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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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO 2peak ) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p < 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p < 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO 2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.ClinicalTrials.gov identifier NCT02378857., (© 2021. The Author(s).)

Objectives: Few data exist on mortality among patients with univentricular heart (UVH) before surgery. Our aim was to explore the results of intention to perform surgery by estimating preoperative vs postoperative survival in different UVH subgroups., Design: Retrospective., Setting: Tertiary centre for congenital cardiology and congenital heart surgery., Participants: All 595 Norwegian children with UVH born alive from 1990 to 2015, followed until 31 December 2020., Results: One quarter (151/595; 25.4%) were not operated. Among these, only two survived, and 125/149 (83.9%) died within 1 month. Reasons for not operating were that surgery was not feasible in 31.1%, preoperative complications in 25.2%, general health issues in 23.2% and parental decision in 20.5%. In total, 327/595 (55.0%) died; 283/327 (86.5%) already died during the first 2 years of life. Preoperative survival varied widely among the UVH subgroups, ranging from 40/65 (61.5%) among patients with unbalanced atrioventricular septal defect to 39/42 (92.9%) among patients with double inlet left ventricle. Postoperative survival followed a similar pattern. Postoperative survival among patients with hypoplastic left heart syndrome (HLHS) improved significantly (5-year survival, 42.5% vs 75.3% among patients born in 1990-2002 vs 2003-2015; p<0.0001), but not among non-HLHS patients (65.7% vs 72.6%; p=0.22)-among whom several subgroups had a poor prognosis similar to HLHS. A total of 291/595 patients (48.9%) had Fontan surgery CONCLUSIONS: Surgery was refrained in one quarter of the patients, among whom almost all died shortly after birth. Long-term prognosis was largely determined during the first 2 years. There was a strong concordance between preoperative and postoperative survival. HLHS survival was improved, but non-HLHS survival did not change significantly. This study demonstrates the complications and outcomes encountering newborns with UVH at all major stages of preoperative and operative treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypertension after heart transplantation (HTx) is common. We investigated predictors of and mechanisms for hypertension development during the first year after HTx, with particular attention toward immunosuppressive agents, reinnervation processes, and donor/recipient sex., Methods: Heart transplant recipients (HTxRs) were consecutively enrolled 7 to 12 wk after surgery and followed prospectively for 12 mo. Ambulatory blood pressure recordings and autonomic cardiovascular control assessments were performed at baseline and follow-up. Possible predictors of posttransplant hypertension development were investigated in bivariate linear regression analyses followed by multiple regression modeling., Results: A total of 50 HTxRs were included; 47 attended the follow-up appointment at 12 mo. Mean systolic and diastolic blood pressure increased significantly during the observational period (systolic blood pressure from 133 to 139 mm Hg, P  = 0.007; diastolic blood pressure from 81 to 84 mm Hg, P  = 0.005). The blood pressure increment was almost exclusively confined to HTxRs with a female donor heart, doubling the cases of systolic hypertension (from 6 to 13/14; 46% to 93%, P  = 0.031) and diastolic hypertension (from 7 to 14/14; 54% to 100%, P  = 0.031) in this subgroup. Autonomic cardiovascular control assessments suggested tonically constricted resistance and capacitance vessels in recipients with female donor hearts. Immunosuppressive agents and reinnervation markers were not associated with hypertension development., Conclusions: Blood pressures increase during the first year after HTx, with female donor sex as a strong predictor of recipient hypertension development. The underlying mechanism seems to be enhanced peripheral vasoconstriction caused by attenuated cardiovascular homeostasis capabilities. Further studies are needed to confirm the results., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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) ms 2 (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) ms 2 (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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Purpose: The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives., Participants: In 1972-1975, 2014 healthy men, 40-59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017., Findings to Date: The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain ('silent ischaemia'), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors., Future Plans: Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens., Competing Interests: Competing interests: JB is an epidemiologist employed by AstraZeneca. SEK has within the past 3 years received ad hoc lecture honoraria from Getz, Intas, Merck KGaA and Sanofi., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Heart transplantation (HTx) surgically transects all connections to the heart, including the autonomic nerves. We prospectively examined signs, timing and consequences of early sympathetic and parasympathetic sinoatrial reinnervation, as well as explored indirect evidence of afferent cardiopulmonary reinnervation., Methods: Fifty HTx recipients were assessed at 2.5, 6, and 12 mo after HTx. For comparison, 50 healthy controls were examined once. Continuous, noninvasive recordings of hemodynamic variables and heart rate variability indices were performed at supine rest, 0.2 Hz controlled breathing, 60° head-up-tilt, during the Valsalva maneuver and during handgrip isometric exercise., Results: In HTx recipients, supine low-frequency heart rate variability gradually increased; supine high-frequency variability did not change; heart rate variability indices during controlled breathing remained unaltered; heart rate responses during tilt and isometric exercise gradually increased; the tachycardia response during Valsalva maneuver increased, while the bradycardia response remained unchanged; and indices of baroreflex sensitivity improved. Responses remained low compared to healthy controls. A negative correlation between indices of preload and heart rate response during head-up tilt emerged at 12 mo., Conclusions: Results suggest that sympathetic reinnervation of the sinoatrial node starts within 6 mo after HTx and strengthens during the first year. No evidence of early parasympathetic reinnervation was found. Indirect signs of afferent reinnervation of cardiopulmonary low-pressure baroreceptors emerged at 12 mo. Better sympathetic sinoatrial control improved heart rate responsiveness to orthostatic challenge and isometric exercise, as well as heart rate buffering of blood pressure fluctuations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Patients with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. The mechanisms and disease development are unclear and early secondary liver cancer is a concern. This study will describe hepatic imaging findings in a national cohort of adolescents with Fontan circulation., Methods: The patients prospectively underwent abdominal contrast enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging. Images were assessed for criteria of fibrosis/cirrhosis including characterization of hepatic nodules. These nodules were in addition, assessed by ultrasonography (US). Nodules ≥ 1 cm were investigated and monitored to evaluate malignant transformation. Clinical and hepatic serological data were recorded., Results: Forty-six patients, median age of 16.5 years (15.4-17.9 years) were enrolled. All patients underwent US examination and MRI was performed in 35/46 patients. On MRI, 60% had hepatomegaly and 37% had signs of fibrosis/cirrhosis. Seven patients had together 13 nodules ≥ 1 cm in diameter. Only 4/13 (17%) where seen on US. Nodules had variable MRI signal characteristics including hepatobiliary contrast enhancement and two nodules revealed portal venous phase 'wash-out' on the first examination. No further imaging signs of malignancy were revealed during the follow-up period of median 24.4 (7-42) months., Conclusion: The majority of adolescents with Fontan circulation had imaging findings of fibrosis/cirrhosis of varying severity. US had low detection rate of hepatic nodules compared to MRI. The imaging work-up before transition to adult cardiology care did not reveal findings suggestive of malignancy. However, the high prevalence of Fontan-associated liver disease calls for surveillance strategies even in childhood.

