Peak Pulmonary Artery Pressure Research Articles

Pulmonary Artery Pressures During Cardiopulmonary Exercise Testing Using Cardiomems

<h3>Purpose</h3> Continuous pulmonary artery (PA) pressure monitoring has proven its value in reducing heart failure and all-cause hospitalizations. Invasive hemodynamic testing has shown that exercise in HFrEF leads to a steep increase in PA pressures and this steep rise is independently associated with reduced peak Vo₂. PA pressure response during exercise is likely more closely related to outcomes than resting hemodynamics in HF. The significance and potentially prognostic value of measuring PA pressures during CPET testing in AHF patients is currently unknown. In this feasibility-study we describe PA pressure curves during CPET in a cohort of advanced HF patients. <h3>Methods</h3> 7 advanced HF patients (Etiology: 4 NICM, 3 ICM; age 61 ± 12y; EF 28 ± 15%; 86% on beta blocker) with CardioMEMS device underwent standard stationary bike - CPET. PA pressures were measured at rest, every 2 minutes during exercise and during recovery. <h3>Results</h3> Max VO2 was 13.3±5.2 ml/kg/min; average duration of exercise was 8:56 min. Mean resting PA pressure was 12.5±5.2 mmHg. Mean peak PA pressure was 26.7±10 mmHg. Mean PA pressures increased on average by 2.5-fold (± 1.14) (Figure 1). The slope of mPAP rise was 3.33±2.1. mPAP uniformly returned to baseline values within 3 minutes of recovery. Pt. 3 was admitted 1 week after CPET testing with subacute worsening HF symptoms and underwent OHT, all other patients continue to follow at the centralized HF program at our institution. <h3>Conclusion</h3> PAP assessment using CardioMEMS is feasible during CPET. mPAP rose sharply during exercise. In HF patients with invasive PA pressure monitor devices, exercise PAP assessment may be a valuable tool to assess for functional capacity with possibly prognostic significance.

Abstract 11365: Electronic Cigarette Vaping with or Without Heating Induces Differential Pathological Remodeling in the Lungs and Right Heart

Introduction: One of the obstacles in dissecting the specific underlying mechanisms of electronic cigarette (EC) “vaping”-related health effects is the complexity in the chemical composition of EC aerosols. As various chemicals are generated through the heating coil in addition to the intact components presented in the aerosol, we hypothesize that the heating-associated by-products and the intact components would have differential pathological impact to the remodeling of right ventricular (RV) and pulmonary system. Methods: Using a prototype exposure system, C57BL/6 mice were exposed to room air or EC vapor with and without heating the EC liquid (ECL) for 3 hours per day, 5 days per week for 6 months. Echocardiography with color Doppler was used to evaluate cardiac structure and function. To assess inflammatory and fibrotic signaling, Western-blotting was performed. Results: Comparable plasma cotinine levels were found between heating and non-heating exposure, respectively (59.34±8.57ng/mL vs 59.02± 4.83ng/mL; n=5-7). Without heating exposure caused thinning of RV free wall (0.57±0.028 mm control vs 0.43±0.03 mm exposed; p&lt;0.05), whereas with heating, an increase in the RV wall thickness (0.79±0.06 mm exposed, p&lt;0.01) and a reduction in RV chamber size at diastole (1.57±0.04mm control vs 1.34±0.03mm exposed, p&lt;0.01) were observed. While exposure without heating elevates peak pulmonary artery (PA) pressure (2.46±0.31 mmHg control vs 3.34±0.13 mmHg exposed; p&lt;0.05), a lower peak (1.36± 0.12 mmHg exposed; p&lt;0.05) and mean pressure gradient (0.75±0.08 mmHg control vs 0.51± 0.05 mmHg exposed; p&lt;0.05) were recorded with heating exposure. As for pulmonary response, exposure without heating did not affect NF-κB p-p65 level, but reduced p65 expression to 37% of controls (±6%, n=5, p&lt;0.0001) and increased TGF-β1 by 67% (±11%, n=5, p&lt;0.05). In contrast, exposure with heated ECL did not affect p65 and TGF-β1 but increased p-p65/p65 by 39.4% (±5%, n = 5, p &lt; 0.05), indicating activation of NF-κB inflammatory signaling. Conclusions: EC exposure without heating the ECL resulted in fibrotic lung, higher peak PA pressure and RV dystrophy without obvious pulmonary inflammation. Heating the ECL, however, contribute to RV hypertrophy and pulmonary inflammation.

Speckle Tracking-Derived Left Atrial Stiffness Predicts Clinical Outcome in Heart Failure Patients with Reduced to Mid-Range Ejection Fraction.

