Even non-expert radiologists report chronic thromboembolic pulmonary hypertension (CTEPH) on CT pulmonary angiography with high sensitivity and almost perfect agreement.

OBJECTIVES: To assess the diagnostic performance and interobserver agreement of CT pulmonary angiography (CTPA) in the detection of chronic thromboembolic pulmonary hypertension (CTEPH) and its features among radiologists of different levels of experience. MATERIALS AND METHODS: In this retrospective, single-center, single-blinded study, three radiologists with different levels of experience in CT imaging (R1:15 years, R2:6 years, and R3:3 years) evaluated CTPA of 51 patients ultimately diagnosed with CTEPH (European Society of Cardiology guidelines) and 49 patients without CTEPH in random order to assess the presence of CTEPH, its features in the pulmonary artery tree, proximal level of involvement, bronchial artery hypertrophy, mosaic perfusion, and right heart overload. RESULTS: CTPAs of 51 patients with CTEPH (median age, 66 years (IQR 56-72), 28 men) and 49 patients without CTEPH (median age, 65 years (IQR 50-74), 25 men) were evaluated. The sensitivity and specificity for the detection of CTEPH was 100% (all radiologists) and 100% (R1), 96% (R2), and 96% (R3) with almost perfect agreement (κ = 0.95). The sensitivity and specificity for detecting CTEPH by mosaic perfusion would be 89% (95%CI 83-93%) and 81% (74-87%). The level of pulmonary artery involvement was reported with moderate agreement (κ = 0.54, 95%CI 0.40-0.65). Substantial agreement was found in the evaluation of mosaic attenuation (κ = 0.75, 95%CI 0.64-0.84), right heart overload (κ = 0.68, 95%CI 0.56-0.79), and bronchial artery hypertrophy (0.71, 95%CI 0.59-0.82) which were the best predictors of CTEPH (p < 0.0001). CONCLUSIONS: CTPA has high sensitivity and specificity in detecting CTEPH and almost perfect agreement among radiologists of different levels of expertise. CLINICAL RELEVANCE: CT pulmonary angiography can be used as a first-line imaging modality in patients with suspected chronic thromboembolic pulmonary hypertension (CTEPH) even when interpreted by non-CTEPH experts. KEY POINTS: • CT pulmonary angiography has high sensitivity and specificity in detecting chronic thromboembolic pulmonary hypertension (CTEPH) and almost perfect interobserver agreement among radiologists of different levels of expertise. • Substantial agreement exists in the assessment of mosaic attenuation, right heart overload, and bronchial artery hypertrophy, which are the best predictors of CTEPH.

Catheter ablation of atrial fibrillation and atrial tachycardia in patients with pulmonary hypertension: a randomized study.

AIMS: Atrial fibrillation (AF), typical atrial flutter (AFL), and other atrial tachycardias (ATs) are common in patients with pulmonary hypertension. Frequently, several supraventricular arrhythmias are successively observed in individual patients. We investigated the hypothesis of whether more extensive radiofrequency catheter ablation of the bi-atrial arrhythmogenic substrate instead of clinical arrhythmia ablation alone results in superior clinical outcomes in patients with pulmonary arterial hypertension (PH) and supraventricular arrhythmias. METHODS AND RESULTS: Patients with combined post- and pre-capillary or isolated pre-capillary PH and supraventricular arrhythmia indicated to catheter ablation were enrolled in three centres and randomized 1:1 into two parallel treatment arms. Patients underwent either clinical arrhythmia ablation only (Limited ablation group) or clinical arrhythmia plus substrate-based ablation (Extended ablation group). The primary endpoint was arrhythmia recurrence >30 s without antiarrhythmic drugs after the 3-month blanking period. A total of 77 patients (mean age 67 ± 10 years; 41 males) were enrolled. The presumable clinical arrhythmia was AF in 38 and AT in 36 patients, including typical AFL in 23 patients. During the median follow-up period of 13 (interquartile range: 12; 19) months, the primary endpoint occurred in 15 patients (42%) vs. 17 patients (45%) in the Extended vs. Limited ablation group (hazard ratio: 0.97, 95% confidence interval: 0.49-2.0). There was no excess of procedural complications and clinical follow-up events including an all-cause death in the Extended ablation group. CONCLUSION: Extensive ablation, compared with a limited approach, was not beneficial in terms of arrhythmia recurrence in patients with AF/AT and PH. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; NCT04053361.

