Bleeding Outcomes After Left Atrial Appendage Closure Compared With Long-Term Warfarin: A Pooled,Patient-Level Analysis of the WATCHMAN Randomized Trial Experience

ObjectivesThe purpose of this study was to compare the relative risk of major bleeding with left atrial appendage (LAA) closure compared with long-term warfarin therapy.BackgroundLAA closure is an alternative approach to chronic oral anticoagulation for the prevention of thromboembolism in patients with atrial fibrillation (AF).MethodsWe conducted a pooled, patient-level analysis of the 2 randomized clinical trials that compared WATCHMAN (Boston Scientific, Natick, Massachusetts) LAA closure with long-term warfarin therapy in AF.ResultsA total of 1,114 patients were included, with a median follow-up of 3.1 years. The overall rate of major bleeding from randomization to the end of follow-up was similar between treatment groups (3.5 events vs. 3.6 events per 100 patient-years; rate ratio [RR]: 0.96; 95% confidence interval [CI]: 0.66 to 1.40; p = 0.84). LAA closure significantly reduced bleeding >7 days post-randomization (1.8 events vs. 3.6 events per 100 patient-years; RR: 0.49; 95% CI: 0.32 to 0.75; p = 0.001), with the difference emerging 6 months after randomization (1.0 events vs. 3.5 events per 100 patient-years; RR: 0.28; 95% CI: 0.16 to 0.49; p < 0.001), when patients assigned to LAA closure were able to discontinue adjunctive oral anticoagulation and antiplatelet therapy. The reduction in bleeding with LAA closure was directionally consistent across all patient subgroups.ConclusionsThere was no difference in the overall rate of major bleeding in patients assigned to LAA closure compared with extended warfarin therapy over 3 years of follow-up. However, LAA closure significantly reduced bleeding beyond the procedural period, particularly once adjunctive pharmacotherapy was discontinued. The favorable effect of LAA closure on long-term bleeding should be considered when selecting a stroke prevention strategy for patients with nonvalvular AF. (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy [PREVAIL]; NCT01182441)     

The Left Atrial Appendage: Anatomy,Function, and Noninvasive Evaluation

The left atrial appendage (LAA) is a finger-like extension originating from the main body of the left atrium. Atrial fibrillation (AF) is the most common clinically important cardiac arrhythmia, occurring in approximately 0.4% to 1% of the general population and increasing with age to >8% in those >80 years of age. In the presence of AF thrombus, formation often occurs within the LAA because of reduced contractility and stasis; thus, attention should be given to the LAA when evaluating and assessing patients with AF to determine the risk for cardioembolic complications. It is clinically important to understand LAA anatomy and function. It is also critical to choose the optimal imaging techniques to identify or exclude LAA thrombi in the setting of AF, before cardioversion, and with current and emerging transcatheter therapies, which include mitral balloon valvuloplasty, pulmonary vein isolation, MitraClip (Abbott Laboratories, Abbott Park, Illinois) valve repair, and the implantation of LAA occlusion and exclusion devices. In this review, we present the current data regarding LAA anatomy, LAA function, and LAA imaging using the currently available noninvasive imaging modalities.     

CMR-Guided Approach to Localize and Ablate Gaps in Repeat AF Ablation Procedure

ObjectivesThe aim of this study was to test the feasibility and usefulness of a new delayed-enhancement cardiac magnetic resonance (DE-CMR)–guided approach to ablate gaps in redo procedures.BackgroundRecurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI) may be related to gaps at the ablation lines. DE-CMR allows identification of radiofrequency lesions and gaps (CMR gaps).MethodsFifteen patients undergoing repeated AF ablations were included (prior procedure was PVI in all patients and roof-line ablation in 8 patients). Pre-procedure 3-dimensional (3D) DE-CMR was performed with a respiratory-navigated (free-breathing) and electrocardiographically gated inversion-recovery gradient-echo sequence (voxel size 1.25 × 1.25 × 2.5 mm). Endocardium and epicardium were manually segmented to create a 3D reconstruction (DE-CMR model). A pixel signal intensity map was projected on the DE-CMR model and color-coded (thresholds 40 ± 5% and 60 ± 5% of maximum intensity). The DE-CMR model was imported into the navigation system to guide the ablation of CMR gaps, with the operator blinded to electrical data. Fifteen conventional procedures were used as controls to compare procedural duration, radiofrequency, and fluoroscopy times.ResultsFifteen patients (56 pulmonary veins [PVs]; 57 ± 8 years of age; 9 with paroxysmal AF) were analyzed. In total, 67 CMR gaps were identified around PVs (mean 4.47 gaps/patient; median length 13.33 mm/gap) and 9 at roof line. All of the electrically reconnected PVs (87.5%) had CMR gaps. The site of electrical PV reconnection (assessed by circular mapping catheter) matched with a CMR gap in 79% of PVs. CMR-guided ablation led to reisolation of 95.6% of reconnected PVs (median radiofrequency time of 13.3 [interquartile range: 7.5 to 21.7] min/patient) and conduction block through the roof line in all patients (1.4 [interquartile range: 0.7 to 3.1] min/patient). Compared with controls, the CMR-guided approach shortened radiofrequency time (1,441 ± 915 s vs. 930 ± 662 s; p = 0.026) but not the procedural duration or fluoroscopy time.ConclusionsDE-CMR can successfully guide repeated PVI procedures by accurately identifying and localizing gaps and may reduce procedural duration and radiofrequency application time.     

