Efficacy, Safety and Feasibility of Superior Vena Cava Isolation in Patients Undergoing Atrial Fibrillation Catheter Ablation: An Up-to-Date Review.

Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI?

Left atrial appendage morphofunctional indices could be predictive of arrhythmia recurrence post-atrial fibrillation ablation: a meta-analysis.

BACKGROUND: Left atrium changes are implicated in atrial fibrillation (AF) substrate and are predictive of AF outcomes. Left atrial appendage (LAA) is an integral component of left atrial structure and could be affected by atrial cardiomyopathy. We aimed to elucidate the association between LAA indices and late arrhythmia recurrence after atrial fibrillation catheter ablation (AFCA). METHODS: The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating LAA and late arrhythmia recurrence in patients undergoing AFCA. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was pre-ablation difference in LAA anatomic or functional indices. RESULTS: A total of 34 studies were found eligible and five LAA indices were analyzed. LAA ejection fraction and LAA emptying velocity were significantly lower in patients with AF recurrence post-ablation [SMD = - 0.66; 95% CI (- 1.01, - 0.32) and SMD = - 0.56; 95% CI (- 0.73, - 0.40) respectively] as compared to arrhythmia free controls. LAA volume and LAA orifice area were significantly higher in patients with AF recurrence post-ablation (SMD = 0.51; 95% CI 0.35-0.67, and SMD = 0.35; 95% CI 0.20-0.49, respectively) as compared to arrhythmia free controls. LAA morphology was not predictive of AF recurrence post-ablation (chicken wing morphology; OR 1.27; 95% CI 0.79-2.02). Moderate statistical heterogeneity and small case-control studies are the main limitations of our meta-analysis. CONCLUSIONS: Our findings suggest that LAA ejection fraction, LAA emptying velocity, LAA orifice area and LAA volume differ between patients suffering from arrhythmia recurrence post-ablation and arrhythmia free counterparts, while LAA morphology is not predictive of AF recurrence.

Advances in the Management of Heart Failure with Reduced Ejection Fraction; The Role of SGLT2is, ARNI, Myotropes, Vericiguat, and Anti-inflammatory Agents: A Mini-review.

Heart failure with reduced ejection fraction (HFrEF) has been associated with poor prognosis, reduced quality of life, and increased healthcare expenditure. Despite tremendous advances in HFrEF management, reduced survival and a high rate of hospitalization remain unsolved issues. Furthermore, HFrEF morbidity and economic burden are estimated to increase in the following years; hence, new therapies are constantly emerging. In the last few years, a series of landmark clinical trials have expanded our therapeutic armamentarium with a ground-breaking change in HFrEF-related outcomes. Sodium-glucose co-transporter 2 inhibitors (mainly dapagliflozin and empagliflozin) have already revolutionized the management of HFrEF patients via a significant reduction in cardiovascular mortality and heart failure hospitalizations. Furthermore, vericiguat and omecamtiv mecarbil have emerged as promising and novel disease-modifying therapies. The former restores the impaired cyclic guanosine monophosphate pathway, and the latter stimulates cardiac myosin without marked arrhythmogenesis. Both vericiguat and omecamtiv mecarbil have been shown to reduce heart failure admissions. Sacubitril/valsartan is an established and effective therapy in HFrEF patients and should be considered as a replacement for angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). Lastly, inflammasome activity is implicated in HFrEF pathophysiology, and the role of anti-inflammatory agents in HFrEF trajectories is readily scrutinized, yet available therapies are ineffective. This mini-review summarizes the major and most recent studies in this field, thus covering the current advances in HFrEF therapeutics.

Choroidal thickness in patients with systemic arterial hypertension: a systematic review and meta-analysis.

