Background: Distal-type chronic thromboembolic pulmonary hypertension (CTEPH) is a fatal disease for which a new therapeutic strategy needs to be developed. We examined the effects of percutaneous ...transluminal pulmonary angioplasty (PTPA). Methods and Results: We prospectively enrolled 12 patients with distal-type CTEPH. After stabilizing their condition with pulmonary vasodilators, we then performed PTPA, which markedly improved pulmonary hemodynamics and pulmonary artery structure, as confirmed by angiography and optical coherence tomography, and also significantly improved their long-term prognosis compared with 39 historical controls. Conclusions: PTPA is a promising therapeutic option for distal-type CTEPH. (Circ J 2012; 76: 485-488)
Although balloon pulmonary angioplasty (BPA) improves haemodynamics and short-term prognosis in patients with inoperable chronic thrombo-embolic pulmonary hypertension (CTEPH), the long-term effects ...of BPA, and procedure-related complications remain to be fully elucidated.
From July 2009 to October 2016, we performed a total of 424 BPA sessions in 84 consecutive patients with inoperable CTEPH. We used 3D reconstructed computed tomography to determine target lesions of pulmonary arteries and optical computed tomography to select balloon size, if needed. In 77 patients (92%) who completed the BPA treatment 65 ± 14 (SD) years-old, male/female 14/63, haemodynamics and exercise capacity were examined at 6 months after last BPA and in the chronic phase >12 months after first BPA, 31 (20, 41) months. The BPA treatment significantly improved mean pulmonary arterial pressure (38 ± 10 to 25 ± 6 mmHg), pulmonary vascular resistance (7.3 ± 3.2 to 3.8 ± 1.0 Wood units), and 6-minute walk distance (380 ± 138 to 486 ± 112 m) (all P < 0.01), and the improvements persisted throughout the follow-up period (43 ± 27 months) (N = 53). In the 424 sessions, haemoptysis was noted in 60 sessions (14%), and non-invasive positive pressure ventilation (NPPV) was used to treat haemoptysis and/or hypoxemia in 33 sessions (8%). Furthermore, 5-year survival was 98.4% (only one patient died of colon cancer) with no peri-procedural death.
These results indicate that BPA improves haemodynamics and exercise capacity in inoperable CTEPH patients with acceptable complication rate and that the beneficial haemodynamic effects of BPA persist for years with resultant good long-term prognosis.
Background:It remains to be determined whether balloon pulmonary angioplasty (BPA) improves biventricular cardiac functions and pulmonary flow in patients with chronic thromboembolic pulmonary ...hypertension (CTEPH).Methods and Results:We enrolled 30 consecutive patients with inoperable CTEPH who underwent BPA, and carried out serial cardiac magnetic resonance imaging (CMR; M/F, 9/21; median age, 65.2 years). No patient died during the treatment or follow-up period. BPA significantly improved WHO functional class (III/IV, 83.0 to 4.0%), 6-min walking distance (330.2±168.7 to 467.3±114.4 m), mean pulmonary artery pressure (40.8±10.7 to 23.2±4.94 mmHg), pulmonary vascular resistance (9.26±4.19 to 3.35±1.40 WU) and cardiac index (2.19±0.64 to 2.50±0.57 L·min·m2; all P<0.01). CMR also showed improvement of right ventricular (RV) ejection fraction (EF; 41.3±12.4 to 50.7±8.64%), left ventricular (LV) end-diastolic volume index (72.1±14.0 to 81.6±18.6 ml/m2) and LV stroke volume index (41.0±9.25 to 47.8±12.3 ml/m2; all P<0.01). There was a significant correlation between change in RVEF and LVEF (Pearson’s r=0.45, P=0.01). Average velocity in the main pulmonary artery was also significantly improved (7.50±2.43 to 9.79±2.92 cm/s, P<0.01).Conclusions:BPA improves biventricular functions and pulmonary flow in patients with inoperable CTEPH. (Circ J 2016; 80: 1470–1477)
Abstract Background Although myocardial interstitial fibrosis has been considered to play a pathogenic role in chronic heart failure (HF), the role of perivascular fibrosis, another form of fibrosis, ...remains to be elucidated. Methods We examined 64 consecutive patients with non-ischemic HF caused by hypertrophic cardiomyopathy (HCM, n = 16), hypertensive heart disease (HHD, n = 11), or dilated cardiomyopathy (DCM, n = 37), diagnosed by both cardiac catheterization and endomyocardial biopsy (right ventricular side of the interventricular septum) in the Tohoku University Hospital between January 2001 and April 2009. We calculated the collagen volume fraction (CVF) and perivascular fibrosis ratio (PFR) in biopsy samples and also examined Thrombolysis in Myocardial Infarction (TIMI) frame count to evaluate coronary blood flow. Results There was no significant correlation between CVF and PFR ( r2 = 0.0007). Although CVF was comparable among HCM, HHD, and DCM (1.11 ± 1.04, 1.89 ± 1.61, and 1.41 ± 1.48, respectively), PFR was significantly higher in HCM than in DCM (1.78 ± 1.09 vs. 1.23 ± 0.44, p < 0.05). PFR was not correlated with cardiac function parameters, such as left ventricular (LV) ejection fraction, cardiac output, LV end-diastolic pressure, LV end-diastolic volume, aortic pressure, or pulmonary artery pressure. However, PFR was significantly correlated with coronary flow in the left anterior descending coronary artery (as evaluated by TIMI frame count) ( r2 = 0.3351, p < 0.0001, in all-cases combined population), but not with that in the left circumflex or right coronary artery. This correlation remained significant in a logistic regression model tested in 7 variables (body mass index, PVR, CVF, presence of hypertension, dyslipidemia, diabetes mellitus, and atrial fibrillation). Conclusions These results indicate that coronary perivascular fibrosis is associated with the impairment of coronary blood flow although not associated with interstitial fibrosis or cardiac function, suggesting that it can be a new therapeutic target to improve coronary microcirculation.