Background and Aim: Left atrial stiffness (LASt) is an important marker of cardiac function, especially in patients with heart failure (HF); it explains symptoms on the basis of pressure transfer to the pulmonary circulation. The aim of this study was to evaluate the relationship between LASt and cardiac events (CE) in HF patients with reduced to mid-range ejection fraction. Methods: The study included 215 consecutive ambulatory HF patients with ejection fraction (EF) < 50% (162 HF reduced EF and 53 HF mid-range EF) of mean age 66 ± 11 years and 24.4% females. Peak LA strain (PALS) was measured by speckle tracking echocardiography and E/e’ recorded from the apical four-chamber view. Non-invasive LASt was calculated using the equation: LASt = E/e’ ratio/PALS. Documented cardiac events (CE) were HF hospitalization and cardiac death. Results: During a median follow up of 41 ± 34 months, 65 patients (30%) had CE. In multivariate analysis model, only raised LV filling pressure (E/e’) (OR = 0.292, (95% CI 0.099 to 0.859), p = 0.02), peak pulmonary artery pressure (PAP) (OR = 1.050 (1.009 to 1.094), p = 0.01), PALS (OR = 0.932 (0.873 to 0.994), p = 0.02) and LASt (OR = 3.781 (1.144 to 5.122), p = 0.001) independently predicted CE. LASt ≥ 0.76% was the most powerful predictor of CE, with 80% sensitivity and 73% specificity (AUC 0.82, CI = 0.73 to 0.87, p < 0.001) followed by PALS ≤ 16%, with 74% sensitivity and 72% specificity (AUC 0.77, CI = 0.71 to 0.84, p < 0.001). These results were consistent irrespective of EF (p < 0.05). Conclusion: In this cohort of ambulatory HFrEF and HFmrEF patients, LASt proved the most powerful predictor of clinical outcome.

In-vitro and in-vivo evaluation of a novel bioprosthetic pulmonary valve for use in congenital heart surgery

BackgroundManagement of congenital malformations of the pulmonary artery and valve can be challenging. The severity often demands early intervention, which is rarely definitive due to the natural growth and multiple surgeries may be required. An artificial valve made entirely from biodegradable materials that will serve as a bioscaffold for host recellularization would be an attractive solution for these patients. Such valves have been experimentally evaluated with various results. In this study, a simple valve design supported by an absorbable proximal stabilization ring is evaluated both in-vitro and in-vivo.MethodsFrom a 6.7 × 5.0 cm sheet of CorMatrix® tissue we created the valve as an inverted tubegraft with three sutured commissures. A non-closed ring of LactoSorb® basally supported the valve. The commissure height was 2 cm. Inserted as an interposition graft the valve was tested in an in-vitro model and an acute porcine model. Right ventricular and pulmonary artery pressures were recorded.ResultsThe in-vitro testing indicated a proper opening and closure function of valve at physiological simulated hemodynamic conditions. The in-vivo evaluation showed a peak right ventricular pressure of 38 mmHg and a peak pulmonary artery pressure of 27 mmHg and thereby a peak valve gradient of 11 mmHg. The pulmonary pressure wave demonstrated a dicrotic notch indicating competence of the valve.ConclusionThis new pulmonary valve made entirely from biodegradable tissue worked in an acute setting and displayed a good hemodynamic profile. The valve gradient observed is equal to or superior of today’s surgical treatment options.

Functional mitral stenosis following mitral valve repair.

This review summarizes the evidence describing functional mitral stenosis (MS) following surgical mitral valve repair. Functional MS is an evolving concept and has been implicated in the repair of functional and organic mitral regurgitation. Following repair of functional mitral regurgitation, an elevation in peak transmitral gradient and pulmonary artery pressure has been observed under physiologic stress. These changes have been associated with worse functional status early after restrictive annuloplasty. Following repair of organic mitral regurgitation, functional MS has also been observed and appears associated with worse functional status late after surgery. Because repair of functional mitral regurgitation commonly involves restrictive annuloplasty, the issue of functional MS must be weighed against the benefits and durability of repair. Functional MS following repair of degenerative mitral regurgitation, however, may be modifiable. Research evaluating various repair techniques and their impact on functional MS following repair of organic is ongoing.