Differential diagnosis of chronic lower limb edema.

Lower extremity edema is a common complaint of patients across all medical specialties. This is a wide group of conditions, ranging from relatively minor conditions such as false swelling in lipedema to life-threatening conditions such as heart failure and nephrotic syndrome. The most common cause of chronic edema is chronic venous disease. High-quality differential diagnosis aims to determine the etiology of edema and initiate targeted treatment.

Atrial fibrillation and atrial tachycardia in patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy.

Atrial fibrillation (AF) and atrial tachycardia (AT) are frequently observed in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with pulmonary endarterectomy (PEA). Their prevalence and impact on prognosis of patients are not known. We analysed the prevalence of AF/AT and the clinical outcome in 197 patients with CTEPH treated with PEA (median age 62; interquartile range 53-68 years; 62% males). The prevalence of AF/AT was 29% (57 patients). Compared to patients without arrhythmia, the subjects with AF/AT were older [60 (50-67) vs. 62 (57-70) years], manifested an increased size of the left atrium [39 (35-44) vs. 45 (40-50) mm], had a reduced 6-min walking distance [411 (321-506) vs. 340 (254-460) m], and higher pulmonary artery systolic pressure after PEA [38 (30-47) vs. 45 (38-71) mmHg], all results with P-value <0.05. During the follow-up with a median 4.2 (1.6-6.3) years, 45 (23%) patients died. In a multivariate Cox regression model only the male gender [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.15-4.50], a reduced 6-min walking distance (HR 3.67, 95% CI 1.74-7.73), and an increased New York Heart Association class (HR 8.56, 95% CI 4.17-17.60) were associated with mortality (P < 0.05). The prevalence of AF/AT in patients with CTEPH treated with PEA is high. Arrhythmias are associated with reduced functional capacity but not with mortality.

The left atrial substrate plays a significant role in the development of complex atrial tachycardia in patients with precapillary pulmonary hypertension.

BACKGROUND: Atrial fibrillation (AF) and related atrial tachyarrhythmias (AT), including type I atrial flutter (AFL) are frequently observed in patients with pulmonary hypertension (PH). Their relationship to hemodynamic changes, atrial size, and ventricular function are still not fully verified. METHODS: We retrospectively studied hemodynamic data, echocardiographic findings and arrhythmia incidence in 814 patients with invasively diagnosed precapillary PH (aged 59 ± 14 years; 46% males). Patients with combined or post-capillary PH were excluded. RESULTS: AF / AT were identified in 225 (28%) of all the study population. Compared to the subgroup without arrhythmia, patients with AF / AT had elevated right atrial pressure (11 ± 5 vs. 9 ± 5 mmHg), wedge pressure (11 ± 3 vs. 10 ± 3), a more enlarged right atrium (50 ± 12 vs. 47 ± 11 mm) and an increased left atrial diameter in the parasternal long axis projection, p <  0.05 for all comparisons. In the multivariate model, the left atrial size, patient age, arterial hypertension, diabetes and type of PH were associated with AF / AT occurrence, p <  0.05. Patients with type I AFL were more frequently male (39 (80%) vs. 62 (42%)), were younger (61 ± 11 vs. 67 ± 10 years), had increased pulmonary artery mean pressure (50 ± 12 vs. 45 ± 12 mmHg), less advanced left atrial dilatation (38 ± 10 vs. 42 ± 7 mm), and a more enlarged right atrium (56 ± 12 vs. 48 ± 11) as compared to subjects with AF or other AT, p <  0.05. CONCLUSIONS: The evidence of elevated wedge pressure and the enlargement of the left atrium especially in patients with AF suggest a parallel involvement of the left atrial substrate in arrhythmia formation despite invasively confirmed evidence of purely isolated precapillary PH. Substantial differences were noticed between patients with type I AFL and the remaining patients with other arrhythmia types.

