Junctional AV ablation in patients with atrial fibrillation undergoing cardiac resynchronization therapy (JAVA-CRT): results of a multicenter randomized clinical trial pilot program.

INTRODUCTION: Cardiac resynchronization therapy (CRT) improves outcomes in sinus rhythm, but the data in atrial fibrillation (AF) is limited. Atrio-ventricular junctional ablation (AVJA) has been proposed as a remedy. The objective was to test if AVJA results in LV end-systolic volume (ESV) reduction ≥ 15% from baseline to 6 months. METHODS: The trial was a prospective multicenter randomized trial in 26 patients with permanent AF who were randomized 1:1 to CRT-D with or without AVJA. RESULTS: LVESV improved similarly by at least 15% in 5/10 (50%) in the CRT-D-only arm and in 6/12 (50%) in the AVJA + CRT-D arm (OR = 1.00 [0.14, 7.21], p = 1.00). In the CRT-D-only arm, the median 6-month improvement in LVEF was 9.2%, not different from the AVJA + CRT-D arm, 8.2%. When both groups were combined, a significant increase in LVEF was observed (25.4% at baseline vs 36.2% at 6 months, p = 0.002). NYHA class from baseline to 6 months for all patients combined improved 1 class in 15 of 24 (62.5%), whereas 9 remained in the same class and 0 degraded to a worse class. CONCLUSION: In patients with permanent AF, reduced LVEF, and broad QRS who were eligible for CRT, there was insufficient evidence that AVJA improved echocardiographic or clinical outcomes; the results should be interpreted in light of a smaller than planned sample size. CRT, however, seemed to be effective in the combined study cohort overall, suggesting that CRT can be reasonably deployed in patients with AF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02946853.

Prognostic value of frontal QRS-T angle in predicting survival after primary percutaneous coronary revascularization/coronary artery bypass grafting for ST-elevation myocardial infarction.

BACKGROUND: Frontal QRS-T angle (FQRST) has previously been correlated with mortality in patients with stable coronary artery disease, but its role as survival predictor after ST-elevation myocardial infarction (STEMI) remains unknown. METHODS: We evaluated 267 consecutive patients with STEMI undergoing reperfusion or coronary artery bypass grafting. Data assessed included demographics, clinical presentation, electrocardiograms, medical therapy, and one-year mortality. RESULTS: Of 267 patients, 187 (70%) were males and most (49.4%) patients were Caucasian. All-cause mortality was significantly higher among patients with the highest (101-180°) FQRST [28% vs. 15%, p = 0.02]. Patients with FQRST 1-50° had higher survival (85.6%) compared with FQRST = 51-100° (72.3%) and FQRST = 101-180° (67.9%), [log rank, p = 0.01]. Adjusting for significant variables identified during univariate analysis, FQRST (OR = 2.04 [95% CI: 1.31-13.50]) remained an independent predictor of one-year mortality. FQRST-based risk score (1-50° = 0 points, 51-100° = 2 points, 101-180° = 5 points) had excellent discriminatory ability for one-year mortality when combined with Mayo Clinic Risk Score (C statistic = 0.875 [95%CI: 0.813-0.937]. A high (>4 points) FQRST risk score was associated with greater mortality (32% vs. 19%, p = 0.02) and longer length of stay (6 vs. 2 days, p < 0.001). CONCLUSION: FQRST represents a novel independent predictor of one-year mortality in patients with STEMI undergoing reperfusion. A high FQRST-based risk score was associated with greater mortality and longer length of stay and, after combining with Mayo Clinic Risk Score, improved discriminatory ability for one-year mortality.

Quality of life outcomes in transcatheter aortic valve replacement patients requiring pacemaker implantation.

