Residual leaks following percutaneous left atrial appendage occlusion and outcomes: a meta-analysis.

BACKGROUND AND AIMS: Residual leaks are not infrequent after left atrial appendage occlusion. However, there is still uncertainty regarding their prognostic implications. The aim of this study is to evaluate the impact of residual leaks after left atrial appendage occlusion. METHODS: A literature search was conducted until 19 February 2023. Residual leaks comprised peri-device leaks (PDLs) on transoesophageal echocardiography (TEE) or computed tomography (CT), as well as left atrial appendage patency on CT. Random-effects meta-analyses were performed to assess the clinical impact of residual leaks. RESULTS: Overall 48 eligible studies (44 non-randomized/observational and 4 randomized studies) including 61 666 patients with atrial fibrillation who underwent left atrial appendage occlusion were analysed. Peri-device leak by TEE was present in 26.1% of patients. Computed tomography-based left atrial appendage patency and PDL were present in 54.9% and 57.3% of patients, respectively. Transoesophageal echocardiography-based PDL (i.e. any reported PDL regardless of its size) was significantly associated with a higher risk of thromboembolism [pooled odds ratio (pOR) 2.04, 95% confidence interval (CI): 1.52-2.74], all-cause mortality (pOR 1.16, 95% CI: 1.08-1.24), and major bleeding (pOR 1.12, 95% CI: 1.03-1.22), compared with no reported PDL. A positive graded association between PDL size and risk of thromboembolism was noted across TEE cut-offs. For any PDL of >0, >1, >3, and >5 mm, the pORs for thromboembolism were 1.82 (95% CI: 1.35-2.47), 2.13 (95% CI: 1.04-4.35), 4.14 (95% CI: 2.07-8.27), and 4.44 (95% CI: 2.09-9.43), respectively, compared with either no PDL or PDL smaller than each cut-off. Neither left atrial appendage patency, nor PDL by CT was associated with thromboembolism (pOR 1.45 and 1.04, 95% CI: 0.84-2.50 and 0.52-2.07, respectively). CONCLUSIONS: Peri-device leak detected by TEE was associated with adverse events, primarily thromboembolism. Residual leaks detected by CT were more frequent but lacked prognostic significance.

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis.

AIM: The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis. RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2 ; 95% CI (-0.64, 1.42); p = .46; LoE moderate]. CONCLUSION: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.

The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an overview of 36 systematic reviews.

The recently published randomized trials (RCTs) evaluating the effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) led researchers to perform a plethora of systematic reviews (SRs), often providing contradictory conclusions. This overview of reviews was aimed at summarizing the evidence of these SRs, quantifying the overlap, re-analyzing the evidence in case new studies that were identified, and mapping knowledge gaps. Literature search was conducted through Medline, Scopus, and Cochrane until March 22, 2023. Overall, 36 SRs synthesizing results from 18 RCTs were identified. A substantial overlap was identified among the SRs synthesizing large heart failure or cardiovascular outcome trials (CVOTs). Regarding the composite outcome of cardiovascular (CV) mortality or hospitalization for heart failure (HHF), all authors reported a significant favorable effect. A beneficial effect was also noted for CV and all-cause mortality, albeit not significant. Our meta-analysis demonstrated a significant improvement in health-related quality-of-life (HRQoL) as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS, MD = 1.97, p < 0.001), Total Symptom Score (KCCQ-TSS, MD = 2.29, p < 0.001), Clinical Summary Score (KCCQ-CSS, MD = 1.59, p < 0.001), and the 6-min walking distance (MD = 10.78 m, p = 0.032). Regarding safety, SGLT2i were associated with a significantly lower risk of serious adverse events compared to placebo (RR = 0.94, p = 0.002). The use of SGLT2i in HFpEF is both efficient and safe. Further research is required to clarify the impact of SGTL2i on different subphenotypes of HFpEF and the cardiorespiratory capacity of these patients.

Efficacy and safety of once-weekly versus once-daily basal insulin analogues in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues. METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis. RESULTS: A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups. CONCLUSION: The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.

Risk assessment of post-myocardial infarction patients with preserved ejection fraction using 45-min short resting Holter electrocardiographic recordings.

