeons varied from 0 to 13.8%. In the subsequent 12 months, follow-up of 214 patients revealed nine additional deaths (three known to be caused by stroke, four not caused by stroke and two of unknown cause) and six more cerebral infarctions (involving both operated and unoperated sides), an annual mortality plus stroke morbidity rate of 4.2%-5.1%. CONCLUSIONS: The morbidity and mortality of carotid endarterectomy in South Australia is acceptable by world standards but is high in the subgroup with a preceding stroke. In this audit, carotid endarterectomy had an average risk at least equal to one year of untreated carotid artery disease and did not diminish the expected stroke and death incidence after one year.