Consensus Guidelines for the Prevention and Management of Periprocedural Complications of Transcatheter Patent Ductus Arteriosus Closure with the Amplatzer Piccolo Occluder in Extremely Low Birth Weight Infants.

Transcatheter closure of patent ductus arteriosus (PDA) in premature infants is a feasible, safe, and an effective alternative to surgical ligation and may be performed with an implant success rate of 97%. Major procedural complications related to transcatheter PDA closure in extremely low birth weight (ELBW) infants are relatively infrequent (< 3%) ,but may be associated with a fatality if not optimally managed. Operators performing transcatheter PDA closures should be knowledgeable about these potential complications and management options. Prompt recognition and treatment are often necessary to avoid serious consequences. With strict guidelines on operator training, proctoring requirements, and technical refinements, transcatheter PDA closure in ELBW infants can be performed safely with low complication rates. This article summarizes the consensus guidelines put forward by a panel of physicians for the prevention and management of periprocedural complications of transcatheter PDA closure with the Amplatzer Piccolo Occluder in ELBW infants.

Amplatzer Piccolo Occluder clinical trial for percutaneous closure of the patent ductus arteriosus in patients ≥700 grams.

OBJECTIVES: Characterize the safety and effectiveness of the Amplatzer Piccolo Occluder for patent ductus arteriosus (PDA) closure. BACKGROUND: The presence of a hemodynamically significant PDA has been associated with an increased risk of morbidity and mortality in children born premature. METHODS: This was a single arm, prospective, multicenter, non-randomized study to evaluate the Amplatzer Piccolo Occluder to treat PDA in patients ≥700 g. From June 2017 to February 2019, 200 patients were enrolled at nine centers, with 100 patients weighing ≤2 kg. Primary effectiveness endpoint was the rate of PDA closure at 6-month follow-up. Primary safety endpoint was the rate of major complications through 6 months. Secondary endpoint was rate of significant pulmonary or aortic obstruction through 6 months' follow-up. RESULTS: The implant success rate was 95.5% (191/200) overall and 99% in patients ≤2 kg (99/100). The primary effectiveness endpoint was achieved in 99.4% of implanted patients. Four patients experienced a primary safety endpoint event (2 transfusions, 1 hemolysis, and 1 aortic obstruction). There were no branch pulmonary artery obstructions. Five patients, all ≤2 kg, were noted to have worsening of tricuspid regurgitation (TR) after the procedure. None of the TR incidences manifested clinically. The Amplatzer Piccolo Occluder received FDA approval in January 2019 and became the first device approved for PDA closure in patients ≥700 g. CONCLUSIONS: This study supports the safety and effectiveness of the Amplatzer Piccolo Occluder, particularly in patients between 700 g and 2 kg where there is currently a significant unmet need in the United States. ClinicalTrials.gov identifier: NCT03055858.

Thoracic impedance measures tissue characteristics in the vicinity of the electrodes, not intervening lung water: implications for heart failure monitoring.

The rationale for intrathoracic impedance (Z) detection of worsening heart failure (HF) presupposes that changes in Z reflect changes in pulmonary congestion, but is confounded by poor specificity in clinical trials. We therefore tested the hypothesis that Z is primarily affected by tissue/water content in proximity to electrodes rather than by lung water distribution between electrodes through the use of a new computational model for deriving the near-field impedance contributions from the various electrodes. Six sheep were implanted with a left atrial pressure (LAP) monitor and a cardiac resynchronization therapy device which measured Z from six vectors comprising of five electrodes. The vector-based Z was modelled as the summation of the near-field impedances of the two electrodes forming the vector. During volume expansion an acute increase in LAP resulted in simultaneous reductions in the near-field impedances of the intra-cardiac electrodes, while the subcutaneous electrode showed several hours of lag (all p<0.001). In contrast, during the simulated formation of device-pocket edema (induced by fluid injection) the near-field impedance of the subcutaneous electrode had an instantaneous response, while the intra-cardiac electrodes had a minimal inconsistent response. This study suggests that the primary contribution to the vector based Z is from the tissue/water in proximity to the individual electrodes. This novel finding may help explain the limited utility of Z for detecting worsening HF.