BACKGROUND: Risk stratification for sudden cardiac death in post-myocardial infarction (post-MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors (NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45-min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post-MI patients with preserved left ventricular ejection fraction (LVEF). METHODS: We studied 99 post-MI ischemia-free patients (mean age: 60.5 ± 9.5 years, 86.9% men) with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high-resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias (premature ventricular complexes, couplets, tachycardias), QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T-wave alternans. RESULTS: PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal-to-normal R-R intervals (SDNN), was significantly decreased in the positive PVS group (42 ms vs. 51 ms, p = .039). SDNN values <50 ms were also associated with PVS inducibility (OR 3.081, p = .032 in univariate analysis, and 4.588, p = .013 in multivariate analysis). No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST-elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS. CONCLUSIONS: HRV assessed from SHR, combined with other noninvasive clinical and echocardiographic variables (diabetes, STEMI history, LVEF), can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post-MI patients with preserved LVEF.

Comparing efficacy and safety in catheter ablation strategies for atrial fibrillation: a network meta-analysis.

BACKGROUND: There is no consensus on the most efficient catheter ablation (CA) strategy for patients with atrial fibrillation (AF). The objective of this study was to compare the efficacy and safety of different CA strategies for AF ablation through network meta-analysis (NMA). METHODS: A systematic search of PubMed, Web of Science, and CENTRAL was performed up to October 5th, 2020. Randomized controlled trials (RCT) comparing different CA approaches were included. Efficacy was defined as arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of 6 months. RESULTS: In total, 67 RCTs (n = 9871) comparing 19 different CA strategies were included. The risk of recurrence was significantly decreased compared to pulmonary vein isolation (PVI) alone for PVI with renal denervation (RR: 0.60, CI: 0.38-0.94), PVI with ganglia-plexi ablation (RR: 0.62, CI: 0.41-0.94), PVI with additional ablation lines (RR: 0.8, CI: 0.68-0.95) and PVI in combination with bi-atrial modification (RR: 0.32, CI: 0.11-0.88). Strategies including PVI appeared superior to non-PVI strategies such as electrogram-based approaches. No significant differences in safety were observed. CONCLUSIONS: This NMA showed that PVI in combination with additional CA strategies, such as autonomic modulation and additional lines, seem to increase the efficacy of PVI alone. These strategies can be considered in treating patients with AF, since, additionally, no differences in safety were observed. This study provides decision-makers with comprehensive and comparative evidence about the efficacy and safety of different CA strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number: CRD42020169494 .

Neuromuscular diseases and their cardiac manifestations under the spectrum of cardiovascular imaging.

Neuromuscular diseases (NMDs) include a broad spectrum of disorders that affect motor unit in every possible site, extending from the cell body of peripheral nerves to the muscle. The different lesion sites make this group of inherited disorders difficult to diagnose. Many NMDs, especially those involving skeletal muscles, can present significant cardiovascular complications, ranging from rhythm disturbances to the development of dilated or hypertrophic cardiomyopathy. Heart disease represents a major cause of morbidity and mortality among NMD patients, underlining the vital need for further familiarization with the pathogenesis and assessment of cardiac involvement. Cardiovascular imaging is the cornerstone for the evaluation of heart disorders in NMDs, with conventional echocardiography still offering a portable, affordable, and easily accessible solution. Meanwhile, newer echocardiographic techniques such as speckle tracking imaging in combination with cardiac magnetic resonance add new insights into further substrate characterization. The purpose of this review is to offer a brief presentation of the main NMDs and their cardiovascular complications, as well as the presentation of data that highlight the importance of cardiovascular imaging in early diagnosis, monitoring, and prognosis of these patients. Lastly, the authors provide a simple guide about which clinical features, imaging findings, and follow-up plan to adopt in each myopathic disorder.

Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). METHODS: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. RESULTS: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. CONCLUSION: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