Background: The global burden of hypertension is constantly increasing with adverse cardiovascular and ocular sequelae. The association between elevated blood pressure and choroidal thickness (CT), as assessed via optical coherence tomography (OCT), is poorly understood. Objectives and Design: Studies including hypertensive adults and normotensive controls undergoing OCT were evaluated for inclusion in this meta-analysis. The primary endpoint was CT difference between hypertensive and normotensive adults. Data Sources and Methods: We conducted a systematic review and after searching 1011 results from MEDLINE, ClinicalTrials.gov, medRxiv and Cochrane Library, six studies were deemed eligible and were pooled according to a random-effect model. Results: A statistically significant reduction in choroidal thickness was found in hypertensive adults (n = 454) as compared with normotensive controls (n = 365) [mean difference: -0.77; 95% confidence intervals: (-1.20, -0.34); p = 0.0004]. The main limitations of this meta-analysis are the relatively small population included and the high statistical heterogeneity (I 2 = 87%) among the various studies. Of note, after excluding one study the heterogeneity was markedly reduced. Conclusion: Choroidal thickness is reduced among hypertensive subjects compared with normotensive controls. This finding mandates further examination in the context of long-term clinical outcomes.

Inflammatory Biomarkers in Coronary Artery Ectasia: A Systematic Review and Meta-Analysis.

Isolated coronary artery ectasia (CAE) is a relatively rare clinical entity, the pathogenesis of which is poorly understood. More and more evidence is accumulating to suggest a critical inflammatory component. We aimed to elucidate any association between neutrophil to lymphocyte ratio and coronary artery ectasia. A systematic MEDLINE database, ClinicalTrials.gov, medRxiv, Scopus and Cochrane Library search was conducted: 50 studies were deemed relevant, reporting on difference in NLR levels between CAE patients and controls (primary endpoint) and/or on high-sensitive CRP, IL-6, TNF-a and RDW levels (secondary endpoint), and were included in our final analysis. (PROSPERO registration number: CRD42021224195). All inflammatory biomarkers under investigation were found higher in coronary artery ectasia patients as compared to healthy controls (NLR; SMD = 0.73; 95% CI: 0.27-1.20, hs-CRP; SMD = 0.96; 95% CI: 0.64-1.28, IL-6; SMD = 2.68; 95% CI: 0.95-4.41, TNF-a; SMD = 0.50; 95% CI: 0.24-0.75, RDW; SMD = 0.56; 95% CI: 0.26-0.87). The main limitations inherent in this analysis are small case-control studies of moderate quality and high statistical heterogeneity. Our findings underscore that inflammatory dysregulation is implicated in coronary artery ectasia and merits further investigation.

Early arrhythmia recurrence after cryoballoon ablation in atrial fibrillation: A systematic review and meta-analysis.

INTRODUCTION: Early arrhythmia recurrence within the 3-month blanking period is a common event that historically has been attributed to reversible phenomena. While its mechanistic links remain obscure, accumulating evidence support the argument of shortening the blanking period. We aimed to elucidate the association between early and late arrhythmia recurrence after atrial fibrillation cryoablation. METHODS: The MEDLINE database, ClinicalTrials. gov, medRxiv, and Cochrane Library were searched for studies evaluating early and late arrhythmia recurrence rates in patients undergoing cryoablation for atrial fibrillation. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was late arrhythmia recurrence. RESULTS: Early arrhythmia recurrence was found predictive of decreased arrhythmia-free survival after evaluating 3975 patients with paroxysmal or persistent atrial fibrillation who underwent cryoablation (odds ratio [OR]: 5.31; 95% confidence interval [CI]: 3.75-7.51). This pattern remained unchanged after subanalyzing atrial fibrillation type (paroxysmal; OR: 7.16; 95% CI: 4.40-11.65 and persistent; OR: 7.63; 95% CI: 3.62-16.07) as well as cryoablation catheter generation (first generation; OR: 5.15, 95% CI: 2.39-11.11 and advanced generation; OR: 5.83, 95% CI: 3.68-9.23). Studies permitting antiarrhythmic drug utilization during the blanking period or examining early recurrence as a secondary outcome were found to be a significant source of statistical heterogeneity. CONCLUSION: Our findings suggest that early arrhythmia recurrence is predictive of late outcomes after cryoablation for atrial fibrillation. Identifying which patients deserve earlier reintervention is an open research avenue.

Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine.

In 2020, SARS-COV-2 put health systems under unprecedented resource and manpower pressure leading to significant number of deaths. Expectedly, researchers sought to shed light on the pathophysiologic background of this novel disease (COVID-19) as well as to facilitate the design of effective therapeutic modalities. Indeed, early enough the pivotal role of inflammatory and thrombotic pathways in SARS-COV-2 infection has been illustrated. The purpose of this article is to briefly present the epidemiologic and clinical features of COVID-19, analyze the pathophysiologic importance of immunologic dysregulation and hypercoagulability in developing disease complications and finally to present an up-to-date systematic review of colchicine's immunomodulating capacity in view of hindering coronavirus complications.

Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review.

The prevalence of atrial fibrillation (AF) is bound to increase globally in the following years, affecting the quality of life of millions of people, increasing mortality and morbidity, and beleaguering health care systems. Increasingly effective therapeutic options against AF are the constantly evolving electroanatomic substrate mapping systems of the left atrium (LA) and ablation catheter technologies. Yet, a prerequisite for better long-term success rates is the understanding of AF pathogenesis and maintenance. LA electrical and anatomical remodeling remains in the epicenter of current research for novel diagnostic and treatment modalities. On a molecular level, electrical remodeling lies on impaired calcium handling, enhanced inwardly rectifying potassium currents, and gap junction perturbations. In addition, a wide array of profibrotic stimuli activates fibroblast to an increased extracellular matrix turnover via various intermediaries. Concomitant dysregulation of the autonomic nervous system and the humoral function of increased epicardial adipose tissue (EAT) are established mediators in the pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate and increased inflammasome activity accelerate and perpetuate arrhythmia substrate. Finally, impaired intracellular protein metabolism, excessive oxidative stress, and mitochondrial dysfunction deplete atrial cardiomyocyte ATP and promote arrhythmogenesis. These overlapping cellular and molecular alterations hinder us from distinguishing the cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic modalities target these molecular perturbations and hold promise in combating the AF burden. Namely, atrial selective ion channel inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing, immunomodulators, and indirect cardiac neuromodulation are discussed here.

Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations.

The global burden of atrial fibrillation (AF) is constantly increasing, necessitating novel and effective therapeutic options. Sodium glucose co-transporter 2 (SGLT2) inhibitors have been introduced in clinical practice as glucose-lowering medications. However, they have recently gained prominence for their potential to exert substantial cardiorenal protection and are being evaluated in large clinical trials including patients with type 2 diabetes and normoglycemic adults. In this review we present up-to-date available evidence in a pathophysiology-directed manner from cell to bedside. Preclinical and clinical data regarding a conceivable antiarrhythmic effect of SGLT2 inhibitors are beginning to accumulate. Herein we comprehensively present data that explore the potential pathophysiological link between SGLT2 inhibitors and AF. With regard to clinical data, no randomized controlled trials evaluating SGLT2 inhibitors effects on AF as a pre-specified endpoint are available. However, data from randomized controlled trial post-hoc analysis as well as observational studies point to a possible beneficial effect of SGLT2 inhibitors on AF. Meta-analyses addressing this question report inconsistent results and the real magnitude of AF prevention by SGLT2 inhibition remains unclear. Still, while (i) pathophysiologic mechanisms involved in AF might be favorably affected by SGLT2 inhibitors and (ii) emerging, yet inconsistent, clinical data imply that SGLT2 inhibitor-mediated cardiorenal protection could also exert antiarrhythmic effects, the argument of whether these novel drugs will reduce AF burden is unsettled and mandates appropriately designed and adequately sized randomized controlled studies.

Moderate procedural sedation and opioid analgesia during transradial coronary interventions to prevent spasm: a prospective randomized study.

