The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials.

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs. CONTROL: SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1. CONCLUSIONS: Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.

Electrical latency predicts the optimal left ventricular endocardial pacing site: results from a multicentre international registry.

Aims: The optimal site for biventricular endocardial (BIVENDO) pacing remains undefined. Acute haemodynamic response (AHR) is reproducible marker of left ventricular (LV) contractility, best expressed as the change in the maximum rate of LV pressure (LV-dp/dtmax), from a baseline state. We examined the relationship between factors known to impact LV contractility, whilst delivering BIVENDO pacing at a variety of LV endocardial (LVENDO) locations. Methods and results: We compiled a registry of acute LVENDO pacing studies from five international centres: Johns Hopkins-USA, Bordeaux-France, Eindhoven-The Netherlands, Oxford-United Kingdom, and Guys and St Thomas' NHS Foundation Trust, London-UK. In all, 104 patients incorporating 687 endocardial and 93 epicardial pacing locations were studied. Mean age was 66 ± 11 years, mean left ventricular ejection fraction 24.6 ± 7.7% and mean QRS duration of 163 ± 30 ms. In all, 50% were ischaemic [ischaemic cardiomyopathy (ICM)]. Scarred segments were associated with worse haemodynamics (dp/dtmax; 890 mmHg/s vs. 982 mmHg/s, P < 0.01). Delivering BiVENDO pacing in areas of electrical latency was associated with greater improvements in AHR (P < 0.01). Stimulating late activating tissue (LVLED >50%) achieved greater increases in AHR than non-late activating tissue (LVLED < 50%) (8.6 ± 9.6% vs. 16.1 ± 16.2%, P = 0.002). However, the LVENDO pacing location with the latest Q-LV, was associated with the optimal AHR in just 62% of cases. Conclusions: Identifying viable LVENDO tissue which displays late electrical activation is crucial to identifying the optimal BiVENDO pacing site. Stimulating late activating tissue (LVLED >50%) yields greater improvements in AHR however, the optimal location is frequently not the site of latest activation.

Endocardial left ventricular pacing across the interventricular septum for cardiac resynchronization therapy: Clinical results of a pilot study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with heart failure, but it can be limited by the inability to place the left ventricular (LV) lead via the coronary sinus. OBJECTIVE: The purpose of this study was to develop an alternative approach, placing the LV lead endocardially via an interventricular septal puncture, and to assess the feasibility and safety of this technique. METHODS: All patients were anticoagulated with warfarin (international normalized ratio 2.5-3.5). A superior approach ventricular transseptal puncture using radiofrequency energy was performed. An active fixation pacing lead was delivered to the mapped site of latest electrical activation on the endocardial LV. RESULTS: Twenty patients were recruited, 15 with failed transvenous LV lead placement and 5 nonresponders to CRT. Mean (± SD) age was 67 ± 12, with 80% male, QRS duration 157 ± 14 ms, ischemic etiology 45%, New York Heart Association functional class 2.9 ± 0.4, and LV ejection fraction 28% ± 7%. The procedure was successful in all, with no serious complications. Clinical composite score improved at 6 months in 65% and worsened in 35%. LV ejection fraction improved >5% in 88%, from 28% ± 7% to 41% ± 9%. Six-minute walking distance improved >10% in 64%, from 248 ± 125 m to 316 ± 109 m. One patient suffered a lacunar ischemic stroke after 5 months with partial neurological recovery, associated with labile international normalized ratios. After 2.0 ± 1.0 years of follow-up, 3 patients died (2 pneumonia, 1 heart failure), and 2 patients suffered transient ischemic attacks. CONCLUSION: LV endocardial pacing via interventricular septal puncture in patients for whom standard CRT is not possible is similarly effective and durable, with significant but potentially acceptable risks.

Procedural Success of Left Ventricular Lead Placement for Cardiac Resynchronization Therapy: A Meta-Analysis.

