Herre J. Reesink

Right Ventricular Failure Following Chronic Pressure Overload Is Associated With Reduction in Left Ventricular Mass : Evidence for Atrophic Remodeling

OBJECTIVES We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. BACKGROUND The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. METHODS We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. RESULTS At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 ± 6 g/m(2) vs. 44 ± 7 g/m(2), p = 0.007) or volunteers (42 ± 6 g/m(2), p = 0.006). After PEA, LV free wall mass index increased (from 38 ± 6 g/m(2) to 44 ± 9 g/m(2), p = 0.001), as right ventricular (RV) ejection fraction improved (from 31 ± 8% to 56 ± 12%, p < 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of α-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. CONCLUSIONS RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.

Clinical ResearchHeart FailureRight Ventricular Failure Following Chronic Pressure Overload Is Associated With Reduction in Left Ventricular Mass: Evidence for Atrophic Remodeling

OBJECTIVES We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. BACKGROUND The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. METHODS We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. RESULTS At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 ± 6 g/m(2) vs. 44 ± 7 g/m(2), p = 0.007) or volunteers (42 ± 6 g/m(2), p = 0.006). After PEA, LV free wall mass index increased (from 38 ± 6 g/m(2) to 44 ± 9 g/m(2), p = 0.001), as right ventricular (RV) ejection fraction improved (from 31 ± 8% to 56 ± 12%, p < 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of α-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. CONCLUSIONS RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.

Pulmonary Endarterectomy Improves Dyspnea by the Relief of Dead Space Ventilation

BACKGROUND In chronic thromboembolic pulmonary hypertension (CTEPH), dyspnea is considered to be related to increased dead space ventilation caused by vascular obstruction. Pulmonary endarterectomy releases the thromboembolic obstruction, thereby improving regional pulmonary blood flow. We hypothesized that pulmonary endarterectomy reduces dead space ventilation and that this reduction contributes to attenuation of dyspnea symptoms. METHODS In this follow-up study we assessed dead space ventilation, hemodynamic severity of disease, and symptomatic dyspnea in 54 consecutive CTEPH patients, before and 1 year after pulmonary endarterectomy. Dead space ventilation was calculated using the Bohr-Enghoff equation. Dyspnea was assessed by Borg scores and the New York Heart Association functional classification. RESULTS Preoperatively, dead space ventilation was increased (0.40 +/- 0.07) and correlated with severity of disease (mean pulmonary artery pressure: r = 0.49, p < 0.001; total pulmonary resistance: r = 0.53, p < 0.001), and resting (r = 0.35, p < 0.05) and post-exercise Borg dyspnea scores (r = 0.44, p < 0.01). Postoperatively, dead space ventilation (0.33 +/- 0.08, p < 0.001) and dyspnea symptoms decreased significantly. Changes in symptomatic dyspnea were independently associated with changes in pulmonary hemodynamics and absolute dead space. CONCLUSIONS Dead space ventilation in CTEPH is increased and correlates significantly with hemodynamic severity of disease and dyspnea symptoms. Pulmonary endarterectomy decreases dead space ventilation. The induced change in dead space upon surgical removal of chronic thromboembolism contributes to the postoperative recovery of symptomatic dyspnea.

Right-to-Left Ventricular Diastolic Delay in Chronic Thromboembolic Pulmonary Hypertension Is Associated With Activation Delay and Action Potential Prolongation in Right Ventricle

Background—Delayed left ventricle (LV)–to–right ventricle (RV) peak shortening results in cardiac output reduction in patients with chronic thromboembolic hypertension (CTEPH) and other types of pulmonary arterial hypertension. Why the synchrony between LV and RV is lost is unknown. We hypothesized that RV electrophysiological remodeling, notably, conduction slowing and action potential prolongation, contribute to this loss in synchrony. Methods and Results—We conducted epicardial mapping during pulmonary endarterectomy in 26 patients with CTEPH and compared these findings with clinical, hemodynamic, and echocardiographic variables. We consecutively placed a multielectrode grid on the epicardium of the RV free wall and LV lateral wall. These regions corresponded to RV and LV areas where echocardiographic Doppler sample volumes were placed to measure RV-to-LV diastolic interventricular delay. RV and LV epicardial action potential duration was assessed by measuring activation-recovery interval. Onset of diastolic relaxation of RV free wall with respect to LV lateral wall (diastolic interventricular delay) was delayed by 38±31 ms in patients with CTEPH versus −12±13 ms in control subjects (P<0.001), because, in patients with CTEPH, RV completed electric activation later than LV (65±20 versus 44±7 ms, P<0.001) and epicardial action potential duration, as assessed by activation-recovery interval measurement, was longer in RV free wall than in LV lateral wall (253±29 versus 240±22 ms, P<0.001). Conclusion—Additive effects of electrophysiological changes in RV, notably, conduction slowing and action potential prolongation, assessed by epicardial activation-recovery interval, contribute to diastolic interventricular delay in patients with CTEPH.

