The clinical significance of isolated systolic hypertension with normal central blood pressure known as spurious hypertension (sHT) in adolescents and its evolution over time is not known.The aim of this study was to analyze changes in office, ambulatory blood pressure (ABPM), central systolic blood pressure (cSBP), hemodynamic parameters, and target organ damage (TOD) over a 1-year follow-up in a group of non-obese children with sHT.Of 294 patients referred for primary hypertension, 138 patients  had hypertension confirmed by ABPM. 48/138 (35%) patients  were diagnosed with sHT ; 43 of them  were followed for 12 ± 3 months during non-pharmacological therapy. At baseline 7 (16%) patients had borderline values of cIMT or LVMi indicating mild TOD. After 12 months, 10/43  patients developed sustained HT , 11/43  maintained sHT, and 22/43  evolved to white coat hypertension or normotension. The cSBP values increased in 27 patients , but the group average remained in the normal range. Prevalence of TOD did not change during observation. The multivariate regression analysis showed that the only predictor of cSBP change over time was a change in serum uric acid level.In conclusion, after 1 year of non-pharmacological treatment, 23% of adolescents with sHT developed sustained hypertension, with the main predictor of cSBP change being the change in serum uric acid.The online version of this article (10.1007/s00467-020-04731-z) contains supplementary material, which is available to authorized users. Spurious hypertension (sHT) is a phenotype of primary hypertension (PH) defined as elevated office and ambulatory systolic blood pressure (SBP), yet maintaining normal central systolic blood pressure (cSBP) and presents clinically as isolated systolic hypertension (ISH). sHT was originally described by O’Rourke et al. in a group of 6 adolescent and young adult males aged 14–23 years who all had office ISH with normal cSBP, none of whom presented with hypertensive target organ damage (TOD) [Because ISH is the dominant hemodynamic phenotype in children with PH and males dominate among hypertensive children, it is important to assess the risk associated with ISH and normal cSBP in youth with PH.To date, only a few studies have assessed the prevalence of sHT among adults with ISH and its clinical relevance. Studies by Saladini et al. and Palatini et al. showed that sHT in young adult males is a mild condition and patients with sHT are at a low risk of developing sustained hypertension 15.2%), similar to the normotensive population 14.7%). Thus, it was proposed that subjects with sHT and low cardiovascular risk do not require extensive diagnostics and pharmacological treatment , 4. The .7%. Thus.2%, simiAlthough ISH is the predominant hemodynamic phenotype of PH in children and young adults, there are only single reports on the prevalence and association of sHT and TOD among adolescents. Previously we showed that 35% of children with office and ambulatory (ABPM) hypertension had brachial systolic hypertension with normal cSBP, i.e., fulfilled criteria of sHT and had a lower risk of TOD . They alThe aim of our study was to analyze the longitudinal changes of office, 24-h ABPM, cSBP, hemodynamic and TOD parameters over a 1-year follow-up period in a group of children with sHT.This study was approved by the Bioethical Commission of the Children’s Memorial Health Institute. All patients and their parents gave informed consent. The study meets the criteria of the 1975 Declaration of Helsinki revised in 2013. The study subjects were recruited from a cross-sectional, previously reported study –12.n = 138; 31 girls; 22%), 48 (35%) patients  presented with sHT phenotype  and 90 (65%) patients had true hypertension . Out of 48 patients with sHT, 43  with median age 16.7 (8.5–17) years were followed for 12 ± 3 months during non-pharmacological therapy and were included in the current study; 5 were lost to follow-up  patients were diagnosed with white coat hypertension (WCH) and 29 (10%) patients with ambulatory prehypertension (AmbPreHT). In the group of patients with both office and 24-h ambulatory hypertension  system device. It has been validated against applanation tonometry systems (Sphygmocor®) and invasive measurements of cSBP and was found to be a reliable and simple alternative to tonometry , 14. MorPWA enables calculation of parameters describing the characteristics of the arterial system including cSBP, augmentation pressure (AugPress), augmentation index (AugInd), central pulse pressure (cPP), cardiac output (CO), cardiac index (CI) and total peripheral resistance (TPR). PWA and cSBP assessed by oscillometric measurements with Vicorder were validated against SphygmoCor and obtained results did not differ between the two methods . We used2.7.All measurements were performed according to the American Society of Echocardiography guidelines. To standardize left ventricular mass to height, LVMi was calculated according to the de Simone formula , 19. LVHThe cIMT measurements were performed using the Aloca Prosound