PS 09-22 CLINICAL FEATURES OF PULMONARY HYPERTENSION

Objective: Pulmonary hypertension (PH) is an important cause of morbidity and mortality, however, the incidence and the clinical profile of this condition remain poorly understood. We aimed to describe clinical and hemodynamic characteristics and to provide estimates for the prevalence of patients diagnosed for PH according to WHO classification of PH. Design and Method: Patients aged more than 18 years at diagnosis with PH were enrolled at 3 centers in South Korea from Dec 1, 2012, to Dec 31, 2014. Patient and disease characteristics, including age at diagnosis and at enrollment, sex, presenting symptoms, PH classification, comorbid disorders, medical and family history, and functional class were recorded. Results: 531 of 733 patients who had confirmed PH (defined as peak pulmonary artery pressure (PAP) ≥ 37 mmHg) were entered in the registry. Median age was 69.7 years; 57% (300 of 531) were female. Estimated Peak PAP, and pulmonary vascular resistance by echocardiography were 49 ± 11.8 mmHg, 2.9 ± 1.8W.U., respectively. Most of patients were asymptomatic (59%) and were in good functional status (less than NYHA II, 350 of 423 (82.7%)), on the other hand, dyspnea (26%) and chest pain (12%) were the most frequent symptoms. Most patients had acquired PH, which were Group II (PH owing to left heart disease, n = 399, 75%) or Group III (PH owing to lung disease and/or hypoxia, n = 61, 12%). Only 19 patients (4%) had pulmonary arterial hypertension (Group I). In subgroup, Group II patients had a higher prevalence of hypertension (p < 0.01), history of angina (p = 0.02). Interestingly, Group IV (Chronic thromboembolic PH) patients were more common in history of alcohol (p = 0.019). Conclusions: Our registry data identifies important clinical features of PH, which is mostly related to acquired etiologies (esp. left heart disease). Moreover, despite severe PH, most patients were in good functional status, which is consistent with preserved right-heart function.

Impaired Left and Right Ventricular Systolic and Diastolic Function in Response to Exercise in Patients with Diastolic Dysfunction.

Diastolic dysfunction (DD) is associated with exercise intolerance. To evaluate mechanisms of exercise intolerance in patients with DD, we performed bicycle stress echocardiography. Doppler measurements were performed at baseline, during exercise and recovery in 26 patients (58 ± 11 years) with DD and normal left ventricular ejection fraction and 6 normal controls (53 ± 5 years). Compared to controls, patients achieved similar target heart rates but lower METs (5.5 ± 2 vs. 9.8 ± 3, P < 0.01) and a higher peak pulmonary artery pressure (PAP) at peak exercise (50 ± 13 vs. 32 ± 7 mmHg, P < 0.01) despite similar PAP at rest and similar mean blood pressure at peak exercise (110.4 ± 18.0 vs. 106.9 ± 11.4 mmHg, P = NS). In patients versus controls, mitral E/E' was similar at baseline (10 ± 3 vs. 8 ± 1.3, P = NS) but higher at recovery (11 ± 2 vs. 7 ± 2, P < 0.05), % mitral filling time was shorter at baseline, onset, and peak exercise, whereas % LV and RV ejection time was similar to controls throughout exercise. Compared to controls, lateral mitral annular S' (11.8 ± 2.5 cm/sec vs. 14.9 ± 1.9 cm/sec, P < 0.02) and tricuspid annular S' (14.8 ± 4.1 cm/sec vs. 19.4 ± 4.0 cm/sec, P < 0.05) were lower at peak exercise in patients. Diastolic filling time is reduced at rest and stress while LV ejection time increases normally during exercise in DD. There is a reduced systolic reserve in LV and RV during exercise in DD. These mechanisms contribute to exercise intolerance and elevation of left atrial and PAP in patients with DD.

Maternal and fetal outcomes in pregnant women undergoing balloon mitral valvotomy for rheumatic mitral stenosis

BackgroundRheumatic mitral stenosis constitutes a major cause of acquired heart disease complicating pregnancy in India. In the present study, we have studied the fetal and maternal outcomes of women undergoing balloon mitral valvotomy during pregnancy. Methods and results49 pregnant ladies were included in this study in whom balloon mitral valvotomy was performed. The mean age of these patients was 25.7±3.1 years. The mean gestational age was 23.5±5.2 weeks (12–36 weeks). The procedure was successful in 48 patients (95.9%). Mean two-dimensional MVA increased from baseline value of 0.93±0.17cm2 to 1.75±0.27cm2 (p value <0.0001). Pre-procedure peak pulmonary artery pressure was 43.05±15.88mmHg, which decreased to 22.31±6.36mmHg (p value <0.0001). Hemodynamic data showed pre-BMV left atrial mean pressure of 29.6±6.6mmHg, which decreased to 13.7±4.8mmHg after the procedure (p value <0.0001). Mean fluoroscopy time was 6.4±1.2min. There was no maternal mortality in our study. One procedure had to be abandoned, because of failed septal puncture. One of the patients developed cardiac tamponade and another patient developed severe mitral regurgitation, which were managed medically. The patient who developed severe mitral regurgitation later underwent mitral valve replacement. Post-procedure follow-up showed an improvement in NYHA status by at least one class in 81.3% of patients. Thirty-nine (81.3%) patients had a term normal vaginal delivery and 8 (16.7%) underwent cesarean section for obstetric indications. One of the patients had abortion on the second day of the procedure. ConclusionPercutaneous mitral valvotomy during pregnancy is safe and provides excellent symptomatic relief and hemodynamic improvement. This should be considered as the treatment of choice when managing pregnant women with severe mitral stenosis.

