Clinical outcomes with biventricular versus right ventricular pacing in patients with atrioventricular conduction defects

There have been increasing concerns about the unexpected effects of right ventricular (RV) pacing. We aimed to systematically evaluate the effect of biventricular (BiV) versus RV pacing on clinical events in patients with impaired AV conduction. We searched PubMed, EMBASE, and Cochrane Library for studies comparing BiV pacing with RV pacing in patients with AV block, through April 2017. We selected randomized controlled trials (RCTs) reporting data on mortality, hospitalization for heart failure (HF), and/or 6-min walk distance (6MWD). A total of 12 RCTs were finally included. Pooled analysis suggested that BiV pacing was associated with a significantly reduced all-cause mortality in contrast to RV pacing (risk ratio (RR)?=?0.77, 95% confidence interval (CI) 0.62 to 0.95, I²?=?9.6%). BiV pacing, compared with RV pacing, significantly reduced the rate of HF hospitalization (RR?=?0.74, 95% CI 0.59 to 0.93, I²?=?10.1%). Sensitivity analyses by excluding studies with AV nodal ablation showed that BiV pacing still had a lower mortality and non-significant reduced HF hospitalization. Patients in BiV and RV pacing mode had a similar 6WMD at follow-up (mean difference?=?4.99 m, 95% CI ??11.34 to 21.33 m, I²?=?0%). Meta-regression analysis showed that the effect size of all-cause mortality or HF hospitalization was not significantly associated with mean LVEF value at baseline. In patients with impaired AV conduction that need frequent ventricular pacing, BiV pacing was associated with reduced mortality and hospitalization for HF, compared with traditional RV pacing mode.     

De novo implantation vs. upgrade cardiac resynchronization therapy: a systematic review and meta-analysis

Patients with conventional pacemakers or implanted defibrillators are often considered for cardiac resynchronization therapy (CRT). Our aim was to summarize the available evidences regarding the clinical benefits of upgrade procedures. A systematic literature search was performed from studies published between 2006 and 2017 in order to compare the outcome of CRT upgrade vs. de novo implantations. Outcome data on all-cause mortality, heart failure events, New York Heart Association (NYHA) Class, QRS narrowing and echocardiographic parameters were analysed. A total of 16 reports were analysed comprising 489,568 CRT recipients, of whom 468,205 patients underwent de novo and 21,363 upgrade procedures. All-cause mortality was similar after CRT upgrade compared to de novo implantations (RR 1.19, 95% CI 0.88–1.60, p = 0.27). The risk of heart failure was also similar in both groups (RR 0.96, 95% CI 0.70–1.32, p = 0.81). There was no significant difference in clinical response after CRT upgrade compared to de novo implantations in terms of improvement in left ventricular ejection fraction (ΔEF de novo ? 6.85% vs. upgrade ? 9.35%; p = 0.235), NYHA class (ΔNYHA de novo ? 0.74 vs. upgrade ? 0.70; p = 0.737) and QRS narrowing (ΔQRS de novo ? 9.6 ms vs. upgrade ? 29.5 ms; p = 0.485). Our systematic review and meta-analysis of currently available studies reports that CRT upgrade is associated with similar risk for all-cause mortality compared to de novo resynchronization therapy. Benefits on reverse remodelling and functional capacity improved similarly in both groups suggesting that CRT upgrade may be safely and effectively offered in routine practice. Clinical Trial Registration: Prospero Database—CRD42016043747     

Long-term efficacy of implantable cardiac resynchronization therapy plus defibrillator for primary prevention of sudden cardiac death in patients with mild heart failure: an updated meta-analysis

Previous studies of implantable cardiac resynchronization therapy plus defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death have suggested that CRT-D therapy is less effective in patients with mild heart failure and a wide QRS complex. However, the long-term benefits are variable. We performed a meta-analysis of randomized trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with a mean follow-up of 66 months were included. Overall, CRT-D therapy was associated with significantly lower all-cause mortality than was implantable cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63–0.96; P = 0.02; I ² = 19 %). However, the risk of cardiac mortality was comparable between two groups (OR, 0.74; 95 % CI, 0.53–1.01; P = 0.06). CRT-D treatment was associated with a significantly lower risk of hospitalization for heart failure (OR, 0.67; 95 % CI, 0.50–0.89; P = 0.005; I ² = 55 %). The composite outcome of all-cause mortality and hospitalization for heart failure was also markedly lower with CRT-D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57–0.77; P < 0.0001; I ² = 0 %). CRT-D therapy decreased the long-term risk of mortality and heart failure events in patients with mild heart failure with a wide QRS complex. However, long-term risk of cardiac mortality was similar between two groups. More randomized studies are needed to confirm these findings, especially in patients with NYHA class I heart failure or patients without LBBB.     