Alpha-7 machine (5.5–12.5 MHz) in accordance with Mannheim Consensus recommendations. The obtained results were averaged independently for the right and left common carotid arteries; the average value for both sides was then converted into SDS based on pediatric normative values . Values The blood used for assessment of plasma glucose levels, lipid profile and serum uric acid (UA) levels, was taken after 12 h of fasting. We used unit c501 as a biochemistry analyzer for spectrophotometric, immunoturbidimetric and ion-selective determination of the above biochemical parameters.All the tests were performed at baseline and after 12 ± 3 months.Calculation of power size to detect change in effect size of 0.5 in longitudinal analysis in paired test showed 89% power in paired test for 43 patients. However, it was lower for comparison 10 vs. 33 patients in unpaired test. Thus, additional tests (Cohen effect size) were done to improve sensitivity of statistical analysis.cSBP and 24-h ABPM were expressed in absolute values as mmHg. We also calculated the index of the patient’s 24-h SBP and DBP value to the upper limit of normal (95th percentile); an index > 1.0 represents abnormal/elevated values in relation to the 95th percentile of normal values. Twenty-four-hour mean arterial pressure (MAP) values were presented as absolute (mmHg) and standard deviation score (SDS) values. SDS values were calculated using LMS method and were based on normative ABPM data published by Wuehl et al. . The chat test  or paired Wilcoxon test .Categorical variables before and after treatment were compared using the McNemar test, categorical variables between two independent groups (change in cSBP and change from sHT to tHT status) were compared using Chi-square test. All continuous variables were checked for normal distribution using the Shapiro-Wilk test. Normally distributed variables are presented as mean ± SD; non-normally distributed variables are shown as medians with interquartile ranges. For pairwise repeated measure comparisons of parameters before and after treatment, we used paired t test ; non-parametric variables were presented as medians and IQR  of all (parametric and non-parametric variables), which, unlike significance tests, is independent of sample size. Cohen d ≤ 0.2 can be considered a “small” effect size, 0.5 represents a “medium” effect size, and 0.8 a “large” effect size [Independent measures of two subgroups were compared using an unpaired R Tables  and 3, bect size . Three vp value  was adjusted for multiple testing using Bonferroni correction, by dividing the obtained p values by the number of performed tests (indicated below each table). Statistics were performed using Python  [The threshold of a significant ingouin) .After 12 ± 3 months, patients’ height increased, whereas BMI-SDS decreased. There were no significant changes during the observation period in biochemical and TOD parameters and the 24-h SBP, DBP, and MAP decreased over time (Table n = 27) also increased heart rate, cardiac output, PWV SDS, cholesterol and serum uric acid concentrations (Table d = 1.05) on the change of cSBP, the change in following variables had a medium to large effect size (Cohen d = 0.5 to 0.8) on the change of cSBP: heart rate, cardiac output, PWV SDS, PWV, cPP, AugPress, cardiac index, weight, LVMi, BMI, stroke volume, and cholesterol .Twenty-seven patients 63%) increased their cSBP over study period, 12 (28%) patients had an elevated cSBP > 1.0 after 12 months of follow-up  developed tHT with elevated 24-h ABPM and cSBP values after 12 months, 22 evolved to WCH or normotension, and 11 maintained their status of sHT.d > 0.8), whereas the effect size of the change of 24-h, peripheral and central pulse pressure, HDL-cholesterol, triglycerides, PWV, and cardiac index was medium to large (Cohen d = 0.5–0.8)  of the change of cSBP.In the multiple regression analysis we did not analyze BP-related parameters , since cSBP is derived from measurements of peripheral BP; i.e., the inherent relationship between peripheral and central BP may represent a potential bias in the prediction of cSBP. The multivariate regression analysis of the top three non-BP-related parameters with the highest effect size on univariate analysis  in 7 of 43 (16%) patients  patients had mildly increased cIMT (above 95th percentile), arterial stiffness (assessed as PWV) was increased (> 97th percentile) in 17 of 43 (40%) patients and elevated LVMi (> 95th percentile) indicating mild LVH  patients maintained (11 subjects) their sHT status or normalized peripheral and central BP (22 subjects). The main determinant of change in BP status was the change in serum UA concentration. These findings suggest that ISH and normal cSBP in adolescents is a heterogenous condition, and in a significant proportion of subjects is associated with the risk of development of sustained hypertension and hypertensive TOD, thus requiring close monitoring. These are novel findings, based on analysis of both peripheral and central blood pressure, and to our knowledge, this