Thorsten Kramm

Chronic thromboembolic pulmonary hypertension (CTEPH): Updated Recommendations of the Cologne Consensus Conference 2011 ✩

In the 2009 European Guidelines on the diagnosis and treatment of pulmonary hypertension (PH), one section covers aspects of pathophysiology, diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The practical implementation of the guidelines for this disease is of crucial importance, because CTEPH is a subset of PH which can potentially be cured by pulmonary endarterectomy (PEA). Nowadays, CTEPH is commonly underdiagnosed and not properly managed. Any patient with unexplained PH should be evaluated for the presence of CTEPH, and a ventilation/perfusion (V/Q) lung scan is recommended as screening method of choice. If the V/Q scan or CT angiography reveals signs of CTEPH, the patient should be referred to a specialized center with expertise in the medical and surgical management of this disease. Every case has to be reviewed by an experienced PEA surgeon for the assessment of operability. In this updated recommendation, important contents of the European guidelines were commented, and more recent information regarding diagnosis and treatment was added.

Value of contrast-enhanced MR angiography and helical CT angiography in chronic thromboembolic pulmonary hypertension.

The aim of this study was to evaluate the diagnostic value of contrast-enhanced MR angiography (ce MRA) and helical CT angiography (CTA) of the pulmonary arteries in the preoperative workup of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The ce MRA and CTA studies of 32 patients were included in this retrospective evaluation. Image quality was scored by two independent blinded observers. Data sets were assessed for number of patent segmental, subsegmental arteries, and number of vascular segments with thrombotic wall thickening, intraluminal webs, and abnormal proximal to distal tapering. Image quality for MRA/CTA was scored excellent in 16 of 16, good in 11 of 14, moderate in 2 of 5, and poor in no examinations. The MRA/CTA showed 357 of 366 patent segmental and 627 of 834 patent subsegmental arteries. CTA was superior to MRA in visualization of thrombotic wall thickening (339 vs 164) and of intraluminal webs (257 vs 162). Abnormal proximal to distal tapering was better assessed by MRA than CTA (189 vs 16). In joint assessment of direct and indirect signs, MRA and CTA were equally effective (353 vs 355). MRA and CTA are equally effective in the detection of segmental occlusions of the pulmonary arteries in CTEPH. CTA is superior for the depiction of patent subsegmental arteries, of intraluminal webs, and for the direct demonstration of thrombotic wall thickening.

Long-term results after thromboendarterectomy for chronic pulmonary embolism

OBJECTIVE In patients with chronic thromboembolic pulmonary hypertension, pulmonary vascular resistance (PVR) can be reduced by pulmonary thromboendarterectomy (PTE). In this study, long-term symptomatic and hemodynamic effects were investigated. METHODS Twenty-two patients (12 female, 10 male, mean age 40 years, preoperative NYHA functional class II/III/IV: n = 1/12/9) were re-evaluated 48-72 months (mean 60 months) after surgery. In addition to clinical assessment, radiologic, hemodynamic and echocardiographic investigations were performed. RESULTS All patients reported a marked improvement of their clinical condition. At follow-up, 11 patients were identified as NYHA class I, 10 as NYHA class II and one patient was in class III. PVR and mean pulmonary artery pressure (mPAP) were significantly reduced (preoperative PVR 800+/-274 dynes/s per cm(-5), follow-up PVR 180+/-28.3 dynes/s per cm(-5); P < 0.001; preoperative mPAP 48.5+/-7.4 mmHg, follow-up mPAP 27.5+/-4.9 mmHg; P < 0.001). There was also a significant increase in arterial blood oxygen tension (preoperative PaO2 59+/-10 mmHg; follow-up PaO2 84+/-12 mmHg; P < 0.001). Chest roentgenograms and echocardiographic examinations revealed significantly decreased right heart dimensions and a recovery of right heart function. CONCLUSION In patients with severe chronic thromboembolic pulmonary hypertension, persistent symptomatic and hemodynamic improvements can be achieved by PTE.

Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy

BACKGROUND In primary pulmonary hypertension, aerosolized prostanoids selectively reduce pulmonary vascular resistance and improve right ventricular function. In this study, hemodynamic effects of inhaled iloprost, a stable prostacyclin analogue, were evaluated in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and early after pulmonary thromboendarterctomy (PTE). METHODS Ten patients (mean age 49 years old [32 to 70 years old], New York Heart Association functional class III and IV) received a dose of 33 micro g aerosolized iloprost immediately before surgery (T1), after intensive care unit admission (T2), and 12-hours postoperatively (T3). Effects on pulmonary and systemic hemodynamics and gas exchange were recorded and compared with preinhalation baseline values. RESULTS Preoperatively, inhaled iloprost did not significantly change mean pulmonary artery pressure (mPAP), cardiac index (CI), or pulmonary vascular resistance (PVR). Postoperatively, inhaled iloprost induced a significant reduction of mPAP and PVR and a significant increase of CI at T2 and T3. Preinhalation versus postinhalation PVR was as follows: at T1, 847 versus 729 dynes. s. cm(-5), p = 0.45; at T2, 502 versus 316 dynes. s. cm(-5), p = 0.008; and at T3, 299 versus 227 dynes. s. cm(-5), p = 0.004. CONCLUSIONS In patients with CTEPH, inhalation of iloprost elicits no significant pulmonary vasodilation before surgery, and may have detrimental effects on systemic hemodynamics. Postoperatively, it significantly reduces mPAP and PVR, and enhances CI. Following PTE, inhalation of iloprost is useful to improve early postoperative hemodynamics.

Improvement of tricuspid regurgitation after pulmonary thromboendarterectomy.

BACKGROUND For patients with chronic thromboembolic pulmonary hypertension who undergo pulmonary thromboendarterectomy (PTE) it has not yet been systematically investigated how operation affects the severity of tricuspid regurgitation (TR). This study sought (1) to evaluate the extent of TR reversibility after operation, (2) to identify potential predictors of the reversibility of TR, and (3) to investigate the influence of geometric and hemodynamic alterations on the extent of TR severity. METHODS Thirty-nine patients (55+/-12 years) undergoing PTE without tricuspid valve repair were investigated before and 13+/-8 days after operation by Doppler color flow mapping. Geometry of the tricuspid valve as well as right ventricular size and function were determined with echocardiography. Mean pulmonary arterial pressure was determined invasively. RESULTS After PTE, mean pulmonary arterial pressure was significantly lower (48+/-10 versus 25+/-7 mm Hg, p < 0.05). Most of the patients had a distinct reduction of TR, and the improvement trend showed on the severity scale: number of patients with 4+TR (23 --> 4), 3+TR (12 --> 12), 2+TR (2 --> 13), and 1+TR (2 --> 10). Examination after PTE revealed profound reduction of right ventricular size and annulus diameter, with a normalization of the valvular geometry. However, none of the study variables were useful as indicators of the postoperative outcome. CONCLUSIONS After PTE without additional valve repair most patients show significantly reduced severity of TR soon afterward; the very few cases in which TR does not improve remain unidentifiable before operation. Our recommendation is consequently to refrain from additional tricuspid repair in patients undergoing PTE.

Assessment of cardiac performance using Tei indices in patients undergoing pulmonary thromboendarterectomy

BACKGROUND This study was designed to evaluate left and right ventricular performance using Tei indices in patients with severe chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy (PTE). The Doppler-derived indices are easily measurable indicators of ventricular function based on nongeometric assessment, which helps overcome some of the difficulties entailed in the geometric assessment of left ventricular (LV) and right ventricular (RV) function in pulmonary hypertension. METHODS The indices were derived for 24 patients (aged 54+/-14 years) before and after PTE. Calculation of these indices was based on the duration of two time intervals using the formula (A - B)/B, where A is the interval between cessation and onset of mitral inflow (or tricuspid inflow) and B is LV or RV ejection time. In addition, LV and RV end-diastolic and end-systolic chamber areas were determined using two-dimensional echocardiography, and systolic function was calculated. Mean pulmonary artery pressure was determined invasively. RESULTS PTE led to a significant reduction of mean pulmonary artery pressure (46+/-10 versus 25+/-6 mm Hg; p < 0.05). LV and RV indices were abnormally high before surgery, declined significantly afterwards, and then almost matched normal values (0.61+/-0.26 versus 0.37+/-0.18; p < 0.05 and 0.55+/-0.22 versus 0.37+/-0.13; p < 0.05). Geometric assessment of the left and right ventricle also showed impaired systolic function before PTE, with significant improvement after surgery. CONCLUSIONS LV and RV Tei indices allow a quantitative assessment of ventricular function in patients undergoing PTE. Lower indices after surgery reflect an improvement of the previously impaired cardiac function. Our results emphasize the value of PTE in the treatment of chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience

Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We report on a prospective series of 56 consecutive patients who underwent 266 BPA interventions (median, five per patient) at two German institutions. All patients underwent a comprehensive diagnostic work-up including right heart catheterisation at baseline and 24 weeks after their last intervention. BPA resulted in improvements in WHO functional class, 6 min walk distance (mean change, +33 m), right ventricular function and haemodynamics, including a decline in mean pulmonary artery pressure by 18% and in pulmonary vascular resistance by 26%. Procedure-related adverse events occurred in 9.4% of the interventions. The most common complications were related to pulmonary vascular injury and consecutive pulmonary bleeding. Most of these events were asymptomatic and self-limiting, but one patient died from pulmonary bleeding, resulting in a mortality rate of 1.8%. BPA resulted in haemodynamic and clinical improvements but was also associated with a considerable number of complications, including one fatal pulmonary bleeding. As the effects of BPA on survival are unknown, randomised controlled outcome trials comparing BPA with approved medical therapies in patients with inoperable CTEPH are required to allow for appropriate risk–benefit assessments. BPA improves haemodynamics and exercise capacity in patients with inoperable CTEPH but complications are not uncommon http://ow.ly/mMYY30b1rch

Aktuelle Frühergebnisse nach pulmonaler Thrombendarteriektomie bei chronischer thromboembolischer pulmonaler Hypertonie

Die pulmonale Thrombendarteriektomie ist ein potentiell kuratives Operationsverfahren bei Patienten mit chronischer thromboembolischer pulmonaler Hypertonie. Von Juni 1989 bis Dezember 1994 wurden in unserer Klinik 109 Patienten einer pulmonalen Thrombendarteriektomie unterzogen. Seit Januar 1995 wurden vielfältige Veränderungen des operativen und postoperativen Therapiekonzepts vorgenommen. Wir berichten über die Frühergebnisse von 32 Thrombendarteriektomien, die von Januar 1995 bis Januar 1997 durchgeführt worden sind. Zweiunddreißig Patienten (16 Frauen und 16 Männer, Durchschnittsalter 55 J.) wurden unter extrakorporaler Zirkulation und Phasen des Kreislaufstillstands in tiefer Hypothermie operiert. Von den 32 Patienten wurden präoperativ 21 dem Stadium III und 11 dem Stadium IV der NYHA-Klassifikation zugeordnet. Der mittlere Pulmonalarteriendruck (mPAP) war auf 51 ± 11 mm Hg und der mittlere pulmonale Gefäßwiderstand auf 967 ± 238 dynes ˙ s ˙ cm-5 erhöht. Die perioperative Letalität betrug 9,3% (3/32). Die 29 überlebenden Patienten wurden im Mittel 35 Stunden (12 bis 190 Stunden) nach der Operation extubiert. Der pulmonalvaskuläre Widerstand konnte durch den Eingriff signifikant von 958 ± 248 dynes ˙ s ˙ cm-5 auf 301 ± 151 dynes ˙ s ˙ cm-5 (p < 0,001) und der mittlere Pulmonalarteriendruck von 51 ± 11 mm Hg auf 28 ± 10 mm Hg gesenkt werden (p < 0,001). Die pulmonale Thrombendarteriektomie ist das Therapieverfahren der Wahl bei chronischer thromboembolischer pulmonaler Hypertonie. Durch Modifikationen des operativen und postoperativen Konzepts und mit zunehmender Erfahrung können die Frühergebnisse des Verfahrens verbessert und eine perioperative Letalität unter 10% erreicht werden. Pulmonary thromboendarterectomy (PTE) is a potentially curative procedure in chronic thromboembolic pulmonary hypertension. From June, 1989, to December, 1994, we performed PTE in 109 consecutive patients. Multiple changes in surgical approach and postoperative management have been implemented since January, 1995. We report the early results of 32 thromboendarterectomies performed from January, 1995, to January, 1997. Thirty-two patients (16 females, 16 males; mean age 55 years) were operated using cardiopulmonary bypass, deep hypothermia and circulatory arrest. Preoperative NYHA functional class was II in 21 and IV in 11 patients. Pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP) were elevated to 967 ± 238 dynes ˙ s ˙ cm-5 and 51 ± 11 mm HG respectively. The perioperative mortality rate was 9.3% (3 of 32). Twenty-nine survivors were weaned from mechanical ventilation and extubated after a mean of 35 hours (12 to 190 hours). PVR was reduced to 301 ± 151 dynes ˙ s ˙ cm-5 (p < 0.001) and mPAP was reduced to 28 ± 10 mm Hg (p < 0.001). Pulmonary thromboendarterectomy is an effective surgical procedure for chronic thromboembolic pulmonary hypertension. By means of modifications in surgical approach and postoperative management, early results can be improved and perioperative mortality can be decreased to less than 10%.

