Non-tuberculous mycobacterial lung disease (NT MLD ) in patients with chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension.

INTRODUCTION: Non-tuberculous mycobacterial lung diseases (NTMLD) occur rarely and are diagnosed mainly in patients belonging to risk groups. Pulmonary hypertension (PH) has not been recognised as a risk factor for NTMLD yet. The aim of the study was to analyse the clinical course and predisposing factors of NTMLD recognised in our centre between 2002 and 2012 in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH). MATERIAL AND METHODS: Thirteen patients (10 - CTEPH, 3 - IPAH) entered the study. PH was recognised during right heart catheterisation. Median value of mean pulmonary artery pressure (mPAP) was 49 mm Hg (39-65 mm Hg). NTMLD was diagnosed according to ATS guidelines (2007). RESULTS: M. kansasii was the most frequent pathogen. Most patients complained of the exaggeration of dyspnoea and productive cough. Computed tomography of the chest with angiography revealed infiltrations with cavitation in seven patients and cavities surrounded by micronodules in six patients. In all CTEPH patients, NTMLD developed in the hypoperfused lung areas. No parenchymal abnormalities preceded the development of NTMLD. After diagnosis all of the patients received antituberculous treatment; in 12/13 improvement was achieved. By the end of March 2014 seven patients died due to right heart insufficiency, no deaths due to NTMLD were noted. CONCLUSIONS: NTMLD should be suspected in patients with CTEPH or IPAH, presenting with productive cough and a new pulmonary infiltrate with cavitation. In patients with CTEPH, special attention should be paid to a new cavitary lesions without accompanying thrombus in the artery supplying the area. High mPAP (CTEPH/IPAH) and hypoperfusion (CTEPH) are predisposing to NTMLD.

[Abnormalities in high-resolution computed tomography of the lungs in patients with idiopathic pulmonary arterial hypertension -- correlation with hemodynamic parameters and prognostic significance]. / [Zmiany w tomografii komputerowej pluc o wysokiej rozdzielczosci u chroych na idiopatyczne tetnicze nadcisnienie plucne--powiazanie z parametrami hemodynamicznymi i znaczenie rokownicze.

INTRODUCTION: The risk stratification in idiopathic pulmonary arterial hypertension (IPAH) patients is currently based on haemodynamic and functional parameters as well as serum biomarker concentrations. Until now the importance of changes appearing in high-resolution computed tomography (HRCT) of the lungs of patients with IPAH has not been investigated. MATERIAL AND METHODS: Lung HRCT scans were analysed retrospectively in 48 IPAH patients (patients): 37 women, 11 men, mean age 41 +/- 15 years. RESULTS: Focal ground-glass opacifications (FGG) were found in 12 patients (25%), and centrilobular nodules (CN) were found in 8 patients (17%). In the remaining 58% of patients HRCT revealed no changes (N). Significantly lower stroke volume was found in the CN group (41.0 +/- 8.5 ml) compared to 60.8 +/- 15.1 ml in the FGG group and 58.1 +/- 18.0 ml in the N group (p = 0.03). Right atrial pressure was significantly higher in the CN group (12.2 +/- 4.86 mm Hg) than in the FGG group (6.9 +/- 3.9 mm Hg) and the N group (7.6 +/- 5.3 mm Hg), p = 0.047. The presence of nodules was combined with considerably increased risk of death, both in univariate analysis (HR 5.35, 95% CI: 1.16-24.7, p = 0.03) and in multivariate analysis (HR 6.98, 95% CI: 1.41-34.59, p = 0.02). Ground-glass opacifications correlated neither with haemodynamic nor functional indexes, and were of no prognostic significance. CONCLUSIONS: The presence of centrilobular nodules in lung HRCT scans of IPAH patients was combined with more severe haemodynamic compromise and was an independent negative prognostic indicator.

