Unaltered neurocardiovascular reactions to mental stress after renal sympathetic denervation.

Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes.Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS.Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN.Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre- (101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN.Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress.

Effect of renal denervation on coronary flow reserve in patients with resistant hypertension.

Renal denervation (RDN) is a potential modality in the treatment of patients with resistant hypertension (RH) and has shown beneficial effect on a variety of cardiovascular surrogate markers. Coronary flow reserve, as assessed by transthoracic Doppler echocardiography (TDE-CFR) is impaired in patients with hypertension and is an independent predictor of cardiac morbidity. However, data on the effect of RDN on TDE-CFR are scarce. The main objective of this study was to assess the effect of RDN on TDE-CFR. Twenty-six consecutive patients with RH (9 female and 17 male; mean age 62 ± 8 years; mean number of antihypertensive drugs 4·2 ± 1·6) underwent bilateral RDN. CFR was assessed at baseline and 6 months after intervention. Mean flow velocity was measured in the left anterior descending artery by transthoracic Doppler echocardiography at baseline and during adenosine infusion (TDE-CFR). Systolic office blood pressure was reduced at follow-up (174 ± 24 versus 162 ± 27 mmHG; P = 0·01). Mean systolic ambulatory blood pressure decreased from 151 ± 21 to 147 ± 18 (P = 0·17). TDE-CFR remained unchanged 6 months after intervention (2·7 ± 0·6 versus 2·7 ± 0·7; P = 0·67). In conclusion, renal denervation was not associated with any changes in regard to coronary flow reserve at 6-month follow-up.

Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double-Blind Controlled Trial.

Background The management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment. Methods and Results In a randomized double-blind study, we assigned patients with chronic heart failure (left ventricular ejection fraction <40%) and impaired renal function (glomerular filtration rate <80 mL/min per 1.73 m2) to receive either levosimendan (loading dose 12 µg/kg+0.1 µg/kg per minute) or dobutamine (7.5  µg/kg per minute) for 75 minutes. A pulmonary artery catheter was used for measurements of systemic hemodynamics, and a renal vein catheter was used to measure renal plasma flow by the infusion clearance technique for PAH (para-aminohippurate) corrected by renal extraction of PAH . Filtration fraction was measured by renal extraction of chromium ethylenediamine tetraacetic acid. A total of 32 patients completed the study. Following treatment, the levosimendan and dobutamine groups displayed similar increases in renal blood flow (22% and 26%, respectively) with no significant differences between groups. Glomerular filtration rate increased by 22% in the levosimendan group but remained unchanged in the dobutamine group ( P=0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine ( P=0.045). Conclusions In patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02133105.

Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension.

Recent reports from worldwide pulmonary hypertension registries show a new demographic picture for patients with idiopathic pulmonary arterial hypertension (IPAH), with an increasing prevalence among the elderly.We aimed to investigate the effects of age and comorbidity on risk stratification and outcome of patients with incident IPAH.The study population (n=264) was categorised into four age groups: 18-45, 46-64, 65-74 and ≥75 years. Individual risk profiles were determined according to a risk assessment instrument, based on the European Society of Cardiology and the European Respiratory Society guidelines. The change in risk group from baseline to follow-up (median 5 months) and survival were compared across age groups. In the two youngest age groups, a significant number of patients improved (18-45 years, Z= -4.613, p<0.001; 46-64 years, Z= -2.125, p=0.034), but no significant improvement was found in the older patient groups. 5-year survival was highest in patients aged 18-45 years (88%), while the survival rates were 63%, 56% and 36% for patients in the groups 46-64, 65-74 and ≥75 years, respectively (p<0.001). Ischaemic heart disease and kidney dysfunction independently predicted survival.These findings highlight the importance of age and specific comorbidities as prognostic markers of outcome in addition to established risk assessment algorithms.

Renal sympathetic denervation in Sweden: a report from the Swedish registry for renal denervation.