Early and mid-term outcome in terms of functional and hemodynamic performance of the st. Jude regent 19-mm aortic mechanical prosthesis versus 19-mm carpentier edwards aortic biological prosthesis.

BackgroundThe aim of the present study is to compare the early and mid-term clinical and hemodynamic results of the aortic valve replacement (AVR) with a St Jude Medical Regent 19-mm prosthesis (SJMR-19) versus Carpentied-Edwars bovine pericardial 19-mm valve (CE-19).MethodsBetween January 2002 and January 2012, 265 patients (Group I) and 58 patients (Group II) with underwent AVR with a SJMR-19 and CE-19 respectively. There were no significant differences between groups regarding the demographic and preoperative echocardiographic data. Thirty-six patients in Group I and 4 in Group II required annulus enlargement in association or not with septal myectomy. The mean follow-up was 34 ± 18.5 months (range 5–60 months).ResultsThere were 14 (5.3 %) hospital deaths in Group I versus 4 (6.8 %) in Group II (p = 0.86). The multivariate logistic regression analysis identified the LVEF ≤ 35 % (p = 0.001), combined operation (p = 0.0005), CPB (p = 0.033), age (p = 0.011), annulus enlargement (p = 0.0009), reoperation (p = 0.039) and chronic renal failure (p = 0.011) as strong predictors for early postoperative death. Within 1 year after surgery peak pulmonary artery pressure, interventricular septal and left ventricular posterior wall thickness decreased significantly in both groups. The M-TPG was 15.7 ± 6.5 mmHg in Group I versus 17 ± 7 mmHg in Group II (p = 0.19). The multivariate regression analysis revealed the annulus enlargement (p = 0.018), small EOAi (p = 0.00004), postoperative LVMi (p = 0.0001) and BSA (p = 0.019) as strong predictors for higher M-TPG. The postoperative LVMi was 119 ± 22.5 gm/m2 in Group I and 122 ± 22 gm/m2 in Group II (p = 0.37), significantly lower than the respective preoperative values 162.5 ± 34 gm/m2 (Group I) and 168 ± 30 gm/m2 (Group II). The actuarial survival and cumulative free-reoperation actuarial survival at 5 years follow-up were 96.7 and 94.5 % respectively in Group I and 97 and 91 % in Group II.. There were non significant differences between groups regarding the actuarial survival and cumulative free-reoperation survival. The Cox model identified the older age (p = 0.022), LVEF ≤ 35 % (p = 0.009), reoperation (p = 0.018), combined surgery (p = 0.00075) and annulus enlargement (p = 0.033) as strong predictors for poor actuarial free-reoperation survival.ConclusionsBoth the SJMR-19 and CE-19 offers excellent postoperative clinical and hemodynamic outcome in patients with small aortic annulus. The LV hypertrophy and transvalvular gradients are reduced significantly indenpendently of the employed SJMR-19 or CE-19 prosthesis. Our data support recent suggestions that small valve size does not influence intermediate free-reoperation survival. The CE-19 is an excellent alternative to SJMR-19 in old patients.

β2-Adrenoreceptor Agonist Inhalation During Ex Vivo Lung Perfusion Attenuates Lung Injury

Attenuation of ischemia reperfusion injury (IRI) is important in lung transplantation. Our group previously reported that β2-adrenoreceptor agonist inhalation during the period before procurement successfully attenuated IRI in donated lungs after cardiac death. We therefore hypothesized that β2-adrenoreceptor agonist inhalation during exvivo lung perfusion (EVLP) after procurement might also have a protective effect. Cardiac-dead beagles were left at room temperature for 210 minutes, and all lungs were subsequently procured and subjected to EVLP for 240 minutes. The beagles were allocated to 2 groups: the β2 group (receiving an aerosolized β2-adrenoreceptor agonist 20 minutes after initiation of EVLP; n= 7) and the control group (receiving an aerosolized control solvent at the same time point; n= 6). Physiologic data, including lung function, were evaluated during EVLP. The β2 group showed significantly lower peak airway pressure and pulmonary artery pressure than the control group. Dynamic pulmonary compliance was higher, pulmonary vascular resistance (PVR) was lower, and the wet-to-dry lung weight ratio was lower in the β2group than in the control group. Cyclic adenosine monophosphate (cAMP) and total adenosine nucleotide (TAN) levels in lung tissue after EVLP were higher in the β2 group than in the control group. The β2 group also showed more cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. After procurement, β2-adrenoreceptor agonist inhalation during EVLP attenuates lung injury in a canine model of organ donation after cardiac death.

Inflammation and congenital heart disease associated pulmonary hypertension.

