Pimobendan improves right ventricular myocardial contraction and attenuates pulmonary arterial hypertension in rats with monocrotaline-induced pulmonary arterial hypertension

Purpose

The present study aimed to evaluate the therapeutic effect of pimobendan treatment for pulmonary hypertension (PH) in rats administered monocrotaline (MCT).

Methods

Fifty-four 12-week-old male Sprague–Dawley rats were injected with monocrotaline or saline solution. Serial echocardiography and right ventricular systolic pressure (RVSP) measurement via a cardiac catheter were performed. After injection of MCT, rats received oral pimobendan (MCT/pimobendan group) or no treatment (MCT group) until undergoing echocardiography and cardiac catheter insertion.

Results

Right ventricular systolic pressure in the MCT/pimobendan group was lower than that in the MCT group at 6 weeks. Right ventricle free wall (RVFW) myocardial systolic velocity (Sm) in the MCT group showed a reduction compared with the saline group at 2 weeks. RVFW Sm in the MCT/pimobendan group was preserved as compared with the saline group at 2 weeks. RVFW Tei index in the MCT/pimobendan group showed a reduction compared with the saline group and the MCT group at 2 weeks. Echocardiography in the MCT/pimobendan group showed improvement compared with MCT rats.

Conclusions

Both a reduction in RVSP and improvement in myocardial contraction were demonstrated with administration of pimobendan in rats with PH induced by MCT. Echocardiography evaluation of systolic function seems to be useful for monitoring excess administration of pimobendan.     

Haemodynamic and neuroendocrine effects of tezosentan in chronic experimental pulmonary hypertension

Purpose

Chronic pulmonary hypertension (PH) therapy is poorly investigated in intensive care. Our aim was to evaluate haemodynamic and neuroendocrine effects of the dual endothelin-1 (ET-1) blocker tezosentan in monocrotaline (MCT)-induced PH.

Methods

Male Wistar rats (180–200?g, n?=?194) randomly received 60?mg?kg^?1 MCT or vehicle, subcutaneously, and 2?days later, a subgroup of MCT-injected rats was gavaged with 300?mg?kg^?1?day^?1 bosentan (MCT BOS, n?=?46), while another (MCT, n?=?125) and control rats (Ctrl, n?=?23) received vehicle. At 25–30?days, 48?h after interrupting bosentan, rats randomly underwent either a dose–response evaluation (0.5–20?mg?kg^?1, n?=?7 each group) or a 4?h perfusion of tezosentan (20?mg?kg^?1 in 10?min?+?10?mg?g^?1?h^?1) or vehicle (n?=?8 per group, each). Haemodynamics, including blood gas analysis, were evaluated after thoracotomy under anaesthesia. After plasma, right ventricle (RV) and lung collection, plasma ET-1, cytokines, nitrate and 6-keto-PGF1α, and lung and right ventricular gene expression and cyclooxygenase (COX) and nitric oxide synthase (NOS) activities were quantified.

Results

Monocrotaline resulted in PH, RV dilation and decreased cardiac output (CO) that were attenuated in MCT BOS. Pulmonary hypertension was attenuated by tezosentan without systemic hypotension. Tezosentan increased CO without changing ventilation-perfusion matching. Both bosentan and tezosentan reduced ET-1 and cytokine plasma levels and tissue expression, and inducible NOS and COX-2 RV activities. Bosentan increased nitrate plasma levels and non inducible NOS activities whereas tezosentan decreased circulating 6-keto-PGF1α but increased lung COX-1 activity.

Conclusions

Tezosentan may be useful for haemodynamic handling and bosentan replacement in critically ill PH patients exerting important beneficial neuroendocrine and anti-inflammatory actions.     

Selective and rapid monitoring of dual platelet inhibition by aspirin and P2Y12 antagonists by using multiple electrode aggregometry

Background

Experimental models of pulmonary embolism (PE) that produce pulmonary hypertension (PH) employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Objective: Test if moderate-severity autologous PE in Sprague-Dawley (SD) and Copenhagen (Cop) rats can produce persistent PH.

Methods

blood was withdrawn from the jugular vein, treated with thrombin-Ca⁺⁺ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days.

Results

Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours) and 97% (5 days) in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days). Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation.

Conclusions

Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.     