The evolution of electrocardiographic signs of right ventricular overload after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Balloon pulmonary angioplasty (BPA) is a treatment option for a patient with chronic thromboembolic pulmonary hypertension. OBJECTIVES: We aimed to investigate the evolution of electrocardiographic (ECG) markers of right ventricular hypertrophy (RVH) after BPA. PATIENTS AND METHODS: Standard 12­lead ECG was performed in 41 patients with chronic thromboembolic pulmonary hypertension before the first BPA and after completion of treatment. RESULTS: In the whole study group, the percentage change in the pulmonary vascular resistance (PVR) after BPA correlated with the percentage change in the values of the following ECG parameters (P <0.05): axis of the QRS (rho = 0.530) and T wave (rho = 0.372); P wave in leads II (rho = 0.340) and III (rho = 0.430); S wave in lead V5 (rho = 0.634); R/S ratio in lead V5 (rho = -0.636); S wave in lead V6 (rho = 0.508); S wave in lead I (rho = 0.496). Then, the group was divided into 2 subgroups: group A, defined as a drop in PVR greater than the median value (49%) for the whole study population; and group B, defined as a drop in PVR below the median value. In group A, the following parameters changed after BPA: T­wave axis (P <0.001), P wave in lead II (P <0.001), S wave in lead V5 (P <0.001), R/S ratio in lead V5 (P <0.001). In group B, despite some hemodynamic and functional improvement, there were no differences in ECG mark ers of RVH after BPA. CONCLUSIONS: An improvement in RVH parameters can be observed on ECG after a hemodynamically effective BPA.

Characteristics and prognosis of patients with decompensated right ventricular failure during the course of pulmonary hypertension.

BACKGROUND: New therapies for pulmonary arterial hypertension have prolonged survival but simultaneously increased the number of hospital admissions because of decompensated right heart failure (DRHF). The optimal approach in DRHF has not been established yet. AIM: Analysis of clinical course of DRHF in a group of patients with pulmonary hypertension treated in a single referral centre. METHODS: We retrospectively analysed 60 episodes of DRHF in 37 patients (29 females, mean age 44+/-17 years) with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension admitted to our hospital between 2005 and 2007. We assessed the cause of decompensation, vital signs at admission, functional class and laboratory values. We classified all episodes into four haemodynamic profiles using the value of systolic blood pressure together with presence of peripheral perfusion abnormalities (profile cold vs. warm) and symptoms of venous congestion (profile wet vs. dry). Primary end-point was in-hospital mortality. RESULTS: The most common causes of DRHF were infection (27%), drug noncompliance (20%), and pulmonary embolism (3%). In 48% no causative factor was indentified. There were 19 (32%) in-hospital deaths. The highest mortality was observed among patients with connective tissue disease (61%). The haemodynamic profile 'warm-wet' was the most common (48%) and the profile 'cold-dry' was the rarest but was associated with a 100% mortality. Patients who died had higher value of functional class (3.84+/-0.38 vs. 3.51+/-0.55, p=0.01) and higher activity of aspartate transaminase (61+/-61 vs. 42+/-78 U/l, p=0.02) compared with those who survived. In multivariate analysis higher dopamine dose (RR 2.0/1 microg/kg/min, 95% CI 1.00-5.00, p <0.001) was an independent factor of in-hospital death. In contrast 'rescue therapy' with iloprost or treprostinil decreased mortality (RR 0.09, 95% CI 0.01-0.99, p=0.04). Mortality in patients receiving dopamine was higher (60 vs. 18%, p=0.001) than in patients treated without dopamine. CONCLUSION: Mortality in patients with pulmonary hypertension and DRHF remains very high and seems to be related to haemodynamic profile on admission. The newly introduced therapy with parenteral prostanoids may be more beneficial than dopamine infusion.

[Wegener's granulomatosis presenting with ischaemic stroke]. / Udar niedokrwienny mózgu w przebiegu ziarniniakowatosci Wegenera.