is the first prospective pediatric study which includes only adolescents and not adults, and included the greatest number of sHT cases described so far.Starting from the first report of O’Rourke et al., several studies on ISH with normal cSBP were conducted in so-called young adults and included both adolescents and adults . Mahmud The finding that 23% of subjects in our study increased their cSBP, i.e., became true hypertensive, is higher than in prospective studies of young adults, in whom the risk of developing sustained hypertension needing treatment was rather low (15.2%) and similar to the control group (14.7%) .Saladini et al. found that among young adults with ISH and normal cSBP the long-term risk of developing sustained hypertension and needing treatment seems to be directly related to the level of cSBP, as 50% of patients with cSBP above normal at baseline developed sustained hypertension stage 2) as compared with only 15.2% of patients with a lower cSBP at baseline . Our 43  as compaMild TOD, mainly in the form of increased PWV was found in 7 of 43 (16%) patients at study start. As reported previously, patients with ISH and normal cSBP had lower prevalence of LVH and lower values of cIMT and PWV than those with elevated cSBP . The finMMP-14 in peripheral blood leucocytes of hypertensive children [MMP-14 is involved in arterial remodeling and enhances MMP-2 activity, which has been found to be the most significant marker of matrix metalloproteinases/tissue inhibitors of the matrix metalloproteinase system activation in hypertensive children [The main determinant of change of cSBP over time was the change of serum UA concentrations. The role of UA in the pathogenesis of PH is well described and elevated serum UA levels are typical for adolescents with PH , 32. Morchildren . This machildren , 35. Incchildren . The asschildren .In contrast to our previous studies we did not find any changes in BMI or WC, both expressed in absolute and standardized values, as predictors of cSBP change. However, it must be underlined that subjects from this study had relatively normal BMI and WC values which were close to the median of the population norm (BMI-SDS and WC-SDS both below 1.0) and had lower BMI and WC than patients with ISH and elevated cSBP, as reported previously .According to O’Rourke’s hypothesis , ISH witOur study has several limitations. Firstly, although we prospectively analyzed the greatest number of patients with sHT reported so far, the number of study subjects was relatively low. Moreover, the role of sex was difficult to analyze due to the low number of females. Secondly, the observation period was limited to 1 year, which may not be long enough to develop any significant changes in hemodynamic and TOD parameters. However, as changes in the ABPM blood pressure status in adolescents are described , cSBP chThe strength of our study stems from the fact that it is the first prospective pediatric study to include an unselected group of adolescents who were referred for work-up of PH and in whom a comprehensive assessment of hemodynamic parameters including ABPM, cSBP, TOD assessment, and laboratory investigations was done. Second, this is the largest prospective study to date analyzing the evolution of ISH with normal cSBP. Third, all subjects had all tests completed at baseline and after 1 year of follow-up. Fourth, although unselected and consecutively referred, our patients were relatively lean, non-obese, which allowed us to study the impact of factors not related to obesity.Our findings document that ISH with normal cSBP is not benign and may progress to elevated cSBP in a significant proportion (23%) of patients. The main determinant of change of cSBP over time was the change of serum UA concentration. Thus, our results suggest that adolescents with ISH and normal cSBP are a heterogenous group and that metabolic abnormalities play a significant role in the rise of cSBP, even in the cohort of non-obese hypertensive children. cSBP is not routinely measured in hypertensive children and adolescents, and management depends on hypertension severity and presence of TOD. Although there is a relationship between brachial blood pressure and cSBP—the higher the brachial blood pressure, the greater the probability of an elevated cSBP—almost one third of our patients with severe ambulatory hypertension had normal cSBP . Thus, aESM 1(DOCX 14 kb)


