Steven Tsui

Improved Outcomes in Medically and Surgically Treated Chronic Thromboembolic Pulmonary Hypertension

RATIONALE The management of chronic thromboembolic pulmonary hypertension (CTEPH) has changed over recent years with the growth of pulmonary endarterectomy surgery and the availability of disease-modifying therapies. OBJECTIVES To investigate the prognosis of CTEPH in a national setting during recent years. METHODS All incident cases diagnosed in one of the five pulmonary hypertension centers in the United Kingdom between January 2001 and June 2006 were identified prospectively. Information regarding baseline characteristics, treatment, and follow-up was subsequently collected from hospital records. MEASUREMENTS AND MAIN RESULTS A total of 469 patients received a diagnosis, of whom 148 (32%) had distal, nonsurgical disease. One- and three-year survival from diagnosis was 82 and 70% for patients with nonsurgical disease and 88 and 76% for those treated surgically (P = 0.023). Initial functional improvement in patients with nonsurgical disease was noted but did not persist at 2 years. Significant functional and hemodynamic improvements were seen in surgically treated patients with an increase in six-minute-walk distance of 105 m (P < 0.001) at 3 months. Five-year survival from surgery in the 35% of patients who survived to 3 months but had persistent pulmonary hypertension was 94%. CONCLUSIONS The prognosis in nonsurgical disease has improved. We have confirmed the previously described good outcome in surgically treated disease. However, we have also demonstrated that the long-term prognosis for patients who have persistent pulmonary hypertension at 3 months after surgery is good. The observed improvements in outcome during the modern treatment era reinforce the importance of identifying patients with this increasingly treatable condition.

Survival after pulmonary thromboendarterectomy: Effect of residual pulmonary hypertension

OBJECTIVE Pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. In many patients hemodynamics are normalized early after surgical intervention. However, the effect of residual pulmonary hypertension on postoperative clinical status and survival is unknown. METHODS Data were collected prospectively on all patients who underwent pulmonary endarterectomy in a continuous national series between 1997 and December 2007. Postoperatively, patients underwent scheduled reinvestigation, including functional testing and right heart catheterization, at 3 months after the operation. They were divided into 2 groups based on mean pulmonary artery pressure: group 1, less than 30 mm Hg; group 2, 30 mm Hg or greater. RESULTS Three hundred fourteen patients underwent pulmonary endarterectomy, survived to hospital discharge, and completed the 3-month follow-up period. At 3 months after pulmonary endarterectomy, there was a significant reduction in mean pulmonary artery pressure for the whole cohort (48±12 to 26±10 mm Hg, P<.001). However, 31% of the patients had residual pulmonary hypertension. Group 1 patients enjoyed significantly better exercise capacity and improved symptoms compared with group 2 patients. In addition, there were significantly fewer patients receiving targeted medical therapy in group 1 versus group 2 (0% vs 25%, P<.001). Conditional survival after discharge from the hospital for the whole cohort was 90.0% at 5 years and was not different between groups (90.3% for group 1 vs 89.9% for group 2, P=.36). CONCLUSIONS For patients undergoing pulmonary endarterectomy, survival after hospital discharge is excellent. Residual pulmonary hypertension significantly compromised symptom status and functional capacity but did not appear to adversely affect medium-term survival. The effect of targeted medical therapy in patients with residual pulmonary hypertension after pulmonary endarterectomy needs to be evaluated further.

Successful Extracorporeal Membrane Oxygenation Support After Pulmonary Thromboendarterectomy

