Developing a personalized remote patient monitoring algorithm: a proof-of-concept in heart failure

Aims Non-invasive remote patient monitoring is an increasingly popular technique to aid clinicians in the early detection of worsening heart failure (HF) alongside regular follow-ups. However, previous studies have shown mixed results in the performance of such systems. Therefore, we developed and evaluated a personalized monitoring algorithm aimed at increasing positive-predictive-value (PPV) (i.e. alarm quality) and compared performance with simple rule-of-thumb and moving average convergence-divergence algorithms (MACD). Methods and results In this proof-of-concept study, the developed algorithm was applied to retrospective data of daily bodyweight, heart rate, and systolic blood pressure of 74 HF-patients with a median observation period of 327 days (IQR: 183 days), during which 31 patients experienced 64 clinical worsening HF episodes. The algorithm combined information on both the monitored patients and a group of stable HF patients, and is increasingly personalized over time, using linear mixed-effect modelling and statistical process control charts. Optimized on alarm quality, heart rate showed the highest PPV (Personalized: 92%, MACD: 2%, Rule-of-thumb: 7%) with an F1 score of (Personalized: 28%, MACD: 6%, Rule-of-thumb: 8%). Bodyweight demonstrated the lowest PPV (Personalized: 16%, MACD: 0%, Rule-of-thumb: 6%) and F1 score (Personalized: 10%, MACD: 3%, Rule-of-thumb: 7%) overall compared methods. Conclusion The personalized algorithm with flexible patient-tailored thresholds led to higher PPV, and performance was more sensitive compared to common simple monitoring methods (rule-of-thumb and MACD). However, many episodes of worsening HF remained undetected. Heart rate and systolic blood pressure monitoring outperformed bodyweight in predicting worsening HF. The algorithm source code is publicly available for future validation and improvement

Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support

Background: Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR). Methods: 18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1–2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation. Results: A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001–0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001–0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19). Conclusions: A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms

Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support

Background: Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR). Methods: 18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1–2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation. Results: A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001–0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001–0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19). Conclusions: A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms

Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells

Waiting list mortality and the potential of donation after circulatory death heart transplantations in the Netherlands

BACKGROUND: With more patients qualifying for heart transplantation (HT) and fewer hearts being transplanted, it is vital to look for other options. To date, only organs from brain-dead donors have been used for HT in the Netherlands. We investigated waiting list mortality in all Dutch HT centres and the potential of donation after circulatory death (DCD) HT in the Netherlands. METHODS: Two different cohorts were evaluated. One cohort was defined as patients who were newly listed or were already on the waiting list for HT between January 2013 and December 2017. Follow-up continued until September 2018 and waiting list mortality was calculated. A second cohort of all DCD donors in the Netherlands (lung, liver, kidney and pancreas) between January 2013 and December 2017 was used to calculate the potential of DCD HT. RESULTS: Out of 395 patients on the waiting list for HT, 196 (50%) received transplants after a median waiting time of 2.6 years. In total, 15% died while on the waiting list before a suitable donor heart became available. We identified 1006 DCD donors. After applying exclusion criteria and an age limit of 50 years, 122 potential heart donors remained. This number increased to 220 when the age limit was extended to 57 years. CONCLUSION: Waiting list mortality in the Netherlands is high. HT using organs from DCD donors has great potential in the Netherlands and could lead to a reduction in waiting list mortality. Cardiac screening will eventually determine the true potential

ECPELLA as a bridge-to-decision in refractory cardiogenic shock:a single-centre experience

Background: In refractory cardiogenic shock, temporary mechanical support (tMCS) may be crucial for maintaining tissue perfusion and oxygen delivery. tMCS can serve as a bridge-to-decision to assess eligibility for left ventricular assist device (LVAD) implantation or heart transplantation, or as a bridge-to-recovery. ECPELLA is a novel tMCS configuration combining venoarterial extracorporeal membrane oxygenation with Impella. The present study presents the clinical parameters, outcomes, and complications of patients supported with ECPELLA. Methods: All patients supported with ECPELLA at University Medical Centre Utrecht between December 2020 and August 2023 were included. The primary outcome was 30-day mortality, and secondary outcomes were LVAD implantation/heart transplantation and safety outcomes. Results: Twenty patients with an average age of 51 years, and of whom 70% were males, were included. Causes of cardiogenic shock were acute heart failure (due to acute coronary syndrome, myocarditis, or after cardiac surgery) or chronic heart failure, respectively 70 and 30% of cases. The median duration of ECPELLA support was 164 h (interquartile range 98–210). In 50% of cases, a permanent LVAD was implanted. Cardiac recovery within 30 days was seen in 30% of cases and 30-day mortality rate was 20%. ECPELLA support was associated with major bleeding (40%), haemolysis (25%), vascular complications (30%), kidney failure requiring replacement therapy (50%), and Impella failure requiring extraction (15%). Conclusion: ECPELLA can be successfully used as a bridge to LVAD implantation or as a bridge-to-recovery in patients with refractory cardiogenic shock. Despite a significant number of complications, 30-day mortality was lower than observed in previous cohorts.</p

ECPELLA as a bridge-to-decision in refractory cardiogenic shock:a single-centre experience

