Arterial stiffness in hypertensive and type 2 diabetes patients in Ghana: comparison of the cardio-ankle vascular index and central aortic techniques

Background

Diabetes and hypertension increase arterial stiffness and cardiovascular events in all societies studied so far; sub-Saharan African studies are sparse. We investigated factors affecting arterial function in Ghanaians with diabetes, hypertension, both or neither.

Method

Testing the hypothesis that arterial stiffness would progressively increase from controls to multiply affected patients, 270 participants were stratified into those with diabetes or hypertension only, with both, or without either. Cardio-ankle vascular index (CAVI), heart–ankle pulse wave velocity (haPWV), aortic PWV (PWVao) by Arteriograph, aortic and brachial blood pressures (BP), were measured.

Results

In patients with both diabetes and hypertension compared with either alone, values were higher of CAVI (mean?±?SD, 8.3?±?1.2 vs 7.5?±?1.1 and 7.4?±?1.1 units; p?<?0.05), PWVao (9.1?±?1.4 vs 8.7?±?1.9 and 8.1?±?0.9 m/s; p?<?0.05) and haPWV (8.5?±?1 vs 7.9?±?1 and 7.2?±?0.7 m/s; p?<?0.05) respectively. In multivariate analysis, age, having diabetes or hypertension and BMI were independently associated with CAVI in all participants (β?=?0.49, 0.2, 0.17 and -0.2 units; p?<?0.01, respectively). Independent determinants of PWVao were heart rate, systolic BP and age (β?=?0.42, 0.27 and 0.22; p?<?0.01), and for haPWV were systolic BP, age, BMI, diabetes and hypertension status (β?=?0.46, 0.32, -0.2, 0.2 and 0.11; p?<?0.01).

Conclusion

In this sub-Saharan setting with lesser atherosclerosis than the western world, arterial stiffness is significantly greater in patients with coexistent diabetes and hypertension but did not differ between those with either diabetes or hypertension only. Simple, reproducibly measured PWV/CAVI may offer effective and efficient targets for intervention.

     

Relation of arterial stiffness to left ventricular structure and function in healthy women

Background

Interactions between the left ventricular (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. However, most of studies covered multiple cardiovascular risk factors, which also contributed to the morphological and functional changes of LV. The aim of this study was to examine the relationship between arterial stiffness and LV structure and function in healthy women with a low burden of risk factors.

Methods

Healthy women from the Twins UK cohort (n?=?147, mean age was 54.07?±?11.90 years) were studied. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV). LV structure and function were assessed by two-dimensional speckle tracking echocardiography.

Results

cf-PWV was significantly associated with most measures of LV geometry and function, including relative wall thickness (RWT), E/e’ ratio, global circumferential and radial strain, apical rotation and LV twist (each p?<? 0.05), but bore no relation to global longitudinal strain. After adjustment for age, body mass index, blood pressure and heart rate, cf-PWV was significantly correlated with RWT, global circumferential strain, apical rotation and LV twist (β?=?0.011, ??0.484, 1.167 and 1.089, respectively, each p?≤? 0.05).

Conclusions

In healthy women with a low burden of risk factors, elevated arterial stiffness was intimately interwoven with increased LV twisting even before LV dysfunction becomes clinically evident.

     

Effect of food intake on myocardial performance index

Background

Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects.

Methods

Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal.

Results

MPI decreased significantly (P?<?0.05) from fasting values 30 min after the meal, and had almost returned to baseline after 110 min. MPI decreased from 0.28?±?0.06 (fasting) to 0.20?±?0.07 30 min after eating. At 110 min after eating the index value was almost back to the baseline value 0.26?±?0.06. (P?=?0.15).

Conclusions

This study shows that myocardial performance index is affected by food intake in healthy subjects.

     

A randomised,open-labelstudy of insulin glargine or neutral protamine Hagedorn insulin in Chinese paediatric patients with type 1 diabetes mellitus

Background

We aimed to describe the safety and efficacy of insulin glargine in Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral protamine Hagedorn (NPH) insulin was the reference therapy.

