Coronary sinus Reducer device for the treatment of refractory angina: A multicenter initial experience.

INTRODUCTION: The coronary sinus Reducer (CSR) device has emerged as a complementary therapy in patients with severe angina refractory to optimal medical therapy and not amenable to revascularization. Our aim was to assess the safety and efficacy of the CSR in a real-world setting. METHODS: Twenty-six patients with refractory angina (RA) and evidence of myocardial ischemia attributable to the left coronary artery considered unsuitable for revascularization were treated with the CSR at two centers between May 2017 and July 2019. Safety endpoints were procedural success and complications. Efficacy endpoints, assessed at six-month follow-up, were reduction in CCS class, improvement in quality of life (QoL) assessed using the short version of the Seattle Angina Questionnaire (SAQ-7), and reduction in antianginal therapy. RESULTS: Twenty-three patients had end-stage coronary artery disease without revascularization targets and three had microvascular disease without epicardial stenosis. Procedural success was achieved in 23 patients, with two device/procedure-related complications and one anatomically-related failure to deliver the device. A total of 24 patients had the device implanted and entered the efficacy analysis. Eighteen patients (75.0%) had a reduction of at least one CCS class, 41.7% had a reduction of at least two classes, and 16.7% became asymptomatic, with a mean reduction in CCS class of 1.3±0.2 (p=0.001) at six-month follow-up. All SAQ-7 domains improved, notably physical limitation (p=0.001), angina frequency (p=0.005) and QoL (p=0.006). There was a mean reduction in anti-ischemic drugs from 3.4±1.1 to 2.9±1.2 (p=0.010). CONCLUSION: In this real-world, multicenter experience, implantation of the CSR was associated with improvement in angina and QoL in patients with RA.

Epicardial and Coronary Sinus Echocardiography.

Catheter-based ultrasonography is a widely used tool in cardiac electrophysiology practice, and intracardiac echocardiography is supplanting other forms of imaging to become the dominant imaging modality. Given advances in pericardial access, intrapericardial echocardiography can be performed using ultrasound catheters as well. Intrapericardial echocardiography and echocardiography from the coronary sinus, also an epicardial structure, allows interventionalists to obtain unique views from virtually any vantage point, compared with other forms of echocardiography. Both intrapericardial echocardiography and coronary sinus echocardiography are safe and important alternatives that can be used during complex procedures in the electrophysiology laboratory.

A MicroRNA Signature in Acute Coronary Syndrome Patients and Modulation by Colchicine.

BACKGROUND: Circulating microRNAs (miRNAs) may play a pathogenic role in acute coronary syndromes (ACS). It is not yet known if miRNAs dysregulated in ACS are modulated by colchicine. We profiled miRNAs in plasma samples simultaneously collected from the aorta, coronary sinus, and right atrium in patients with ACS. METHODS: A total of 396 of 754 miRNAs were detected by TaqMan real-time polymerase chain reaction from EDTA-plasma in a discovery cohort of 15 patients (n = 3 controls, n = 6 ACS standard therapy, n = 6 ACS standard therapy plus colchicine). Fifty-one significantly different miRNAs were then measured in a verification cohort of 92 patients (n = 13 controls, n = 40 ACS standard therapy, n = 39 ACS standard therapy plus colchicine). Samples were simultaneously obtained from the coronary sinus, aortic root, and right atrium. RESULTS: Circulating levels of 30 of 51 measured miRNAs were higher in ACS standard therapy patients compared to controls. In patients with ACS, levels of 12 miRNAs (miR-17, -106b-3p, -191, -106a, -146a, -130a, -223, -484, -889, -425-3p, -629, -142-5p) were lower with colchicine treatment. Levels of 7 of these 12 miRNA were higher in ACS standard therapy patients compared to controls and returned to levels seen in control individuals after colchicine treatment. Three miRNAs suppressed by colchicine (miR-146a, miR-17, miR-130a) were identified as regulators of inflammatory pathways. MicroRNAs were comparable across sampling sites with select differences in the transcoronary gradient of 4 miRNA. CONCLUSION: The levels of specific miRNAs elevated in ACS returned to levels similar to control individuals following colchicine. These miRNAs may mediate ACS (via inflammatory pathways) or increase post-ACS risk, and could be potentially used as biomarkers of treatment efficacy.

Efficacy of Coronary Sinus Reducer in Patients With Non-revascularized Chronic Total Occlusions.

