Pulmonary vein stenosis in heart transplant patients.

BACKGROUND: Pulmonary vein stenosis (PVS) is a rare pediatric condition associated with significant mortality and morbidity. PVS in patients following heart transplant (HT) has not yet been described. METHODS: Patients who had clinically significant PVS following a heart transplant during the time period of April 1, 2013 to April 30, 2023, at Seattle Children's Hospital were identified. Clinically significant PVS was defined as an atretic vein or a vein with a gradient of ≥4 mmHg across at least one vein by echocardiogram or during cardiac catheterization. Patients who had a diagnosis of PVS prior to their transplant were excluded. A total of six patients were identified. We collected clinical data on these patients from their pre-transplant course to their most recent status. RESULTS: The median age at HT was 7.5 months (range 2-13 months). The median time from HT to diagnosis of PVS was 3.5 months (range 0.3-13 months). At the last follow-up, the patients had had two to five pulmonary vein interventions, and there were no mortalities. The donor-to-recipient weight and total cardiac volume (TCV) ratios were less than 2.0 in five of six of the patients. CONCLUSIONS: PVS is a rare complication that is associated with patients who undergo HT during infancy. PVS develops soon after HT and screening should occur accordingly. Interestingly, high donor-to-recipient weight and TCV ratios are not necessarily associated with the development of PVS. Further work will need to be performed in order to determine the significance of PVS in post-HT patients.

The NEONATE score predicts freedom from interstage mortality or transplant in a modern cohort.

BACKGROUND: Derived from the National Pediatric Cardiology Quality Improvement Collaborative registry, the NEONATE risk score predicted freedom from interstage mortality or heart transplant for patients with single ventricle CHD and aortic arch hypoplasia discharged home following Stage 1 palliation. OBJECTIVES: We sought to validate the score in an external, modern cohort. METHODS: This was a retrospective cohort analysis of single ventricle CHD and aortic arch hypoplasia patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative Phase II registry from 2016 to 2020, who were discharged home after Stage 1 palliation. Points were allocated per the NEONATE score (Norwood type-Norwood/Blalock-Taussig shunt: 3, Hybrid: 12; extracorporeal membrane oxygenation post-op: 9, Opiates at discharge: 6, No Digoxin at discharge: 9, Arch Obstruction on discharge echo: 9, Tricuspid regurgitation ≥ moderate on discharge echo: 12; Extra oxygen plus ≥ moderate tricuspid regurgitation: 28). The composite primary endpoint was interstage mortality or heart transplant. RESULTS: In total, 1026 patients met inclusion criteria; 61 (6%) met the primary outcome. Interstage mortality occurred in 44 (4.3%) patients at a median of 129 (IQR 62,195) days, and 17 (1.7%) were referred for heart transplant at a 167 (114,199) days of life. The median NEONATE score was 0(0,9) in those who survived to Stage 2 palliation compared to 9(0,15) in those who experienced interstage mortality or heart transplant (p < 0.001). Applying a NEONATE score cut-off of 17 points that separated patients into low- and high-risk groups in the learning cohort provided 91% specificity, negative predictive value of 95%, and overall accuracy of 87% (85.4-89.5%). CONCLUSION: In a modern cohort of patients with single ventricle CHD and aortic arch hypoplasia, the NEONATE score remains useful at discharge post-Stage 1 palliation to predict freedom from interstage mortality or heart transplant.

Mycophenolic acid therapeutic drug monitoring using area under the curve in pediatric heart transplant recipients.