BACKGROUND: Permanent pacemaker implantation is the most common complication after Transcatheter aortic valve replacement (TAVR) and is associated with worse outcomes and mortality. However, its impact on quality-of-life (QoL) outcomes remains unknown. METHODS: We included 383 consecutive patients undergoing TAVR from January 2012 to 2016 who completed a baseline Kansas City Cardiomyopathy Questionnaire (KCCQ-12) health survey. The clinical, laboratory, angiographic, QoL, mortality, and occurrence of poor outcomes (KCCQ-12 score < 45 or KCCQ decrease of ≥10 points) were obtained. RESULTS: The mean age was 83 ± 8 years, 51% were men, and majority were Caucasians (n = 364, 95%). Permanent pacemaker (PPM) was implanted in 11.5% of patients post-TAVR. PPM patients were more likely to have prior conduction disease including RBBB (25% vs 12%, P = .02) and PQ interval >250 ms (11% vs 5%, P = .07). One-month median KCCQ-12 scores were significantly lower among PPM patients (84.7 vs 68.8, P = .04), but did not differ significantly at 1-year (86.5 vs 90.6, P = .5) post-TAVR. Occurrence of poor outcomes did not differ significantly among those with or without PPM at 1 month (11% vs 7%, P = .39) and 1 year (13% vs 9%, P = .45), respectively. However, patients with poor QoL outcomes at 1 month post-TAVR also had significantly worse mortality during follow-up in unadjusted (31.3% vs 4.5%, P < .001) and adjusted (HR = 5.30, 95% [CI: 1.85-15.22, P = .002])analyses, respectively. CONCLUSION: Permanent pacemaker implantation is associated with short-term reduction in QoL without long-term implications post-TAVR. Patients with poor QoL post-TAVR also have significantly higher mortality.

The use of cardiac-CT alone to exclude left atrial thrombus before atrial fibrillation ablation: Efficiency, safety, and cost analysis.

BACKGROUND: Atrial fibrillation (AF) is a growing financial burden on the healthcare system. Cardiac computed tomographic angiography (CCTA) is needed for pulmonary vein mapping before AF ablation (AFA). CCTA has shown to be an alternative to transesophageal echocardiogram (TEE) to rule out left atrial appendage thrombus (LAAT) pre-AFA. We aim to examine the safety, cost-effectiveness, and time-efficiency of utilizing CCTA alone to rule out LAAT before AFA. METHODS: We prospectively screened patients with paroxysmal AF undergoing cryoablation. CCTA with delayed enhancement was performed within 72 hours of AFA. Once LAAT was ruled out, patients were enrolled and planned TEE was cancelled. A retrospective control cohort that had both CCTA and TEE prior to AFA was identified. Direct cost data, electrophysiology laboratory utilization time, and 30-day stroke outcomes were collected from the EMR, follow-up phone calls, or clinic visits, and comparative analyses were performed. RESULTS: Seventy patients met the inclusion criteria in the prospective CCTA-only cohort, and 71 for the retrospective CCTA+TEE cohort. Baseline characteristics were similar between the two groups. There was a nonsignificant reduction in overall cost ($15,870 ± 1,710 vs $16,557 ± 2,508, P = 0.06) in CCTA-only cohort, whereas the electrophysiology laboratory utilization time was significantly reduced (241.6 ± 41.7 vs 181.3 ±36.4 minutes, P < 0.001). There were no strokes reported on 30-day follow-up in the CCTA-only group. CONCLUSIONS: In low-to-intermediate stroke risk patients with paroxysmal AF undergoing cryoablation, eliminating TEE and employing CCTA-only strategy to rule-out LAAT improves electrophysiology laboratory efficiency without influencing periprocedural cost or increasing postprocedural stroke risk.

Validation of a smartphone-based event recorder for arrhythmia detection.

INTRODUCTION: Ambulatory cardiac monitoring devices such as external loop recorders (ELRs) are often used in the outpatient clinic to evaluate palpitations. However, ELRs can be bulky and uncomfortable to use, especially in public, at work, or in social situations. An alternative approach is a smartphone-based electrocardiographic (ECG) recorder/event recorder (Kardia Mobile [KM]), but the comparative diagnostic yield of each approach has not been studied. METHODS: Thirty-three patients with palpitations wore an ELR and carried a KM for a period of 14-30 days. They were instructed to transmit ECGs via KM and also to activate the ELR whenever they had symptoms. The tracings obtained from both devices were independently analyzed by two cardiologists, and the overall arrhythmia yield, as well as patient preference and compliance, were evaluated. The paired binomial data obtained from both devices were compared using an unconditional test of noninferiority. RESULTS: Of the 38 patients enrolled in the study, more patients had a potential diagnosis for their symptoms (i.e., at least one symptomatic recording during the entire monitoring period) with KM than with the ELR (KM = 34 [89.5%] vs ELR = 26 [68.4%]; χ2  = 5.1, P = 0.024). In the per protocol analysis, all 33 patients (100%) had a potential diagnosis using the KM device, which was significantly higher compared to 24 patients (72.2%) using the ELR (χ2  = 10.4, P = 0.001). CONCLUSIONS: KM is noninferior to an ELR for detecting arrhythmias in the outpatient setting. The ease of use and portability of this device make it an attractive option for the detection of symptomatic arrhythmias.

