Lack of Effect of Nitrates on Exercise Stress Test Results in Patients with Microvascular Angina

Purpose

To assess the effects of short-acting nitrates on exercise stress test (EST) results and the relation between EST results and coronary blood flow (CBF) response to nitrates in patients with microvascular angina (MVA).

Methods

We completed 2 symptom/sign limited ESTs on 2 separate days, in a random sequence and in pharmacological washout, in 29 MVA patients and in 24 patients with obstructive coronary artery disease (CAD): one EST was performed without any intervention (control EST, C-EST), and the other after sublingual isosorbide dinitrate, 5 mg (nitrate EST, N-EST). CBF response to nitroglycerin (25 μg) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography.

Results

At C-EST. ST-segment depression ≥1 mm (STD) was induced in 26 (90 %) and 23 (96 %) MVA and CAD patients, respectively (p?=?0.42), whereas at N-EST, STD was induced in 25 (86 %) and 14 (56 %) MVA and CAD patients, respectively (p?=?0.01). Time and rate pressure product at 1 mm STD increased during N-EST, compared to C-EST, in CAD patients (475?±?115 vs. 365?±?146 s, p?<?0.001; and 23511?±?4352 vs. 20583?±?6234 bpm?mmHg, respectively, p?=?0.01), but not in MVA patients (308?±?160 vs. 284?±?136 s; p?=?0.19; and 21290?±?5438 vs. 20818?±?4286 bpm?mmHg, respectively, p?=?0.35). In MVA patients, a significant correlation was found between heart rate at STD during N-EST and CBF response to nitroglycerin (r?=?0.40, p?=?0.04).

Conclusions

Short-acting nitrates improve EST results in CAD, but not in MVA patients. In MVA patients a lower nitrate-dependent coronary microvascular dilation may contribute to the lack of effects of nitrates on EST results.     

Early cardiovascular remodelling in Fabry disease

Aims

Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH).

Methods and results

This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) without LVH (n?=?19). A group of control subjects (n?=?19) matched for age, sex, body mass index and cardiovascular risk factors were also included. All subjects underwent echocardiography, carotid ultrasound scan, endothelial flow-mediated dilatation (FMD) and nailfold capillaroscopy (NFC) assessment. When compared to the subjects in the control group, FDMC patients showed significantly lower mean values of systolic myocardial velocity (7.33?±?1.28 vs. 10.08?±?1.63 cm/s, p?<?0.0001), longitudinal systolic strain (?18.07?±?1.72 vs. ?21.15?±?2.22 %, p?<?0.0001), significantly higher E/E’ mean values (7.15?±?1.54 vs. 5.98?±?1.27, p?=?0.016) and intima-media thickness mean values (0.80?±?0.20 vs. 0.61?±?0.19 mm, p?=?0.005), significantly lower FMD (8.3?±?4.6 vs. 12.2?±?5.0 %, p?=?0.02), more atypical capillaries and irregular NFC architecture in FDMC than control subjects (52.6 vs. 0 %, p?<?0.0001; 78.9 vs. 36.8 %, p?=?0.02 respectively).

Conclusions

FD progressively involves cardiac, macrovascular and microvascular systems in an early stage. These features are present even in asymptomatic mutation carriers without LVH.     

Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity

Aims/hypothesis

Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity.

Methods

Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined.

Results

Maternal insulin increased from a fasting level of 67?±?25 pmol/l (mean ± SD) to 918?±?492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4?±?0.3 to 7.4?±?1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297?±?99 to 235?±?84 ms (p?=?0.01) and then remained stable until 120 min (235?±?84 vs 251?±?91 ms, p?=?0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r?=?0.68, p?=?0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283?±?79 ms) than those of insulin-sensitive mothers (178?±?46 ms, p?=?0.03).

Conclusions/interpretation

Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.     

Effects of calcium–vitamin D co-supplementation on glycaemic control,inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial

Aims/hypothesis

This study was designed to assess the effects of calcium and vitamin D supplementation on the metabolic status of pregnant women with gestational diabetes mellitus (GDM).

Methods

This randomised placebo-controlled trial was performed at maternity clinics affiliated to Kashan University of Medical Sciences, Kashan, Iran. Participants were 56 women with GDM at 24–28 weeks’ gestation (18 to 40 years of age). Subjects were randomly assigned to receive calcium plus vitamin D supplements or placebo. All study participants were blinded to group assignment. Individuals in the calcium–vitamin D group (n?=?28) received 1,000 mg calcium per day and a 50,000 U vitamin D₃ pearl twice during the study (at study baseline and on day 21 of the intervention), and those in the placebo group (n?=?28) received two placebos at the mentioned times. Fasting blood samples were taken at study baseline and after 6 weeks of intervention.