Effects of AV delay and VV delay on left atrial pressure and waveform in ambulant heart failure patients: insights into CRT optimization.

BACKGROUND: We hypothesized that left atrial pressure (LAP) obtained by a permanent implantable sensor is sensitive to changes in cardiac resynchronization therapy (CRT) settings and could guide CRT optimization to improve the response rate. We investigated the effect of CRT optimization on LAP and its waveform parameters in ambulant heart failure (HF) patients. METHODS: CRT optimization was performed in eight ambulant HF patients, using echocardiography as reference. LAP waveform was acquired at each of eight atrioventricular (AV) intervals and five inter-ventricular (VV) intervals. Selected waveform parameters were also evaluated for their sensitivity to CRT changes and agreement with echocardiography-guided optimal settings. RESULTS: Optimal AV and VV intervals varied considerably between patients. All patients exhibited significant changes in waveform morphology with AV optimization. Optimal AV delay determined from echocardiography ranged between 140 ms and 225 ms. Mean LAP tended to be lower at optimal setting 14 ± 3 mmHg compared to shorter (<100 ms) or longer (>160 ms) AV settings (P = 0.16). There were clear trends to smaller peak a-wave (P = 0.11) and gentler positive a-slope (P = 0.15) and positive v-slope (P = 0.09) with longer AV delays. Mean LAP and negative v-wave slope correlated well with echo-guided optimal setting, r = 0.91 (P = 0.001) and 0.79 (P = 0.03), respectively. No significant effects on LAP or waveform were seen during VV optimization. CONCLUSIONS: LAP and its waveform changes considerably with AV optimization. There is good agreement between echo-guided optimal setting and LAP. LAP could provide an objective guide to CRT optimization. (Clinical Trial Registry information: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00632372).

Transcatheter Closure of Postinfarct VSD With the Amplatzer PIVSD Occluder: Results of a US Study.

Background: A postinfarct ventricular septal defect (PIVSD) is associated with high mortality and morbidity, particularly in patients with hemodynamic instability who are not suitable candidates for surgical repair. The Amplatzer PIVSD Occluder (Abbott) is indicated for transcatheter PIVSD closure in patients who are not satisfactory candidates for surgical repair. The objective of this study was to evaluate associated clinical outcomes. Methods: A total of 131 patients underwent transcatheter PIVSD closure using the Amplatzer PIVSD Occluder between 2011 and 2021 as part of a postapproval, multicenter, retrospective, observational study. The patients were analyzed in 2 cohorts. Cohort 1 included 99 patients (age 68.6 ± 11.9 years) implanted from 2011 to 2016 and evaluated technical success, procedure survival, and 6-month survival. Cohort 2 included 32 patients (age 66.4 ± 10.9 years) implanted from 2012 to 2021 with postprocedure echocardiograms and evaluated 24-hour closure, 6-month closure, and 6-month survival. Results: Technical success was achieved in 76.8% (76/99), procedure survival in 84.3% (75/89), and 6-month survival was observed in 37.2% of cohort 1 patients. Twenty-four-hour closure and 6-month closure were achieved in 53.1% (17/32) and 66.7% (4/6) of cohort 2 patients, respectively. Six-month survival was 46.4% of cohort 2 patients. Of the 16 deaths in cohort 2, 11 were cardiac-related, 4 were noncardiac-related, and 1 was of unknown etiology. Conclusions: This study demonstrates high morbidity of patients undergoing PIVSD closure using the Amplatzer PIVSD Occluder and that the device continues to be a safe alternative to medical therapy in patients who are not satisfactory candidates for surgical repair of a PIVSD.

