Facilitated Myocardial Ablation Using Heat-Sensitive Liposomes Containing Doxorubicin: A Proof-of-Concept Preclinical Study.

The authors sought to evaluate a method for improving radiofrequency (RF) lesion durability using doxorubicin encased in heat-sensitive liposomes (HSL-dox). Using a porcine model, RF ablations were performed in the right atrium after systemic infusion of either HSL-dox or saline control given immediately before mapping and ablation. Lesion geometry was measured with voltage mapping immediately postablation and after 2 weeks of survival. After 2 weeks, lesions demonstrated less regression in scar area in HSL-dox-exposed animals compared with control animals. We demonstrate improved RF lesion durability in animals treated with HSL-dox, and the cardiotoxic effect was more pronounced after RF applications with higher power and longer duration.

Long-term cardiac arrhythmia and chronotropic evaluation in patients with severe anorexia nervosa (LACE-AN): A pilot study.

BACKGROUND: Anorexia nervosa (AN) is associated with autonomic dysfunction and carries a high risk of sudden death, putatively attributed to ventricular tachyarrhythmias. To date, long-term cardiac monitoring has not been performed to confirm this speculation. METHODS AND RESULTS: We assessed the safety and acceptability of an insertable cardiac monitor (ICM) in patients with severe AN with markedly reduced body mass index (BMI), and investigated heart rate (HR) and rhythm before and after weight restoration. Autonomic function was assessed as HR response to a standardized activity protocol at baseline and four additional visits over 360 days. The Florida Patient Acceptance Survey (FPAS) was used to measure ICM acceptability. During a mean follow-up of 10 months, no ICM-related complications occurred and ICM was well-accepted by the 11 study participants (nine women, aged 19-59 years, baseline BMI = 12.7 ± 1.6 kg/m2 ). Both resting and peak HR increased with weight restoration and were directly associated with BMI (both P < .001). No ventricular tachyarrhythmias occurred during the study period, but two participants (18%) experienced eight sinus pauses (3.0-7.0 seconds) and three runs of supraventricular tachycardia. CONCLUSIONS: Long-term cardiac rhythm monitoring with an ICM is feasible, safe, and acceptable in patients with severe AN. Autonomic dysfunction in AN results in not only profound resting bradycardia, but also some degree of chronotropic incompetence, both of which improve with weight restoration. Clinically significant bradyarrhythmias are more common than ventricular tachyarrhythmias in AN, and may represent a competing underlying mechanism for the high risk of sudden death in this population.

Electrophysiologic testing for diagnostic evaluation and risk stratification in patients with suspected cardiac sarcoidosis with preserved left and right ventricular systolic function.

INTRODUCTION: While cardiac sarcoidosis (CS) carries a risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD), risk stratification of patients with CS and preserved left ventricular/right ventricular (LV/RV) systolic function remains challenging. We sought to evaluate the role of electrophysiologic testing and programmed electrical stimulation of the ventricle (EPS) in patients with suspected CS with preserved ventricular function. METHODS: One hundred twenty consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function underwent EPS. All patients had either probable CS defined by an abnormal cardiac positron emission tomography or cardiac magnetic resonance imaging, or possible CS with normal advanced imaging but abnormal echocardiogram (ECG), SAECG, Holter, or clinical factors. Patients were followed for 4.5 ± 2.6 years for SCD and VAs. RESULTS: Seven of 120 patients (6%) had inducible ventricular tachycardia (VT) with EPS and received an implantable cardioverter defibrillator (ICD). Three patients (43%) with positive EPS later had ICD therapies for VAs. Kaplan-Meier analysis stratified by EPS demonstrated a significant difference in freedom from VAs and SCD (P = 0.009), though this finding was driven entirely by patients within the cohort with probable CS (P = 0.018, n = 69). One patient with possible CS and negative EPS had unrecognized progression of the disease and unexplained death with evidence of CS at autopsy. CONCLUSIONS: EPS is useful in the risk stratification of patients with probable CS with preserved LV and RV function. A positive EPS was associated with VAs. While a negative EPS appeared to confer low risk, close follow-up is needed as EPS cannot predict fatal VAs related to new cardiac involvement or disease progression.