Background: Children with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. Reliable noninvasive monitoring techniques are lacking or under development., Objective: To investigate surrogate indicators of hepatic fibrosis in adolescents with Fontan circulation by evaluating hepatic magnetic resonance (MR) T1 mapping and extracellular volume fraction measurements compared to US shear-wave elastography., Materials and Methods: We analyzed hepatic native T1 times and extracellular volume fractions with modified Look-Locker inversion recovery. Liver stiffness was analyzed with shear-wave elastography. We compared results between 45 pediatric patients ages 16.7±0.6 years with Fontan circulation and 15 healthy controls ages 19.2±1.2 years. Measurements were correlated to clinical and hemodynamic data from cardiac catheterization., Results: MR mapping was successful in 35/45 patients, revealing higher hepatic T1 times (774±44 ms) than in controls (632±52 ms; P<0.001) and higher extracellular volume fractions (47.4±5.0%) than in controls (34.6±3.8%; P<0.001). Liver stiffness was 1.91±0.13 m/s in patients vs. 1.20±0.10 m/s in controls (P<0.001). Native T1 times correlated with central venous pressures (r=0.5, P=0.007). Native T1 was not correlated with elastography in patients (r=0.2, P=0.1) or controls (r = -0.3, P=0.3). Extracellular volume fraction was correlated with elastography in patients (r=0.5, P=0.005) but not in controls (r=0.2, P=0.6)., Conclusion: Increased hepatic MR relaxometry and shear-wave elastography values in adolescents with Fontan circulation suggested the presence of hepatic fibrosis or congestion. Central venous pressure was related to T1 times. Changes were detected differently with MR relaxometry and elastography; thus, these techniques should not be used interchangeably in monitoring hepatic fibrosis.

