Immediate pharmacotherapy intensification after cardiac resynchronization therapy: incidence, characteristics, and impact.

AIMS: Cardiac resynchronization therapy (CRT) is an established treatment for drug-refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real-world outcomes among CRT recipients with a history of hospitalization for acute HF. METHODS AND RESULTS: This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120 ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II-IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline-directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30 days of CRT implantation. The primary endpoint was all-cause death or first hospitalization for HF; the secondary endpoint was all-cause death. We enrolled 194 patients (75% male; mean age, 65 ± 13 years; 78% with non-ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159 ± 26 vs. 171 ± 32 ms; P = 0.004), higher estimated glomerular filtration rate (55.2 ± 20.0 vs. 47.8 ± 24.7 mL/min/1.73 m2 ; P = 0.022), and more dilated cardiomyopathy. During a median follow-up period of 29 months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6 months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6 months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27-0.97; P = 0.043). CONCLUSIONS: Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS ≥ 120 ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others.

Unidirectional conduction characterizing epicardial connections in patients with atrial tachyarrhythmias.

INTRODUCTION: Electrophysiological characteristics of epicardial connections (ECs) in atria and pulmonary veins (PVs) are unclear despite their important contributions to atrial fibrillation (AF). Unidirectional conduction associated with source-sink mismatch can occur in ECs due to their fine fibers with abrupt changes in orientation. We detailed the prevalence and electrophysiological characteristics of unidirectional conduction in the atria and investigated its association with the clinical manifestation of AF. METHODS: This study retrospectively reviewed electrophysiological studies and radiofrequency catheter ablation in 261 consecutive patients with AF. RESULTS: Unidirectional conduction was observed during ablation encircling the PVs in eight (3.1%) patients, and all occurred in the suspected (N = 4) or definitively (N = 4) recognized ECs. These ECs included three intercaval bundles, four septopulmonary bundles, and one Marshall bundle, and were first manifested in a second procedure in 6 (75%) patients. The unidirectional property was from PV to atrium (exit conduction) in all intercaval bundles and three septopulmonary bundles, and from atrium to PV (entrance conduction) in the remaining two bundles. Intercaval bundles acted as a limb of bi-atrial macro-reentrant tachycardia (50%, three of the six including previous cases). Ablation of the exit outside the PVs, including the right atrium, eliminated ECs in three (38%) patients. All patients remain free from arrhythmia recurrence after a mean 13-month follow-up. CONCLUSION: A unidirectional conduction property was closely associated with the EC, as estimated by histological findings. Recognition of this fact by electrophysiologists may help to clarify mechanisms for AF and atrial tachycardia and guide the creation of efficient and safe ablation lesion sets.

Inter-atrial epicardial muscular fibers as a possible source of atrial tachyarrhythmias.

A 22-year-old woman without structural heart disease underwent catheter ablation of frequent premature atrial contractions (PACs). Radiofrequency applications from both the right and left atrium were effective in suppressing or eliminating these PACs. The distance between the right atrial ablation site and the successful ablation site at the right-sided pulmonary venous carina measured 18 mm on the CARTO map, and no cardiac structure, i.e. the inter-atrial septum, was present between those sites. Taken together, the epicardial muscular fibers in the inter-atrial groove were considered to play a role as an arrhythmogenic source of this atrial tachyarrhythmia. Learning objective: Epicardial muscular fibers connecting the right atrium and right-sided pulmonary venous carina are known to preclude isolation of the veins. This epicardial connection in the interatrial groove can be an arrhythmogenic source or part of a reentrant circuit of atrial tachyarrhythmias.

Impact of catheter ablation and subsequent recurrence of atrial fibrillation on glucose status in patients undergoing continuous glucose monitoring.