Increased blood flow may trigger pulmonary arterial wall inflammation, which may influence progression of pulmonary artery hypertension in patients with congenital heart disease. In this study, we aimed to investigate the correlation between preoperative inflammation markers and pulmonary arterial hypertension. A total of 201 patients with pulmonary hypertension were enrolled in this study retrospectively; they had undergone open heart surgery between January 2012 and December 2013. Patients' preoperative C-reactive protein (CRP), neutrophil to lymphocyte ratio, red blood cell distribution width, pulmonary pressures, and postoperative outcomes were evaluated. Patient age, neutrophil to lymphocyte ratio, red blood cell distribution width, and CRP were found to be significantly correlated with both preoperative peak and mean pulmonary artery pressures. These data were entered into a linear logistic regression analysis. Patient age, neutrophil to lymphocyte ratio, and CRP were found to be independently correlated with peak pulmonary pressure (P &lt; .001, P &lt; .001, and P = .004) and mean pulmonary artery pressure (P &lt; .001, P &lt; .001, and P = .001), whereas preoperative mean pulmonary artery pressure was found to be independently correlated with intensive care unit stay (P &lt; .001). No parameter was found to be significantly correlated with extubation time and mortality. Eighteen patients had experienced pulmonary hypertensive crisis; in this subgroup, patients' mean pulmonary artery pressure and neutrophil to lymphocyte ratio were found to be significant (P = .047, P = .003). Preoperative inflammation markers may be correlated with the progression of pulmonary hypertensive disease, but further studies with larger sample size are needed to determine the predictive role of these markers for postoperative outcomes.

Central cardiac limit to aerobic capacity in patients with exertional pulmonary venous hypertension: implications for heart failure with preserved ejection fraction.

The mechanism of functional limitation in heart failure with preserved ejection fraction remains controversial. We examined the contributions of central cardiac and peripheral mechanisms and hypothesized that the pulmonary vascular response to exercise is an important determinant of aerobic capacity among patients with exertional pulmonary venous hypertension (ePVH). We compared 31 ePVH patients (peak VO2<80% of predicted and peak pulmonary arterial wedge pressure≥20 mm Hg) with 31 age- and sex-matched controls (peak VO2>80% predicted) who underwent invasive cardiopulmonary exercise testing for unexplained exertional intolerance. ePVH patients had lower peak cardiac output (73±14% versus 103±18% predicted; P<0.001) compared with controls, related both to impaired chronotropic response (peak heart rate 111±25 beats per minute versus 136±24 beats per minute; P<0.001) and to reduced peak stroke volume index (47±10 mL/min per m(2) versus 54±15 mL/min per m(2); P=0.03). Peak systemic O2 extraction was not different between groups (arterial-mixed venous oxygen content difference: 13.0±2.1 mL/dL versus 13.4±2.4 mL/dL; P=0.46). ePVH patients had higher resting (150±74 versus 106±50 dyne/s per cm(-5); P=0.009), peak (124±74 dyne/s per cm(-5) versus 70±41 dyne/s per cm(-5); P<0.001), and isoflow pulmonary vascular resistance (124±74 dyne/s per cm(-5) versus 91±33 dyne/s per cm(-5) at cardiac output≈10.6 L/min; P=0.04). Pulmonary vascular resistance decreased with exercise in all control subjects but increased in 36% (n=11) of ePVH patients. Abnormal pulmonary vascular response was not associated with peak VO2. Reduced cardiac output response, rather than impaired peripheral O2 extraction, constrains oxygen delivery and aerobic capacity in ePVH. Pulmonary vascular dysfunction is common in patients with ePVH at rest and during exercise.

Left ventricular global longitudinal strain is associated with exercise capacity in failing hearts with preserved and reduced ejection fraction.

AimsHeart failure patients with reduced and preserved left ventricular (LV) ejection fraction (EF) show reduced exercise capacity. We explored the relationship between exercise capacity and systolic and diastolic myocardial function in heart failure patients.Methods and resultsExercise capacity, by peak oxygen uptake (VO2), was assessed in 100 patients (56 ± 12 years, NYHA functional class: 2.5 ± 0.9, EF: 42 ± 19%). LV systolic function, as EF and global longitudinal strain (GLS), and right ventricular function were assessed by echocardiography. Left atrial volume index and the ratio of peak early diastolic filling velocity (E) to early diastolic mitral annular velocity (e′) were measures of diastolic function. Thirty-seven patients had heart failure with preserved EF (HFpEF), defined as EF ≥50% and echocardiographic diastolic dysfunction. LV GLS and peak pulmonary arterial systolic pressure were independently correlated to peak VO2 in the total study population and in HFpEF separately. LV GLS was superior to EF in identifying patients with impaired peak VO2 <20 mL/kg/min as shown by receiver operating characteristic analyses [areas under curves 0.93 (0.89–0.98) vs. 0.85 (0.77–0.93), P < 0.05]. In patients with HFpEF, GLS was reduced below normal (−17.5 ± 3.2%) and correlated to E/e′ (R = 0.45, P = 0.005) and left atrial volume index (R = 0.48, P = 0.003), while EF did not.ConclusionGLS correlated independently to peak VO2 in patients with reduced and preserved EF and was superior in identifying patients with reduced exercise capacity. In HFpEF, systolic function by GLS was impaired. There was a significant relationship between diastolic function and GLS, confirming a coupling between diastolic and longitudinal systolic function in HFpEF.