BACKGROUND Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension. However, some patients develop severe cardiorespiratory compromise soon after separating from cardiopulmonary bypass, either from early reperfusion pulmonary edema or right ventricular failure secondary to residual pulmonary hypertension. Since 2005 we have used venoarterial extracorporeal membrane oxygenation (ECMO) support in this group that has no other therapeutic option. We review our experience of early ECMO support in the severely compromised patients post-PTE. METHODS We conducted a retrospective review of all patients undergoing PTE from a single national referral center between August 2005 and August 2007. RESULTS One hundred twenty-seven consecutive patients underwent PTE surgery. Seven patients (5.5%) had extreme cardiorespiratory compromise in the immediate postoperative period and required venoarterial ECMO support. Their mean age was 51.3 years with 3 males. When compared with patients not requiring ECMO, these patients had significantly poorer hemodynamic indices before the operation with mean pulmonary artery pressure of 62 mm Hg versus 51 mm Hg (p = 0.02) and pulmonary vascular resistance of 907 dynes/sec/cm(-5) versus 724 dynes/s(-1)/cm(-5) (p < 0.02). Mean duration of support was 119 hours (49 to 359 hours). Five patients were successfully weaned from ECMO support (73%) and 4 left the hospital alive, giving a salvage rate of 57%. For those who did not require ECMO support, hospital mortality was 4.2%. CONCLUSIONS Early venoarterial ECMO support has a role as rescue therapy post-PTE in patients with severe compromise who would probably otherwise die.

The Papworth Experience With the Levitronix CentriMag Ventricular Assist Device

OBJECTIVES The Levitronix CentriMag ventricular assist device (VAD) is a centrifugal pump designed for short-term extracorporeal support in cardiogenic shock. The aim of this study is to report our clinical experience with the Levitronix CentriMag for uni- and biventricular support. METHODS Between July 2004 and December 2006, 27 patients were supported using the Levitronix CentriMag device. Nineteen were male. Mean age was 47.9 (range 19 to 72) years. Indications for support at implantation were cardiogenic shock that included: end-stage heart failure and too ill to undergo transplantation, with questionable neurologic status (9 subjects); right ventricular failure after left VAD (LVAD) implantation (5 subjects); post-cardiotomy status (7 subjects); and acute donor graft failure after heart transplantation (6 subjects). RESULTS Post-VAD 30-day survival was 30% (8 patients). Mean support time was 11 days for all patients (range 1 to 51 days). Mean support time for 14 Levitronix biventricular VADs was 11 (range 1 to 51) days. Mean support time for 7 Levitronix LVADs was 13.7 (range 1 to 30) days. The highest survival rates after Levitronix support were after donor graft failure (50%) and after cardiotomy (42%). Levitronix right VAD (RVAD) support after long-term LVAD insertion incurred 100% hospital mortality. Of those who survived, 8 patients were discharged home after VAD support and remain alive to date. Two patients were bridged to primary and another bridged to repeat heart transplantation. Five patients were weaned to recovery. Re-operation for bleeding occurred in 8 patients, clinical evidence of cerebral thromboembolism in 3, overwhelming sepsis in 1, and aortic thrombus formation in 1. Clot formation in the tubing was observed in 1 patient, necessitating emergent replacement at bedside, which was successful. CONCLUSIONS The Levitronix CentriMag system is a reliable and facile temporary circulatory support system as a bridge to decision in patients with refractory acute cardiogenic shock.

Circulatory arrest versus cerebral perfusion during pulmonary endarterectomy surgery (PEACOG): a randomised controlled trial

BACKGROUND For some surgical procedures to be done, a patients blood circulation needs to be stopped. In such situations, the maintenance of blood flow to the brain is perceived beneficial even in the presence of deep hypothermia. We aimed to assess the benefits of the maintenance of antegrade cerebral perfusion (ACP) compared with deep hypothermic circulatory arrest (DHCA). METHODS Patients aged 18-80 years undergoing pulmonary endarterectomy surgery in a UK centre (Papworth Hospital, Cambridge) were randomly assigned with a computer generated sequence to receive either DHCA for periods of up to 20 min at 20°C or ACP (1:1 ratio). The primary endpoint was change in cognitive function at 12 weeks after surgery, as assessed by the trail-making A and B tests, the Rey auditory verbal learning test, and the grooved pegboard test. Patients and assessors were masked to treatment allocation. Primary analysis was by intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN84972261. FINDINGS We enrolled 74 of 196 screened patients (35 to receive DHCA and 39 to receive ACP). Nine patients crossed over from ACP to DHCA to allow complete endarterectomy. At 12 weeks, the mean difference between the two groups in Z scores (the change in cognitive function score from baseline divided by the baseline SD) for the three main cognitive tests was 0·14 (95% CI -0·14 to 0·42; p=0·33) for the trail-making A and B tests, -0·06 (-0·38 to 0·25; p=0·69) for the Rey auditory verbal learning test, and 0·01 (-0·26 to 0·29; p=0·92) for the grooved pegboard test. All patients showed improvement in cognitive function at 12 weeks. We recorded no significant difference in adverse events between the two groups. At 12 weeks, two patients had died (one in each group) [corrected]. INTERPRETATION Cognitive function is not impaired by either ACP or DHCA. We recommend circulatory arrest as the optimum modality for patients undergoing pulmonary endarterectomy surgery. FUNDING J P Moulton Charitable Foundation.