Surgical treatment of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease characterized by a mean pulmonary artery pressure that exceeds 25 mm Hg and is caused by intraluminal thrombi organisation, stenosis and occlusions of pulmonary artery and its branches and peripheral vascular remodelation. It is a chronic complication of acute pulmonary embolism. The obstruction of pulmonary artery branches increases pulmonary vascular resistance (PVR) and this leads to the right ventricular overload and right-sided heart failure. The treatment of choice is surgical pulmonary endarterectomy (PEA), a procedure that is performed in deep hypothermic cardiac arrest. The only center that specializes into the surgical treatment of patients with CTEPH in the Czech Republic is the Complex Cardiovascular Centre at the General Teaching Hospital in Prague. Between years 2004-2017 there were 314 patients opera-ted (including 50 patients from Slovakia, where this treatment is not available). Patients with peripheral type of CTEPH, who are not indicated for operation and also patients with residual pulmonary hypertension after PEA can be indicated for specific vasodilatation therapy. In indicated cases the treatment may involve the balloon angioplasty or lung transplantation.

Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry.

BACKGROUND: Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90-95), 91% (95% CI, 87-93), and 89% (95% CI, 86-92) in operated patients (n=404), and only 88% (95% CI, 83-91), 79% (95% CI, 74-83), and 70% (95% CI, 64-76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension-targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49-11.62; P=0.0065 and HR, 4.76; 95% CI, 1.76-12.88; P=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95-1.90; P=0.0992 and HR, 1.50; 95% CI, 1.20-1.88; P=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36-6.69; P=0.0065 and HR, 2.15; 95% CI, 1.18-3.94; P=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension-targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients. CONCLUSIONS: The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients.

Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Epidemiological data from national registries are growing worldwide, but are still unavailable in Eastern Europe. METHODS: A PAH registry was initiated in January 2007 using a nationwide network of echocardiographic centers and four diagnostic centers that specialize in PAH. All patients aged above 18 years, diagnosed with PAH and monitored between January 2000 and December 2007 were included. Patients diagnosed with PAH between January and December 2007 were classified as incident. The survival analyses were performed up to the end of 2010. Prognostic factors at the time of diagnosis were identified using uni- and multivariable Cox proportional hazard models. RESULTS: Overall, 191 patients were included (100 prevalent cases, 91 incident cases). Patients were predominantly female (n = 125) and had a mean age of 51.9 ± 16.9 years. Incident patients were significantly older at the time of diagnosis than prevalent patients (p < 0.001). Most patients (60.7%) had idiopathic PAH; 20.4% had PAH associated with congenital heart disease and 11.4% had PAH associated with connective tissue disease. Estimates of prevalence and incidence of PAH in adults were 22.4 cases per million and 10.7 cases per million per year, respectively. The 1-, 2- and 3-year survival rates in the incident PAH cohort were 89% (95% confidence intervals [CI] 83-95%), 78% (95% CI 70-87%) and 74% (95% CI 65-83%), respectively. Lower survival rates were significantly associated with higher age (hazard ratio [HR] 6.6 95% CI 1.4-30.9) and lower creatinine clearance (HR 3.3 95% CI 1.1-9.7). CONCLUSION: This is the first study in Eastern Europe to describe the prevalence, incidence and survival of patients with PAH from a national representative registry. This registry from the Czech Republic highlights that diagnosis of PAH is frequently made late in the disease continuum when patients have significant functional impairment.

[Past and present issues of the pulmonary circulation in the General University Hospital in Prague]. / Minulost a soucasnost problematiky plicní cirkulace ve Vseobecné fakultní nemocnici v Praze.