Ambulatory Rhythm Monitoring to Detect Late High-Grade Atrioventricular Block Following Transcatheter Aortic Valve Replacement.

BACKGROUND: High-grade atrioventricular block (H-AVB) is a well-described in-hospital complication of transcatheter aortic valve replacement (TAVR). Delayed high-grade atrioventricular block (DH-AVB) has not been systematically studied among outpatients post-TAVR, using latest-generation TAVR technology and in the early post-TAVR discharge era. OBJECTIVES: The purpose of this study was to assess utility of ambulatory event monitoring (AEM) in identifying post-TAVR DH-AVB and associated risk factors. METHODS: Patients without pre-existing pacing device undergoing TAVR at the University of Colorado Hospital from October 2016 to March 2018, and who did not require permanent pacemaker implantation pre-discharge, were discharged with 30-day AEM to assess for DH-AVB (≥2 days post-TAVR). Clinical and follow-up data were collected and compared among those without incident H-AVB. RESULTS: Among 150 consecutive TAVR patients without a prior pacing device, 18 (12%) developed H-AVB necessitating permanent pacemaker <2 days post-TAVR, 1 died pre-discharge, and 13 declined AEM; 118 had 30-day AEM data. DH-AVB occurred in 12 (10% of AEM patients, 8% of total cohort) a median of 6 days (range 3 to 24 days) post-TAVR. DH-AVB versus non-AVB patients were more likely to have hypertension and right bundle branch block (RBBB). Sensitivity and specificity of RBBB in predicting DH-AVB was 27% and 94%, respectively. CONCLUSIONS: DH-AVB is an underappreciated complication of TAVR among patients without pre-procedure pacing devices, occurring at rates similar to in-hospital, acute post-TAVR H-AVB. RBBB is a risk factor for DH-AVB but has poor sensitivity, and other predictors remain unclear. In this single-center analysis, AEM was helpful in expeditious identification and treatment of 10% of post-TAVR outpatients. Prospective study is needed to clarify incidence, risk factors, and patient selection for outpatient monitoring.

Esophageal position, measured luminal temperatures, and risk of atrioesophageal fistula with atrial fibrillation ablation.

BACKGROUND: Despite improvement in catheter ablation for atrial fibrillation (AF), ability to recognize and prevent esophageal injury remains challenging. We hypothesized that esophageal course may impact esophageal heating, as measured through ablation, and thereby, risk of injury. METHODS: We evaluated all patients undergoing first-time AF ablation with preprocedural computed tomography (CT) imaging from 2014 to 2016 at our institution, focusing on esophageal position at the left atrial (LA)/pulmonary vein junction. Esophageal luminal temperatures (ELTs) were analyzed by esophageal course. In exploratory work by investigation of published reports of atrioesophageal fistula (AEF), we evaluated for a relationship between esophageal course and risk of AEF. RESULTS: Of 68 patients, 48.5% had midline, 36.8% leftward, and 14.7% rightward esophageal positions. Of 20 patients (29% of cohort) with esophageal confinement-defined as a midline or leftward position relative to the LA, vertebrae, and aorta, with luminal distortion-14 had leftward position. No significant differences in patient or procedure characteristics were noted between confinement and nonconfinement cohorts. The average peak ELT was significantly higher in those with confinement (36.9°C vs 36.2°C, P < 0.05) and confinement with a left-sided esophagus (37.1°C vs 36.2°C, P < 0.05). There was a significant correlation between esophageal confinement and risk of AEF (odds ratio [OR]: 2.7, 95% confidence interval [CI]: 1.2-6.2, P < 0.01). CONCLUSION: Approximately one-third of patients undergoing AF ablation display leftward esophageal course along the ablation zone on preprocedure CT imaging, with a significant portion exhibiting esophageal confinement. In those with confinement, higher peak ELTs are noted with ablation. Esophageal confinement may be a risk factor for development of AEF.

Use of half-normal saline irrigant with cooled radiofrequency ablation within the great cardiac vein to ablate premature ventricular contractions arising from the left ventricular summit.