Ten-Year Follow-Up of Mitral Valve Replacement with the Epic Porcine Valve in a Medicare Population.

BACKGROUND: Bioprosthetic surgical mitral valve replacement (SMVR) remains an important treatment option in the era of transcatheter valve interventions. We present 10-year clinical outcomes of Medicare beneficiaries undergoing SMVR with a contemporary low-profile mitral porcine valve. METHODS: This is a single-arm observational study using Medicare fee-for-service claims data. De-identified patients undergoing SMVR with the Epic™ Mitral valve (Abbott, Minnesota, USA) in the United States between 1/1/2008-12/31/2019 were selected by ICD-9/10 procedure codes and then linked to a manufacturer device tracking database. All-cause mortality, heart failure (HF) re-hospitalization, and mitral valve reintervention (surgical or transcatheter valve-in-valve) were evaluated at 10-years using the Kaplan Meier method. RESULTS: Among 75,739 Medicare beneficiaries undergoing SMVR during the study period, 14,015 were implanted with the Epic™ Mitral valve, of which 76.5% (10,720) had underlying HF. Mean age was 74±8 years. Survival at 10-years in patients without preoperative HF was 40.4% (95% CI 37.4%-43.4%) compared to 25.4% (95% CI 23.8%-27.0%) for patients with HF (p < 0.001). The 10-year freedom from HF rehospitalization was 51.3% (95% CI 49.4%-53.1%). Freedom from mitral valve reintervention was 91.4% (95% CI 89.7%-92.7%) at 10 years. CONCLUSIONS: This real-world nationwide study of Medicare beneficiaries receiving the Epic™ Mitral valve demonstrates >90% freedom from all-cause valve reintervention and >50% freedom from HF rehospitalization at 10-years post-implant. Long-term survival and HF rehospitalization in this population with mitral valve disease undergoing SMVR was found to be impacted by underlying HF.

An implantable left atrial pressure sensor lead designed for percutaneous extraction using standard techniques.

BACKGROUND: An implantable left atrial pressure (LAP) monitoring system for guiding the management of patients with advanced heart failure has the potential to require extraction, particularly in the setting of infection. The LAP sensor lead was designed to be suitable for ease of percutaneous extraction using standard techniques for extracting pacemaker and defibrillator leads. The clinical experience, to date, with percutaneous extraction of the LAP sensor lead is presented. METHODS: A total of 82 patients underwent successful implantation of the LAP sensor lead using transseptal catheterization. Five patients of the 82 patients during a cumulative follow-up period of 267 patient-years (median of 2.9 years/patient) underwent percutaneous extraction using manual traction with a locking stylet and/or an excimer laser sheath to bore through adhesions. The distal fixation anchors of the LAP sensor lead are designed to fold forward during extraction so that the sensor module can easily separate from the interatrial septum. RESULTS: Percutaneous extraction of the LAP sensor lead was accomplished successfully in all five patients with no embolic events, vascular tears, perforations, or other complications requiring surgical intervention. Manual traction alone was sufficient to detach the LAP sensor lead from the interatrial septum in all cases. Use of the excimer laser sheath was needed in selected cases to bore through scar tissue within the venous insertion site, but not within the heart. CONCLUSIONS: The extraction of the LAP sensor lead was accomplished safely using standard techniques and equipment for percutaneously extracting pacemaker and defibrillator leads.

3-year follow-up of a prospective, multicenter study of the Amplatzer Piccolo™ Occluder for transcatheter patent ductus arteriosus closure in children ≥ 700 grams.