My paper 20years later: Effect of positive end-expiratory pressure on right ventricular function in humans.

In 1992, we published a report on the effect of positive end-expiratory pressure (PEEP) on right ventricular (RV) function in humans. We measured RV volumes and pressures and pericardial pressure (Ppc) as PEEP was increased from zero to 15 cm H20 in 12 patients after thoracotomy, using a pulmonary arterial catheter equipped with a rapid responding thermistor that allowed measurement of RV ejection fraction (RVef), while Ppc was measured via a pericardial balloon catheter. RV end-diastolic volume (EDV) was estimated as the ratio of stroke volume (SV) to RVef, whereas RV end-systolic volume (ESV) were estimated as RV EDV-SV. PEEP increased Ppc and Pra, but RVef unaltered. There was no relation between either RV filling pressure (Pra-Ppc) and EDV or the change in RV filling pressure and EDV, although EDV varied significantly with PEEP (p<0.05). The relations between EDV and both SV and RVef were weak (r=0.54 and 0.55, respectively). RVef varied inversely with ESV (r=-0.77), although it showed no relation to transmural peak pulmonary artery pressure (r=0.28). However, both absolute and relative changes in EDV corresponded closely with respective ESV values (r=0.94). We concluded that EDV varies independently of changes in filling pressure and that changes in ESV occur independently of changes in ejection pressure. These data can be explained by assuming that the RV shape changes can dissociate changes in RV EDV from changes in RV wall stress (preload). Thus, changes in RV EDV may or may not alter SV but should proportionately change ESV to a degree dependent on election pressure and contractility. Subsequent studies confirmed our findings which can be summarized as 1) RV filling is independent of Pra; thus central venous pressure cannot be used to estimate RV preload; and 2) for cardiac output to increase by the Starling mechanism the RV must dilate increasing RV ESV. Since the pericardium limits absolute biventricular volume, there is a finite limit to which cardiac output can increase by the Starling mechanism defined not by left ventricular contractility but by RV function. And 3) if fluid loading causes Pra to increase without increasing cardiac output, then resuscitation should stop as the patient is going into acute cor pulmonale. These truths help bedside clinicians understand the echocardiographic and hemodynamic signatures of both RV failure and volume responsiveness.

Adverse Effects of Hemorrhagic Shock Resuscitation With Stored Blood Are Ameliorated by Inhaled Nitric Oxide in Lambs*

Transfusion of stored RBCs is associated with increased morbidity and mortality in trauma patients. Plasma hemoglobin scavenges nitric oxide, which can cause vasoconstriction, induce inflammation, and activate platelets. We hypothesized that transfusion of RBCs stored for prolonged periods would induce adverse effects (pulmonary vasoconstriction, tissue injury, inflammation, and platelet activation) in lambs subjected to severe hemorrhagic shock and that concurrent inhalation of nitric oxide would prevent these adverse effects. Animal study. Research laboratory at the Massachusetts General Hospital, Boston, MA. Seventeen awake Polypay-breed lambs. Lambs were subjected to 2 hours of hemorrhagic shock by acutely withdrawing 50% of their blood volume. Lambs were resuscitated with autologous RBCs stored for 2 hours or less (fresh) or 39 ± 2 (mean ± SD) days (stored). Stored RBCs were administered with or without breathing nitric oxide (80 ppm) during resuscitation and for 21 hours thereafter. We measured hemodynamic and oxygenation variables, markers of tissue injury and inflammation, plasma hemoglobin concentrations, and platelet activation. Peak pulmonary arterial pressure was higher after resuscitation with stored than with fresh RBCs (24 ± 4 vs 14 ± 2 mm Hg, p < 0.001) and correlated with peak plasma hemoglobin concentrations (R = 0.56, p = 0.003). At 21 hours after resuscitation, pulmonary myeloperoxidase activity was higher in lambs resuscitated with stored than with fresh RBCs (11 ± 2 vs 4 ± 1 U/g, p = 0.007). Furthermore, transfusion of stored RBCs increased plasma markers of tissue injury and sensitized platelets to adenosine diphosphate activation. Breathing nitric oxide prevented the pulmonary hypertension and attenuated the pulmonary myeloperoxidase activity, as well as tissue injury and sensitization of platelets to adenosine diphosphate. Our data suggest that resuscitation of lambs from hemorrhagic shock with autologous stored RBCs induces pulmonary hypertension and inflammation, which can be ameliorated by breathing nitric oxide.