A 62-year-old man was referred to our institution for high-density, symptomatic premature ventricular contractions (PVCs) with resultant decrease in left ventricular (LV) function having failed prior ablation attempts. Successful, durable ablation of the patient's mid-myocardial PVC arising from the LV summit region was achieved through the proximal great cardiac vein with ablation depth augmented by use of half-normal saline irrigant. Though standard ablation of ventricular arrhythmias using normal saline irrigation from the coronary venous system has been well-reported, this may be of limited value in addressing mid-myocardial sites of origin. This novel case describes the safe use of cooled radiofrequency ablation with use of half-normal saline irrigant from the distal coronary sinus as an option to address complex sites of PVC origin such as the LV summit.

Repeat ablation of refractory ventricular arrhythmias in patients with nonischemic cardiomyopathy: Impact of midmyocardial substrate and role of adjunctive ablation techniques.

INTRODUCTION: Multiple ablations are often necessary to manage ventricular arrhythmias (VAs) in nonischemic cardiomyopathy (NICM) patients. We assessed characteristics and outcomes and role of adjunctive, nonstandard ablation in repeat VA ablation (RAbl) in NICM. METHODS AND RESULTS: Consecutive NICM patients undergoing RAbl were analyzed, with characteristics of the last VA ablations compared between those undergoing 1 versus multiple-repeat ablations (1-RAbl vs. >1RAbl), and between those with or without midmyocardial substrate (MMS). VA-free survival was compared. Eighty-eight patients underwent 124 RAbl, 26 with > 1RAbl, and 26 with MMS. 1-RAbl and > 1-RAbl groups were similar in age (57 ± 16 vs. 57 ± 17 years; P = 0.92), males (76% vs. 69%; P = 0.60), LVEF (40 ± 17% vs. 40 ± 18%; P = 0.96), and amiodarone use (31% vs. 46%, P = 0.22). One-year VA freedom between 1-RAbl vs. > 1RAbl was similar (82% vs. 80%; P = 0.81); adjunctive ablation was utilized more in >1RAbl (31% vs. 11%, P = 0.02), and complication rates were higher (27% vs. 7%, P = 0.01), most due to septal substrate and anticipated heart block. >1-RAbl patients had more MMS (62% vs. 16%, P < 0.01). Although MMS was associated with worse VA-free survival after 1-RAbl (43% vs. 69%, P = 0.01), when >1RAbl was performed, more often with nonstandard ablation, VA-free survival was comparable to non-MMS patients (85% vs. 81%; P = 0.69). More RAbls were required in MMS versus non-MMS patients (2.00 ± 0.98 vs. 1.16 ± 0.37; P < 0.001). CONCLUSION: For NICM patients with recurrent, refractory VAs despite previous ablation, effective arrhythmia control can safely be achieved with subsequent ablation, although >1 repeat procedure with adjunctive ablation is often required, especially with MMS.

Radiofrequency Ablation Using an Open Irrigated Electrode Cooled With Half-Normal Saline.

OBJECTIVES: This study evaluated the use of half-normal saline (HNS) as the radiofrequency ablation (RFA) cooling irrigant. BACKGROUND: Some instances of ventricular arrhythmia may originate deep within myocardium and can be refractory to standard ablation using open irrigated RFA. Recent data suggest that deeper ablation lesions can be created by decreasing the irrigant ionic concentration delivered through open irrigated RFA than by using normal saline (NS). METHODS: Bovine myocardium was placed in a circulating saline bath. Two RFA catheters were oriented across from each other, with myocardium in between. Sequential unipolar HNS-irrigated RFA was performed and compared to bipolar ablation by using NS or HNS. Unipolar HNS ablation of the ventricles in a porcine model was performed and compared to ablation using NS. RESULTS: Sequential ex vivo unipolar RFA with HNS produced larger lesions than sequential unipolar RFA with NS and produced lesions of similar size to those created with bipolar RFA using NS. Ex vivo bipolar RFA using HNS created the largest lesions. In vivo unipolar HNS ablation in porcine endocardium created larger lesion volumes, 152.9 ± 29.2 µl, compared to 94.7 ± 33.4 µl for unipolar ablation using NS. CONCLUSIONS: By decreasing ionic concentration and charge density in RFA using HNS instead of NS irrigant, larger ablation lesions can be created and are similar in size to lesions created using bipolar ablation. This may be a useful ablation strategy for deep myocardial circuits refractory to standard ablation. Further studies are needed to evaluate this novel RFA strategy.