Outcomes of ICDs and CRTs in patients with chronic kidney disease: a meta-analysis of 21,000 patients

Purpose

The efficacy of implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) in patients with chronic kidney disease (CKD) remains unclear. The aim of this meta-analysis is to explore the association between ICD/CRT and mortality in CKD patients.

Methods

An electronic search was conducted using MEDLINE. We included studies that reported outcomes of interest in CKD patients stratified by the presence of ICD, CRT, or none. The primary outcome was all-cause mortality. Outcomes were pooled using random effects model. Odds ratios (OR) were reported for dichotomous variables.

Results

The literature search resulted in 11 studies (observational studies) including 21,136 adult patients: seven studies compared ICD vs. no ICD and four studies compared CRT vs. ICD. All-cause mortality was significantly lower in the ICD group in comparison to that in the no ICD group (OR 0.66 (95% confidence interval [CI] 0.45; 0.98), P?=?0.04). Among dialysis-only patients, all-cause mortality was significantly lower in the ICD group (OR 0.49 (95% CI 0.38; 0.64), P?<?0.001). All-cause mortality was significantly lower in the CRT group in comparison to that in the ICD group (OR 0.73 (95% CI 0.57; 0.92), P?=?0.01).

Conclusions

The use of ICDs is associated with lower all-cause mortality in observational studies of CKD patients. CRT use was also associated with lower all-cause mortality in CKD patients in comparison to ICDs. A randomized controlled trial is required to definitively define the role of ICDs/CRTs in CKD patients.

     

Improvement in acute contractility and hemodynamics with multipoint pacing via a left ventricular quadripolar pacing lead

Introduction

A quadripolar left ventricular (LV) pacing can deliver multipoint pacing (MPP). It is unknown if this confers improved cardiac function compared to conventional cardiac resynchronization therapy (CRT).

Methods and results

We aimed to characterize changes in acute cardiac contractility and hemodynamics with multisite left ventricular “multipoint” pacing (MPP) in a prospective multicenter study in patients implanted with a CRT-defibrillator incorporating a quadripolar LV lead. The device was programmed to deliver MPP acutely pacing with eight configurations of varying timing delays. Global peak LV radial strain and LV outflow velocity time integral (LVOT VTI) were measured for conventional CRT and each MPP configuration. Out of the eight tested MPP configurations, the one that yielded the best echocardiographic measurement for each patient was defined as “optimal MPP”. Forty CRT recipients had complete radial strain datasets suitable for analysis. Compared to conventional CRT, the mean peak radial strain was significantly higher for the optimal MPP configuration (18.3?±?7.4 vs. 9.3?±?5.3 %, p?<?0.001), and at least one MPP configuration was significantly superior (>20 %) in 63 % of patients. LVOT VTI data were collected in a subset of 13 patients. In these patients, mean VTI was significantly higher for optimal MPP compared to conventional CRT (13.5?±?2.7 vs. 10.9?±?3.3 cm, p?<?0.01).

Conclusion

MPP delivered via a quadripolar LV lead resulted in a significant improvement in acute cardiac contractility and hemodynamics compared to conventional CRT in the majority of patients studied.