Embolization for Hemoptysis in Chronic Thromboembolic Pulmonary Hypertension: Report of Two Cases and a Review of the Literature

Hemoptysis is a known complication in patients with bronchial artery hypertrophy due to a variety of chronic pulmonary disorders. Bronchial artery hypertrophy is observed in most patients with chronic thromboembolic pulmonary hypertension (CTEPH), but surprisingly little is known about the incidence of hemoptysis in these patients. In this paper, we report on 2 patients with CTEPH and recurrent severe hemoptysis, who were treated by bronchial artery embolization. One patient recovered and 1 patient died as a consequence of the bleeding. A systematic review revealed 21 studies on the underlying pathology in 1,844 patients with moderate to severe hemoptysis. CTEPH was reported to be the cause of bleeding in 0.1% (n = 2), pulmonary arterial hypertension without chronic thromboembolic disease in 0.2% (n = 4), and acute pulmonary embolism in 0.7% (n = 12) of the patients. In contrast to this, 5 patients (6%) in our own series of 79 CTEPH patients suffered from moderate to severe hemoptysis requiring medical intervention. Severe hemoptysis appears to be an uncommon, but possibly underreported, life-threatening complication in CTEPH patients. As most CTEPH patients require life-long anticoagulants a therapeutic dilemma may ensue. Therefore, we propose that even mild hemoptysis in CTEPH patients warrants prompt evaluation, and treatment by embolization should be offered as first choice in CTEPH patients.

Longitudinal Follow-Up of Six-Minute Walk Distance After Pulmonary Endarterectomy

BACKGROUND The 6-minute walk test is a useful tool to assess functional outcome after pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension. However, little is known about the longitudinal dynamics in functional improvement. We performed a longitudinal follow-up of 6-minute walk distance, New York Heart Association functional class, and echocardiography after PEA. METHODS We studied 71 patients with chronic thromboembolic pulmonary hypertension who underwent PEA. A 6-minute walk test and echocardiography were performed before PEA, at 3 months after, and at annual follow-up. At the time of this report, 52 patients had returned for 2-year follow-up, 32 for 3-year follow-up, 23 for 4-year follow-up, and 11 for 5-year follow-up. RESULTS Preoperatively, the 6-minute walk distance (6-MWD) correlated with hemodynamic severity of disease (mean pulmonary artery pressure: r = -0.55, p < 0.001); total pulmonary resistance: r = -0.59, p < 0.001) After PEA, 6-MWD increased from 440 ± 109 to 524 ± 83 meters at 1 year (n = 71, p < 0.001). Further improvement was observed from 523 ± 87 meters at 1 year to 536 ± 91 meters at 2 years (n = 52, p < 0.012). After 2 years, no further improvement was observed. At 1 year, the change in 6-MWD from baseline correlated significantly with the change observed in pulmonary hemodynamics. Changes in 6-MWD and hemodynamics were more pronounced in patients with residual pulmonary hypertension after PEA, despite the worse absolute outcome. CONCLUSIONS In patients with chronic thromboembolic pulmonary hypertension, 6-MWD showed a gradual improvement up to 2 years after PEA. Patients with residual pulmonary hypertension benefited most from treatment, despite the worse absolute outcome.