Serum adiponectin level in children with nephrotic syndrome in relation to right ventricular functions and metabolic profiles

Background: Adiponectin (ADPN), a protein hormone (cytokine), is exclusively expressed on and secreted from adipocytes. It is a particularly interesting compound because it may have a protective influence on the cardiovascular system. Objective: This study was designed to evaluate serum ADPN level, right ventricular functions and metabolic profiles among children with nephrotic syndrome (NS) and asses the correlations between ADPN as a protective hormone and each of right ventricular functions and metabolic profiles. Patients and Methods: A total of 47 children (28 boys; 19 girls) with steroid-responsive nephrotic syndrome (SRNS) were studied. They included two groups: Group A: included 25 children with SRNS in relapse. Group B: included 22 children with SRNS in remission for periods ranging from 3-9 months. A control group included 28 children with matched age and sex. Methods: Serum level of ADPN was estimated by ELISA and nitric oxide (NO) by chemical detection. In addition to total cholesterol, triglycerides, high-density lipoprotein (HDL), low density lipoprotein (LDL), total protein, and albumin by Enzymatic Colorimetric kits. Also, 24-hour urine samples were collected for detection of proteinuria. Electrocardiogram (ECG) and echocardiography measuring right ventricular wall functions were done. Results: Serum levels of ADPN and NO were significantly higher in children with SRNS in relapse in comparison with children with SRNS in remission or control group. Children with SRNS in relapse showed significantly higher levels of total cholesterol, triglycerides, LDL and proteinuria while significantly lower levels of total protein, albumin and HDL as compared with SRNS in remission or control group. Echocardiographic findings revealed that a significant decrease in right ventricular ejection fraction (RVEF %) and significant increase in right ventricular end diastolic diameter (RVEDD), right ventricular peak pressure (RVPP) and pulmonary artery pressure (PAP) were found in cases with SRNS in relapse in comparison to cases with SRNS in remission and control hypertrophy in relapsed cases. Finally, in children with SRNS in relapse it was found that serum ADPN level was significantly positively correlated with each of serum NO, total cholesterol, triglycerides, LDL, proteinuria, RVEDD, RVPP and PAP, while significantly negatively correlated with serum total protein, albumin and RVEF%. Conclusion: During relapse of SRNS, serum ADPN level is higher than its level in SRNS in remission. This higher level may represent a physiologic response to the altered metabolic profiles and right ventricular strain so as to minimize cardiovascular complications.

Safety and efficacy of exercise training in various forms of pulmonary hypertension

The objective of this prospective study was to assess safety and efficacy of exercise training in a large cohort of patients with different forms and World Health Organization (WHO) functional classes of chronic pulmonary hypertension (PH). 183 patients with PH (pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH due to respiratory or left heart diseases received exercise training in hospital for 3 weeks and continued at home. Adverse events have been monitored during the in-hospital training programme. Efficacy parameters were evaluated at baseline, and after 3 and 15 weeks. After 3 and 15 weeks, patients significantly improved the distance walked in 6 min (6MWD) compared to baseline, scores of quality of life, WHO functional class, peak oxygen consumption, oxygen pulse, heart rate and systolic pulmonary artery pressure at rest and maximal workload. The improvement in 6MWD was similar in patients with different PH forms and functional classes. Even in severely affected patients (WHO functional class IV), exercise training was highly effective. Adverse events, such as respiratory infections, syncope or presyncope, occurred in 13% of patients. Exercise training in PH is an effective but not a completely harmless add-on therapy, even in severely diseased patients, and should be closely monitored.

Oesophageal dilatation on high-resolution CT chest in systemic sclerosis: What does it signify?

To evaluate the significance of oesophageal dilatation on high-resolution CT (HRCT) chest in patients with systemic sclerosis. We retrospectively retrieved the database of patients with systemic sclerosis seen at our hospital between January 2008 and January 2009. A total of 50 patients (46 women and four men) who had HRCT chest, pulmonary function testing and echocardiography within 1 month were included in the study. Peak pulmonary artery (PA) pressures and pulmonary function testing were charted. The HRCT chest was interpreted by a chest radiologist. Oesophageal dilatation was defined as a luminal coronal diameter of ≥9 mm in infra-aortic oesophagus. Extent of ground glass, reticulation and honeycombing was objectively scored. Statistical analysis using independent t-test showed that diffusion capacity of carbon monoxide was significantly lower (P = 0.042) and peak PA pressures were significantly higher (P = 0.045) in patients with oesophageal dilatation (n = 29) as compared with those without oesophageal dilatation (n = 21). The two cohorts had no significant difference in their total lung capacity and HRCT determined extent of interstitial lung disease. Patients with oesophageal dilatation on HRCT chest had significantly lower diffusion capacity of carbon monoxide and higher peak PA pressures, which suggest that these patients tend to have more severe pulmonary vascular disease.

