BACKGROUND AND OBJECTIVES: Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single udenafil administration to determine the appropriate therapeutic dose. METHODS: Eighteen patients were randomly allocated into one of 3 groups: placebo, udenafil 50 mg (U50), and udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration. RESULTS: The mPAP significantly decreased in both the U50 and U100 (−11 mmHg and −8 mmHg from baseline, respectively, p < 0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=−8.5 mmHg and Δ=−14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events. CONCLUSIONS: This is the first demonstration of the acute hemodynamic changes induced by udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01553721.
Arterial Pressure ; Catheters ; Connective Tissue Diseases ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Diagnosis ; Erectile Dysfunction ; Hemodynamics ; Humans ; Hypertension ; Hypertension, Pulmonary ; Male ; Phosphodiesterase 5 Inhibitors ; Pulmonary Wedge Pressure ; Vascular Resistance

A 60-year-old man visited the hospital after experiencing dyspnea after exertion for 2 weeks. An electrocardiogram showed sinus arrest with junctional escape rhythm at 40 beats/min. Transthoracic echocardiography showed that the right ventricular systolic pressure (RVSP) was approximately 71 mmHg and that the left ventricular ejection fraction was preserved. The ratio of peak early diastolic transmitral inflow velocity to early diastolic peak mitral annular velocity (E/E') was 29. Cardiac catheterization revealed a systolic pulmonary artery pressure (SPAP) of 63 mmHg, a mean pulmonary artery pressure of 27 mmHg, and a pulmonary capillary wedge pressure of 22 mmHg with a rhythm of 40 beats/min. The patient was diagnosed with pulmonary hypertension (group 2) due to sick sinus syndrome. SPAP decreased to 48 mmHg during atrial pacing at 60 beats/min. After permanent pacemaker insertion, RVSP decreased from 71 mmHg to 44 mmHg. In this case, passive group 2 pulmonary hypertension occurred due to sick sinus syndrome.
Blood Pressure ; Cardiac Catheterization ; Cardiac Catheters ; Dyspnea ; Echocardiography ; Electrocardiography ; Humans ; Hypertension, Pulmonary* ; Middle Aged ; Pulmonary Artery ; Pulmonary Wedge Pressure ; Sick Sinus Syndrome* ; Stroke Volume ; United Nations

OBJECTIVEAs an important method of hemodynamic assessment in idiopathic pulmonary arterial hypertension (IPAH), cardiac catheterization combined with pulmonary vasoreactivity testing remains with limited experience in children, and the acute pulmonary vasodilator agents as well as response criteria for vasoreactivity testing remain controversial. The aim of this study was to investigate the clinical importance, agent selection, and responder definition of cardiac catheterization combined with pulmonary vasoreactivity testing in pediatric IPAH.

METHODThe patients admitted to Department of Pediatric Cardiology of Beijing Anzhen Hospital between April 2009 and September 2013 with suspected IPAH, under 18 years of age, with WHO functional class II or III, were enrolled. All the patients were arranged to receive left and right heart catheterization and pulmonary vasoreactivity testing with inhalation of pure oxygen and iloprost (PGI2) respectively. Hemodynamic changes were analyzed, and two criteria, the European Society of Cardiology recommendation criteria (Sitbon criteria) and traditional application criteria (Barst criteria), were used to evaluate the test results.

RESULTThirty-nine cases of children with suspected IPAH underwent cardiac catheterization. In 4 patients IPAH was excluded; 4 patients developed pulmonary hypertension crisis. The other 31 patients received standard cardiac catheterization and pulmonary vasoreactivity testing. Baseline mean pulmonary artery pressure (mPAP) was (66 ± 16) mmHg (1 mmHg = 0.133 kPa), and pulmonary vascular resistance index (PVRI) (17 ± 8) Wood U · m². After inhalation of pure oxygen, mPAP fell to (59 ± 16) mmHg, and PVRI to (14 ± 8) Wood U · m² (t = 4.88 and 4.56, both P < 0.001) . After inhalation of PGI2, mPAP fell to (49 ± 21) mmHg, and PVRI to (12 ± 9) Wood U · m² (t = 7.04 and 6.33, both P < 0.001). According to the Sitbon criteria, the proportion of pure oxygen responders was 6.5% (3/31) , while PGI2 responders was 35.5%, and the difference was significant (P = 0.004). According to the Barst criteria, the proportion of pure oxygen responders was 16.1% (5/31), while PGI2 responders was 51.6% (16/31), and the difference was significant (χ² = 0.09, P = 0.001).

CONCLUSIONFor children with IPAH, cardiac catheterization combined with pulmonary vasoreactivity testing has important value in differential diagnosis, severity estimation, and treatment (including the emergency treatment) choices. Pulmonary hypertension crisis is an important complication of cardiac catheterization in pediatric IPAH. Younger age, general anesthesia, crisis history, and poor heart function are important risk factors for pulmonary hypertension crisis. PGI2 is a relatively ideal agent for vasoreactivity testing in children with IPAH, which has more responders than traditionally used pure oxygen.

