Marcin Kurzyna

Definitions and diagnosis of pulmonary hypertension.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥ 25 mm Hg at rest, measured during right heart catheterization. There is still insufficient evidence to add an exercise criterion to this definition. The term pulmonary arterial hypertension (PAH) describes a subpopulation of patients with PH characterized hemodynamically by the presence of pre-capillary PH including an end-expiratory pulmonary artery wedge pressure (PAWP) ≤ 15 mm Hg and a pulmonary vascular resistance >3 Wood units. Right heart catheterization remains essential for a diagnosis of PH or PAH. This procedure requires further standardization, including uniformity of the pressure transducer zero level at the midthoracic line, which is at the level of the left atrium. One of the most common problems in the diagnostic workup of patients with PH is the distinction between PAH and PH due to left heart failure with preserved ejection fraction (HFpEF). A normal PAWP does not rule out the presence of HFpEF. Volume or exercise challenge during right heart catheterization may be useful to unmask the presence of left heart disease, but both tools require further evaluation before their use in general practice can be recommended. Early diagnosis of PAH remains difficult, and screening programs in asymptomatic patients are feasible only in high-risk populations, particularly in patients with systemic sclerosis, for whom recent data suggest that a combination of clinical assessment and pulmonary function testing including diffusion capacity for carbon monoxide, biomarkers, and echocardiography has a higher predictive value than echocardiography alone.

Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension.

OBJECTIVES The purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH). BACKGROUND Bosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH. METHODS Patients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment. RESULTS Baseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m(2) (p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm(2) (p = 0.003), LV systolic eccentricity index = -0.12 (p = 0.047), RV end-systolic area = -2.3 cm(2) (p = 0.057), RV:LV diastolic areas ratio = -0.64 (p = 0.007), Doppler RV index = -0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05). CONCLUSIONS Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.

Detectable Serum Cardiac Troponin T as a Marker of Poor Prognosis Among Patients With Chronic Precapillary Pulmonary Hypertension

Background—Right ventricular failure is a leading cause of death in patients with chronic pulmonary hypertension (PH). We checked whether detection of cardiac troponin T (cTnT), a specific marker of myocyte injury, could be useful in prognostic stratification of those patients. Methods and Results—Initial evaluation of 56 clinically stable patients (age 41±15 years) with pulmonary arterial (51 patients) or inoperable chronic thromboembolic (5 patients) PH (mean pulmonary arterial pressure 60±18 mm Hg) included cTnT test, allowing detection of its serum levels ≥0.01 ng/mL [cTnT(+)]. cTnT was detectable in 8 of 56 (14%) patients (mean±SD, 0.034±0.022; range, 0.010 to 0.077 ng/mL). Despite similar pulmonary hemodynamics, they had higher heart rate (92±15 versus 76±14 bpm, P =0.004), lower mixed venous oxygen saturation (50±10% versus 57±9%, P =0.04), and higher serum N-terminal pro-B–type natriuretic peptide (4528±3170 versus 2054±2168 pg/mL, P =0.03) and walked less during the 6-minute walk test (298±132 versus 396±101 m, P =0.02). Cumulative survival estimated by Kaplan-Meier curves was significantly worse at 24 months in cTnT(+) compared with cTnT(−) (29% versus 81%, respectively, log-rank test P =0.001). Multivariate analysis revealed cTnT status (hazard ratio, 4.89; 95% CI, 1.18 to 20.29; P =0.03), 6-minute walk test (hazard ratio, 0.93 for each 10 m; P =0.01), and pulmonary vascular resistance (hazard ratio, 1.13; P =0.01) as independent markers of mortality. All 3 cTnT(+) patients who survived the follow-up period converted to cTnT(−) during treatment. Conclusions—Detectable cTnT is a so-far ignored independent marker of increased mortality risk in patients with chronic precapillary PH, supporting the role of progressive myocyte injury in the vicious circle leading to hemodynamic destabilization.

N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism.

Plasma brain natriuretic peptide (BNP), released from myocytes of ventricles upon stretch, has been reported to differentiate pulmonary from cardiac dyspnoea. Limited data have shown elevated plasma BNP levels in acute pulmonary embolism (APE), frequently accompanied by dyspnoea and right ventricular (RV) dysfunction. The aim of this study was to assess plasma N‐terminal proBNP (NT‐proBNP) in APE, and to establish whether it reflects the severity of RV overload and if it can be used to predict adverse clinical outcome. On admission, NT‐proBNP and echocardiography for RV overload were performed in 79 APE patients (29 males), aged 63±16 yrs. Plasma NT‐proBNP was elevated in 66 patients (83.5%) and was higher in patients with (median 4,650 pg·mL−1 (range 61–60,958)) than without RV strain (363 pg·mL−1 (16–16,329)). RV‐to-left ventricular ratio and inferior vena cava dimension correlated with NT‐proBNP. All 15 in-hospital deaths and 24 serious adverse events occurred in the group with elevated NT‐proBNP, while all 13 (16.5%) patients with normal values had an uncomplicated clinical course. Plasma NT‐proBNP predicted in-hospital mortality. Plasma N‐terminal pro-brain natriuretic peptide is elevated in the majority of cases of pulmonary embolism resulting in right ventricular overload. Plasma levels reflect the degree of right ventricular overload and may help to predict short-term outcome. Acute pulmonary embolism should be considered in the differential diagnosis of patients with dyspnoea and abnormal levels of brain natriuretic peptide.