BACKGROUND: Renal denervation (RDN) is a catheter-based intervention to treat patients with resistant hypertension. The biological effects of RDN are not fully understood, and randomized controlled trials have generated conflicting evidence. This report presents data from the Swedish Registry for Renal Denervation, an investigator-driven nationwide registry. PURPOSE: To assess the safety and efficacy of RDN on patients with resistant hypertension in a real-world clinical setting. METHODS: This nationwide database contains patient characteristics, procedural details, and follow-up data on all RDN procedures performed in Sweden. Consecutive procedures between 2011 and 2015 were included. RESULTS: The data analysis consists of 252 patients (mean age 61 ±â€Š10 years, 38% women; mean 4.5 ±â€Š1.5 antihypertensive drugs). Office SBP and DBP and 24-h ambulatory blood pressure (BP) decreased 6 months after RDN (176 ±â€Š23/97 ±â€Š17 to 161 ±â€Š26/91 ±â€Š16 mmHg, both P < 0.001; and 155 ±â€Š17/89 ±â€Š14 to 147 ±â€Š18/82 ±â€Š12 mmHg, both P < 0.001). Significant office and ambulatory BP reductions persisted throughout the observation period of 36 months. Major procedure-related vascular complications occurred in four patients. Renal function and number of antihypertensive drugs were unchanged during follow-up. CONCLUSION: In this complete national cohort, RDN was associated with a sustained reduction in office and ambulatory BP in patients with resistant hypertension. The procedure proved to be feasible and associated with a low-complication rate, including long-term adverse events.

Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study.

BACKGROUND: Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. METHODS AND RESULTS: Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] <40%, New York Heart Association class II-III,) and renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] < 75 mL • min-1 • 1.73 m-2) on stable medical therapy were enrolled. Mean age was 65 ± 11 years; 62% had ischemic HF. The average number of ablations per patient was 13 ± 3. No protocol-defined safety events were associated with the procedure. One subject experienced a renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 ± 1228 vs 1428 ± 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 ± 5.1 vs 9.9 ± 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 ± 9% vs 29 ± 11%; P= .536), 6-minute walk test (384 ± 96 vs 391 ± 97 m; P= .584), or eGFR (52.6 ± 15.3 vs 52.3 ± 18.5 mL • min-1 • 1.73 m-2; P= .700). CONCLUSIONS: RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study.

Coronary flow reserve in patients with resistant hypertension.

Resistant hypertension is associated with increased risk for cardiovascular events. Coronary flow reserve (CFR) is impaired in patients with hypertension and an independent predictor of cardiac mortality. However, there are no published data on CFR in the subset of treatment-resistant hypertension. The aim of this study was to assess CFR in patients with resistant hypertension. Twenty-five consecutive patients with primary resistant hypertension, scheduled for renal denervation, 25 matched patients with controlled hypertension, and 25 healthy controls underwent transthoracic colour Doppler echocardiography at rest and during adenosine infusion. Patients with hypertension were pair-matched with regard to age, sex, ischemic heart disease, diabetes mellitus, smoking status, and body-mass index. Healthy controls were selected according to age and sex. Mean flow velocity was measured in the left coronary anterior descending artery. Baseline mean flow velocities were similar in patients with controlled and resistant hypertension. CFR was significantly lower in patients with resistant hypertension as compared to individuals with non-resistant hypertension (2.7 ± 0.6 vs. 3.1 ± 0.8; p = 0.03). Systolic office blood pressure was significantly higher in patients with resistant hypertension (169 ± 20 vs. 144 ± 21 mm Hg; p < 0.01). Heart rate, ventricular mass, and ejection fraction were similar in the two groups. Healthy controls showed significantly lower baseline velocity, higher CFR, and lower blood pressure as compared to hypertensives. Resistant hypertension was associated with impaired CFR as compared to individuals with non-resistant hypertension indicating impaired cardiac microvascular function which may contribute to the increased risk of adverse outcome in patients with resistant hypertension.

Characteristics and survival of adult Swedish PAH and CTEPH patients 2000-2014.

OBJECTIVES: The Swedish Pulmonary Arterial Hypertension Register (SPAHR) is an open continuous register, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients from 2000 and onwards. We hereby launch the first data from SPAHR, defining baseline characteristics and survival of Swedish PAH and CTEPH patients. DESIGN: Incident PAH and CTEPH patients 2008-2014 from all seven Swedish PAH-centres were specifically reviewed. RESULTS: There were 457 PAH (median age: 67 years, 64% female) and 183 CTEPH (median age: 70 years, 50% female) patients, whereof 77 and 81%, respectively, were in functional class III-IV at diagnosis. Systemic hypertension, diabetes, ischaemic heart disease and atrial fibrillation were common comorbidities, particularly in those >65 years. One-, 3- and 5-year survival was 85%, 71% and 59% for PAH patients. Corresponding numbers for CTEPH patients with versus without pulmonary endarterectomy were 96%, 89% and 86% versus 91%, 75% and 69%, respectively. In 2014, the incidence of IPAH/HPAH, associated PAH and CTEPH was 5, 3 and 2 per million inhabitants and year, and the prevalence was 25, 24 and 19 per million inhabitants. CONCLUSION: The majority of the PAH and CTEPH patients were diagnosed at age >65 years, in functional class III-IV, and exhibiting several comorbidities. PAH survival in SPAHR was similar to other registers.