Clinical trial registration

Clinicaltrials.gov identifier NCT01044784     

CTLA-4 +49A/G gene polymorphism and type 1 diabetes mellitus in the Chinese population: a meta-analysis of 2238 subjects

Previous studies reported that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) +49A/G gene polymorphism is correlated with type 1 diabetes mellitus (T1DM) risk. However, their results remain disputable. This study aims to discuss the relationship between CTLA-4 +49A/G gene polymorphism and T1DM in a Chinese population. The current meta-analysis involved 2238 participants from seven individual studies. The pooled odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI) were assessed by the random- or fixed-effects model. A significant relationship between CTLA-4 +49A/G gene polymorphism and T1DM was detected under allelic (OR: 1.84, 95 % CI: 1.62–2.10, P?<?0.00001), dominant (OR: 1.152, 95 % CI: 1.062–1.249, P?=?0.001), recessive (OR: 1.631, 95 % CI: 1.443–1.844, P?<?0.00001), and additive (OR: 1.292, 95 % CI: 1.224–1.363, P?<?0.00001) genetic models. A significant relationship exists between CTLA-4 +49A/G gene polymorphism and increased T1DM risk in the Chinese population. Individuals having the G allele of CTLA-4 +49A/G gene polymorphism have a higher risk for T1DM in the Chinese population.     

Response and outcomes of cardiac resynchronization therapy in patients with renal dysfunction

Purpose

Renal dysfunction is often associated with chronic heart failure, leading to increased morbi-mortality. However, data regarding these patients after cardiac resynchronization therapy (CRT) is sparse. We sought to evaluate response and long-term mortality in patients with heart failure and renal dysfunction and assess renal improvement after CRT.

Methods

We analyzed 178 consecutive patients who underwent successful CRT device implantation (age 64 ± 11 years; 69% male; 92% in New York Heart Association (NYHA) functional class ≥ III; 34% with ischemic cardiomyopathy). Echocardiographic response was defined as ≥ 15% reduction in left ventricular end-systolic diameter and clinical response as a sustained improvement of at least one NYHA functional class. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m².

Results

Renal dysfunction was present in 34.7%. Renal dysfunction was not an independent predictor of echocardiographic response (OR 1.109, 95% CI 0.713–1.725, p 0.646) nor clinical response (OR 1.003; 95% CI 0.997–1.010; p 0.324). During follow-up (mean 55.2 ± 32 months), patients with eGFR < 60mL/min/1.73 m² had higher overall mortality (HR 4.902, 95% CI 1.118–21.482, p 0.035). However, clinical response in patients with renal dysfunction was independently associated with better long-term survival (HR 0.236, 95% CI 0.073–0.767, p 0.016). Renal function was significantly improved in patients who respond to CRT (ΔeGFR + 5.5 mL/min/1.73 m² at baseline vs. follow-up, p 0.049), while this was not evident in nonresponders. Improvements in eGFR of at least 10 mL/min/1.73 m² were associated with improved survival in renal dysfunction patients (log-rank p 0.036).

Conclusion

Renal dysfunction was associated with higher long-term mortality in CRT patients, though, it did not influence echocardiographic nor functional response. Despite worse overall prognosis, renal dysfunction patients who are responders showed long-term survival benefit and improvement in renal function following CRT.

     

Fostamatinib,an oral spleen tyrosine kinase inhibitor,in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials

Fostamatinib is a selective inhibitor of spleen tyrosine kinase which has a role in the pathogenesis of RA. Multiple RCTs have been performed to study the effects of fostamatinib. The objective of this study was to perform a meta-analysis to analyze the efficacy and safety of fostamatinib in the management of RA. We searched PubMed, EMBASE and Cochrane CENTRAL through 11/9/15. Random effect model was used to estimate odds ratio (OR) and 95 % confidence interval. We measured outcomes with efficacy analysis using ACR20/50/70 response criteria and safety with adverse events. Five studies were included in the meta-analysis with total of 2105 patients including 1419 in fostamatinib group and 686 in placebo. Fostamatinib was effective in achieving ACR20, ACR50 and ACR70 responses compared to placebo (48 vs. 32.8 %, OR 1.86, 95 % CI 1.32–2.62, P = 0.0004, I ² 63 %; 26.4 vs. 12.5 %, OR 2.50, 95 % CI 1.93–3.23, P < 0.00001, I ² 0 % and 12.7 vs. 4.4 %, OR 3.00, 95 % CI 1.99–4.51, P < 0.00001, I ² 0 %, respectively). Response to fostamatinib was rapid and significant effect on ACR20 response was seen by week 1 (OR 3.70, 95 % CI 2.33–5.87, P < 0.00001, I ² 42 %). Safety analysis showed an increased risk of infection (OR 1.59, 95 % CI 1.2–2.11; P = 0.001; I ² 0 %), diarrhea (OR 3.54; 95 % CI 2.43–5.16; P < 0.00001; I ² 2 %), hypertension (OR 2.55, 95 % CI 1.54–4.22, P = 0.0003; I ² 42 %) and neutropenia (OR 5.68, 95 % CI 1.97–16.42, P = 0.001, I ² 35 %) and showed a trend toward the increase in ALT ≥3 times ULN (OR 1.76, 95 % CI 0.99–3.13; P = 0.05; I ² 0 %). This meta-analysis concludes that fostamatinib has moderate effect in the treatment of RA with mostly mild-to-moderate adverse events and dose-dependent, transient neutropenia and hypertransaminasemia.     