Results

The study was completed by 51 participants (calcium–vitamin D n?=?25, placebo n?=?26). However, as the analysis was based on an intention-to-treat approach, all 56 women with GDM (28 in each group) were included in the final analysis. After the administration of calcium plus vitamin D supplements, we observed a significant reduction in fasting plasma glucose (?0.89?±?0.69 vs +0.26?±?0.92 mmol/l, p?p?=?0.02) and HOMA-IR (?0.91?±?1.18 vs +0.63?±?2.01, p?=?0.001) and a significant increase in QUICKI (+0.02?±?0.03 vs ?0.002?±?0.02, p?=?0.003) compared with placebo. In addition, a significant reduction in serum LDL-cholesterol (?0.23?±?0.79 vs +0.26?±?0.74 mmol/l, p?=?0.02) and total cholesterol: HDL-cholesterol ratio (?0.49?±?1.09 vs +0.18?±?0.37, p?=?0.003) and a significant elevation in HDL-cholesterol levels (+0.15?±?0.25 vs ?0.02?±?0.24 mmol/l, p?=?0.01) was seen after intervention in the calcium–vitamin D group compared with placebo. In addition, calcium plus vitamin D supplementation resulted in a significant increase in GSH (+51.14?±?131.64 vs ?47.27?±?203.63 μmol/l, p?=?0.03) and prevented a rise in MDA levels (+0.06?±?0.66 vs +0.93?±?2.00 μmol/l, p?=?0.03) compared with placebo.

Conclusions/interpretation

Calcium plus vitamin D supplementation in women with GDM had beneficial effects on their metabolic profile.

Trial registration

www.irct.ir IRCT201311205623N11

Funding

The study was supported by a grant (no. 92110) from Kashan University of Medical Sciences.     

Genetics correlates with lung function and nocturnal ventilation in myotonic dystrophy

Background

Dystrophia myotonica (DM) is the most frequent adult-onset muscular dystrophy. Type 1 is caused by the cytosine–thymine–guanine (CTG) repeat expansion in the DM protein kinase gene. Respiratory muscle weakness and altered central ventilatory control lead to hypercapnia and lung volume restriction.

Purpose

This study aims to review the respiratory involvement in DM patients and study its relation with genetics.

Methods

Retrospective study of patients with DM referred for respiratory assessment was made. Noninvasive ventilation (NIV) was considered to daytime hypercapnia or symptoms of nocturnal hypoventilation.

Results

Forty-two consecutive patients (37.9?±?13.6 years) were evaluated. Mean CTG length was 642.8?±?439.2 repeats. In the first evaluation, mean forced vital capacity (FVC) was 74.4?±?20.2 %, maximal expiratory pressure (MEP) 35?±?16 %, maximal inspiratory pressure 52?±?23 %, peak cough flow (PCF) 327.3?±?97.7 L/min, arterial pressure of oxygen 79.7?±?11.3 mmHg, arterial pressure of carbon dioxide 45.5?±?6.2 mmHg, overnight minimal peripheral oxygen saturation (SpO₂) 79.6?±?11.6 %, and apnea–hypopnea index 13.9?±?9.9. CTG length was found to be related with MEP (r?=??0.67; p?=?0.001) and SpO₂ (r?=??0.37; p?=?0.039). NIV was started in 25 patients. Ventilated patients had lower FVC (2.19 to 3.21 L; p?<?0.001) and PCF (285.3 to 388.5 L/min; p?=?0.003) and more CTG repeats (826.6 to 388.5 repeats; p?=?0.02). NIV compliance was poor in seven patients (28 %) and related with hypercapnia (r?=?0.87; p?=?0.002) and inspiratory positive airway pressure setting (r?=?0.65; p?=?0.009). Ventilation improved symptoms and nocturnal hypoventilation. Comparing the first and last evaluations, only PCF was significantly lower (275.0 to 310.8 L/min; p?=?0.019).

Conclusions

Ventilatory insufficiency is very common in patients with DM and CTG length may be useful to predict it. Prolonged NIV improves symptoms, nocturnal hypoventilation and maintains daily blood gases. Routine evaluation of PCF should not be forgotten and assisted coughing training provided.     

Incidence,predictors, and clinical course of atrial tachyarrhythmias in patients with pulmonary hypertension

Background

The prevalence and predictors of atrial tachyarrhythmias (ATa) in patients with pulmonary hypertension (PH) is less well understood.