Although glucose metabolism and atrial fibrillation (AF) have complex interrelationships, the impact of catheter ablation of AF on glucose status has not been well evaluated. Continuous glucose monitoring (CGM) with a FreeStyle Libre Pro (Abbott) was performed for 48 h pre-procedure, during the procedure, and for 72 h post-procedure in 58 non-diabetes mellitus (DM) patients with symptomatic AF and 20 patients with supraventricular or ventricular arrhythmias as a control group. All ablation procedures including pulmonary vein isolation were performed successfully. Glucose levels during procedures consistently increased in the AF and control groups (83.1 ± 16.1 to 110.0 ± 20.5 mg/dL and 83.3 ± 14.7 to 98.6 ± 16.3 mg/dL, respectively, P < 0.001 for both), and Δ glucose levels (max minus min/procedure) were greater in the AF group than control group (P < 0.001). There was a trend toward higher mean glucose levels at 72 h after the procedures compared with those before the procedures in both the AF and control groups (from 103.4 ± 15.6 to 106.1 ± 13.0 mg/dL, P = 0.063 and from 100.2 ± 17.1 to 102.9 ± 16.9 mg/dL, P = 0.052). An acute increase in glucose level at the time of early AF recurrence (N = 9, 15.5%) could be detected by simultaneous CGM and ECG monitoring (89.7 ± 18.0 to 108.3 ± 30.5 mg/dL, P = 0.001). In conclusion, although AF ablation caused a statistically significant increase in the glucose levels during the procedures, it did not result in a pathologically significant change after ablation in non-DM patients. Simultaneous post-procedure CGM and ECG monitoring alerted us to possible acute increases in glucose levels at the onset of AF recurrence.

An Epicardial Connection With a Unidirectional Conduction Property From the Left Atrium to Pulmonary Vein.

The presence of an epicardial connection between the left-sided pulmonary vein and left atrium was suggested during catheter ablation of atrial fibrillation because of sustainable unidirectional entrance conduction after complete endocardial ablation, centrifugal breakout deep inside the pulmonary vein, and immediate elimination of the conduction by point ablation. (Level of Difficulty: Advanced.).

Epicardial Connections as Intra-Atrial Conduction Routes in a Patient With Advanced Atrial Remodeling.

In a patient with long-standing persistent atrial fibrillation, elimination of an epicardial connection between the right-sided pulmonary venous carina and the right atrium during catheter ablation resulted in intra-atrial conduction injuries in the presence of advanced atrial remodeling. (Level of Difficulty: Advanced.).

Comparison of Soluble ST2, Pentraxin-3, Galectin-3, and High-Sensitivity Troponin T of Cardiovascular Outcomes in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking. METHODS AND RESULTS: A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102-3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066). CONCLUSIONS: This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.

A simple pacing maneuver to unmask an epicardial connection involving the right-sided pulmonary veins.

INTRODUCTION: An epicardial connection (EC) between the right-sided pulmonary venous (PV) carina and right atrium (RA) is one of the mechanisms for which carinal ablation is required for right-sided PV isolation. The purpose of the study was to devise a simple pacing maneuver to differentiate an EC from a residual conduction gap on the antral ablation line during radiofrequency catheter ablation. METHODS AND RESULTS: This study included 133 consecutive patients. After one round of ablation, electrograms at the posterior antrum outside the ablation line were recorded during sinus rhythm (SR) and coronary sinus (CS) pacing, and intervals between the antral and PV potentials were measured in each rhythm. The ΔintervalSR-CS was calculated as the difference between the interval during SR and that during CS pacing. Presence of an EC was confirmed by observation of a RA posterior wall breakthrough during right-sided PV pacing, which was then targeted for ablation. Patients with nonachievement of first-pass isolation (N = 35) and with PV reconnection during the procedure (N = 9) were classified into the EC-group (N = 20) and gap-group (N=24), respectively. The prevalence of carina breakthrough during SR was higher in the EC-group than the gap-group (18 [95%] vs. 1 [4%] patients, p < .0001). The ΔintervalSR-CS was larger in the EC-group versus gap-group (71 [interquartile range, 57-97] vs. 6 [2-9] ms, p < .0001). In all patients with an EC, RA ablation resulted in delay (32 [20-40] ms) (N = 15) or elimination of PV potentials (N = 5). CONCLUSION: An EC can be efficiently discriminated from a conduction gap by a simple pacing maneuver.

Predictors of Recurrence after Catheter Ablation of Paroxysmal Atrial Fibrillation in Different Follow-Up Periods.

