Balloon Pulmonary Angioplasty in Technically Operable and Technically Inoperable Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: In this study, we aimed to assess the efficacy and safety of balloon pulmonary angioplasty (BPA) in patients with technically inoperable distal-type chronic thromboembolic pulmonary hypertension (d-CTEPH) and technically operable proximal-type disease (p-CTEPH) by analyzing the results of BPA treatment in two collaborating CTEPH referral centers. METHODS AND RESULTS: We assessed hemodynamic results, functional efficacy, complication and survival rate after BPA treatment in 70 CTEPH patients (median age 64 years; (interquartile range (IQR): 52-73 years)), of whom 16 (median age 73 years; (QR 62-82 years)) were in the p-CTEPH subgroup. Altogether, 377 BPA procedures were performed, resulting in significant (p < 0.001) improvement in mean pulmonary artery pressure (mPAP 48.6 ± 10 vs. 31.3 ± 8.6 mmHg), pulmonary vascular resistance (694 ± 296 vs. 333 ± 162 dynes*s*cm-5), six-minute walk test (365 ± 142 vs. 433 ± 120 metres) and N-terminal pro B-type natriuretic peptide (1307 (510-3294) vs. 206 (83-531) pg/mL). The rate of improvement did not differ between the sub-groups. Lung injury episodes and severe hemoptysis were similarly infrequent in d-CTEPH and p-CTEPH (6.4% vs. 5%; p = 0.55 and 1.0% vs. 2.5; p = 0.24, respectively). There was no significant difference between the sub-groups regarding survival (p = 0.53 by log-rank test). CONCLUSION: BPA may be beneficial in patients with p-CTEPH who cannot undergo pulmonary endarterectomy (PEA). Larger long-term studies are needed to better define the efficacy, safety, and optimal BPA procedural standards in this population.

Assessment of electrocardiographic markers of acute and long-term hemodynamic improvement in patients with pulmonary hypertension.

BACKGROUND: The remodeling of the right heart in patients with chronic pulmonary hypertension (cPH) is associated with the appearance of electrocardiographic (ECG) abnormalities. We investigated the resolution of ECG markers of right ventricular hypertrophy (RVH) caused by acute and long-term hemodynamic improvement. METHODS: Twenty-nine (29) patients with chronic thromboembolic pulmonary hypertension (CTEPH) and seven patients with pulmonary arterial hypertension (PAH) were included in the analysis. Patients with CTEPH achieved a significant long-term hemodynamic improvement following the treatment with balloon pulmonary angioplasty (BPA); all the patients with PAH reported significant acute hemodynamic relief after a single inhalation of iloprost, fulfilling the criteria of responder. Standard 12-lead ECG was performed before and after intervention. RESULTS: The interval between baseline and control ECG in CTEPH and PAH groups was 28 (IQR: 17-36) months and 15 min (IQR: 11-17), respectively. Despite similar hemodynamic improvement in both groups, only the CTEPH group presented significant changes in most analyzed ECG parameters: T-wave axis (p = .002), QRS-wave axis (p = .012), P-wave amplitude (p < .001) and duration in II (p = .049), R-wave amplitude in V1 (p = .017), R:S ratio in V1 (p = .046), S-wave amplitude in V5 (p = .004), R-wave amplitude in V5 (p = .044), R:S ratio in V5 (p = .004), S-wave amplitude in V6 (p = .026), R-wave amplitude in V6 (p = .01), and R-wave amplitude in aVR (p = .031). In patients with PAH, significant differences were found only for P wave in II (duration: p = .035; amplitude: p = .043) and QRS axis (p = .018). CONCLUSIONS: The effective treatment of cPH ensures improvement in ECG parameters of RVH, but it requires extended time.

