Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea.

Daytime pulmonary hypertension (PH) is relatively common in obstructive sleep apnea (OSA) and is thought to be associated with pulmonary vascular remodeling (PRm). The extent to which PH is reversible with treatment is uncertain. To study this, we measured pulmonary hemodynamics (Doppler echocardiography) in 20 patients with OSA (apnea-hypopnea index [AHI] 48.6 +/- 5.2/h, mean +/- SEM) before and after 1 and 4 mo of CPAP treatment (compliance 4.7 +/- 0.5 h/night). Patients had normal lung function, and no cardiac disease or systemic hypertension. Doppler studies were performed at three levels of inspired oxygen concentration (11%, 21%, and 50%) and during incremental increases in pulmonary blood flow (10, 20, and 30 microg/kg/min dobutamine infusions). Treatment resulted in a decrease in pulmonary artery pressure (Ppa, 16.8 +/- 1.2 mm Hg before CPAP versus 13.9 +/- 0.6 mm Hg after 4 mo CPAP, p < 0.05) and total pulmonary vascular resistance (231.1 +/- 19.6 versus 186.4 +/- 12.3 dyn. s. cm(-)(5), p < 0.05). The greatest treatment effects occurred in the five patients who were pulmonary hypertensive at baseline. The pulmonary vascular response to hypoxia decreased after CPAP (DeltaPpa/DeltaSa(O(2)) 10.0 +/- 1.6 mm Hg before versus 6.3 +/- 0.8 mm Hg after 4 mo CPAP, p < 0.05). The curve of Ppa versus cardiac output (Q), derived from the incremental dobutamine infusion, shifted downward in a parallel fashion during treatment. Systemic diastolic blood pressure also fell significantly. Improvements in pulmonary hemodynamics were not attributable to changes in left ventricular diastolic function or Pa (O(2)). We conclude that CPAP treatment reduces Ppa and hypoxic pulmonary vascular reactivity in OSA and speculate that this may be due to improved pulmonary endothelial function.     

The clinical significance of reversed flow in the main pulmonary artery detected by doppler color flow imaging

BACKGROUND: Using Doppler color flow imaging, abnormal flow patterns were reported to occur with pulmonary artery (PA) dilation. We have frequently observed red signals in the main PA, suggesting reversed flow (RF) in patients without overt pulmonary hypertension. The clinical implication of these signals has not been extensively studied. PATIENTS AND METHODS: We studied 191 of 412 patients referred for echocardiography (99 men and 92 women; mean +/- SD age, 62 +/- 13 years), in whom the main PA diameter had been adequately measured. If a red signal was observed by color flow imaging, a pulsed Doppler echocardiogram of the red signal was recorded simultaneously. The presence of the red signal was correlated with the PA diameter and the PA systolic pressure determined using the modified Bernoulli equation. In 54 patients who also underwent cardiac catheterization studies, the red signal was correlated with PA and pulmonary capillary wedge (PCW) pressures, and with pulmonary vascular resistance. RESULTS: Red signals adjacent to the medial PA border were detected in parallel with systolic blue signals in 127 patients (66%). Pulsed Doppler recordings revealed that they were caused by RF occurring immediately after the forward systolic signal and persisted in diastole. The PA diameter (28 +/- 4.8 mm) and the estimated PA systolic pressure (34 +/- 16 mm Hg) of patients with the RF signal were significantly greater (p < 0.001 and p < 0.05, respectively) than those of patients without the signal (22 +/- 2.5 mm and 28 +/- 6.0 mm Hg, respectively). Among patients who had hemodynamic studies, PA and PCW pressures were significantly higher (p < 0.05) in the 41 patients with the RF signal (22 +/- 12 mm Hg vs 15 +/- 2.6 mm Hg and 11 +/- 5.5 mm Hg vs 8 +/- 3.1 mm Hg, respectively). CONCLUSION:: RF signals in the main PA occur mostly as a result of PA dilation, which may be caused by primary pulmonary hypertension or chronic elevation of left atrial pressure in left-sided cardiac abnormalities.     

Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension

STUDY OBJECTIVES: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. STUDY DESIGN: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. SETTING: Cardiac catheterization laboratory in a tertiary care teaching hospital. PATIENTS: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. MEASUREMENTS AND RESULTS: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean +/- SEM] 49 +/- 2 mm Hg vs 44 +/- 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 +/- 68 vs 669 +/- 64 dyne x s x cm(-5); p < 0.01) and RV end-diastolic pressure (RVEDP; 12 +/- 1 vs 10 +/- 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 +/- 2 vs 35 +/- 3 mL/m(2); p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 +/- 5 vs 76 +/- 5 mm Hg; p < 0.01), PA was unchanged (48 +/- 2 vs 45 +/- 3 mm Hg; p = not significant), and PVR decreased (791 +/- 53 vs 665 +/- 53 dyne x s x cm(-5); p < 0.01). RV +dP/dt at DP15 increased (425 +/- 22 vs 465 +/- 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 +/- 5 vs 94 +/- 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 +/- 1 vs 14 +/- 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 +/- 90 vs 389 +/- 21 mm Hg/s; p < 0.05). CONCLUSIONS: Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility. Nitroprusside caused a similar degree of pulmonary vasodilation. In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased.     

Plasma beta-endorphin and adenosine concentration in pulmonary hypertension

To determine whether beta-endorphin plays a role in the regulation of pulmonary vascular tone in patients with pulmonary hypertension, we investigated the relations between hemodynamics and beta-endorphin and adenosine concentrations in 3 clinical situations: (1) normal hemodynamics (7 subjects, mean pulmonary artery [PA] pressure 18.5 +/- 1 mm Hg); (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) (8 patients, mean PA pressure 31 +/- 3 mm Hg); and (3) severe primary pulmonary hypertension (PPH) (8 patients, mean PA pressure 70 +/-5 mm Hg). Plasma beta-endorphin and adenosine were measured in a distal PA and in the femoral artery in room air and during oxygen inhalation. Beta-endorphin levels were similar in the pulmonary and systemic circulations. No difference was observed between patients with COPD and PPH, but relative to controls, both had significantly higher beta-endorphin levels. Pulmonary adenosine was significantly lower in patients with pulmonary hypertension than in controls (-60% in COPD [p <0.005] and -70% in PPH [p <0.001]). Pure oxygen administration significantly decreased adenosine and beta-endorphin levels, much more so in patients with COPD and PPH. We found a negative correlation between beta-endorphin and adenosine concentrations (r = -0.751, p <0.001): the higher the adenosine, the lower the beta-endorphin level. These observations suggest that because adenosine release by pulmonary vascular endothelium is reduced in pulmonary hypertension, the resulting worsened hypoperfusion and tissue oxygenation may cause increased beta-endorphin release.     

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.     

Effects of lipo-prostaglandin E1 on pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension

OBJECTIVE: To determine whether lipid microspheres containing prostaglandin E1 (lipo-PGE1) improve pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension (PAH). METHODS: Forty-nine patients with PAH (8 patients with primary pulmonary hypertension, 21 patients with collagen vascular disease, 20 patients with congenital systemic-to-pulmonary shunts) were randomly classified into a conventional therapy group (n = 22) or a group receiving lipo-PGE1 plus conventional drugs (lipo-PGE1 group; n = 27). Echocardiographic pulmonary parameters, New York Heart Association (NYHA) functional class, and Bruce treadmill test results for exercise capacity were recorded before and after treatment. RESULTS: After 2 weeks of treatment with lipo-PGE1 (10 microg bid for 14 days), there were significant improvements in the values (+/- SD) for systolic pulmonary arterial pressure (SPAP) [76.9 +/- 27.9 mm Hg vs 66.5 +/- 22.8 mm Hg, p < 0.001]; total pulmonary resistance (27.2 +/- 13.3 dyne.s.cm(-5) vs 20.2 +/- 10.7 dyne.s.cm(-5), p < 0.001); left ventricular ejection fraction (58.7 +/- 9.6% vs 64.4 +/- 6.8%, p < 0.001); and cardiac output (3.1 +/- 0.8 L/min vs 3.7 +/- 1.1 L/min, p < 0.01). The NYHA functional class decreased from 3.0 +/- 0.6 to 2.5 +/- 0.6 (p < 0.001), and the exercise capacity increased from 2.8 +/- 1.0 to 4.3 +/- 1.3 metabolic equivalents (MET) [p < 0.001]. Compared with the conventional therapy group, the lipo-PGE(1) group achieved significant reduction of SPAP (10.4 +/- 10.3 mm Hg vs 2.2 +/- 5.6 mm Hg, p = 0.002) and a significant elevation of exercise capacity (1.5 +/- 0.9 MET vs 0.6 +/- 1.1 MET, p = 0.018). CONCLUSION: Lipo-PGE1 can decrease pulmonary artery pressure and increase exercise capacity in patients with PAH.     

