A randomized clinical study using optical coherence tomography to evaluate the short-term effects of high-intensity interval training on cardiac allograft vasculopathy: a HITTS substudy.

Cardiac allograft vasculopathy (CAV) remains a leading cause of long-term mortality after heart transplantation. Both preventive measures and treatment options are limited. This study aimed to evaluate the short-term effects of high-intensity interval training (HIT) on CAV in de novo heart transplant (HTx) recipients as assessed by optical coherence tomography (OCT). The study population was a subgroup of the 81-patient HITTS study in which HTx recipients were randomized to HIT or moderate intensity continuous training (MICT) for nine consecutive months. OCT images from baseline and 12 months were compared to assess CAV progression. The primary endpoint was defined as the change in the mean intima area. Paired OCT data were available for 56 patients (n = 23 in the HIT group and n = 33 in the MICT group). The intima area in the entire study population increased by 25% [from 1.8±1.4 mm2 to 2.3±2.0 mm2 , P < .05]. The change was twofold higher in the MICT group (.6±1.2 mm2 ) than in the HIT group (.3±.6 mm2 ). However, the treatment effect of HIT was not significant (treatment effect = -.3 mm2 , 95% CI [-.825 to .2 mm2 ] P = .29). These results suggest that early initiation of HIT compared with MICT does not attenuate CAV progression in de novo HTx recipients.

Functional evidence of low-pressure cardiopulmonary baroreceptor reinnervation 1 year after heart transplantation.

PURPOSE: Heart transplantation (HTx) implies denervation of afferent neural connections. Reinnervation of low-pressure cardiopulmonary baroreceptors might impact the development and treatment of hypertension, but little is known of its occurrence. The present prospective study investigated possible afferent reinnervation of low-pressure cardiopulmonary baroreceptors during the first year after heart transplantation. METHODS: A total of 50 heart transplant recipients (HTxRs) were included and were evaluated 7-12 weeks after transplant surgery, with follow-up 6 and 12 months later. In addition, a reference group of 50 healthy control subjects was examined once. Continuous, non-invasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 20° head-up tilt, during Valsalva maneuver and during 1 min of 30% maximal voluntary handgrip. In addition, routine clinical data including invasive measurements were used in the analyses. RESULTS: During the first year after HTx, the heart rate (HR) response to 20° head-up tilt partly normalized, a negative relationship between resting mean right atrial pressure and HR tilt response developed, low-frequency variability of the RR interval and systolic blood pressure at supine rest increased, and the total peripheral resistance response to Valsalva maneuver became stronger. CONCLUSION: Functional assessments suggest that afferent reinnervation of low-pressure cardiopulmonary receptors occurs during the first year after heart transplantation, partially restoring reflex-mediated responses to altered cardiac filling.

Ready for SDM: evaluating a train-the-trainer program to facilitate implementation of SDM training in Norway.

BACKGROUND: Healthcare providers need training to implement shared decision making (SDM). In Norway, we developed "Ready for SDM", a comprehensive SDM curriculum tailored to various healthcare providers, settings, and competence levels, including a course targeting interprofessional healthcare teams. The overall aim was to evaluate a train-the-trainer (TTT) program for healthcare providers wanting to offer this course within their hospital trust. METHODS: Our observational descriptive design was informed by Kirkpatrick´s Model of Educational Outcomes. The South-Eastern Regional Health Authority invited healthcare providers from all health trusts in its jurisdiction to attend. The TTT consisted of a one-day basic course with lectures on SDM, exercises and group reflections followed by a two-day advanced course including an SDM observer training. Immediately after each of the two courses, reaction and learning (Kirkpatrick levels 1 and 2) were assessed using a self-administered questionnaire. After the advanced course, observer skills were operationalized as accuracy of the participants' assessment of a consultation compared to an expert assessment. Within three months post-training, we measured number of trainings conducted and number of healthcare providers trained (Kirkpatrick level 3) using an online survey. Qualitative and quantitative descriptive analysis were performed. RESULTS: Twenty-one out of 24 (basic) and 19 out of 22 (advanced) healthcare providers in 9 health trusts consented to participate. The basic course was evaluated as highly acceptable, the advanced course as complex and challenging. Participants identified a need for more training in pedagogical skills and support for planning implementation of SDM-training. Participants achieved high knowledge scores and were positive about being an SDM trainer. Observer skills regarding patient involvement in decision-making were excellent (mean of weighted t = .80). After three months, 67% of TTT participants had conducted more than two trainings each and trained a total of 458 healthcare providers. CONCLUSION: Findings suggest that the TTT is a feasible approach for supporting large-scale training in SDM. Our study informed us about how to improve the advanced course. Further research shall investigate the efficacy of the training in the context of a comprehensive multifaceted strategy for implementing SDM in clinical practice. TRIAL REGISTRATION: Retrospectively registered at ISRCTN (99432465) March 25, 2020.