The effect of physical activity or exercise on key biomarkers in atherosclerosis--a systematic review.

OBJECTIVE: This systematic review aimed to summarize published papers on the effect of physical activity (PA)/exercise on key atherosclerotic factors in patients with risk factors for or established cardiovascular disease (CVD). METHODS: Studies involving PA and cytokines, chemokines, adhesion molecules, CRP and angiogenic factors were searched for in Medline and Cochrane library. Original human studies of more than 2 weeks of PA intervention were included. Study quality was assessed according to the GRADE system of evidence. RESULTS: Twenty-eight papers fulfilled the inclusion criteria. PA decreases the cytokines, tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interferon-y IFN-y (high, moderate and low evidence, respectively). The effect of PA on chemokines; stromal derived factor-1 (SDF-1), interleukin-8 (IL-8) (insufficient evidence) and monocyte chemoattractant protein-1 (MCP-1) (low evidence) was inconclusive. Aerobic exercise decreased the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) (moderate and high evidence, respectively), while effects of PA on E- and P-selectin were inconclusive. PA decreases C-reactive protein (CRP) (high evidence). The angiogenic actors, endothelial progenitor cells (EPCs) are increased (high evidence) and VEGF is decreased (moderate evidence) by PA. The effect of PA on these factors seems to depend on the type and duration of exercise intervention and patient factors, such as presence of ischemia. CONCLUSION: As presented in this review, there is a high level of evidence that physical activity positively affects key players in atherosclerosis development. These effects could partly explain the scientifically proven anti-atherogenic effects of PA, and do have important clinical implications.

Effect of catheter-based renal sympathetic denervation on 24-h ambulatory blood pressure in patients with resistant hypertension.

We investigated the effect of renal denervation on office blood pressure (OBP) and 24-h ambulatory blood pressure (BP) measurement (ABPM) at baseline and 6 months after intervention in 25 consecutive patients with resistant hypertension. Mean baseline 24-h ABPM and OBP were 158/88 mmHg and 169/96 mmHg, respectively. Patients were treated with an average of 4 ± 1 antihypertensive drugs. Among the 22 patients included in data analysis, mean ambulatory systolic and diastolic BP were reduced by 6 mmHg from 158 ± 17 to 152 ± 20 mmHg (p < 0.05) and by 3 mmHg from 88 ± 12 to 85 ± 14 mmHg (p = ns) after 6 months follow-up, respectively. Blood pressure reduction was most pronounced during daytime with a decrease of 9 mmHg from 164 ± 17 to 155 ± 19 (p < 0.05) in systolic (SBP) and 6 mmHg from 94 ± 14 to 88 ± 14 mmHg in diastolic BP (DBP) (p < 0.05). Night-time SBP mmHg and DBP were similar at baseline compared with follow-up. Systolic and diastolic OBP during follow-up were significantly reduced by 17 mmHg from 169 ± 20 to 152 ± 21 (p < 0.05) and by 9 mmHg from 96 ± 16 to 87 ± 13 mmHg (p < 0.05), respectively. These results provide new insight into the effect of renal denervation on ABPM day- and night-time blood pressure profile in comparison with OBP. The decrease in ABPM was identified during daytime registration and was less pronounced compared with reduction of OBP.

Right ventricular ejection fraction during exercise as a predictor of mortality in patients awaiting lung transplantation: a cohort study.

OBJECTIVE: The occurrence of right ventricular dysfunction is a well-known indicator of poor prognosis in patients with chronic cardiopulmonary disease. The role of right ventricular ejection fraction (RVEF) at rest and during exercise as predictors of outcome in patients awaiting lung transplantation (LTx) is unclear. DESIGN: We performed a retrospective analysis of lung transplant candidates who had undergone equilibrium radionuclide angiography (ERNA), to determine baseline and exercise RVEF. Lung function, gas exchange and pulmonary haemodynamics were also assessed. PATIENTS AND MAIN OUTCOME MEASURES: 152 patients (mean age 47±11 years; 59% women) were included in the study. Primary endpoint was death on the waiting list for LTx. Main diagnoses were α-1 antitrypsin deficiency (n=35), chronic obstructive pulmonary disease (n=41), cystic fibrosis (n=10), interstitial lung disease (n=34) and pulmonary arterial hypertension (n=32). Twenty-five patients died (16, 4%). LTx was performed in 121 patients. The mean RVEF at rest was equal to mean RVEF during exercise (38±12%). In univariate analysis RVEF at rest, RVEF during exercise, heart rate and forced volume capacity (FVC) % of predicted were factors significantly associated with risk of death. In multivariate analysis RVEF during exercise and FVC% of predicted were independent predictors of death. CONCLUSIONS: In lung transplant candidates, right ventricular function during exercise is a stronger predictor of outcome than right ventricular function at rest. RVEF during exercise assessed by ERNA could be incorporated into priority-based allocation algorithms for LTx.