Unexplained pulmonary hypertension in elderly patients

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) preferentially affects young women. However, a subset of patients with IPAH is elderly. Our objective was to compare elderly (age >/= 65 years) vs younger persons with unexplained pulmonary hypertension (PH) and a presumptive diagnosis of IPAH. METHODS: Clinical, echocardiographic, hemodynamic, and survival data were collected on consecutive patients with suspected IPAH after evaluation in a large tertiary center PH clinic. RESULTS: Of 197 patients (mean age +/- SD, 52 +/- 16 years; 80% female), 48 patients (24%) were elderly. Elderly and younger patients had similar symptom severity, systolic pulmonary artery (PA) pressure (82.7 +/- 20.3 mm Hg vs 86.9 +/- 18.8 mm Hg, respectively; p = 0.21), and severity of right ventricular enlargement and dysfunction. Elderly patients had higher pulmonary capillary wedge pressure (PCWP) [15.3 +/- 7.3 mm Hg vs 11.1 +/- 5.3 mm Hg; p < 0.0001] and more frequently failed (56%) to meet hemodynamic criteria for IPAH (PH with PCWP < 15 mm Hg) than did younger patients (19%). Elderly patients also had higher systemic systolic (p < 0.0001) and pulse (p < 0.0001) pressures and more cardiovascular disease. Among those patients with normal PCWP, elderly patients had worse survival than young patients (p = 0.007). Among those patients with elevated PCWP, elderly patients had lower PA pressures (p = 0.04) and better survival (p = 0.02). CONCLUSIONS: Elderly patients with clinically suspected IPAH often fail to meet hemodynamic criteria for IPAH due to elevated PCWP. Studies to define the proper diagnostic strategy and the safety and efficacy of pulmonary vasodilators in elderly patients with unexplained PH are needed.     

Long-term effect of continuous positive airway pressure on BP in patients with hypertension and sleep apnea

OBJECTIVE: To analyze the long-term effect of continuous positive airway pressure (CPAP) on ambulatory BP in patients with obstructive sleep apnea (OSA) and hypertension, and to identify subgroups of patients for whom CPAP could be more effective. METHODS: We conducted a prospective, long-term follow-up trial (24 months) in 55 patients with OSA and hypertension (mean CPAP use, 5.3 +/- 1.9 h/d [+/- SD]). Twenty-four-hour ambulatory BP monitoring (ABPM) was measured at baseline and after intervention with CPAP on an intention-to-treat basis. In addition, the correlation between the changes in 24-h mean arterial pressure (24hMAP) and CPAP compliance, OSA severity, and baseline ABPM was assessed. RESULTS: At the end of follow-up, a significant decrease was shown only in diastolic BP (- 2.2 mm Hg; 95% confidence interval [CI], - 4.2 to - 0.1; p = 0.03) but not in 24hMAP or other ABPM parameters. However, a correlation between changes in 24hMAP and baseline systolic BP (r = - 0.43, p = 0.001), diastolic BP (r = - 0.38, p = 0.004), and hours of use of CPAP (r = - 0.30, p = 0.02) was observed. A significant decrease in the 24hMAP was achieved in a subgroup of patients with incompletely controlled hypertension at entry (- 4.4 mm Hg; 95% CI, - 7.9 to - 0.9 mm Hg; p = 0.01), as well as in those with CPAP compliance > 5.3 h/d (- 5.3 mm Hg; 95% CI, - 9.5 to - 1.2 mm Hg; p = 0.01). Linear regression analysis showed that baseline systolic BP and hours of CPAP were independent predictors of reductions in BP with CPAP. CONCLUSION: Long-term CPAP reduced BP modestly in the whole sample. However, patients with higher BP at entry and good CPAP compliance achieved significant reductions in BP.     