OBJECTIVES: The aim of this study was to test the hypothesis that moderate procedural sedation can reduce the incidence of radial artery spasm. BACKGROUND: Transradial access for left heart catheterization and percutaneous coronary intervention is increasingly used for emergent and elective procedures, in lieu of the femoral approach. However, increased rates of access site crossover have been reported, with radial artery spasm being a major contributor to this effect. METHODS: Patients undergoing elective transradial percutaneous coronary intervention were prospectively randomized to receive fentanyl and midazolam during the procedure or no treatment (control subjects). The primary endpoint was angiographically confirmed radial artery spasm. Patient discomfort was quantified with a visual analogue scale. RESULTS: Two thousand thirteen patients (age 64.5 ± 8.4 years) were randomized. Spasm occurred in 2.6% of the treatment group versus 8.3% of control subjects (p < 0.001; odds ratio [OR]: 0.29). The number needed to treat to avoid 1 case of spasm was 18 (95% confidence interval [CI]: 12.9 to 26.6). The access site crossover rate was 34% lower in the treatment group: 9.9% versus 15.0% (OR: 0.62; 95% CI: 0.48 to 0.82). Patient discomfort visual analogue scale score was 18.8 ± 12.5 in the treatment group versus 27.4 ± 17.4 in control subjects (p < 0.001). No significant differences were observed in the 30-day rate of death or repeat hospital stay for any cause: 4.6% versus 4.5% (OR: 1.02; 95% CI: 0.67 to 1.56). CONCLUSIONS: Routine administration of relatively low doses of an opioid/benzodiazepine combination during transradial interventional procedures is associated with a substantial reduction in the rate of spasm, the need for access site crossover, and the procedure-related level of patient discomfort.

Renoprotective effect of remote ischemic post-conditioning by intermittent balloon inflations in patients undergoing percutaneous coronary intervention.

OBJECTIVES: The aim of the present study was to assess the efficacy of remote ischemic post-conditioning (RIPC) by repeated intermittent balloon inflations in preventing acute kidney injury (AKI) in patients with a non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). BACKGROUND: AKI complicating PCI is associated with increased morbidity and mortality. Remote ischemic preconditioning, using cycles of upper limb ischemia-reperfusion as a conditioning stimulus, has been recently shown to prevent AKI in patients undergoing elective coronary angiography. METHODS: Eligible patients were randomized to receive RIPC by cycles of inflation and deflation of the stent balloon during PCI or a sham procedure (control patients). The primary endpoint was AKI, defined as an increase of ≥ 0.5 mg/dl or ≥ 25% in serum creatinine within 96 h from PCI. The 30-day rate of death or re-hospitalization for any cause was one of the secondary endpoints. RESULTS: A total of 225 patients were included (median age, 68 years; 36% female). The AKI rate in the RIPC group was 12.4% versus 29.5% in the control group (p = 0.002; odds ratio: 0.34; 95% confidence interval: 0.16 to 0.71). The number needed to treat to avoid 1 case of AKI was 6 (95% confidence interval: 3.6 to 15.2). The 30-day rate of death or re-hospitalization for any cause was 22.3% in the control group versus 12.4% in RIPC patients (p = 0.05). CONCLUSIONS: RIPC by serial balloon inflations and deflations during PCI was found to confer protection against AKI in patients with a non-ST-segment elevation myocardial infarction undergoing PCI. The reduction in the rate of AKI translated into a clear trend (of borderline significance) toward better 30-day clinical outcome.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia.

We describe the case of a 51-year-old woman with a 10-year history of dyspnoea and fatigue on slight effort, presyncopal episodes, and ventricular extrasystolic arrhythmia. Tests were negative for coronary artery disease, valvular disease, or left ventricular dysfunction. The patient fulfilled the clinical criteria for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and the diagnosis was confirmed histologically with an endomyocardial biopsy. During 5-year follow up she also exhibited significant structural progression to the left ventricle. This is a rare case of ARVC/D manifested in middle age, with a negative family history, negative test for desmosome mutations, and negative myocardial immunohistochemical analysis, evidence that tends to suggest an acquired form of the disease. We also present a brief review of the clinical, electrocardiographic, structural, pathological/anatomical and genetic characteristics of the disease, the diagnostic criteria, prognosis, management, and sudden death prevention, as well as the way we have managed our patient until the present day.