Can pulmonary hypertension and increased pulmonary vascular resistance be ruled in and ruled out by echocardiography?

BACKGROUND: Several treatment options are available for pulmonary vascular disease, and more patients are considered for right heart catheterization. The aims of this study were to evaluate the diagnostic ability of echocardiography to detect pulmonary hypertension and increased pulmonary vascular resistance (PVR). METHODS: This retrospective study comprised 118 patients investigated within 48 hours of right heart catheterization. Echocardiography was used to assess pulmonary artery systolic pressure and pulmonary artery mean pressure, filling pressures, cardiac output, and PVR. To diagnose increased PVR, three echocardiographic variables related to pressure reflection in the pulmonary circulation were used. Separate cutoff values aimed at ruling in (high positive likelihood ratio [PLR]) and ruling out (low negative likelihood ratio) pulmonary hypertension (pulmonary artery mean pressure >25 mm Hg) and increased PVR (>3 Wood units) were determined from a derivation group (n = 59, receiver operating characteristic curve analysis) and evaluated in a test group (n = 59). RESULTS: The linear relations between hemodynamic variables assessed with simultaneous echocardiography and right heart catheterization were moderate to strong (R = 0.55 to 0.95), and there were no significant differences, but the limits of agreement were wide. With Doppler pulmonary artery systolic pressure >39 mm Hg, the PLR for pulmonary artery mean pressure >25 mm Hg was 4.7, and with Doppler pulmonary artery systolic pressure ≤29 mm Hg, the negative likelihood ratio was 0.12. The PLR for pressure reflection variables with ruling-in cutoff values ranged from 4.3 to 6.4. With all three variables positive, the PLR was 9.9. The negative likelihood ratio with ruling-out cutoff values ranged from 0.22 to 0.08. CONCLUSIONS: Echocardiography that includes assessment of pressure reflection in the pulmonary circulation can rule in and rule out pulmonary hypertension and increased PVR.

Adaptation and validation of the Cambridge pulmonary hypertension outcome review for Sweden.

BACKGROUND: The Cambridge pulmonary hypertension outcome review (CAMPHOR) is the first pulmonary hypertension-specific instrument for the assessment of the patient's perceived symptoms, activity limitations and quality of life (QoL). PURPOSE: To produce and validate a Swedish language version of the CAMPHOR. METHODS: Bilingual (n = 5) and lay panels (n = 5) were conducted to translate the CAMPHOR into Swedish. This new questionnaire was then field-tested with 14 patients and finally, it underwent psychometric evaluation by means of a postal validation study involving 38 patients with pulmonary hypertension (PH). RESULTS: Few problems were experienced in translating the CAMPHOR into Swedish. The field-test participants found the scales relevant, comprehensible and easy to complete. Psychometric analyses showed that the Swedish adaptation was successful. The Swedish CAMPHOR scales had good internal consistency. Cronbach's alpha coefficients were 0.92 for the symptoms scale, 0.92 for activity limitations and 0.95 for the quality of life. Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the scales. The Swedish scales also indicated known groups validity. CONCLUSIONS: The Swedish version of the CAMPHOR is a reliable and valid measure of the impact of pulmonary hypertension on the lives of affected patients. It is recommended for use in clinical studies and routine practice in pulmonary hypertension patients.

Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial.

BACKGROUND: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.

Echocardiography can identify patients with increased pulmonary vascular resistance by assessing pressure reflection in the pulmonary circulation.

