Obstructive sleep apnea increases the risk of cardiac events after percutaneous coronary intervention: a meta-analysis of prospective cohort studies

Purpose

Recent studies have shown an association between obstructive sleep apnea (OSA) and coronary artery disease; however, the association between OSA and cardiac outcomes in patients after percutaneous coronary intervention (PCI) remains undetermined.

Methods

PubMed, EMBASE, and CENTRAL were searched from inception to July 2016 for cohort studies that followed up with patients after PCI, and evaluated their overnight sleep patterns within 1 month for major adverse cardiac events (MACEs) as primary outcomes including cardiac death, non-fatal myocardial infarction (MI), and coronary revascularization and secondary outcomes including re-admission for heart failure and stroke. Outcomes data were pooled using fixed-effect meta-analysis, and heterogeneity was assessed with the I ² statistics. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale checklist, and publication bias was evaluated by a visual investigation of funnel plots.

Results

We identified seven pertinent studies including 2465 patients from 178 related articles. OSA was associated with MACEs (odds ratio [OR], 1.52, 95% confidence interval [CI], 1.20–1.93, I ² = 29%), which included cardiac death (OR 2.05, 95% CI, 1.15–3.65, I ² = 0%), non-fatal MI (OR 1.59, 95% CI, 1.14–2.23, I ² = 15%), and coronary revascularization (OR 1.69, 95% CI, 1.28–2.23, I ² = 0%). However, OSA was not associated with re-admission for heart failure (OR 1.71, 95% CI, 0.99–2.96, I ² = 0%) and/or stroke (OR 1.68, 95% CI, 0.91–3.11, I ² = 0%) according to the pooled results.

Conclusions

In patients after PCI, OSA appears to increase the risk of cardiac death, non-fatal MI, and coronary revascularization.

     

T wave positivity in lead aVR is associated with mortality in patients with cardiac resynchronization therapy

Purpose

Positive T wave polarity in lead aVR (TPaVR) is associated with a poor prognostic indicator in patients with heart failure reduce ejection fraction (HFrEF). Our aim was to investigate the relationship between positive TPaVR and mortality in patients with cardiac resynchronization therapy defibrillator (CRT-D).

Methods

We included retrospectively 224 HFrEF patients with CRT-D in sinus rhythm. Laboratory, electrocardiographic (ECG), and echocardiographic data were recorded. T wave polarity was measured in lead DI, DII, and aVR from surface ECG.

Results

The patients were divided as living and deceased. They followed for 2.5?±?0.9 years. Thirty-three patients (14.7%) died. Six patients (18.2%) were TPaVR positive before CRT-D and this number increased to 22 (66.6%) after CRT-D in the deceased group. Pulse (p?=?0.049), hyperlipidemia (p?=?0.022), and NT-proBNP levels were higher in the deceased group (p?=?0.001). TPaVR before CRT-D (p?<?0.001) and TPaVR after CRT-D (p?<?0.001) were significantly positive in the deceased group. Positive TPaVR after CRT-D was the only independent predictor for mortality in binominal logistic regression analysis (OR 1.211, 95% CI 1.105–1.328, p?<?0.001).

Conclusions

In CRT-D patients, a positive TPaVR in surface ECG may be a strong mortality indicator.

     

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.     

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis

Purpose

Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear.

Methods

We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database.

Results

Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62–1.13; p = 0.25; I ² = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35–2.06; p = 0.72; I ² = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18–1.73; p = 0.32; I ² = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), ?1.78; 95 % CI, ?2.31 to ?1.24; p < 0.00001; I ² = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, ?2.03 mmHg; 95 % CI, ?3.64 to ?0.42; p = 0.01; I ² = 0 %; for diastolic BP: MD, ?1.79 mmHg; 95 % CI, ?2.89 to ?0.68; p = 0.001; I ² = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke.

Conclusions

CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.

     

Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

IL-17 has a role in inflammation in RA, and its levels in joints correlate with disease severity. Multiple RCTs have been performed to study effects of anti-IL-17 agents. The objective of this study was to perform a systematic review and meta-analysis to analyze the efficacy and safety of anti-IL-17 agents in the management of RA. This work is based on a systematic review of studies retrieved by a sensitive search strategy in PubMed, EMBASE and Cochrane CENTRAL from inception through 9/7/15. Study selection criteria were the following: adult patients (age ≥ 18 years) with RAs, random selection of patients for anti-IL-17 therapy and treatment response compared to placebo. We performed systematic literature review per PRISMA guideline and two investigators independently selected seven randomized clinical trials (RCTs) for meta-analysis. We used random effect model calculating odds ratio (OR) and 95 % confidence interval (CI) to measure the efficacy with ACR20/50/70 responses and the safety with adverse events. Seven studies with total of 1226 patients including 905 in anti-IL-17 group and 321 in placebo were included in the meta-analysis. Anti-IL-17 was effective in achieving ACR20 and ACR50 compared to placebo (OR 2.47, 95 % CI 1.29–4.72, P = 0.006, I ² 77 % and OR 2.94, 95 % CI 1.37–6.28, P = 0.005, I ² 64 %, respectively). Data analysis for ACR70 showed a favorable trend toward anti-IL-17 (OR 2.62, 95 % CI 1–6.89, P = 0.05, I ² 15 %). Subgroup analysis of ACR20 for individual anti-IL-17 agents showed that ixekizumab was more effective than placebo, while secukinumab showed a trend toward achieving the ACR20 response. However, brodalumab was not effective compared to placebo. Safety analysis did not show increased risk of any or serious adverse effects by anti-IL-17 compared to placebo (OR 1.23, 95 % CI 0.94–1.61, P = 0.13, I ² = 0 % and OR 1.28, 95 % CI 0.57–2.88, P = 0.55, I ² = 0 %, respectively). This meta-analysis concludes that anti-IL-17 is effective in the treatment of RA without increased risk of any or serious adverse effects; however, the results are limited by significant heterogeneity and small duration of studies.     

Defining the role of ultrafiltration therapy in acute heart failure: a systematic review and meta-analysis

Ultrafiltration (UF) has emerged as an alternative therapy for acute decompensated heart failure (ADHF) due to its physiological benefits such as improvement in neurohormonal activation. We performed a systematic review and a meta-analysis to evaluate the efficacy, safety, and the impact on outcomes for UF therapy as compared to conventional medical treatment. The PubMed and Cochrane databases were searched from inception to December 2015 for randomized controlled trials that examined UF therapy in ADHF and used diuretic-based regimens as the control group. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we explored the impact on weight change, fluid removal, renal function, rehospitalization rate, and mortality. Mantel–Haenszel odds ratio (OR) was calculated for dichotomous data and weighted mean difference (WMD) for continuous data. Seven studies with a total of 771 patients met our selection criteria. UF therapy led to greater weight loss (WMD 1.35, 95 % CI 0.49–2.21, p < 0.01) and fluid removal (WMD 1.81, 95 % CI 1.01–2.62, p = <0.01) while the impact of UF on renal function was comparable with medical treatment (WMD 0.06, 95 % CI ?0.11 to 0.22, p = 0.48), UF decreased heart failure rehospitalization rate (OR 0.60, 95 % CI 0.37–0.98, p = 0.04) but did not change mortality (OR 1.03, 95 % CI 0.68–1.57, p = 0.89). Compared with diuretic-based medical treatment, UF therapy is more efficient in decongestion of patients with ADHF. It does not have a deleterious impact on renal function and can improve heart failure-related rehospitalization rate, albeit without conferring a survival benefit.     

Resistance exercise enhances oxygen uptake without worsening cardiac function in patients with systolic heart failure: a systematic review and meta-analysis

Recent literature suggests that resistance training (RT) improves peak oxygen uptake (\( \dot{\mathrm{V}}{\mathrm{O}}_2 \) peak), similarly to aerobic exercise (AE) in patients with heart failure (HF), but its effect on cardiac remodeling is controversial. Thus, we examined the effects of RT and AE on \( \dot{\mathrm{V}}{\mathrm{O}}_2 \) peak and cardiac remodeling in patients with heart failure (HF) via a systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane Library and CINAHL, AMEDEO and PEDro databases search were extracted study characteristics, exercise type, and ventricular outcomes. The main outcomes were \( \dot{\mathrm{V}}{\mathrm{O}}_2 \) peak (ml kg^?1 min^?1), LVEF (%) and LVEDV (mL). Fifty-nine RCTs were included. RT produced a greater increase in \( \dot{\mathrm{V}}{\mathrm{O}}_2 \) peak (3.57 ml kg^?1 min^?1, P < 0.00001, I ² = 0%) compared to AE (2.63 ml kg^?1 min^?1, P < 0.00001, I ² = 58%) while combined RT and AE produced a 2.48 ml kg^?1 min^?1 increase in \( \dot{\mathrm{V}}{\mathrm{O}}_2 \); I ² = 69%) compared to control group. Comparison among the three forms of exercise revealed similar effects on \( \dot{\mathrm{V}}{\mathrm{O}}_2 \) peak (P = 0.84 and 1.00, respectively; I ² = 0%). AE was associated with a greater gain in LVEF (3.15%; P < 0.00001, I ² = 17%) compared to RT alone or combined exercise which produced similar gains compared to control groups. Subgroup analysis revealed that AE reduced LVEDV (? 10.21 ml; P = 0.007, I ² = 0%), while RT and combined RT and AE had no effect on LVEDV compared with control participants. RT results in a greater gain in \( \dot{\mathrm{V}}{\mathrm{O}}_2 \) peak, and induces no deleterious effects on cardiac function in HF patients.     