Background: Community pharmacies in many countries around the world provide healthcare services for patients. Pharmacists trained as medication experts provide a wide range of patient care services related to medication therapy, patient education, disease prevention, and health promotion. Professional training, expertise, and skills qualify pharmacists to engage in health screenings. These screening programs performed by community pharmacists can help to identify risk factors, facilitate early detection of common diseases, and assist physicians with making effective diagnoses. Objectives: In this study, we created and tested a novel model to provide professional monitoring and counseling on blood pressure by community pharmacists. The aims of the study were to identify the prevalence of elevated blood pressure among patients visiting a community pharmacy and describe the demographic characteristics of patients with hypertension . Methods: The research project was conducted in an accredited community pharmacy in Poznan, Poland, from January to April 2019. A total of 118 anonymous patients (30.5% men and 69.5% women) participated in this study. To qualify for this study, participants had to be older than 18 years of age and have no previous diagnosis of hypertension or other cardiovascular disease. Results: Based on the blood pressure screenings, 61.9% of patients were qualified for the standard consultation , 21.2% for the intensive consultation , 16.9% patients with elevated blood pressure for the high-risk consultation (HRC: referred to a physician), and 3.4% received a diagnosis of hypertension. We qualified 35.6% with a high-pressure value (greater than 140/90 mmHg). Conclusions: The novel model for blood pressure control screening and counseling implemented in a generally accessible community pharmacy may help with early detection of hypertension problems, lead to initiation of effective patient counseling by a community pharmacist, and result in early referral of the patient to a physician. A globally observed increase in the burden of hypertension is a serious public health problem. Although the percentage of patients treated for hypertension, especially patients achieving the treatment goal, has more than doubled, it is still lower in Poland than the average in western Europe, the USA, and Canada . TherefoThe incidence of hypertension and its complications is very high in many countries around the world. With the increase in life expectancy and rapid urbanization, even greater prevalence of hypertension is expected in the future. In 2015, 1.13 billion people suffered from hypertension . In PolaCounseling provided by pharmacists is an important step toward improvement of disease control and outcomes and, eventually, the overall health and wellbeing of patients, improved quality of life, and better understanding of medicines and diseases . A commuIn Poland, involvement of pharmacists in performing simple diagnostic screenings related to pharmacotherapy is encouraged. Unfortunately, there are no procedures or protocols to guide cooperation between pharmacist and patient during the measurement of blood pressure in a community pharmacy. To address this need, we established our model of blood pressure measurement in a community pharmacy.We aimed to implement and test the new blood pressure screening model in a community pharmacy setting and assess the prevalence of elevated blood pressure and common risk factors for hypertension among patients visiting the community pharmacy. In addition, we attempted to evaluate the effectiveness of blood pressure screening services provided by community pharmacists.Research was conducted between January and April 2019 in a community pharmacy in Poznan, Poland. Study participants were randomly selected from patients who visited the community pharmacy as customers and were informed about the possibility of receiving free blood pressure screening. Individuals who agreed to having their blood pressure measured in the pharmacy were enrolled in this study. Participants had to meet two inclusion criteria: over the age of 18 years and no previous diagnosis of hypertension. Each participant was explained the scope of the study and informed that they could resign from further participation at any stage of the research project. A written consent was obtained from each participant. Three pharmacists were familiarized with the study protocol and trained by the investigators on implementation of the patient-counseling model during the blood pressure screenings in the community pharmacy. The new counseling model is presented in Participation in this study was anonymous. All collected data were securely stored in the Department of Pharmaceutical Technology, Pharmacy Practice Division at Poznan University of Medical Sciences. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee 1146/18.p < 0.05.The Statistica PL 12 (StatSoft) package was used to perform the statistical analysis. The correlations between analyzed nominal data were performed by Chi-square test of independence. All statistical analyses were performed at p = 0.0001). The calculated BMI (body mass index) of patients enabled us to observe a direct proportional relationship between the calculated BMI and the blood pressure values presented in p = 0.0001). A significant relationship between the BMI and age (p = 0.0018), and number of risk factors (p = 0.001) is presented in p < 0.0001).A total number of 118 participants were included in screenings for blood pressure in a community pharmacy (69.5% women and 30.5% men). p = 0.0380; p = 0.0003). The mean value of systolic and diastolic pressure in people diagnosed with hypertension was the highest among