Wegener's granulomatosis (WG) is a systemic disease of unknown origin characterized by necrotizing granulomatous vasculitis that involves primarily the upper and the lower respiratory tracts and the kidneys. A 44-year-old woman presenting with unusual neurological manifestation is reported. The patient with multiple pulmonary round shadows and hilar lymphadenopathy on the chest X-ray pictures, suffered from sudden hemiparesis episode. Computed tomography revealed ischemic stroke focus. A diagnosis of WG was confirmed by histological examination of specimen obtained during open lung biopsy. During the combination chemotherapy with prednisolone and cyclophosphamide, neurological symptoms decreased and clinical condition significantly improved.

Acute and chronic dissection of pulmonary artery: new challenges in pulmonary arterial hypertension?

Right ventricular failure is a leading cause of mortality in patients with pulmonary arterial hypertension (PAH). However, up to 25% of such patients die unexpectedly, without warning signs of hemodynamical decompensation. We previously documented that pulmonary artery (PA) dilatation significantly increases the risk of those deaths. Some of them may be due to dissection of PA resulting in cardiac tamponade. However, direct confirmation of this mechanism is difficult as most of such deaths occur outside hospitals. We present 4 patients with severe PAH and PA dilatation in whom PA dissection has been confirmed. Three patients had IPAH, one had PAH associated with congenital heart disease. All patients had mean pulmonary artery pressure (PAP) > 50 mmHg at diagnosis and dissection occurred late in the course of apparently well controlled disease (6 to 14 years). Several clinical elements were common to our patients - high systolic PAP, long lasting PH, progressive dilatation of PA to more than 50 mm with chest pain prior to dissection. However, clinical course followed three different patterns: sudden death due to cardiac tamponade, hemopericarditis caused by blood leaking from dissected aneurysm with imminent but not immediate cardiac tamponade, or chronic asymptomatic PA dissection. Indeed, two of our patients are alive and on lung transplantation waiting list for more than 2 years now. Further research is needed to suggest optimal management strategies for patients with stable PAH but significantly dilated proximal pulmonary arteries or confirmed PA dissection depending on the clinical presentation and expected outcome.

Sequential treatment with sildenafil and riociguat in patients with persistent or inoperable chronic thromboembolic pulmonary hypertension improves functional class and pulmonary hemodynamics.

BACKGROUND: This study evaluated the incremental effect of riociguat on pulmonary hemodynamics in patients with inoperative or persistent chronic thromboembolic pulmonary hypertension (CTEPH) treated previously with sildenafil. METHODS: The retrospective study included 28 patients diagnosed with CTEPH who were ineligible for surgical treatment due to distal thrombi location or who suffered from persistent CTEPH after pulmonary endarterectomy and who were treated with sildenafil at a dose of 25 mg TID for a minimum of 3 months. Sildenafil was subsequently discontinued, and riociguat therapy was started with gradually increasing doses. Right heart catheterization was performed and WHO functional class (FC) was assessed in each patient at three time points: before starting sildenafil therapy (baseline), before the transition to riociguat, and after 3 to 6 months of therapy with riociguat. RESULTS: Compared to baseline, the use of sildenafil and riociguat significantly decreased pulmonary vascular resistance (PVR) (10.47 ±â€¯3.56 vs. 7.81 ±â€¯3.58 Wood units, p < 0.001) and mean pulmonary arterial pressure (PAP) (54.1 ±â€¯11.6 vs. 46.1 ±â€¯13.2 mm Hg; p < 0.001) while increasing cardiac output (CO) (4.31 ±â€¯0.88 vs. 4.85 ±â€¯0.87 L/min; p = 0.007). Switching from sildenafil to riociguat reduced PVR by 14% (p = 0.005) and the mean PAP by 6% (p = 0.03) while increasing CO by 11% (p = 0,002). The number of patients with WHO FC III and IV symptoms decreased from 71,4% to 57,1% (p = 0,02) after the change from sildenafil to riociguat. CONCLUSIONS: Replacing sildenafil with riociguat in patients with inoperable or persistent CTEPH may improve pulmonary hemodynamics and FC.

[Vascular complications in a 51-year-old female with a primary antiphospholipd syndrome--a case report]. / Powiklania naczyniowe u 51-letniej chorej z pierwotnym zespolem antyfosfolipidowym--opis przypadku.