Prophylactic mesh to prevent parastomal hernia: a meta-analysis of randomized controlled studies

The aim of the present meta-analysis was to determine whether prophylactic mesh decreases the odds of parastomal hernia formation. Randomized controlled trials referenced in MEDLINE or EMBASE between 1946 and 2016 comparing prophylactic mesh to standard stoma formation were included. The primary outcome was occurrence of parastomal hernia. Secondary outcomes were parastomal hernia requiring surgical intervention and complications. Odds ratios were calculated for the primary and secondary outcomes. Subgroup analyses were conducted based on mesh type, mesh location, laparoscopic versus open, and method of hernia diagnosis. Nine randomized controlled trials with 569 participants were included. There was a significant decrease in the odds of developing a parastomal hernia in the prophylactic mesh group [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.11–0.38, p < 0.00001, I ² = 36%], as well as decreased odds of requiring surgical repair (OR 0.36, 95% CI 0.15–0.87, p = 0.02, I ² = 0%). There was no evidence that prophylactic mesh increased the odds of surgical complications (seven studies, OR 1.34, 95% CI 0.73–2.46, p = 0.34, I ² = 34%) or stoma-specific complications (eight studies, OR 0.65, 95% CI 0.40–1.05, p = 0.08, I ² = 0%). There was a subgroup effect with synthetic mesh associated with a lower incidence of parastomal hernias which was not appreciated in the biologic mesh group (test of subgroup effect p = 0.01). Five studies had a high risk of bias. The Grades of Recommendation, Assessment, Development and Evaluation quality of evidence was moderate. Prophylactic mesh is associated with decreased odds of parastomal hernia formation and the need for surgical repair. There is no evidence that mesh placement increases the odds of complications.     

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     

Clinical outcome of left ventricular multipoint pacing versus conventional biventricular pacing in cardiac resynchronization therapy: a systematic review and meta-analysis

Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with systolic heart failure. Unlike conventional biventricular pacing (BIP), the left ventricular multipoint pacing (MPP) can increase the number of left ventricular pacing sites via a quadripolar lead positioned in the coronary sinus. This synthetic study was conducted to integratively and quantitatively evaluate the clinical outcome of MPP in comparison with BIP. We systematically searched the databases of EMBASE, Ovid medline, and Cochrane Library through May 2018 for studies comparing the clinical outcome of MPP with BIP in the patients who accepted CRT. Hospitalization for reason of heart failure, left ventricular eject fraction (LVEF), CRT response, all-cause morbidity, and cardiovascular death rate was collected for meta-analysis. A total of 11 studies with 29,606 participants were included in this meta-analysis. Compared with BIP group, MPP decreased heart failure hospitalization (OR, 0.41; 95% CI, 0.33 to 0.50; P <?0.00001), improved LVEF (mean difference, 4.97; 95% CI, 3.11 to 6.83; P <?0.00001), increased CRT response (OR, 3.64; 95% CI, 1.68 to 7.87; P?=?0.001), and decreased all-cause morbidity (OR, 0.41; 95% CI, 0.26–0.66; P?=?0.0002) and cardiovascular death rate (OR, 0.21; 95% CI, 0.11–0.40; P <?0.00001). The published literature demonstrates that MPP was more effective than BIP in the heart failure patients who accepted cardiac resynchronization therapy.     

Effect of colchicine in prevention of pericardial effusion and atrial fibrillation: a meta-analysis

Randomized, controlled trials (RCTs) have assessed the effect of colchicine therapy in prevention of pericardial effusion (PE) and atrial fibrillation (AF). However, the effects are still inconclusive. PubMed, Cochrane Library, Google Scholar, and EMBASE database were searched. Primary outcome was the risk of PE and AF. Ten RCTs with 1981 patients and a mean follow-up of 12.6 months were included. Colchicine therapy was not associated with a significantly lower risk of post-operative PE (RR, 0.89; 95 % CI 0.70–1.13; p = 0.33, I ² = 72.8 %) and AF (RR, 0.77; 95 % CI 0.52–1.13; p = 0.18, I ² = 47.3 %). However, rates of pericarditis recurrence, symptoms persistence, and pericarditis-related hospitalization were significantly decreased with colchicine treatment. In addition, cardiac tamponade occurrence was similar between groups, and adverse events were significantly higher in the colchicine group. Colchicine may not significantly decrease the post-operative risk of PE and AF. However, only limited studies about patients undergoing cardiac surgery provide data about PE and AF.     