Acute inferior ST-segment elevation myocardial infarction treated with primary angioplasty using only a Pronto aspiration catheter.

In a patient with acute myocardial infarction treated with primary angioplasty, a large amount of thrombus was removed from the middle segment of the right coronary artery using a Pronto V3 extraction catheter (Vascular Solutions, Inc., Minneapolis, Minnesota). Repeat angiography revealed no significant residual stenosis and no further intervention was undertaken.

The effect of rapid decreases of blood pressure by different mechanisms on coronary flow and flow reserve in normal coronary arteries.

BACKGROUND: Changes in mean blood pressure (MBP) alter coronary blood flow (CBF). We evaluated the acute effects of three hypotensive medications on CBF parameters in angiographically normal coronary arteries. METHODS: We performed CBF measurements using the Doppler wire at rest and during hyperemia produced by intracoronary adenosine (18 microg) as follows: 1) in the normal left circumflex coronary artery in 20 patients with coronary artery disease (measurements were performed without drugs, and after intravenous infusion of nitroprusside [0.5 to 2 microg/kg/min] and nitroglycerin [10 to 90 microg/min]; drugs were titrated to decrease MBP 20% to 25% below the control values, and heart rate was held constant using right atrial pacing); and 2) in the normal left anterior descending coronary artery in 19 patients without coronary artery disease (measurements were performed before and after intravenous clonidine infusion [150 microg in 5 min]; time-averaged peak velocity [APV], CBF, and coronary flow reserve [CFR] were measured). RESULTS: Similar decreases in MBP were obtained in the two patient groups. Lumen diameter at the site of Doppler measurements increased after all medications (P <.005), whereas CBF did not change significantly. The CFR decreased after nitroprusside (1.79 +/- 0.48 v 2.54 +/- 0.45, P=.000), did not change significantly after nitroglycerin (2.74 +/- 0.43 v 2.54 +/- 0.45, P =.097), and increased after clonidine (3.12 +/- 0.70 v 2.76 +/- 0.75, P =.006). CONCLUSIONS: In normal coronary arteries the infusion of three hypotensive medications to produce the same decreases in MBP is associated with different effects on CFR (increase with clonidine, decrease with nitroprusside, and no change with nitroglycerin).

Relative coronary flow velocity reserve improves correlation with stress myocardial perfusion imaging in assessment of coronary artery stenoses.

STUDY OBJECTIVE: To evaluate the angiographic and coronary flow velocity parameters that best correlate with the results of stress myocardial perfusion imaging. DESIGN: Criterion standard. SETTING: Tertiary care center. PATIENTS: Forty-eight patients undergoing diagnostic coronary angiography for angina or silent ischemia. INTERVENTIONS: We performed angiographic and coronary flow velocity measurements at rest and during hyperemia at the post-stenotic segment and in the adjacent angiographically normal branch of the left coronary artery. Relative coronary flow velocity reserve (RCFVR) was calculated as the ratio of post-stenotic to reference vessel coronary flow velocity reserve (CFVR). The best cutoff points for reversible perfusion defects were calculated using receiver operating characteristic curves. MEASUREMENTS AND RESULTS: Post-stenotic CFVR showed fairly good correlations with minimal lumen diameter and percentage of diameter stenosis (r = 0.57 and r = 0.55, respectively; p < 0.001). RCFVR showed stronger correlations with these angiographic indexes of stenosis severity (r = 0.66 and r = 0.68, respectively; p < 0.0001). Based on receiver operating characteristic cutoff values (1.67 for post-stenotic CFVR and 0.64 for RCFVR), RCFVR had better agreement with myocardial perfusion imaging results, compared to post-stenotic CFVR (92% vs 75%, respectively). This agreement was more meaningful in patients with moderate coronary artery stenoses (50 to 75%). The area under the curve was 0.65 (not significant) for post-stenotic CFVR and 0.88 (p < 0.01) for RCFVR. CONCLUSIONS: RCFVR describes better than post-stenotic CFVR the functional significance of coronary artery stenoses.