Craig Stolen | Boston Scientific Corporation (original) (raw)

Papers by Craig Stolen

Journal of cardiovascular translational research, Feb 1, 2024

Journal of Cardiac Failure, Oct 31, 2023

Heart & Lung, Mar 1, 2020

Journal of Heart and Lung Transplantation, Apr 1, 2012

Purpose: Chemotherapy-induced cardiomyopathy (CIC) is increasing in prevalence due to increased c... more Purpose: Chemotherapy-induced cardiomyopathy (CIC) is increasing in prevalence due to increased cancer survival. Late onset severe cardiac functional impairment after cure of cancer allows consideration for heart transplantation (HT). Methods and Materials: A retrospective analysis of 980 patients from our heart failure clinic was performed. Patient demographics were collated and patients with CIC were evaluated in relation to their subsequent need for HT and long term follow up. Results: 16/980 (1.6%) patients were diagnosed with CIC and HT required in 6 (38%). Mean age at presentation with CIC was 32.3 years (range 8-63). Mean age of CIC presentation for HT recipients was 22.3 (range 8-25). Overall cancer diagnosis: Ewing's sarcoma (5), Osteosarcoma (2), lymphoma (5), Wilm's tumour (2), breast cancer (1) and 1 patient lymphoma followed 8 years later by sarcoma with subsequent cardiomyopathy. All CIC patients had been treated with Anthracyclines. Cyclophophamide was used in 3 and Cisplatin in 2. Rate of HT by diagnosis: Ewing' Sarcoma (60%), osteosarcoma (50%) and lymphoma (20%), no other malignancy diagnoses were transplanted. 44% of overall CIC but no HT recipient received chest radiotherapy. Mean interval cancer treatment to cardiomyopathy was 12.8 years. Mean time CIC diagnosis to transplant 6 years (range 0-11). Overall mortality was 19%. One death occurred 9 months post HT from rejection. At a mean of 6 years post HT (range 0-10) there have been no cases of recurrent malignancy. Conclusions: Chemotherapy-induced cardiomyopathy typically presents late and predominantly affects young patients post lymphoma or sarcoma treated with anthracyclines. The rate of need for HT in CIC is high although this may be reflective of referral bias. Patients who subsequently undergo HT are younger but with judicious selection have a low risk of recurrence.

Journal of Heart and Lung Transplantation, Apr 1, 2012

International Journal of Cardiology, Dec 1, 2007

tein expression in a dose-dependent manner. The most potent dose of DDR2 siRNA to reduce DDR2 pro... more tein expression in a dose-dependent manner. The most potent dose of DDR2 siRNA to reduce DDR2 protein expression was 10 µM. DDR2 protein and mRNA expression significantly increased at 14 days after carotid injury as compared to sham group. DDR2 siRNA significantly reduced the DDR2 protein and mRNA expression induced by balloon injury. The immunohistochemical stain demonstrated that DDR2 siRNA decreased MMP2 protein labeling induced after balloon injury, a pattern similar to that of DDR2 protein labeling. Thickness of intimal area was significantly increased 14 days after carotid injury. DDR2 siRNA significantly reduced the thickness of intimal area. The thickness of intimal area was reduced by 50% by DDR2 siRNA. DDR2 siRNA did not affect the serum level of interferon-γ. Conclusions: DDR2 increases migration of SMCs and the expression of DDR2 in the carotid artery significantly increases after injury.RNA interference for DDR2 attenuates neointimal formation after carotid injury. DDR2 plays a pivotal role in the pathogenesis of intimal thickening after mechanical injury.