Background and objectives: Pulmonary vein (PV) reconnection is a major reason for recurrence after catheter ablation of paroxysmal atrial fibrillation (PAF). However, the timing of the recurrence varies between patients, and recurrence >1 year after ablation is not uncommon. We sought to elucidate the characteristics of atrial fibrillation (AF) that recurred in different follow-up periods. Materials and Methods: Study subjects comprised 151 consecutive patients undergoing initial catheter ablation of PAF. Left atrial volume index (LAVi) and atrial/brain natriuretic peptide (ANP/BNP) levels were systematically measured annually over 3 years until AF recurred. Results: Study subjects were classified into four groups: non-recurrence group (n = 84), and short-term- (within 1 year) (n = 30), mid-term- (1-3 years) (n = 26), and long-term-recurrence group (>3 years) (n = 11). The short-term-recurrence group was characterized by a higher prevalence of diabetes mellitus (hazard ratio 2.639 (95% confidence interval, 1.174-5.932), p = 0.019 by the Cox method), frequent AF episodes (≥1/week) before ablation (4.038 (1.545-10.557), p = 0.004), and higher BNP level at baseline (per 10 pg/mL) (1.054 (1.029-1.081), p < 0.0001). The mid-term-recurrence group was associated with higher BNP level (1.163 (1.070-1.265), p = 0.0004), larger LAVi (mL/m2) (1.033 (1.007-1.060), p = 0.013), and longer AF cycle length at baseline (per 10 ms) (1.194 (1.058-1.348), p = 0.004). In the long-term-recurrence group, the ANP and BNP levels were low throughout follow-up, as with those in the non-recurrence group, and AF cycle length was shorter (0.694 (0.522-0.924), p = 0.012) than those in the other recurrence groups. Conclusions: Distinct characteristics of AF were found according to the time to first recurrence after PAF ablation. The presence of secondary factors beyond PV reconnections could be considered as mechanisms for the recurrence of PAF in each follow-up period.

Interatrial distance predicts the necessity of additional carina ablation to isolate the right-sided pulmonary veins.

BACKGROUND: Ablation of the pulmonary vein (PV) carina is occasionally required for PV isolation (PVI). Marshall bundle and epicardial connections between the right-sided PV (RtPV) carina and right atrium (RA) may be one of the mechanisms that necessitates carina ablation. OBJECTIVE: We sought to clarify anatomical characteristics predictive of the necessity of carina ablation. METHODS: Forty-five consecutive patients undergoing radiofrequency catheter ablation of atrial fibrillation were prospectively included in this study. Left atrial (LA) and PV size and morphology, and interatrial distance in the posterior aspect, were measured on cardiac computed tomography (CT) images. RESULTS: For right-sided PVI, the patients were divided into 2 groups based on the necessity of RtPV carina ablation, Carina-ABL group (n = 21) and Non-Carina-ABL group (n = 24). The distance between the anterior portion of the RtPV carina and RA was shorter in the Carina-ABL group vs in the Non-Carina-ABL group (7.7 ± 1.7 mm/m2 vs 9.5 ± 2.3 mm/m2; P = .005), whereas other anatomical parameters (LA and RA volumes, right inferior PV angle, and ostial diameters of the RtPVs) did not differ between the groups. For left-sided PVI, the ostial diameter and circumference of the left superior PV were smaller in the Carina-ABL group (n = 13) vs the Non-Carina-ABL group (n = 32) (8.6 ± 2.1 mm/m2 vs 7.3 ± 1.5 mm/m2; P = .044, and 34.9 ± 6.0 mm/m2 vs 30.1 ± 5.1 mm/m2; P = .017, respectively). CONCLUSIONS: A shorter interatrial distance for right-sided PVI and a smaller PV ostium for left-sided PVI were associated with the necessity of additional carina ablation. The presence and location of the epicardial fibers may be affected by the atrial and PV geometry.

Upgrade of cardiac resynchronization therapy by utilizing additional His-bundle pacing in patients with inotrope-dependent end-stage heart failure: a case series.