Intracoronary Thrombolysis in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: an Updated Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the standard reperfusion treatment in ST-segment elevation myocardial infarction (STEMI). Intracoronary thrombolysis (ICT) may reduce thrombotic burden in the infarct-related artery, which is often responsible for microvascular obstruction and no-reflow. METHODS: We conducted, according to the PRISMA statement, the largest meta-analysis to date of ICT as adjuvant therapy to PPCI. All relevant studies were identified by searching the PubMed, Scopus, Cochrane Library, and Web of Science. RESULTS: Thirteen randomized controlled trials (RCTs) involving a total of 1876 patients were included. Compared to the control group, STEMI ICT-treated patients had fewer major adverse cardiac events (MACE) (OR 0.65, 95% CI, 0.48-0.86, P = 0.003) and an improved 6-month left ventricular ejection fraction (MD 3.78, 95% CI, 1.53-6.02, P = 0.0010). Indices of enhanced myocardial microcirculation were better with ICT (Post-PCI corrected thrombolysis in myocardial infarction (TIMI) frame count (MD - 3.57; 95% CI, - 5.00 to - 2.14, P < 0.00001); myocardial blush grade (MBG) 2/3 (OR 1.76; 95% CI, 1.16-2.69, P = 0.008), and complete ST-segment resolution (OR 1.97; 95% CI, 1.33-2.91, P = 0.0007)). The odds for major bleeding were comparable between the 2 groups (OR 1.27; 95% CI, 0.61-2.63, P = 0.53). CONCLUSIONS: The present meta-analysis suggests that ICT was associated with improved MACE and myocardial microcirculation in STEMI patients undergoing PPCI, without significant increase in major bleeding. However, these findings necessitate confirmation in a contemporary large RCT.

Association of non-invasive electrocardiographic risk factors with left ventricular systolic function in post-myocardial infarction patients with mildly reduced or preserved ejection fraction: Insights from the PRESERVE-EF study.

BACKGROUND: Electrocardiographic non-invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post-myocardial infarction (post-MI) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE-EF trial. METHODS: We studied 575 post-MI ischemia-free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non-sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T-wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence. RESULTS: There was a statistically significant relationship between LPs (Chi-squared = 4.975; p < .05), nsVT (Chi-squared = 5.749, p < .05), PVCs (r= -.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02-3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18-5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%-49% versus the preserved LVEF: ≥50%. CONCLUSION: Late potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post-MI patients with mildly reduced or preserved LVEF.

QT interval extracted from 30-minute short resting Holter ECG recordings predicts mortality in heart failure.

BACKGROUND: Prolonged repolarization duration is a significant total mortality (TM) predictor in post-myocardial infarction patients. AIM: We examined the clinical significance of QT interval that was extracted from a Short Resting Holter ECG (SRH ECG - 30-min duration) as a TM predictor in heart failure (HF) patients. METHODS: One hundred forty-five HF patients (male = 84%, mean age = 64 ± 12 years, mean LVEF = 33 ± 10%) underwent an SRH ECG recording for 30 min. These high-resolution ECG signals were analyzed and the QT interval was calculated and corrected according to the Fridericia formula. After 42.1 months, 26 patients died. RESULTS: Univariate analysis for Deceased and Living groups: QTc:455 ± 33 ms vs 441 ± 32 ms (p = 0.04), LVEF:32 ± 10% vs 34 ± 9% (p < 0.5), Mean Heart Rate: 73 ± 11 bpm vs 69 ± 12 bpm (p = 0.2), SDNN/HRV: 45 ± 42 ms vs 41 ± 29 ms (p = 0.4), QRS: 123 ± 26 ms vs 119 ± 29 ms (p = 0.5). Multivariate Cox regression analysis with model adjusted for QTc, Mean Heart Rate, LVEF, QRS, revealed that QTc-Fridericia interval was an independent TM predictor (H.R.:1.017, 95% C.I.: 1.003-1.030, p = 0.01). The cut-off point of 490 ms (90th percentile) in the same model presented HR: 2.9 for TM (95%C.I.: 1.066-7.882, p = 0.03). Kaplan Meier curves depicted a clear difference in survival between the two patients' groups (QTc Group≥490 ms vs QTc Group <490 ms). The curve diverge was important (log-rank, p = 0.02). CONCLUSION: A fast risk stratification approach with SRH ECG recording is an efficient method for flash evaluation of mortality risk in HF patients.

Ultrasound-guided versus anatomic landmark-guided vascular access in cardiac electrophysiology procedures: A systematic review and meta-analysis.