BACKGROUND: Pulmonary hypertension is a frequent finding in patients with cardiopulmonary disorders. It is important to recognize pulmonary hypertension due to increased pulmonary vascular resistance (PVR), as this affects treatment and prognosis. Patients with increased PVR have an increased pulmonary pressure reflection. We hypothesized that pressure reflection can be described by echocardiography and that variables related to pressure reflection can identify patients with increased PVR. METHODS AND RESULTS: The study comprised 98 patients investigated within 24 hours of right heart catheterization and 20 control subjects. The pressure reflection variables were obtained by pulsed Doppler in the pulmonary artery and continuous Doppler of tricuspid regurgitation. We selected 3 variables related to pressure reflection: the interval from valve opening to peak velocity in the pulmonary artery (AcT, ms), the interval between pulmonary artery peak velocity and peak tricuspid velocity (tPV-PP, ms), and the right ventricular pressure increase after peak velocity in the pulmonary artery (augmented pressure, AP, mm Hg). The correlation between simultaneous catheter- and echocardiography-determined AP was strong (n=19, R=0.83). The AcT, tPV-PP, and AP in patients with a PVR of >3 Woods units (n=71) was (mean+/-SD) 77+/-16 ms, 119+/-36 ms, and 22+/-12 mm Hg, respectively, and differed from patients with a PVR of

Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial.

BACKGROUND: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate > or =20 mL/min/1.73m and <90 mL/min/1.73 m) >1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P<0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.

Doppler echocardiography can provide a comprehensive assessment of right ventricular afterload.

BACKGROUND: The purpose of this study was to evaluate novel Doppler echocardiographic methods for a comprehensive assessment of right ventricular afterload, including pulmonary artery (PA) mean pressure (PAMP) and the PA pressure waveform. METHODS: The study comprised 109 patients who underwent right-heart catheterization simultaneously (group A, n = 31) with Doppler echocardiography on 35 occasions or nonsimultaneously (group B, n = 78) within 24 hours of Doppler echocardiography. Right ventricular afterload variables were obtained using pulsed Doppler in the PA and continuous Doppler of tricuspid regurgitation. The intervals from QRS to the opening and closing of the pulmonary valve and to the peak velocity of tricuspid regurgitation were measured. PA end-diastolic pressure, PA systolic pressure, and PA notch pressure were calculated. The Doppler-derived pressure curve was separated into 3 parts with fitted second-order curves. RESULTS: Catheter PAMP and Doppler PA systolic pressure in group A were strongly related (R = 0.85). The regression equation from group A (PAMP = 0.65 x Doppler PA systolic pressure - 1.2 mm Hg) was used to calculate PAMP in group B. There was no difference between catheter PAMP (mean, 39 +/- 18 mm Hg; range, 8-95 mm Hg) and Doppler PAMP (mean, 39 +/- 15 mm Hg; range, 12-83 mm Hg) (P = .85). The systolic areas under the curves for catheter and Doppler PAMP in group A were 20 +/- 4.7 and 20 +/- 4.0 mm Hg s, respectively (P = .52), and the diastolic areas were 21 +/- 5.7 and 22 +/- 6.3 mm Hg s, respectively (P = .21). CONCLUSION: A comprehensive assessment of right ventricular afterload that includes PAMP and the PA pressure waveform can be provided by Doppler echocardiography in patients with a wide range of PA pressures and different diagnoses.

Endothelin-1 across the lung circulation in patients with pulmonary arterial hypertension and influence of epoprostenol infusion.

BACKGROUND: The endothelin-1 (ET-1) system plays a pathophysiologic role in patients with pulmonary arterial hypertension (PAH). Results from previous studies assessing the transpulmonary gradient of ET-1 have been inconsistent. The influence of an intravenous epoprostenol infusion on the transpulmonary ET-1 gradient is unknown. METHODS: In a prospective investigation, serum concentrations of ET-1 were measured in 39 consecutive patients (31 women; mean age, 20-77 years) with pulmonary hypertension (33 with PAH) and compared with 20 controls. The effect of intravenous epoprostenol administration on the transpulmonary gradient of ET-1 was analyzed in 13 patients with pulmonary hypertension. Blood samples were taken simultaneously from the pulmonary artery and radial artery. RESULTS: The serum levels of ET-1 were significantly higher in the arterial (3.9 +/- 1.28 vs 2.53 +/- 0.24 pg/ml, p < 0.001) and mixed venous blood samples (3.9 +/- 1.21 vs 2.52 +/- 0.29 pg/ml, p < 0.001) in patients with pulmonary hypertension than in controls. The arterial/venous ratio of ET-1 in patients (1.0 +/- 0.1) and in the control group (1.0 +/- 0.05) was similar (p = 0.79). During intravenous epoprostenol infusion, there were no changes in the mean transpulmonary ET-1 gradient (0.98 +/- 0.07 vs 0.96 +/- 0.09, p = 0.52), despite significant hemodynamic changes. CONCLUSION: The ET-1 radial artery/pulmonary artery ratio of unity indicates a balanced release and clearance of ET-1 across the lung circulation in controls and in patients with different forms of pulmonary hypertension. ET-1 levels across the pulmonary circulation did not change during epoprostenol infusion.