BACKGROUND: His-bundle pacing (HBP) alone may become an alternative to conventional cardiac resynchronization therapy (CRT) utilizing right ventricular apical (RVA) and left ventricular (LV) pacing (BiVRVA+LV) in selected patients, but the effects of CRT utilizing HBP and LV pacing (BiVHB+LV) on cardiac resynchronization and heart failure (HF) are unclear. CASE SUMMARY: We presented two patients with inotrope-dependent end-stage HF in whom the upgrade from conventional BiVRVA+LV to BiVHB+LV pacing by the addition of a lead for HBP improved their HF status. Patient 1 was a 32-year-old man with lamin A/C cardiomyopathy, atrial fibrillation, and complete atrioventricular (AV) block. Patient 2 was a 70-year-old man with ischaemic cardiomyopathy complicated by AV block and worsening of HF resulting from ablation for ventricular tachycardia storm. The HF status of both patients improved dramatically following the upgrade from BiVRVA+LV to BiVHB+LV pacing. DISCUSSION: End-stage HF patients suffer from diffuse intraventricular conduction defect not only in the LV but also in the right ventricle (RV). The resulting dyssynchrony may not be sufficiently corrected by conventional BiVRVA+LV pacing or HBP alone. Right ventricular apical pacing itself may also impair RV synchrony. An upgrade to BiVHB+LV pacing could be beneficial in patients who become non-responsive to conventional BiV pacing as the His-Purkinje conduction defect progresses.

Clinical Applications of Natriuretic Peptides in Heart Failure and Atrial Fibrillation.

Natriuretic peptides (NPs) have become important diagnostic and prognostic biomarkers in cardiovascular diseases, particularly in heart failure (HF). Diagnosis and management of coronary artery disease and atrial fibrillation (AF) can also be guided by NP levels. When interpreting NP levels, however, the caveat is that age, sex, body mass index, renal dysfunction, and race affect the clearance of NPs, resulting in different cut-off values in clinical practice. In AF, NP levels have been associated with incident AF in the general population, recurrences after catheter ablation, prediction of clinical prognosis, and the risk of stroke. In this article, we first review and summarize the current evidence and the roles of B-type NP and atrial NP in HF and coronary artery disease and then focus on the increasing utility of NPs in the diagnosis and management of and the research into AF.

Structural relation between the superior vena cava and pulmonary veins in patients with atrial fibrillation.

The superior vena cava (SVC) is a main source of non-pulmonary vein (PV) ectopies that initiate atrial fibrillation (AF). Although the critical role of structural remodeling of the left atrium (LA) in the occurrence of AF was extensively investigated by atrial voltage mapping, that of PVs and the SVC has been less explored. Study subjects comprised 47 patients undergoing catheter ablation of lone AF. During sinus rhythm, PV, SVC, and atrial voltage maps were acquired, and sleeve length of each PV and SVC was determined by an electroanatomical mapping system. The sleeves of the superior PVs were significantly longer than those of the inferior PVs (left superior PV (LSPV): 21 ± 5, left inferior PV: 14 ± 4, right superior PV (RSPV): 19 ± 5, right inferior PV: 15 ± 5, and SVC: 23 ± 10 mm, p < 0.0001). The LSPV sleeve was longer in men than in women (22 ± 6 vs. 19 ± 4 mm, p < 0.05). The sleeve length in the LSPV correlated positively with the body surface area (BSA) (p = 0.003, R = 0.42). Of note, there was a significant correlation in sleeve length between the RSPV and SVC (p < 0.0001, R = 0.64). In conclusion, not right- but left-sided PV sleeves were associated with the BSA of the patients, whereas a structural relation between the right-sided PVs and the SVC was implied based on sleeve mapping. This novel finding may provide mechanistic implications for the development of AF in future studies.