Effects of piroximone on the right ventricular function in severe heart failure patients

Objectives

To assess the effects of piroximone, a phosphodiesterase inhibitor, on right ventricular function in patients with heart failure.

Design

Randomized study: patients were randomly assigned to the piroximone infusion rate of 5 or 10 μg/kg/min.

Setting

Cardiologic intensive care unit.

Patients

12 consecutive patients with severe heart failure.

Interventions

Right heart catheterization was performed using a Swan-Ganz ejection fraction thermodilution catheter.

Measurements and results

Measurements of right ventricular ejection fraction (RVEF), end-diastolic and end-systolic right ventricular volumes were obtained using the thermodilution principle. To determine contractility indexes, the relationships between end-systolic pulmonary arterial pressure (ESPAP) over right ventricular end-systolic volume (RVESV) and ESPAP over RVEF were calculated during the infusion of prostacyclin at incremental infusion rates of 2, 4, 6 and 8 ng/kg/min. The slope of the relation between ESPAP over RVESV shifted during piroximone therapy from 7.635±1.632 to 1.975±0.432 (p<0.01) and from 6.092±1.99 to 1.028±0.853 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively. The slope of the relation between ESPAP over RVEF decreased from ?0.414±0.296 to ?0.821±0.257 (p<0.01) and from ?0.127±0.048 to ?0.533±0.135 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively.

Conclusions

This study suggests a positive action of piroximone on right ventricular contractility at these 2 dosages. This approach using this type of catheter allowed us to determine right ventricular inotropic indexes.     

Our paper 20 years later: Inhaled nitric oxide for the acute respiratory distress syndrome—discovery,current understanding,and focussed targets of future applications

Introduction

More than 20 years have passed since we reported our results of treating patients with the acute respiratory distress syndrome (ARDS) with inhaled nitric oxide (iNO). The main finding was that iNO alleviated pulmonary hypertension (PH) by selective vasodilation of pulmonary vessels in ventilated lung areas. This, in turn, improved arterial oxygenation.

Methods

We now set out to review the time span between the discovery of NO in 1987 and today in order to identify and describe interesting areas of research and clinical practice surrounding the application of iNO.

Major Findings

Enhancement of ventilation–perfusion matching and alleviation of PH in ARDS, treatment of PH of the newborn, and treatment of perioperative PH in congenital heart disease serve as just a few exciting examples for the successful use of iNO. Breathing NO prevents PH induced by stored blood transfusions or sickle cell disease. Exploiting the anti-inflammatory properties of NO helps to treat malaria.

Discussion

Regarding the use of iNO in ARDS, there remains the unresolved question of whether important outcome parameters can be positively influenced. At first glance, several randomized controlled trials and meta-analyses seem to send the clear message: “There is none!” Careful analyses, however, leave sufficient room for doubt that the ideal study to produce the unequivocal proof for the inability of iNO to positively impact on important outcome parameters has, as yet, not been conducted.

Conclusion

In summary, the discovery of and research on the many positive effects of iNO has improved care of critically ill patients worldwide. It is a noble effort to continue on this path.     

Synthesis and Ex Vivo Autoradiographic Evaluation of Ethyl-��-d-galactopyranosyl-(1,4��)-2��-deoxy-2��-[18F]fluoro-��-d-glucopyranoside��A Novel Radioligand for Lactose-Binding Protein: Implications for Early Detection of Pancreatic Carcinomas with PET

Introduction

Previous studies demonstrated that the lactose-binding protein (hepatocellular carcinoma?Cintestine?Cpancreas and pancreatitis-associated proteins (HIP/PAP)) is upregulated >130 times in peritumoral pancreatic tissue as compared to normal pancreatic tissue. Therefore, we developed a new radiolabeled ligand of HIP/PAP, the ethyl-??-d-galactopyranosyl-(1,4??)-2??-deoxy-2??-[¹⁸F]fluoro-??-d-glucopyranoside (Et-[¹⁸F]FDL) for noninvasive imaging of pancreatic carcinoma using positron emission tomography and computerized tomography (PET/CT).

