Electrocardiographic Diagnosis of Biventricular Pacing in Patients with Nonapical Right Ventricular Leads

Background: Assessment of left ventricular (LV) capture is of paramount importance in patients with biventricular (BiV) pacing. Our goal was to identify electrocardiographic features that differentiate between BiV and right ventricular (RV)‐only pacing in patients with nonapical RV leads. Methods: The study enrolled 300 consecutive patients with BiV devices and nonapical RV leads, and obtained from them 558 electrocardiograms with either BiV pacing (n = 300) or RV‐only pacing (n = 258). RV pacing served as a surrogate for loss of LV capture. Electrocardiograms from the first 150 patients were used to identify BiV‐specific features, and to construct an algorithm to differentiate between BiV and RV‐only pacing. Electrocardiograms from the second 150 patients were used to validate the algorithm. Results: The following electrocardiographic features typical of BiV pacing were identified: QS in lead V6 (specificity = 98.7%, sensitivity = 54.7%), dominant R in lead V1 (specificity = 100%, sensitivity = 23.3%), q in lead V6 (specificity = 96%, sensitivity = 22.7%), and a QRS < 160 ms (specificity = 100%, sensitivity = 66.0%). The algorithm based on those features was found to have an overall diagnostic accuracy of 95.0%, a specificity of 96.0%, and a sensitivity of 93.5%. Conclusions: The study identified QRS features that were very specific for BiV pacing in patients with nonapical RV leads. Sequential arrangement of those features resulted in an algorithm that was very accurate for differentiating between BiV pacing and loss of LV capture. (PACE 2012; 35:1199–1208)     

The genetic influences on oxycodone response characteristics in human experimental pain

Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu‐, kappa‐ and delta‐opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single‐nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.     

A population analysis of the DGAT1 inhibitor GSK3008356 and its effect on endogenous and meal‐induced triglyceride turnover in healthy subjects

Non‐alcoholic steatohepatitis (NASH) is a liver disease in which fatty infiltration is accompanied by liver inflammation. GSK3008356 is under development as a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme involved in the formation of triglyceride (TG). Decreased DGAT1 activity can reduce circulating TG and liver TG, and therefore could potentially prevent or treat NASH. The aim of the current study was to develop a population pharmacokinetic–pharmacodynamic (PKPD) model that characterizes the PK disposition of GSK3008356 and its relation to the changes in blood TG. Drug concentrations were measured in 104 healthy adults receiving various single (SD) and repeat doses (RD) in a first time in human (FiH) study. A 30% fat meal was given at hour 2 postdose, and blood postprandial TG concentrations were measured at various time points. The population PKPD model consists of several parts including a PK model, drug effect model, meal effect model, and a turnover model. The pharmacokinetic data were described using a 3‐compartment model. Drug effect was described by an inhibitory sigmoidal Emax model. Since TG levels change with the introduction of a meal, a bi‐exponential meal effect model was utilized. The total change in TG was fitted using a turnover model with drug and meal effects on the TG production rate. The current analysis presents a PKPD modeling strategy of time‐varying TG data coming from both endogenous and exogenous sources. In general, the presented model could be utilized in the model‐based drug development of drugs that influence TG levels in blood.     

The correlation between SNPs within the gene of adrenergic receptor and neuropeptide Y and risk of cervical vertigo

Background

The current investigation was aimed to explore the potential associations of SNPs within ADRB2, ADRB1, NPY, and ADRA1A with risk and prognosis of cervical vertigo.

Methods

Altogether 216 patients with cervical vertigo and 204 healthy controls were gathered, and their DNAs were extracted utilizing the whole‐blood DNA extraction kit. Besides, the PCR reactions were conducted using the TaqMan^R single nucleotide polymorphism (SNP) genotyping assays, and the SNPs were detected on the 7900HT real‐time fluorogenic quantitative polymerase chain reaction (PCR) instrument. Finally, the severity of cervical vertigo was classified according to the JOA scoring, and the recovery rate (RR) of cervical vertigo was calculated in light of the formula as:

Results

The SNPs within ADRA1A [rs1048101 (T>C) and rs3802241 (C>T)], NPY [rs16476 (A>C), rs16148 (T>C), and rs5574 (C>T)], ADRB1 [rs28365031 (A>G)] and ADRB2 [rs2053044 (A>G)] were all significantly associated with regulated risk of cervical vertigo (all P < .05). Haplotypes of ADRA1A [CT and TC] and NPY [CCT and ATT] were also suggested as the susceptible factors of cervical vertigo in comparison with other haplotypes. Furthermore, the SNPs within ADRA1A [rs1048101 (T>C)], NPY [rs16476 (A>C), rs16148 (T>C)], as well as ADRB1 [rs28365031 (A>G)] all appeared to predict the prognosis of cervical vertigo in a relatively accurate way (all P < .05). Ultimately, the haplotypes of ADRA1A (CC) and NPY (CCT) tended to decrease the RR.