Effect of a cardiac rehabilitation program on exercise oscillatory ventilation in Japanese patients with heart failure

Although exercise oscillatory ventilation has emerged as a potent independent risk factor for adverse prognosis in heart failure, it is not well known whether cardiac rehabilitation can improve oscillatory ventilation. In this study, we investigated the magnitude of oscillations in ventilation before and after cardiac rehabilitation in chronic heart failure patients with exercise oscillatory ventilation. Cardiac rehabilitation (5-month program) was performed in 26 patients with chronic heart failure who showed an oscillatory ventilation pattern during cardiopulmonary exercise testing (CPX). After the 5-month rehabilitation program was completed, the patients again underwent CPX. To determine the magnitude of oscillations in ventilation, the amplitude and cycle length of the oscillations were calculated and compared with several other parameters, including biomarkers that have established prognostic value in heart failure. At baseline before cardiac rehabilitation, both oscillation amplitude (R = 0.625, P < 0.01) and cycle length (R = 0.469, P < 0.05) were positively correlated with the slope of minute ventilation vs. carbon dioxide production. Plasma BNP levels were positively correlated with amplitude (R = 0.615, P < 0.01) but not cycle length (R = 0.371). Cardiac rehabilitation decreased oscillation amplitude (P < 0.01) but failed to change cycle length. The change in amplitude was positively correlated with the change in BNP levels (R = 0.760, P < 0.01). Multiple regression analysis showed that only the change in amplitude was an independent predictor of the change in BNP levels (R = 0.717, P < 0.01). A 5-month cardiac rehabilitation program improves exercise oscillatory ventilation in chronic heart failure patients by reducing the oscillation amplitude. This effect is associated with a reduction of plasma BNP levels, potentially contributing to an improvement of heart failure.     

Renal function on admission modifies prognostic impact of diuretics in acute heart failure: a propensity score matched and interaction analysis

Although intravenous diuretics have been mainstay drugs in patients with acute heart failure (AHF), they have been suggested to have some deleterious effects on prognosis. We postulated that renal function may modify their deleterious effects in AHF patients. The study population consisted of 1094 AHF patients from three hospitals. Renal dysfunction (RD) was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² on admission, and the cohort was divided into a high-dose furosemide (≥100 mg/48 h) and low-dose furosemide group according to the amount of intravenous furosemide used within 48 h from admission. In the whole cohort, in-hospital mortality rate was higher in the high-dose furosemide group than the low-dose furosemide group (12.5 vs. 6.6 %, respectively, P = 0.001). However, this difference in the in-hospital mortality rates was significant only in the RD subgroup (15.6 vs. 7.0 %, respectively, P < 0.001), and not in the non-RD subgroup (2.5 vs. 5.9 %, respectively, P = 0.384). Propensity score-matched analysis was performed to evaluate the impact of high-dose furosemide on prognosis. After propensity score matching, high-dose furosemide was not associated with in-hospital mortality (OR 1.25, 95 % CI 0.73–2.16, P = 0.408). However, there was a qualitative difference in OR for in-hospital mortality between AHF with RD (OR 1.77, 95 % CI 0.96–3.28, P = 0.068) and without RD (OR 0.23, 95 % CI 0.05–1.10, P = 0.064), and there was a significant interaction between eGFR and prognostic impact of high-dose furosemide (P for OR interaction = 0.013). An inverse relationship was observed between eGFR and OR for in-hospital death in the group treated with high-dose furosemide (decreasing OR with better eGFR). The deleterious effect of diuretics was significantly modified with renal function in AHF. This association may be one reason for poorer prognosis of AHF patients complicated with renal impairment.     

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.     

Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials

Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I² statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR?=?0.57, 95 % CI?=?0.54–0.61, p-value <0.00001], biochemical response [58.37 % vs. 21.87 %, RR?=?0.52, 95 % CI?=?0.48–0.56, p-value <0.00001], histological response [58.99 % vs. 27.13 %, RR?=?0.56, 95 % CI?=?0.50–0.63, p-value <0.0001], seroconversion of HBeAg [10.66 % vs. 5.56 %, RR?=?0.94, 95 % CI?=?0.91–0.97, p-value?=?0.0005], and HBeAg loss [14.59 % vs. 9.64 %, RR?=?0.92, 95 % CI?=?0.88–0.96, p-value?=?0.0002]. The safety analysis were carried out for adverse events such as headache [17.22 % vs. 17.34 %, OR?=?1.09, 95 % CI?=?0.81–1.46, p-value?=?0.58], abdominal pain [16.46 % vs. 14.34 %, OR?=?1.24, 95 % CI?=?0.90–1.72, p-value?=?0.19], and pharyngitis [22.22 % vs. 18.23 %, OR?=?1.12, 95 % CI?=?0.86–1.45, p-value?=?0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects.     

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.

     

Correlations of the changes in bioptic findings with echocardiographic,clinical and laboratory parameters in patients with inflammatory cardiomyopathy

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction—LVEF <40 %) with heart failure symptoms ≤6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm² and/or >7 T-lymphocytes/mm² in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm² and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm² (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = ?0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = ?0.33; p = 0.038 and R = ?0.45; p = 0.003) and with the change in LVEDV (R = ?0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment option in patients with recent onset biopsy-proven inflammatory cardiomyopathy.     

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.     

Bilateral internal thoracic artery grafting in octogenarians: where are the benefits?

The use of bilateral internal thoracic artery (BITA) grafting for myocardial revascularization is usually discouraged in the very elderly because of increased risk of perioperative complications. The aim of the study was to analyze early and late outcomes of BITA grafting in octogenarians. From January 1999 throughout February 2014, 236 consecutive octogenarians with multivessel coronary artery disease underwent primary isolated coronary bypass surgery at the authors’ institution. Six of these patients underwent emergency surgery and were excluded from this retrospective study; consequently, 135 BITA patients were compared with 95 single internal thoracic artery (SITA) patients according to early and late outcomes. Between BITA and SITA patients, there was no significant difference in the operative risk (EuroSCORE II: 8 ± 7.7 vs. 7.6 ± 6.1 %, p = 0.65). There was a lower aortic manipulation in BITA patients. Hospital mortality (3 vs. 4.2 %, p = 0.44) and perioperative complications were similar except that only BITA patients experienced sternal wound infection (5.2 %, p = 0.022). The mean follow-up was 4.7 ± 3.3 years. There were no differences between the two groups in overall survival (p = 0.79), freedom from cardiac and cerebrovascular deaths (p = 0.73), major adverse cardiac and cerebrovascular events (p = 0.63) and heart failure hospital readmission (p = 0.64). Predictors of decreased late survival were diabetes (p = 0.0062) and congestive heart failure (p = 0.0004). BITA grafting can be routinely used in octogenarians with atherosclerotic ascending aorta without an increase in hospital mortality or major adverse cardiac and cerebrovascular complications. However, there is an increased risk of sternal wound infection without a demonstrable long-term benefit.     

Colchicine in addition to conventional therapy for pericarditis recurrence

Background

Randomized controlled trials (RCTs) have investigated the use of colchicine and conventional therapy for reducing the recurrence of pericarditis in patients with acute pericarditis or post-pericardiotomy syndrome. However, the benefits of these treatments are variable.

Methods

Studies were retrieved from PubMed, the Cochrane Library, and the EMBASE database.

Results

We identified nine RCTs with 1832 patients and a mean follow-up of 13.1 months. Overall, colchicine therapy significantly decreased the risk of pericarditis recurrence (odds ratio, OR 0.42; 95?% confidence interval, CI 0.33–0.52; P?<?0.001; I²?=?17.0?%). Colchicine therapy was associated with significantly lower rates of pericarditis-associated rehospitalization (OR 0.29; 95?% CI 0.16–0.53; P?<?0.0001; I²?=?0.0?%) and persistence of symptoms (OR 0.29; 95?% CI, 0.21–0.41; P?=?0.000; I²?=?0.0?%) at 72 h. Adverse events were higher in the colchicine group (relative risk, RR 1.48; 95?% CI, 1.06–2.07; P?=?0.02; I²?=?0.0?%). Subgroup analysis showed that recurrence of pericarditis was significantly lower in the colchicine therapy group, irrespective of prednisone use and the cause of pericarditis.

Conclusion

Colchicine significantly decreases the rate of pericarditis recurrence, regardless of prednisone use and the cause of pericarditis. Larger studies are needed to confirm this effect.