OBJECTIVE: This study describes 3-year follow-up of 200 infants weighing ≥ 700 grams who underwent transcatheter patent ductus arteriosus (PDA) closure with the Amplatzer Piccolo™ Occluder. STUDY DESIGN: Between June 2017 and February 2019, 200 children were enrolled in this U.S. study (NCT03055858). PDA closure, survival, and device- or procedure-related events were evaluated. A total of 156 of the available 182 patients (86%) completed the study. RESULTS: The implant success rate was 95.5% (191/200). At 3 years, PDA closure was observed in 100% (33/33) of patients. Survival was >95% with 9 reported deaths. No deaths were adjudicated as device- or procedure-related. Notable events included aortic obstruction (2) requiring stent placement and tricuspid regurgitation (5), for which no interventions were required. CONCLUSIONS: This follow-up study demonstrates high rates of PDA closure, low serious complication rates, and survival > 95% at 3 years. The Amplatzer Piccolo™ Occluder is a safe and effective therapy for PDA treatment in premature infants. CLINICALTRIALS: gov identifier: NCT0305585.

Ten-year outcomes of surgical aortic valve replacement with a contemporary supra-annular porcine valve in a Medicare population.

Objective: Bioprosthetic surgical aortic valve replacement remains an important treatment option in the era of transcatheter interventions. Real-world outcomes are not well characterized because of limited prospective follow-up studies. We present the 10-year clinical outcomes of Medicare beneficiaries undergoing surgical aortic valve replacement with a contemporary supra-annular porcine valve. Methods: This is a single-arm observational study using Medicare fee-for-service claims data. De-identified patients undergoing surgical aortic valve replacement with the Epic Supra valve (Abbott) in the United States between January 1, 2008, and December 31, 2019, were selected by International Classification of Diseases 9th and 10th Revision procedure codes and then linked to a manufacturer device tracking database. All-cause mortality, heart failure rehospitalization, and aortic valve reintervention (surgical or transcatheter valve-in-valve) were evaluated at 10 years using the Kaplan-Meier method. Results: Among 272,591 Medicare beneficiaries undergoing surgical aortic valve replacement during the study period, 11,685 received the Epic Supra valve, of whom 51.6% (6029) had underlying heart failure. Mean age was 76 ± 7 years. Survival at 10 years in patients without preoperative heart failure was 43.5% (95% confidence interval, 41.8-45.2) compared with 24.1% (95% confidence interval, 22.6-25.5) for patients with heart failure (P < .001). The 10-year freedom from heart failure rehospitalization was 64.0% (95% confidence interval, 62.6-65.3). Freedom from aortic valve reintervention was 94.6% (95% confidence interval, 93.8-95.3) at 10 years. Conclusions: This real-world nationwide study of US Medicare beneficiaries receiving the Epic Supra valve demonstrates more than 94% freedom from all-cause valve reintervention and 64% freedom from heart failure rehospitalization at 10 years postimplant. Long-term survival and heart failure rehospitalization in this population with aortic valve disease undergoing surgical aortic valve replacement were found to be impacted by underlying heart failure.

Monitoring of heart failure: comparison of left atrial pressure with intrathoracic impedance and natriuretic peptide measurements in an experimental model of ovine heart failure.

Monitoring of HF (heart failure) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aimed to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may have an impact on the potential for early therapeutic intervention. Six sheep were implanted with a LAP (left atrial pressure) sensor and a CRT-D (cardiac resynchronization therapy defibrillator) capable of monitoring impedance along six lead configuration vectors. An estimate of ALAP (LAP from admittance) was determined by linear regression. HF was induced by rapid ventricular pacing at 180 and 220 bpm (beats/min) for a week each, followed by a third week with daily pacing suspensions for increasing durations (1-5 h). Incremental pacing induced progressively severe HF reflected in increases in LAP (5.9 ± 0.4 to 24.5 ± 1.6 mmHg) and plasma atrial (20 ± 3 to 197 ± 36 pmol/l) and B-type natriuretic peptide (3.7 ± 0.7 to 32.7 ± 5.4 pmol/l) (all P<0.001) levels. All impedance vectors decreased in proportion to HF severity (all P<0.001), with the LVring (left ventricular)-case vector correlating best with LAP (r2=0.63, P<0.001). Natriuretic peptides closely paralleled rapid acute changes in LAP during alterations in pacing (P<0.001), whereas impedance changes were delayed relative to LAP. ALAP exhibited good agreement with LAP. In summary, impedance measured with an LV lead correlates significantly with changes in LAP, but exhibits a delayed response to acute alterations. Natriuretic peptides respond rapidly to acute LAP changes. Direct LAP, impedance and natriuretic peptide measurements all show promise as early indicators of worsening HF. ALAP provides an estimate of LAP that may be clinically useful.