Conclusions

The SNPs within ADRB2, ADRB1, NPY, and ADRA1A might act as the diagnostic biomarkers and treatment targets for cervical vertigo.

     

Single Transseptal Big Cryoballoon Pulmonary Vein Isolation using an Inner Lumen Mapping Catheter

Background: The single big cryoballon technique for pulmonary vein isolation (PVI) has been limited by the need for two transseptal punctures (TP). We therefore investigated feasibility and safety of a simplified approach using a single TP and a novel circumferential mapping catheter (CMC). Methods: Patients underwent 28‐mm cryoballoon PVI using a single TP. The CMC (Achieve^© Medtronic Inc., Minneapolis, MN, USA) served as (1) guidewire and (2) as a PV mapping tool. Primary endpoint was PVI without switching to a regular guidewire. Secondary endpoints included: (1) PV signal quality during freezing, (2) time to PVI, (3) classification of successful ablation technique, (4) complications, and (5) procedural data. Results: A total of 32 patients (126 PVs) were studied (mean age: 62 ± 11 years, 24 males, left atrium: 40 ± 4 mm). The primary endpoint was achieved in 29/32 patients (91%) and 123/126 PVs (98%) with a procedure and fluoroscopy time of 126 ± 26 minutes and 18.9 ± 7.5 minutes, respectively. Real‐time visualization of PVI could be observed in 61/126 (48%) PVs. Time to sustained PVI versus nonsustained PVI was 66 ± 56 seconds versus 129 ± 76 seconds (P < 0.001). One phrenic nerve palsy was observed. After a follow‐up of 250 ± 84 days 23/32 patients (72%) remained in sinus rhythm. Conclusion: The “simplified single big cryoballoon” PVI strategy appears to be safe and feasible. However, real‐time PV recording was achieved in <50% of PVs. Therefore, further catheter refinements are warranted. (PACE 2012; 35:1304–1311)     

Early‐onset hypoparathyroidism and chronic keratitis revealing APECED

Early diagnosis of potentially life‐threatening autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) is crucial, but is often delayed due to the clinical heterogeneity of the disorder. Even in the absence of the classic disease triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency, a diagnosis of APECED should be considered in children who have hypoparathyroidism and chronic keratitis, with a past medical history showing a mild and transient Candida infection.     

The ECG Lead I Paradox in Cardiac Resynchronization Therapy

Background: In cardiac resynchronization therapy (CRT), the morphology of the QRS complex plays an important role in the determination of the pacing site and effectiveness of stimulation. Patients and Methods: Review of the electrocardiograms (ECGs) of 737 patients with a CRT device showed a negative QRS complex in lead I during right ventricular (RV) pacing and a positive QRS complex during left ventricular (LV) pacing in four patients. The RV lead was positioned in the high RV septum and the coronary sinus leads in a posterior or postero‐lateral basal level. Reversed ECG lead or pacemaker lead connection, anodal RV stimulation, and scar tissue‐related depolarization abnormalities were excluded as possible causes. Conclusion: Pacing from the high RV septum may rarely lead to a negative QRS complex and basal positions of the LV lead to a positive QRS complex in lead I during LV pacing. The lead I paradox becomes obvious when both phenomena, that are not interrelated, are present in the same patient.     

HIV‐associated pulmonary arterial hypertension: from bedside to the future

Pulmonary arterial hypertension (PAH) is a life‐threatening complication of HIV infection. The prevalence of HIV‐associated PAH (HIV‐PAH) seems not to be changed over time, regardless of the introduction of highly active antiretroviral therapy (HAART). In comparison with the incidence of idiopathic PAH in the general population (1–2 per million), HIV‐infected patients have a 2500‐fold increased risk of developing PAH. HIV‐PAH treatment is similar to that for all PAH conditions and includes lifestyle changes, general treatments and specific treatments.