Methods

This open-label, randomised, Phase III study was conducted at 10 sites in China. Children aged ≥6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin aspart was given as bolus insulin. The primary endpoint was absolute change in glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and safety. The study was registered at clinicaltrials.gov (NCT01223131).

Results

In total,196 patients were screened, and 162 were randomised (107 and 55 patients were randomised to insulin glargine and NPH insulin, respectively). The mean?±?SD of absolute change in HbA1c was–0.25?±?1.68% (–2.69?±?18.32 mmol/mol) in the insulin glargine group and –0.54?±?1.67% (–5.55?±?20.32 mmol/mol) in the NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments were generally well tolerated. A numerically lower rate of symptomatic hypoglycaemia per patient year was observed for insulin glargine versus NPH insulin (24.3?±?45.8 versus32.3?±?43.2); severe hypoglycaemia was rare (<2%).

Conclusions

Initiation of insulin glargine can aid Chinese paediatric patients with T1DM to safely reduce their HbA1c levels.

     

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation

Background

Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim

The aim was to study characteristics of induced AF and its modification by flecainide.

Methods

The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results

At AF onset, AFR was 295?±?52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269?±?36 fpm in the control group (ns), and 364?±?26 fpm in the horses with spontaneous persistent AF (P?<?0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269?±?36 fpm to a plateau of 313?±?14 fpm before decreasing to 288?±?28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P?<?0.05).

Conclusion

AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.

     

Left atrial strain - an early marker of left ventricular diastolic dysfunction in patients with hypertension and paroxysmal atrial fibrillation

Background

2D strain imaging of the left atrium (LA) is a new echocardiographic method which allows us to determine contractile, conduit and reservoir functions separately. This method is particularly useful when changes are subtle and not easily determined by traditional parameters, as it is in arterial hypertension and atrial fibrillation (AF). The aims of our study were: to determine LA contractile, conduit and reservoir function by 2D strain imaging in patients with mild arterial hypertension and paroxysmal AF; to assess LA contractile, conduit and reservoir functions’ relation with LV diastolic dysfunction (DD) parameters.

Methods

LA contractile, conduit and reservoir functions together with echocardiographic signs of LV DD were assessed in 63 patients with arterial hypertension and paroxysmal AF. Patients were grouped according to number of signs showing LV DD (annular e’ velocity: septal e’?<?7 cm/s, lateral e’?<?10 cm/s, average E/e’ ratio?>?14, LA volume index >?34 ml/m², peak tricuspid regurgitation velocity?>?2.8 m/s) present. Number of patients with 0 signs – 17, 1 sign – 26, 2 signs – 19. Contractile, conduit and reservoir functions were compared between the groups.

Results

Mean contractile, conduit and reservoir strains in all the patients were???14.14 (± 5.83) %, 15.98 (± 4.85) % and 31.03 (± 7.64) % respectively. Contractile strain did not differ between the groups. Conduit strain was higher in patients with 0 signs compared with other groups (p =?0.016 vs 1 sign of LV DD and p =?0.001 vs 2 signs of LV DD). Reservoir strain was higher in patients with 0 signs compared with other groups (p =?0.014 vs 1 sign of LV DD and p <?0.001 vs 2 signs of LV DD).

Conclusions

The patients with paroxysmal AF and primary arterial hypertension have decreased reservoir, conduit and pump LA functions even in the absence of echocardiographic signs of LV DD. With increasing number of parameters showing LV DD, LA conduit and reservoir functions decrease while contractile does not change. LA conduit and reservoir functions decrease earlier than the diagnosis of LV DD can be established according to the guidelines in patients with primary arterial hypertension and AF.

     

Left atrial enlargement and clinical considerations in patients with or without a residual interatrial shunt after closure of the left atrial appendage with the WATCHMAN™-device

Background

Interventional closure of the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation, high thromboembolic and bleeding risk or bleeding history is an alternative therapeutic strategy to oral anticoagulation. It is not known if the exclusion of the LAA from the blood circulation affects the left atrial volume (LAV) and consequently its prognostic value or the circulatory performance of the heart in humans.