Left atrial appendage dysfunction in acute embolic stroke young patients with sinus rhythm: Correlation with Tissue Doppler mitral annular systolic velocity

BackgroundTrans-esophageal echocardiogram (TEE) is a gold standard test for diagnosis of left atrial (LA) appendage function.AimTo evaluate left atrial appendage (LAA) dysfunction using mitral annular systolic velocity measured by tissue Doppler imaging “Sm” in acute embolic stroke young patients with sinus rhythm.MethodsTransthoracic (TTE) and transesophageal echocardiography (TEE) were performed in 70 consecutive patients with sinus rhythm without obvious left ventricular dysfunction within 2 weeks after embolic stroke. Two groups were identified: LAA dysfunction [LAA emptying peak flow velocity (LAA-eV) <0.55 m/s, n = 28, age 52 ± 11 years] and without LAA dysfunction (LAA-eV ≥ 0.55 m/s, n = 42, age 54 ± 10 years) on TEE. Tissue Doppler mitral annular systolic velocity “Sm” was obtained in apical four chambers view on TTE and D-dimer level estimated for all patients.ResultsSm was significantly lower in patients with than in those without LAA dysfunction (P < 0.0001). There was a significant correlation between Sm, LAVI, LAEF%, E/A ratio and LAA-eV in all selected patients groups. The optimum cut-off value of Sm for predicting LAA dysfunction was below or equal 8 cm/s (sensitivity 89.6% and specificity 94.2%).ConclusionTissue Doppler mitral annular systolic velocity is an independent non-invasive easy predictor of LAA dysfunction and significantly correlated with LAA-eV (p < 0.0001) in acute embolic stroke young patients with sinus rhythm.     

Changes in Left Atrial Appendage Dimensions Following Volume Loading During Percutaneous Left Atrial Appendage Closure

ObjectivesThis study sought to determine whether volume loading alters the left atrial appendage (LAA) dimensions in patients undergoing percutaneous LAA closure.BackgroundPercutaneous LAA closure is increasingly performed in patients with atrial fibrillation and contraindications to anticoagulation, to lower their stroke and systemic embolism risk. The safety and efficacy of LAA closure relies on accurate device sizing, which necessitates accurate measurement of LAA dimensions. LAA size may change with volume status, and because patients are fasting for these procedures, intraprocedural measurements may not be representative of true LAA size.MethodsThirty-one consecutive patients undergoing percutaneous LAA closure who received volume loading during the procedure were included in this study. After an overnight fast and induction of general anesthesia, patients had their LAA dimensions (orifice and depth) measured by transesophageal echocardiography before and after 500 to 1,000 ml of intravenous normal saline, aiming for a left atrial pressure >12 mm Hg.ResultsSuccessful implantation of LAA closure device was achieved in all patients. The average orifice size of the LAA at baseline was 20.5 mm at 90°, and 22.5 mm at 135°. Following volume loading, the average orifice size of the LAA increased to 22.5 mm at 90°, and 23.5 mm at 135°. The average increase in orifice was 1.9 mm (p < 0.0001). The depth of the LAA also increased by an average of 2.5 mm after volume loading (p < 0.0001).ConclusionsIntraprocedural volume loading with saline increased the LAA orifice and depth dimensions during LAA closure. Operators should consider optimizing the left atrial pressure with volume loading before final device sizing.     