Circulation, Nov 25, 2014

Background: Early identification of a favorable cardiac resynchronization therapy (CRT) response ... more Background: Early identification of a favorable cardiac resynchronization therapy (CRT) response holds great clinical import. These studies often utilized a single biomarker or were performed at one point in time. The present study utilized an innovative approach whereby a panel of biomarkers were quantified in patients prior to CRT implant (Baseline) and then at 3 and 6 months post-CRT in a robust group of patients whereby CRT response had also been pre-specified. Methods/Results: Plasma was collected from patients (SMART-AV trial), and a positive CRT response was pre-specified as a ≥15 mL reduction in LV end-systolic volume at 6 months post-CRT (Responders:n=390/Non-Responders:n=388). Through initial cohort testing and multivariate modeling, serial measures of a 12 biomarker cassette was selected using high sensitivity multiplex profiling, which consisted of C-reactive protein, soluble glycoprotein 130, soluble interleukin-2 receptor, soluble tumor necrosis factor receptor-II, interferon gamma, N-terminal brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorgenicity-2 (sST-2), matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), and tissue inhibitors of MMP (TIMP-1, -2, -4). Analysis of variance (ANOVA) for repeated measures identified that NT-proBNP, sST-2, and MMP-2 changed across time following CRT (by ANOVA, p Conclusion: The unique findings from this study identified that time dependent changes in a specific biomarker signature occur early in those patients likely to respond favorably to CRT, and as such, may be of potential utility for point of care testing and integration into the CRT evaluation algorithm.

Heart & Lung, May 1, 2017

To evaluate to performance of an algorithm developed using diagnostic sensor data from implanted ... more To evaluate to performance of an algorithm developed using diagnostic sensor data from implanted cardiac resynchronization therapy defibrillators (CRT-D) to detect impending heart failure decompensation events. Background: Heart Failure (HF), a growing health-care challenge globally, involves costly hospitalizations with adverse impact on patient outcomes. Reliable monitoring for early signs of worsening HF is needed to enable proactive interventions for prevention of acute decompensations. We hypothesize that an algorithm combining information from a diverse set of implanted device based sensors judiciously chosen to target different aspects of HF pathophysiology can effectively detect worsening HF. Methods: MultiSENSE enrolled patients with HF and reduced EF (HFrEF) implanted with CRT-D, converted into an investigational device to enable chronic ambulatory data collection. HF events (HFEs) were defined as HF admissions or unscheduled visits with augmented intravenous HF treatment, and were independently adjudicated. Patients were assigned to Development or Test set cohorts in chronological order of enrollment. The development set was used to construct a composite index and alert algorithm (HeartLogic) combining Heart Sounds, Respiration, Thoracic Impedance, Heart Rate and Activity; whereas the test set was sequestered for its subsequent independent validation. Sensitivity was defined as the proportion of usable HFEs detected by Heart-Logic alerts. Unexplained alert rate (UAR) was defined as the ratio of alerts not explained by HF to the total usable follow-up duration. The two co-primary endpoints: 1. Sensitivity performance goal (PG) of > 40%; 2. UAR PG of < 2 alerts per patient year were tested with a 2-sided 95% confidence interval (CI). Results: Overall, 900 (Development ¼ 500, Test ¼ 400) patients had sensor data collection enabled and followed for up to a year. Primary endpoints were evaluated using the 320 patient years of follow-up data and 50 adjudicated usable HFEs in the Test Set cohort (72% male; age 66.8 AE 10.3 years; NYHA Class at enrollment I/II/III/IV/unknown: 5%/69%/25%/1%/1%; LVEF 30.0 AE 11.4%). With an observed sensitivity of 70% (Lower 2-sided 95% CI: 55.4%) and UAR of 1.47 (Upper 2-sided 95% CI: 1.65), both endpoints were significantly exceeded. Conclusion: The HeartLogic multi-sensor HF diagnostic algorithm significantly exceeded its pre-specified endpoints demonstrating compelling performance for worsening HF detection.

Journal of Cardiovascular Translational Research, Oct 9, 2015

The goal of this paper is to provide an updated review for scientists and clinicians on the major... more The goal of this paper is to provide an updated review for scientists and clinicians on the major areas in cardiovascular medicine published in the Journal. Leading topics in regenerative and personalized medicine are presented along with a critical overview of the field. New standards in large preclinical animal models of pulmonary hypertension and left bundle branch block are highlighted. Finally, clinical care in the area of atherosclerosis, the aortic valve, platelet biology, and myocarditis is discussed as well as autonomic modulation therapies Regenerative Medicine Following myocardial infarction, the heart loses millions of cardiomyocytes. Because the heart has a limited regenerative capacity, the lost cells are not replaced by all new myocytes but with scar, composed of