Reversibilität von Veränderungen der links- und rechtsventrikulären Geometrie und Hämodynamik bei pulmonaler Hypertonie. Echokardiographische Charakterisierung bei Patienten vor und nach pulmonaler Thrombendarteriektomie

Durch pulmonale Thrombendarteriektomie kann bei Patienten mit chronischer embolisch bedingter pulmonaler Hypertonie eine akute rechtsventrikuläre Nachlastsenkung erzielt werden. Der Einfluß auf die rechts- und linksventrikuläre Geometrie und Hämodynamik wurde prospektiv mit Hilfe der transthorakalen Echokardiographie an einem Kollektiv von 14 Patienten (8 Frauen, 6 Männer; Alter 55 ± 20 Jahre) vor und nach 18 ± 12 Tagen postoperativ untersucht. Nach operativer Desobliteration der Pulmonalarterien fand sich eine Abnahme des invasiv bestimmten totalen pulmonalen Gefäßwiderstands von 986 ± 318 auf 323 ± 280 dyn x s/cm5; p < 0,05. Der echokardiographisch erfaßte systolische pulmonalarterielle Druck sank von 71 ± 40 auf 41 ± 40 mm Hg + ZVD; p < 0,05. Die enddiastolische sowie endsystolische rechtsventrikuläre Fläche nahm von 33 ± 12 auf 23 ± 8 cm2 bzw. von 26 ± 10 auf 16 ± 6 cm2 ab; p < 0,05. Die systolische rechtsventrikuläre Flächenverkürzungsfraktion stieg von 20 ± 12 auf 30 ± 16%; p < 0,05. Die rechtsventrikuläre systolische Druckanstiegsgeschwindigkeit blieb unverändert (516 ± 166 vs. 556 ± 128 mm Hg/sec). Die linksventrikuläre Ejektionsfraktion war prä- und postoperativ normal (64 ± 16 vs. 62 ± 12%). Der echokardiographisch bestimmte Herzindex stieg von 2,8 ± 0,74 auf 4,1 ± 1,74 l/min/m2. Eine Normalisierung der präoperativ alterierten Septumbewegung war anhand der linksventrikulären Exzentrizitätsindizes nachweisbar (enddiastolischer Index: 1,9 ± 1 vs. 1,1 ± 0,3, endsystolischer Index: 1,7 ± 0,6 vs. 1,1 ± 0,4; p < 0,05). Das diastolische Füllungsverhalten der linken Kammer normalisierte sich (E-zu-A-Verhältnis: 0,62 ± 0,34 vs. 1,3 ± 0,8; p < 0,05). Bereits kurzfristig nach pulmonaler Thrombendarteriektomie findet sich eine ausgeprägte Abnahme der rechtsventrikulären Nachlast. Die Folge ist – selbst wenn eine schwerste pulmonale Hypertonie bestand – eine deutliche Erholung der systolischen rechtsventrikulären Funktion. Gleichzeitig kommt es aufgrund der Normalisierung der paradoxen Septumbewegung zur Normalisierung des diastolischen linksventrikulären Füllungsverhaltens. Aus beiden resultiert ein signifikanter Anstieg des Herzzeitvolumens. Patienten mit chronischer embolisch bedingter pulmonaler Druckerhöhung profitieren kardial von der pulmonalen Thrombendarteriektomie und sollten bei gegebener Indikation einer solchen Operation zugeführt werden. Pulmonary thrombendarterectomy (PTE) leads to an acute decrease of right ventricular (RV) afterload in patients with chronic thromboembolic pulmonary hypertension. We investigated the changes in right and left ventricular (LV) geometry and hemodynamics by means of transthoracic echocardiography. The prospective study was performed in 14 patients (8 female, 6 male; age 55 ± 20 years) before and 18 ± 12 days after PTE. Total pulmonary vascular resistance and systolic pulmonary artery pressure were significantly decreased (PVR: preoperative 986 ± 18, postoperative 323 ± 280 dyn x s/cm5, p < 0.05; PAP preoperative 71 ± 40, postoperative 41 ± 40 mm Hg + right atrial pressure, p < 0.05). Enddiastolic and endsystolic RV area decreased from 33 ± 12 to 23 ± 8 cm2, respectively, from 26 ± 10 to 16 ± 6 cm2, p < 0.05. There was an increase in systolic RV fractional area change from 20 ± 12 to 30 ± 16% , p < 0.05. RV systolic pressure rise remained unchanged (516 ± 166 vs. 556 ± 128 mm Hg/sec). LV ejection fraction remained within normal ranges (64 ± 16 vs. 62 ± 12%). Echocardiographically determined cardiac index increased from 2.8 ± 0.74 to 4.1 ± 1.74 l/min/m2. A decrease in LV excentricity indices (enddiastolic: 1.9 ± 1 vs. 1.1 ± 0.3, endsystolic: 1.7 ± 0.6 vs. 1.1 ± 0.4, p < 0.05) proved a normalization of preoperatively altered septum motion. LV diastolic filling returned to normal limits: (E/A ratio: 0.62 ± 0.34 vs. 1.3 ± 0.8; p < 0.05); Peak E velocity: 0.51 ± 0.34 vs. 0.88 ± 0.28 m/sec, p < 0.05; Peak A velocity: 0.81 ± 0.36 vs. 0.72 ± 0.42 m/sec, ns; E deceleration velocity: 299 ± 328 vs. 582 ± 294 cm/sec2, p < 0.05; Isovolumic relaxation time: 134 ± 40 vs. 83 ± 38 m/sec, p < 0.05). We could show a marked decrease in RV afterload shortly after PTE with a profound recovery of right ventricular systolic function – even in case of severe pulmonary hypertension. A decrease in paradoxic motion of the interventricular septum and normalization of LV diastolic filling pattern resulted in a significant increase of cardiac index.