INTRODUCTION: Electrophysiology (EP) procedures are nowadays the gold-standard method for tachyarrhythmia treatment with impressive success rates, but also with a considerable risk of complications, mainly vascular. A systematic review and meta-analysis was performed to evaluate the safety of ultrasound (US)-guided femoral vein access in EP procedures compared to the traditional anatomic landmark-guided method. METHODS: We searched Pubmed (MEDLINE), Embase, Web of Science, and Cochrane electronic databases for relevant entries, dated from January 1st, 2000 to June 30th, 2021. Only observational studies and randomized controlled trials were included in this analysis. Data extraction included study details, patient characteristics, procedure details, and all types of vascular complications. Complications were classified as major if any intervention, prolongation of hospitalization, or readmission was required. RESULTS: 9 studies (1 randomized controlled trial and 8 observational), with 7858 participants (3743 in the US-guided group, 4115 in the control group), were included in the meta-analysis. Overall vascular complication rates were significantly decreased in the US-guided group compared to the control group (1.2 versus 3.2%, RR = 0.38, 95% CI, 0.27-0.53), in all EP procedures. Sub-group analysis of AF ablation procedures yielded similar results (RR 0.41, 95% CI, 0.29-0.58, p < 0.00001). The event reduction effect was significant for both major and minor vascular complications. CONCLUSION: US-guided vascular access in EP procedures is associated with significantly reduced vascular complications, compared to the standard anatomic landmark-guided approach, regardless of procedure complexity.

Syncope associated with supraventricular tachycardia: Diagnostic role of implantable loop recorders.

Syncope represents a relatively uncommon symptom of supraventricular tachycardia (SVT). It is likely that an impaired autonomic vasomotor response to the hemodynamic stress of tachycardia is the determinant of hemodynamic changes leading to cerebral hypoperfusion and syncope. In this regard, tilt-table test may detect abnormalities in the autonomic nervous function and predict the occurrence of syncope during SVT. Electrophysiology studies may reproduce the SVT, distinguish it from other life-threatening ventricular tachyarrhythmias, and exclude other causes of syncope. Not infrequently mixed syncope mechanisms are revealed during the above diagnostic workup raising doubts about the operating mechanism in the clinical setting. In such cases of uncertainty, an implantable loop recorder, providing long-term cardiac monitoring, may play a pivotal role in the establishment of the diagnosis, confirming the association of an arrhythmic event with the symptom. Herein, we present four such cases with recurrent unexplained syncope finally attributed to paroxysmal SVT guiding them to a potentially radical treatment through radiofrequency catheter ablation.

Iron deficiency as therapeutic target in heart failure: a translational approach.

Heart failure (HF) is a potentially debilitating condition, with a prognosis comparable to many forms of cancer. It is often complicated by anemia and iron deficiency (ID), which have been shown to even further harm patients' functional status and hospitalization risk. Iron is a cellular micronutrient that is essential for oxygen uptake and transportation, as well as mitochondrial energy production. Iron is crucially involved in electrochemical stability, maintenance of structure, and contractility of cardiomyocytes. There is mounting evidence that ID indeed hampers the homeostasis of these properties. Animal model and stem cell research has verified these findings on the cellular level, while clinical trials that treat ID in HF patients have shown promising results in improving real patient outcomes, as electromechanically compromised cardiomyocytes translate to HF exacerbations and arrhythmias in patients. In this article, we review our current knowledge on the role of iron in cardiac muscle cells, the contribution of ID to anemia and HF pathophysiology and the capacity of IV iron therapy to ameliorate the patients' arrhythmogenic profile, quality of life, and prognosis.

Excessive Supraventricular Ectopic Activity and Adverse Cardiovascular Outcomes: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality. RECENT FINDINGS: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately. RESULTS: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70-2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24-4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25-2.07). Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes.

Arrhythmic risk stratification in post-myocardial infarction patients with preserved ejection fraction: the PRESERVE EF study.

AIMS: Sudden cardiac death (SCD) annual incidence is 0.6-1% in post-myocardial infarction (MI) patients with left ventricular ejection fraction (LVEF)≥40%. No recommendations for implantable cardioverter-defibrillator (ICD) use exist in this population. METHODS AND RESULTS: We introduced a combined non-invasive/invasive risk stratification approach in post-MI ischaemia-free patients, with LVEF ≥ 40%, in a multicentre, prospective, observational cohort study. Patients with at least one positive electrocardiographic non-invasive risk factor (NIRF): premature ventricular complexes, non-sustained ventricular tachycardia, late potentials, prolonged QTc, increased T-wave alternans, reduced heart rate variability, abnormal deceleration capacity with abnormal turbulence, were referred for programmed ventricular stimulation (PVS), with ICDs offered to those inducible. The primary endpoint was the occurrence of a major arrhythmic event (MAE), namely sustained ventricular tachycardia/fibrillation, appropriate ICD activation or SCD. We screened and included 575 consecutive patients (mean age 57 years, LVEF 50.8%). Of them, 204 (35.5%) had at least one positive NIRF. Forty-one of 152 patients undergoing PVS (27-7.1% of total sample) were inducible. Thirty-seven (90.2%) of them received an ICD. Mean follow-up was 32 months and no SCDs were observed, while 9 ICDs (1.57% of total screened population) were appropriately activated. None patient without NIRFs or with NIRFs but negative PVS met the primary endpoint. The algorithm yielded the following: sensitivity 100%, specificity 93.8%, positive predictive value 22%, and negative predictive value 100%. CONCLUSION: The two-step approach of the PRESERVE EF study detects a subpopulation of post-MI patients with preserved LVEF at risk for MAEs that can be effectively addressed with an ICD. CLINICALTRIALS.GOV IDENTIFIER: NCT02124018.