Journal of Cardiovascular Translational Research, Jun 4, 2013

Heart Rhythm, May 1, 2019

Background: Predicting a favorable cardiac resynchronization therapy (CRT) response holds great c... more Background: Predicting a favorable cardiac resynchronization therapy (CRT) response holds great clinical importance. Objective: To examine proteins from broad biological pathways and develop a prediction tool for response to CRT. Methods: Plasma was collected from patients prior to CRT (SMART-AV trial) whereby a CRT response was pre-specified as a ≥15 mL reduction in LV end-systolic volume (LVESV) at 6 months, which resulted in a binary CRT response (Responders: 52%, Non-Responders: 48%; n=758).

ESC Heart Failure

AimsThe HeartLogic multisensor index has been found to be a sensitive predictor of worsening hear... more AimsThe HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions.Methods and resultsThe PREEMPT‐HF study is a global, multicentre, prospective, observational, single‐arm, post‐market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6 months and a final in‐clinic visit at 12 months was required for collection of all‐cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no...

Europace

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston... more Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific Corporation Background The LUX-Dx PERFORM Study is designed to evaluate safety and performance of the LUX-Dx insertable cardiac monitor (ICM) in a general patient population. Enrollment and device insertions are complete, and all patients have completed 30 days of follow-up. This abstract describes the study population, characterizes device insertion, and reports on preliminary data for ICM system-related complications. Methods The LUX-Dx PERFORM study is a prospective, multi-center, single arm, post-market, observational study. The ICM system-related complication-free rate (CFR) at 30 days post-insertion was calculated using Kaplan-Meier methodology and the 97.5% one-side lower confidence limit (LCL) was compared to the prespecified performance target of 94%. All ICM system-related adverse events were adjudicated by independent physician reviewers. Results 727 patients were ...

Journal of Cardiac Failure, Apr 1, 2023

Clinical Cardiology

Despite the wide adoption of insertable cardiac monitors (ICMs), high false‐positive rates, subop... more Despite the wide adoption of insertable cardiac monitors (ICMs), high false‐positive rates, suboptimal signal quality, limited ability to detect atrial flutter, and lack of remote programming remain challenging. The LUX‐Dx PERFORM study was designed to evaluate novel technologies engineered to address these issues. Here, we present preliminary results from the trial focusing on the safety of ICM insertion, remote monitoring rates, and the feasibility of remote programming. LUX‐Dx PERFORM is a multicenter, prospective, single‐arm, post‐market, observational study with planned enrollment of up to 827 patients from 35 sites in North America. A preliminary cohort consisting of the first 369 patients who were enrolled between March and October 2021 was selected for analysis. Three hundred sixty‐three (363) patients had ICM insertions across inpatient and outpatient settings. The mean time followed was 103.4 ± 61.8 days per patient. The total infection rate was 0.8% (3/363). Interim resul...

Journal of Cardiac Failure, Aug 1, 2022

BACKGROUND Patients with heart failure and reduced ejection fraction (HFrEF) suffer from a relaps... more BACKGROUND Patients with heart failure and reduced ejection fraction (HFrEF) suffer from a relapsing and remitting disease, where early treatment changes may improve outcomes. We assessed the clinical integration and safety of the HeartLogic multi-sensor index and alerts in heart failure care. METHODS The Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) study enrolled 200 patients with HFrEF (< 35%), NYHA class II-III symptoms, implanted with a CRT-D or ICD, who had either a hospitalization for HF within 12 months or unscheduled visit for HF exacerbation within 90 days or an elevated natriuretic peptide concentration (BNP≥150 pg/mL or NT-proBNP≥600 pg/mL). This phase included development of an alert management guide and evaluated changes in medical treatment, natriuretic peptide levels, and safety. RESULTS Mean age of participants was 67 years, 68% were men, 81% were white, and 61% had a HF hospitalization in prior 12 months. During follow-up there were 585 alert cases with an average of 1.76 alert cases/pt-yr. HF medications were augmented during 74% of the alert cases. HF treatment augmentation within 2 weeks from an initial alert was associated with more rapid recovery of the HeartLogic Index. Five SAEs (0.015 per pt-year) occurred in relation to alert-prompted medication change. NTproBNP levels decreased from median of 1316 pg/mL at baseline to 743 pg/mL at 12 months (p<0.001). CONCLUSIONS HeartLogic alert management was safely implemented in HF care and may optimize HF management. This phase supports further evaluation in larger studies. TRIAL REGISTRATION ClinicalTrials.gov (NCT03237858).

Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expr... more Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazidesensitiveamineoxidase and as an adhesion molecule. Blockade of VAP-1has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.

ESC Heart Failure, 2021

Aims Implantable device-based sensor measurements including heart sounds, markers of ventilation,... more Aims Implantable device-based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID-19 (Cov-19) and how these compared with those presenting with decompensated HF or pneumonia. Methods and results This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov-19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT-HF, and MANAGE-HF trials. The earliest sensor changes prior to Cov-19 were observed in respiratory rate (6 days) and temperature (5 days). There was a threefold to four-fold greater increase in respiratory rate, rapid shallow breathing index, and night heart rate compared with those presenting with HF or pneumonia. Furthermore, activity levels fell more in those presenting with Cov-19, a change that was often sustained for some time. In contrast, there were no significant changes in 1st or 3rd heart sound (S 1 and S 3) amplitude in those presenting with Cov-19 or pneumonia compared with the known changes that occur in HF decompensation. Conclusions Multi-sensor device diagnostics may provide early detection of Cov-19, distinguishable from worsening HF by an extreme and fast rise in respiratory rate along with no changes in S3.

Journal of Cardiac Failure, 2021

The SARS-CoV-2 pandemic has established a new set of challenges to healthcare delivery. Remotely ... more The SARS-CoV-2 pandemic has established a new set of challenges to healthcare delivery. Remotely monitored physiologic sensors on implantable cardiac devices can provide insight into the differential diagnosis of dyspnea in the heart failure population. We report on a unique pattern of sensor deviations that appear to occur specifically with SARS-CoV-2 infection.

Journal of Cardiac Failure

Journal of cardiovascular translational research, Feb 1, 2024

Journal of Cardiac Failure, Oct 31, 2023

Heart & Lung, Mar 1, 2020

Journal of Heart and Lung Transplantation, Apr 1, 2012

Purpose: Chemotherapy-induced cardiomyopathy (CIC) is increasing in prevalence due to increased c... more Purpose: Chemotherapy-induced cardiomyopathy (CIC) is increasing in prevalence due to increased cancer survival. Late onset severe cardiac functional impairment after cure of cancer allows consideration for heart transplantation (HT). Methods and Materials: A retrospective analysis of 980 patients from our heart failure clinic was performed. Patient demographics were collated and patients with CIC were evaluated in relation to their subsequent need for HT and long term follow up. Results: 16/980 (1.6%) patients were diagnosed with CIC and HT required in 6 (38%). Mean age at presentation with CIC was 32.3 years (range 8-63). Mean age of CIC presentation for HT recipients was 22.3 (range 8-25). Overall cancer diagnosis: Ewing's sarcoma (5), Osteosarcoma (2), lymphoma (5), Wilm's tumour (2), breast cancer (1) and 1 patient lymphoma followed 8 years later by sarcoma with subsequent cardiomyopathy. All CIC patients had been treated with Anthracyclines. Cyclophophamide was used in 3 and Cisplatin in 2. Rate of HT by diagnosis: Ewing' Sarcoma (60%), osteosarcoma (50%) and lymphoma (20%), no other malignancy diagnoses were transplanted. 44% of overall CIC but no HT recipient received chest radiotherapy. Mean interval cancer treatment to cardiomyopathy was 12.8 years. Mean time CIC diagnosis to transplant 6 years (range 0-11). Overall mortality was 19%. One death occurred 9 months post HT from rejection. At a mean of 6 years post HT (range 0-10) there have been no cases of recurrent malignancy. Conclusions: Chemotherapy-induced cardiomyopathy typically presents late and predominantly affects young patients post lymphoma or sarcoma treated with anthracyclines. The rate of need for HT in CIC is high although this may be reflective of referral bias. Patients who subsequently undergo HT are younger but with judicious selection have a low risk of recurrence.