Clinical and biophysical evaluation of variable bipolar configurations during radiofrequency ablation for treatment of ventricular arrhythmias.

BACKGROUND: Bipolar radiofrequency ablation (bRFA) has been used to create larger ablation lesions and to treat refractory arrhythmias. However, little is known about optimal bRFA settings. OBJECTIVE: The purpose of this study was to evaluate various bRFA settings, including active and ground catheter tip orientation and use of variable active and ground catheters during bRFA. METHODS: Two ablation catheters, 1 active and 1 ground, were oriented across from each other, with viable bovine myocardium in between. The catheter tips were placed in various combinations perpendicular or parallel to the myocardium. The active catheter was either a 3.5-mm externally irrigated or 8-mm tip, and the ground catheter was either a 4-mm, 3.5-mm irrigated, or 8-mm tip. Retrospective analysis was undertaken for all bRFA performed at University of Colorado. RESULTS: The largest and deepest lesions were produced using irrigated active and ground tips, oriented perpendicularly. In 14 cases (10 patients) of bRFA for ventricular tachycardia and premature ventricular complexes, acute success was achieved in 13 of 14 procedures. Long-term success was achieved in 7 of 10 patients, but 3 patients required multiple bRFA ablations. CONCLUSION: Active and ground catheter tip orientation and type are important determinants of lesion sizes during bRFA. The largest and deepest lesions, without a higher incidence of steam pops, were achieved using 2 irrigated catheters. As the largest published series to date, bRFA ablation can be performed safely and effectively in humans. Larger studies are necessary to better evaluate bRFA efficacy and safety.

Enhanced Radiofrequency Ablation With Magnetically Directed Metallic Nanoparticles.

BACKGROUND: Remote heating of metal located near a radiofrequency ablation source has been previously demonstrated. Therefore, ablation of cardiac tissue treated with metallic nanoparticles may improve local radiofrequency heating and lead to larger ablation lesions. We sought to evaluate the effect of magnetic nanoparticles on tissue sensitivity to radiofrequency energy. METHODS AND RESULTS: Ablation was performed using an ablation catheter positioned with 10 g of force over prepared ex vivo specimens. Tissue temperatures were measured and lesion volumes were acquired. An in vivo porcine thigh model was used to study systemically delivered magnetically guided iron oxide (FeO) nanoparticles during radiofrequency application. Magnetic resonance imaging and histological staining of ablated tissue were subsequently performed as a part of ablation lesion analysis. Ablation of ex vivo myocardial tissue treated with metallic nanoparticles resulted in significantly larger lesions with greater impedance changes and evidence of increased thermal conductivity within the tissue. Magnet-guided localization of FeO nanoparticles within porcine thigh preps was demonstrated by magnetic resonance imaging and iron staining. Irrigated ablation in the regions with greater FeO, after FeO infusion and magnetic guidance, created larger lesions without a greater incidence of steam pops. CONCLUSIONS: Metal nanoparticle infiltration resulted in significantly larger ablation lesions with altered electric and thermal conductivity. In vivo magnetic guidance of FeO nanoparticles allowed for facilitated radiofrequency ablation without direct infiltration into the targeted tissue. Further research is needed to assess the clinical applicability of this ablation strategy using metallic nanoparticles for the treatment of cardiac arrhythmias.

Incidence of Atrial Fibrillation following Alcohol Septal Ablation for Hypertrophic Cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at a fourfold to sixfold higher risk of developing atrial fibrillation (AF) compared to the general population, though incidence rates among patients undergoing alcohol septal ablation (ASA) are not well characterized. The purpose of this study was to evaluate atrial fibrillation incidence following ASA. METHODS: We studied 132 consecutive HCM patients without comorbid AF that underwent 154 ASA procedures. The incidence of AF in follow-up was assessed through chart abstraction including electrocardiography. Survival free of AF was estimated using Kaplan-Meier methodology. RESULTS: Over a mean follow-up of 3.6 ± 2.7 years (maximum 11.3 years), 10 (7.6%) patients developed new-onset AF. Of those who developed AF, both resting and provoked left ventricular outflow tract (LVOT) gradients had improved significantly (difference -79.78 mm Hg, P ≤ 0.005). Severity of mitral regurgitation improved in 7 (70%) patients. Survival free of AF was estimated to be 99.1%, 93.7%, and 91.7% at 1, 3, and 5 years. CONCLUSIONS: Despite relieving LVOT obstruction and improving mitral regurgitation severity via ASA, new-onset AF remained a common complication of hypertrophic cardiomyopathy.