INTRODUCTION: Pharmacokinetics of mycophenolic acid (MPA) display substantial interpatient variability, with up to 10-fold difference of exposure in individual patients under a fixed-dose regimen. MPA trough level (C0) monitoring is common in clinical practice but has not proven sufficiently informative in predicting MPA exposure or patient outcomes, especially in children. No limited sampling strategies (LSSs) have been generated from pediatric heart transplant (HTx) recipients to estimate MPA AUC. METHODS: Single-center, observational analysis of 135 de novo pediatric HTx recipients ≤21 years old who underwent MPA AUC between 2011 and 2021. RESULTS: Median age was 4 years (IQR .6-12.1). Median time from transplant to MPA AUC sampling was 15 days (IQR 11-19). MMF doses (mg or mg/day) had low, negative Pearson correlation coefficients (r) while doses adjusted for weight or body surface area had low correlation with Trapezoidal MPA AUC0-24 h (r = .3 and .383, respectively). MPA C0 had weak association (r = .451) with Trapezoidal MPA AUC0-24 h . LSS with two pharmacokinetic sampling time points at 90 (C3 ) and 360 (C5 ) min after MMF administration (estimated AUC0-24 h  = 32.82 + 4.12 × C3  + 11.53 × C5 ) showed strong correlation with Trapezoidal MPA AUC0-24 h (r = .87). CONCLUSION: MMF at fixed or weight-adjusted doses, as well as MPA trough levels, correlate poorly with MPA AUC0-24 h . We developed novel LSSs to estimate Trapezoidal MPA AUC from a large cohort of pediatric HTx recipients. Validation of our LSSs should be completed in a separate cohort of pediatric HTx recipients.

Expanding use of the HeartMate 3 ventricular assist device in pediatric and adult patients within the Advanced Cardiac Therapies Improving Outcomes Network (ACTION).

BACKGROUND: We report current outcomes in patients supported with the HeartMate 3 (HM3) ventricular assist device in a multicenter learning network. METHODS: The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HM3 implants between 12/2017 and 5/2022. Clinical characteristics, postimplant course, and adverse events were collected. Patients were stratified according to body surface area (BSA) (<1.4 m2, 1.4-1.8 m2, and >1.8 m2) at device implantation. RESULTS: During the study period, 170 patients were implanted with the HM3 at participating network centers, with median age 15.3years; 27.1% were female. Median BSA was 1.68 m2; the smallest patient was 0.73 m2 (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with BSA <1.4 m2 had a higher incidence of infection, renal dysfunction, and ischemic stroke. CONCLUSIONS: In this updated cohort of predominantly pediatric patients supported with the HM3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care.

Assessment of the adverse effects of sirolimus versus everolimus in pediatric heart transplant recipients.

BACKGROUND: Literature is limited comparing adverse effects (AEs) of the proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (EVL) in pediatric heart transplant (HTx) recipients. METHODS: Single-center, observational cohort analysis assessing first use of SRL or EVL in pediatric HTx recipients <21 years of age with up to 2 years follow-up between 2009 and 2020. RESULTS: Eighty-seven patients were included, with 52 (59.8%) receiving EVL and 35 (40.2%) receiving SRL. Tacrolimus with PSI was the most common regimen. Intergroup comparison revealed lower baseline estimated glomerular filtration rate (eGFR) and greater increase in eGFR from baseline to 6 months and latest follow-up in SRL cohort compared to EVL cohort. There was greater increase in HDL cholesterol in SRL cohort compared to EVL cohort. Intragroup analysis revealed eGFR and HDL cholesterol increased significantly within SRL cohort, triglycerides and glycosylated hemoglobin increased in EVL cohort, and LDL cholesterol and total cholesterol increased in both cohorts (all p < .05). There were no differences in hematological indices or rates of aphthous ulcers, effusions, or infections between cohorts. Incidence of proteinuria was not significantly different among those screened within cohorts. Of those included in our analysis, one patient in SRL cohort (2.9%) and two in EVL cohort (3.8%) had PSI withdrawn due to AE. CONCLUSION: Low-dose PSIs in calcineurin inhibitor minimization regimens appear well-tolerated with low withdrawal rate secondary to AE in pediatric HTx recipients. While incidence of most AE was similar between PSI, our results suggest EVL may be associated with less favorable metabolic impact than SRL in this population.

Early Clinical Experience with Dapagliflozin in Children with Heart Failure.