Changes in Estimated Glomerular Filtration after Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is a novel treatment option for inoperable or persistent chronic thromboembolic pulmonary hypertension (CTEPH). Little is known about renal function in CTEPH patients undergoing BPA. OBJECTIVES: The aim of this study was to assess the frequency of contrast-induced acute kidney injury (CI-AKI) in patients with CTEPH undergoing BPA and to evaluate the relationship between hemodynamic and renal function. METHODS: A total of 41 CTEPH patients were included and 250 consecutive BPA sessions were analyzed for frequency of CI-AKI. The serum creatinine (SC) concentration was measured and the glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease equation before and 72 h after each BPA procedure. CI-AKI was defined as an increase of 25% or 0.5 mg/dL in SC from the baseline value within 48-72 h of contrast administration. SC and GFR were assessed before and after 3-6 months of completing the BPA treatment and correlated with hemodynamic parameters. RESULTS: The SC concentration and GFR did not change significantly within 72 h after BPA (+1%, p = 0.921, and +4%, p = 0.112, respectively). CI-AKI was noted in 2 cases (0.8%). Significant improvement was noted in GFR (75.4 ± 21.2 vs. 80.9 ± 22.4 mL/min/1.73 m2; p = 0.012) in addition to improvement in right atrial pressure (RAP; 9.1 ± 4.1 to 5.0 ± 2.2 mm Hg; p < 0.001), mean pulmonary artery pressure (49.1 ± 10.7 to 29.8 ± 8.3 mm Hg; p < 0.001), cardiac index (CI; 2.42 ± 0.6 to 2.70 ± 0.6 L/min/m2; p = 0.004), and pulmonary vascular resistance (9.42 ± 3.6 to 4.4 ± 2.3 Wood units; p < 0.001). In a subpopulation of 12 patients with impaired renal function at baseline, the relative increase in GFR was significantly correlated with relative improvement in CI (r = 0.060; p = 0.037), RAP (r = -0.587; p = 0.044), and mixed venous saturation (r = 0.069; p = 0.012). CONCLUSIONS: Hemodynamically effective BPA procedures improve renal function in patients with CTEPH with a minimal risk of CI-AKI in the course of treatment.

Treatment of chronic thromboembolic pulmonary hypertension in a multidisciplinary team.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) may be treated with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapy (MT). Assessment in a multidisciplinary team of experts (CTEPH team) is currently recommended for treatment decision making. The aim of the present study was to report the effects of such an interdisciplinary concept. METHODS AND RESULTS: A total of 160 patients were consulted by the CTEPH team between December 2015 and September 2018. Patient baseline characteristics, CTEPH team decisions and implementation rates of diagnostic and therapeutic procedures were analysed. Change in World Health Organization (WHO) functional class and survival rates were evaluated by treatment strategy. A total of 51 (32%) patients were assessed as operable and 109 (68%) were deemed inoperable. Thirty-one (61% of operable patients) underwent PEA. Patients treated with PEA, BPA(+MT) and MT alone were 50.9 ± 14.7, 62.9 ± 15.1 and 68.9 ± 12.7 years old, respectively. At the follow-up, PEA patients had the highest WHO functional class improvement. Patients treated with BPA(+MT) had significantly better survival than PEA (p = 0.04) and MT patients (p = 0.04; 2-year survival of 92%, 79% and 79%, respectively). CONCLUSIONS: The CTEPH team ensures that necessary diagnostic procedures are performed. A relatively low proportion of patients was assessed by the CTEPH team as operable and underwent surgery, which in survivors resulted in the best functional improvement. Although patients undergoing BPA(+MT) were older than patients treated with PEA, their survival was better than patients subjected to PEA or MT alone. The reviews of this paper are available via the supplemental material section.

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.

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.

Improvement in Quality of Life and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty.