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

BACKGROUND: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. METHODS: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. RESULTS: One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.     

Percutaneous Left Atrial Appendage Closure With the Watchman Device: Long-Term Results Up to 5 Years

ObjectivesThe aim of this study was to evaluate long-term outcomes in patients with atrial fibrillation undergoing percutaneous left atrial appendage (LAA) closure with the Watchman device.BackgroundAtrial fibrillation is one of the most common arrhythmias and is associated with a high risk for cardioembolic ischemic events, most notably stroke. Percutaneous LAA closure is an alternative to oral anticoagulation, because most thrombi originate from the LAA.MethodsAll consecutive patients with minimum CHADS₂ or CHA₂DS₂-VASc scores of 1 who underwent LAA closure with the Watchman device between June 2006 and August 2010 were eligible. Follow-up examinations were performed after 45 days to 3 months, 6 months, and 1 year and thereafter annually. Afterward, alternating office visits and telephone follow-up were performed every 6 months.ResultsA total of 102 patients were included. The mean age was 71.6 ± 8.8 years, and 37.3% were women. The mean CHADS₂ and CHA₂DS₂-VASc scores were 2.7 ± 1.3 and 4.3 ± 1.7, respectively. Procedural success was achieved in 96.1% of patients. During a mean follow-up period of 3.0 ± 1.6 years, the annual rates of transient ischemic attack, stroke, intracranial hemorrhage, and death were 0.7%, 0.7%, 1.1%, and 3.5%, respectively.ConclusionsLAA closure with the Watchman device is safe and feasible for stroke protection in patients with atrial fibrillation. Low ischemic events rates demonstrate its effectiveness during long-term follow-up.     

Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy

BACKGROUND: Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P-selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF. METHODS: We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels. CONCLUSION: There is evidence of platelet activation (ie, high PMP and sP-selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se.     

Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and hypertension are independently associated with increased stiffness of large arteries that may contribute to left ventricular (LV) remodeling. We sought to investigate the impact of OSA, hypertension, and their association with arterial stiffness and heart structure. DESIGN: We studied 60 middle-aged subjects classified into four groups according to the absence or presence of severe OSA with and without hypertension. All participants were free of other comorbidities. The groups were matched for age, sex, and body mass index. MEASUREMENTS AND RESULTS: Full polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography were performed in all participants. Compared with normotensive subjects without OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior wall thickness, LV mass index, and percentage of LV hypertrophy had similar increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05 for all comparisons), with a significant further increase in PWV, LV mass index, and percentage of LV hypertrophy in subjects with OSA and hypertension. Multivariate regression analysis showed that PWV was associated with systolic BP (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable associated with LV mass index was PWV (p < 0.0001). CONCLUSIONS: Severe OSA and hypertension are associated with arterial stiffness and heart structure abnormalities of similar magnitude, with additive effects when both conditions coexist. Increased large arterial stiffness contributes to ventricular afterload and may help to explain heart remodeling in both OSA and hypertension.     

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.     

Clinical application of tissue Doppler imaging in patients with idiopathic pulmonary hypertension

BACKGROUND: Tissue Doppler (TD) echocardiographic imaging of mitral and tricuspid annulus has been applied to assess right ventricular (RV) and left ventricular (LV) function in many cardiac diseases, but its clinical application, including response to long-term targeted therapy in patients with idiopathic pulmonary hypertension (PH), has not been addressed. METHODS: Seventy patients with idiopathic PH were compared with 35 age-matched control subjects to examine myocardial velocities by TD. Of these, 35 patients underwent repeat imaging after long-term targeted therapy. In addition, 50 consecutive patients with idiopathic PH with simultaneous right-heart catheterization and echocardiography were examined. RESULTS: No significant differences were noted between PH patients and the control group in lateral mitral annulus systolic velocity and early diastolic velocity (Ea) by TD, but septal velocities were significantly lower (p < 0.01). With targeted therapy, myocardial velocities at the septum and RV free wall increased significantly (p < 0.05). Likewise, E/Ea ratio increased, albeit still in the normal range. In all 50 patients with invasive measurements, lateral E/Ea ratio readily identified normal mean pulmonary capillary wedge pressure (PCWP). CONCLUSIONS: TD imaging of the lateral mitral annulus can reliably predict the presence of normal/reduced mean PCWP in patients with idiopathic PH, and track the improvement in RV function and LV filling with long-term targeted therapy.     