A Prospective, Multicenter Trial of the VentrAssist Left Ventricular Assist Device for Bridge to Transplant : Safety and Efficacy

BACKGROUND The increasing prevalence of chronic heart failure has stimulated the ongoing development of left ventricular assist devices (LVADs) for both bridge-to-transplant (BTT) and destination therapy (DT). The aim of this prospective, multicenter clinical trial was to determine the efficacy and safety of a third-generation LVAD, the VentrAssist, in a BTT cohort. METHODS Patients (n = 33) with end-stage chronic heart failure who required circulatory support as BTT therapy were implanted with a VentrAssist device. The primary outcome was survival until transplant or transplant eligibility with the device in situ at trial end-point (Day 154 after implant). The secondary outcomes were pump flow index and end-organ function. Safety, patient functional status and resource use were also assessed. RESULTS At trial end-point, the success rate was 82% (39.4% transplanted, 42.4% transplant-eligible). The LVAD pump flow index (median >or=2.7 liters/min/m(2)) was sufficient to maintain an adequate circulation and significantly improve end-organ function. Of the 77 protocol-defined serious adverse events, most occurred within 30 days of implantation. No patients died as a direct result of pump failure or malfunction. After implantation, patient functional status improved, with 70% of patients achieving hospital discharge, and resource use was reduced. CONCLUSIONS This trial demonstrated a favorable efficacy and safety profile for use of the VentrAssist LVAD in BTT patients.

Are stentless valves superior to modern stented valves? A prospective randomized trial.

Background— It is presumed that stentless aortic bioprostheses are hemodynamically superior to stented bioprostheses. A prospective randomized controlled trial was undertaken to compare stentless versus modern stented valves. Methods and Results— Patients with severe aortic valve stenosis (n=161) undergoing aortic valve replacement (AVR) were randomized intraoperatively to receive either the C-E Perimount stented bioprosthesis (n=81) or the Prima Plus stentless bioprosthesis (n =80). We assessed left ventricular mass (LVM) regression with transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI). Transvalvular gradients were measured postoperatively by Doppler echocardiography to compare hemodynamic performance. There was no difference between groups with regard to age, symptom status, need for concomitant coronary artery bypass surgery, or baseline LVM. LVM regressed in both groups but with no significant difference between groups at 1 year. In a subset of 50 patients, MRI was also used to assess LVM regression, and again there was no significant difference between groups at 1 year. Hemodynamic performance of the 2 valves was similar with no difference in mean and peak systolic transvalvular gradients 1 year after surgery. In patients with reduced ventricular function (left ventricular ejection fraction [LVEF] <60%), there was a significantly greater improvement in LVEF from baseline to 1 year in stentless valve recipients. Conclusions— Both stented and stentless bioprostheses are associated with excellent clinical and hemodynamic outcomes 1 year after AVR. Comparable hemodynamics and LVM regression can be achieved using a second-generation stented pericardial bioprosthesis. In patients with ventricular impairment, stentless bioprostheses may allow for greater improvement in left ventricular function postoperatively.