Effect of High-Intensity Interval Training in De Novo Heart Transplant Recipients in Scandinavia.

BACKGROUND: There is no consensus on how, when, or at what intensity exercise should be performed after heart transplantation (HTx). We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in the maintenance state after HTx, but studies have not investigated HIT effects in the de novo HTx state. We hypothesized that HIT could be introduced early after HTx and that it could lead to clinically meaningful increases in exercise capacity and health-related quality of life. METHODS: This multicenter, prospective, randomized, controlled trial included 81 patients a mean of 11 weeks (range, 7-16 weeks) after an HTx. Patients were randomized 1:1 to 9 months of either HIT (4×4-minute intervals at 85%-95% of peak effort) or moderate-intensity continuous training (60%-80% of peak effort). The primary outcome was the effect of HIT versus moderate-intensity continuous training on the change in aerobic exercise capacity, assessed as the peak oxygen consumption (Vo2peak). Secondary outcomes included tolerability, safety, adverse events, isokinetic muscular strength, body composition, health-related quality of life, left ventricular function, hemodynamics, endothelial function, and biomarkers. RESULTS: From baseline to follow-up, 96% of patients completed the study. There were no serious exercise-related adverse events. The population comprised 73% men, and the mean±SD age was 49±13 years. At the 1-year follow-up, the HIT group demonstrated greater improvements than the moderate-intensity continuous training group; the groups showed significantly different changes in the Vo2peak (mean difference between groups, 1.8 mL·kg-1·min-1), the anaerobic threshold (0.28 L/min), the peak expiratory flow (11%), and the extensor muscle exercise capacity (464 J). The 1.8-mL·kg-1·min-1 difference was equal to ≈0.5 metabolic equivalents, which is regarded as clinically meaningful and relevant. Health-related quality of life was similar between the groups, as indicated by results from the Short Form-36 (version 2), Hospital Anxiety and Depression Scale, and a visual analog scale. CONCLUSIONS: We demonstrated that HIT was a safe, efficient exercise method in de novo HTx recipients. HIT, compared with moderate-intensity continuous training, resulted in a clinically significantly greater change in exercise capacity based on the Vo2peak values (25% versus 15%), anaerobic threshold, peak expiratory flow, and muscular exercise capacity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier NCT01796379.

Long-term effects of high-intensity training vs moderate intensity training in heart transplant recipients: A 3-year follow-up study of the randomized-controlled HITTS study.

The randomized controlled High-Intensity Interval Training in De Novo Heart Transplant Recipients in Scandinavia (HITTS) study compared 9 months of high-intensity interval training (HIT) with moderate intensity continuous training in de novo heart transplant recipients. In our 3-year follow-up study, we aimed to determine whether the effect of early initiation of HIT on peak oxygen consumption (VO2peak ) persisted for 2 years postintervention. The study's primary end point was the change in VO2peak (mL/kg/min). The secondary end points were muscle strength, body composition, heart rate response, health-related quality of life, daily physical activity, biomarkers, and heart function. Of 78 patients who completed the 1-year HITTS trial, 65 entered our study and 62 completed the study tests. VO2peak increased from baseline to 1 year and leveled off thereafter. During the intervention period, the increase in VO2peak was larger in the HIT arm; however, 2 years later, there was no significant between-group difference in VO2peak . However, the mean change in the anaerobic threshold and extensor muscle endurance remained significantly higher in the HIT group. Early initiation of HIT after heart transplantation appears to have some sustainable long-term effects. Clinical trial registration number: NCT01796379.