Prognostic significance of beta-blocker up-titration in conjunction with cardiac resynchronization therapy in heart failure management

Clinical practice guidelines emphasize that optimal pharmacotherapy, including beta-blockers (BB), is a prerequisite before receiving cardiac resynchronization therapy (CRT) in eligible patients with heart failure (HF). However, the optimal dose of BB before CRT implantation cannot be tolerated in a number of patients. Sixty-three consecutive patients who underwent CRT in 2006–2013 were retrospectively investigated. Before receiving CRT, BB could not be introduced in 20 patients (32 %); the daily carvedilol-equivalent dose in other 43 patients was 5.6 ± 7.0 mg because of significant HF and bradycardia. After receiving CRT, BB could be introduced in almost all patients (n = 61, 97 %), and the daily BB dose increased from 5.6 ± 7.0 to 13.2 ± 7.8 mg (P < 0.001). Multivariate analysis indicated that the change of BB dose after CRT was independently associated with improved left ventricular end-systolic volume (LVESV) [β = ?0.36; 95 % confidence interval (CI) ?2.13 to ?0.45; P < 0.01] after 6-months follow-up. Furthermore, Cox proportional hazard analysis also showed that the change in the BB dose (hazard ratio, 0.92; 95 % CI, 0.87–0.98; P < 0.01) as well as the New York Heart Association functional classification was an independent predictor of cardiac events. After initiating CRT, BB therapy can be introduced and up-titrated in intolerant HF patients. The up-titrated dose of BB after CRT was an independent predictor for the improvement of LVESV and HF prognosis.     

Atrial resynchronization therapy in patients with atrial fibrillation and heart failure with and without systolic left ventricular dysfunction: a pilot study

Purpose

The superiority of catheter ablation (CA) for persistent (and long-standing persistent) atrial fibrillation (AF) is currently not well defined. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the clinical outcomes of CA compared with medical therapy in persistent AF patients.

Methods

We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov for RCTs comparing CA with medical therapy in patients with persistent AF. For CA vs medical rhythm control, the primary outcome was freedom from atrial arrhythmia. For CA vs medical rate control, the primary outcome was the change in the left ventricular ejection fraction (LVEF).

Results

Eight studies with a total of 809 patients were included in the final analysis. Compared with medical rhythm control, CA was superior in achieving freedom from atrial arrhythmia (RR 2.08, 95% CI [1.67, 2.58]; P?<?0.00001). Similar result was found in CA arm without antiarrhythmic drug use after operation (RR 1.82, 95%CI [1.33, 2.49]; P?=?0.0002). CA was also superior in reducing the probability of cardioversion (RR 0.59, 95%CI [0.46, 0.76]; P?<?0.0001) and hospitalization (RR 0.54, 95%CI [0.39, 0.74]; P?=?0.0002). Compared with the medical rate control in persistent AF patients with heart failure (HF), CA significantly improved the LVEF (MD 7.72, 95%CI [4.78, 10.67]; P?<?0.00001) and reduced Minnesota Living with Heart Failure Questionnaire scores (MD 11.1395% CI [2.52–19.75]; P?=?0.01).

Conclusions

CA appeared to be superior to medical therapy in persistent AF patients and might be considered as a first-line therapy for some persistent AF patients especially for those with HF.