Methods

The novel precursor and radiolabeling methods for synthesis of Et-[¹⁸F]FDL produced no isomers; the average decay-corrected radiochemical yield was 68%, radiochemical purity >99%, and specific activity >74 GBq/µmol. The radioligand properties of Et-[¹⁸F]FDL were evaluated using an ex vivo autoradiography and immunohistochemistry in pancreatic tissue sections obtained from mice-bearing orthotopic pancreatic tumor xenografts.

Results and Discussion

Et-[¹⁸F]FDL binding to peritumoral pancreatic tissue sections strongly correlated with HIP/PAP expression (r?=?0.81) and could be completely blocked by treatment with 1 mM lactose.

Conclusion

These results suggest that Et-[¹⁸F]FDL is a promising agent which should be evaluated for detection of early pancreatic carcinomas by PET/CT imaging.     

Inhaled nitric oxide reverses cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance. Preliminary results

Background

In order to test the hypothesis that inhaled nitric oxide (NO) reverses the pulmonary hypertension induced by αα-diaspirin crosslinked hemoglobin (ααHb), were studied anesthetized pigs that were administered with a total dose of 200 mg/kg of 10% ααHb. Inhaled NO (5 ppm) was administered for 10 min, and then discontinued for 10 min. This cycle was then repeated with 10 ppm inhaled NO.

Results

ααHb caused pulmonary arterial pressure (PAP) to increase from 27 ± 1.7 to 40 ± 3.0 mmHg (P<0.05) and dynamic lung compliance to decrease from 29± 1.5 to 23± 1.6 ml/cmH₂O (P < 0.05). After both doses of inhaled NO, but particularly 10 ppm, PAP was reduced (P < 0.05) and lung compliance increased (P < 0.05) from the ααHb levels. When inhaled NO was discontinued PAP again increased and lung compliance decreased to levels significantly different from baseline (P < 0.05).

Conclusion

We conclude that cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance can be selectively counteracted by inhaled NO.     

Inhalation of NO during myocardial ischemia reduces infarct size and improves cardiac function

Purpose

Bioactive NO carriers in circulating blood formed during NO inhalation selectively distribute blood flow to areas in need, and may thus improve collateral perfusion to the area-at-risk in acute myocardial infarction (AMI). Here, we tested the hypothesis that NO inhalation during the ischemic phase of AMI may improve left ventricular function and reduce infarct size in rats.

Methods

Following left anterior descending coronary artery (LAD) occlusion, rats received 50?ppm NO for 2?h of ischemia, during subsequent 3?h of reperfusion, or for 5?h of ischemia and reperfusion. Effects of inhaled NO were compared to those of intravenous nitrite as a putative carrier formed during NO inhalation. Downstream signaling via soluble guanylate cyclase was tested by inhibition with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ).

Results

NO inhalation during myocardial ischemia increased left ventricular systolic pressure, contractility, relaxation, and cardiac output, and reduced myocardial infarction size and area-at-risk as compared to untreated controls. NO inhalation during the reperfusion phase caused a comparable protective effect. Combined inhalation during ischemia and reperfusion did not further improve left ventricular hemodynamics, but had an additive protective effect on the myocardial area-at-risk. NO inhalation increased circulating nitrite levels, and mimicking of this effect by intravenous nitrite infusion achieved similar protection as NO inhalation during myocardial ischemia, while ODQ blocked the protective NO effect.

Conclusions

Inhalation of NO during myocardial ischemia improves left ventricular function and reduces infarct size by mechanisms that increase levels of circulating nitrite and involve soluble guanylate cyclase. NO inhalation may represent a promising early intervention in AMI.     

Step climbing capacity in patients with pulmonary hypertension

Background

Patients with pulmonary hypertension (PH) typically have exercise intolerance and limitation in climbing steps.

Objectives

To explore the exercise physiology of step climbing in PH patients, on a laboratory-based step test.

Methods

We built a step oximetry system from an ‘aerobics’ step equipped with pressure sensors and pulse oximeter linked to a computer. Subjects mounted and dismounted from the step until their maximal exercise capacity or 200 steps was achieved. Step-count, SpO₂ and heart rate were monitored throughout exercise and recovery. We derived indices of exercise performance, desaturation and heart rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level were measured. Lung function tests and hemodynamic parameters were extracted from the medical record.