Ventricular Tachycardia in Congenital Pulmonary Stenosis.

With modern surgical techniques, there is significantly increased life expectancy for those with congenital heart disease. Although congenital pulmonary valve stenosis is not as complex as tetralogy of Fallot, there are many similarities between the 2 lesions, such that patients with either of these conditions are at risk for ventricular arrhythmias and sudden cardiac death. Those patients who have undergone surgical palliation for congenital pulmonary stenosis are at an increased risk for development of ventricular arrhythmias and may benefit from a more aggressive evaluation for symptoms of palpitations or syncope.

Impact of Alcohol Consumption on Atrial Fibrillation Outcomes Following Pulmonary Vein Isolation.

BACKGROUND: Moderate to heavy alcohol use has been shown to be associated with increased atrial fibrillation (AF) incidence. However, the relationship between alcohol use and AF recurrence after pulmonary vein isolation (PVI) is not well known. OBJECTIVE: We sought to study the impact of different alcohol consumption levels on outcomes after AF ablation. METHODS: A retrospective analysis was performed of 226 consecutive patients undergoing first time PVI for AF. Clinical data were collected including alcohol intake classified into 3 groups: none-rare (< 1 drink/ week), moderate (1-7 drinks/ week), and heavy (> 7 drinks/ week). Patients were followed for recurrences within the first 3 months (blanking period; early recurrence) and after 3 months up to 1 year (late recurrence) after the ablation. RESULTS: Paroxysmal and persistent AF had early recurrence rates of 29.1% and 32.2%, and late recurrence rates of 30.2% and 44.1%, respectively. The none-rare alcohol group had a higher frequency of diabetes mellitus (p=0.007). Neither moderate or heavy alcohol consumption, in reference to the none-rare group, was significantly predictive of early or late AF recurrence on adjusted multivariate logistic regression analysis (p>0.05). CONCLUSION: Despite known associations between alcohol and incidence of AF, alcohol consumption is not associated with early or late AF recurrence after PVI in this cohort.

Incidence and predictors of late complete heart block after alcohol septal ablation treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was designed to identify the incidence of late complete heart block (CHB) first identified at least 48 hours post alcohol septal ablation (ASA). BACKGROUND: Septal reduction with ASA is a therapeutic option for patients with symptomatic hypertrophic obstructive cardiomyopathy (HCM). CHB, resulting from the septal infarct, is a known complication with a reported incidence of 9-22%. The incidence of CHB more than 48 hours post-procedure is unknown. METHODS: Consecutive patients who underwent ASA were analyzed and clinical characteristics associated with late CHB were assessed. Late CHB was defined as first identification of CHB more than 48 hours after ASA. RESULTS: From 2002-2013, 145 subjects underwent 168 ASA procedures and were followed for a mean of 3.2 +/- 2.3 years. The incidence of late CHB was 8.9% (15/168 ASA procedures). Heart block occurred from 48 hours to 3-years post-procedure. In a multivariable model, patients with any CHB were more likely to have had multiple ASA procedures (OR 4.14; 95% CI: 1.24, 13.9; P < 0.05) and high resting and provoked left ventricular outflow tract (LVOT) gradient assessed by catheterization (OR per 10 mmHg gradient 1.14; 95% CI: 1.0, 1.20; P < 0.05). After multivariable adjustment, only a high provokable LVOT gradient remained an independent predictor of late CHB (OR per 10 mmHg gradient 1.14 [95% CI 1.02-1.29]). CONCLUSIONS: Late CHB is a common complication of ASA for treatment of symptomatic HCM. Post-discharge electrocardiographic surveillance for atrioventricular conduction disease should be considered after ASA, especially for those with a high provokable LVOT gradient.

Outcomes of patients with definite and suspected isolated cardiac sarcoidosis treated with an implantable cardiac defibrillator.

