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Objectives: Previous reports indicate bone deficits in patients with Fontan circulation. However, the consequences of these deficits on bone strength and when these changes occur are unclear.

Aim: To compare the tibial bone strength-strain index between young patients (6-19 years) with Fontan circulation and age- and sex-matched controls, and to determine strength-strain-index in subgroups of children (6-12 years) and adolescents (13-19 years) versus controls.

Method: The tibia was examined with peripheral quantitative CT. Based on the assessed data, bone strength-strain index was calculated in the lateral and anterior-posterior directions.

Results: Twenty patients with Fontan and twenty controls (mean age 13.0 ± 4.4 years; 50% females) were examined. Patients had a lower strength-strain index in the lateral direction compared to controls (808.4 ± 416.8mm³ versus 1162.5 ± 552.1mm³, p = 0.043). Subgroup analyses showed no differences regarding strength-strain index in children (6-12 years) with Fontan circulation compared to controls. However, the adolescents (13-19 years) with Fontan circulation had lower strength-strain indexes in both the lateral and anterior-posterior directions compared to controls (1041.4 ± 299.8mm³ versus 1596.4 ± 239.6mm³, p < 0.001, and 771.7 ± 192.4mm³ versus 1084.9 ± 215.0mm³, p = 0.004). When adjusted for height, there were differences between patients (6-19 years) and controls in strength-strain indexes in both the lateral and anterior-posterior directions. In subgroup analyses, the results remained robust.

Conclusion: Young patients (6-19 years) with Fontan circulation have a lower strength-strain index in the tibia compared to controls. Subgroup analyses show that this deficit is mainly driven by the differences in adolescents (13-19 years), which might suggest that bone strength decreases with age.

Introduction: Thanks to achievements in paediatric heart surgery and medicine, the population of adults with surgically repaired or palliated congenital heart defects is growing. Many of these adults have reduced exercise capacity, weaker muscular strength and shorter height, all of which suggest an altered body composition.

The overall aim of this thesis was to evaluate the body composition, in terms of bone, muscle and fat mass, in adults with complex congenital heart disease (CHD). Changes as such may be of prognostic importance and thus suggest future therapeutic targets outside the traditional hunting grounds of the cardiologist.

Material and methods: The overall material consisted of two cohorts. The first cohort, recruited in a Swedish multicentre study, comprised 73 adult patients with complex CHD and 73 controls, matched for age and sex. Participants were examined with full body dual-energy x-ray absorptiometry (DXA), providing muscle, bone and fat mass for arms, legs and trunk respectively (papers I and II).

The second cohort, recruited within a single centre study, comprised 49 adult patients with complex CHD and 49 age and sex matched controls. Participants were examined with peripheral quantitative computed tomography (pQCT), providing slices of forearm and calf, describing muscle, bone and fat area and corresponding density (papers III and IV). 

Muscular strength in selected muscle groups was also evaluated in both cohorts.

Results: More than half of the adults with complex CHD had a pathologically low skeletal muscle mass and strength compared to controls, a trait referred to as sarcopenia. There was a strong association between forearm muscle mass and grip strength.

Bone mass was lower in adults with complex CHD, according to both DXA and pQCT analyses, also when adjusting for shorter height. Patients also had lower full body bone mineral density (BMD) as measured with DXA. However, analysis of BMD in limbs with pQCT showed no such reduction. Despite this latter finding, the strength-strain index (a surrogate marker for bone strength provided by pQCT in the lower limbs) was still lower in patients compared to controls.

Female patients had a higher amount of fat, both in terms of fat mass and proportion of fat, in comparison to controls. The fat mass was predominantly distributed around the internal organs, known as visceral adipose tissue. Male patients showed no such difference regarding fat mass compared to controls.

Conclusion: Consequences of living with complex CHD go far beyond the heart; this young population presents a reduced skeletal muscle mass as well as reduced bone strength – both premature traits of frailty, prone to increase with further ageing. Also, women with complex CHD have an increased amount of visceral adipose tissue, which may elevate the risk of acquired heart disease.