Methods

We performed a retrospective study including 311 patients with PH, confirmed by right heart catheterization in our center between 2007 and 2011. Baseline characteristics, clinical, echocardiographic, and hemodynamic data were collected and compared between patients with and without ATa.

Results

The mean age was 61?±?13 years with 64 % females. The mean pulmonary artery pressure (mPAP) was 46?±?20 mmHg, mean left ventricular ejection fraction (LVEF) was 55?±?13 %, and mean pulmonary capillary wedge pressure (PCWP) was 19?±?9 mmHg. Of the 311 patients with PH, 121 (39 %) patients had ATa. Patients with ATa were older (p?p?=?0.03), diabetes (p?=?0.015), coronary artery disease (p?p?p?=?0.001), impaired LVEF (p?=?0.02), and left atrial enlargement (p?p?=?0.022). In multivariate analysis using Cox-proportional hazard model, the independent predictors of mortality were age (HR 1.05; p?=?0.003), coronary artery disease (HR 2.34; p?=?0.047), LVEF (HR 0.793; p?=?0.023), and mPAP (HR 1.023; p?=?0.003).

Conclusion

ATa are common in patients with PH. Left heart disease, left atrial enlargement, and elevated PCWP but not right atrial enlargement or mPAP predict the occurrence of ATa in patients with PH.     

The effect of continuous positive airway pressure therapy on blood pressure and arterial stiffness in hypertensive patients with obstructive sleep apnea

Aim

We aimed to evaluate the effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) and arterial stiffness in hypertensive patients with obstructive sleep apnea (OSA).

Patients and methods

We studied 38 hypertensive patients who suffered from severe OSA. Ambulatory BP measurement was performed at baseline and after at least 3 months of uninterrupted CPAP therapy. In 19 of these patients, we also measured pulse wave velocity (PWV) at baseline, after the first night of CPAP therapy and at 3 months. Fifteen normotensive subjects without OSA comprised the control group.

Results

CPAP therapy reduced systolic BP from 141.5?±?12.1 to 133.5?±?9.7 mmHg (p?=?0.007) and diastolic BP from 87.8?±?6.8 to 83?±?5.4 mmHg (p?=?0.004). CPAP also reduced the PWV from 8.81?±?1.4 to 8.18?±?1 m/s after the first night of CPAP therapy (p?=?0.003) and to 7.37?±?1 m/s at 3 months (p?=?0.007).

Conclusions

To the best of our knowledge, this is the first study demonstrating that CPAP therapy in hypertensive patients with OSA improves arterial stiffness from the first night and that this favorable effect is maintained for at least 3 months of CPAP use. A reduction in BP was also observed, even though BP control was not always achieved.     

Insulin pump use in pregnancy is associated with lower HbA1c without increasing the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1 diabetes

Aims/hypothesis

The aim of this study was to compare glycaemic control and maternal–fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI).

Methods

In a retrospective study, glycaemic control and outcomes of 387 consecutive pregnancies in women with type 1 diabetes who attended specialised clinics at three centres 2006–2010 were assessed.

Results

Women using insulin pumps (129/387) were older and had a longer duration of diabetes, more retinopathy, smoked less in pregnancy, and had more preconception care (p?<?0.01 for each). Among 113 pregnancies >20 weeks’ gestation in women on insulin pumps and 218 in women on MDI, there was a significant difference in HbA_1c in the first trimester (mean HbA_1c 6.90?±?0.71% (52?±?7.8 mmol/mol) vs 7.60?±?1.38% (60?±?15.1 mmol/mol), p?<?0.001), which persisted until the third trimester (mean HbA_1c 6.49?±?0.52% (47?±?5.7 mmol/mol) vs 6.81?±?0.85% (51?±?9.3 mmol/mol), p?=?0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs MDI (1.8% vs 3.0%, p?=?0.72). Despite lower HbA_1c, women on insulin pumps did not have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p?=?0.90) or more weight gain (16.3?±?8.7 vs 15.2?±?6.2 kg, p?=?0.18). More large-for-gestational-age infants in the pump group (55.0% vs 39.2%, p?=?0.007) may have resulted from confounding by parity.

Conclusions/interpretation

In this large multicentre study, women using insulin pumps in pregnancy had lower HbA_1c without increased risk of severe hypoglycaemia or diabetic ketoacidosis but no improvement in other pregnancy outcomes. This information can help inform care providers and patients about the glycaemic effectiveness and safety of insulin pumps in pregnancy.     