High-intensity interval training and health-related quality of life in de novo heart transplant recipients - results from a randomized controlled trial.

BACKGROUND: Studies on the effect of high-intensity interval training (HIT) compared with moderate intensity continuous training (MICT) on health-related quality of life (HRQoL) after heart transplantation (HTx) is scarce. No available studies among de novo HTx recipients exists. This study aimed to investigate the effect of HIT vs. MICT on HRQoL in de novo recipients. METHODS: The HITTS study randomized eighty-one de novo HTx recipients to receive either HIT or MICT (1:1). The HIT intervention were performed with 2-4 interval bouts with an intensity of 85-95% of maximal effort. The MICT group exercised at an intensity of 60-80% of their maximal effort with a duration of 25 min. HRQoL was assessed by the Short Form-36 version 2 (SF-36v2) and the Hospital Anxiety and Depression Scale, mean 11 weeks after surgery and after a nine months' intervention. The participants recorded their subjective effect of the interventions on their general health and well-being on a numeric visual analogue scale. Clinical examinations and physical tests were performed. Differences between groups were investigated with independent Student t-tests and with Mann-Whitney U tests where appropriate. Within-group differences were analyzed with Paired-Sample t-tests and Wilcoxon Signed Rank tests. Correlations between SF-36 scores and VO2peak were examined with Pearson's correlations. RESULTS: Seventy-eight participants completed the intervention. Both exercise modes were associated with improved exercise capacity on the physical function scores of HRQoL. Mental health scores remained unchanged. No differences in the change in HRQoL between the groups occurred except for Role Emotional subscale with a larger increase in the HIT arm. Better self-reported physical function was associated with higher VO2peak and muscle strength. CONCLUSION: HIT and MICT resulted in similar mean changes in HRQoL the first year after HTx. Both groups experienced significant improvements in the physical SF-36v2. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01796379 Registered 18 February 2013.

Autonomic cardiovascular control changes in recent heart transplant recipients lead to physiological limitations in response to orthostatic challenge and isometric exercise.

PURPOSE: Heart transplantation causes denervation of the donor heart, but the consequences for cardiovascular homeostasis remain to be fully understood. The present study investigated cardiovascular autonomic control at supine rest, during orthostatic challenge and during isometric exercise in heart transplant recipients (HTxR). METHODS: A total of 50 HTxRs were investigated 7-12 weeks after transplant surgery and compared with 50 healthy control subjects. Continuous, noninvasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 60° head-up tilt and during 1 min of 30% of maximal voluntary handgrip. Plasma and urine catecholamines were assayed, and symptoms were charted. RESULTS: At supine rest, heart rate, blood pressures and total peripheral resistance were higher, and stroke volume and end diastolic volume were lower in the HTxR group. During tilt, heart rate, blood pressures and total peripheral resistance increased less, and stroke volume and end diastolic volume decreased less. During handgrip, heart rate and cardiac output increased less, and stroke volume and end diastolic volume decreased less. Orthostatic symptoms were similar across the groups, but the HTxRs complained more of pale and cold hands. CONCLUSION: HTxRs are characterized by elevated blood pressures and total peripheral resistance at supine rest as well as attenuated blood pressures and total peripheral resistance responses during orthostatic challenge, possibly caused by low-pressure cardiopulmonary baroreceptor denervation. In addition, HTxRs show attenuated cardiac output response during isometric exercise due to efferent sympathetic denervation. These physiological limitations might have negative functional consequences.

Long-term effects of high-intensity interval training in heart transplant recipients: A 5-year follow-up study of a randomized controlled trial.

