High-intensity interval training in de novo heart transplant recipients with long-term follow-up

High-intensity interval training (HIT) is an effective method to increase VO2peak in maintenance heart transplant (HTx) recipients. There is limited evidence of HIT in the de novo HTx recipients, and the long-term effects of early initiation of HIT after HTx is unknown. The main aims of this thesis were to investigate the effects of HIT compared to moderate intensity continuous training (MICT) on VO2peak in de novo HTx recipients, with a 1-yr and a 3-yr follow-up. A secondary aim was to investigate pre-dictors for VO2peak in de novo HTx. At 1-yr follow-up there was a significantly higher mean change in VO2peak in the HIT group compared to the MICT group. The mean difference between groups was 1.8 mL/kg/min which is regarded as clinically meaningful. At 3-yrs follow-up, there was no longer a statistically significant mean difference between the groups in VO2peak. The mean difference between groups was still significant regarding muscular exercise capacity and the anaerobic threshold. HIT, performed decentralized instead of in the specialist health care setting, was found to be a safe and effective meth-od of exercise in this medically stable cohort of de novo HTx recipients, and showed also some sustainable long-term effects

Helserelatert livskvalitet etter hjertetransplantasjon : En tverrsnittstudie

FORMÅL: Å kartlegge helserelatert livskvalitet hos medisinsk stabile hjertetransplanterte 1 – 8 år etter HTx. TEORETISK FORANKRING: Den teoretiske modellen av Wilson og Cleary ble benyttet for å undersøke assosiasjoner mellom prediktorvariabler og helserelatert livskvalitet. Teori vedrørende måleinstrumenter og teori om helserelatert livskvalitet etter HTx ble anvendt. METODE: En tverrsnittstudie med 52 hjertetransplanterte (37 menn) fra hele Norge transplantert for 1 – 8 år siden. Gjennomsnittsalder 52 ± 16 år. Helserelatert livskvalitet ble undersøkt med Short Form 36 (SF-36v2) og Kansas City Cardiomyopathy Questionnaire (KCCQ). Prediktorvariabler var: funksjonsrelaterte, kliniske, sosiodemografiske og symptomer på angst og depresjon. RESULTATER: SF-36 skår ble vist som standardiserte skår (gjennomsnitt 50 ± 10). KCCQ skår ble presentert på en skala fra 0 – 100. Høyere skår representerer bedre livskvalitet. Gjennomsnittsskår på SF-36 skalaene og sumskårene var fra 49 (fysisk rollebegrensning) til 55 (mental helse). Sammenlignet med referansepopulasjonen i USA hadde hjertetransplanterte like god eller bedre helserelatert livskvalitet. Sammenlignet med yngre pasienter hadde eldre pasienter lavere skår på fysisk funksjon og Physical Component Summary (PCS) og høyere skår på mental helse og Mental Component Summary (MCS). På KCCQ skalaene og sumskårene skåret pasientene i gjennomsnitt fra 90 (mestringstro) til 94 (fysiske begrensninger). Alder forklarte 13 % av variasjonen i PCS. Alder, symptomer på depresjon og angst forklarte 49 % av variasjonen i MCS. VO2peak og symptomer på depresjon forklarte 33 % av variasjonen i KCCQ klinisk sumskår. Å være i arbeid, symptomer på depresjon og VO2peak forklarte 36 % av variasjonen i KCCQ funksjonsstatus sumskår. KONKLUSJON: Medisinsk stabile hjertetransplanterte 1 – 8 år etter HTx hadde god helserelatert livskvalitet målt ved et generisk (SF-36) og et hjertesviktspesifikt (KCCQ) spørreskjema. Prediktorer for helserelatert livskvalitet var bl.a. alder, å være i arbeid, VO2peak og symptomer på angst og depresjon

Effect of high-intensity interval training in young heart transplant recipients: results from two randomized controlled trials