participants referred to a physician and was 164/100 mmHg . Additional analysis of results by age, sex, and education showed no statistically significant differences.Regarding the HRC patients, 50.0% of participants applied for a follow-up consultation in the pharmacy and 15.0% received recommendations for a more advanced health examination. We diagnosed 20.0% of patients with hypertension . Partici2, the pressure was >140/90 mmHg. Positive correlation between BMI values and prevalence of prehypertension and hypertension was previously reported in other studies [We focused on community-pharmacy-based screenings of blood pressure in individuals without previously diagnosed hypertension. Among 16.9% participants, we measured blood pressure above 140/90 mmHg. In 2018 during the May Measurement Month, world screening confirmed that 40.5% of screened individuals were not aware of the presence of elevated blood pressure ,12. As d studies ,14,15. L studies . SimilarAs a result of blood pressure screenings in a community pharmacy, 16.9% of participants with elevated blood pressure (≥140/90 mmHg) were unaware of it and were referred to a physician. In Poland, almost 40.0% of adults do not know their own blood pressure, and about 30.0% are unaware of having hypertension . EducatiOne of the most striking observations to emerge from the data was that out of 78 participants who were younger than 40 years of age and underwent blood pressure screenings, over 14.0% were assigned for HRC. Literature reports confirm that more often younger individuals are diagnosed with hypertension, especially when these individuals have obesity, high levels of uric acid, and hypertriglyceridemia ,21. In aEarly detection of hypertension allows for faster initiation of pharmacotherapy and other treatments. Community pharmacies, due to their easy accessibility to patients and qualified professional staff, are an ideal healthcare setting to perform screenings for the most common diseases. Currently in Polish community pharmacies, health screenings and counseling to improve early disease detection, health promotion, and associated education are unavailable ,24. TherThis screening program included a relatively small sample number of subjects older than 50 years of age, which is quite limited. One of the reasons may be adequate high prevalence of already diagnosed hypertension in this population. It should be emphasized that patients under the age of 40 years, as a group less exposed to chronic diseases, are at greater risk of suffering from undetected hypertension. Younger patients also ask for medical consultations less often. In the obtained results, over 14.0% of patients were qualified for the HRC, which seems to confirm the legitimacy of implementing screening services in places more accessible to patients, such as community pharmacies. Finally, data were collected in a single community pharmacy, so more detailed studies are needed in the future.


The present study evaluated how heart failure (HF) negatively impacts health-related quality of life (HRQoL) in hypertrophic cardiomyopathy (HCM) patients and explored the major clinical determinants associated with HRQoL impairment in this population.This was a cross-sectional single-center study of health-related HRQoL that included 91 consecutive patients with HCM. Evaluation was performed based on a comprehensive protocol that included the recommended diagnostic studies, as well as administration of the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ) (CV Outcomes Inc) as a health status measure.The cohort included 52 (57%) males, median age 58 (20–85) years. The median global KCCQ score was 67 (12.5–100) corresponding to a moderate impairment in HRQoL. There was an inverse correlation between the median global KCCQ score and NYHA class . Patients with pulmonary hypertension (PHT), defined as resting pulmonary artery systolic pressure of ≥ 45 mmHg, presented a significantly worse HRQoL as compared to those without PHT . The KCCQ score mildly correlated with age , history of syncope , estimated glomerular filtration rate (eGFR) , plasmatic creatinine  and urea levels , left ventricular (LV) end-systolic dimensions , maximal provoked intraventricular gradient , LV ejection fraction , average E/e′ , pulmonary acceleration time , pulmonary artery systolic pressure . In ordinal regression, the independent predictors of HRQoL were NYHA class and eGFR.Patients with HCM and HF present a moderate degree of alteration in HRQoL. This is especially true for patients with PHT and more severe functional impairment. Renal failure and NYHA class are potential markers of HRQoL in clinical practice. Health related quality of life (HRQoL) in patients with hypertrophic cardiomyopathy (HCM) is often overlooked in routine clinical practice.HCM is a genetically determined heart condition characterized by left ventricular hypertrophy (LVH) of various morphologies most often caused by mutations in sarcomere genes, which encode different components of the myocardial contractile apparatus . AccordiThe most frequent clinical manifestations in HCM patients are related to heart failure (HF), with exertional dyspnea occurring in over 90% of symptomatic patients , 4. MoreWhile frequently overlooked in routine clinical practice, HRQoL is a global measure of disease-related symptom burden and an important clinical objective. We need to acknowledge the fact that all therapeutical interventions ideally aim to improve both symptoms (translated into HRQoL) and prognosis. While there is abundant data regarding interventions and strategies to improve long-term prognosis, very little information is currently available on HRQoL and its determinant factors in HCM patients. In a tertiary center study, HCM patients had deteriorated HRQoL compared to the general population . InteresThe primary aim of the study was to evaluate the level of HRQoL in patients with HCM and HF from a national referral center. The secondary aims included the identification of predictors as well as potential differences in HRQoL between different subpopulations.We performed a cross-sectional single-center study including all consecutive HCM patients diagnosed according to current ESC guidelines who were referred for evaluation between June 2016 and January 2017 at the Expert Center for Rare Genetic Cardiovascular Diseases at “Prof. Dr. C. C. Iliescu” Institute for Cardiovascular Diseases. To be eligible for the study, patients had to present: (1) the sarcomeric form of HCM defined by a wall thickness ≥ 15 mm in any patient and/or ≥ 13 mm in family members of a confirmed HCM index case in one or more LV myocardial segments as measured by echocardiography that is not solely explained by abnormal loading conditions and (2) signs and/or symptoms of HF.Patients were excluded if other causes of LV hypertrophy (LVH) were strongly suspected or already confirmed  which included: inborn errors of metabolism , drug-induced LVH, mitochondrial disease, malformation syndromes or amyloidosis. Patient medical records were reviewed and the following data were included: age, sex, type of HCM—obstructive (HOCM) or non-obstructive (NHOCM), clinical examination findings, comorbid conditions, laboratory, electrocardiographic and imaging results.Patients participating in this study provided written and oral informed consent permitting use of patient medical information for research.All patients were administered the translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ) (CV Outcomes Inc) as a health status measure , 8. KCCQPatients were considered to present HOCM if an intraventricular gradient ≥ 30 mmHg in the resting state or after provocation maneuvers  was identified and NHOCM if they did not present such an intraventricular gradient. Estimated glomerular filtration rate (eGFR) was determined using the online version of the Modification of Diet in Renal Disease (MDRD) Study equation based on creatinine and patient characteristics. Transthoracic echocardiography image acquisition and measurements were performed according to current European Association of Cardiovascular Imaging (EACVI) guidelines and recommendations . LV ejecPatient characteristics for the entire group were summarized using the median  for continuous and ordinal variables and counts (percentage) for categorical variables. Normality of data was tested using the Shapiro–Wilk test.U test for continuous and ordinal variables and Fisher’s exact test for categorical variables.Data analysis was performed using non-parametric tests. Comparisons between 2 groups were performed using the Mann–Whitney The Jonckheere–Tepstra test followed by post-hoc pairwise analysis if the test was significant at the 0.05 level was used when considering more than two groups for continuous and ordinal variables. Non-parametric correlation analysis using Kendall’s tau-b correlation coefficient and ordinal regression analysis were conducted to identify variables that were associated with HRQoL. Variables with a significant Kendall’s tau-b correlation coefficient were initially considered in an ordinal regression model and reduced by backward elimination. A two-sided p value of less than 0.05 was considered statistically significant for all tests. IBM SPSS Statistics version 23  was used for data analysis.For the estimation of the mean KCCQ score with a presumed standard deviation of 20 points, with an error of ± 5 points and 95% confidence, we calculated a sample size of 64 patients.A total of 91 patients with HCM and HF were included. Baseline demographic and clinical characteristics data are summarized in Table The global HRQoL reflected by the median KCCQ score was 67 12.5–100) points corresponding to a moderate degree of impairment in HRQoL in our cohort. The symptom frequency assessment domain had the highest median score 75 (0–100) points while the lowest median score was 62.5 (12.5–100) points in the quality of life assessment domain , as well as NYHA class III patients, 90.6 versus 57.2 points (p = 0.001), but there were no significant differences between patients presenting class II and III