Journal of Heart and Lung Transplantation, Apr 1, 2012

International Journal of Cardiology, Dec 1, 2007

tein expression in a dose-dependent manner. The most potent dose of DDR2 siRNA to reduce DDR2 pro... more tein expression in a dose-dependent manner. The most potent dose of DDR2 siRNA to reduce DDR2 protein expression was 10 µM. DDR2 protein and mRNA expression significantly increased at 14 days after carotid injury as compared to sham group. DDR2 siRNA significantly reduced the DDR2 protein and mRNA expression induced by balloon injury. The immunohistochemical stain demonstrated that DDR2 siRNA decreased MMP2 protein labeling induced after balloon injury, a pattern similar to that of DDR2 protein labeling. Thickness of intimal area was significantly increased 14 days after carotid injury. DDR2 siRNA significantly reduced the thickness of intimal area. The thickness of intimal area was reduced by 50% by DDR2 siRNA. DDR2 siRNA did not affect the serum level of interferon-γ. Conclusions: DDR2 increases migration of SMCs and the expression of DDR2 in the carotid artery significantly increases after injury.RNA interference for DDR2 attenuates neointimal formation after carotid injury. DDR2 plays a pivotal role in the pathogenesis of intimal thickening after mechanical injury.

Circulation, Nov 25, 2014

Background: Early identification of a favorable cardiac resynchronization therapy (CRT) response ... more Background: Early identification of a favorable cardiac resynchronization therapy (CRT) response holds great clinical import. These studies often utilized a single biomarker or were performed at one point in time. The present study utilized an innovative approach whereby a panel of biomarkers were quantified in patients prior to CRT implant (Baseline) and then at 3 and 6 months post-CRT in a robust group of patients whereby CRT response had also been pre-specified. Methods/Results: Plasma was collected from patients (SMART-AV trial), and a positive CRT response was pre-specified as a ≥15 mL reduction in LV end-systolic volume at 6 months post-CRT (Responders:n=390/Non-Responders:n=388). Through initial cohort testing and multivariate modeling, serial measures of a 12 biomarker cassette was selected using high sensitivity multiplex profiling, which consisted of C-reactive protein, soluble glycoprotein 130, soluble interleukin-2 receptor, soluble tumor necrosis factor receptor-II, interferon gamma, N-terminal brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorgenicity-2 (sST-2), matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), and tissue inhibitors of MMP (TIMP-1, -2, -4). Analysis of variance (ANOVA) for repeated measures identified that NT-proBNP, sST-2, and MMP-2 changed across time following CRT (by ANOVA, p Conclusion: The unique findings from this study identified that time dependent changes in a specific biomarker signature occur early in those patients likely to respond favorably to CRT, and as such, may be of potential utility for point of care testing and integration into the CRT evaluation algorithm.