RESULTSof responders are not completely consistent using different criteria, and comprehensive evaluation should be done according to the goals of treatment in clinical practice.

Administration, Inhalation ; Adolescent ; Anesthesia, General ; Cardiac Catheterization ; Child ; Child, Preschool ; Familial Primary Pulmonary Hypertension ; diagnosis ; physiopathology ; Female ; Hemodynamics ; Humans ; Iloprost ; administration & dosage ; Infant ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Circulation ; drug effects ; Pulmonary Wedge Pressure ; drug effects ; Severity of Illness Index ; Vascular Resistance ; drug effects ; Vasodilator Agents ; administration & dosage

OBJECTIVEThe assessment of pulmonary vascular reactivity plays an important role in the management of idiopathic pulmonary arterial hypertension (IPAH). The aim of this study was to explore the indications and methodology of pulmonary vasodilator testing in children with IPAH.

METHODSFrom October 2009 to June 2011, a cohort of pediatric patients with IPAH in WHO functional classes II to III were enrolled in the study. Right heart catheterization was performed in all patients. After baseline hemodynamics were obtained, adenosine infusions were started at a dose of 50 µg/(kg·min), increased by 25 µg/(kg·min) at 2 min intervals to a maximum of 250 µg/(kg·min) or until a positive acute response.

RESULTSA total of 15 patients with IPAH were enrolled in the study. The mean age of the patients was 6.3 yrs. Mean pulmonary artery pressure (mPAP) was (67.1 ± 15.9) mm Hg. Pulmonary capillary wedge pressure (PCWP) was (9.7 ± 2.9) mm Hg. Pulmonary vascular resistance index (PVRI) was (17.9 ± 7.5) Wood U·m(2). Three patients were responders, defined as a fall in mPAP of at least 10 mm Hg to a pressure level of 40 mm Hg or lower. Twelve patients were nonresponders according to the same criteria. Five out of the 15 patients experienced adverse effects, including chest discomfort (n = 1), systemic hypotension (n = 3) and bradycardia (n = 1). All side effects abated within 30-60 s of the discontinuation of the adenosine infusion.

CONCLUSIONAdenosine is an effective vasodilator in children with IPAH and can be used for safe and rapid assessment of vasodilator reserve in these patients.

Adenosine ; Adolescent ; Child ; Child, Preschool ; Familial Primary Pulmonary Hypertension ; Female ; Humans ; Hypertension, Pulmonary ; physiopathology ; Infant ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Wedge Pressure ; Vascular Resistance ; Vasodilator Agents

BACKGROUNDHemodynamic evaluation is crucial for the management of patients with pulmonary hypertention. Clinicians often prefer a rapid and non-invasive method. This study aimed to examine the feasibility of transthoracic echocardiography for the measurements of hemodynamic parameters in patients with pulmonary hypertension.

METHODSA prospective single-center study was conducted among 42 patients with pulmonary hypertension caused by different diseases. Transthoracic echocardiography and right-heart catheterization were performed within 24 hours. Pulmonary artery systolic, diastolic and mean pressure (PASP, PADP and PAMP), cardiac output (CO), and pulmonary capillary wedge pressure (PCWP) were measured by both methods. A linear correlation and a Bland-Altman analysis were performed to compare the two groups of hemodynamic parameters.

RESULTSA good correlation was found between invasive and non-invasive measurements for PASP (r = 0.96), PADP (r = 0.85), PAMP (r = 0.88), CO (r = 0.82), and PCWP (r = 0.81). Further agreement analysis done by the Bland-Altman method showed that bias and a 95% confidence interval for PASP, PADP, and CO were clinically acceptable while great discrepancies existed for PAMP and PCWP.

CONCLUSIONSThe non-invasive measurements by PASP, PADP, and CO in patients with pulmonary hypertension correlate well with the invasive determinations. Transthoracic echocardiography (TTE) was inappropriate for estimating PCWP and PAMP.

Adolescent ; Adult ; Cardiac Catheterization ; Cardiac Output ; Echocardiography ; Female ; Hemodynamics ; Humans ; Hypertension, Pulmonary ; physiopathology ; Male ; Middle Aged ; Prospective Studies ; Pulmonary Wedge Pressure

Adolescent ; Cyanosis ; complications ; Heart Septal Defects, Atrial ; complications ; Humans ; Male ; Pulmonary Wedge Pressure

Echocardiography, Transesophageal ; Humans ; Monitoring, Physiologic ; standards ; Pulmonary Circulation ; physiology ; Pulmonary Wedge Pressure ; Stroke Volume