The extent of future complications remains to be seen. However, the standard treatments for both sarcopenia and osteoporosis include optimal nutritional intake and increased physical exercise. These measures should start sooner rather than later, preferably evaluated through existing quality registers and interventional trials.

Bakgrund: Tack vare stora framsteg inom barnhjärtkirurgin överlever allt fler barn med medfödda hjärtfel, så kallade hjärtebarn, till vuxen ålder. Många av dessa vuxna med medfödda hjärtfel har nedsatt kondition, nedsatt styrka och lite kortare längd – vilket väcker misstanken om avvikande kropps­samman­sätt­ning.

Syftet med avhandlingen var att kartlägga kroppssammansättningen hos vuxna med komplexa medfödda hjärtfel, då dylika förändringar kan påverka prognos och behandling.

Material och metod: Materialet bestod av två kohorter: den första kom från en svensk multicenterstudie med 73 vuxna med komplexa medfödda hjärtfel och 73 ålders- och könsmatchade kontroller. Dessa genomgick helkroppsunder-sökning med dual-energy x-ray absorptiometry (DXA), en metod för att mäta muskel-, ben- och fettmassa. (artikel I och II)

Den andra kohorten kom från en singelcenterstudie, innefattande hela norra regionen, med 49 patienter och likaledes matchade kontroller. Dessa undersöktes med peripheral quantitative computed tomography (pQCT) som genom datortomografiska snitt av underarm och underben kartlägger muskel-, ben- och fettarea. (artikel III och IV)

Resultat: Hälften av patienterna med komplexa medfödda hjärtfel hade sänkt muskelmassa och muskelstyrka (sarkopeni), vilket ofta förknippas med försämrad prognos. Detta sågs både i studien med DXA och studien med pQCT.

Båda metoderna visade även sänkt benmassa. DXA visade på sänkt bendensitet, något som inte kunde bekräftas med pQCT. Däremot uppmättes sämre hållfasthet i skelettet med den senare metoden.

Kvinnliga patienter hade större andel fett än de manliga, framför allt distribuerat i buken, vilket är extra ohälsosamt.

Slutsats: Att leva med ett komplext medfött hjärtfel påverkar inte bara hjärtat utan hela kroppen. Sarkopeni och den lägre hållfastheten i skelettet riskerar att förvärras med stigande ålder och ökar risken för framtida sjukdomar och frakturer. Dessutom medför den ökade andelen bukfett hos kvinnorna förhöjd risk för förvärvad hjärt-kärlsjukdom.

Hur mycket den avvikande kroppssammansättningen kommer att påverka sjuklighet och överlevnad när vuxna med komplexa medfödda hjärtfel åldras får framtida studier utvisa. Men utifrån erfarenheter från andra patientgrupper finns det ingen anledning att vänta med förebyggande behandling mot såväl sarkopeni och benskörhet som förvärvad hjärtsjukdom – närmare bestämt uppmuntra till följsamhet till befintliga kostråd samt motion.

Background: We aimed to study bone mineral density (BMD) and skeletal strength in the growing population of adults with moderate or complex congenital heart disease (CHD).

Methods: Peripheral quantitative computed tomography (pQCT) was performed on the radius and tibia in 49 adults with moderate or complex CHD, and in 49 age and sex matched controls (n ​= ​23 [47%] female, mean age 36 ​± ​15.5 years.) Strength in the radius and tibia were presented, respectively, in terms of Strength-Strain Index (SSI).