A 51-year-old woman with antiphospholipid syndrome was readmitted to the hospital two years after successful surgical pulmonary thrombendarteriectomy for severe chronic thromboembolic pulmonary hypertension (CTEPH). Exertional dyspnea, chest pain and ECG pattern could suggest relapse of pulmonary thromboembolism. However, no signs of pulmonary hypertension were found at echocardiography. Coronary angiography revealed proximal critical occlusion in the left anterior descending artery which was successfully treated with PTCA and stenting. Coronary artery disease may mimic relapse of CTEPH and this should be remembered especially in patients with antiphospholipid syndrome, who have increased risk of coronary artery disease especially in the presence of other classical risk factors.

[The usefulness of plasma cystatin C determination as a marker of glomerular filtration rate]. / Przydatnosc oznaczania cystatyny C dia oceny wielkosci przesaczania klebuszkowego.

Cystatin C is a low molecular weight protein; a cysteine proteinase inhibitor. As it is freely filtrated in the renal glomeruli, and not reabsorbed into circulation, therefore it may be used as a marker of glomerular filtration rate (GFR). We discuss clinical studies which were focused on the feasibility of plasma Cys C determination as a marker of GFR in various populations. Many of these studies suggest that plasma Cys C may be superior to plasma creatinine for the detection of patients with early decline in renal function. Recent data indicate, that Cys C may be a risk marker or factor of death or cardiovascular event in high-risk populations.

Changing the strategy of balloon pulmonary angioplasty resulted in a reduced complication rate in patients with chronic thromboembolic pulmonary hypertension. A single-centre European experience.

BACKGROUND AND AIM: To assess the safety and efficacy of a refined balloon pulmonary angioplasty (BPA) strategy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: There were 157 BPA sessions performed in 56 CTEPH patients (47 non-operable, nine after pulmonary endarterectomy; aged 58.6 ± 17.9 years; 28 females) with severely impaired pulmonary haemodynamics (mean pulmonary artery pressure [mPAP]: 51.3 ± 12.2 mm Hg, pulmonary vascular resistance [PVR]: 10.1 ± 3.9 Wood Units). The first 50 sessions aimed to recanalise chronic occlusions and prevent reocclusion with aggressive anticoagulation. The next 107 sessions aimed to relieve "web" and "ring" lesions using reduced tip load guidewires and less intensive anticoagulation. RESULTS: There was significant reduction in haemoptysis (22% vs. 7%, p = 0.01), vessel injury (30% vs. 13%, p = 0.01), and reperfusion pulmonary injuries (22% vs. 4%, p = 0.01) after changing the BPA strategy. Mortality at 14 days was also reduced (6% vs. 0%; p = 0.05). The cumulative survival rate was 94.6% at 24 months after the first BPA, which was more favourable than medically treated historic controls. In the 31 patients with > 3 BPA sessions, there was significant reduction of PVR (10.3 ± 3.7 vs. 5.9 ± 2.8 Wood Units; p = 0.01), mPAP (50.7 ± 10.8 vs. 35.6 ± 9.3 mm Hg; p = 0.01) and improvement in World Health Organisation functional class (3.19 ± 0.48 vs. 1.97 ± 0.80; p < 0.001). CONCLUSIONS: Balloon pulmonary angioplasty improves haemodynamics and outcome but requires refined strategy to limit early complication rate.

Outcome of Medically Versus Surgically Treated Patients With Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an ominous disease leading to progressive right heart failure. Selected patients can be treated by pulmonary endarterectomy (PEA). We assessed long-term clinical outcome of patients with CTEPH who underwent PEA and patients who remained on medical treatment alone. A total of 112 consecutive patients with CTEPH referred between 1998 and 2008 to one center were followed for a mean of 35 (range 0-128) months after diagnosis. All the patients had advanced pulmonary hypertension at baseline. The operated group had higher World Health Organization functional class compared to the nonoperated group. No other differences in hemodynamic, echocardiographic, or biochemical parameters were observed at baseline. Despite the perioperative mortality rate of 9.1%, patients who underwent PEA had significantly lower long-term mortality compared to nonoperated patients (12.7% vs 34.8%; P = .003), and PEA survivors showed sustained clinical improvement. All efforts should be undertaken to perform PEA in all patients with operable CTEPH.