Clinical characteristics and long-term clinical course of patients with Brugada syndrome without previous cardiac arrest: a multiparametric risk stratification approach.

AIMS: Risk stratification in Brugada syndrome (BrS) still represents an unsettled issue. In this multicentre study, we aimed to evaluate the clinical characteristics and the long-term clinical course of patients with BrS. METHODS AND RESULTS: A total of 111 consecutive patients (86 males; aged 45.3 ± 13.3 years) diagnosed with BrS were included and followed-up in a prospective fashion. Thirty-seven patients (33.3%) were symptomatic at enrolment (arrhythmic syncope). An electrophysiological study (EPS) was performed in 59 patients (53.2%), and ventricular arrhythmias were induced in 32 (54.2%). A cardioverter defibrillator was implanted in 34 cases (30.6%). During a mean follow-up period of 4.6 ± 3.5 years, appropriate device therapies occurred in seven patients. Event-free survival analysis (log-rank test) showed that spontaneous type-1 electrocardiogram pattern (P = 0.008), symptoms at presentation (syncope) (P = 0.012), family history of sudden cardiac death (P < 0.001), positive EPS (P = 0.024), fragmented QRS (P = 0.004), and QRS duration in lead V2 > 113 ms (P < 0.001) are predictors of future arrhythmic events. Event rates were 0%, 4%, and 60% among patients with 0-1 risk factor, 2-3 risk factors, and 4-5 risk factors, respectively (P < 0.001). Current multiparametric score models exhibit an excellent negative predictive value and perform well in risk stratification of BrS patients. CONCLUSIONS: Multiparametric models including common risk factors appear to provide better risk stratification of BrS patients than single factors alone.

Electrophysiological markers predicting impeding AV-block during ablation of atrioventricular nodal reentry tachycardia.

BACKGROUND: Radiofrequency (RF) ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated with atrioventricular block (AVB) often predicted by junctional beats (JB) with loss of ventriculo-atrial (VA) conduction. METHODS: We analyzed retrospectively 153 patients undergoing ablation of SP for typical AVNRT. Patients were divided into two age groups: 127 ≤ 70 years and 26 > 70 years. We analyzed the interval between the atrial electrogram in the His-bundle position and the distal ablation catheter [A(H)-A(RFd)] and between the distal ablation catheter and the proximal coronary sinus catheter [A(RFd)-A(CS)] before RF applications with and without JB. We evaluated if these intervals can be used as predictors of JB incidence and also of JB with loss of VA conduction. We also assessed if age influences the risk of loss of VA conduction. RESULTS: The A(H)-A(RFd) and A(RFd)-A(CS) intervals were significantly shorter in RF applications causing JB than those without JB (33 ± 11 ms vs 39 ± 9 ms, P < 0.001, 14 ± 9 ms vs 20 ± 7 ms, P < 0.001, respectively). The A(H)-A(RFd) and A(RFd)-A(CS) intervals were also significantly shorter in RFs causing JB with VA block than those with VA conduction (29 ± 11 ms vs 35 ± 11 ms, P < 0.001, 8 ± 8 ms vs 17 ± 8 ms, P < 0.001, respectively). Patients > 70 years had shorter intervals (36 ± 11 ms vs 29 ± 8 ms, P  =  0.012, 17 ± 8 ms vs 13 ± 7 ms, P  =  0.027, respectively), while VA block was more common in this age group. CONCLUSIONS: The A(H)-A(RFd) and A(RFd)-A(CS) intervals can be used as markers for predicting JB occurrence as well as impending AVB. JB with loss of VA conduction occur more often in older patients possibly due to a higher position of SP.