Robotic ablation of atrial fibrillation with a new remote catheter system

Purpose

Pulmonary vein isolation (PVI) is widely established as a curative treatment option for atrial fibrillation (AF). A wide range of techniques to improve catheter manipulation and steerability has been developed over the past years. A new remote catheter system (RCS) has recently become available (Amigo Remote Catheter System, Catheter Robotics, Budd Lake, NJ, USA). Here, we present a dual-center study on the RCS for left atrial mapping and PVI in patients with paroxysmal AF compared to a control group undergoing conventional PVI.

Methods

One hundred nineteen patients who underwent PVI for paroxysmal AF were studied. Forty patients underwent PVI with the use of the RCS. Seventy-nine patients, who underwent conventional PVI, served as control group. Procedural data were compared between the two groups.

Results

PVI was achieved in all patients. In the RCS group compared to standard ablation group, there were no significant differences in procedure duration (159.1?±?45.4 vs. 146?±?30.1 min, p?=?0.19), total energy delivery (78,146.3?±?26,992.4 vs. 87,963.9?±?79,202.1 Ws, p?=?0.57), and total fluoroscopy time (21.2?±?8.6 vs. 23.9?±?5.4 min, p?=?0.15). Operator fluoroscopy exposure was significantly reduced in the RCS group (13.4?±?6.1 vs. 23.9?±?5.4 min, p?Conclusions These initial results suggest that left atrial mapping and PVI are feasible with the use of the Amigo RCS. Acute procedural efficacy is comparable to the standard approach. The use of the Amigo RCS leads to a significant reduction of operator fluoroscopy exposure.     

Electrocardiographic P wave changes after thoracoscopic pulmonary vein isolation for atrial fibrillation

Background

Changes in P wave duration (PWD) and P wave area (PWA) have been described following catheter ablation for atrial fibrillation (AF). We hypothesize that video-assisted thoracoscopic pulmonary vein isolation (VATS-PVI) for AF results in decrease of PWD, PWA and P wave dispersion, which may resemble reverse electrical remodeling of the atrium after restoration of sinus rhythm.

Methods

VATS-PVI consisted of PVI and ganglionic plexus ablation in 29 patients (mean age, 59?±?7 years; 23 males; 17 paroxysmal AF) and additional left atrial lesions in patients with persistent AF. PWD and PWA were measured in ECG lead II, aVF and V2 of ECGs during sinus rhythm before, directly after, and 6 months postprocedure. P wave dispersion was derived from the 12 lead ECG.

Results

Prior to VATS-PVI, PWD did not correlate with left atrial size and no difference in left atrial size was found between patients with paroxysmal or persistent AF (p?=?0.27). Following VATS-PVI, PWD initially prolonged in all patients from 115?±?4.6 ms to 131?±?3.6 ms (p?<?0.01) but shortened to 99?±?3.2 ms after 6 months (p?<?0.01). PWA was 5.60?±?0.32 mV*ms at baseline, 6.44?±?0.32 mV*ms post-VATS-PVI (P?=?NS), and 5.40?±?0.28 mV*ms after 6 months (p?=?NS vs. baseline, p?<?0.05 vs. post-VATS-PVI). P wave dispersion decreased in the persistent AF group from baseline 67?±?3.3 to 64?±?2.5 ms post-VATS-PVI (p?=?0.30) and to 61?±?3.4 ms after 6 months (p?<?0.05).

Conclusions

PWD increases significantly directly after successful VATS-PVI in both groups. There was significant decrease in PWD after 6 months. Similarly, P wave dispersion decreased in the persistent group. These changes suggest an immediate procedure related effect, but the later changes may represent reverse electrical atrial remodeling following cessation of AF.     

Effects of obstructive sleep apnea severity on serum lipid levels in Greek children with snoring

Background

Although obstructive sleep apnea (OSA) is related to dyslipidemia in adults, limited data are available regarding its effects on serum lipids during childhood. Aim of this study was to assess the potential relationships between severity of OSA and cholesterol or triglyceride levels in a cohort of Greek children.

Methods

Data from children with snoring who underwent polysomnography and complete serum lipids measurements during a specified study period were analyzed retrospectively.