     

Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing

Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient’s 12-lead ECG. During a mean 15.6 years (range 3.3–30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22–2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15–2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03–1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01–1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.     

Patients with left ventricular ejection fraction greater than 58 % have fewer incidences of future acute decompensated heart failure admission and all-cause mortality

Based on our previous observation, inertia stress (IS) of late systolic aortic flow was often observed in left ventricles with relatively higher left ventricular (LV) ejection fraction (EF). Most left ventricles with relatively lower LVEF did not have IS. Accordingly, lack of IS may correlate with LV diastolic dysfunction through the loss of LV elastic recoil and may contribute to the pathogenesis of heart failure (HF) and reduced survival. We enrolled 144 consecutive patients that underwent cardiac catheterization for the diagnosis of coronary artery disease. Left ventricular ejection fraction (LVEF) was obtained from left ventriculography. The IS was calculated from the LV pressure (P)?dP/dt relation. The study endpoint of this retrospective outcome-observational study was combined subsequent acute decompensated heart failure (ADHF) and all-cause mortality. During the follow-up period (median 6.1 years), seven unscheduled hospitalizations for ADHF and nine all-cause deaths were observed. The event-free survival rate was significantly higher among patients with IS than among patients without IS (log-rank, p = 0.001). On a multivariate Cox regression analysis, lack of IS was a prime predictor of the endpoint during follow-up (hazard ratio: 6.98; 95 % confidence interval: 1.48–33.03; p = 0.01). An LVEF ≥ 58 % was a surrogate indicator for the presence of IS, and patients with LVEF ≥ 58 % had fewer incidences of the endpoint than patients with LVEF < 58 %. In conclusion, lack of IS or LVEF < 58 % should be a predictor of future ADHF and all-cause mortality.     

Mechanistic implication of decreased plasma atrial natriuretic peptide level for transient rise in the atrial capture threshold early after ICD or CRT-D implantation

Purpose

Despite the use of steroid-eluting leads, a transient but not persistent rise in the atrial/ventricular capture threshold (TRACT/TRVCT) can occur early after pacemaker implantation in patients with sick sinus syndrome. This study aimed to assess the prevalence, predictors, and mechanisms of TRACT/TRVCT in patients with heart failure undergoing implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) implantation.

Method

One hundred twenty consecutive patients underwent ICD (N?=?70) or CRT (N?=?50) implantation. Capture threshold was measured at implantation, 7-day, 1-month, and 6-month post-implantation. TRACT/TRVCT was defined as a threshold rise at 7 days by more than twice the height of the threshold at implantation, with full recovery during follow-up. Atrial and brain natriuretic peptide (ANP and BNP) levels were measured before implantation.

Results

TRACT and TRVCT were observed in 13 (11%) and 10 (8%) patients, respectively. Patients with TRACT had lower ANP level (median 72 [42–105] vs. 99 [49–198] pg/mL, P?=?0.06), lower ANP/BNP ratio (0.29 [0.20–0.36] vs. 0.50 [0.33–0.70], P?<?0.01), lower atrial sensing amplitude (2.0?±?0.8 vs. 2.7?±?1.3 mV, P?=?0.02), and lower left ventricular ejection fraction (32?±?12 vs. 40?±?14%, P?=?0.04) than those without TRACT. TRACT recovered within 1 month, whereas TRVCT recovered within 6 months. In multivariable analysis, ANP/BNP ratio was the only independent predictor of TRACT (OR, 0.018; 95% CI, 0.001–0.734; P?=?0.034).

Conclusions

Atrial degenerative change characterized by lower ANP/BNP ratio was associated with the occurrence of TRACT in patients with heart failure. TRVCT could also occur, but it required a longer recovery time than TRACT.

     

Electrocardiographic characteristics for predicting idiopathic right ventricular outflow tract premature ventricular complex-induced cardiomyopathy

Purpose

In spite of several proposed predictors for premature ventricular complex (PVC)-induced cardiomyopathy (PVC-CMP), the specific ECG features of idiopathic right ventricular outflow tract (RVOT) PVC-CMP remain unknown.