Background Little is known about the effect of exercise in young heart transplant recipients, and results on group level is lacking. This study summarizes the findings of the youngest participants in two previous randomized controlled trials. Method This is a hypothesis-generating study reporting the main results from the youngest participants in two larger randomized controlled trials investigating the effect of high-intensity interval training (HIT). The article summarizes the main results from 28 young participants (< 40 year of age) who have participated in two previous studies which evaluated the effect of HIT vs. controls in adult heart transplant recipients. One of the studies included de novo heart transplant recipients and the other included maintenance heart transplant recipients. All study tests were performed in-hospital, in the specialist health care setting, but the exercise intervention was carried out locally, in cooperation with the primary health care. In both studies the exercise intervention lasted for 9–12 months. In one study, HIT (85–95% of peak effort) was compared to controls (no specific intervention), and in the other study HIT was compared to moderate, continuous exercise (MICT, 60–80% of peak effort). The main outcome measure was peak oxygen uptake (VO2peak) and a secondary endpoint was muscle strength. Results The summarized findings from the youngest heart transplant recipients in these two studies demonstrated mainly that the improvement in peak oxygen uptake among the younger recipients (< 40 years) was much larger (4.7 vs. 1.2 ml/kg/min and 7.0 vs. 2.2 ml/kg/min) compared to the improvement among the older recipients (≥ 40 years), and in accordance with results from adult heart transplant populations: HIT, compared to MICT, induced the largest improvement in peak oxygen consumption, also in the younger heart transplant recipients. Conclusions These results suggest that young heart transplant recipients have a greater effect of HIT than of MICT and may also suggest that younger recipients benefit more from high-intensity interval training than their older co-patients. However, larger randomized studies focusing on the young heart transplant population is strongly needed to confirm this hypothesis. Trial registration Clinical trial registrations: NCT01796379 and NCT01091194

Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial

Aims Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients. Methods and results This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin 100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39). Conclusion Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%

Muscular exercise capacity and body fat predict VO2peak in heart transplant recipients

Heart transplant (HTx) recipients usually have reduced exercise capacity, with reported VO2peak levels of 50–70% of predicted values. This study aimed to evaluate central and peripheral factors predictive of VO2peak. Conclusions: Chronotropic incompetence is not a limiting factor for exercise capacity in a population of relatively fit HTx patients. The most significant predictors, representing only peripheral factors, are similar to those often determining VO2peak in healthy, non-athletic individuals. Our findings emphasize the importance of a low percentage of body fat and high muscular exercise capacity in order to attain a sufficient VO2peak level after HTx

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

Agreement between PG-SGA category and fat-free mass in colorectal cancer patients

Background and aims Low fat-free mass (FFM) is associated with adverse outcomes in colorectal cancer (CRC) patients. Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used tool developed to detect patients with malnutrition or at risk of malnutrition. The aim of this study was to investigate the agreement between PG-SGA category and FFM in patients with non-metastatic CRC. Methods Ninety-seven patients were included and categorized as well nourished (PG-SGA:A, n = 67) or malnourished (PG-SGA:B, n = 30). No patients were severely malnourished (PG-SGA: C). Bioelectrical impedance analysis (BIA) was used to assess FFM. Low FFM was defined as low fat-free mass index (FFMI) according to cut-off values recently proposed by The European Society for Clinical Nutrition and Metabolism (ESPEN). Results Twenty-nine percent of the patients were identified with low FFMI. The proportion with low FFMI was significantly higher among patients classified as malnourished by PG-SGA compared to well nourished (p = 0.015). The sensitivity was however low, as the PG-SGA categorization classified only 50.0% of the patients with low FFMI as malnourished (PG-SGA B). Using the PG-SGA scores (cut-off point > 4), the sensitivity increased to 60.7%. Physical examination in the PG-SGA identified only 64.3% of the patients with low FFMI as muscle depleted. Conclusion Our results indicate a low agreement between PG-SGA category and low FFMI among patients with non-metastatic CRC. In clinical practice, PG-SGA should be supplemented by muscle mass assessments by BIA or other methods in order to detect low FFM in this patient group

Clinical features and determinants of VO2peak in de novo heart transplant recipients