Results

Overall, obese children (n?=?261) had lower HDL cholesterol levels than non-obese subjects (n?=?113) (49.6?±?10.5 vs. 53.9?±?11.4 mg/dL; p?=?0.001) and higher triglyceride concentrations (69.8?±?32.2 vs. 63.2?±?27 mg/dL; p?=?0.041). Non-obese subjects with moderate-to-severe OSA did not differ in triglycerides, total, and LDL cholesterol concentrations but had lower HDL cholesterol, when compared to non-obese children with primary snoring/mild OSA (50.4?±?13.1 vs. 54.9?±?10.7 mg/dL; p?=?0.008). The risk for having low HDL cholesterol (??40 mg/dL) was threefold higher in non-obese subjects with moderate-to-severe OSA than in those with primary snoring/mild OSA, even after adjustment for age and gender [OR?=?3.44 (95% CI 1.44 to 8.24; p?=?0.006)]. Concentrations of serum lipids in obese children were not associated with severity of OSA. HDL cholesterol was 48.5?±?8.7 mg/dL in subjects with moderate-to-severe OSA and 50.0?±?11.1 mg/dL in children with primary snoring/mild OSA (p?=?0.519).

Conclusions

HDL cholesterol levels are inversely related to severity of OSA in non-obese children with snoring.     

Warm winter is associated with low incidence of ST elevation myocardial infarctions and less frequent acute coronary angiographies in an alpine country

Background

Weather conditions influence symptoms in chronic stable coronary artery disease (CAD). Whether the ongoing climate change, with continuous and rapid temperature increases, also has an impact on the incidence and outcome of non-ST elevation (NSTEMI) and ST elevation (STEMI) myocardial infarctions referred for acute coronary angiography (CA) is less clear.

Methods

According to weather data from the Institute of Meteorology and Geophysics, Innsbruck University, the 2005/2006 winter was very cold (CW) and the 2006/2007 winter extraordinarily warm (WW). As the overall invasive management of patients with acute coronary syndromes did not change substantially within these winters, we compared patients referred for acute CA suffering an acute STEMI or NSTEMI, their risk factors and in-hospital mortality rates between these two consecutive winters.

Results

As expected, the average temperature was lower (??1.6 vs. +?5.9°C; p?<?0.001) and humidity was higher (82 vs. 79%; p?<?0.012) in CW compared to WW, with no significant differences in other weather conditions (rainfall: 59 vs. 39 days; sunshine: 3.9 vs. 4.3 h/day; air pressure: 713.04 vs. 713.76 hPa). There were no differences in the number of overall CA (987 vs. 983) between these two winters, whereas the number of acute CA (12.9 vs. 10.4% of overall CA; p?=?0.046) and the diagnosis of STEMI as an indication of acute CA (74.0% vs. 62.7%; p?=?0.046) were higher in CW. Furthermore, patients in CW were younger (58.2?±?12.4 vs. 61.7?±?11.7 years; p?<?0.03), had higher LDL cholesterol (134.8?±?44.6 vs. 116.7?±?36.0 mg/dl; p?<?0.003) and were less frequently hypertensives (52.8 vs. 70.6%; p?<?0.01). Other traditional risk factors were not different between WW and CW. In addition, there were no differences in in-hospital mortality rates in invasively diagnosed CAD, patients’ nationalities (Austrians: 78.0 vs. 77.5%) and time from pain to arrival in the cath lab in STEMI patients (3.9?±?3.5 vs. 3.8?±?3.1 h).

Conclusion

The average temperature increase of 7.5°C from the cold to the warm winter was associated with a decrease in acute coronary angiographies, in particular due to a lower incidence of STEMI referred for primary percutaneous intervention.     

In patients with type 1 diabetes simultaneous pancreas and kidney transplantation preserves long-term kidney graft ultrastructure and function better than transplantation of kidney alone

Aims/hypothesis

In patients with type 1 diabetes and end-stage renal disease (ESRD) we aimed to determine whether long-term normoglycaemia, as achieved by successful simultaneous pancreas and kidney (SPK) transplantation, would preserve kidney graft structure and function better than live donor kidney (LDK) transplantation alone.

Methods

Estimated GFR (eGFR) was calculated in SPK (n?=?25) and LDK (n?=?17) recipients in a stable phase 3 months after transplantation and annually during follow-up. Kidney graft biopsies were obtained at follow-up for measurement of glomerular volume (light microscopy), glomerular basement membrane (GBM) and podocyte foot process widths and mesangial volume fraction (electron microscopy).

Results

SPK and LDK recipients were similar in age and diabetes duration at engraftment. Donor age was higher in the LDK group. Median follow-up time was 10.1 years. Mean HbA_1c levels during follow-up were 5.5?±?0.4% (37?±?5 mmol/mol) and 8.3?±?1.5% (68?±?16 mmol/mol) in the SPK and LDK group, respectively (p?p?=?0.008) and increased mesangial volume fraction (median 0.23 [range 0.13–0.59] vs 0.16 [0.10–0.41]; p?=?0.007) at follow-up. Absolute eGFR change from baseline was ?11?±?21 and ?23?±?15 ml min^?1 1.73 m^?2 (p?=?0.060), whereas eGFR slope was ?1.1 (95% CI ?1.7, ?0.5) and ?2.6 (95% CI ?3.1, ?2.1)?ml min^?1 1.73 m^?2 per year in the SPK and LDK group, respectively (p?=?0.001).