BACKGROUND: Previous studies have demonstrated that high-intensity interval training (HIT) is superior to moderate-continuous exercise in general and in cardiovascular diseases. Recently, we also found HIT safe and efficient after heart transplantation (HTx). This study reports the 5-year long-term effects. DESIGN AND METHODS: Forty-one HTx patients who had completed the previous 12-month randomized controlled trial, comparing HIT intervention with usual care, were eligible. In particular, we measured VO2peak , muscular capacity, intravascular ultrasound, and questionnaires measuring physical and mental health. RESULTS: The baseline mean±SD values were as follows: age; 49.1±16.5 years, men; 68%, time since HTx: 4.1±2.2 years. Within the HIT group, initial VO2peak increased significantly from 27.7±5.7 to 31.2±5.3 mL/kg/min. However, during the next 4 years, VO2peak decreased to 26.0±6.2 mL/kg/min. The control group showed slightly decreasing VO2peak values during the entire 5-year period. The HIT group reported significantly less anxiety symptoms, but there were no long-term differences in VO2peak , muscular capacity, or cardiac allograft vasculopathy between the groups. The similar VO2peak values correspond to our findings of similar everyday activity. CONCLUSION: Our findings suggest that intermittent periods of HIT may be necessary to maintain the initial benefits gained from the intervention. However, HIT probably reduces the burden of anxiety, which is a frequent health issue following HTx.

The development and feasibility of a personal health-optimization system for people with bipolar disorder.

BACKGROUND: People with bipolar disorder often experience ill health and have considerably reduced life expectancies. Suboptimal treatment is common and includes a lack of effective medicines, overtreatment, and non-adherence to medical interventions and lifestyle measures. E- and m-health applications support patients in optimizing their treatment but often exhibit conceptual and technical shortcomings. The objective of this work was to develop and test the usability of a system targeting suboptimal treatment and compare the service to other genres and strategies. METHODS: Based on the frameworks of shared decision-making, multi-criteria decision analysis, and single-subject research design, we interviewed potential users, reviewed research and current approaches, and created a first version using a rapid prototyping framework. We then iteratively improved and expanded the service based on formative usability testing with patients, healthcare providers, and laypeople from Norway, the UK, and Ukraine. The evidence-based health-optimization system was developed using systematic methods. The System Usability Scale and a questionnaire were administered in formative and summative tests. A comparison of the system to current standards for clinical practice guidelines and patient decision aids was performed. RESULTS: Seventy-eight potential users identified 82 issues. Driven by user feedback, the limited first version was developed into a more comprehensive system. The current version encompasses 21 integrated core features, supporting 6 health-optimization strategies. One crucial feature enables patients and clinicians to explore the likely value of treatments based on mathematical integration of self-reported and research data and the patient's preferences. The mean ± SD (median) system usability score of the patient-oriented subsystem was 71 ± 18 (73). The mean ± SD (median) system usability score in the summative usability testing was 78 ± 18 (75), well above the norm score of 68. Feedback from the questionnaire was generally positive. Eighteen out of 23 components in the system are not required in international standards for patient decision aids and clinical practice guidelines. CONCLUSION: We have developed the first evidence-based health-optimization system enabling patients, clinicians, and caregivers to collaborate in optimizing the patient's health on a shared platform. User tests indicate that the feasibility of the system is acceptable.

Design and rationale of the HITTS randomized controlled trial: Effect of High-intensity Interval Training in de novo Heart Transplant Recipients in Scandinavia.

There is no consensus on how, when, and at what intensity exercise should be performed and organized after heart transplantation (HTx). Most rehabilitation programs are conducted in HTx centers, which might be impractical and costly. We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in maintenance HTx recipients, but there are no studies among de novo patients, and whether HIT is feasible and superior to moderate training in HTx recipients is unclear. A total of 120 clinically stable HTx recipients older than 18 years will be recruited from 3 Scandinavian HTx centers. Participants are randomized to HIT or moderate training, shortly after surgery. All exercises are supervised in the patients' local communities. Testing at baseline and follow-up includes the following: VO2peak (primary end point), muscle strength, body composition, quality of life, myocardial performance, endothelial function, biomarkers, and progression of cardiac allograft vasculopathy. A subgroup (n = 90) will also be tested at 3-year follow-up to assess long-term effects of exercise. So far, the HIT intervention is well tolerated, without any serious adverse events. We aim to test whether decentralized HIT is feasible, safe, and superior to moderate training, and whether it will lead to significant improvement in exercise capacity and less long-term complications.