Length of pressure-controlled reperfusion is critical for reducing ischaemia-reperfusion injury in an isolated rabbit lung model

BackgroundIschaemia-reperfusion injury is still a major problem after lung transplantation. Several reports describe the benefits of controlled graft reperfusion. In this study the role of length of the initial pressure-controlled reperfusion (PCR) was evaluated in a model of isolated, buffer-perfused rabbit lungs.MethodsHeart-lung blocks of 25 New Zealand white rabbits were used. After measurement of baseline values (haemodynamics and gas exchange) the lungs were exposed to 120 minutes of hypoxic warm ischaemia followed by repeated measurements during reperfusion. Group A was immediately reperfused using a flow of 100 ml/min whereas groups B, C and D were initially reperfused with a maximum pressure of 5 mmHg for 5, 15 or 30 minutes, respectively. The control group had no period of ischaemia or PCR.ResultsUncontrolled reperfusion (group A) caused a significant pulmonary injury with increased pulmonary artery pressures (PAP) and pulmonary vascular resistance and a decrease in oxygen partial pressure (PO2), tidal volume and in lung compliance. All groups with PCR had a significantly higher PO2 for 5 to 90 min after start of reperfusion. At 120 min there was also a significant difference between group B (264 ± 91 mmHg) compared to groups C and D (436 ± 87 mmHg; 562 ± 20 mmHg, p < 0.01). All PCR groups showed a significant decrease of PAP compared to group A.ConclusionUncontrolled reperfusion results in a severe lung injury with rapid oedema formation. PCR preserves pulmonary haemodynamics and gas exchange after ischaemia and might allows for recovery of the impaired endothelial function. 30 minutes of PCR provide superior results compared to 5 or 15 minutes of PCR.