Time course of restoration of systolic and diastolic right ventricular function after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

BACKGROUND In chronic thromboembolic pulmonary hypertension, right ventricular (RV) pressure overload causes RV remodeling and dysfunction. Successful pulmonary endarterectomy (PEA) initiates restoration of RV remodeling and global function. Little is known on the restoration of systolic and diastolic RV function. Using transthoracic echocardiography, we studied the time course and extent of postoperative restoration of systolic and diastolic RV function. METHODS In chronic thromboembolic pulmonary hypertension (n = 55, 36 women, age 52 ± 14 years), transthoracic echocardiography was performed before PEA (pre-PEA) and 2 weeks, 3 months, and 1 year postoperatively. RESULTS Two weeks postoperatively, RV afterload and dimension had decreased significantly, without further improvement during follow-up. Global RV function, expressed by the myocardial performance index, showed a gradual improvement (from pre-PEA 0.58 ± 0.29 to 0.45 ± 0.38, 0.39 ± 0.19, and 0.37 ± 0.18). In contrast, 2 weeks after PEA systolic RV function, as assessed by tricuspid annular plane systolic velocity excursion and peak tricuspid annular systolic velocity of the RV, had worsened, with a subsequent incomplete restoration during follow-up: tricuspid annular plane systolic velocity excursion from 19.3 ± 5.0 to 12.4 ± 2.5, 15.3 ± 3.0, and 16.8 ± 2.9 mm and systolic velocity of the right ventricle from 11.4 ± 3.0 to 9.6 ± 2.0, 10.0 ± 1.8, and 10.3 ± 1.7 cm/s. Postoperative diastolic RV function also showed a biphasic response: tricuspid inflow-to-annulus ratio from 6.1 ± 3.0 to 9.5 ± 3.5, 6.8 ± 2.4, and 6.3 ± 2.2 cm/s. Dynamics and ultimate level of restoration of systolic and diastolic RV function were similar in patients with and without residual pulmonary hypertension. CONCLUSIONS Postoperative reduction in RV afterload caused an immediate improvement in RV dimension and global function. In contrast, systolic and diastolic RV function deteriorated after PEA with subsequently a gradual yet incomplete restoration during 1-year follow-up.

Bosentan Treatment Is Associated With Improvement of Right Ventricular Function and Remodeling in Chronic Thromboembolic Pulmonary Hypertension

Medical pretreatment before pulmonary endarterectomy (PEA) can optimize right ventricular (RV) function and may improve postoperative outcome in high‐risk patients. Using cardiac magnetic resonance imaging (cMRI), we determined whether the dual endothelin‐1 antagonist bosentan improves RV function and remodeling in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who waited for PEA.

Pulmonary arterial stent implantation in an adult with Williams syndrome.

We report a 38-year-old patient who presented with pulmonary hypertension and right ventricular dysfunction due to pulmonary artery stenoses as a manifestation of Williams syndrome, mimicking chronic thromboembolic pulmonary hypertension. The patient was treated with balloon angioplasty and stent implantation. Short-term follow-up showed a good clinical result with excellent patency of the stents but early restenosis of the segments in which only balloon angioplasty was performed. These stenoses were subsequently also treated successfully by stent implantation. Stent patency was observed 3 years after the first procedure.

Pulmonary artery diameter to predict pulmonary hypertension in pulmonary sarcoidosis

Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis with a prevalence ranging from 5% to 74% [1]. The aetiology of PH in sarcoidosis is not fully understood. Usually, it is attributed to the destruction of the distal capillary bed by lung fibrosis and/or chronic hypoxaemia. However, the severity of PH does not correlate consistently with the degree of pulmonary fibrosis, and PH exists in sarcoidosis patients without fibrosis, suggesting a multifactorial mechanism. The presence of PH is associated with a poor prognosis, and early diagnosis and treatment might improve outcome [1]. Echocardiography should always be performed when PH is suspected [2]. However, the accuracy of echocardiography in patients with interstitial lung diseases is often limited due to poor image quality and unreliable tricuspid regurgitation signal to measure the right ventricular systolic pressure (RVSP) [3]. Further invasive investigation with the gold standard, right heart catheterisation (RHC), is often required. In order to optimise the noninvasive diagnostic approach, there is a need for more accurate predictors of PH. Computed tomography (CT) may raise suspicion of PH in symptomatic patients or those examined for unrelated indications by showing an increased pulmonary artery (PA) diameter (≥29 mm) and PA diameter/ascending aorta diameter (AAD) ratio (≥1.0) [2]. Similarly, PA diameter indexed to body surface area (BSA) has been suggested as possible predictor of PH. However, these parameters have never been investigated in pulmonary sarcoidosis specifically. Pulmonary artery indexed for body surface area is the most accurate predictor for PH on CT in pulmonary sarcoidosis http://ow.ly/T863m