Effects of cardiopulmonary bypass and circulatory arrest on endothelium-dependent vasodilatation in the lung ☆ ☆☆ ★ ★★ ♢

Endothelial injury with failure of pulmonary endothelium-dependent vasodilatation has been proposed as a possible cause for the increased pulmonary vascular resistance observed after cardiopulmonary bypass, but the mechanisms underlying this response are not understood. An in vivo piglet model was used to investigate the role of endothelium-dependent vasodilatation in postbypass pulmonary hypertension. The pulmonary vascular responses to acetylcholine, a receptor-mediated endothelium-dependent vasodilator, and nitric oxide, an endothelium-independent vasodilator, were studied in one group of animals after preconstriction with the thromboxane A2 analog U46619 (n = 6); a second group was studied after bypass with 30 minutes of deep hypothermic circulatory arrest (n = 6). After preconstriction with U46619, both acetylcholine and nitric oxide caused significant decreases in pulmonary vascular resistance (34% +/- 6% decrease, p = 0.007, and 39% +/- 4% decrease, p = 0.001). After cardiopulmonary bypass with circulatory arrest, acetylcholine did not significantly change pulmonary vascular resistance (0% +/- 8% decrease, p = 1.0), whereas nitric oxide produced a 32% +/- 4% decrease in pulmonary vascular resistance (p = 0.007). These results demonstrate a loss of receptor-mediated endothelium-dependent vasodilatation with normal vascular smooth muscle function after circulatory arrest. Administration of the nitric oxide synthase blocker Ngamma-nitro-L-arginine-methyl-ester after circulatory arrest significantly increased pulmonary vascular resistance; thus, although endothelial cell production of nitric oxide may be diminished, it continues to be a major contributor to pulmonary vasomotor tone after cardiopulmonary bypass with deep hypothermic circulatory arrest. In summary, cardiopulmonary bypass with deep hypothermic circulatory arrest results in selective pulmonary endothelial cell dysfunction with loss of receptor-mediated endothelium-dependent vasodilatation despite preserved ability of the endothelium to produce nitric oxide and intact vascular smooth muscle function.

Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy Results From the United Kingdom National Cohort

Background— Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. Methods and Results— Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s−1·cm−5 at reassessment correlated with worse long-term survival. Conclusions— Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.

Functional and haemodynamic outcome 1 year after pulmonary thromboendarterectomy

OBJECTIVE Chronic thromboembolic pulmonary hypertension (CTEPH) results in severe symptoms and impaired survival. Pulmonary thromboendarterectomy (PTE) is considered the gold standard treatment. Many units have reported excellent early results post PTE, but there is less information on whether benefit is sustained. We sought to determine the medium-term functional and haemodynamic outcome for patients following PTE and the longer-term survival after discharge from hospital. METHODS Data were collected prospectively on all patients who underwent PTE in the UK between 1997 and June 2006. Patients were reassessed at 3 and 12 months after operation. Follow-up over time was assessed using repeated measures ANOVA, the Friedman test or Wilcoxon signed ranks test as appropriate. RESULTS Two hundred and twenty-nine patients underwent PTE, survived to hospital discharge, and completed follow-up. At 3 months following operation, there was a significant reduction in mean pulmonary artery pressure (47+/-14 to 25+/-14mmHg, p<0.001), a significant increase in cardiac index (1.9+/-0.7 to 2.5+/-0.6l/minm(2), p<0.001) and a significant increase in 6-min walk distance (269+/-123 to 375+/-104m, p<0.001). At 12-month follow-up, the haemodynamic improvements were sustained and there was a further increase in 6-min walk distance (375+/-104 to 392+/-108m, p=0.004). NYHA class was significantly reduced at 3 months, with the improvement sustained at 12 months. Conditional survival following discharge from hospital was 92.5% at 5 years and 88.3% at 10 years. CONCLUSIONS PTE is a very effective therapy for CTEPH. This is the first report from a continuous national series to fully characterise haemodynamic and functional outcome 1 year after PTE. Patients enjoy continued improvement in haemodynamic status that translates into better exercise capacity, reduced symptoms and excellent survival.