Periprocedural Intracardiac Echocardiography for Left Atrial Appendage Closure: A Dual-Center Experience

ObjectivesThis dual-center study sought to demonstrate the utility and safety of intracardiac echocardiography (ICE) in providing adequate imaging guidance as an alternative to transesophageal echocardiography (TEE) during Amplatzer Cardiac Plug device implantation.BackgroundOver 90% of intracardiac thrombi in atrial fibrillation originate from the left atrial appendage (LAA). Patients with contraindications to anticoagulation are potential candidates for LAA percutaneous occlusion. TEE is typically used to guide implantation.MethodsICE-guided percutaneous LAA closure was performed in 121 patients to evaluate the following tasks typically achieved by TEE: assessment of the LAA dimension for device sizing; guidance of transseptal puncture; verification of the delivery sheath position; confirmation of location and stability of the device before and after release and continuous monitoring to detect procedural complications. In 51 consecutive patients, we compared the measurements obtained by ICE and fluoroscopy to choose the size of the device.ResultsThe device was successfully implanted in 117 patients, yielding a technical success rate of 96.7%. Procedural success was achieved in 113 cases (93.4%). Four major adverse events (3 cardiac tamponades and 1 in-hospital transient ischemic attack) occurred. There was significant correlation in the measurements for device sizing assessed by angiography and ICE (r = 0.94, p < 0.0001).ConclusionsICE imaging was able to perform the tasks typically provided by TEE during implantation of the Amplatzer Cardiac Plug device for LAA occlusion. Therefore, we provide evidence that the use of ICE offered accurate measurements of LAA dimension in order to select the correct device sizes.     

Redefining Diastolic Dysfunction Grading: Combination of E/A ≤0.75 and Deceleration Time >140 ms and E/ε′ ≥10

ObjectivesThis study sought to examine left atrial (LA) mechanics and the prognostic impact of patients with echocardiographic findings of E/A ratio ≤0.75, deceleration time (DcT) of mitral E-wave >140 ms, but E/ε′ ≥10.BackgroundTraditional diastolic dysfunction (DD) grading system could not classify every patient into a specific group. We considered the group of patients with E/A ≤0.75, DcT >140 ms, but E/ε′ ≥10 (proposed new DD grade) as a new group in the DD grading system.MethodsA total of 1,362 consecutive patients were stratified according to the new DD grading system, and the LA volumes, strain, and strain rates were measured by 2-dimensional speckle-tracking analysis. All patients were followed up to determine cardiac death and major adverse cardiac events.ResultsAn E/A ≤0.75, DcT >140 ms, but E/ε′ ≥10 was observed in 227 patients (17%). LA volumes in patients with the new DD grade were between those of the impaired relaxation group and the pseudonormal group. LA strain of the new DD grade was similar to that of the pseudonormal group, whereas LA booster function was preserved as in the impaired relaxation group. During a mean follow-up of 3.0 ± 1.1 years, 25 patients had cardiac death and 61 had major adverse cardiac events. Event-free survival for major adverse cardiac events of the new DD grade was worse than that of the impaired relaxation group but similar to that of the pseudonormal group.ConclusionsThe new DD grade is frequently observed and has a prognosis similar to that of the pseudonormal group but significantly worse than that of the impaired relaxation group. However, LA booster function was maintained at the expense of LA volume enlargement. Thus, the new grade should be a distinct entity for routine DD grading.     

Pulmonary vein dilation in patients with atrial fibrillation: detection by magnetic resonance imaging

INTRODUCTION: The positive relationship between left atrial (LA) size and atrial fibrillation (AF) is well recognized; however, there is little information on the association of pulmonary vein (PV) diameter and AF. The purpose of this study was to investigate by magnetic resonance angiography the change of PV and LA size in patients with no history of AF, patients with paroxysmal AF (PAF), and patients with chronic AF (CAF). METHODS AND RESULTS: The study included 47 patients. Group I included 15 patients with normal sinus rhythm and no history of documented AF. Group II included 24 patients with drug-refractory PAF who underwent electrophysiologic study and radiofrequency ablation of PV foci. Group III included 8 patients with CAF who were converted to sinus rhythm by external electrical cardioversion. Age and concomitant heart diseases were similar among the three groups. We measured the diameter of each PV at its junction with the LA in addition to LA dimensions by gadolinium-enhanced magnetic resonance angiography with three-dimensional reconstruction. Significant dilation of both superior PVs (P < 0.01) and transverse diameter of LA (P < 0.01) was seen in the three groups. There were no significant changes of both inferior PVs, corrected PV (PV/LA) diameter, or longitudinal diameter of LA among the three groups. Only 28% patients showed arrhythmogenic foci from the largest PV. CONCLUSION: Significant dilation of both superior PVs with simultaneous LA enlargement was demonstrated i     