The coronary sinus reducer (CSR) has been introduced as therapy for patients with refractory angina with no other treatment options. Aim of this study is to investigate the efficacy of the CSR in patients with refractory angina and presence of coronary chronic total occlusions (CTO). In this multicentre, international retrospective study, patients undergoing CSR implantation were screened and divided in 2 groups according to the presence/absence of CTO lesions. Baseline and clinical characteristics were analyzed in the 2 groups. Primary-outcome consisted of the variation in Canadian Cardiovascular Society (CCS) class at 6-month follow-up. Between January 2014 and December 2018, 205 patients with refractory angina were consecutively treated with the study device in the participating centers, 103 (50.2%) of which had a CTO lesion at coronary angiogram and formed the CTO-group. Baseline characteristics of the study population were well balanced between the 2 groups. CSR was successfully implanted in all cases. Baseline CCS class was 3  ±  0.5 in the CTO-group versus 3.1  ±  0.6 in the non-CTO group (p = 0.45), and improved at follow-up to 1.6  ±  0.9 versus 2  ±  1.1 respectively (p <0.01), with a significantly higher improvement in CCS class in the CTO-group (1.4  ±  0.9 vs 1.1  ±  1 respectively, p = 0.01). Any improvement in CCS class was registered in 79 (80.6%) CTO-patients, while a significantly lower percentage (65 patients, 66.3%) of the non-CTO patients reported benefits in CCS class (p = 0.03). In conclusions, patients suffering from refractory angina with non-revascularized CTO lesions have a better response to CSR implantation than patients without CTOs. CSR implantation should be considered a valid complementary therapy to CTO-PCI in these patients.

Sustained and self-terminating atrial fibrillation induced immediately after pulmonary vein isolation exhibit differences in coronary sinus electrical activity from onset.

INTRODUCTION: Little data exists on the electrophysiological differences between sustained atrial fibrillation (sAF; >5 minutes) vs self-terminating nonsustained AF (nsAF; <5 minutes). We sought to investigate the electrophysiological characteristics of coronary sinus (CS) activity during postpulmonary vein isolation (PVI) sAF vs nsAF. METHODS AND RESULTS: We studied 142 patients post-PVI for paroxysmal AF (PAF). In a 50-patient subset, CS electrograms in the first 30 seconds of induced AF were analyzed manually. A custom-made algorithm for automated electrogram annotation was derived for validation on the whole patient set. In patients with sAF post-PVI, CS fractionated potentials were ablated. Manual analysis showed that patients with sAF exhibited higher activation pattern variability (2.1 vs 0.5 changes/sec; P < .001); fewer proximal-to-distal wavefronts (25 vs 61%; P < .001); fewer unidirectional wavefronts (60 vs 86%; P < .001); more pivot locations (4.3 vs 2.1; P < .001); shorter cycle lengths (190 vs 220 ms; P < .001); and shorter cumulative isoelectric segments (35 vs 44%; P = .045) compared to nsAF. These observations were confirmed on the whole study population by automated electrogram annotation and sample entropy computation (SampEn: 0.29 ± 0.15 in sAF vs 0.15 ± 0.05 in nsAF; P < .0001). The derived model predicted sAF with 78% sensitivity, 88% specificity; agreement with manual model: 88% (Cohen's kappa= 0.76). CS defragmentation resulted in AF termination or noninducibility in 49% of sAF. CONCLUSION: In PAF patients post-PVI, induced sAF shows greater activation sequence variability, shorter cycle length, and higher SampEn in the CS compared to nsAF. Automated electrogram annotation confirmed these results and accurately distinguished self-terminating nsAF episodes from sAF based on 30-second recordings at AF onset.

Dynamic Atrial Substrate During High-Density Mapping of Paroxysmal and Persistent AF: Implications for Substrate Ablation.

OBJECTIVES: This study sought to determine the impact of rate and direction on left atrial (LA) substrate. BACKGROUND: The extent to which substrate mapped in sinus rhythm varies according to cycle length and direction of wave front propagation is unknown. METHODS: A total of 73 consecutive patients with atrial fibrillation (AF) underwent electroanatomic LA mapping before pulmonary vein isolation using multipolar catheter during distal coronary sinus (CS) pacing at 600 ms and 300 ms. Additional maps were created during left superior pulmonary vein pacing at 300 ms. Bipolar voltage, conduction velocity (CV), and complex signals were determined. RESULTS: Mean age was 61 ± 9 years, 67% were men, and 53% had persistent AF. Global mean voltage was lower with CS pacing at 300 ms compared with 600 ms (1.56 ± 0.47 mV vs. 1.74 ± 0.48 mV; p < 0.001). This was seen in all LA segments. Global CV was reduced (30.4 ± 13.0 cm/s vs. 38.6 ± 14.0 cm/s; p < 0.001) with greater complex signals at 300 ms (8.9% vs. 5.3%; p < 0.005). Compared with CS pacing, left superior pulmonary vein pacing demonstrated highly regional changes with decreased voltage (1.04 ± 0.43 mV vs. 1.47 ± 0.53 mV; p = 0.01) and CV (24.4 ± 13.0 cm/s vs. 39.9 ± 16.6 cm/s; p = 0.008), and greater complex signals posteriorly. Longer AF duration in paroxysmal AF (p = 0.02) and shorter duration in persistent AF (p = 0.015) and left ventricular ejection fraction (p = 0.016) were independent predictors of voltage change. CONCLUSIONS: In patients with AF, variation in cycle length and direction of wave front activation produce both generalized and regional changes in voltage, CV, and complex fractionation, resulting in significant changes in substrate maps. This study highlights the potential limitations of static low-voltage maps to identify the AF ablation target zone.