Endothelial AMP-activated protein kinase (AMPK) plays an important role for vascular homeostasis, and its role is impaired by vascular inflammation. However, the role of endothelial AMPK in the ...pathogenesis of pulmonary arterial hypertension (PAH) remains to be elucidated.
To determine the role of endothelial AMPK in the development of PAH.
Immunostaining showed that endothelial AMPK is downregulated in the pulmonary arteries of patients with PAH and hypoxia mouse model of pulmonary hypertension (PH). To elucidate the role of endothelial AMPK in PH, we used endothelial-specific AMPK-knockout mice (eAMPK(-/-)), which were exposed to hypoxia. Under normoxic condition, eAMPK(-/-) mice showed the normal morphology of pulmonary arteries compared with littermate controls (eAMPK(flox/flox)). In contrast, development of hypoxia-induced PH was accelerated in eAMPK(-/-) mice compared with controls. Furthermore, the exacerbation of PH in eAMPK(-/-) mice was accompanied by reduced endothelial function, upregulation of growth factors, and increased proliferation of pulmonary artery smooth muscle cells. Importantly, conditioned medium from endothelial cells promoted pulmonary artery smooth muscle cell proliferation, which was further enhanced by the treatment with AMPK inhibitor. Serum levels of inflammatory cytokines, including tumor necrosis factor-α and interferon-γ were significantly increased in patients with PAH compared with healthy controls. Consistently, endothelial AMPK and cell proliferation were significantly reduced by the treatment with serum from patients with PAH compared with controls. Importantly, long-term treatment with metformin, an AMPK activator, significantly attenuated hypoxia-induced PH in mice.
These results indicate that endothelial AMPK is a novel therapeutic target for the treatment of PAH.
Antithrombin resistance (ATR) is a newly identified strong genetic predisposition to venous thromboembolism (VTE) caused by genetic variations in prothrombin with substitutions of Arg at position 596 ...with either Leu, Gln, or Trp. In the present report, we identified a missense variant p.Arg596Gln in 3 patients from 2 families with unprovoked VTE who each experienced their first VTE event at 19, 67, and 19 years old. The three patients did not show any positive markers for thrombophilia on routine testing, suggesting that patients with unprovoked VTE who have negative findings on thrombophilia tests may carry a prothrombin variant with ATR.
Abstract
Various forms of supraventricular tachycardia (SVT) occur in patients with severe pulmonary hypertension (PH). Despite the high efficacy of radiofrequency catheter ablation (RFCA) for SVT, ...insufficient data exist regarding patients with PH. Thirty SVTs in 23 PH patients (age 47 35–60 years; mean pulmonary artery pressure 44 32–50 mmHg) were analyzed. Procedural success rate, short- and long-term clinical outcomes, were evaluated during a median follow-up of 5.1 years. Single-procedure success rate was 83%; 94% (17/18) in typical atrial flutter, 73% (8/11) in atrial tachycardia (AT), and 100% (1/1) in atrioventricular nodal reentrant tachycardia. Antiarrhythmic drugs, serum brain natriuretic peptide levels and number of hospitalizations significantly decreased after RFCA than that before (
p
= 0.002, 0.04, and 0.002, respectively). Four patients had several procedures. After last RFCA, 12 patients had SVT and 8 patients died. Kaplan–Meier curves showed that patients with SVT after the last RFCA had a lower survival rate compared to those without (
p
= 0.0297). Multivariate analysis identified any SVT after the last RFCA as significant risk factor of mortality (hazard ratio: 9.31;
p
= 0.016). RFCA for SVT in patients with PH is feasible and effective in the short-term, but SVT is common during long-term follow-up and associated with lower survival.
Background:Although balloon pulmonary angioplasty (BPA) improves the hemodynamics and prognosis of patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), the mechanisms of ...improvement in oxygenation remain to be elucidated.Methods and Results:From August 2013 to May 2015, we performed a total of 113 BPA procedures in 24 patients with inoperable CTEPH (mean 4.7 procedures per patient). Median age was 70 60, 74 years and 18 were female (75%). We examined hemodynamics, respiratory functions, and intrapulmonary shunt before and after the BPA procedure. Mean pulmonary arterial pressure (37 28, 45 to 2319, 27 mmHg, P<0.01), pulmonary vascular resistance (517 389, 696 to 268 239, 345 dyne/s/cm5) and 6-min walk distance (390 286, 484 to 490 411, 617 m, P<0.01) were significantly improved after BPA therapy. Furthermore, arterial oxygen partial pressure (PaO2, 54.8 50.0, 60.8 to 65.2 60.6, 73.2 %, P<0.01) and intrapulmonary shunt (23.4±6.0% to 19.3±5.0%, P<0.01) were also significantly ameliorated. In the multivariate analysis, decrease in intrapulmonary shunt after BPA was significantly correlated with improvement of both PaO2(r2=0.26, P<0.01) and SaO2(r2=0.49, P<0.01) after BPA.Conclusions:These results indicated that BPA improved not only pulmonary hemodynamics but also oxygenation with a resultant decrease in intrapulmonary shunt. (Circ J 2016; 80: 2227–2234)
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