Peak oxygen uptake and self-reported physical health are strong predictors of long-term survival after heart transplantation.

BACKGROUND: Peak oxygen uptake (VO2peak ) is known as the gold standard measure of cardiopulmonary fitness. We therefore hypothesized that measures of physical health would predict long-term survival in heart transplant recipients (HTx). METHODS: This retrospective study investigated survival in two HTx populations; the cardiopulmonary exercise test (CPET) cohort comprised 178 HTx patients who completed a VO2peak test during their annual follow-up (1990-2003), and the SF-36 cohort comprised 133 patients who completed a quality of life questionnaire, SF-36v1 (1998-2000). RESULTS: Mean (SD) age in the CPET cohort was 52 (12) yr and 54 (11) yr in the SF-36 cohort. Mean observation time was, respectively, 11 and 10 yr. Mean (SD) VO2peak was 19.6 (5.3) mL/kg/min, and median (IR) physical function (PF) score was 90 (30). VO2peak and PF scores were both significant predictors in univariate Cox regression. Multiple Cox regression analyses adjusted for other potential predictors showed that VO2peak , age, and cardiac allograft vasculopathy (CAV) were the most important predictors in the CPET cohort, whereas age, PF score, smoking, and CAV were the most important predictors in the SF-36 cohort. In Kaplan-Meier analysis, VO2peak and PF scores above the median value were related to significant longer survival time. CONCLUSION: Peak oxygen uptake and self-reported physical health are strong predictors for long-term survival in HTx recipients. VO2peak is a crucial measurement and should be more frequently used after HTx.

A Review of High-Intensity Interval Training in Heart Transplant Recipients: Current Knowledge and Future Perspectives.

OBJECTIVE: This review reports how exercise-based rehabilitation strategies have developed over the past decades, and it specifically focuses on the effectiveness, safety, and implementation of high-intensity interval training (HIIT). It provides an overview of the historical progression, main research findings, and considerations surrounding HIIT as the preferred exercise modality for recipients of heart transplant (HTx). REVIEW METHODS: The review includes a timeline of studies spanning from 1976-2023. The 2017 Cochrane systematic review on exercise-based cardiac rehabilitation in recipients of HTx serves as the main knowledge base (≥2015). Additionally, literature searches in PubMed/Medline and ClinicalTrials.gov have been performed, and all reviews and studies reporting the effects of moderate- to high-intensity exercise in recipients of HTx, published in 2015 or later have been screened. SUMMARY: High-intensity interval training has gained prominence as an effective exercise intervention for recipients of HTx, demonstrated by an accumulation of performed studies in the past decade, although implementation in clinical practice remains limited. Early restrictions on HIIT in HTx recipients lacked evidence-based support, and recent research challenges these previous restrictions. High-intensity interval training results in greater improvements and benefits compared with moderate-intensity continuous training in the majority of studies. While HIIT is now regarded as generally suitable on a group level, individual assessment is still advised. The impact of HIIT involves reinnervation and central and peripheral adaptations to exercise, with variations in recipent responses, especially between de novo and maintenance recipients, and also between younger and older recipients. Long-term effects and mechanisms behind the HIIT effect warrant further investigation, as well as a focus on optimized HIIT protocols and exercise benefits.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Effects of high-intensity interval training on cardiac remodelling, function and coronary microcirculation in de novo heart transplant patients: a substudy of the HITTS randomised controlled trial.