Methods

We aimed to prospectively assess potential changes in baseline LAV, left ventricular ejection fraction (LVEF), NT-proBNP-level and the covered distance in the 6-min walk-test 6 weeks and 6 months after LAA closure with the WATCHMAN? device. We used serial 3-dimensional transthoracic and transesophageal echocardiography to assess LAV, residual interatrial shunt and device performance in 58 consecutive patients with successful LAA closure.

Results

Accurate 3D–echocardiographic data for LAV measurements were evaluable for 51 (91%) patients. Maximum LAV (LAVmax) at baseline was 102.8?±?30.8 ml and increased significantly to 107.7?±?32.8 ml after 6 weeks (p?<?0.01) and 113.5?±?34.2 ml after 6 months (p?<?0.01). Minimal LAV (LAVmin) increased from 76.9?±?29.5 ml at baseline to 81.8?±?30.2 ml after 45 days (p?<?0.01) and 82.1?±?33.3 ml after 6 months (p?<?0.01). Similarly, their indexes to BSA (LAVImax and LAVImin) increased significantly, as well. Patients without a residual left-to-right interatrial shunt showed a significantly higher increase in LAVmax or LAVmin. Baseline LVEF, NT-proBNP-level or the distance covered at the 6-min walk test did not significantly change 6 weeks or 6 months after LAA closure.

Conclusions

LAVmax and LAVmin increase significantly after interventional LAA closure. LA enlargement does not correlate with clinical progression of heart failure. Persistent left-to-right interatrial shunt counteracts the LA enlargement. A reduced LA compliance after exclusion of the LAA from the blood circulation with consecutive increase in LA pressure may be a potential cause of LA enlargement and warrants further investigation.

Trial registration

German Clinical Trials Register ID: DRKS00010768; Registration Date 07.07.2016.

     

A randomized,placebo-controlled clinical trial evaluating the safety and efficacy of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus inadequately controlled by glimepiride and metformin

Background

Type 2 diabetes (T2D) is a progressive disease that often requires a patient to use multiple antihyperglycemic agents to achieve glycemic control with disease progression. Omarigliptin is a once-weekly dipeptidyl peptidase-4 inhibitor. The purpose of this trial was to assess the efficacy and safety of adding omarigliptin to the treatment regimen of patients with T2D inadequately controlled by dual therapy with metformin and glimepiride.

Methods

Patients with T2D and HbA1c ≥7.5% and ≤10.5% while on metformin (≥1500 mg/day) and glimepiride (≥4 mg/day) were randomized to omarigliptin 25 mg once-weekly (N = 154) or placebo (N = 153) for 24 weeks. The primary objective was to assess whether omarigliptin was superior to placebo in reducing HbA1c at Week 24. Secondary objectives were to assess the effects of omarigliptin vs. placebo on FPG and the proportion of subjects attaining HbA1c goals of <7% and <6.5%.

Results

From a mean baseline HbA1c of 8.5% (omarigliptin) and 8.6% (placebo), the least squares (LS) mean change from baseline in HbA1c at Week 24 was ?0.67% in the omarigliptin group and ?0.06% in the placebo group, with a between-group difference (95% CI) of ?0.61% (?0.85, ?0.38). Treatment with omarigliptin resulted in a significantly greater reduction in FPG relative to placebo (LS mean difference [95% CI] -0.9 mmol/L [?1.4, ?0.4]; p < 0.001). The proportion of patients achieving glycemic goals of <7.0% and <6.5% was higher in the omarigliptin group relative to the placebo group. The overall incidences of adverse events (AEs), serious AEs, drug-related AEs and discontinuations were generally similar between treatment groups. The incidence of symptomatic hypoglycemia was 10.5% in the omarigliptin group and 8.5% in the placebo group. Relative to baseline, omarigliptin and placebo treatments were associated with LS mean changes in body weight of ?0.1 kg and ?0.9 kg, respectively.

Conclusion

In patients with T2D and inadequate glycemic control on dual therapy with metformin and glimepiride, compared with placebo, once-weekly omarigliptin provided greater improvement in glycemic control and was generally well tolerated.

Trial registration

ClinicalTrials.gov: NCT01704261, EudraCT Number: 2012-002612-10. Trial Registration Date: October 8, 2012.