Diagnostic value of endobronchial ultrasonography with a guide sheath for peripheral pulmonary lesions without X-ray fluoroscopy

STUDY OBJECTIVES: We evaluated the feasibility and efficacy of transbronchial biopsy (TBB) and bronchial brushing by endobronchial ultrasonography (EBUS) with a guide sheath (GS) as a guide for diagnosing peripheral pulmonary lesions (PPLs) without radiographic fluoroscopy. PATIENTS: One hundred twenty-one patients with 123 PPLs (mean diameter, 31.0 mm) whose bronchoscopic findings were normal. METHODS: An EBUS-GS was inserted and advanced to the PPL without fluoroscopy. Once we obtained the EBUS image, the probe was withdrawn and the GS was left in place. TBB and/or bronchial brushing were performed via the GS. When an EBUS image could not be obtained, we changed to the bronchoscopic examination under fluoroscopy. RESULTS: Seventy-six of 123 PPLs (61.8%) were diagnosed by EBUS-GS guidance without fluoroscopy. The diagnostic yield for PPLs > 20 mm in diameter (75.6%) was significantly higher than that for those 相似文献   

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.     

New definition and natural history of patients with diffuse pulmonary arteriovenous malformations: twenty-seven-year experience

BACKGROUND: Patients with diffuse pulmonary arteriovenous malformations (PAVM), a small but important subset of the PAVM population, have significant morbidity and mortality rates. METHODS: Thirty-six patients (21 female and 15 male) with diffuse PAVM from a cohort of 821 consecutive patients with PAVM were evaluated. Diffuse PAVM were categorized angiographically: involvement of one or more segmental pulmonary arteries in one or both lungs. Hereditary hemorrhagic telangiectasia (HHT) status, gender, presence or absence of large (> or = 3-mm diameter artery) focal PAVM, oxygen saturations, complications including hemoptysis, years of follow-up, and survival were tabulated. RESULTS: HHT was present in 29 of 36 patients (81%), and diffuse PAVM were more commonly bilateral (26 of 36 patients, 72%) than unilateral (10 of 36 patients, 28%) [p = 0.02]. Female gender was associated with bilateral diffuse PAVM (19 of 26 patients, 73%) [p = 0.01]. Focal PAVM were present in both groups but more commonly in patients with bilateral involvement (16 of 26 patients, 62%) [p = 0.02]. Initial oxygen saturations (pulse oximetry, standing) of patients with unilateral and bilateral diffuse PAVM were 87 +/- 7% and 79 +/- 8% (mean +/- SD), respectively (p = 0.02). The last or current values for patients with unilateral and bilateral involvement are 95 +/- 3% and 85 +/- 7%, respectively (p < 0.0001). Nine deaths occurred, and all were in patients with bilateral involvement. Deaths were due to hemoptysis of bronchial artery origin (n = 2), hemorrhage from duodenal ulcer (n = 1), spontaneous liver necrosis (n = 3), brain hemorrhage (n = 1), brain abscess (n = 1), and operative death during attempted lung transplant (n = 1). CONCLUSIONS: Patients with diffuse PAVM are a high-risk group, and yearly follow-up is recommended.     

Atrial septostomy in treatment of end-stage right heart failure in patients with pulmonary hypertension