Comparative pathology of an implantable left atrial pressure sensor.

A left atrial pressure (LAP) monitoring system was developed for guiding the management of patients with heart failure. The LAP sensor is implanted into the left atrium via transseptal catheterization and affixed to the interatrial septum by nitinol anchors. The long-term safety of permanent implantation of the LAP sensor in patients was evaluated based on the comparative pathology in animals. Tissue specimens of the LAP sensor from 7 patients, 49 canines, and 14 ovine were examined for thrombosis and tissue overgrowth. Implant duration ranged from 22 to 1,686 days. Gross examination showed minimal-to-moderate tissue overgrowth with no evidence of migration, erosion, or perforation. There was no excessive host-to-device reaction or active thrombogenesis in any of the subjects that followed the antithrombotic therapy protocol. Micro-computed tomography scanning confirmed the structural integrity of the device. Low vacuum scanning electron microscopy and histology showed neoendocardial tissue overgrowth with no inflammation or fibrin. The pathology of both animal models was found to closely approximate the pathology in humans and favorably supports the long-term safety of the device.

Usefulness of monitoring congestive heart failure by multiple impedance vectors.

INTRODUCTION: We investigated trends in intrathoracic impedance measured between multiple implanted electrodes for monitoring pulmonary edema secondary to congestive heart failure (CHF) in an experimental model. METHODS: Biventricular ICDs were implanted in 16 dogs and 5 sheep. Continuous RV pacing (230- 250 bpm) was applied over several weeks. Meanwhile, impedance was measured every hour along 4 intrathoracic and 2 intracardiac vectors. Four cardiogenic impedance vectors were also monitored. Cardiac function was assessed biweekly by catheterization and echocardiography. Left atrial (LA) pressure was measured daily by an implanted LA pressure sensor. RESULTS: All animals developed CHF after 2-4 weeks of pacing as evidenced by changes in function (EF, 52 vs. 34%; LV end-diastolic volume, 65 vs. 97 ml; LV end-diastolic pressure, 7 vs. 16 mmHg; LA volume, 17 vs. 33 ml; LA pressure, 7 vs. 26 mmHg), clinical symptoms, or autopsy. Steady state impedance decreased during CHF: LV-Can, 17+/-9%; LV-RV, 15+/-8%; LV-RA, 13+/-6%; RV-Can, 13+/-8%; RVcoil-Can, 8+/-6%; RA-Can, 6+/-6%. Change in LV-Can impedance was greater than that of RA-Can, RV-Can, and RVcoil-Can (P0.05). LV-Can impedance correlated well with LA pressure (r(2)=0.73), while RV-Can and RVcoil-Can were weakly correlated (r(2)=0.43 and r(2)=0.52, respectively). Changes in LV-RV and LV-RA impedances were also larger than those of RVcoil-Can and RA-Can (P0.05). Meanwhile, all impedances were associated with circadian variability at baseline (5+/-2%) which diminished during CHF (2+/-1%); P=0.02. Furthermore, significant variations were observed in cardiogenic impedances during progression into CHF as evidenced by reduced peak-to-peak amplitude and increased fractionation of the signals. CONCLUSIONS: All impedance vectors decreased during CHF. Impedance measurement employing left heart sensors correlated well wit- - h LA pressure, and may improve detection of CHF onset compared to sensing by RA or RV leads alone. This approach has important clinical implications for managing heart failure patients in the ambulatory setting.