Results: Patients had similar total BMD as controls in both the radius (807 ​± ​82 vs. 792 ​± ​75 ​mg/cm³, p ​= ​0.3) and tibia (663 ​± ​86 vs. 689 ​± ​67 ​mg/cm³, p ​= ​0.1). In the radius, patients had a lower xSSI than controls (154 ​± ​46 vs. 175 ​± ​54 ​mm³, p ​= ​0.04) but a similar ySSI (178 ​± ​58 vs. 195 ​± ​55 ​mm³, p ​= ​0.1). In the tibia, patients had a lower xSSI (1492 ​± ​399 vs. 1780 ​± ​372 ​mm³, p ​< ​0.001) as well as ySSI (1066 ​± ​304 vs. 1250 ​± ​281, p ​= ​0.002). In a multiple linear regression model, only height was independently associated with decreased skeletal strength in patients tibia in terms of xSSI [F(2,46) ​= ​40.002, p ​< ​0.001, R² ​= ​0.635].

Conclusion: Adults with moderate or complex CHD had reduced strength in the radius and tibia, despite a normal BMD as assessed with pQCT. Their reduced bone strength could increase the risk of future fractures.

Aims: The majority of children with complex congenital heart disease (CHD) survive into adulthood due to advances in medical care. Adult patients with CHD have an increased incidence of diagnoses related to ageing such as heart failure, dementia, cancer and sarcopenia, despite a relatively low age. They also have a shorter life expectancy. It is unknown if their bone structures also show signs of premature ageing. We therefore investigated Bone Mineral Content (BMC) and bone mineral density (BMD) in an adult population with complex CHD.

Methods: The total body BMC and BMD was examined using dual energy X-ray absorptiometry (DXA) in 73 adults with complex CHD (mean age 35.8 ± 14.3, women n = 22) and 73 age and sex matched controls.

Results: The adults with complex CHD had lower total body BMC (2.6 ± 0.5 kg vs. 2.9 ± 0.5 kg, p < 0.001) and BMD (1.18 ± 0.12 g/cm² vs. 1.26 ± 0.11 g/cm², p < 0.001) compared to controls. BMD was lower for patients with single ventricle physiology and for the other complex diagnoses, and it persisted after correction for most common risk factors for osteoporosis.

Conclusion: Adults with complex CHD have reduced total body BMC and BMD compared to healthy controls. These results are a sign of frailty that conforms with other previously reported signs of premature ageing. The risk of osteoporosis is low in our relatively young population, but it is assumed to increase with ageing. We recommend that clinicians pay close attention to risk factors for osteoporosis, and are generous in administering DXA-measurements in order to prevent future fractures among adults with complex CHD.

Background: Adults with complex congenital heart disease (CHD) have reduced aerobic capacity and impaired muscle function. We therefore hypothesized that patients have a lower skeletal muscle mass and higher fat mass than controls.

Methods: Body composition was examined with full body Dual-Energy x-ray Absorptiometry (DXA) in 73 patients with complex CHD (mean age 35.8 ± 14.3, women n = 22) and 73 age and sex matched controls. Patients fulfilling criteria for low skeletal muscle mass in relation to their height and fat mass were defined as sarcopenic.

Results: Male patients (n = 51) were shorter (177.4 ± 6.6 cm vs. 180.9 ± 6.7 cm, p = 0.009) and weighed less (76.0 ± 10.8 kg vs. 82.0 ± 12.4 kg, p = 0.01) than controls. Also, patients had a lower appendicular lean mass-index (ALM-index) (7.57 ± 0.97 kg/m2 vs. 8.46 ± 0.90 kg/m2, p < 0.001). Patients’ relative tissue fat mass (27.9 ± 7.0% vs. 25.4 ± 8.6%, p = 0.1) did not differ. Forty-seven percent of the men (n = 24) were classified as sarcopenic.

Female patients (n = 22) were also shorter (163.5 ± 8.7 cm vs. 166.7 ± 5.9 cm, p = 0.05) but had a higher BMI (25.7 ± 4.2 vs. 23.0 ± 2.5, p = 0.02) than controls. Patients also had a lower ALM-index (6.30 ± 0.75 vs. 6.67 ± 0.55, p = 0.05), but their relative body fat mass (40.8 ± 7.6% vs. 32.0 ± 7.0%, p < 0.001) were higher. Fifty-nine percent of the women (n = 13) were classified as sarcopenic.