BACKGROUND: Right ventricular (RV) failure is the main cause of death in patients with pulmonary hypertension (PH). Balloon atrial septostomy (BAS) is believed to relieve symptoms of PH by increasing systemic flow and reducing RV preload. METHODS: Fourteen BAS procedures were performed in 11 patients (5 men and 6 women; mean [+/- SD] age, 33 +/- 12 years) with RV failure in the course of PH that was refractory to conventional treatment. BAS consisted of a puncture of the interatrial septum and subsequent dilatations with balloons of increasing diameter in a step-by-step manner. RESULTS: After BAS, the mean oxygen saturation of aortic blood decreased (before, 93 +/- 4%; after, 84 +/- 4%; p = 0.001), while mean cardiac index increased (before, 1.54 +/- 0.34 L/min/m(2); after, 1.78 +/- 0.35 L/min/m(2); p = 0.001), resulting in a positive trend for mean systemic oxygen transport (before, 270 +/- 64 mL/min; after, 286 +/- 81 mL/min; p = 0.08). Pulmonary vascular resistance (PVR) slightly increased immediately after the procedure, and this rise inversely correlated with mixed venous blood partial oxygen pressure both before BAS (r = -0.69; p = 0.009) and after BAS (r = -0.64; p = 0.018). Mean functional class improved from 3.2 +/- 0.4 to 2.6 +/- 0.7 (p = 0.03) after 1 month. At follow-up (mean time to follow-up, 8.1 +/- 6.2 months; range, 0.8 to 20.2 months), seven patients died and two underwent lung transplantation. There was no difference in the survival rate compared to that obtained from National Institutes of Health equation. A significant size reduction in the created defect was observed in six patients, requiring repeat BAS procedures in three cases. CONCLUSIONS: The current BAS technique improves cardiac index and functional class without significant periprocedural complications, except for a transient increase in PVR related to acute desaturation of mixed venous blood. At long-term follow-up, a high incidence of spontaneous decrease in orifice size has been observed.     

Airway wall thickening in patients with cough variant asthma and nonasthmatic chronic cough

BACKGROUND: Chronic cough, which may be of asthmatic or nonasthmatic origin, is an important clinical issue. Airway inflammation, and remodeling demonstrated by subbasement membrane thickening has been associated with cough variant asthma (CVA) as well as with nonasthmatic chronic cough (NAC). CT studies have shown airway wall thickening in patients with asthma who wheeze. We examined airway wall thickness by CT in adult patients with chronic cough and examined its pathophysiologic implication. METHODS: Nonsmoking, steroid-na?ve patients with CVA (n = 27), NAC (n = 26), and healthy control subjects (n = 15) were studied. Airway dimensions were assessed by a validated CT technique, in which we measured airway wall area (WA) corrected by body surface area (BSA), the ratio of WA to outer wall area (percentage of wall area [WA%]), absolute wall thickness (T)/ square root BSA, and airway luminal area/BSA of a segmental bronchus. Correlations between CT parameters and clinical indexes such as disease duration and cough sensitivity were examined. RESULTS: In patients with CVA, WA/BSA, WA%, and T/ square root BSA were all significantly greater than those in control subjects. In patients with NAC, WA/BSA and T/ square root BSA were significantly greater than in control subjects. The increase of WA/BSA and T/ square root BSA of NAC patients was less than that of CVA patients. In a subset of patients with NAC, WA% correlated with capsaicin cough sensitivity (n = 9, r = 0.75, p = 0.034). CONCLUSIONS: Walls of central airways are thickened in patients with CVA, and also to a lesser degree in patients with NAC. Airway wall thickening in NAC may be associated with cough hypersensitivity.     

The association between small airway obstruction and emphysema phenotypes in COPD

BACKGROUND: Airflow limitation in COPD is due to a variable combination of small airway obstruction and centrilobular emphysema (CLE) and/or panlobular emphysema (PLE), but the relationship between these three different phenotypes is poorly understood. This study compares the severity of small airway obstruction in both forms of emphysema and determines its relationship with FEV(1). METHODS: We compared the lung histology of nonsmoking control subjects without emphysema (n = 10) to that of patients with CLE (n = 30) and PLE with (n = 8) and without alpha(1)-antitrypsin (AAT) deficiency (n = 11). The degree of airspace enlargement was measured using the mean interalveolar wall distance (IAWD) [mean linear intercept, Lm], and the evenness of airspace destruction was assessed by the coefficient of variation (CV) of the IAWD. The severity of small airway obstruction was determined by dividing total wall area by the length of the basement membrane to obtain wall thickness. RESULTS: Lm was greater in all three subgroups of emphysema than in control subjects, and in AAT deficiency than in PLE or CLE. The CV of IAWD was greater in AAT deficiency and CLE than in control subjects and in CLE than in AAT deficiency or PLE. Although small airway wall thickness was greater in CLE and PLE with AAT deficiency than in control subjects, the association between wall thickness and both Lm and FEV(1) was observed only in CLE. CONCLUSIONS: Small airway wall thickening occurs in CLE and PLE with AAT deficiency but is more closely associated with degree of emphysema and airflow limitation in CLE.