     

Comparison of mitral annulus geometry between patients with ischemic and non-ischemic functional mitral regurgitation: implications for transcatheter mitral valve implantation

Background

Transcatheter mitral valve replacement (TMVR) is a new therapeutic option for high surgical risk patients with mitral regurgitation (MR). Mitral valve (MV) geometry quantification is of paramount importance for success of the procedure and transthoracic 3D echocardiography represents a useful screening tool. Accordingly, we sought to asses MV geometry in patients with functional MR (FMR) that would potentially benefit of TMVR, focusing on the comparison of mitral annulus (MA) geometry between patients with ischemic (IMR) and non ischemic mitral regurgitation (nIMR).

Methods

We retrospectively selected 94 patients with severe FMR: 41 (43,6%) with IMR and 53 (56,4%) with nIMR. 3D MA analysis was performed on dedicated transthoracic 3D data sets using a new, commercially-available software package in two moments of the cardiac cycle (early-diastole and mid-systole). We measured MA dimension and geometry parameters, left atrial and left ventricular volumes.

Results

Maximum (MA area 10.7?±?2.5 cm² vs 11.6?±?2.7 cm², p?>?0.05) and the best fit plane MA area (9.9?±?2.3 cm² vs 10.7?±?2.5 cm², p?>?0.05, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid-systolic 3D area (9.8?±?2.3 cm² vs 10.8?±?2.7 cm², p?<?0.05) and perimeter (11.2?±?1.3 cm vs 11.8?±?1.5 cm, p?<?0.05) with longer and larger leaflets, and wider aorto-mitral angle (135?±?10° vs 141?±?11°, p?<?0.05). Conversely, the area of MA at the best fit plane did not differ between IMR and nIMR patients (9?±?1.1 cm² vs 9.9?±?1.5 cm², p?>?0.05).

Conclusions

Patients with ischemic and non-ischemic etiology of FMR have similar maximum dimension, yet systolic differences between the two groups should be taken into account to tailor prosthesis’s selection.

Trial registration

N.A.

     

Sublingual grass allergen specific immunotherapy: a retrospective study of clinical outcome and discontinuation

Background

Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population.

Methods

Patients (n?=?329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy.

Results

207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39?±?11 years (range 19–70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37?±?12 vs. 41?±?11 years, p?<?0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p?=?0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason.

Conclusion

Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

     

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations

Introduction

Elucidating molecular alterations due to mitochondrial Complex I (CI) mutations may help to understand CI deficiency (CID), not only in mitochondriopathies but also as it is caused by drugs or associated to many diseases.

Objectives

CID metabolic expression was investigated in Leber’s hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.

Methods

NMR-based metabolomics analysis was performed in intact skin fibroblasts from LHON patients. It used several datasets: one-dimensional ¹H-NMR spectra, two-dimensional ¹H-NMR spectra and quantified metabolites. Spectra were analysed using orthogonal partial least squares-discriminant analysis (OPLS-DA), and quantified metabolites using univariate statistics. The response to idebenone (IDE) and resveratrol (RSV), two agents improving CI activity and mitochondrial functions was evaluated.

Results

LHON fibroblasts had decreased CI activity (??43%, p?<?0.01). Metabolomics revealed prominent alterations in LHON including the increase of fatty acids (FA), polyunsaturated FA and phosphatidylcholine with a variable importance in the prediction (VIP)?>?1 in OPLS-DA, p?<?0.01 in univariate statistics, and the decrease of amino acids (AA), predominantly glycine, glutamate, glutamine (VIP?>?1) and alanine (VIP?>?1, p?<?0.05). In LHON, treatment with IDE and RSV increased CI activity (+?40 and +?44%, p?<?0.05). IDE decreased FA, polyunsaturated FA and phosphatidylcholine (p?<?0.05), but did not modified AA levels. RSV decreased polyunsaturated FA, and increased several AA (VIP?>?1 and/or p?<?0.05).

Conclusion

LHON fibroblasts display lipid and amino acid metabolism alterations that are reversed by mitochondria-targeted treatments, and can be related to adaptive changes. Findings bring insights into molecular changes induced by CI mutation and, beyond, CID of other origins.

     

Instantaneous wave-free ratio and fractional flow reserve in clinical practice

Objectives

To compare fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) measurements in an all-comer patient population with moderate coronary artery stenoses.