Conclusions/interpretation

In patients with type 1 diabetes and long-term normoglycaemia after successful SPK transplantation, kidney graft ultrastructure and function were better preserved compared with LDK transplantation alone.     

Left atrial reverse remodeling and prevention of progression of atrial fibrillation with atrial resynchronization device therapy utilizing dual-site right atrial pacing in patients with atrial fibrillation refractory to antiarrhythmic drugs or catheter ablation

Introduction

Dual-site right atrial pacing (DAP) produces electrical atrial resynchronization but its long-term effect on the atrial mechanical function in patients with refractory atrial fibrillation (AF) has not been studied.

Methods

Drug-refractory paroxysmal (PAF) and persistent AF (PRAF) patients previously implanted with a dual-site right atrial pacemaker (DAP) with minimal ventricular pacing modes (AAIR or DDDR mode with long AV delay) were studied. Echocardiographic structural (left atrial diameter [LAD] and left ventricular [LV] end diastolic diameter [EDD], end systolic diameter [ESD]) and functional (ejection fraction [EF]) parameters were serially assessed prior to, after medium-term (n?=?39) and long-term (n?=?34) exposure to DAP.

Results

During medium-term follow-up (n?=?4.5 months), there was improvement in left atrial function. Mean peak A wave flow velocity increased with DAP as compared to baseline (75?±?19 vs. 63?±?23 cm/s, p?=?0.003). The long-term impact of DAP was studied with baseline findings being compared with last follow-up data with a mean interval of 37?±?25 (range 7–145) months. Mean LAD declined from 45?±?5 mm at baseline to 42?±?7 mm (p?=?0.003). Mean LVEF was unchanged from 52?±?9 % at baseline and 54?±?6 % at last follow-up (p?=?0.3). There was no significant change in LV dimensions with mean LVEDD being 51?±?6 mm at baseline and 53?±?5 mm at last follow-up (p?=?0.3). Mean LVESD also remained unchanged from 35?±?6 mm at baseline to 33?±?6 mm at last follow-up (p?=?0.47). During long-term follow-up, 30 patients (89 %) remained in sinus or atrial paced rhythm as assessed by device diagnostics at 3 years.

Conclusions

DAP can achieve long-term atrial reverse remodeling and preserve LV systolic function. DAP when added to antiarrhythmic drug (AAD) and/or catheter ablation (ABL) maintains long-term rhythm control and prevents AF progression in elderly refractory AF patients. Reverse remodeling with DAP may contribute to long-term rhythm control.     

Assessment of atrial conduction time in patients with polycystic ovary syndrome

Background

Polycystic ovary syndrome (PCOS) is closely related to increased cardiovascular risk in women of reproductive age. Atrial conduction abnormalities in these patients have not been investigated in terms of atrial electromechanical delay measured by tissue Doppler imaging (TDI) as an early predictor of atrial fibrillation development. The aim of this study was to evaluate whether TDI-derived atrial conduction time is prolonged in PCOS.

Methods

The study included 51 patients with PCOS and 48 age-matched healthy controls. P-wave dispersion (PWD) was calculated on the 12-lead surface electrocardiogram. Systolic and diastolic left ventricular (LV) functions, atrial electromechanical coupling, intraatrial and interatrial electromechanical delays were measured with conventional echocardiography and TDI.

Results

PWD was higher in PCOS women (50.45?±?3.7 vs 34.73?±?6.7 ms, p?=?0.008). Interatrial and intraatrial electromechanical delay were found longer in patients with PCOS compared to controls (41.9?±?9.0 vs 22.2?±?6.6 ms, p?p?r?=?0.54, p?C-reactive protein levels (r?=?0.68, p?r?=?0.53, p?r?=?0.31, p?=?0.04; r?=?0.37, p?=?0.021, respectively) and negatively correlated with flow propagation velocity (r?=??0.38, p?=?0.014).

Conclusion

This study shows that atrial electromechanical delay is prolonged in PCOS patients. Atrial electromechanical delay prolongation is related to low-grade inflammation, insulin resistance, and LV diastolic dysfunction in PCOS.     

The relationship between defibrillation threshold and total mortality

Background

The relationship between the defibrillation threshold (DFT) and total mortality is unclear.