Objective: We investigated bone mineral density (BMD) at different ages after the Fontan completion, and we evaluated the relationship between BMD, vitamin D levels, and pertinent patient variables., Methods: A cross-sectional sample of 64 patients was examined with dual-energy X-ray absorptiometry (DXA) scans to determine BMD. Of these patients, 24 were also examined with BoneXpert software to determine bone mass density (BMX), expressed as the bone health index (BHI). Blood samples from all patients were analyzed. Patients were divided into three different age groups; A: 4-9 years old (n = 22), B: 10-15 years old (n = 21), and C: 16-18 years old (n = 21)., Results: Overall, BMD z scores were (mean ± SD): -1.0 ± 1.3 for the lumbar spine and -0.2 ± 1.2 for the total body. Groups B and C had significantly lower z score values compared to group A. Of patients in group C, 35% had z score values ≤-2 SD of the mean of the healthy population. There was no difference related to systemic ventricular anatomy (left or right); however, patients with lateral tunnels had lower BMD than patients with extra cardiac conduits. Overall, the BHI z score was (mean ± SD): -1.2 ± 0.9, but low BMX did not correlate with low BMD. The 25-hydroxy vitamin D level was 58 ± 30 nmol/L. Vitamin D levels decreased with age: in group C, 33.3% of patients exhibited vitamin D deficiencies. Vitamin D levels were not correlated with bone mineral densities., Conclusion: BMD levels decreased with age in patients with Fontan circulation. Different bone components were involved. Vitamin D levels also decreased with age, but they were not consistently associated with bone mineral densities. The single factor most predictive of low BMD was a lateral tunnel Fontan, compared to an extra cardiac Fontan., (© 2019 Wiley Periodicals, Inc.)

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.

Purpose: To determine if individuals chronically (>1 yr) prescribed antihypertensive medications have a normal BP response to peak exercise compared with unmedicated individuals., Methods: Participants included 2555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 yr were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the American Heart Association., Results: The unmedicated group had a greater prevalence ( P < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence ( P < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher ( P < 0.01) in medicated compared with unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP ( P = 0.613), risk factors ( P = 0.104), or cardiorespiratory fitness ( P = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP ( P = 0.039), but not for men ( P = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors, and cardiorespiratory fitness ( P = 0.022)., Conclusions: Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension., (Copyright © 2024 by the American College of Sports Medicine.)

We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30-45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score -0.4, 95% CI -2.8-0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

Unlabelled: The main purpose of this study was to investigate whether circulating natriuretic peptides in premature infants reflect the hemodynamic significance of a patent ductus arteriosus (PDA). The study comprises 120 examinations in 55 premature infants with a mean gestational age of 27.2 wk and a mean birthweight of 933 g. Based on clinical and echocardiographic findings, the hemodynamic influence of ductal shunting was classified as small, moderate or large. Blood samples for N-terminal proatrial natriuretic peptide (Nt-proANP) and brain natriuretic peptide (BNP) were analysed after completion of the clinical part of the study. Linear regression indicated a very strong association between Nt-proANP and BNP (adjusted R = 0.89). The mean levels of Nt-proANP and BNP increased with the size of the shunt through a PDA, and peptide values followed hemodynamic alterations. The size of PDA accounted for 50% and 47% of the total variation in the plasma values of Nt-proANP and BNP, respectively. In detecting an echocardiographically significant PDA, the area under a ROC curve was 0.94 for Nt-proANP and 0.90 for BNP.Conclusion: The magnitude of shunting through a PDA is the main determinant of plasma levels of natriuretic peptides in premature infants. Nt-proANP and BNP seem to have the same pattern of secretion. Our findings indicate that measurements of natriuretic peptides may provide clinically relevant information in the hemodynamic assessment of premature infants. [ABSTRACT FROM AUTHOR]