Methods

A total of 130 patients (49 males, mean age 44 years) with symptomatic and drug-refractory idiopathic RVOT PVCs undergoing radiofrequency catheter ablation (RFCA) were enrolled. The patients were categorized into two groups, including those with and without RVOT PVC-CMP (left ventricular ejection fraction (LVEF) <?50%, n?=?25 and LVEF ≥?50%, n?=?105, respectively). The 12-lead PVC morphologies were assessed.

Results

Patients with RVOT PVC-CMP had a lower LVEF (42?±?5% vs. 60?±?7%, P?<?0.01) and higher PVC burden (24?±?14% vs. 15?±?11%, P?=?0.02) when compared to patients without RVOT PVC-CMP. The PVC features in those with PVC-CMP displayed a significantly wider QRS duration (143?±?14 ms vs. 132?±?17 ms, P?<?0.01) and higher peak deflection index (PDI; 0.60?±?0.07 vs. 0.55?±?0.08, P?<?0.01). A multivariate analysis demonstrated that the QRS duration (odds ratio (OR) 1.130, 95% confidence interval (CI) 1.020–1.253, P?=?0.02) and PDI (OR 1.240, 95% CI 1.004–1.532, P?=?0.04) were independently associated with RVOT PVC-CMP. Based on the receiver-operating characteristic analysis, a QRS duration >?139 ms and PDI >?0.57 could predict RVOT PVC-CMP (area under the curve (AUC) 0.710 and AUC 0.690, respectively). The elimination and suppression of PVCs by RFCA resulted in the recovery of the LVEF in RVOT PVC-CMP.

Conclusions

The ECG parameters, including a wider QRS duration and higher PDI, could predict the development of RVOT PVC-CMP, which could be effectively treated by RFCA.

     

Baricitinib,a Janus kinase inhibitor,in the treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

Janus kinases (JAKs) play an important role in intracellular signaling for multiple cytokines in the pathogenesis of RA. Baricitinib is an oral, selective JAK 1 and 2 inhibitor which has been shown to be effective in the treatment of RA in several clinical trials. This meta-analysis aims to aggregate currently available data to assess the overall efficacy and safety of baricitinib in RA. We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through 09/24/17 with restriction to English language. We excluded meeting abstracts without full text publication. We used RevMan 5.3 to perform meta-analysis between groups on baricitinib (2 and 4 mg daily) and placebo using random effect model calculating odds ratio (OR) as well as 95% confidence interval (CI). Compared to placebo, 2 mg of baricitinib was more effective in achieving ACR20 [54 vs. 36.6%; OR 2.09; 95% CI 1.60–2.71; p?<?0.00001; I² 0%], ACR50 [31.6 vs. 10.3%; OR 2.3; 95% CI 1.68–3.15; p?<?0.00001; I² 0%], and ACR70 responses [18.7 vs. 5.1%; OR 4.05; 95% CI 2.54–6.44; p?<?0.00001; I² 0%]. Similarly, 4 mg of baricitinib daily was more effective than placebo. Baricitinib 2 mg once daily did not increase any adverse events [65.3 vs. 62.4%; OR 1.03; 95% CI 0.80–1.34; p?=?0.8; I² 0%], serious adverse events [3.5 vs. 5%; OR 0.68; 95% CI 0.37–1.27; p?=?0.22; I² 0%], and herpes zoster [1.2 vs. 0.4%; OR 2.34; 95% CI 0.27–20.47; p?=?0.44; I² 37%] as compared to placebo. Similarly, 4 mg of baricitinib did not increase the risk of serious adverse events but increased herpes zoster infection [OR 3.88; 95% CI 1.36–11.06; p?=?0.01; I² 0%] when compared to placebo. Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6 months of treatment.     