PURPOSE: Cardiac sarcoidosis (CS) patients are at increased risk for sudden death. Isolated CS is rare and can be difficult to diagnose. METHODS: In this multicenter retrospective review, patients with CS and an implantable cardiac defibrillator (ICD) were identified. RESULTS: Of 235 patients with CS and ICD, 13 (5.5 %) had isolated CS, including 7 (3.0 %) with definite isolated CS (biopsy or necropsy-proven) and 6 (2.6 %) with suspected isolated CS based on a constellation of clinical, ECG, and imaging findings. Among 13 patients with isolated CS, 10 (76.9 %) were male, mean age was 53.8 ± 7.6 years, and mean left ventricular ejection fraction was 38.3 ± 16.5. Diagnosis was made by cardiac magnetic resonance (CMR) (n = 2), biopsy (n = 3), CMR and biopsy (n = 2), CMR and positron emission tomography (PET) (n = 2), PET (n = 1), late enhanced cardiac CT (n = 1), pathology at heart transplant (n = 1), and autopsy (n = 1). Eight of 13 (61.5 %) patients with isolated CS had a secondary prevention indication (VT in 6 and VF in 2) vs. 80 of 222 (36.0 %) with sarcoidosis in other organs (p = 0.04). Over a mean of 4.2 years, 9 of 13 (69.2 %) patients with isolated CS received appropriate ICD therapy, including anti-tachycardia pacing (ATP) and/or shock, compared with 75 of 222 (33.8 %) patients with cardiac and extracardiac sarcoidosis (p = 0.0150). Six of 7 (85.7 %) patients with definite isolated CS received appropriate ICD intervention, compared with 78 of 228 patients (34.2 %) without definite isolated CS (p = 0.0192.) CONCLUSIONS: In this retrospective study, patients with isolated CS had very high rates of appropriate ICD therapy. Prospective, long-term follow-up of consecutive patients with isolated CS is needed to determine the true natural history and rates of ventricular arrhythmias in this rare and difficult-to-diagnose disease.

Syncope and cardiac arrest during strenuous exercise associated with a novel mutation in LQTS1.

Exercise-induced syncope should alert clinicians to the possibility of LQTS and must be distinguished from other malignant causes of syncope such as hypertrophic cardiomyopathy, catecholaminergic ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy. Emerging genotype-phenotype links have connected mutations resulting in LQTS with risk of developing atrial fibrillation and cardiomyopathy.

Measured Lead Parameters and Electrogram Sensing Over Time in Patients With Cardiac Sarcoidosis and an Implanted Cardiac-Defibrillator.

OBJECTIVES: The study sought to characterize the performance of implanted leads among a cohort of patients with cardiac sarcoidosis (CS) and implantable cardiac-defibrillators (ICDs). BACKGROUND: An ICD is indicated for some patients with CS for the prevention of sudden cardiac death. CS can lead to myocardial inflammation and scar that may interfere with lead performance. METHODS: We performed a case-control study within the cohort of patients at the University of Colorado Hospital with CS and an ICD (n = 48) compared with randomly selected controls (n = 117) who had other indications for an ICD. We compared the measured lead parameters at the time of routine interrogation to assess the differences between groups over time. The mean duration of follow-up was 51 months. Survival analysis was performed by the method of Kaplan and Meier and by Cox proportional hazards regression. RESULTS: There was no significant difference in measured lead impedance, capture thresholds, or sensed electrograms at implantation between the CS and control groups. There were no significant differences between the mean parameters between groups over the follow-up period. However, patients with CS have a high incidence of significant (>50%) drop in measured electrograms (16 of 46 [33%] CS patients vs. 4 of 117 [3.4%] controls; hazard ratio: 10.49, 95% confidence interval: 3.47 to 31.67). As a result of alterations in lead parameters, 2 patients (4.3%) required lead revision, and 6 patients (13%) required ICD testing to ensure adequate detection of induced ventricular fibrillation. CONCLUSIONS: Reductions over time in ICD sensing of P- and/or R-wave electrograms are common in patients with CS. Although further investigation is needed to determine the mechanism of these changes, these findings suggest that patients with CS who have an ICD should be closely monitored for clinically relevant changes in P- and R-wave amplitudes.