The development of right heart catheterization is closely connected not only with its pioneer Werner Forssmann but also with the University Hospital in Prague. Shortly after Forssmann´s pioneering performance of catheterization, Dr. Otto Klein measured cardiac output using the Fick´s principle in 11 patients in University Hospital. In the 60s and 70s of last century, there was established an research group represented by Severin Daum, Frantisek Boudik, Vlastimil Jezek, Alois Ourednik and Zdenek Suso at 2nd Internal Clinic of General Cardiopulmonary Hospital. After 1999, the issue of pulmonary hypertension has been re-emerged by Professor Michal Aschermann and this had significant clinical implications. The highly specialized centre for pulmonary arterial hypertension (PAH) was found at the clinic and in Cardio Centre of General University Hospital it has been initiated a successful program of pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension (CTEPH) since 2004. Surgical treatment is also provided to patients from Slovakia. The number of patients, wide range of therapy and its results, including the excellent results of surgical treatment situates the centre among the most important centres in Europe dealing with pulmonary hypertension.

Placental growth factor may predict increased left ventricular mass index in patients with mild to moderate chronic kidney disease--a prospective observational study.

BACKGROUND: Placental growth factor [PlGF) is a cardiovascular (CV) risk marker, which is related to left ventricle hypertrophy (LVH) in animal models. Currently there are no data available regarding the possible relationship of PlGF and the development of LVH or diastolic dysfunction in patients with chronic kidney disease (CKD) and the relationship of PlGF to other CV risk factors in CKD patients. The aim of our study was to determine the possible association of PlGF and several other CV risk markers to echocardiographic parameters in CKD population. METHODS: We prospectively examined selected laboratory (PlGF, fibroblast growth factor-23 -FGF23, vitamin D, parathyroid hormone, extracellular newly identified RAGE-binding protein - EN-RAGE, B-type natriuretic peptide - BNP) and echocardiographic parameters in 62 patients with CKD 2-4. Mean follow-up was 36 ±10 months. Laboratory and echocardiographic data were collected 2-3 times, at the shortest interval of 12 months apart. Multivariate regression analysis was used to detect independent correlations of variables. RESULTS: Increased left ventricular mass index (LVMI, g/m2.7) was found in 29% patients with CKD 2-4, left ventricular (LV) diastolic dysfunction was detected in 74.1% patients (impaired LV relaxation in 43.5% patients and pseudonormal pattern in 30.6% patients). After 36 ± 10 months increased LVMI was found in 37.1% patients with CKD 2-4, LV diastolic dysfunction was detected in 75.8% patients (impaired LV relaxation in 43.5% patients and pseudonormal pattern in 32.3% patients). Following independent correlations were found: LVMI was related to PlGF, cholesterol, BNP, systolic blood pressure and serum creatinine. EN-RAGE correlated positively with left atrial diameter and inversely with E/A ratio. During the follow-up we found a significant increase in LVMI and left atrial diameter, whereas a significant decrease in LVEF was noted. CONCLUSION: According to our data, PlGF is independently related to increased LV mass in CKD, whereas EN-RAGE is more likely related to diastolic dysfunction in this population.

Correction: Jansa et al. Hospitalisation Is Prognostic of Survival in Chronic Thromboembolic Pulmonary Hypertension. J. Clin. Med. 2022, 11, 6189.

Error in Figure [...].

Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. METHODS AND RESULTS: The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%- 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. CONCLUSIONS: Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension-targeted treatments.

Epidemiology of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic.

This study investigated the epidemiology and survival outcomes of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic, wherein pulmonary endarterectomy (PEA) surgery was the only targeted treatment option until 2015. This study included all consecutive adults newly diagnosed with CTEPH in the Czech Republic between 2003 and 2016. Incidence/prevalence rates were calculated using general population data extracted from the Institute of Health Information and Statistics of the Czech Republic. Kaplan-Meier estimates of survival from diagnosis until 2018 were calculated. Of a total of 453 patients observed, 236 (52.1%) underwent PEA (median time from diagnosis to PEA: 2.9 months) and 71 (34.1%) had residual pulmonary hypertension (PH) post-PEA. CTEPH incidence rate (95% confidence interval [CI]) between 2006 and 2016 was 4.47 (4.05; 4.91) patients per million (ppm) per year, and the prevalence (95% CI) was 37.43 (33.46; 41.73) ppm in 2016. The rate of CTEPH-related hospitalizations (95% CI) per 100 person-years was 24.4 (22.1; 26.9) for operated patients and 34.2 (30.9; 37.7) for not-operated patients. Median overall survival (95% CI) for all patients from CTEPH diagnosis was 11.2 (9.4; not reached) years. Five-year survival probability (95% CI) was 95.3% (89.9; 97.9) for operated patients without residual PH, 86.3% (75.3; 92.7) for operated patients with residual PH and 61.2% (54.0; 67.6) for not-operated patients. This study reported epidemiological estimates of CTEPH in the Czech Republic consistent with estimates from other national systematic registries; and indicates an unmet medical need in not-operated patients and operated patients with residual PH.