Objectives: High-intensity interval training (HIT) improves peak oxygen consumption (VO2peak) in de novo heart transplant (HTx) recipients. It remains unclear whether this improvement early after HTx is solely dependent on peripheral adaptations, or due to a linked chain of central and peripheral adaptations. The objective of this study was to determine whether HIT results in structural and functional adaptations in the cardiovascular system. Methods: Eighty-one de novo HTx recipients were randomly assigned to participate in either 9 months of supervised HIT or standard care exercise-based rehabilitation. Cardiac function was assessed by echocardiogram and the coronary microcirculation with the index of microcirculatory resistance (IMR) at baseline and 12 months after HTx. Results: Cardiac function as assessed by global longitudinal strain was significantly better in the HIT group than in the standard care group (16.3±1.2% vs 15.6±2.2%, respectively, treatment effect = -1.1% (95% CI -2.0% to -0.2%), p=0.02), as was the end-diastolic volume (128.5±20.8 mL vs 123.4±15.5 mL, respectively, treatment effect=4.9 mL (95% CI 0.5 to 9.2 mL), p=0.03). There was a non-significant tendency for IMR to indicate improved microcirculatory function (13.8±8.0 vs 16.8±12.0, respectively, treatment effect = -4.3 (95% CI -9.1 to 0.6), p=0.08). Conclusion: When initiated early after HTx, HIT leads to both structural and functional cardiovascular adaptations. Trial registration number: NCT01796379.

Factors Associated With Sinoatrial Reinnervation After Heart Transplantation.

Background: Factors associated with sympathetic and parasympathetic sinoatrial reinnervation after heart transplantation (HTx) are inadequately studied. Methods: Fifty transplant recipients were examined at 7 to 12 wk (index visit), 6, 12, 24, and 36 mo after HTx. Supine rest heart rate variability in the low-frequency (LF) domain (sympathetic and parasympathetic sinoatrial reinnervation) and the high-frequency (HF) domain (parasympathetic sinoatrial reinnervation) were measured repeatedly and related to selected recipient, donor, and perisurgical characteristics. We primarily aimed to identify index visit factors that affect the sinoatrial reinnervation process. Secondarily, we examined overall associations between indices of reinnervation and repeatedly measured recipient characteristics to generate new hypotheses regarding the consequences of reinnervation. Results: LF and HF variability increased time dependently. In multivariate modeling, a pretransplant diagnosis of nonischemic cardiomyopathy (P = 0.038) and higher index visit handgrip strength (P = 0.028) predicted improved LF variability. Recipient age, early episodes of rejection, and duration of extracorporeal circulation were not associated with indices of reinnervation. Study average handgrip strength was positively associated with LF and HF variability (respectively, P = 0.005 and P = 0.029), whereas study average C-reactive protein was negatively associated (respectively, P = 0.015 and P = 0.008). Conclusions: Indices of both sympathetic and parasympathetic sinoatrial reinnervation increased with time after HTx. A pretransplant diagnosis of nonischemic cardiomyopathy and higher index visit handgrip strength predicted higher indices of mainly sympathetic reinnervation, whereas age, rejection episodes, and duration of extracorporeal circulation had no association. HTx recipients with higher indices of reinnervation had higher average handgrip strength, suggesting a link between reinnervation and improved frailty. The more reinnervated participants had lower average C-reactive protein, suggesting an inhibitory effect of reinnervation on inflammation, possibly through enhanced function of the inflammatory reflex. These potential effects of reinnervation may affect long-term morbidity in HTx patients and should be scrutinized in future research.

Kinetics of Torque Teno virus in heart transplant patients.

End-stage heart failure often requires heart transplantation as a life-prolonging treatment. Immunosuppressive therapy is necessary to avoid rejection, but is associated with serious adverse effects. New approaches are needed to monitor immune function in heart transplant patients. We here report the kinetics of Torque Teno Virus (TTV) after transplantation in a large cohort of heart transplant patients and examine its possible role in predicting rejection. We included 106 patients from Aarhus University Hospital and Oslo University Hospital. Patients were followed for 3 years with clinical assessments, biopsies, TTV measurements, and flowcytometric phenotyping. We observed TTV levels reaching a maximum 3 months after transplantation for all 106 patients, after which levels gradually declined. 38 patients (38 %) had biopsy-proven rejection within the first year. We did not find evidence of an association between TTV and serum trough levels, events of rejection, nor flow cytometric immunophenotype. We report data on a large cohort of heart transplant patients and contribute to the understanding of how TTV behaves in transplant patients. Despite not finding an association with rejection, our results provide important insights into the kinetics of TTV levels after transplantation, which may be useful in future studies of immune function in heart transplant patients.