AIM: To study exercise capacity and determinants of early peak oxygen consumption (VO2peak) in a cohort of de novo heart transplant (HTx) recipients. METHODS: To determine possible central (chronotropic responses, cardiopulmonary and hemodynamic function) and peripheral factors (muscular exercise capacity and body composition) predictive of VO2peak, a number of different measurements and tests were performed, as follows: Cardiopulmonary exercise testing (CPET) was performed mean 11 wk after surgery in 81 HTx recipients > 18 years and was measured with breath by breath gas exchange on a treadmill or bicycle ergometer. Metabolic/respiratory measures include VO2peak and VE/VCO2 slope. Additional measures included muscle strength testing, bioelectrical impedance analysis, echocardiography, blood sampling and health-related quality of life. Based on the VO2peak (mL/kg per minute) median value, the study population was divided into two groups defined as a low-capacity group and a high-capacity group. Potential predictors were analyzed using multiple regression analysis with VO2peak (L/min) as the dependent variable. RESULTS: The mean ± standard deviation (SD) age of the total study population was 49 ± 13 years, and 73% were men. This de novo HTx cohort demonstrated a median VO2peak level of 19.4 mL/kg per min at 11 ± 1.8 wk post-HTx. As compared with the high-capacity group, the low-capacity group exercised for a shorter time, had lower maximal ventilation, O2 pulse, peak heart rate and heart rate reserve, while the VE/VCO2 slope was higher. The low-capacity group had less muscle strength and muscular exercise capacity in comparison with the high-capacity group. In order of importance, O2 pulse, heart rate reserve, muscular exercise capacity, body mass index, gender and age accounted for 84% of the variance in VO2peak (L/min). There were no minor or major serious adverse events during the CPET. CONCLUSION: Although there is great individual variance among de novo HTx recipients, early VO2peak measures appear to be influenced by both central and peripheral factors

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

Strong evidence for parasympathetic sinoatrial reinnervation after heart transplantation

Background Heart transplantation (HTx) surgically denervates the heart. We examined indices of sinoatrial reinnervation, with emphasis on (1) the occurrence and timing of parasympathetic reinnervation, and (2) the consequences of reinnervation for heart rate (HR) responsiveness and arterial baroreceptor sensitivity. Methods Fifty HTx recipients were prospectively followed for 36 months after surgery. Hemodynamic variables and heart rate variability were continuously recorded at supine rest, 60 degrees head-up-tilt, during the Valsalva maneuver and during handgrip isometric exercise. Results Suggesting parasympathetic reinnervation: at baseline rest, root of the mean squared differences of successive RR intervals increased from median 3.9(5.9) to 7.1(5.1) ms (p < 0.001); high-frequency power increased from 4.0(12) to 5.7(18.9) ms2 (p = 0.018); and baroreceptor sensitivity increased from 0.04(0.36) to 1.3(2.4) ms/mmHg (p < 0.001). Suggesting sympathetic reinnervation: at baseline rest low-frequency power increased from 0.49(2.5) to 7.5(18.1) ms2 (p < 0.001); and HR responses to sympathetic stimulation during (1) head-up tilt increased from 1.9(4.2) to 9.1(8.2) bpm (p < 0.001), (2) Valsalva increased from 1.6(1.4) to 8.3(10.8) bpm (p < 0.001) and (3) handgrip increased from 0.3(0.6) to 1.9(5.1) bpm (p < 0.001). Signs of sympathetic reinnervation emerged within 6 months, while signs of parasympathetic reinnervation emerged by 24 months. Conclusions Root of the mean squared differences of successive RR intervals, high-frequency and low-frequency variability, HR responsiveness and arterial baroreflex sensitivity all increased after HTx, suggesting functional parasympathetic and sympathetic sinoatrial reinnervation. Accordingly, the pathological regulatory state present in heart transplant recipients, which is responsible for a host of functional and clinical abnormalities, is being partially offset over time by restored autonomic control of the heart in many heart transplant recipients