Background

Visual assessment of the severity of coronary artery stenoses is often discordant in moderate lesions. FFR allows reliable functional severity assessment in these cases but requires adenosine-induced hyperaemia with associated additional time, costs and side effects. The iFR is a hyperaemia-independent index.

Methods and results

Between November 2015 and February 2017, 356 consecutive patients were included in whom 515 coronary stenoses were measured using both iFR and FFR. Mean iFR and FFR were 0.90?±?0.09 and 0.86?±?0.08, respectively. iFR correlated well with FFR [r?=?0.75; p?<?0.001]. Receiver operating characteristic analysis identified an area under the curve of 0.92. An iFR-only strategy with a treatment cut-off ≤0.89 revealed a diagnostic classification agreement with the FFR-only strategy in 420 lesions (82%) with a sensitivity of 87%, a specificity of 80%, a positive predictive value of 56% and a negative predictive value of 96%.

Conclusions

Real-time iFR measurements have good negative predictive value compared to FFR, but moderate diagnostic accuracy (82%). It exposes fewer patients to adenosine, reduces procedure time and costs. Further prospective trials are needed to evaluate specific clinical settings, cut-off values and endpoints.

     

Gonadal response after a single-dose stimulation test with recombinant human chorionic gonadotropin (rhCG) in patients with isolated prepubertal cryptorchidism

Background

The evaluation of prepubertal gonadal Leydig cells secretion requires gonadotropin stimulation. Urinary hCG (human chorionic gonadotropin) is currently unavailable in many countries, however, recombinant hCG (rhCG) can be used. Our aim was to evaluate rhCG-stimulated testicular hormones in a group of patients with cryptorchidism.

Methods

We evaluated 31 prepubertal boys (age range, 0.75–9.0 years) presenting with unilateral (n?=?24) or bilateral (n?=?7) cryptorchidism. Patients with other genital abnormalities, previous use of hCG or testosterone or previous surgeries were excluded. Blood samples were obtained at baseline and 7 days after a single subcutaneous dose of rhCG (Ovidrel® 250 mcg) to measure the testosterone, DHT (dihydrotestosterone), AMH (anti-Mullerian hormone), and inhibin B levels.

Results

rhCG stimulation significantly increased testosterone levels from 10 ng/dl to 247.8?±?135.8 ng/dl, increased DHT levels from 4.6?±?0.8 to 32.3?±?18.0 ng/dl, and increased the T/DHT ratio from 2.2?±?0.4 to 8.0?±?3.5. There was also a significant increase in inhibin B (from 105.8?±?65.2 to 132.4?±?56.1 pg/ml; p?<?0.05) and AMH levels (from 109.4?±?52.6 to 152.9?±?65.2 ng/ml; p?<?0.01) after the rhCG stimulation.

Conclusions

In this cohort, hormonal responses can be elicited after the rhCG stimulation test, suggesting that rhCG is a promising stimulation test to replace the urinary hCG test during the evaluation of gonadal Leydig cells function. The clinical applicability and adequate performance of rhCG testing must be investigated in future studies.

     

Cardiac shockwave therapy in patients with chronic refractory angina pectoris

Background

Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT.

Methods

We included 33 patients (mean age 70?±?7 years, mean left ventricular ejection fraction 55?±?12?%) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3–7 spots/session, 100 impulses/spot, 0.09 mJ/mm²) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session.

Results

One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p?<?0.01) and the angina symptoms diminished from CCS class III to CCS class II (p?<?0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2?±?7.7?% to 56.4?±?9.4?%, p?=?0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4?±?2.8 to 8.8?±?3.6 min p?=?0.015). No clinically relevant side effects were observed.

Conclusion

CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.

     

Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study)

Background

Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTPEH). The objective of this study was to evaluate right heart size and function assessed by echocardiography during long term treatment with riociguat.

Methods

Patients who started riociguat treatment (1.0–2.5?mg tid) within the trials phase II, PATENT, PATENTplus, EAS, CHEST and continued treatment for 3–12?months were included in this study. Echocardiography was analysed off-line at baseline, after 3, 6 and 12?months by investigators who were blinded to clinical data. Last and baseline observation carried forward method (LOCF, BOCF) were performed as sensitivity analysis.