Different Impact of Changes in Left Ventricular Ejection Fraction Between Heart Failure Classifications in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Left ventricular ejection fraction (LVEF) can dramatically change when the patient has acute decompensated heart failure (ADHF). We investigated the impact of LVEF and subsequent changes on prognosis in patients with ADHF through a prospective study.Methods and Results: A total of 516 hospitalized patients with ADHF were evaluated. Echocardiography was performed on admission, prior to discharge, and 1 year after discharge. The primary endpoint was a composite of cardiovascular death and hospitalization. In heart failure with reduced EF (HFrEF; LVEF <40%), LVEF did not significantly improve during hospitalization (P=0.348); however, it improved after discharge (P<0.001). In contrast, LVEF improved during hospitalization (P<0.001) in HF with preserved EF (HFpEF; LVEF ≥50%). In HF with mid-range EF (HFmrEF; LVEF 40-49%), LVEF consistently improved throughout the observation period (P<0.001). A multivariable Cox model showed that improved LVEF after discharge was associated with a better outcome in HFrEF (hazard ratio [HR]: 0.951; 95% confidence interval [CI]: 0.928-0.974; P<0.001), while improved LVEF during hospitalization was associated with a better outcome in HFpEF (HR: 0.969; 95% CI: 0.940-0.998; P=0.038). CONCLUSIONS: Improved LVEF after discharge in HFrEF and during hospitalization in HFpEF was associated with a better prognosis in patients with ADHF. Longitudinal improvements in LVEF had different prognostic impact, depending on the HF type by LVEF measurement.

Comparison of effects of aldosterone receptor antagonists spironolactone and eplerenone on cardiovascular outcomes and safety in patients with acute decompensated heart failure.

Differences in the clinical impacts of the aldosterone receptor antagonists spironolactone and eplerenone in patients with heart failure (HF) are unclear. Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with eplerenone were compared with 90 treated with spironolactone. The primary endpoint was a composite of cardiovascular death and hospitalization. A serial evaluation of the clinical parameters was performed 1 year after discharge. The mean dose of spironolactone was 27 ± 8 mg and of eplerenone was 34 ± 15 mg. During follow-up (mean 594 ± 317 days), primary endpoints occurred in 27 patients in the eplerenone group (30.0%) and 25 patients in the spironolactone group (27.8%). There were no significant intergroup differences in the primary endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated glomerular filtration rate did not differ significantly between groups. Although gynecomastia in men was common in the spironolactone group (p = 0.018), the discontinuation rates due to adverse events were similar in the two groups (p = 0.135). Subgroup analyses suggested that eplerenone was associated with a lower hazard rate of the primary endpoint in female patients (interaction, p = 0.076). Among patients with HF, eplerenone and spironolactone have similar impacts on cardiovascular outcomes and safety.

Epicardial connection between the right-sided pulmonary venous carina and the right atrium in patients with atrial fibrillation: A possible mechanism for preclusion of pulmonary vein isolation without carina ablation.

BACKGROUND: Ablation of the pulmonary venous carina is occasionally required for pulmonary vein isolation (PVI) despite its nonessential role in ipsilateral PVI from the anatomical (endocardial) viewpoint. Although the Bachmann bundle (BB) is a common and main interatrial band, local variations in small tongues of muscular fibers were frequently found in autopsy studies. OBJECTIVE: We sought to clarify the effect of the electrical conduction pattern from the right atrium (RA) to the left atrium (LA) during sinus rhythm on the necessity of performing right-sided pulmonary venous carina ablation to achieve PVI. METHODS: Study subjects comprised 37 consecutive patients undergoing initial catheter ablation of lone atrial fibrillation. During sinus rhythm, RA and LA activation maps were acquired using an electroanatomical mapping system. LA breakthroughs were classified into 3 sites: BB, fossa ovalis (FO), and right-sided pulmonary venous carina. Patients were divided into the carina-ABL (ablation) or non-carina-ABL group on the basis of the necessity of pulmonary venous carina ablation to achieve PVI. RESULTS: Patients were classified in the non-carina-ABL group (n = 26 [70%]) and carina-ABL group (n = 8 [22%]) after excluding 3 patients (8%) because of their complex ablation lesion sets. Breakthrough occurred in the BB (n = 21 patients [62%]), FO (n = 7 [21%]), carina (n = 1 [3%]), carina and BB (n = 3 [9%]), and carina and FO (n = 2 [6%]). Carina breakthrough occurred in 6 patients (75%) in the carina-ABL group but in no patients in the non-carina-ABL group (P < .0001). CONCLUSION: PVI was not achievable without carina ablation in one-fifth of patients, probably because of epicardial connections present between the right-sided pulmonary venous carina and the RA.