Oral sildenafil to control pulmonary hypertension after congenital heart surgery

This study investigates the role of oral sildenafil in decreasing pulmonary pressure after congenital heart surgery. Between September 2002 and September 2004, among a group of postoperative children with large septal defects, moderate to severe pulmonary hypertension [pulmonary artery (PA) to aortic (Ao) pressure ratio of 0.76 +/- 0.17] and systemic desaturation (Ao Sat = 0.89 +/- 0.11), oral sildenafil (0.3 mg x kg(-1), every 3 hours) was administered for a period of 24-48 hours (sildenafil group). These patients were compared to a group of 22 children with similar pathologies who did not receive sildenafil (control group). Postoperative PA pressure (28.61 +/- 7.80 vs 39.40 +/- 10.80 mm Hg) and PA/Ao pressure (0.28 +/- 0.08 vs 0.41 +/- 0.11) were significantly lower in the sildenafil group ( p = 0.001 and 0.001 respectively). Pulmonary hypertensive crisis was detected in 4 patients in the control group, but none in the sildenafil group ( p = 0.02). There was no significant rise in PA pressure following discontinuation of the drug (26.30 +/- 6.66 vs 28.49 +/- 10.93 mm Hg, p = 0.366). No significant complications were noticed regarding sildenafil use. Low doses of oral sildenafil appear to be effective and safe to control postoperative PA pressure in children. Absence of rebound pulmonary hypertension, availability, and low cost of the drug are considered as its major advantages.     

Pulmonary artery pulse pressure and wave reflection in chronic pulmonary thromboembolism and primary pulmonary hypertension

OBJECTIVES: The purpose of this time-domain study was to compare pulmonary artery (PA) pulse pressure and wave reflection in chronic pulmonary thromboembolism (CPTE) and primary pulmonary hypertension (PPH). BACKGROUND: Pulmonary artery pressure waveform analysis provides a simple and accurate estimation of right ventricular afterload in the time-domain. Chronic pulmonary thromboembolism and PPH are both responsible for severe pulmonary hypertension. Chronic pulmonary thromboembolism and PPH predominantly involve proximal and distal arteries, respectively, and may lead to differences in PA pressure waveform. METHODS: High-fidelity PA pressure was recorded in 14 patients (7 men/7 women, 46 +/- 14 years) with CPTE (n = 7) and PPH (n = 7). We measured thermodilution cardiac output, mean PA pressure (MPAP), PA pulse pressure (PAPP = systolic - diastolic PAP) and normalized PAPP (nPAPP = PPAP/MPAP). Wave reflection was quantified by measuring Ti, that is, the time between pressure upstroke and the systolic inflection point (Pi), deltaP, that is, the systolic PAP minus Pi difference, and the augmentation index (deltaP/PPAP). RESULTS: At baseline, CPTE and PPH had similar cardiac index (2.4 +/- 0.4 vs. 2.5 +/- 0.5 l/min/m2), mean PAP (59 +/- 9 vs. 59 +/- 10 mm Hg), PPAP (57 +/- 13 vs. 53 +/- 13 mm Hg) and nPPAP (0.97 +/- 0.16 vs. 0.89 +/- 0.13). Chronic pulmonary thromboembolism had shorter Ti (90 +/- 17 vs. 126 +/- 16 ms, p < 0.01) and higher deltaP/PPAP (0.26 +/- 0.01 vs. 0.09 +/- 0.07, p < 0.01). CONCLUSIONS: Our study indicated that: 1) CPTE and PPH with severe pulmonary hypertension had similar PA pulse pressure, and 2) wave reflection is elevated in both groups, and CPTE had increased and anticipated wave reflection as compared with PPH, thus suggesting differences in the pulsatile component of right ventricular afterload.     

Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension

AIMS: Decreased total compliance of the pulmonary vascular bed is associated with increased mortality in patients with pulmonary arterial hypertension (PAH). We investigated whether proximal pulmonary artery stiffness, in terms of area distensibility and noninvasively assessed relative area change (RAC), calculated as relative cross-sectional area change, predicts mortality in patients with PAH. METHODS AND RESULTS: Eighty-six subjects underwent right-heart catheterization and MRI to assess area distensibility and RAC. Patients were followed up to 48 months. Kaplan-Meier plot and Cox proportional hazards regression analyses assessed the predictive value of area distensibility and RAC. In 70 patients, the diagnosis PAH was confirmed, and 16 subjects served as control subjects. In comparison with control subjects, proximal pulmonary arteries of patients were distended (685 +/- 214 mm2 vs 411 +/- 153 mm2, p < 0.001), less distensible (area distensibility = 0.46 +/- 0.38.10(-2) mm Hg(-1) vs 3.69 +/- 1.96.10(-2) mm Hg(-1), p < 0.0001), and RAC was smaller (20 +/- 10% vs 58 +/- 21%, p < 0.0001) [mean +/- SD]. RAC showed an inverse curvilinear relation with mean pulmonary artery pressure (R2 = 0.47). Eighteen patients (26%) died because of cardiopulmonary causes. Patients with a pulmonary artery RAC 16% (log-rank p < 0.001). RAC predicted mortality better than area distensibility. CONCLUSION: Noninvasively measured pulmonary artery RAC predicts mortality in patients with PAH.     

Bosentan in pulmonary arterial hypertension secondary to scleroderma

OBJECTIVE:. To assess the efficacy and tolerability of bosentan in pulmonary arterial hypertension secondary to systemic sclerosis (SSc-PAH) including patients with restrictive lung disease. METHODS: We retrospectively reviewed 23 SSc-PAH patients with PAH at baseline [PA systolic pressure (PASP) >or= 45 mm Hg by echocardiogram or mean PA pressure > 25 mm Hg at rest by cardiac catheterization], World Health Organization (WHO) functional classes II-IV, and with data available for 18 months. Bosentan dose was 62.5 mg twice daily for 1 month then 125 mg twice daily. Outcomes were WHO functional class, PASP, and pulmonary function tests (PFT) at 3-month intervals for 18 months. RESULTS: WHO class at baseline 3.1 +/- 0.1 (mean +/- SE); 3 months, 2.5 +/- 0.2*; 6 months, 2.4 +/- 0.2*; 9 months, 2.5 +/- 0.2* (*p < 0.02 vs baseline, n = 21 to 23), indicating clinical improvement at 9 months. After 9 months, results were not significant versus baseline. Reduction in WHO class by at least one rank was 57% at 3 months; none worsened. After 9 months, WHO class tended to worsen compared to baseline. Baseline PASP was 54 +/- 2 mm Hg (n = 23) and did not change significantly with therapy. Restriction (total lung capacity 76% +/- 4% of predicted) and reduced diffusing capacity (39% +/- 3% of predicted) were unchanged during therapy. Abnormal transaminases in 2 patients (9%) necessitated discontinuing drug in both. CONCLUSION: Bosentan is clinically beneficial in patients with SSc-PAH including patients with restrictive lung disease, but pulmonary hemodynamics and PFT results remained stable during treatment.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome

The frequency of daytime pulmonary hypertension (PH) in patients with obstructive sleep apnea syndrome (OSAS) has not been well established and its mechanisms are still under debate. We have thus performed right heart catheterization, in addition to standard spirography and arterial blood gas measurements, in a series of 46 consecutive patients in whom OSAS was firmly diagnosed by whole-night polysomnography. Only 9 of the 46 patients (20%) had PH defined by a mean resting pulmonary arterial pressure (Ppa) greater than or equal to 20 mm Hg. Among the patients without resting PH, 14 had exercising PH (defined by a Ppa greater than 30 mm Hg during 40-watt, steady-state exercise). Patients with resting PH differed from the others by a lower daytime PaO2 (60.8 +/- 7.6 versus 76.2 +/- 9.4 mm Hg; p less than 0.001), a higher daytime PaCO2 (44.6 +/- 4.2 versus 38.0 +/- 4.0 mm Hg; p less than 0.001), and lower VC and FEV1 (p less than 0.001). There was no difference between the 2 groups with regard to apnea index (62 +/- 34 versus 65 +/- 40) or the lowest sleep SaO2 (59 +/- 21 versus 66 +/- 18%) or the time spent in apnea. For the group as a whole, there was a good correlation between Ppa and daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), and FEV1 (r = -0.52; p less than 0.001), but there was no significant correlation between Ppa and the apnea index, the lowest sleep SaO2, or the time spent in apnea.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency and mechanism of daytime pulmonary hypertension in patients with obstructive sleep apnoea syndrome

In order to study the frequency and the mechanisms of daytime pulmonary hypertension (PH) in obstructive sleep apnoea syndrome (OSAS) lung function tests, blood gas analysis and right-heart catheterization were performed in 46 consecutive patients. OSAS was assessed by polysomnography. 9 patients only (20%) had PH (mean pulmonary artery pressure (Ppa) greater than or equal to 20 mmHg). Patients with PH had lower daytime PaO2 (60.8 +/- 7.6 vs. 76.2 +/- 9.4 mmHg; p less than 0.001), higher daytime PaCO2 (44.8 +/- 4.2 vs. 38.0 +/- 4.0 mmHg; p less than 0.001), lower forced vital capacity (FVC) and forced expiratory volume (FEV1) (p less than 0.001), but the severity of OSAS was not different whether PH was present or not (apnoea index: 62 +/- 34 hour in the PH group vs. 65 +/- 40 hour, apnoea + hypopnoea index 102 +/- 33 hour in the PH group vs. 86 +/- 36 hour, lowest sleep SaO2: 59 +/- 21% in the PH group vs. 66 +/- 18%). There were significant correlations between Ppa and: daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), FEV1 (r = -0.52; p less than 0.001) but not between Ppa and apnoea index, apnoea + hypopnoea index, lowest sleep SaO2. PH and daytime hypoxaemia were associated either with chronic airway obstruction or with severe obesity.     

The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans

Arterial hypertension is known to be frequently associated with thyroid dysfunction, with a particularly high prevalence in chronic hypothyroidism. However, to our knowledge no comprehensive study addressed causal mechanisms possibly involved in this association. We here report the physiological relationships between blood pressure and neuro-humoral modifications induced by acute hypothyroidism in normotensive subjects. Twelve normotensive patients with previous total thyroidectomy were studied. Ambulatory 24-h blood pressure monitoring was performed, and free T(3), free T(4), TSH, PRA, aldosterone, cortisol, adrenaline, and noradrenaline were assayed 6 wk after oral L-T(4) withdrawal (phase 1) and 2 months after resumption of treatment (phase 2). During the hypothyroid state (TSH, 68.1 +/- 27.7 microIU/ml; mean +/- SD), daytime arterial systolic levels slightly, but significantly, increased (125.5 +/- 9.7 vs. 120.4 +/- 10.8 mm Hg; P < 0.05), and daytime diastolic levels (84.6 +/- 7.9 vs. 76.4 +/- 6.8 mm Hg; P < 0.001), noradrenaline (2954 +/- 1578 vs. 1574 +/- 962 pmol/liter; P < 0.001), and adrenaline (228.4 +/- 160 vs. 111.3 +/- 46.1 pmol/liter; P < 0.05) also increased. PRA remained unchanged (0.49 +/- 0.37 vs. 0.35 +/- 0.21 ng/ml.h; P = NS), whereas both aldosterone (310.3 +/- 151 vs. 156.9 +/- 67.5 pmol/liter; P < 0.005) and cortisol (409.2 +/- 239 vs. 250.9 +/- 113 pmol/liter; P < 0.02) significantly increased. By using univariate logistic regression daytime arterial diastolic values, noradrenaline and aldosterone were found to be significantly related to the hypothyroid state (P < 0.02, P < 0.036, and P < 0.024, respectively). In conclusion, our data show that thyroid hormones participate in the control of systemic arterial blood pressure homeostasis in normotensive subjects. The observed sympathetic and adrenal activation in hypothyroidism, which is reversible with thyroid hormone treatment, may also contribute to the development of arterial hypertension in human hypothyroidism.     

Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study.

AIMS: We tested the hypothesis that: (i) obstructive sleep apnoea (OSA) by itself originates pulmonary hypertension (PH); and (ii) the application of continuous positive airway pressure (CPAP) can reduce pulmonary pressure. METHODS AND RESULTS: In this randomized and cross-over trial, 23 middle-aged OSA (apnoea-hypopnoea index, 44.1 +/- 29.3 h(-1)) and otherwise healthy patients and 10 control subjects were included. OSA patients randomly received either sham or effective CPAP for 12 weeks. Echocardiographic parameters, blood pressure recordings, and urinary catecholamine levels were obtained at baseline and after both treatment modalities. At baseline, OSA patients had higher pulmonary artery systolic pressure than control subjects (29.8 +/- 8.8 vs. 23.4 +/- 4.1 mmHg, respectively, P = 0.036). Ten out of 23 patients [43%, (95% CI: 23-64%)] and none of the control subjects had PH at baseline (P = 0.012). Two patients were removed from the study because of inadequate CPAP compliance. Effective CPAP induced a significant reduction in the values for pulmonary systolic pressure (from 28.9 +/- 8.6 to 24.0 +/- 5.8 mmHg, P < 0.0001). The reduction was greatest in patients with either PH or left ventricular diastolic dysfunction at baseline. CONCLUSION: Severe OSA is independently associated with PH in direct relationship with disease severity and presence of diastolic dysfunction. Application of CPAP reduces pulmonary systolic pressure levels.     

Hemodynamic effects of inhaled nitric oxide in women with mitral stenosis and pulmonary hypertension

Mitral stenosis (MS) is associated with elevated left atrial pressure, increased pulmonary vascular resistance (PVR), and pulmonary hypertension (PH). The hemodynamic effects of inhaled nitric oxide (NO) in adults with MS are unknown. We sought to determine the acute hemodynamic effects of inhaled NO in adults with MS and PH. Eighteen consecutive women (mean age 58 +/- 15 years) with MS and PH underwent heart catheterization. Hemodynamic measurements were recorded at baseline, after NO inhalation at 80 ppm, and after percutaneous balloon valvuloplasty (n = 10). NO reduced pulmonary artery systolic pressure (62 +/- 14 mm Hg [baseline] vs 54 +/- 15 mm Hg [NO]; p <0.001) and PVR (3.7 +/- 2.5 Wood U [baseline] vs 2.2 +/- 1.4 Wood U [NO]; p <0.001). NO had no effect on mean aortic pressure, left ventricular end-diastolic pressure, left atrial pressure, cardiac output, or systemic vascular resistance. Mitral valve area increased after valvuloplasty (0.9 +/- 0.2 cm2 [baseline] vs 1.6 +/- 0.3 cm2 [postvalvuloplasty]; p <0.001). A decrease in left atrial pressure (25 +/- 4 mm Hg [baseline] vs 17 +/- 4 mm Hg [after valvuloplasty]; p <0.001) and pulmonary artery systolic pressure (58 +/- 12 mm Hg [baseline] vs 45 +/- 8 mm Hg [after valvuloplasty]; p <0.001) was observed after valvuloplasty. No change in cardiac output or PVR was observed. Thus inhaled NO, but not balloon valvuloplasty, acutely reduced PVR in women with MS and PH. This suggests that a reversible, endothelium-dependent regulatory abnormality of vascular tone is an important mechanism of elevated PVR in MS.     