Idiopathic basal crux ventricular arrhythmias with left bundle branch block and superior axis: A comparison with inferior-septal valvular arrhythmias.

INTRODUCTION: Left bundle branch block (LBBB) with superior axis is common in patients with idiopathic-ventricular arrhythmia (VA) originating from the tricuspid annulus (TA) and rarely from the cardiac basal crux and mitral annulus (MA). We described the electrocardiography and electrophysiological findings of idiopathic-VA presenting with LBBB and superior axis. METHODS AND RESULTS: We described 42 idiopathic-VA patients who had an LBBB and superior axis; 15 basal crux-VA, 17 TA-VA, and 10 MA-VA. No patient had a structural heart disease. Among patients with idiopathic-VA referred for ablation, we investigated the electrocardiogram and clinical characteristics of basal crux-VA as compared with other LBBB and superior axis-VA. The left ventricular ejection fraction with MA-VA was significantly lower in comparison with basal crux-VA (P = .01). All patients had a positive R wave in lead I and aVL. The maximum deflection index with basal crux-VA was significantly higher in comparison with TA-VA or MA-VA (P = .01). Patients with basal crux-VA presented with QS wave in lead II more frequently as compared with TA-VA or MA-VA (P = .001). All MA-VA patients had Rs wave in V6, and basal crux-VA, and TA-VA patients had a monophasic R wave or Rs wave in V6. Basal crux-VA patients underwent ablation in the middle cardiac vein (MCV) or coronary sinus (success rate: 94%, recurrence rate: 6%). CONCLUSIONS: We could distinguish basal crux-VA, TA-VA, and MA-VA, using a combination of clinical and electrocardiographic findings. These findings might be useful for counseling patients about an ablation strategy. Ablation via the MCV is effective for eliminating basal crux-VA.

Electrically vs. imaging-guided left ventricular lead placement in cardiac resynchronization therapy: a randomized controlled trial.

AIMS: To test in a double-blinded, randomized trial whether the combination of electrically guided left ventricular (LV) lead placement and post-implant interventricular pacing delay (VVd) optimization results in superior increase in LV ejection fraction (LVEF) in cardiac resynchronization therapy (CRT) recipients. METHODS AND RESULTS: Stratified according to presence of ischaemic heart disease, 122 patients were randomized 1:1 to LV lead placement targeted towards the latest electrically activated segment identified by systematic mapping of the coronary sinus tributaries during CRT implantation combined with post-implant VVd optimization (intervention group) or imaging-guided LV lead implantation by cardiac computed tomography venography, 82Rubidium myocardial perfusion imaging and speckle tracking echocardiography targeting the LV lead towards the latest mechanically activated non-scarred myocardial segment (control group). Follow-up was 6 months. Primary endpoint was absolute increase in LVEF. Additional outcome measures were changes in New York Heart Association class, 6-minute walk test, and quality of life, LV reverse remodelling, and device related complications. Analysis was intention-to-treat. A larger increase in LVEF was observed in the intervention group (11 ± 10 vs. 7 ± 11%; 95% confidence interval 0.4-7.9%, P = 0.03); when adjusting for pre-specified baseline covariates this difference did not maintain statistical significance (P = 0.09). Clinical response, LV reverse remodelling, and complication rates did not differ between treatment groups. CONCLUSION: Electrically guided CRT implantation appeared non-inferior to an imaging-guided strategy considering the outcomes of change in LVEF, LV reverse remodelling and clinical response. Larger long-term studies are warranted to investigate the effect of an electrically guided CRT strategy.

Unique electrocardiographic pattern "w" wave in lead I of idiopathic ventricular arrhythmias arising from the distal great cardiac vein.