Results

Seventy-one patients (45% PAH, 55% CTEPH; 53.5% female; 60?±?13?years, mean pulmonary arterial pressure 46?±?10?mmHg, mean PVR 700?±?282dynes·sec·cm-5) were included. After 6?months, RA and RV area, RV thickness tricuspid regurgitation velocity showed a significant reduction. After 12?months, patients receiving riociguat therapy showed a significant reduction in right atrial (??2.6?±?4.4?cm2, 95% CI -3.84, ??1.33; p?<?0.001, n?=?49) and right ventricular (RV) area (??3.5?±?5.2?cm2, 95% CI -5.1, ??1.9; p?<?0.001; n?=?44), RV thickness (??0.76?±?2.2?mm, 95% CI -1.55, 0.03; n?=?32), and a significant increase in TAPSE (2.95?±?4.78?mm, 95% CI 1.52, 4.39; n?=?45) and RV fractional area change (8.12?±?8.87?mm, 95% CI 4.61, 11.62; n?=?27).Both LOCF and BOCF showed similar results but lower effect sizes.

Conclusion

Patients under long-term treatment with riociguat show significantly reduced right heart size and improved RV function in PAH and CTEPH. Further controlled prospective studies are needed to confirm these results.

     

Bile acid quantification of 20 plasma metabolites identifies lithocholic acid as a putative biomarker in Alzheimer’s disease

Introduction

There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. Liquid chromatography–mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.

Objectives

The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.

Methods

Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.

Results

Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50?±?6 nM, p?=?0.004) compared to healthy controls (32?±?3 nM). Lithocholic acid plasma levels of MCI patients (41?±?4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p?<?0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8–9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.

Conclusion

In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.

     

The ability of left ventricular end-diastolic volume variations measured by TEE to monitor fluid responsiveness in high-risk surgical patients during craniotomy: a prospective cohort study

Background

This study was aimed to evaluate the ability of left ventricular end-diastolic volume variations (LVEDVV) measured by transesophageal echocardiography (TEE) compared with stroke volume variation (SVV) obtained by the FloTrac/Vigileo monitor to predict fluid responsiveness, in patients undergoing craniotomy with goal direct therapy.

Methods

We used SVV obtained by the FloTrac/Vigileo monitor to manage intraoperative hypotension in adult patients undergoing craniotomy (ASA III – IV) after obtaining IRB approval and informed consent. The LVEDVV were measured by TEE through the changes of left ventricular short diameter of axle simultaneously. When cardiac index (CI)?≤?2.5 and SVV?≥?15%, comparisons were made between the two devices before and after volume expansion.

Results

We enrolled twenty-six patients referred for craniotomy in this study and 145 pairs of data were obtained. Mean Vigileo-SVV and TEE-LVEDVV were 17.8?±?2.78% and 22.1?±?7.25% before volume expansion respectively, and were 10.95?±?2.8% and 13.58?±?3.78% after volume expansion respectively (P <?0.001). The relationship between Vigileo-SVV and TEE-LVEDVV was significant (r2?=?0.55; p <?0.001). Agreement between Vigileo-SVV and TEE-LVEDVV was 3.3%?±?3.9% (mean bias ± SD, Bland-Altman).

Conclusions

For fluid responsiveness of patients during craniotomy in ASA III-IV, LVEDVV measured by left ventricular short diameter of axle using M type echocaidiographic measurement seems an acceptable monitoring indicator. This accessible method has promising clinical applications in situations where volume and cardiac function monitoring is of great importance during surgery.

Trial registration

Chinese Clinical Trial Registry, ChiCTR-TRC-13003583, August 20, 2013.

     

Layer-specific strain analysis in patients with suspected stable angina pectoris and apparently normal left ventricular wall motion

Background

Non-invasive imaging tests are widely used in the evaluation of stable angina pectoris (SAP). Despite these tests, non-significant coronary lesions are not a rare finding in patients undergoing elective coronary angiography (CAG). Two-dimensional (2D) speckle tracking global longitudinal strain (GLS) imaging is a more sensitive and accurate technique for measuring LV function than conventional 2D methods. Layer-specific strain analysis is a relatively new method that provides endocardial and epicardial myocardial layer assessment. The aim of the present study was to evaluate longitudinal layer-specific strain (LSS) imaging in patients with suspected SAP.