OBJECTIVES: The goal of this study was to assess the contemporary and historical success rates of transvenous left ventricular (LV) lead placement for cardiac resynchronization therapy (CRT), their change over time, and the reasons for failure. BACKGROUND: In selected patients, CRT improves morbidity and mortality, but the placement of the LV lead can be technically challenging. METHODS: A literature search was used to identify all studies reporting success rates of LV lead placement for CRT via the coronary sinus (CS) route. A total of 164 studies were identified, and a meta-analysis was performed. RESULTS: The studies included 29,503 patients: 74% (95% confidence interval [CI]: 72% to 76%) were male; their mean age was 66 years (95% CI: 65 to 67); their mean New York Heart Association functional class was 2.8 (95% CI: 2.7 to 2.9); the mean LV ejection fraction was 26% (95% CI: 25% to 28%); and the mean QRS duration was 155 ms (95% CI: 150 to 160). The overall rate of failure of implantation of an LV lead was 3.6% (95% CI: 3.1 to 4.3). The rate of failure in studies commencing before 2005 was 5.4% (95% CI: 4.4% to 6.5%), and from 2005 onward it was 2.4% (95% CI: 1.9% to 3.1%; p < 0.001). Causes of failure (reported for 39% of failures) also changed over time. Failure to cannulate and navigate the CS decreased from 53% to 30% (p = 0.01), and the absence of any suitable, acceptable vein increased from 39% to 64% (p = 0.007). The proportion of leads in a lateral or posterolateral final position (reported for 26% of leads) increased from 66% to 82% (p = 0.004). CONCLUSIONS: The reported rate of failure to place an LV lead via the CS has decreased steadily over time. A greater proportion of failures in recent studies are due to coronary venous anatomy that is unsuitable for this technique.

Multisite left ventricular pacing in cardiac resynchronization therapy.

Cardiac resynchronization therapy is an effective treatment for selected patients with heart failure and left bundle branch block dyssynchrony. Unfortunately, about a third of patients, so-called nonresponders, do not display any symptomatic or structural improvements after the treatment. In another 5% of patients, the left ventricular lead cannot be implanted due to technical limitations. Novel quadripolar pacing lead and associated multisite pacing technology has the potential to help improve both of these problems. The technology and applications of these leads are reviewed and the novel technique of multisite pacing from two poles of one quadripolar lead is discussed. This technology may improve response to cardiac resynchronization therapy for some patients.

Development of a technique for left ventricular endocardial pacing via puncture of the interventricular septum.

BACKGROUND: Left ventricular (LV) pacing through the coronary sinus is the standard approach for cardiac resynchronization therapy. When this route is unavailable, the alternatives have major limitations. LV endocardial pacing through the interventriuclar septum may offer a simpler solution. We describe an initial case series to demonstrate technical feasibility and to describe our refinement of the puncture technique. METHODS AND RESULTS: Ten patients with previous failed coronary sinus lead implant or with nonresponse to cardiac resynchronization therapy and a suboptimal LV lead position were selected. All patients were anticoagulated. Left ventriculography and coronary angiography were performed to identify LV borders and septal vessels. Subclavian vein access was used for a superior approach ventricular transseptal puncture under fluoroscopic guidance, using a steerable sheath and a standard transseptal needle, radiofrequency needle, or radiofrequency energy delivered through a guidewire. An active-fixation pacing lead was successfully delivered to the endocardial wall of the lateral LV in all patients (9 men; age, 62±10 years). LV lead implant procedure time shortened with experience. The use of radiofrequency energy delivered through a guidewire was the most effective technique. Mean threshold and R wave at implant were 0.8±0.3 V and 10.8±3.9 mV. At follow-up (mean, 8.7 months; minimum, 0; and maximum 19), thresholds were stable, and there were no thromboembolic events. Of 9 patients, 8 were classed as clinical responders (1 had inadequate follow-up to assess response). CONCLUSIONS: LV endocardial pacing through a ventricular septal puncture is a feasible approach for cardiac resynchronization therapy.

High-sensitivity cardiac troponins: no more 'negatives'.

According to recently published expert guidelines, cardiac troponins are the only accepted biomarkers to define acute myocardial infarction. New high sensitivity cardiac troponin assays provide exciting opportunities for early rule-out and rule-in strategies and for identifying high-risk patients early in their presentation to guide early treatment and intervention. This review briefly discusses the history of troponin testing, before going on to cover clinical uses of the new highly sensitive assays in the early assessment of acute myocardial infection. Common clinical pitfalls with the use of these assays are discussed, as is the use of highly sensitive troponins more widely as prognostic markers. Likely future developments in this area are discussed.

Pathophysiology of coronary artery disease: the case for multiparametric imaging.

Interventions to treat coronary artery disease are available but they must be targeted at the correct individuals (and indeed lesions), in order to gain maximal benefit with the minimal adverse effects. Coronary contrast angiography is not able to provide all the information required for the assessment of the effects of artery disease. Other imaging modalities are of growing importance as they can reduce radiation exposure and invasiveness of screening, as well as providing important extra information. The ideal 'multiparametric' imaging technique would assess anatomy, viability and lesion activity in a single quick scan. Currently, MRI is the technology closest to achieving this ideal, although the existing technology still has some limitations. This review discusses the currently available techniques for the imaging of coronary anatomy and of myocardial viability, and considers their benefits and limitations. We also discuss the developing field of imaging molecularly targeted to active coronary lesions. Finally we provide a 5-year view of the current and likely future optimal imaging strategies.