Right Ventricular Versus Biventricular Pacing for Heart Failure and Atrioventricular Block.

The use of cardiac resynchronization therapy (CRT) is well accepted as an important option for the treatment of patients with systolic heart failure and prolonged QRS duration. CRT for patients with narrow QRS complexes is reserved for patients who are undergoing implantation of new or replacement pacemakers or implantable cardioverter defibrillators with an anticipated significant requirement for ventricular pacing. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial examined the role of CRT in heart failure patients with atrioventricular block and demonstrated significantly better outcomes with CRT compared to right ventricular pacing. On the other hand, conflicting preliminary data were reported by the Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) Trial investigators. In this review, we will discuss the adverse consequences of chronic right ventricular pacing, the options of alternate pacing sites in the right ventricle versus biventricular pacing, and the findings from the BLOCK HF Trial as well as the preliminary data from the BioPace Trial. Our goal is to explore the role of biventricular pacing in patients with atrioventricular block.

Assessment of ventricular tachycardia scar substrate by intracardiac echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) is increasingly used to guide complex ablation procedures. This study aimed to assess the scar substrate of ventricular tachycardia (VT) by ICE in patients undergoing VT ablation. METHODS: In 22 patients undergoing VT ablation (10 ischemic, 12 nonischemic), the Biosense CARTOSOUND module (Biosense Webster, Diamond Bar, CA, USA) was used for three-dimensional reconstruction of the ventricles. The characteristics and appearance with ICE imaging of voltage-defined scar zones (bipolar voltage <0.5 mV), border zones (0.5-1.5 mV), and normal myocardium (>1.5 mV) on electroanatomic maps were evaluated. The standard image analysis software Image J (National Institutes of Health, Bethesda, MD, USA) was used to analyze signal intensity (mean pixel signal intensity unit [SIU]) and heterogeneity (standard deviation of signal intensity in analyzed area) on ICE images. RESULTS: A total of 83 myocardial areas were analyzed from two-dimensional ICE images (15 scars, 31 border zones, and 37 normal). Voltage-defined scar zones had increased signal intensities compared to border zones (149 SIU vs 104 SIU, P < 0.0001) and normal myocardium (88 SIU, P < 0.0001). Border zones were more likely to have heterogeneous densities compared to normal myocardium (standard deviation of signal intensity 20 SIU vs 12 SIU, P < 0.0001). In receiver-operator characteristic analyses, signal intensity ≥ 137 SIU differentiated scar from nonscar zones (area under curve 0.91, P < 0.0001). Software-based color enhancement of areas with signal intensity ≥ 137 SIU allowed identification of the VT substrate in all 15 patients with voltage-defined scar zones. CONCLUSIONS: ICE provides important information about the VT anatomical substrate and may have potential to identify areas of scarred myocardium.

Sex Differences In Outcomes Of Ablation Of Atrial Fibrillation.

Sex-related differences in the presentation, treatment, and outcomes of cardiovascular disease have been reported in many areas of cardiovascular medicine, including the clinical course and treatment of atrial fibrillation (AF). Women appear to be more symptomatic, have a lower quality of life, and are less tolerant of antiarrhythmic drugs than men. However, the rate of referral of women for catheter ablation of AF is significantly lower than men, and women are referred much later after failing more antiarrhythmic drugs. There is a trend toward a lower success rate and a higher failure rate for catheter-based AF ablation in women. This finding may be related to the later referral of women for the procedure, resulting in high risk features such as more severe hypertension, greater left atrial size, and more persistent AF at the time of the procedure, all of which are associated with future recurrences. The complication rate from AF ablation is significantly higher in women, particularly with respect to bleeding and vascular complications such as hematomas and pseudoaneurysms. Individualized care including earlier referrals, pre-procedural case planning, and close monitoring intra- and post procedure may improve the outcomes for women with catheter ablation of AF.

Acute management of atrial fibrillation: from emergency department to cardiac care unit.

Atrial fibrillation (AF) is the most common tachyarrhythmia encountered in clinical practice. One-third of hospitalizations in the United States are attributed to AF, with increasing rates in the past decade. Significant morbidity and mortality, including ∼15% to 20% of all ischemic strokes, result from AF. AF is associated with many causes and comorbidities. Hallmarks of acute AF management are accurate diagnosis, clinical stabilization, symptom relief through rate or rhythm control, thromboembolic stroke risk modification, and treatment of underlying causes. Meticulous and individualized acute evaluation based on these goals facilitates successful transition to long-term collaborative optimization of outcomes.