NYHA symptoms, 65.6 versus 57.2 points p = 0.360) . They also presented significant differences in most of the questionnaire’s assessment domains: the physical limitation summary score, median 50 versus 75 points (p = 0.004), the quality of life summary score, median 50 versus 75 points (p = 0.026) and the social limitation summary score, median 58.3 versus 83.3 points (p = 0.033), while no significant differences were observed in the symptom frequency summary score, median 75 versus 81.2 points (p = 0.299). Patients with a permanent pacemaker presented lower scores in the symptom frequency summary score, median scores of 47.9 versus 81.2 points (p = 0.046), without any significant differences in global HRQoL, median KCCQ scores of 54.4 versus 69.2 points (p = 0.085), or any of the other questionnaire’s assessment domains. The study cohort included 7 patients with ICD (8.1%) and while these patients presented a trend towards a worse HRQoL with lower median KCCQ scores, the observed difference was not significant, 57.2 points versus 67 points, p = 0.67.There were no significant differences in HRQoL between patients with HOCM and NHOCM, both groups presenting similar median KCCQ scores . There were also no significant differences observed between the two groups in the questionnaire’s assessment domains: the physical limitation summary score, median 75 versus 66.6 points (p = 0.60), the symptom frequency summary score, median 87.5 versus 76.3 points (p = 0.126), the quality of life summary score, median 75 versus 50 points (p = 0.125) and in the social limitation summary score, median 75 versus 70.8 points (p = 0.598).The KCCQ score presented fair correlations with the eGFR (creatinine clearance), plasmatic urea level and NYHA functional class. The mean KCCQ score also presented weak but significant correlations with age, previous history of syncope, R wave amplitude in the aVL lead on resting ECG and various echocardiographic parameters: 2D-LV end-systolic dimensions, LVEF, average peak mitral inflow-to-mitral relaxation velocity ratio E/e’, pulmonary artery systolic pressure (PASP), pulmonary acceleration time (PAT) and maximal provoked intraventricular gradient Table .Table 4CWe also evaluated the potential differences between patients with the highest HRQoL, defined as patients belonging to the fourth quartile of distribution of the KCCQ score, and patients with the worst HRQoL, defined as patients belonging to the first quartile of distribution of the KCCQ score Fig. . Patient2 of 0.32, p < 0.001  as predictive factors for HRQoL quantified by means of the KCCQ score, with an adjusted R01 Table .Table 5OThe present study demonstrated that, even in the modern therapeutic era, patients with HCM and HF report a moderate degree of impairment in HRQoL.Patient reported outcome measures (PROM) are an important tool for understanding patients perception of their functional well-being and health status. The KCCQ is a valid, reliable and responsive health status measure for patients with HF and was demonstrated by many studies to be a clinically meaningful outcome in cardiovascular research, patient management and quality assessment . MoreoveOur findings are in agreement with previous studies that demonstrated a significantly worse HRQoL in the HCM patient population as compared to sex and age matched patients from the general population, including in specific patient populations such as implantable cardioverter defibrillators (ICDs) HCM recipients –14. ThouA nationwide study performed in Sweden recently demonstrates a markedly poor HRQoL in HCM patients with ICDs . AlthougIn the present study, significant gender differences in the global KCCQ score was observed, with a poorer global HRQoL as well as a higher symptom burden among females. This supports the concept that gender together with comorbidities may indeed determine a worse HRQoL.There are several issues impacting our data related to the HRQoL in patients with HCM and HF in this exploratory study that deserve mention. First and foremost, we had a small sample size, which may have limited our power to detect certain differences between patient subgroups. We also enrolled only inpatients, which could represent a source of bias and influence our interpretation of the data. Stress echocardiography was not performed systematically in every patient, which may have misclassified some patients as non-obstructive phenotypes, but all patients underwent provocation maneuvers . Cardiac magnetic resonance imaging data were only partially available and, as such, not used in the analysis, though certainly the refinement of data provided by this technique might have influenced our results.In conclusion, the present data extends our understanding beyond reaffirmation that patients with HCM and HF present at least a moderate degree of alteration in quality of life. This is especially true for patients with pulmonary hypertension and more severe functional impairment. Renal failure and NYHA class are potential markers of quality of life in clinical practice.