In-hospital major bleeding predicts mortality in patients with pulmonary embolism: an analysis of ZATPOL Registry data.

BACKGROUND: There are no data on the association between in-hospital bleeding and mortality in patients with pulmonary embolism (PE). OBJECTIVES: To assess whether in-hospital major bleeding predicts in-hospital and 90-day mortality in patients with PE confirmed objectively using validated diagnostic criteria. METHODS: ZATPOL is a prospective national registry of consecutive patients with suspected PE admitted to 86 cardiology departments across Poland from January 2007 to September 2008. We retrospectively studied the influence of in-hospital bleeding on outcomes. RESULTS: Of 2015 patients enrolled, 1216 were locally diagnosed with PE. Validated diagnostic criteria according to the European Society of Cardiology guidelines were met in 1112 patients. In the latter group, major bleeding occurred in 3.6%, and 0.5% had fatal bleeding. Thrombolytic therapy was administered to 11% of patients. Vascular access site bleeding was the most common (40%). Except for hypotension or shock and cancer, major bleeding was the strongest independent predictor of both in-hospital (OR 3.47; P=0.003) and 90-day mortality (OR 2.75; P=0.009). Other factors independently associated with in-hospital mortality were: shock or hypotension (OR 7.45; P<0.001), cancer (OR 1.9; P=0.044), and presence of ≥1 concomitant disease (OR 2.59; P<0.001). Other predictors of 90-day mortality were: shock or hypotension (OR 5.23; P<0.001), cancer (OR 3.57; P<0.001), presence of ≥1 concomitant disease (OR 2.01; P=0.001) and age>71 years (OR 1.5; P=0.063). CONCLUSION: In-hospital major bleeding is a newly described strong independent predictor of both in-hospital and 90-day mortality in patients with objectively confirmed PE.

Pulmonary artery dilatation correlates with the risk of unexpected death in chronic arterial or thromboembolic pulmonary hypertension.

BACKGROUND: Right ventricular failure does not explain all cases of death in patients with chronic pulmonary hypertension. Searching for alternative explanations, we evaluated the prognostic significance of main pulmonary artery (PA) dilatation in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: A retrospective outcome analysis was made of 264 patients (aged 46 ± 17 years; women, 69%; PAH, 82%) who underwent both CT scan measurement of the PA and right-sided heart catheterization (mean PA pressure, 57.6 ± 16.5 mm Hg) at initial evaluation. RESULTS: The diameter of the PA ranged from 28 to 120 mm (mean, 39 ± 8.6 mm; median, 38 mm) and was largest in patients with unrepaired congenital defects (42.6 ± 7.6 mm). Pulmonary pulse pressure (P = .04), lower age (P = .03), and duration of symptoms (P < .001) were independently but weakly related to PA diameter. During follow-up (median, 38 months), 99 patients (37%) died. Of these 99 deaths, 73 (74%) were due to heart failure or comorbidities, and 26 (26%) were unexpected deaths (UE-Ds). PA diameter (hazard ratio [HR], 1.06 per 1 mm; 95% CI, 1.03-1.08), heart rate (HR, 1.30 per 10 beats/min; 95% CI, 1.01-1.66), and systolic pulmonary arterial pressure (HR, 1.02 per 1 mm Hg; 95% CI, 1.01-1.04) were the only independent predictors of UE-D and differed from the usual predictors found in the study group for all-cause mortality. PA diameter ≥ 48 mm had 95% specificity and 39% sensitivity and carried 7.5 times higher risk of UE-D (95% CI, 3.4-16.5; P < .0001) during follow-up. CONCLUSIONS: PA dilatation emerges as an independent risk factor for death unexplained by right ventricular failure or comorbidities in patients with PAH and CTEPH. The possible mechanisms include, but are not limited to, PA compression of the left main coronary artery, PA rupture, or dissection with cardiac tamponade.

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

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