50th Anniversary of the first successful permanent pacemaker implantation in the United States: historical review and future directions.

June 2010 marks the 50th anniversary of the first successful human cardiac pacemaker implantation in the United States. On June 6, 1960, in Buffalo, New York, Dr. William Chardack implanted a pacemaker, designed and built by Wilson Greatbatch, an electrical engineer and inventor, in a 77-year old man with complete atrioventricular block, extending the patient's life by 18 months. This landmark event ushered in a new era of implantable cardiac pacemakers with batteries and leads of high reliability and increasing durability. Over the past half century, the field of electrophysiology and implantable devices for the management of cardiac conduction disturbances has evolved dramatically. Today's pacemakers include increasingly complex features such as telemetry monitoring, auto programmability, and hemodynamic sensors. New-generation leads present a sophisticated design with improved geometry and steroid-eluting tips to reduce chronic inflammation, maintaining a low pacing threshold and high sensing capability. The lithium iodide battery remains the mainstay of implantable pacemaker systems, exhibiting a multiple-year lifespan, slow terminal decay, and a reduced size and cost of production. Although Greatbatch's first successful pacemaker implantation remains a seminal scientific contribution to modern cardiovascular disease management, emerging developments in this field may challenge its preeminence. Important challenges such as imaging compatibility, lead durability, and infection prevention are being addressed. Novel concepts such as leadless and biologic pacing are under active investigation. In conclusion, Greatbatch's historic achievement 50 years ago reminds us that technologic progress is timeless, as efforts to enhance clinical outcomes and the quality of life continue unimpeded into the 21st century.

Glia induce dendritic growth in cultured sympathetic neurons by modulating the balance between bone morphogenetic proteins (BMPs) and BMP antagonists.

Dendritic growth in cultured sympathetic neurons requires specific trophic interactions. Previous studies have demonstrated that either coculture with glia or exposure to recombinant bone morphogenetic proteins (BMPs) is both necessary and sufficient to induce dendrite formation. These observations led us to test the hypothesis that BMPs mediate glial-induced dendritic growth. In situ hybridization and immunocytochemical studies indicate that the spatiotemporal expression of BMP5, -6, and -7 in rat superior cervical ganglia (SCG) is consistent with their proposed role in dendritogenesis. In vitro, both SCG glia and neurons were found to express BMP mRNA and protein when grown in the presence or absence of the other cell type. However, addition of ganglionic glia to cultured sympathetic neurons causes a marked increase in BMP proteins coincident with a significant decrease in follistatin and noggin. Functional assays indicate that glial-induced dendritic growth is significantly reduced by BMP7 antibodies and completely inhibited by exogenous noggin and follistatin. These data suggest that glia influence the rapid perinatal expansion of the dendritic arbor in sympathetic neurons by increasing BMP activity via modulation of the balance between BMPs and their antagonists.

Interferon gamma induces retrograde dendritic retraction and inhibits synapse formation.

The expression of interferon gamma (IFNgamma) increases after neural injury, and it is sustained in chronic inflammatory conditions such as multiple sclerosis and infection with human immunodeficiency virus. To understand how exposure to this proinflammatory cytokine might affect neural function, we examined its effects on cultures of neurons derived from the central and peripheral nervous systems. IFNgamma inhibits initial dendritic outgrowth in cultures of embryonic rat sympathetic and hippocampal neurons, and this inhibitory effect on process growth is associated with a decrease in the rate of synapse formation. In addition, in older cultures of sympathetic neurons, IFNgamma also selectively induces retraction of existing dendrites, ultimately leading to an 88% decrease in the size of the arbor. Dendritic retraction induced by IFNgamma represents a specific cellular response because it occurs without affecting axonal outgrowth or cell survival, and it is not observed with tumor necrosis factor alpha or other inflammatory cytokines. IFNgamma-induced dendritic retraction is associated with the phosphorylation and nuclear translocation of signal transducer and activator of transcription 1 (STAT1), and expression of a dominant-negative STAT1 construct attenuates the inhibitory effect of IFNgamma. Moreover, retrograde dendritic retraction is observed when distal axons are selectively exposed to IFNgamma. These data imply that IFNgamma-mediated STAT1 activation induces both dendritic atrophy and synaptic loss and that this occurs both at the sites of IFNgamma release and at remote loci. Regressive actions of IFNgamma on dendrites may contribute to the neuropathology of inflammatory diseases.