Heart & Lung, May 1, 2017

To evaluate to performance of an algorithm developed using diagnostic sensor data from implanted ... more To evaluate to performance of an algorithm developed using diagnostic sensor data from implanted cardiac resynchronization therapy defibrillators (CRT-D) to detect impending heart failure decompensation events. Background: Heart Failure (HF), a growing health-care challenge globally, involves costly hospitalizations with adverse impact on patient outcomes. Reliable monitoring for early signs of worsening HF is needed to enable proactive interventions for prevention of acute decompensations. We hypothesize that an algorithm combining information from a diverse set of implanted device based sensors judiciously chosen to target different aspects of HF pathophysiology can effectively detect worsening HF. Methods: MultiSENSE enrolled patients with HF and reduced EF (HFrEF) implanted with CRT-D, converted into an investigational device to enable chronic ambulatory data collection. HF events (HFEs) were defined as HF admissions or unscheduled visits with augmented intravenous HF treatment, and were independently adjudicated. Patients were assigned to Development or Test set cohorts in chronological order of enrollment. The development set was used to construct a composite index and alert algorithm (HeartLogic) combining Heart Sounds, Respiration, Thoracic Impedance, Heart Rate and Activity; whereas the test set was sequestered for its subsequent independent validation. Sensitivity was defined as the proportion of usable HFEs detected by Heart-Logic alerts. Unexplained alert rate (UAR) was defined as the ratio of alerts not explained by HF to the total usable follow-up duration. The two co-primary endpoints: 1. Sensitivity performance goal (PG) of > 40%; 2. UAR PG of < 2 alerts per patient year were tested with a 2-sided 95% confidence interval (CI). Results: Overall, 900 (Development ¼ 500, Test ¼ 400) patients had sensor data collection enabled and followed for up to a year. Primary endpoints were evaluated using the 320 patient years of follow-up data and 50 adjudicated usable HFEs in the Test Set cohort (72% male; age 66.8 AE 10.3 years; NYHA Class at enrollment I/II/III/IV/unknown: 5%/69%/25%/1%/1%; LVEF 30.0 AE 11.4%). With an observed sensitivity of 70% (Lower 2-sided 95% CI: 55.4%) and UAR of 1.47 (Upper 2-sided 95% CI: 1.65), both endpoints were significantly exceeded. Conclusion: The HeartLogic multi-sensor HF diagnostic algorithm significantly exceeded its pre-specified endpoints demonstrating compelling performance for worsening HF detection.

Journal of Cardiovascular Translational Research, Oct 9, 2015

The goal of this paper is to provide an updated review for scientists and clinicians on the major... more The goal of this paper is to provide an updated review for scientists and clinicians on the major areas in cardiovascular medicine published in the Journal. Leading topics in regenerative and personalized medicine are presented along with a critical overview of the field. New standards in large preclinical animal models of pulmonary hypertension and left bundle branch block are highlighted. Finally, clinical care in the area of atherosclerosis, the aortic valve, platelet biology, and myocarditis is discussed as well as autonomic modulation therapies Regenerative Medicine Following myocardial infarction, the heart loses millions of cardiomyocytes. Because the heart has a limited regenerative capacity, the lost cells are not replaced by all new myocytes but with scar, composed of

Journal of Cardiovascular Translational Research, Jun 4, 2013

Heart Rhythm, May 1, 2019

Background: Predicting a favorable cardiac resynchronization therapy (CRT) response holds great c... more Background: Predicting a favorable cardiac resynchronization therapy (CRT) response holds great clinical importance. Objective: To examine proteins from broad biological pathways and develop a prediction tool for response to CRT. Methods: Plasma was collected from patients prior to CRT (SMART-AV trial) whereby a CRT response was pre-specified as a ≥15 mL reduction in LV end-systolic volume (LVESV) at 6 months, which resulted in a binary CRT response (Responders: 52%, Non-Responders: 48%; n=758).

ESC Heart Failure

AimsThe HeartLogic multisensor index has been found to be a sensitive predictor of worsening hear... more AimsThe HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions.Methods and resultsThe PREEMPT‐HF study is a global, multicentre, prospective, observational, single‐arm, post‐market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6 months and a final in‐clinic visit at 12 months was required for collection of all‐cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no...

Europace

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston... more Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific Corporation Background The LUX-Dx PERFORM Study is designed to evaluate safety and performance of the LUX-Dx insertable cardiac monitor (ICM) in a general patient population. Enrollment and device insertions are complete, and all patients have completed 30 days of follow-up. This abstract describes the study population, characterizes device insertion, and reports on preliminary data for ICM system-related complications. Methods The LUX-Dx PERFORM study is a prospective, multi-center, single arm, post-market, observational study. The ICM system-related complication-free rate (CFR) at 30 days post-insertion was calculated using Kaplan-Meier methodology and the 97.5% one-side lower confidence limit (LCL) was compared to the prespecified performance target of 94%. All ICM system-related adverse events were adjudicated by independent physician reviewers. Results 727 patients were ...