Pulmonary hypertension, how to diagnose and who to treat?

Pulmonary arterial hypertension is a fatal disease with an estimated survival rate of only 50% after 5 years [1]. Over the last years, knowledge in the field of pulmonary hypertension has grown consistently and significantly. New diagnostic tools, as well as the efficacy of new medications and drug combinations, have been described. How to define and diagnose pulmonary arterial hypertension is the first important issue. Should echocardiography be the method of choice? It is easy to access, cheap and noninvasive. However, the cut-off values are debatable. In the ESC guidelines of 2009 [2] an estimated peak pulmonary artery pressure of >50 mmHg is stated as ‘pulmonary hypertension is likely’, while a PAP of 37–50 is defined as ‘possible PH’. However, the gold standard remains heart catheterisation. Now the definition is made using a mean pulmonary artery pressure of 25 mmHg or more. Age and gender seem to have an important impact on the incidence and severity of PH. For instance, female patients with an atrial septal defect do present with pulmonary hypertension, while in male ASD patients pulmonary hypertension is seldom if ever seen. In order to simplify the clinical management of patients, the classification of pulmonary hypertension was changed in 2009 [3]. Pre-capillary PH is defined as a wedge pressure <15 mmHg and can be divided into pulmonary arterial hypertension, PH due to lung disease, chronic thromboembolic PH or PH with unclear and/or multifactorial mechanisms. Post-capillary PH is defined as a wedge pressure above 15 mmHg and is due to left-sided heart disease. Who should be screened for pulmonary hypertension? Should all patients undergoing non-cardiac surgery by tested? Echocardiography and certainly heart catheterisation are not routinely performed, but when complications arise postoperatively, pulmonary hypertension is not seldom detected and although the underlying cause may vary, the prognosis is unfavourable. One could argue that echocardiography screening preoperatively in patients over the age of 60 years may detect high-risk patients for general surgery. Patients known with pulmonary hypertension should be counselled against surgery, or if it is decided to proceed with surgery a team of surgeons, anaesthetists, intensivists and others should make a treatment plan for optimal perioperative care. Advances in treatment of pulmonary arterial hypertension over the past 15 to 20 years have dramatically reduced the morbidity and mortality of the disease. A reduction of 43% in mortality and 61% in hospitalisations was found in a recent meta-analysis [4]. However the current medication is expensive and has major drawbacks so it is very important to treat the patients who might benefit. At the moment there are probably many patients left untreated who could benefit, for instance adult patients with PH associated with congenital heart disease. There is also an interesting group of patients with primary left-sided heart disease who have disproportionately high pulmonary pressures. In patients who have undergone a successful procedure for aortic or mitral stenosis the pulmonary arterial pressures may remain elevated, although the wedge pressure has normalised. The indication to treat these patients with disproportionately high pulmonary pressures remains controversial. For patients with left-sided systolic dysfunction with secondary pulmonary hypertension, no benefit of treatment was found and in fact may have a negative effect on outcome, but for the patients with disproportionately high pulmonary hypertension no studies are available as yet. We hope you enjoy reading this focus issue of the Netherlands Heart Journal, dedicated to several aspects of the rapidly evolving field of Pulmonary Hypertension [5–9].

Effects of substitutive therapy on right ventricular systolic and diastolic functions in patients with idiopathic hypogonadotropic hypogonadism

There have been controversial studies evaluating ventricular functions in patients with idiopathic hypogonadotropic hypogonadism (IHH). A recent study has demonstrated that low serum testosterone levels are associated with increased cardiovascular mortality. We aimed to investigate ventricular functions by standard echocardiography and examine the effects of substitutive therapy on right ventricular (RV) functions in patients with IHH by means of pulsed wave tissue Doppler imaging (PWTDI). Twenty-three patients with IHH and 31 controls were evaluated by standard echocardiography and PWTDI. Isovolumic acceleration (IVA), myocardial systolic wave (Sm) velocity, myocardial precontraction time (PCTm), and PCTm to contraction time (CTm) ratio were determined as systolic indices. Myocardial relaxation time (RTm), early (Em) velocity, late (Am) velocity, and Em to Am ratio were determined as diastolic indices. Peak pulmonary artery pressure (PAP) was significantly higher in control subjects (p=0.008). IVA and Sm values were similar in patients and controls. Em, Am velocities, and their ratios did not differ. PCTm was significantly longer (p=0.001) and PCTm to CTm ratio was significantly higher in patients (p=0.001). These parameters also decreased after replacement therapy, albeit not statistically significantly (p>0.05). PAP was significantly higher after substitutive therapy (p=0.009). Ventricular functions are normal in patients with IHH. Substitutive therapy has no effects on RV functions. However, substitutive therapy may increase PAP in small amounts, which has no immediate clinical implication with short-term use.