Methods

A university hospital prospectively maintained implantable defibrillator (ICD) database identified 508 patients who underwent ICD implantation and had DFT testing performed at implant. Patients were placed in one of three groups based on the implant DFT (high (≥20 J), moderate (19–11 J), or low DFT (≤10 J)).

Results

Sixty-seven patients had a high DFT, 216 had a moderate DFT, and 225 had a low DFT. The mean left ventricular ejection fraction (LVEF) was 0.25, 0.28, and 0.30 in the high, moderate, and low DFT groups, respectively, (p?=?0.04). There were significantly more patients with a subcutaneous electrode in the high DFT group (p?<?0.001), more patients taking amiodarone (p?<?0.001), and more patients on oral anticoagulation (p?=?0.04). There were a total of 140 deaths during the follow-up period (mean 3.2?±?1.7 years). There were 24 deaths in the high DFT group (35.8 %), 62 in the moderate DFT group (28.7 %), and 54 in the low DFT group (24.0 %) (p?=?0.05). Implant DFT was a significant predictor of mortality (p?=?0.01), as was age, LVEF (p?<?0.001), CAD (p?=?0.01), amiodarone use (p?=?0.02), and hematoma at implant (p?=?0.01). An elevated DFT was an independent predictor of mortality after controlling for all significant univariate variables (p?=?0.004).

Conclusions

A high-implant DFT predicts an adverse prognosis, even when an adequate ICD safety margin is present.     

Effects of 12 weeks’ treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study

Aims/hypothesis

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA_1c and cardiovascular risk factors in type 2 diabetes.

Methods

Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n?=?20) or placebo (n?=?21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA_1c and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements.

Results

Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049?±?17,659 vs 27,270?±?32,004 pmol/l × min (p?=?0.838). In the placebo group AUC for insulin decreased from 27,392?±?14,348 pmol/l × min to 22,938?±?11,936 pmol/l × min (p?=?0.002). Esomeprazole treatment (n?=?20) caused a ninefold increase in the AUC for gastrin. HbA_1c increased from 7.0?±?0.6% (53?±?5 mmol/mol) to 7.3?±?0.8% (56?±?6 mmol/mol) in the esomeprazole-treated group and from 7.0?±?0.6% (53?±?5 mmol/mol) to 7.4?±?0.8% (57?±?6 mmol/mol) in the placebo group (n?=?21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p?>?0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p?<?0.05). No change in BP was seen in the patients treated with esomeprazole.

Conclusions/interpretation

Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT00699426

Funding

The study was funded by Novo Nordisk A/S and Christian Hansen A/S.     

Phasic jaw motor episodes in healthy subjects with or without clinical signs and symptoms of sleep bruxism: a pilot study

Background

To investigate the association between each clinical diagnosis criterion for sleep bruxism (SB) and the frequency of jaw motor events during sleep.

Methods

Video-polysomnography was performed on 17 healthy adult subjects (mean age, 26.7?±?2.8 years), with at least one of the following clinical signs and symptoms of SB: (1) a report of frequent tooth grinding, (2) tooth attrition with dentine exposure through at least three occlusal surfaces, (3) morning masticatory muscle symptoms, and (4) masseter muscle hypertrophy. Episodes of rhythmic masticatory muscle activity (RMMA) and isolated tonic activity were scored visually. These variables were compared with regards to the presence or absence of each clinical sign and symptom.

Results

In 17 subjects, 4.0?±?2.5/h (0.1–10.2) RMMA and 1.0?±?0.8/h (0–2.4) isolated tonic episodes were observed (total episodes: 5.0?±?2.4/h (1.2–11.6)). Subjects with self-reported grinding sounds (n?=?7) exhibited significantly higher numbers of RMMA episodes (5.7?±?2.3/h) than those without (n?=?10; 2.8?±?1.8/h) (p?=?0.011). Similarly, subjects with tooth attrition (n?=?6) showed significantly higher number of RMMA episodes (5.6?±?3.1/h) than those without (n?=?11; 3.2?±?1.6/h) (p?=?0.049). The occurrence of RMMA did not differ between the presence and absence of morning masticatory muscle symptoms or muscle hypertrophy.

Conclusions

Clinical signs and symptoms frequently used for diagnosing SB can represent different clinical and physiological aspects of jaw motor activity during sleep.     

Glucocorticoid treatment impairs microvascular function in healthy men in association with its adverse effects on glucose metabolism and blood pressure: a randomised controlled trial

Aims/hypothesis

Glucocorticoids (GCs) are widely used anti-inflammatory agents that frequently induce side effects, including insulin resistance, diabetes and hypertension. Here, we investigated the contribution of microvascular dysfunction to the development of these adverse effects in healthy men.