Conclusions: The body composition was altered toward lower skeletal muscle mass in patients with complex CHD. Approximately half of the patients were classified as sarcopenic. Contrary to men, the women had increased body fat and a higher BMI. Further research is required to assess the cause, possible adverse long-term effects and whether sarcopenia is preventable or treatable.

Background: Adults with congenital heart disease (CHD) have a low muscle mass (measured with Dual energy x-ray absorptiometry). Our aims were to confirm these results using peripheral quantitative computed tomography (pQCT), and to study the relationship between muscle cross sectional area (CSA) and isometric muscle strength. 

Methods: In this cross sectional study, we performed pQCT and tested isometric muscle strength in the forearm and calf of 49 adults with complex CHD and 49 age and sex matched controls (for each group: mean age 36±15.5 years; n=23 females, 47%). 

Results: In the forearm, after adjusting for height, patients had lower muscle CSA and lower isometric strength compared to controls (women: 24.1±6.7 vs. 26.2±6.7 cm2, p=0.05 and 30.0±1.0 vs. 33.4±1.0 kg, p=0.03; men: 36.0±1.2 vs. 42.5±1.2 cm2, p=0.001 and 47.2±1.9 vs. 53.4±1.9 kg, p=0.03). In addition, both patients and controls had strong correlations between muscle CSA and isometric strength. In the calf, female patients did not have lower muscle CSA than controls after correcting for height (60.5±1.4 vs. 62.7±1.4cm2, p=0.3), whereas men did (69.9±1.7 vs. 80.3±1.7 cm2, p<0.001). Isometric strength in the calf was lower in female patients than controls (487±35 vs. 614±35 N, p=0.02) but not in males (588±44 vs. 697±44 N, p=0.08), and there was no correlation with muscle CSA. 

Conclusion: In conclusion, adults with complex CHD have low forearm muscle CSA as assessed with pQCT. Grip strength correlates well with forearm muscle CSA and may serve as an indirect measurement of muscle mass.

Objective 

To study bone mineral density (BMD) and skeletal strength in adults with complex congenital heart disease (CHD) in comparison to a matched control group.

Methods

Peripheral quantitative computed tomography (pQCT) was performed on standardized sites of the radius and tibia in 49 adults with complex CHD, and in 49 age and sex matched controls (n = 23 [47 %] female, mean age 36 ± 15.5 years.) Strength for lateral and anterior acting forces in the radius and tibia were presented, respectively, in terms of x- and y-Strength-Strain Index (SSI).

Results 

Patients had similar total BMD as controls in both the radius (807 ± 82 vs. 792 ± 75 mg/cm3, p = 0.3) and tibia (663 ± 86 vs.689 ± 67 mg/cm3, p = 0.1). In the radius, patients had a lower xSSI than controls (154 ± 46 vs. 175 ± 54 mm3, p = 0.04) but a similar ySSI (178 ± 58 vs. 195 ± 55 mm3, p = 0.1). In the tibia, patients had a lower xSSI (1492 ± 399 vs. 1780 ± 372 mm3, p < 0.001) as well as ySSI (1066 ± 304 vs. 1250 ± 281, p = 0.002). In a multiple linear regression model, only height was independently associated with decreased skeletal strength in patients tibia in terms of xSSI [F(2,46) = 40.002, p < 0.001, R2 = 0.635]. Being a patient, with single ventricle physiology or other diagnose of complex CHD, was independently associated with decreased tibia xSSI [F(2,95) = 7.085, p = 0.001, η2 = 0.13].

Conclusion 

Adults with complex CHD had reduced strength in the radius and tibia, despite a normal BMD as assessed with pQCT. Whether their reduced bone strength entails increased risk of future fractures is currently unknown.