Results

Eighty-six subjects [52 pulmonary arterial hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were recruited. Exercise performance (climbing time, height gained, velocity, energy expenditure, work-rate and climbing index) on the step test was significantly worse with PH and/or worsening WHO functional class (ANOVA, p < 0.001). There was a good correlation between exercise performance on the step and 6-min walking distance–climb index (r = ?0.77, p < 0.0001). The saturation deviation (mean of SpO₂ values <95 %) on the step test correlated with diffusion capacity of the lung (ρ = ?0.49, p = 0.001). No correlations were found between the step test indices and other lung function tests, hemodynamic parameters or NT-proBNP levels.

Conclusions

Patients with PAH/CTEPH have significant limitation in step climbing ability that correlates with functional class and 6-min walking distance. This is a significant impediment to their daily activities.     

Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility

Objective

Prostacyclins have been suggested to exert positive inotropic effects which would render them particularly suitable for the treatment of right ventricular (RV) dysfunction due to acute pulmonary hypertension (PHT). Data on this subject are controversial, however, and vary with the experimental conditions. We studied the inotropic effects of epoprostenol at clinically recommended doses in an experimental model of acute PHT.

Design and setting

Prospective laboratory investigation in a university hospital laboratory.

Subjects

Six pigs (36?±?7?kg).

Interventions

Pigs were instrumented with biventricular conductance catheters, a pulmonary artery (PA) flow probe, and a high-fidelity pulmonary pressure catheter. Incremental doses of epoprostenol (10, 15, 20, 30, 40?ng?kg^–1?min^–1) were administered in undiseased animals and after induction of acute hypoxia-induced PHT.

Measurements and results

In acute PHT epoprostenol markedly reduced RV afterload (slopes of pressure-flow relationship in the PA from 7.0?±?0.6 to 4.2?±?0.7?mmHg?min?l^–1). This was associated with a paradoxical and dose-dependent decrease in RV contractility (slope of preload-recruitable stroke-work relationship from 3.0?±?0.4 to 1.6?±?0.2?mW?s?ml^–1; slope of endsystolic pressure-volume relationship from 1.5?±?0.3 to 0.7?±?0.3?mmHg?ml^–1). Left ventricular contractility was reduced only at the highest dose. In undiseased animals epoprostenol did not affect vascular tone and produced a mild biventricular decrease in contractility.

Conclusions

Epoprostenol has no positive inotropic effects in vivo. In contrast, epoprostenol-induced pulmonary vasodilation in animals with acute PHT was associated with a paradoxical decrease in RV contractility. This effect is probably caused indirectly by the close coupling of RV contractility to RV afterload. However, data from normal animals suggest that mechanisms unrelated to vasodilation are also involved in the observed negative inotropic response to epoprostenol.     

Approach to Assessing Myocardial Perfusion in Rats Using Static [13N]-Ammonia Images and a Small-Animal PET

Purpose

Semi-quantitative, static positron emission tomography (PET) has been used to perform an initial approach to the assessment of [13N]-ammonia perfusion studies aimed to elucidating the effect of injecting human embryonic stem cell-derived (hES) hemangioblasts on infarcted rat hearts.

Procedures

Female NIH nude rats underwent occlusion of the left anterior descending coronary artery for 30?min before reperfusion. Either one million hES-derived hemangioblasts (n?=?5) or control media (n?=?4) were injected into the site of the infarct 1?day post-myocardial infarction (MI) under high-resolution echocardiography guidance. PET imaging was performed 6?weeks after MI induction, and uptake polar maps were created by sampling the left ventricle at equidistant slices from the base to the apex and measuring the average myocardium value at three contiguous voxels to minimize partial volume effects. Statistical comparison between treatment and control groups was done with a Mann?CWhitney U test.

Results

Myocardium uptake ratios for treated and untreated subjects show statistically significant difference (98% certainty).

Conclusions

The straightforward procedure described here (similar to those commonly used in clinical routine) was sufficient to yield statistically significant perfusion differences between the treated and untreated animals despite the small sample size.     

A metabolomic approach for diagnosis of experimental sepsis

Background

The search for reliable diagnostic biomarkers of sepsis remains necessary. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for defining the metabolic phenotype of sepsis.

Objective

To develop a novel NMR-based metabolomic approach for diagnostic evaluation of sepsis.