Pediatric heart failure (HF) is associated with significant morbidity and mortality. Medical treatment for pediatric HF is largely derived from adult studies. Previously, there has been no described use of dapagliflozin in pediatric HF patients. We describe our single-center experience using dapagliflozin in addition to standard HF medical therapy in 38 pediatric HF patients since January 2020. Median age was 12.2 years (interquartile range 6.2-17.5). Majority of patients had dilated cardiomyopathy (68.4%) and reduced left ventricular ejection fraction (LVEF) of 40% or less (65.8%). HF regimens commonly included sacubitril/valsartan, beta-blocker, mineralocorticoid receptor antagonist, and loop diuretic. Median follow-up from dapagliflozin initiation for the whole cohort was 130 days (IQR 76-332). Median B-type natriuretic peptide decreased significantly from 222 to 166 pg/mL at latest clinical follow-up (P = .04). Estimated glomerular filtration rate trended lower at latest follow-up but was not significant from baseline. There were no clinically significant changes in blood chemistries or vital signs after initiation of dapagliflozin. No patients experienced symptomatic hypoglycemia or hypovolemia. Six patients (15.8%) experienced a symptomatic urinary tract infection necessitating antibiotic treatment. In a separate analysis of 16 patients with dilated cardiomyopathy who received dapagliflozin for a median of 313 days (IQR 191-414), median LVEF increased significantly from 32 to 37.2% (P = .006). Dapagliflozin, when added to a background of guideline-directed medical therapy, appears well tolerated in children with HF. Larger studies are needed to evaluate safety and efficacy of dapagliflozin in this population.

Increased risk of infections in pediatric Fontan patients after heart transplantation.

BACKGROUND: Infectious complications are a major cause of morbidity and mortality after HT. Fontan patients may be more susceptible to post-HT infections. METHODS: This was a single-center, retrospective cohort analysis of pediatric patients undergoing HT for FF physiology or DCM, who underwent induction with ATG. The primary endpoint was an infection in the first 180 days post-HT, defined as positive (1) blood/urine/respiratory culture; (2) viral PCR; (3) skin or wound infection; and/or (4) culture-negative infection if ≥5 days of antibiotics were completed. Secondary endpoints included (1) cell counts after ATG; (2) PTLD; and (3) rejection (≥Grade 2R ACR or pAMR2) in the first 180 days post-HT. RESULTS: A total of 59 patients (26 FF, 33 DCM) underwent HT at 14.7 (IQR 10.6, 19.5) and 11.7 (IQR 1.4, 13.6) years of age, respectively. The median total ATG received was 7.4 (IQR 4.9, 7.7) vs 7.5 (IQR 7.3, 7.6) mg/kg (p = NS) for FF and DCM patients, respectively. Twenty-three patients (39%) developed an infection 180 days post-HT, with a higher rate of infection in FF patients (54% vs 27%, p = .03). Adjusted for pre-transplant absolute lymphocyte count, FF patients had a higher risk of infection at 30 days post-HT (OR 7.62, 95% CI 1.13-51.48, p = .04). There was no difference in the incidence of PTLD (12% vs 0%; p = .08) or rejection (12% vs 21%; p = .49). CONCLUSION: Compared to DCM patients, FF patients have a higher risk of infection. Modifications to induction therapy for FF patients should be considered.

Characteristics of Interstage Death After Discharge from Stage I Palliation.

BACKGROUND: Interstage mortality (IM) remains high for patients with single-ventricle congenital heart disease (SVCHD) in the period between Stage 1 Palliation (S1P) and Glenn operation. We sought to characterize IM. METHODS: This was a descriptive analysis of 2184 patients with SVCHD discharged home after S1P from 60 National Pediatric Cardiology Quality Improvement Collaborative sites between 2008 and 2015. Patients underwent S1P with right ventricle-pulmonary artery conduit (RVPAC), modified Blalock-Taussig-Thomas shunt (BTT), or Hybrid; transplants were excluded. RESULTS: IM occurred in 153 (7%) patients (median gestational age 38 weeks, 54% male, 77% white), at 88 (IQR 60,136) days of life, and 39 (IQR 17,84) days after hospital discharge; 13 (8.6%) occurred ≤ 30 days after S1P. The mortality rate for RVPAC was lower (5.2%; 59/1138) than BTT (9.1%; 65/712) and Hybrid (20.1%; 27/134). More than half of deaths occurred at home (20%) or in the emergency department (33%). The remainder occurred while inpatient at center of S1P (cardiac intensive care unit 36%, inpatient ward 5%) or at a different center (5%). Fussiness and breathing problems were most often cited as harbingers of death; distance to surgical center was the biggest barrier cited to seeking care. Cause of death was unknown in 44% of cases overall; in the subset of patients who underwent post-mortem autopsy, the cause of death remained unknown in 30% of patients, with the most common diagnosis being low cardiac output. CONCLUSIONS: Most IM occurred in the outpatient setting, with non-specific preceding symptoms and unknown cause of death. These data indicate the need for research to identify occult causes of death, including arrhythmia.