Journal of Cardiac Failure, Apr 1, 2023

Clinical Cardiology

Despite the wide adoption of insertable cardiac monitors (ICMs), high false‐positive rates, subop... more Despite the wide adoption of insertable cardiac monitors (ICMs), high false‐positive rates, suboptimal signal quality, limited ability to detect atrial flutter, and lack of remote programming remain challenging. The LUX‐Dx PERFORM study was designed to evaluate novel technologies engineered to address these issues. Here, we present preliminary results from the trial focusing on the safety of ICM insertion, remote monitoring rates, and the feasibility of remote programming. LUX‐Dx PERFORM is a multicenter, prospective, single‐arm, post‐market, observational study with planned enrollment of up to 827 patients from 35 sites in North America. A preliminary cohort consisting of the first 369 patients who were enrolled between March and October 2021 was selected for analysis. Three hundred sixty‐three (363) patients had ICM insertions across inpatient and outpatient settings. The mean time followed was 103.4 ± 61.8 days per patient. The total infection rate was 0.8% (3/363). Interim resul...

Journal of Cardiac Failure, Aug 1, 2022

BACKGROUND Patients with heart failure and reduced ejection fraction (HFrEF) suffer from a relaps... more BACKGROUND Patients with heart failure and reduced ejection fraction (HFrEF) suffer from a relapsing and remitting disease, where early treatment changes may improve outcomes. We assessed the clinical integration and safety of the HeartLogic multi-sensor index and alerts in heart failure care. METHODS The Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) study enrolled 200 patients with HFrEF (< 35%), NYHA class II-III symptoms, implanted with a CRT-D or ICD, who had either a hospitalization for HF within 12 months or unscheduled visit for HF exacerbation within 90 days or an elevated natriuretic peptide concentration (BNP≥150 pg/mL or NT-proBNP≥600 pg/mL). This phase included development of an alert management guide and evaluated changes in medical treatment, natriuretic peptide levels, and safety. RESULTS Mean age of participants was 67 years, 68% were men, 81% were white, and 61% had a HF hospitalization in prior 12 months. During follow-up there were 585 alert cases with an average of 1.76 alert cases/pt-yr. HF medications were augmented during 74% of the alert cases. HF treatment augmentation within 2 weeks from an initial alert was associated with more rapid recovery of the HeartLogic Index. Five SAEs (0.015 per pt-year) occurred in relation to alert-prompted medication change. NTproBNP levels decreased from median of 1316 pg/mL at baseline to 743 pg/mL at 12 months (p<0.001). CONCLUSIONS HeartLogic alert management was safely implemented in HF care and may optimize HF management. This phase supports further evaluation in larger studies. TRIAL REGISTRATION ClinicalTrials.gov (NCT03237858).

Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expr... more Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazidesensitiveamineoxidase and as an adhesion molecule. Blockade of VAP-1has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.

ESC Heart Failure, 2021

Aims Implantable device-based sensor measurements including heart sounds, markers of ventilation,... more Aims Implantable device-based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID-19 (Cov-19) and how these compared with those presenting with decompensated HF or pneumonia. Methods and results This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov-19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT-HF, and MANAGE-HF trials. The earliest sensor changes prior to Cov-19 were observed in respiratory rate (6 days) and temperature (5 days). There was a threefold to four-fold greater increase in respiratory rate, rapid shallow breathing index, and night heart rate compared with those presenting with HF or pneumonia. Furthermore, activity levels fell more in those presenting with Cov-19, a change that was often sustained for some time. In contrast, there were no significant changes in 1st or 3rd heart sound (S 1 and S 3) amplitude in those presenting with Cov-19 or pneumonia compared with the known changes that occur in HF decompensation. Conclusions Multi-sensor device diagnostics may provide early detection of Cov-19, distinguishable from worsening HF by an extreme and fast rise in respiratory rate along with no changes in S3.

Journal of Cardiac Failure, 2021

The SARS-CoV-2 pandemic has established a new set of challenges to healthcare delivery. Remotely ... more The SARS-CoV-2 pandemic has established a new set of challenges to healthcare delivery. Remotely monitored physiologic sensors on implantable cardiac devices can provide insight into the differential diagnosis of dyspnea in the heart failure population. We report on a unique pattern of sensor deviations that appear to occur specifically with SARS-CoV-2 infection.

Journal of Cardiac Failure