Proximal pulmonary emboli modify right ventricular ejection pattern

Analysis of the systolic flow velocity curve (SFVC) in the right ventricular outflow tract is considered as an alternative to the tricuspid valve pressure gradient (TVPG) method for echo-Doppler assessment of pulmonary arterial pressure (P(pa)). The present study checked whether or not SFVC is affected by the cause of pulmonary hypertension. Doppler recordings of 86 patients (39 female, aged 55.5+/-15.2 yrs) with acute (AP-PE) or chronic (CP-PE) proximal pulmonary embolism, chronic obstructive pulmonary disase (COPD) or primary pulmonary hypertension (PPH) were retrospectively analysed by two observers unaware of the purpose of the study. Despite having the lowest TVPG (48+/-13 mmHg), patients with AP-PE had the shortest acceleration time (t(acc); 56+/-15 ms) and time to midsystolic deceleration (t(msd); 105+/-16 ms). t(acc) <60 ms in patients with TVPG <60 mmHg had 98% specificity and 48% sensitivity for AP-PE. In PPH, SFVC was less abnormal (t(acc) 64+/-14 ms, t(msd) 125+/-25 ms, both p<0.03) despite having a TVPG twice as high (92+/-12 mmHg, p< 0.001). In contrast to t(acc), TVPG showed strong correlation with direct P(pa) measurements whenever performed (r=-0.43, p=0.02, versus r=0.80, p<0.001; n=30). There was no correlation between t(acc) and TVPG in a pooled study group and SFVC seemed strongly affected by the presence of both AP-PE and CP-PE. While potentially useful for evaluation of the true right ventricular afterload during pulsatile flow conditions, the systolic flow velocity curve does not provide a reliable estimate of pulmonary arterial pressure.

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.

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.

Recurrent Hemoptysis: An Emerging Life-Threatening Complication in Idiopathic Pulmonary Arterial Hypertension

Hemoptysis is a rarely reported complication of idiopathic pulmonary arterial hypertension (IPAH). We present the case of a 27-year-old woman with IPAH, who suffered from recurrent hemoptysis and who was treated with sitaxsentan and treprostinil and remained stable in World Health Organization functional class II. During several episodes of active hemoptysis, the patient underwent bronchial artery embolization (BAE), always with good immediate results. She developed severe respiratory insufficiency and died of electromechanical dissociation 2 days after another episode, despite effective bleeding control. Recurrent hemoptysis in patients with IPAH emerges as a potential indication for urgent placement on the lung transplant list, independent from the classic prognostic factors of functional class and indices of right-sided ventricular function. Repeated BAE should not be considered as a definitive treatment in patients with pulmonary arterial hypertension with recurrent bleeding, although it may help in bridging patients to lung transplant.

Effectiveness of intrapericardial administration of streptokinase in purulent pericarditis.

Background and Purpose:Purulent pericarditis is very rare. However, among patients suffering from this disease the mortality rate is very high. The aim of this study was to evaluate the effectiveness and side effects of intrapericardial streptokinase administration in patients with confirmed purulent pericarditis.Patients and Methods:Three patients, one 50-year-old man and two women aged 64 and 40 years, who were admitted to the intensive care unit (ICU) due to purulent pericarditis, entered the study. In all three cases a subxiphoid pericardiotomy followed by insertion of a drainage line into the pericardial space was performed. Antibiotic therapy was started immediately on admission to the hospital. Despite continued antibiotic therapy in all three patients, daily drainage from the pericardium—during several days after surgery—staggered between 50–200 ml/day. Due to considerable purulent pericardial drainage loculations and/or fibrin deposits confirmed by echocardiography, streptokinase (500,000 IU dissolved in 50 ml of normal saline) was administered into the pericardial space over 10 min, using the previously inserted drainage catheter. This regimen was repeated after 12 and 24 h. The total dose of streptokinase was 1,500,000 IU.Results:The clinical effect of intrapericardial streptokinase administration was excellent. Several days after intrapericardial administration of streptokinase, drainage of purulent pericardial fluid stopped. No complications associated with intrapericardial streptokinase administration were observed. In the follow-up echocardiography (in two patients repeated 6 and 9 months after delivery of streptokinase), pericardial fluid and echocardiographic signs of pericardial constriction were not observed.Conclusion:Intrapericardial administration of streptokinase in purulent pericarditis is effective and safe.ZusammenfassungBei drei Patienten mit purulenter Perikarditis konnte der Perikarderguss durch chirurgische Perikardiotomie nicht suffizient drainiert werden. Die komplikationslose Sanierung des lokulierten fibrinösen Ergusses gelang nach intraperikardialer Streptokinaseinstillation (50-ml-Lösung mit 500 000 IE Streptokinase, instilliert über 10 min in erster Sitzung, gefolgt von derselben Dosis nach 12 und 24 h). Im weiteren Verlauf ergab sich eine Restitutio ad integrum, ohne dass sich später eine konstriktive Perikarditis entwickelte.

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.