Medical management of pediatric heart failure.

Pediatric heart failure is a complex, heterogenous syndrome that occurs relatively rarely in children, but carries a high burden of morbidity and mortality. This article reflects on the current state of medical therapy for both acute and chronic pediatric heart failure, based on expert consensus guidelines, and the extrapolation of data from trials performed in adults. For the management of acute heart failure specifically, we rely on an initial assessment of the perfusion and volume status of a patient, to guide medical therapy. This paradigm was adapted from adult studies that demonstrated increased morbidity and mortality in heart failure patients whose hemodynamics or examination findings were consistent with a PCWP >18 mmHg and a CI ≤2.2 L/min/m2. The cornerstone of treatment in the acute setting therefore relies on achieving a euvolemic state with adequate cardiac output. In the chronic setting, patients are typically maintained on a regimen of an angiotensin converting enzyme inhibitor, a beta-blocker, and spironolactone. For those with refractory heart failure, intravenous milrinone therapy has become a mainstay of bridging children to cardiac transplantation. The pediatric-specific data driving these clinical practices are limited and often times, conflicting. The future of pediatric heart failure depends on collaboration, quality improvement, and a commitment to pediatric-specific indications for new medical and device therapies.

Structure and Antiparasitic Activity Relationship of Alkylphosphocholine Analogues against Leishmania donovani.

Miltefosine (Milt) is the only oral treatment for visceral leishmaniasis (VL) but its use is associated with adverse effects, e.g., teratogenicity, vomiting, diarrhoea. Understanding how its chemical structure induces cytotoxicity, whilst not compromising its anti-parasitic efficacy, could identify more effective compounds. Therefore, we systemically modified the compound's head, tail and linker tested the in vitro activity of three alkylphosphocholines (APC) series against Leishmania donovani strains with different sensitivities to antimony. The analogue, APC12, with an alkyl carbon chain of 12 atoms, was also tested for anti-leishmanial in vivo activity in a murine VL model. All APCs produced had anti-leishmanial activity in the micromolar range (IC50 and IC90, 0.46- > 82.21 µM and 4.14-739.89 µM; 0.01- > 8.02 µM and 0.09-72.18 µM, respectively, against promastigotes and intracellular amastigotes). The analogue, APC12 was the most active, was 4-10 fold more effective than the parent Milt molecule (APC16), irrespective of the strain's sensitivity to antimony. Intravenous administration of 40 mg/kg APC12 to L. donovani infected BALB/c mice reduced liver and spleen parasite burdens by 60 ± 11% and 60 ± 19%, respectively, while oral administration reduced parasite load in the bone marrow by 54 ± 34%. These studies confirm that it is possible to alter the Milt structure and produce more active anti-leishmanial compounds.

Development of a validated risk score for interstage death or transplant after stage I palliation for single-ventricle heart disease.