BACKGROUND: The effect of balloon pulmonary angioplasty (BPA) on improvement in functional and hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) is known, but the quality of life (QoL) of patients treated with BPA has never been studied before.Methods and Results:Twenty-five patients with inoperable or persistent CTEPH were enrolled in the study and filled out the 36-item Short Form (SF-36v2) questionnaire twice: prior to commencement of BPA treatment and after ≥3 BPA sessions. In addition WHO functional class, distance on the 6-min walk test (6MWT) and hemodynamic parameters such as right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were assessed. QoL improved significantly in all domains, except for physical pain. Improvement in RAP (10.5±3.4 vs. 6.2±2.2 mmHg; P<0.05), mPAP (51.7±10.6 vs. 35.0±9.1 mmHg; P<0.05), CI (2.2±0.5 vs. 2.5±0.4 L/min·m2; P=0.04), PVR (10.4±3.9 vs. 5.5±2.2 Wood units; P<0.05), functional class (96% vs. 20% in WHO class III and IV, P<0.05) and improvement in 6MWT distance (323±135 vs. 410±109 m; P<0.05) was observed. The only significant correlation was between the mental component summary score of QoL after completion of treatment and percentage improvement in the 6MWT (-0.404, P<0.05). CONCLUSIONS: Alongside improvement in functional and hemodynamic parameters, BPA also provides significant improvement in QoL.

The effect of hyperoxia on central blood pressure in healthy subjects.

INTRODUCTION: Hyperoxia increases total peripheral resistance by acting locally but also inhibits the activity of carotid body chemoreceptors. We studied the effect of hyperoxia on central pressure in normotensive subjects. MATERIAL AND METHODS: Medical air followed by 100% oxygen was provided to 19 subjects (12/7 female/male, age 28.2 ±1.1 years) for 15 min through a non-rebreather mask. Central blood pressure was then measured using applanation tonometry. RESULTS: After the first 2 min of hyperoxia, heart rate decreased significantly (65 ±2.6 beats/min vs. 61 ±2.1 beats/min, p = 0.0002). Peripheral and central blood pressure remained unchanged, while hemoglobin oxygen saturation and subendocardial viability ratio index increased (97 ±0.4% vs. 99 ±0.2%, p = 0.03; 168 ±8.4% vs. 180 ±8.2%, p = 0.009). After 15 min of 100% oxygen ventilation, heart rate and peripheral and central blood pressures remained unchanged from the first 2 min. The augmentation index, augmentation pressure and ejection duration increased as compared to baseline values and those obtained at 2 min (-5.1 ±2.9% vs. -1.2 ±2.6%, p = 0.005 and -4.6 ±2.7% vs. -1.2 ±2.6%, p = 0.0015; -1.3 ±0.7 mm Hg vs. -0.2 ±1.2 mm Hg, p = 0.003 and -1.1 ±0.7 mm Hg vs. -0.2 ±1.2 mm Hg, p = 0.012; 323 ±3.6 ms vs. 330 ±3.5 ms, p = 0.0002 and 326 ±3.5 ms vs. 330 ±3.5 ms, p = 0.021, respectively). CONCLUSIONS: The present study shows that hyperoxia does not affect central blood pressure in young healthy subjects and may improve myocardial blood supply estimated indirectly from applanation tonometry.

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia.

Beyond their hypolipidemic effect, statins reduce cardiovascular risk in hypertensive subjects via various mechanisms; one suggested mechanism is that they reduce sympathetic activity. We investigated the hypothesis that simvastatin decreased muscle sympathetic nerve activity (MSNA) in 31 hypertensive subjects with hypercholesterolemia (aged 38.7 ± 10 years). In this randomized, placebo-controlled, double-blinded study, patients were treated with simvastatin (40 mg day(-1); n=15) or placebo (n=16) for 8 weeks. Before and after treatment, we measured MSNA, blood pressure and heart rate. Baroreceptor control of the heart rate, or baroreceptor sensitivity (BRS), was computed by the sequence method, a cross-analysis of systolic blood pressure and the electrocardiogram R-R interval. Blood samples were tested for plasma levels of catecholamines, neuropeptide Y, aldosterone, endothelin and renin activity. Simvastatin significantly reduced MSNA (from 36.5 ± 5 to 27.8 ± 6 bursts per min, P=0.001), heart rate (from 77 ± 6.7 to 71 ± 6.1 beats per min, P=0.01) and both total and low-density lipoprotein cholesterol (from 249 ± 30.6 to 184 ± 28.3 mg dl(-1), P=0.001 and from 169 ± 30.6 to 117 ± 31.2 mg dl(-1), P=0.01, respectively). Simvastatin also improved BRS (from 10.3 ± 4.1 to 17.1 ± 4.3 ms per mm Hg, P=0.04). No changes were observed in systolic or diastolic blood pressures, or in plasma levels of catecholamines, neuropeptide Y, endothelin, aldosterone and renin activity. After simvastatin therapy, MSNA and BRS were inversely related (r=-0.94, P<0.05). In conclusion, we found that, in patients with hypertension and hypercholesterolemia, simvastatin reduced MSNA, and this was related to increased baroreceptor sensitivity.