Hospitalisation Is Prognostic of Survival in Chronic Thromboembolic Pulmonary Hypertension.

This analysis investigated the prognostic value of hospitalisation in chronic thromboembolic pulmonary hypertension (CTEPH) using data from the Czech Republic, wherein pulmonary endarterectomy (PEA) was the only targeted treatment option until 2015. Using a landmark method, this analysis quantified the association between a first CTEPH-related hospitalisation event occurring before 3-, 6-, 9-, and 12-month landmark timepoints and subsequent all-cause mortality in adult CTEPH patients diagnosed between 2003 and 2016 in the Czech Republic. Patients were stratified into operable and inoperable, according to PEA eligibility. CTEPH-related hospitalisations were defined as non-elective. Hospitalisations related to CTEPH diagnosis, PEA, balloon pulmonary angioplasty, or clinical trial participation were excluded. Of 436 patients who survived to ≥3 months post diagnosis, 309 were operable, and 127 were inoperable. Sex- and age-adjusted hazard ratios (HRs) showed CTEPH-related hospitalisation was a statistically significant prognostic indicator of mortality at 3, 9, and 12 months in inoperable patients, with an approximately 2-fold increased risk of death in the hospitalisation group (HRs [95% CI] ranging from 1.98 [1.06-3.70] to 2.17 [1.01-4.63]). There was also a trend of worse survival probabilities in the hospitalisation groups for operable patients, with the difference most pronounced at 3 months, with a 76% increased risk of death (adjusted HR [95% CI] 1.76 [1.15-2.68]). This first analysis on the prognostic value of CTEPH-related hospitalisations demonstrates that a first CTEPH-related hospitalisation is prognostic of mortality in CTEPH, particularly for inoperable patients. These patients may benefit from medical and/or interventional therapy.

Are pulmonary artery pulsatility indexes able to differentiate chronic pulmonary thromboembolism from pulmonary arterial hypertension? An echocardiographic and catheterization study.

The differentiation between chronic pulmonary thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH) remains a clinical challenge. The aim of our study was to evaluate the usefulness of both echocardiographically and invasively derived pulmonary artery pulsatility indexes in the etiologic differentiation of patients with CTEPH and PAH. We retrospectively analyzed the results of echocardiographic and invasive hemodynamic examinations in 125 patients with either CTEPH (n = 62) or PAH (n = 63). Invasive data were obtained in 52 patients with CTEPH and 43 PAH patients. Using echocardiography, pulmonary artery systolic (PASP), diastolic (PADP) and mean (PAMP) pressures were estimated from velocities of tricuspid regurgitation and pulmonary regurgitation, respectively. Pulse pressure (PP) was calculated as the difference between PASP and PADP. To obtain pulmonary artery pulsatility indexes, we normalized PP by PASP (PP/PASP), by PAMP (PP/PAMP) and by PADP (PP/PADP). Pulsatility indexes assessed by echocardiography did not differ between CTEPH and PAH patients except for PP/PAMP [PP/PAMP (1.82 ± 0.33 vs. 1.40 ± 0.3, p < 0.001)]. Invasively derived pulsatility indexes were significantly higher in subjects with CTEPH (0.60 ± 0.08 vs. 0.53 ± 0.09 for PP/PASP; 0.98 ± 0.21 vs. 0.81 ± 0.21 for PP/PAMP; 1.58 ± 0.52 vs. 1.21 ± 0.41 for PP/PADP; all p < 0.001). The areas under the receiver-operating characteristic curves analysis showed that no cutoff value allowed discriminating between CTEPH and PAH by using echocardiographically or invasively derived pulsatility indices. Invasively derived pulmonary artery pulsatility indexes as well as echocardiographically determined PP/PAMP indexes are higher in CTEPH compared to PAH. However, due to the important overlap no optimal threshold values of these parameters can be given to allow satisfactory discrimination of the two diseases in clinical practice.