Methods

Male Sprague?CDawley rats (weight 325?C375?g) underwent cecal ligation and puncture (n?=?14, septic group) or sham procedure (n?=?14, control group) and 24?h later were euthanized. Lung tissue, bronchoalveolar lavage (BAL) fluid, and serum samples were obtained for ¹H NMR and high-resolution magic-angle spinning analysis. Unsupervised principal components analysis was performed on the processed spectra, and a predictive model for diagnosis of sepsis was constructed using partial least-squares discriminant analysis.

Results

NMR-based metabolic profiling discriminated characteristics between control and septic rats. Characteristic metabolites changed markedly in septic rats as compared with control rats: alanine, creatine, phosphoethanolamine, and myoinositol concentrations increased in lung tissue; creatine increased and myoinositol decreased in BAL fluid; and alanine, creatine, phosphoethanolamine, and acetoacetate increased whereas formate decreased in serum. A predictive model for diagnosis of sepsis using these metabolites classified cases with sensitivity and specificity of 100%.

Conclusions

NMR metabolomic analysis is a potentially useful technique for diagnosis of sepsis. The concentrations of metabolites involved in energy metabolism and in the inflammatory response change in this model of sepsis.     

Effects of different tidal volumes in pulmonary and extrapulmonary lung injury with or without intraabdominal hypertension

Purpose

We hypothesized that: (1) intraabdominal hypertension increases pulmonary inflammatory and fibrogenic responses in acute lung injury (ALI); (2) in the presence of intraabdominal hypertension, higher tidal volume reduces lung damage in extrapulmonary ALI, but not in pulmonary ALI.

Methods

Wistar rats were randomly allocated to receive Escherichia coli lipopolysaccharide intratracheally (pulmonary ALI) or intraperitoneally (extrapulmonary ALI). After 24?h, animals were randomized into subgroups without or with intraabdominal hypertension (15?mmHg) and ventilated with positive end expiratory pressure?=?5?cmH₂O and tidal volume of 6 or 10?ml/kg during 1?h. Lung and chest wall mechanics, arterial blood gases, lung and distal organ histology, and interleukin (IL)-1??, IL-6, caspase-3 and type III procollagen (PCIII) mRNA expressions in lung tissue were analyzed.

Results

With intraabdominal hypertension, (1) chest-wall static elastance increased, and PCIII, IL-1??, IL-6, and caspase-3 expressions were more pronounced than in animals with normal intraabdominal pressure in both ALI groups; (2) in extrapulmonary ALI, higher tidal volume was associated with decreased atelectasis, and lower IL-6 and caspase-3 expressions; (3) in pulmonary ALI, higher tidal volume led to higher IL-6 expression; and (4) in pulmonary ALI, liver, kidney, and villi cell apoptosis was increased, but not affected by tidal volume.

Conclusions

Intraabdominal hypertension increased inflammation and fibrogenesis in the lung independent of ALI etiology. In extrapulmonary ALI associated with intraabdominal hypertension, higher tidal volume improved lung morphometry with lower inflammation in lung tissue. Conversely, in pulmonary ALI associated with intraabdominal hypertension, higher tidal volume increased IL-6 expression.     

Comparison of the effects of aromatase inhibitors and tamoxifen on radiation-induced lung toxicity: results of an experimental study

Purpose

The purpose of this study is to compare the effects of anastrozole, letrozole and tamoxifen on radiation-induced pulmonary fibrosis.

Methods

Eighty female Wistar albino rats were divided into eight groups. Group (G) 1 was defined as control group. G2 was radiation therapy (RT) only group. Groups 3, 4 and 5 were tamoxifen, anastrozole and letrozole control groups respectively. Groups 6, 7 and 8 were RT plus tamoxifen, anastrozole and letrozole groups, respectively. A single dose of 12 Gy RT was given to both lungs. Tamoxifen, anastrozole and letrozole were started 1 week before the RT and continued until the animals were sacrificed 16 weeks after the RT. As an end point, the extent of pulmonary fibrosis for each rat was quantified with image analysis of histological sections of the lung. Kruskal–Wallis and Mann–Whitney U tests were used for statistical analyses.