Methods

Patients who underwent CAG for SAP were retrospectively screened. A total of 79 patients with no history of heart disease and wall motion abnormalities were included in the study. Forty-three patients with coronary lesions >?70% constituted the coronary artery disease (CAD) group and 36 patients without significant CAD constituted the control group. Layer-specific GLS transmural, endocardium, and epicardium values (GLS-trans, GLS-endo, and GLS-epi, respectively) were compared between the groups.

Results

Patients in the CAD group had significantly lower GLS values in all layers (GLS-trans: -18.2 + 2.4% vs -22.2 + 2.2% p?<?.001; GLS-endo: -20.8 + 2.8% vs -25.3 + 2.6%, p?<?.001; GLS-epi: 15.9 + 2.4% vs -19.5 + 1.9%, p?<?.001). Multivariate adjustment demonstrated GLS-trans as the only independent predictor of CAD [OR:0.472, CI (0.326–0.684), p?<?.001]. Additionally, the GLS values were all lower in myocardial perfusion scintigraphy (MPS) true-positive patients compared with MPS false-positive patients (GLS-trans: -17.7?±?2.4 vs. -21.9?±?2.4%, p?<?.001; GLS-endo: -20.2?±?2.9% vs -24.9?±?2.9%, P?<?.001; GLS-epi: 15.4?±?2.6% vs. -19.2?±?1.8%, P?<?.001).

Conclusion

Resting layer-specific strain as assessed by 2D speckle tracking analysis demonstrated that GLS values were reduced in all layers of myocardium with SAP and with no wall motion abnormalities. LSS analysis can improve the identification of patients with significant CAD but further prospective larger scale studies are needed to put forth the incremental value of LSS analysis over transmural GLS.

     

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis,tricarboxylic acid and urea metabolism

Background

Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet.

Objectives

We aimed to study the effects of interventional LAAC on systemic metabolism.

Methods

Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ? p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1).

Results

During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta ?0.19, p?<?0.01) and the increase of sarcosine (beta 0.16, p?<?0.01).

Conclusions

Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

     

The usefulness of the McGrath MAC laryngoscope in comparison with Airwayscope and Macintosh laryngoscope during routine nasotracheal intubation: a randomaized controlled trial

Background

McGrath MAC video laryngoscope offers excellent laryngosopic views and increases the success rate of orotracheal intubation in some cases. The aim of this study was to determine the usefulness of McGrath MAC for routine nasotracheal intubation by comparing McGrath MAC with Airway scope and Macintosh laryngoscope.

Methods

A total of 60 adult patients with ASA physical status class 1 or 2, aged 20–70 years were enrolled in this study. Patients were scheduled for elective oral surgery under general anesthesia with nasotracheal intubation. Exclusion criteria included lack of consent and expected difficult airway. Patients were randomly allocated to three groups: McGrath MAC (n?=?20), Airway scope (n?=?20), and Macintosh laryngoscope (n?=?20). After induction, nasotracheal intubation was performed by six expert anesthesiologists with more than 6 years of experience.

Results

There were no significant differences in preoperative airway assessment among the three groups. Successful tracheal intubation time was 26.8?±?5.7 (mean?±?standard deviation) s for McGrath MAC, 36.4?±?11.0 s for Airway scope, and 36.5?±?8.9 s for Macintosh laryngoscope groups. The time for successful tracheal intubation for McGrath MAC group was significantly shorter than that for Airway scope and Macintosh laryngoscope (p?<?0.01). McGrath MAC significantly improved the Cormack Lehane grade for nasotracheal intubation compared with Macintosh laryngoscope (p?<?0.05).

Conclusion

McGrath MAC significantly facilitates routine nasotracheal intubation compared with Airwayscope and Macintosh laryngoscope by shortening the tracheal intubation time and improving the Cormack Lehane grade.

Trial registration

UMINCTR Registration number UMIN000023506. Registered 5 Aug 2016.