OBJECTIVE: To develop a risk score to predict mortality or transplant in the interstage period. BACKGROUND: The "interstage" period between the stage 1 and stage 2 palliation is a time of high morbidity and mortality for infants with single-ventricle congenital heart disease. METHODS: This was an analysis of patients with single-ventricle congenital heart disease requiring arch reconstruction who were enrolled in the National Pediatric Cardiology Quality Improvement Collaborative registry from 2008 to 2015. The primary composite endpoint was interstage mortality or transplant. Multivariable logistic regression and classification and regression tree analysis were performed on two-thirds of the patients ("learning cohort") to build a risk score for the composite endpoint, that was validated in the remaining patients ("validation cohort"). RESULTS: In the 2128 patients analyzed in the registry, the overall event rate was 9% (153 [7%] deaths, 42 [2%] transplants). In the learning cohort, factors independently associated with the composite endpoint were (1) type of Norwood; (2) postoperative ECMO; (3) discharge with Opiates; (4) No Digoxin at discharge; (5) postoperative Arch obstruction, (6) moderate-to-severe Tricuspid regurgitation without an oxygen requirement, and (7) Extra Oxygen required at discharge in patients with moderate-to-severe tricuspid regurgitation. This model was used to create a weighted risk score ("NEONATE" score; 0-76 points), with >75% accuracy in the learning and validation cohorts. In the validation cohort, the event rate in patients with a score >17 was nearly three times those with a score ≤17. CONCLUSIONS: We introduce a risk score that can be used post-stage 1 palliation to predict freedom from interstage mortality or transplant.

Drug combinations as effective anti-leishmanials against drug resistant Leishmania mexicana.

Leishmania is a parasite that causes the disease leishmaniasis, and 700 000 to 1 million new cases occur each year. There are few drugs that treat the disease and drug resistance in the parasite limits the clinical utility of existing drugs. One way to combat drug resistance is to use combination therapy rather than monotherapy. In this study we have compared the effect of single and combination treatments with four different compounds, i.e. alkylphosphocholine analogues APC12 and APC14, miltefosine (MIL), ketoconazole (KTZ), and amphotericin B (AmpB), on the survival of Leishmania mexicana wild-type promastigotes and a cell line derived from the WT with induced resistance to APC12 (C12Rx). The combination treatment with APC14 and APC16 had a synergistic effect in killing the WT while the combination treatment with KTZ and APC12 or APC14 or APC12 and APC14 had a synergistic effect against C12Rx. More than 90% killing efficiency was obtained using APC12 alone at >1 mg ml-1 against the C12Rx strain; however, combinations with APC14 produced a similar killing efficiency using APC12 at 0.063-0.25 mg ml-1 and APC14 at 0.003-0.5 mg ml-1. These results show that combination therapy can negate induced drug resistance in L. mexicana and that the use of this type of screening system could accelerate the development of drug combinations for clinical use.

Safety of inhaled hydrogen gas in healthy mice.

The purpose of this work was to determine the safety of inhaled hydrogen gas in healthy animals. Female mice were exposed to medical air with or without hydrogen gas (concentration 2.4%) for 72 hours (n = 25 mice/group). Mice underwent a standardized and validated neurobehavioral examination, SmithKline Beecham, Harwell, Imperial College, Royal London Hospital, Phenotype Assessment (SHIRPA) protocol, prior to and following the exposure period. Blood was withdrawn for serologic evaluation and all major organ tissues were evaluated histologically. The average hydrogen concentration within the chamber was 2.27%. Following exposure, there was no significant change in body weight in either group. Similarly, there was no significant change in the total SHIRPA score, although hydrogen-treated mice exhibited significantly lower spontaneous locomotor activity (P < 0.0001) in a subset of the test; all other aspects of the mouse neurologic exam were normal in hydrogen-treated animals. Brain histopathology was also normal in all mice, as was the histology of all other major organs. There were no significant differences in complete blood count, serum chemistry, or arterial blood gases between control and hydrogen-treated mice (P > 0.05 for all). Hydrogen gas did not appear to cause significant adverse effects when administered to healthy mice for 72 hours, with the possible exception of decreased spontaneous locomotor activity. The study was approved by the Institutional Animal Care and Use Committee at Boston Children's Hospital, USA (approved number 18-01-3536) on January 25, 2018.

Early Repolarization in Normal Adolescents is Common.