Background: In refractory cardiogenic shock, temporary mechanical support (tMCS) may be crucial for maintaining tissue perfusion and oxygen delivery. tMCS can serve as a bridge-to-decision to assess eligibility for left ventricular assist device (LVAD) implantation or heart transplantation, or as a bridge-to-recovery. ECPELLA is a novel tMCS configuration combining venoarterial extracorporeal membrane oxygenation with Impella. The present study presents the clinical parameters, outcomes, and complications of patients supported with ECPELLA. Methods: All patients supported with ECPELLA at University Medical Centre Utrecht between December 2020 and August 2023 were included. The primary outcome was 30-day mortality, and secondary outcomes were LVAD implantation/heart transplantation and safety outcomes. Results: Twenty patients with an average age of 51 years, and of whom 70% were males, were included. Causes of cardiogenic shock were acute heart failure (due to acute coronary syndrome, myocarditis, or after cardiac surgery) or chronic heart failure, respectively 70 and 30% of cases. The median duration of ECPELLA support was 164 h (interquartile range 98–210). In 50% of cases, a permanent LVAD was implanted. Cardiac recovery within 30 days was seen in 30% of cases and 30-day mortality rate was 20%. ECPELLA support was associated with major bleeding (40%), haemolysis (25%), vascular complications (30%), kidney failure requiring replacement therapy (50%), and Impella failure requiring extraction (15%). Conclusion: ECPELLA can be successfully used as a bridge to LVAD implantation or as a bridge-to-recovery in patients with refractory cardiogenic shock. Despite a significant number of complications, 30-day mortality was lower than observed in previous cohorts.</p

ECPELLA as a bridge-to-decision in refractory cardiogenic shock:a single-centre experience

Background: In refractory cardiogenic shock, temporary mechanical support (tMCS) may be crucial for maintaining tissue perfusion and oxygen delivery. tMCS can serve as a bridge-to-decision to assess eligibility for left ventricular assist device (LVAD) implantation or heart transplantation, or as a bridge-to-recovery. ECPELLA is a novel tMCS configuration combining venoarterial extracorporeal membrane oxygenation with Impella. The present study presents the clinical parameters, outcomes, and complications of patients supported with ECPELLA. Methods: All patients supported with ECPELLA at University Medical Centre Utrecht between December 2020 and August 2023 were included. The primary outcome was 30-day mortality, and secondary outcomes were LVAD implantation/heart transplantation and safety outcomes. Results: Twenty patients with an average age of 51 years, and of whom 70% were males, were included. Causes of cardiogenic shock were acute heart failure (due to acute coronary syndrome, myocarditis, or after cardiac surgery) or chronic heart failure, respectively 70 and 30% of cases. The median duration of ECPELLA support was 164 h (interquartile range 98–210). In 50% of cases, a permanent LVAD was implanted. Cardiac recovery within 30 days was seen in 30% of cases and 30-day mortality rate was 20%. ECPELLA support was associated with major bleeding (40%), haemolysis (25%), vascular complications (30%), kidney failure requiring replacement therapy (50%), and Impella failure requiring extraction (15%). Conclusion: ECPELLA can be successfully used as a bridge to LVAD implantation or as a bridge-to-recovery in patients with refractory cardiogenic shock. Despite a significant number of complications, 30-day mortality was lower than observed in previous cohorts.</p

Developing a personalized remote patient monitoring algorithm: a proof-of-concept in heart failure

AIMS: Non-invasive remote patient monitoring is an increasingly popular technique to aid clinicians in the early detection of worsening heart failure (HF) alongside regular follow-ups. However, previous studies have shown mixed results in the performance of such systems. Therefore, we developed and evaluated a personalized monitoring algorithm aimed at increasing positive-predictive-value (PPV) (i.e. alarm quality) and compared performance with simple rule-of-thumb and moving average convergence-divergence algorithms (MACD). METHODS AND RESULTS: In this proof-of-concept study, the developed algorithm was applied to retrospective data of daily bodyweight, heart rate, and systolic blood pressure of 74 HF-patients with a median observation period of 327 days (IQR: 183 days), during which 31 patients experienced 64 clinical worsening HF episodes. The algorithm combined information on both the monitored patients and a group of stable HF patients, and is increasingly personalized over time, using linear mixed-effect modelling and statistical process control charts. Optimized on alarm quality, heart rate showed the highest PPV (Personalized: 92%, MACD: 2%, Rule-of-thumb: 7%) with an F1 score of (Personalized: 28%, MACD: 6%, Rule-of-thumb: 8%). Bodyweight demonstrated the lowest PPV (Personalized: 16%, MACD: 0%, Rule-of-thumb: 6%) and F1 score (Personalized: 10%, MACD: 3%, Rule-of-thumb: 7%) overall compared methods. CONCLUSION: The personalized algorithm with flexible patient-tailored thresholds led to higher PPV, and performance was more sensitive compared to common simple monitoring methods (rule-of-thumb and MACD). However, many episodes of worsening HF remained undetected. Heart rate and systolic blood pressure monitoring outperformed bodyweight in predicting worsening HF. The algorithm source code is publicly available for future validation and improvement