Atorvastatin reduces sympathetic activity and increases baroreceptor reflex sensitivity in patients with hypercholesterolaemia and systemic arterial hypertension.

BACKGROUND: Increased sympathetic activity might be related to pathogenesis of hypertension as well as to end organ damage. Animal studies suggest that statins decrease sympathetic activity and increase baroreceptor reflex sensitivity (BRS). AIM: To examine whether atorvastatin decreases muscle sympathetic nerve activity (MSNA) and BRS in hypercholesterolaemic and hypertensive patients. METHODS: Ten patients with essential hypertension and untreated hypercholesterolaemia (aged 43 +/- 12 years) and eight healthy subjects (aged 37 +/- 7 years) were enrolled in the study. In both groups the recordings of microneurography, ECG, blood pressure and BRS were performed twice, before and after 8 weeks during which the patients (but not controls) were treated with atorvastatin. RESULTS: Compared with controls, the patients had higher MSNA values (36.0 +/- 6.6 vs. 29.8 +/- 3.7 bursts/minute), mean BP levels (145.1 +/- 10 vs. 124.1 +/- 11.1 mmHg) and total cholesterol concentration (252.6 +/- 22.6 vs. 179.8 +/- 20.7 mg/dl) baseline values. Statin therapy resulted in a decrease of total cholesterol (252.6 +/- 22.0 vs. 173.8 +/- 26.2 mg/dl, p < 0.05) and MSNA (36.0 +/- 6.6 vs. 28.6 +/- 4.8 bursts/min, p < 0.05), whereas BRS values were increased (12.6 +/- 5.6 vs. 18.1 +/- 5.9 ms/mmHg, p < 0.05). Post-treatment BRS was inversely related to post-treatment MSNA (r = -0.73, p < 0.05). In the controls there were no changes in MSNA (29.8 +/- 3.7 vs. 28.9 +/- 2.9 bursts/min), BRS (11.9 +/- 5.0 vs. 13.1 +/- 4.8 ms/mmHg), total cholesterol, BP and heart rate between the first and the second measurement. CONCLUSION: Atorvastatin reduces MSNA and increases BRS in hypertensive and hypercholesterolaemic patients. Decrease in sympathetic activity may be the result of improvement of baroreceptor function by atorvastatin.

The effect of enalapril and telmisartan on clinical and biochemical indices of sympathetic activity in hypertensive patients.

OBJECTIVE: To compare the effect of ARB and ACE inhibitor on sympathetic activity in 32 hypertensives. DESIGN AND METHODS: After a four-week wash-out period, patients were randomized to four weeks of therapy with enalapril or telmisrtan, with crossover to another drug for another four weeks. Blood pressure (BP), NPY, and catecholamine levels and HRV (frequency analysis) were measured during wash-out, in basal condition, and after postural stimulation test (PST). RESULTS: Both drugs significantly reduced BP and NPY as compared to initial values, while no differences in BP and NPY between drugs were observed. Increase in NPY during PST was significantly higher in the enalapril than in the telmisartan group and during the wash-out period. No differences between enalapril and telmisartan in plasma catecholamines were observed. Telmisartan decreased low frequency/high frequency ratio as compared to initial values and enalapril values. CONCLUSIONS: Despite similar BP control, telmisartan attenuated autonomic balance more effectively than enalapril.