Computed tomography angiographic parameters of pulmonary artery as prognostic factors of residual pulmonary hypertension after pulmonary endarterectomy.

OBJECTIVES: This study aimed to retrospectively assess using computed tomography pulmonary angiography (CTPA) for predicting residual pulmonary hypertension (RPH) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA). METHODS: We retrospectively analyzed data of 131 patients with CTEPH who underwent PEA in our center (2008-2015). We measured several diameters of the pulmonary artery and thoracic aorta preoperatively. We evaluated the relationship between these measurements (and their indices) and signs of RPH represented by pulmonary artery systolic pressure (PASP) estimated by echocardiography. RESULTS: Significant correlations were observed between the aortopulmonary index and prediction of any residual hypertension and moderate/severe hypertension 1 year after PEA, and any residual hypertension and severe hypertension 2 years after PEA. The aortopulmonary index was significantly related to a reduction in PASP 1 year after the operation. A lower aortopulmonary index (≤0.88 for the ascending aorta and ≤0.64 for the descending aorta) predicted lower RPH. CONCLUSIONS: Preoperative CTPA parameters can be used to assess the risk of RPH after PEA. The aortopulmonary index has significant predictive value for RPH and a reduction in PASP after PEA. Lower values of the aortopulmonary index suggest a better outcome after PEA.

The impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension - results of a retrospective clinical registry.

AIMS: The primary objective of the registry was to assess the impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH) that was inoperable or persistent/recurrent after pulmonary endarterectomy (PEA). In contrast to randomized pivotal trials, this non-interventional registry evaluated the effectiveness and safety of riociguat in a real-world setting. METHODS: Retrospective data were collected from patients' charts as recorded in routine clinical practice from the initiation of riociguat therapy up to approximately 5 months and 1 year after this initiation. RESULTS: In total, 51 patients from a single site were enrolled. After 5 months (mean duration) of riociguat treatment, the following improvements from baseline were observed: change of distance in the 6-minute walking distance (6MWD) (P=0.066); change of score from the quality of life questionnaire (EQ5D-5L) (P=0.020), and overall self-assessment of health status (P=0.001). New York Heart Association (NYHA) class improved in 24.3% of patients. After 11.2 months (mean duration) of riociguat treatment, the following improvements from baseline were observed: change of distance in the 6MWD test (P=0.006), and overall self-assessment of health status (P=0.009). NYHA class improved in 46.4% of patients. Riociguat was well tolerated. In total, 4 patients reported side effects, with hospitalization required in one case and 2 patients who had to discontinue the treatment. Annual survival rate was 89.1%. CONCLUSION: Riociguat improves functional NYHA class, distance in the 6MWD test and quality of life in a real-world patient population.

The prevalence and clinical outcome of supraventricular tachycardia in different etiologies of pulmonary hypertension.

PURPOSE: Patients with pulmonary hypertension (PH) frequently suffer from supraventricular tachycardias (SVT). The main purpose of our study was to identify the cumulative incidence of SVT in patients with different etiologies of PH. The secondary objective was to analyse the clinical impact of SVT. METHODS: We retrospectively studied the prevalence of SVT and the clinical outcome in 755 patients (41% males; 60 ± 15 years; mean follow-up 3.8 ± 2.8 years) with PH of different etiologies. The prevalence of SVT was analysed separately in isolated pre-capillary PH (Ipc-PH) and in patients with combined post- and pre-capillary PH (Cpc-PH). RESULTS: The prevalence of SVT in the Ipc-PH group (n = 641) was 25% (n = 162). The most prevalent arrhythmias were atrial fibrillation followed by a typical atrial flutter (17% and 4.4% of all Icp-PH patients). An excessive prevalence of SVT was found in patients with pulmonary arterial hypertension associated with congenital heart disease (35%, p = 0.01). Out of the overall study population, Cpc-PH was present in 114 (15%) patients. Patients with Cpc-PH manifested a higher prevalence of SVT than subjects with Ipc-PH (58; 51% vs. 162; 25%; p <0.0001) and were more likely to have persistent or permanent atrial fibrillation (38; 29% vs. 61; 10%; p <0.0001). Parameters significantly associated with mortality in a multivariate analysis included age, male gender, functional exercise capacity and right atrial diameter (p < 0.05). Neither diagnosis of SVT nor type of arrhythmia predicted mortality. CONCLUSIONS: The study detected a significant prevalence of SVT in the population of PH of different origins. Different spectrum and prevalence of arrhythmia might be expected in different etiologies of PH. Patients with an elevated post-capillary pressure showed a higher arrhythmia prevalence, predominantly due to an excessive number of atrial fibrillations. The diagnosis of SVT was not associated with mortality.

Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension: Impact on Clinical and Hemodynamic Parameters, Quality of Life and Risk Profile.

Balloon pulmonary angioplasty (BPA) is a novel treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not eligible for pulmonary endarterectomy (PEA) or suffer from persistent pulmonary hypertension after PEA. The aim of this study was to evaluate the real-life efficacy and safety of BPA in a consecutive group of patients who were diagnosed and treated in the national referral center for CTEPH in the Czech Republic. Here we report data from 160 BPA procedures performed in 64 patients. Efficacy analysis was performed in the subgroup of 25 patients who completed BPA series. Significant improvements were observed in New York Heart Association functional class (4% to 79% in I/II, p < 0.001), 6 min walking test distance (+54.3 m, p < 0.001), risk profile (15.8% to 68.5% with presence of 2/3 low risk criteria, p < 0.001), pulmonary artery mean pressure (-18%, p < 0.001), pulmonary vascular resistance (-32%, p < 0.001), stroke volume (+17%, p = 0.011) and quality of life (+37% in assessment of overall health status by a patient, p < 0.001). We observed 1 fatal periprocedural complication (1.6% of all 64 patients) and 19 BPA-related non-fatal complications (11.9% of all 160 interventions) that predominantly included hemoptysis (10.0% of all sessions). Overall survival at 12 months was 94.6%.

Population pharmacokinetics of riociguat and its metabolite in patients with chronic thromboembolic pulmonary hypertension from routine clinical practice.

Pharmacokinetic data for riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have previously been reported from randomized clinical trials, which may not fully reflect the population encountered in routine practice. The aim of the current study was to characterize the pharmacokinetic of riociguat and its metabolite M1 in the patients from routine clinical practice. A population pharmacokinetic model was developed in NONMEM 7.3, based on riociguat and its metabolite plasma concentrations from 49 patients with CTEPH. One sample with riociguat and M1 concentrations was available from each patient obtained at different time points after last dose. Age, bodyweight, sex, smoking status, concomitant medications, kidney and liver function markers were tested as potential covariates of pharmacokinetic of riociguat and its metabolite. Riociguat and M1 disposition was best described with one-compartment models. Apparent volume of distribution (Vd/F) for riociguat and M1 were assumed to be the same. Total bilirubin and creatinine clearance were the most predictive covariates for apparent riociguat metabolic clearance to M1 (CLf,M1/F) and for apparent riociguat clearance through remaining pathways (CLe,r/F), respectively. CLf,M1/F, CLe,r/F, Vd/F of riociguat and M1, and clearance of M1 (CLe,M1/F) for a typical individual with 70 mL/min creatinine clearance and 0.69 mg/dL total bilirubin were 0.665 L/h (relative standard error = 17%)), 0.66 (18%) L/h, 3.63 (15%) L and 1.47 (19%) L/h, respectively. Upon visual identification of six outlying individuals, an absorption lag-time of 2.95 (6%) h was estimated for these patients. In conclusion, the only clinical characteristics related to riociguat exposure in patients with CTEPH from routine clinical practice are total bilirubin and creatinine clearance. This confirms the findings of the previous population pharmacokinetic studies based on data from randomized clinical trials.