Impact of valve prosthesis-patient mismatch on pulmonary arterial pressure after mitral valve replacement

OBJECTIVES: We sought to determine the impact of valve prosthesis-patient mismatch (PPM) on pulmonary arterial (PA) pressure after mitral valve replacement (MVR). BACKGROUND: Pulmonary arterial hypertension is a serious complication of mitral valve disease, and it is a major risk factor for poor outcome after MVR. We hypothesized that valve PPM might be a determinant of PA hypertension after MVR. METHODS: Systolic PA pressure was measured by Doppler echocardiography in 56 patients with normally functioning mitral prosthetic valves. Mitral valve effective orifice area (EOA) was determined by the continuity equation and indexed for body surface area. RESULTS: Thirty patients (54%) had PA hypertension defined as systolic PA pressure >40 mm Hg, whereas 40 patients (71%) had PPM defined as an indexed EOA < or =1.2 cm(2)/m(2). There was a significant correlation (r = 0.64) between systolic PA pressure and indexed EOA. The average systolic PA pressure and prevalence of PA hypertension were 34 +/- 8 mm Hg and 19% in patients with no PPM versus 46 +/- 8 mm Hg and 68% in patients with PPM (p < 0.001). In multivariate analysis, the indexed EOA was by far the strongest predictor of systolic PA pressure. CONCLUSIONS: Persistent PA hypertension is frequent after MVR and strongly associated with the presence of PPM. The clinical implications of these findings are important given that PPM can largely be avoided by using a simple prospective strategy at the time of operation.     

Left ventricular function in patients with obstructive sleep apnoea syndrome before and after treatment with nasal continuous positive airway pressure

BACKGROUND: Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function. OBJECTIVES: In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP). METHODS: Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean +/- SD = 52 +/- 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12-14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group. RESULTS: Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 +/- 11.6 ms, p < 0.05; E/A = 0.94 +/- 0.26, p < 0.02; SF = 39.9 +/- 4.1%, not significant (NS); IVST = 9.9 +/- 1.2 mm, NS; PWT = 8.3 +/- 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 +/- 9.2 mm Hg, BP/diastolic/night-time = 90.3 +/- 10.7 mm Hg). After 12-14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 +/- 8.8 ms, p < 0.05; E/A = 1.07 +/- 0.3, p < 0.05; BP/diastolic/daytime = 86.3 +/- 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 +/- 8. 6 mm Hg, p < 0.05) in our patient group. CONCLUSIONS: We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension.     

Correlation of left ventricular diastolic filling characteristics with right ventricular overload and pulmonary artery pressure in chronic thromboembolic pulmonary hypertension

OBJECTIVES: This study was designed to determine a quantitative relationship between right ventricular (RV) pressure overload and left ventricular (LV) diastolic filling characteristics in patients with chronic thromboembolic pulmonary hypertension (CTEPH). BACKGROUND: Right ventricular pressure overload in patients with CTEPH causes abnormal LV diastolic filling. However, a quantitative relationship between RV pressure overload and LV diastolic function has not been established. METHODS: We analyzed pre- and postoperative diastolic mitral inflow velocities and right heart hemodynamic data in 39 consecutive patients with CTEPH over the age of 30 (55 +/- 11 years) with mean pulmonary artery pressure >30 mm Hg who underwent pulmonary thromboendarterectomy (PTE). RESULTS: After PTE, mean pulmonary artery pressure (mPAP) decreased from 50 +/- 11 to 28 +/- 9 mm Hg (p < 0.001) while cardiac output (CO) increased from 4.4 +/- 1.1 to 5.7 +/- 0.9 l/m (p < 0.001). Mitral E/A ratio (E/A) increased from 0.74 +/- 0.22 to 1.48 +/- 0.69 (p < 0.001). E/A was < 1.25 in all patients pre-PTE. After PTE, all patients with E/A >1.50 had mPAP <35 mm Hg and CO >5.0 l/min. E/A correlated inversely with mPAP (r = 0.55, p < 0.001) and directly with CO (r = 0.53, p < 0.001). CONCLUSIONS: E/A is consistently abnormal in patients with CTEPH and increases post-PTE. Moreover, E/A varies inversely with mPAP and directly with CO. Following PTE, E/A >1.5 correlates with the absence of severe pulmonary hypertension (mPAP >35 mm Hg) and the presence of normal cardiac output (> 5.0 l/m).