BACKGROUND: The ECG characteristics of the distal coronary venous system ventricular arrhythmias (VAs) share common features with VAs arising from the aortic cusps or the endocardial left ventricular outflow tract (LVOT) beneath the cusps. The purpose of this study was to identify specific electrocardiographic and electrophysiological characteristics of VAs originating from the distal great cardiac vein (GCV). METHODS: Based on the successful ablation site, patients with idiopathic VAs from the distal GCV, left coronary cusp (LCC) or the subvalvular left ventricular outflow tract (LVOT) area were included in the present study. RESULTS: The final population consisted of 39 patients (35 males, mean age 51 ± 23 years). All VAs displayed a right bundle branch block (RBBB) morphology with inferior axis. Among these patients, 15 were successfully ablated at the GCV, 15 at the LCC and 9 at the subvalvular region. A "w" pattern in lead I was present in 12 out of 15 (80%) VAs originating from the distal GCV compared to none of VAs arising from the other two sites (p < 0.01). VAs with a GCV origin exhibited more commonly increased intrinsicoid deflection time, higher maximum deflection index and wider QRS duration compared to LCC and subvalvular sites (p < 0.05). Acceptable pace mapping at the successful ablation site was achieved in 10 patients. After an average of 36 ± 24 months follow up, 14 (93.3%) patients were free from VAs recurrence. CONCLUSION: A "w" pattern in lead I may distinguish distal GCV VAs from VAs arising from the LCC or the subvalvular region.

Pseudoblock of the Posterior Mitral Line With Epicardial Bridging Connections Is a Frequent Cause of Complex Perimitral Tachycardias.

BACKGROUND: The mitral isthmus is the critical element of perimitral reentrant tachycardias. Prolongation in transisthmus conduction time and differential pacing techniques are commonly used to determine block. However, these may not distinguish block from slow conduction or conduction via epicardial bridging connections. The aim of this study was to examine these standard criteria for mitral line block with endocardial and epicardial activation mapping. METHODS: In 56 patients, posterior mitral line was performed using radiofrequency ablation. Conduction block was defined as transisthmus time (≥100 ms) and reversal of coronary sinus activation during pacing from the left atrial appendage. These results were compared with high-resolution activation mapping (Rhythmia) of the endocardium and epicardium via the coronary sinus. RESULTS: Mitral block determined by pacing was achieved in 51 out of 56 (91%) patients. In 11 out of 51 (21.6%), activation mapping demonstrated residual endocardial (3/11; 27.2%) or epicardial (8/11; 72.7%) connections. Epicardial bridging connections were distant from the line (2.4±1.6 cm), inserting laterally at the proximal-middle coronary sinus and septally at the left atrial ridge. Patients with residual conduction were prone to complex circuits involving the epicardium (7/11; 63.6%). Mitral line block was achieved in 75% by targeting these insertion site(s). The transisthmus conduction time had limited predictive value for distinguishing block from pseudoblock. CONCLUSIONS: Standard criteria for posterior mitral line block may not distinguish block from pseudoblock. In particular, epicardial bridging connections can result in prolonged transisthmus conduction time and reversal in coronary sinus activation to falsely suggest block. These connections are a frequent cause for complex circuits, and their insertion site(s) can be targeted for ablation.

Is adenosine useful for the identification of atrial fibrillation triggers?

INTRODUCTION: Both isoproterenol (Iso) and adenosine (Ado) are used to induce atrial fibrillation (AF) in the electrophysiology lab. However, the utility of Ado has not been systematically established. OBJECTIVE: The purpose of this study was to compare Ado to Iso for the induction of paroxysmal AF. METHODS: Forty patients (16 women; mean age, 60 ± 12 years) with paroxysmal AF, presenting for ablation were prospectively included of whom 36 (90%) received Ado (18-36 mg) and/or Iso (3-20 µg/min incremental dose) in a randomized order (26 [72%] received both drugs). RESULTS: AF was induced with Iso in 15 of 32 (47%) and with Ado in 12 of 30 (40%) patients (P = 0.9). Iso-triggered AF started from the left pulmonary veins (PVs) in 11 of 15 (73%), from the right PVs in 3 of 15 (20%), and from the coronary sinus (CS) in 1 of 15 (7%) cases. Ado-induced AF episodes originated from the left PVs in 6 of 12 (50%), from the right atrium (RA) in 4 of 12 (33%), and from the CS in 2 of 12 (17%) cases. Altogether, Iso-induced AF was more likely initiated from the PVs (93%) compared with Ado (50%) ( P = 0.02). Ado-induced non-PV triggers were not predictive of arrhythmia recurrence after PV isolation. CONCLUSION: Ado much more frequently induces non-PV triggers, especially from the RA. The clinical significance of these foci, however, is questionable.