Heart involvement in systemic lupus erythematosus: a systemic review and meta-analysis

Cardiovascular diseases are one of the most important causes of the disability and mortality in patients with systemic lupus erythematosus (SLE). The present study examined the cardiac abnormalities in patients with SLE by echocardiography. Case-control studies were obtained by searching PubMed MEDLINE, Embase, and MD Consult. Systemic review and meta-analysis were performed to assess the cardiac abnormalities based on the changes in the echocardiography in patients with SLE. Twenty-two studies including 1117 SLE patients and 901 healthy controls were enrolled into this study. We found that patients with SLE developed the pericardial effusion (odds ratio (OR) (95 % confidence interval (CI)) 30.52 (9.70–96.02); p < 0.00001) and the combined valvular alterations (OR (95 %CI) 11.08 (6.98–17.59); p < 0.00001). In addition, SLE patients also exhibited an increase in the left atrial diameter (LAD) (WMD—weighted mean difference (95 %CI) 0.18 (0.06–0.29); p = 0.002), the left ventricular internal diameter in diastole (LVDd) (WMD (95 %CI) 0.07 (0.02–0.12); p = 0.01), and the left ventricular mass index (LVMI) (WMD (95 %CI) 5.69 (2.69–8.69); p = 0.0002). In contrast, the left ventricular systolic function (WMD (95 %CI) ?1.22 (?1.69 to ?0.75); p < 0.00001) and diastolic function including E/A ratio and E/E’ ratio (WMD (95  % CI) ?0.13 (?0.24 to ?0.01); p = 0.04; WMD (95  % CI) 1.71 (0.43 to 2.99); p = 0.009) were decreased in SLE patients. Patients with SLE are associated with significant alterations in cardiac structure and function as demonstrated by echocardiography. Data from this study suggest that echocardiographic assessment should be considered as a part of routine examinations for SLE patients clinically.     

Study of cannabinoid receptor 2 Q63R gene polymorphism in Lebanese patients with rheumatoid arthritis

The cannabinoid (CB) receptor 2, primarily expressed in immune cells, was shown to play important immune-regulatory functions. In particular, the CB2-R63 functional variant has been shown to alter the ability of the CB2 receptor to exert its inhibitory function on T lymphocytes. The aim of this study was to investigate the association between a common dinucleotide polymorphism, Q63R, in the cannabinoid receptor 2 gene (CNR2) and rheumatoid arthritis (RA) in the Lebanese population. One hundred five unrelated Lebanese RA patients and one hundred five controls from different Lebanese governorates were recruited in this study. Genomic DNA was extracted, polymerase chain reaction was performed, and CNR2 was genotyped in a blinded fashion. The χ² test was used to determine the differences in genotypes and allele frequencies. CNR2 genotyping showed significantly higher frequencies of the CB2-R63 variant (allele frequencies, P?<?0.00001; genotype distribution, P?<?0.00001) in RA patients when compared with healthy controls. Moreover, RR carriers had more than 10-fold risk for developing RA (OR?=?10.8444, 95% CI?=?5.0950–23.0818; P?<?0.0001), and QR carriers had more than 3-fold risk (OR?=?3.8667, 95% CI?=?1.7886–8.3591; P?=?0.0006) as compared with QQ carriers. Our preliminary results suggest a role of CB2-Q63R gene polymorphism in the etiology of RA, thus supporting its potential use as a pharmacological target for selective agonists in clinical practice.     

Conduction system versus biventricular pacing in heart failure with non-left bundle branch block

Introduction

The benefits of cardiac resynchronization therapy (CRT) with biventricular pacing (BiV) is significantly lower when applied to heart failure (HF) patients with non-left bundle branch block (LBBB) conduction delay. We investigated clinical outcomes of conduction system pacing (CSP) for CRT in non-LBBB HF.

Methods

Consecutive HF patients with non-LBBB conduction delay undergoing CSP were propensity matched for age, sex, HF-etiology, and atrial fibrillation (AF) in a 1:1 ratio to BiV from a prospective registry of CRT recipients. Echocardiographic response was defined as an increase in left ventricular ejection fraction (LVEF) by ≥10%. The primary outcome was the composite of HF-hospitalizations or all-cause mortality.