Results

The congestion, inflammation and pulmonary fibrosis scores were significantly different between all the study groups (p values were <0.001 for each). When compared with RT only group, concomitant RT and tamoxifen group increased the radiation-induced pulmonary fibrosis (p?=?0.005). However, using either anastrozole or letrozole with RT did not increase the radiation-induced pulmonary fibrosis (p values were 0.768 and 0.752, respectively).

Conclusion

Concomitant use of tamoxifen with RT seems to increase radiation-induced pulmonary toxicity. However, the use of both anastrozole and letrozole appears to be safe with concomitant RT, without increasing the risk of pulmonary fibrosis. This finding should be clarified with further clinical studies.     

CPAP for acute cardiogenic pulmonary oedema from out-of-hospital to cardiac intensive care unit: a randomised multicentre study

Purpose

Continuous positive airway pressure (CPAP) is a useful treatment for patients with acute cardiogenic pulmonary oedema (CPE). However, its usefulness in the out-of-hospital setting has been poorly investigated and only by small and single-centre studies. We designed a multicentre randomised study to assess the benefit of CPAP initiated out of hospital.

Methods

A total of 207 patients with CPE were randomly allocated by emergency mobile medical units to receive either standard treatment alone or standard treatment plus CPAP. CPAP was maintained after admission to the intensive care unit (ICU). Inclusion criteria were orthopnoea, respiratory rate greater than 25?breaths/min, pulse oximetry less than 90% in room air and diffuse crackles. The primary end point was assessed during the first 48?h and combined: death, presence of intubation criteria, persistence of either all inclusion criteria or circulatory failure at the second hour or their reappearance before 48?h. Absence of all criteria defined successful treatment.

Results

CPAP was used for 60?min [40, 65] (median [Q1, Q3]) in the pre-hospital setting and 120?min [60, 242] in ICU and was well tolerated in all patients. Treatment was successful in 79% of patients in the CPAP group and 63% in the control group (p?=?0.01), especially for persistence of inclusion criteria after 2?h (12 vs. 26%) and for intubation criteria (4 vs. 14%). CPAP was beneficial irrespective of the initial PaCO₂ or left ventricular ejection fraction.

Conclusion

Immediate use of CPAP in out-of-hospital treatment of CPE and until CPE resolves after admission significantly improves early outcome compared with medical treatment alone.     

Primary echocardiographic results of the Carpentier–Edwards Perimount Magna

Purpose

The aim of this study was to investigate the primary echocardiographic results of aortic valve replacement using 21- and 19-mm Carpentier–Edwards Perimount Magna bioprosthesis aortic xenografts in patients with small aortic annulus.

Methods

Twenty patients (mean body surface area 1.63?±?0.16?m²) underwent aortic valve replacement between June 2008 and December 2009. Eight and 12 patients received 21- and 19-mm Magna bioprostheses, respectively. After 12?months, hemodynamic data were obtained by echocardiography to estimate the prosthesis–patient mismatch.

Results

At follow-up, significant decreases in peak and mean left ventricular aortic pressure gradients were observed in the 12 patients with aortic stenosis (P?<?0.05). Regression of the left ventricular mass was observed in all the patients (P?<?0.05). The mean measured effective orifice area (EOA) and EOA index (EOAI) were 1.61?±?0.28?cm² and 0.99?±?0.16?cm²/m², respectively. Prosthesis–patient mismatch (EOAI ≤0.85) was documented in three patients.

Conclusion

The primary echocardiographic findings suggested that the hemodynamic performance of the 19- and 21-mm Carpentier–Edwards Perimount Magna bioprostheses was satisfactory in the patients with a small aortic annulus.     

CLUE: a randomized comparative effectiveness trial of IV nicardipine versus labetalol use in the emergency department

Introduction

Our purpose was to compare the safety and efficacy of food and drug administration (FDA) recommended dosing of IV nicardipine versus IV labetalol for the management of acute hypertension.

Methods

Multicenter randomized clinical trial. Eligible patients had 2 systolic blood pressure (SBP) measures ≥180 mmHg and no contraindications to nicardipine or labetalol. Before randomization, the physician specified a target SBP ± 20 mmHg (the target range: TR). The primary endpoint was the percent of subjects meeting TR during the initial 30 minutes of treatment.