Methods

In a randomised, placebo-controlled, dose–response intervention study, 32 healthy normoglycaemic men (age: 21?±?2 years; BMI: 21.9?±?1.7 kg/m²) were allocated to receive prednisolone 30 mg once daily (n?=?12), prednisolone 7.5 mg once daily (n?=?12) or placebo (n?=?8) for 2 weeks using block randomisation. A central office performed the treatment allocation, and medication was dispersed by the hospital pharmacy that was also blinded. Treatment allocation was kept in concealed envelopes. Participants, study personnel conducting the measures and assessing the outcome were blinded to group assignment. The study was conducted at a university hospital. Primary endpoint was prednisolone-induced changes in microvascular function, which was assessed by capillary microscopy. Insulin sensitivity was determined by hyperinsulinaemic–euglycaemic clamp and postprandial glycaemic excursions by standardised meal tests.

Results

Compared with placebo, prednisolone 7.5 mg and 30 mg decreased insulin-stimulated capillary recruitment by 9?±?4% and 17?±?3%, respectively (p?<?0.01). In addition, prednisolone 7.5 mg and 30 mg reduced insulin sensitivity (M value) by ?11.4?±?4.5 μmol kg^?1 min^?1 and ?25.1?±?4.1 μmol kg^?1 min^?1 (p?<?0.001) and increased postprandial glucose levels by 11?±?5% and 27?±?9% (p?<?0.001), respectively. Only high-dose prednisolone increased systolic blood pressure (6?±?1.2 mmHg, p?=?0.006). Prednisolone-induced changes in insulin-stimulated capillary recruitment were associated with insulin sensitivity (r?=?+0.76; p?<?0.001), postprandial glucose concentrations (r?=??0.52; p?<?0.03) and systolic blood pressure (r?=??0.62; p?<?0.001). Prednisolone increased resistin concentrations, which were negatively related to insulin-stimulated capillary recruitment (r?=??0.40; p?=?0.03). No effects were noted on adiponectin and leptin concentrations. Prednisolone treatment was well tolerated; none of the participants left the study.

Conclusions/interpretation

Prednisolone-induced impairment of insulin-stimulated capillary recruitment was paralleled by insulin resistance, increased postprandial glucose levels, hypertension and increased circulating resistin concentrations in healthy men. We propose that GC-induced impairments of microvascular function may contribute to the adverse effects of GC treatment on glucose metabolism and blood pressure.

Trial registration

isrctn.org ISRTCN 78149983

Funding

The study was funded by the Dutch Top Institute Pharma T1-106.     

Effect of musculoskeletal pain on sleep architecture in patients with obstructive sleep apnea

Rationale

Obstructive sleep apnea and chronic musculoskeletal pain both affect sleep. Sleep architecture of patients suffering from both is largely unknown.

Objectives

This study seeks to define the sleep architecture of patients with chronic musculoskeletal pain and obstructive sleep apnea.

Methods

Patients with obstructive sleep apnea diagnosed by sleep study during the past 3 years were included. Patients with clinical documentation of chronic musculoskeletal pain constituted cases, while others were classified as controls.

Measurements

Demographics, clinical factors affecting sleep, medications affecting sleep, Epworth sleepiness scores, and polysomnographic parameters; total sleep time, sleep efficiency, sleep stages, rapid eye movement (REM) sleep onset, apnea–hypopnea index, arousal index, and periodic leg movements were recorded.

Results

There were 393 subjects: 200 cases (obstructive sleep apnea and chronic musculoskeletal pain) and 193 controls (obstructive sleep apnea alone). There was significant difference in total sleep time (274.5?±?62.5 vs. 302.2?±?60.1 min, p?=?0.0001), sleep efficiency (73.54?±?15.8 vs. 78.76?±?14.3 %, p?=?0.0003), and REM sleep onset (148.18?±?80.5 vs. 124.8?±?70.9 min, p?=?0.006). Subgroup analysis within the obstructive sleep apnea with chronic musculoskeletal pain group revealed that subjects had better total sleep time and sleep efficiency if they were on REM sleep affecting medications (suppressants and stimulants). Those on REM sleep suppressants slept 25.7 min longer and had 6.4 % more efficient sleep than those not on REM suppressants (p?=?0.0034 and p?=?0.0037).

Conclusion

Patients with obstructive sleep apnea and chronic musculoskeletal pain sleep not only significantly less but also with inferior sleep quality. Their REM sleep is also less in duration and its onset is delayed. Despite low TST and SE, these patients may not exhibit sleepiness.