Results

A total of 96 patients were recruited (mean age 70 ± 11years, 22% female, 68% ischemic HF and 49% AF). Significant reductions in QRS duration and LV dimensions were seen only after CSP, while LVEF improved significantly in both groups (p < 0.05). Echocardiographic response occurred more frequently in CSP than BiV (51% vs. 21%, p < 0.01), with CSP independently associated with four-fold increased odds (adjusted odds ratio 4.08, 95% confidence interval [CI] 1.34–12.41). The primary outcome occurred more frequently in BiV than CSP (69% vs. 27%, p < 0.001), with CSP independently associated with 58% risk reduction (adjusted hazard ratio [AHR] 0.42, 95% CI 0.21–0.84, p = 0.01), driven by reduced all-cause mortality (AHR 0.22, 95% CI 0.07–0.68, p < 0.01), and a trend toward reduced HF-hospitalization (AHR 0.51, 95% CI 0.21–1.21, p = 0.12).

Conclusions

CSP provided greater electrical synchrony, reverse remodeling, improved cardiac function and survival compared to BiV in non-LBBB, and may be the preferred CRT strategy for non-LBBB HF.     

Chronic Right Ventricular Pacing in the Heart Failure Population

Purpose of Review

We review the trials that have demonstrated potentially harmful effects from right ventricular (RV) apical pacing as well as reviewing the evidence of alternative RV pacing sites and cardiac resynchronization therapy (CRT) for patients who have heart failure and atrioventricular (AV) block.

Recent Findings

The role of CRT in patients with AV block and impaired left ventricular function remains an important consideration. The BLOCK HF trial demonstrated better outcomes with CRT pacing over RV pacing in patients with left ventricular systolic dysfunction (LVSD) and AV block who were expected to have a high RV pacing burden, but failed to demonstrate a mortality benefit.

Summary

CRT seems to have a beneficial effect on left ventricular reverse remodeling, systolic function, and clinical outcomes in patients with New York Heart Association (NYHA) functional class I–III heart failure, moderate to severe LVSD, and AV block compared to RV pacing. However, it is less clear whether there is a similar benefit from CRT in patients with a high percentage of RV pacing who have normal or mild LVSD in the treatment of AV block.

     

The search for putative unifying genetic factors for components of the metabolic syndrome

Aims/hypothesis

The metabolic syndrome is a cluster of factors contributing to increased risk of cardiovascular disease and type 2 diabetes but unifying mechanisms have not been identified. Our aim was to study whether common variations in 17 genes previously associated with type 2 diabetes or components of the metabolic syndrome and variants in nine genes with inconsistent association with at least two components of the metabolic syndrome would also predict future development of components of the metabolic syndrome, individually or in combination.

Methods

Genetic variants were studied in a large prospective study of 16,143 non-diabetic individuals (mean follow-up time 23 years) from the Malmö Preventive Project. In this study, development of at least three of obesity (BMI?≥?30 kg/m²), dyslipidaemia (triacylglycerol?≥?1.7 mmol/l and/or lipid-lowering treatment), hypertension (blood pressure?≥?140/90 mmHg and/or antihypertensive medication) and hyperglycaemia (fasting plasma glucose?≥?5.6 mmol/l and/or known diabetes) was defined as development of the metabolic syndrome. The risk of developing at least three components of the metabolic syndrome or the individual components was calculated by logistic regression adjusted for age at baseline, follow-up time and sex.

Results

Polymorphisms in TCF7L2 (rs7903146, OR 1.10, 95% CI 1.04–1.17, p?=?0.00097), FTO (rs9939609, OR 1.08, 95% CI 1.02–1.14, p?=?0.0065), WFS1 (rs10010131, OR 1.07, 95% CI 1.02–1.13, p?=?0.0078) and IGF2BP2 (rs4402960, OR 1.07, 95% CI 1.01–1.13, p?=?0.021) predicted the development of at least three components of the metabolic syndrome in both univariate and multivariate analysis; in the case of TCF7L2, WFS1 and IGF2BP this was due to their association with hyperglycaemia (p?p?=?0.0033 and p?=?0.027, respectively) and for FTO it was due to its association with obesity (p?=?0.004). A polymorphism in the GCKR gene predicted dyslipidaemia (rs1260326, OR 1.15, 95% CI 1.09–1.22, p?p?p?p?

Conclusions/interpretation

Polymorphisms in susceptibility genes for type 2 diabetes (TCF7L2, WFS1, IGF2BP2) and obesity (FTO) predispose to the metabolic syndrome by increasing the risk of one specific component of the metabolic syndrome. The findings argue against a unifying genetic component for the metabolic syndrome.