In adults with structurally normal hearts, the early repolarization pattern (ERP) on electrocardiogram (ECG) may be associated with an increased risk of sudden cardiac death. The prevalence and significance of the ERP in children is unknown. This study examines the prevalence of the ERP, the population in which it is found, and whether there exists any correlation with increased LV mass or family history of significant cardiac events. This was a secondary review of data obtained from healthy adolescents undergoing a limited ECG and transthoracic echocardiogram (TTE) as part of a cardiac screening study. Subjects were excluded if ECG revealed known arrhythmic syndromes or TTE revealed structural abnormalities. ERP was defined as (1) notching or slurring of the terminal QRS; (2) elevation of the QRS-ST junction ≥1 mV; and (3) upwardly concave positive T-wave. Left ventricular (LV) mass was defined as mass/height2.7. Patient demographics, LV mass, family history of sudden death, arrhythmia, and/or ICD/pacemaker placement were compared for subjects with and without ERP on ECG. Data from 575 subjects (median age 15, range 13-18; 36% female; 93% Caucasian) were reviewed. The incidence of ERP was 40% (n = 228) and was seen in the inferior, lateral, or combination of these leads in 42, 10, and 48% of subjects with ERP, respectively. There was no difference in gender (p = 0.7), race (p = 0.7), age (p = 0.3), history of syncope (p = 0.2), LV mass (p = 0.8), family history of (a) sudden death (p = 0.5), (b) arrhythmia (p = 0.2), or (c) ICD/pacemaker requirement (p = 0.8) in subjects with ERP versus those without. However, a greater percentage of patients with ERP were noted to play football, when compared to those without ERP (34 vs. 13%, p < 0.001). ERP is common in healthy adolescents, and does not correlate with concerning personal/family history or elevated LV mass. Longitudinal studies are required to determine whether ERP in childhood confers an increased mortality risk.

Ambulatory Monitoring and Arrhythmic Outcomes in Pediatric and Adolescent Patients With Duchenne Muscular Dystrophy.

BACKGROUND: Patients with Duchenne Muscular Dystrophy (DMD) develop cardiac fibrosis and dilated cardiomyopathy. We described the frequency of significant Holter findings in DMD, the relationship between cardiac function and arrhythmia burden, and the impact of these findings on clinical management. METHODS AND RESULTS: A retrospective review was done of patients with DMD who received a Holter from 2010 to 2014. Clinical and arrhythmic outcomes were analyzed. Patients were classified based on left ventricular ejection fraction (LVEF): ≥55%, 35% to 54% and <35%. Significant Holter findings included atrial tachycardia, ventricular tachycardia and atrial fibrillation/flutter. Logistic regression was used to assess predictors of significant Holter findings and change in care. The study included 442 Holters in 235 patients. Mean age was 14±4 years. Patients with cardiac dysfunction were older, and had increased late gadolinium enhancement and left ventricular dilation (P<0.01). There were 3 deaths (1%), all with normal function and none cardiac. Patients with LVEF <35% had more arrhythmias including nonsustained atrial tachycardia (P=0.01), frequent premature ventricular contractions, ventricular couplets/triplets, and nonsustained ventricular tachycardia (P<0.001) compared to the other groups. LVEF <35% (P<0.001) was the only predictor of clinically significant Holter finding. Four patients (40%) had change in medication in the LVEF <35% group compared to 9 (3%) in the ≥55% and 4 (4%) in the 35% to 54% groups (P<0.001). CONCLUSIONS: Sudden cardiac events are rare in DMD patients with an LVEF >35%. Significant Holter findings are rare in patients with DMD who have an LVEF >35%, and cardiac dysfunction appears to predict significant Holter findings. Holter monitoring is highest yield among DMD patients with cardiac dysfunction.

Adjunctive renal sympathetic denervation to modify hypertension as upstream therapy in the treatment of atrial fibrillation (H-FIB) study: clinical background and study design.

BACKGROUND: Hypertension is the most important risk factor directly attributable to the high prevalence of atrial fibrillation (AF), and is one of the few modifiable risk factors for AF. Activation and overactivity of the sympathetic nervous system (SNS) have been implicated in the pathogenesis of both essential hypertension and AF. Catheter-based renal sympathetic denervation (RSDN) appears to be an effective adjunctive treatment for refractory hypertension, and may be beneficial in other conditions characterized by SNS overactivity, such as left ventricular hypertrophy and atrial arrhythmias. OBJECTIVE: The H-FIB study is a multicenter prospective, double-blind, randomized (1:1) controlled trial. The primary efficacy endpoint is antiarrhythmic drug-free freedom from AF recurrence through 12 months. METHODS: Patients with a history of significant hypertension who are receiving treatment with at least one antihypertensive agent who are planned for a first time ablation for symptomatic paroxysmal or persistent AF will be randomized to either AF ablation alone (control group) or AF ablation + RSDN (study group). CONCLUSIONS: H-FIB is a multicenter, randomized trial that will test the hypothesis that adjunctive renal sympathetic denervation, at the time of AF ablation, will increase the freedom from recurrent AF.

Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension.

OBJECTIVES: This study sought to assess whether renal sympathetic denervation (RSDN) can be achieved using an off-the-shelf saline-irrigated radiofrequency ablation (RFA) catheter typically employed for cardiac tissue ablation. BACKGROUND: RSDN using a specialized solid-tip RFA catheter has recently been demonstrated to safely reduce systemic blood pressure in patients with refractory hypertension. For cardiac tissue ablation, RFA technology has evolved from nonirrigated to saline-irrigated ablation electrodes to improve both safety and effectiveness. METHODS: Ten patients with resistant hypertension underwent renal angiography, followed by bilateral RSDN with a saline-irrigated RFA catheter. Ambulatory blood pressure recordings (24 h) were obtained at baseline, 1, 3, and 6 months after the procedure. Repeat renal angiography was performed during follow-up to assess for arterial stenosis or aneurysm. In 5 patients, pre- and post-procedural serum measures of renal function and sympathetic activity were obtained: aldosterone; metanephrine; normetanephrine; plasma renin activity; and creatinine. RESULTS: Over a 6-month period: 1) the systolic/diastolic blood pressure decreased by -21/-11 mm Hg; 2) all patients experienced a decrease in systolic blood pressure of at least 10 mm Hg (range 10 to 40 mm Hg); 3) there was no evidence of renal artery stenosis or aneurysm at repeat angiography; and 4) there was a significant decrease in metanephrine (-12 ± 4, p = 0.003), normetanephrine (-18 ± 4, p = 0.0008), and aldosterone levels (-60 ± 33 ng/l, p = 0.02) at 3 months. There was no significant change in plasma renin activity (-0.2 mg/l/hod, p = 0.4). There was no significant change in serum creatinine (-1 mmol/l, p = 0.4). CONCLUSIONS: These data provide the proof-of-principle that RSDN can be performed using an off-the-shelf saline-irrigated RFA catheter.

Initial clinical experience with a novel visualization and virtual electrode radiofrequency ablation catheter to treat atrial flutter.

BACKGROUND: Linear ablation lesions are used to treat a variety of cardiac arrhythmias. However, successful long-term outcome is hampered by both the uncertainty of catheter-tissue contact for any individual lesion and the difficulty in ensuring point-to-point lesion contiguity. OBJECTIVE: A novel virtual electrode radiofrequency ablation catheter equipped with an endoscope to directly visualize the target tissue was used to ensure tissue contact and lesion contiguity along the cavotricuspid isthmus (CTI) to treat typical atrial flutter. METHODS: In this feasibility study of five patients with drug-resistant CTI-dependent atrial flutter, catheter ablation was performed using the visualization virtual electrode radiofrequency ablation catheter. After standard femoral access, the ablation catheter was advanced to the tricuspid annulus under fluoroscopic and intracardiac echocardiography guidance. In three of five patients, the ablation procedure was performed during atrial flutter; the other two ablations were during coronary sinus pacing. RESULTS: Conversion to sinus rhythm was noted after the delivery of 12 ± 7 lesions. Bidirectional CTI conduction block was successfully achieved in all patients. Initial, transient CTI block was first observed after delivering 19 ± 13 lesions; ultimately, 34 ± 18 lesions were required to achieve permanent bidirectional CTI block. The mean ablation and procedure times were 72 ± 42 and 151 ± 17 minutes. The mean fluoroscopy times for the ablation alone and the entire procedure were 13 ± 8 and 17 ± 7 minutes, respectively. CONCLUSIONS: This study introduces the clinical feasibility of a novel paradigm for contiguous linear ablation: virtual electrode ablation under direct endoscopic visualization.