BACKGROUND: Accurate assessment of the preload and the fluid responsiveness is of great importance for optimizing cardiac output, especially in those patients with coronary artery occlusive disease (CAOD). In this study, we evaluated the relationship between the parameters of preload with the changes in the stroke volume index (SVI) after fluid loading in patients who were undergoing coronary artery bypass grafting (CABG). The purpose of this study was to find the predictors of fluid responsiveness in order to assess the feasibility of using certain parameters of preload as a guide to fluid therapy. MATERIAL AND METHOD: We studied 96 patients who were undergoing CABG. After induction of anesthesia, the hemodynamic parameters were measured before (T1) and 10 min after volume replacement (T2) by an infusion of 6% hydroxyethyl starch 130/0.4 (10 mL/kg) over 20 min. RESULT: The right ventricular end-diastolic volume index (RVEDVI), as well as the central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP), failed to demonstrate significant correlation with the changes in the SVI (%). Only the right ventricular ejection fraction (RVEF) measured at T1 showed significant correlation with the changes of the SVI by linear regression (r=0.272, p=0.017). However, when the area under the curve of receiver operating characteristics (ROC) was evaluated, none of the parameters were over 0.7. The volume-induced increase in the SVI was 10% or greater in 31 patients (responders) and under 10% in 65 patients (non-responders). None of the parameters of preload measured at T1 showed a significant difference between the responders and non-responders, except for the RVEF. CONCLUSION: The conventional parameters measured with a volumetric pulmonary artery catheter failed to predict the response of SVI following fluid administration in patients suffering with CAOD.
Anesthesia ; Cardiac Output ; Catheters ; Central Venous Pressure ; Coronary Artery Bypass ; Coronary Vessels ; Fluid Therapy ; Hemodynamics ; Hetastarch ; Humans ; Linear Models ; Pulmonary Artery ; Pulmonary Wedge Pressure ; ROC Curve ; Stress, Psychological ; Stroke Volume

BACKGROUND: Ethanol injection during a sclerotherapy for the treatment of arteriovenous malformation, which performed under general anesthesia, can cause significant hemodynamic changes, even cardiovascular collapse. However, guideline for adequate management of hemodynamic change or preventing detrimental complication has still not been proposed. METHODS: Twenty-two piglets were randomly allocated to one of two groups: a 2.5 ml and a 4.0 ml ethanol. After baseline hemodynamic measurements, 2.5 ml or 4.0 ml of absolute ethanol was repeatedly administered in distal portion of renal vein with 10 minute intervals, and hemodynamic parameters were measured immediately before and after bolus injection of absolute ethanol until 10 minutes after final injection. RESULTS: Compared with 2.5 ml group, systolic, mean and diastolic pulmonary arterial pressures (PAP) and pulmonary vascular resistance (PVR) of 4.0 ml group showed significant differences from the first bolus injection of absolute ethanol. Hemodynamic parameters of 2.5 ml group did not show the increasing or decreasing tendency during a session, whereas, in 4.0 ml group, systolic, mean and diastolic PAP and PVR showed significantly increasing tendency. However, systemic arterial blood pressure, heart rate, central venous pressure, pulmonary capillary wedge pressure, cardiac output, and systemic vascular resistance did not show increasing or decreasing tendency in both groups. CONCLUSIONS: Based on the hemodynamic alterations observed from piglet model, the bolus injection of absolute ethanol during sclerotherapy in congenital arteriovenous malformation requires careful hemodynamic monitoring. We strongly recommend that anesthesiologist should carefully monitor the hemodynamic parameters after injection of relatively large amount of absolute ethanol.
Anesthesia, General ; Arterial Pressure ; Arteriovenous Malformations ; Cardiac Output ; Central Venous Pressure ; Ethanol ; Heart Rate ; Hemodynamics ; Organothiophosphorus Compounds ; Pulmonary Wedge Pressure ; Renal Veins ; Sclerotherapy ; Vascular Resistance

Congenital pulmonary vein stenosis is a rare cardiac malformation with a poor prognosis and is not easy to diagnose, because symptoms emerge in infants accompanying progressively worsening pulmonary hypertension. A nine-month-old infant visited our hospital due to recurrent respiratory infections and hemoptysis. He was diagnosed with congenital pulmonary vein stenosis by cardiac catheterization. Cardiac catheterization findings revealed that two pulmonary veins were stenotic and one pulmonary vein was occluded. Pulmonary artery catheterization showed the evidence of severe pulmonary hypertension with a mean pulmonary artery pressure of 55 mmHg and a pulmonary artery wedge pressure of 30 mmHg. Due to the aggravation of pulmonary hypertension symptoms, we performed sutureless pericardial marsupialization to reduce the obstruction and the restenosis, but he died a week. In cases of infants with recurrent hemoptysis, we should rule out congenital pulmonary vein stenosis.
Cardiac Catheterization ; Cardiac Catheters ; Catheterization, Swan-Ganz ; Constriction, Pathologic* ; Hemoptysis* ; Humans ; Hypertension, Pulmonary ; Infant* ; Prognosis ; Pulmonary Artery ; Pulmonary Veins* ; Pulmonary Wedge Pressure ; Respiratory Tract Infections