Results

Of 226 randomized patients, 110 received nicardipine and 116 labetalol. End organ damage preceded treatment in 143 (63.3%); 71 nicardipine and 72 labetalol patients. Median initial SBP was 212.5 (IQR 197, 230) and 212 mmHg (IQR 200,225) for nicardipine and labetalol patients (P = 0.68), respectively. Within 30 minutes, nicardipine patients more often reached TR than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within TR than labetalol (47.3% vs. 32.8%, P = 0.026). Rescue medication need did not differ between nicardipine and labetalol (15.5 vs. 22.4%, P = 0.183). Labetalol patients had slower heart rates at all time points (P < 0.01). Multivariable modeling showed nicardipine patients were more likely in TR than labetalol patients at 30 minutes (OR 2.73, P = 0.028; C stat for model = 0.72)

Conclusions

Patients treated with nicardipine are more likely to reach the physician-specified SBP target range within 30 minutes than those treated with labetalol.

Trial registration

ClinicalTrials.gov: NCT00765648     

Assessment of right ventricular geometry and mechanics in chronic obstructive pulmonary disease patients living at high altitude

Degree of increase in pulmonary artery pressure (PAP) and adaptive responses in right ventricular morphology and mechanics play an important role in the prognosis of chronic obstructive pulmonary disease (COPD) patients. Three dimensional echocardiography and deformation imaging are recent advancements in echocardiography that allow more through assessment of right ventricle. We aimed to investigate right ventricular geometry and mechanics in a stable COPD population living at moderately high altitude. A total of 26 stable COPD patients with variable disease severity were included to this study. Pulmonary function tests, six minutes walking test (6MWT) and two- and three-dimensional echocardiography were performed for evaluation and data collection. Both systolic (43.06 ± 11.79 mmHg) and mean (33.38 ± 9.75 mmHg) PAPs were significantly higher in COPD patients compared to controls (p < 0.05, p < 0.001; respectively). Right ventricular volumes were similar between groups, although right ventricular free wall thickness was significantly increased in COPD group. The number of subjects with a sub-normal (<40 %) right ventricular ejection fraction was significantly higher in COPD group (45.8 vs. 17.4 %, p < 0.05), and the mean right ventricular strain was significantly lower (?21.05 ± 3.80 vs. ?24.14 ± 5.37; p < 0.05). Only mean PAP and body surface area were found as independent predictors for 6MWT distance. Increased PAP and reduced right ventricular contractility were found in COPD patients living at moderately high altitude, although right ventricular volumes were normal. Similar findings can be expected in other COPD patients with high PAP, since these findings probably represents the effect of increased PAP on right ventricular mechanics.     

Prognostic utility of T-wave alternans in a real-world population of patients with left ventricular dysfunction: the PREVENT-SCD study

Background

The predictive value of T-wave alternans (TWA) for lethal ventricular tachyarrhythmia in patients with left ventricular (LV) dysfunction is controversial. Also, long-term arrhythmia risk of patients ineligible for the TWA test is unknown.

Methods

This was a multicenter, prospective observational study of patients with LV ejection fraction ??40% due to ischemic or non-ischemic cardiomyopathies, designed to evaluate the prognostic value of TWA for lethal ventricular tachyarrhythmia. The primary end point was a composite of sudden cardiac death, sustained rapid ventricular tachycardia (VT) or ventricular fibrillation (VF), and appropriate defibrillator therapy for rapid VT or VF.

Results

Among 453 patients enrolled in the study, 280 (62%) were eligible for the TWA test. TWA was negative in 82 patients (29%), who accounted for 18% of the total population. The median of follow-up was 36?months. The 3-year event-free rate for the primary end point was significantly higher in TWA-negative patients (97.0%) than in TWA non-negative patients (89.5%, P?=?0.037) and those ineligible for the TWA test (84.4%, P?=?0.003). Multivariable analysis identified both non-negative TWA [hazard ratio (HR) 4.43; 95% confidence interval (CI) 1.02?C19.2; P?=?0.047) and ineligibility for the TWA test (HR 6.89; 95% CI 1.59?C29.9; P?=?0.010) to be independent predictors of the primary end point.

Conclusions

TWA showed high negative predictive ability for lethal ventricular tachyarrhythmia in patients with LV dysfunction, although the TWA-negative patients accounted for only 18% of the entire population. Those ineligible for the TWA test had the highest risk for lethal ventricular tachyarrhythmia.