Unlabelled: Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development.Conclusions: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition. [ABSTRACT FROM AUTHOR]

Objectives: A marked, sequential decline in coronary heart disease (CHD) mortality is established, but not its causes. Does it reflect modern treatment effects or a spinoff of primary prevention? The aim of this study was to explore this issue using a prospective cohort follow-up design.Design: In 1972-1975 and 1980-1982 Cohorts 1 (n = 613) and 2 (n = 667) of identical age (males, mean 56 years) were examined, and thereafter followed closely for 14 years. CHD risk- and treatment patterns, incidence of non-fatal myocardial infarctions (MIs) and total-, cardiovascular and CHD mortality rates were studied.Results: CHD risk factors were more favourable, medical treatment more aggressive and 14-years CHD mortality, as expected, lower in Cohort 2 (7.7%/4.8%, p = 0.032). However, hospital- and prospective ECG data revealed opposite trends in non-fatal cohort CHD incidence, and aggregated numbers of CHD deaths and non-fatal MI cases were 16.7%/16.0% in Cohort 1/2 (p = 0.90).Conclusions: A marked, sequential reduction in CHD mortality was followed by a reciprocal increase in non-fatal MIs. This phenomenon may prevail in low CHD-endemic areas, and may call for altered primary preventive measures for reduction in total CHD incidence. [ABSTRACT FROM AUTHOR]

Plasma levels of natriuretic peptides are used as diagnostic markers of heart failure. The aim of this study was to analyse the relation between plasma levels of N-terminal proatrial natriuretic peptide (Nt-proANP) and renal function, and to develop reference values in children. Nt-proANP was measured in the plasma of 86 patients whose glomerular filtration rate (GFR) was determined by use of the X-ray contrast medium iohexol and a fluorescence technique. Blood samples for Nt-proANP were also collected in 399 reference children, aged 0-15 years. The relationship between Nt-proANP and GFR was examined using a multiple regression analysis. The mean value of Nt-proANP was markedly higher in children with heart failure than in children with malignant or urologic diseases (p<0.001). The variability in plasma levels of Nt-proANP was mainly (adjusted R[sup 2]=0.81) explained by the following four variables: presence of heart failure, GFR, age and previous treatment with anthracyclins. Plasma levels of the peptide are raised at birth, but fall rapidly to adult levels. We conclude that the plasma levels of Nt-proANP are age-dependent. Moderately elevated values were registered in children with severe renal impairment. Heart failure is regularly associated with excessive elevation of Nt-proANP in plasma. Our findings suggest that the influence of heart failure on levels of this peptide in children greatly exceeds the influence of renal dysfunction. [ABSTRACT FROM AUTHOR]

Aims Since atherosclerosis is a chronic inflammation and the erythrocyte sedimentation rate is an appropriate test for monitoring chronic inflammatory responses, we wanted to investigate whether the erythrocyte sedimentation rate might carry prognostic information on the risk of sustaining coronary heart disease events.Method The erythrocyte sedimentation rate was determined in 2014 apparently healthy men aged 40–60 years during an extensive cardiovascular survey in 1972–75, and the test was repeated in an identical follow-up examination 7 years later. Cause-specific mortality and rates of non-fatal myocardial infarction were followed for 23 years.Results The erythrocyte sedimentation rate was strongly correlated with age, haemoglobin level, smoking status, total cholesterol level and systolic blood pressure. After adjusting for all these associations in multivariate Cox regression analyses, the erythrocyte sedimentation rate emerged as a strong short- and long-term predictor of coronary heart disease mortality, particularly in men who had developed angina pectoris and/or had a positive exercise ECG test at the second survey. Increases in non-coronary heart disease deaths and in non-fatal myocardial infarctions were only seen in the upper erythrocyte sedimentation rate range.Conclusions The erythrocyte sedimentation rate is a strong predictor of coronary heart disease mortality, and appears to be a marker of aggressive forms of coronary heart disease. The erythrocyte sedimentation rate probably gives substantial information in addition to that given by fibrinogen on the risk of coronary heart disease death. [ABSTRACT FROM PUBLISHER]