To analyze the levels of B-cell-produced antibodies in the vitreous humor of patients with or without diabetic retinopathy (DR) both qualitatively and quantitatively.  A total of 52 type 2 diabetes mellitus (T2DM) with DR patients and 52 control subjects without diabetes mellitus or inflammatory diseases were included in this prospective study. The levels of immunoglobulin (Ig)A, IgM, and IgG subtypes were measured using a magnetic color-bead-based multiplex assay. p < 0.001), but there was no significant difference in the 4 IgG subtypes between the two groups after Bonferroni correction. Pearson's correlation analysis revealed low negative correlations between levels of antibodies  and estimated glomerular filtration rate . Furthermore, multiple linear regression analysis yielded three equations to predict the concentrations of IgA, IgM, and total antibodies in the vitreous humor according to eGFR and other clinical variables .  The concentrations of IgA, IgM, and total antibodies in the DR group were significantly higher than those in the control group  and eGFR. Diabetes mellitus (DM) is a chronic metabolic disorder that is characterized by hyperglycemia, resulting in insulin resistance. According to the latest statistics, there are 463 million people currently with DM in the world, and this continues to rise . Type 2 B cells play key roles in the production of cytokines and antibodies in humans and mice , 11 and In the current study, the concentrations of B-cell-produced immunoglobulin (Ig)A, IgM, and IgG subtypes in vitreous humor of T2DM patients with DR and control subjects were analyzed. Furthermore, the correlations between the concentrations of these antibodies and clinical variables of DR were investigated.This prospective study was conducted from May 2018 to March 2020 in accordance with the tenets of the Declaration of Helsinki. This study obtained ethical approval from the local Research Ethics Committee of the Guangdong Provincial People's Hospital (Number: 2016232A) before conducting the study. Informed consent was obtained from all patients. A flow chart of included population and analyses is shown in μl of undiluted vitreous humor sample was used for the reaction and finally analyzed the fluorescence intensity from the immunoassay using the Bio-Plex™ 200 System .The Bio-Plex Pro™ Human Isotyping Panel, 6-plex kit  was used to measure the concentrations of 6 human antibodies, including IgA, IgM, IgG1, IgG2, IgG3, and IgG4. The experimental procedures were conducted according to the manufacturer's instructions. Next, 40 t-tests were performed to compare other clinical variables and concentrations of the antibodies between the two groups. Bonferroni-corrected significance threshold (p = 0.006) was used for the multiplicity of measurement of antibodies between the two groups. Pearson's correlation test was used to analyze the associations between the clinical variables and the concentrations of antibodies. Furthermore, multiple linear regression analysis was used to yield equations for calculating the concentrations of antibodies according to the clinical variables that are statistically significant in Pearson's correlation analysis. Sample size calculation was performed by using a web-based simple power/sample size calculation, UCSF Biostatistics: Power and Sample Size Programs, https://www.stat.ubc.ca/~rollin/stats/ssize/, α = 0.006 (after Bonferroni correction), power = 0.90, and two-sided test. A two-tailed p < 0.05 was considered to be statistically significant.Statistical analyses were performed using IBM SPSS statistics version 19.0 . One-way ANOVA was performed for evaluating the sex differences between the DR group and the control group. Data normality was confirmed by Shapiro-Wilk test. Independent, two-tailed Student's p < 0.001), while eGFR was significantly decreased (p < 0.001) when compared to those in the control group. There were no significant differences in other clinical characteristics including age, gender, systolic blood pressure, and diastolic blood pressure between the two groups .Fifty-two DR patients  and 52 non-DR subjects  were recruited, including 63 males and 41 females. Clinical characteristics of the DR and the control group are presented in p < 0.001). A detailed description on the levels of IgA, IgM, and total antibodies between the two groups was shown in p > 0.006 for all).The concentrations of B-cell-produced antibodies between the DR and the control group are shown in r = 0.317, p = 0.001) and negatively correlated with eGFR . The concentration of IgM was positively correlated with UACR  and negatively correlated with eGFR .There were low correlations between clinical variables and levels of B-cell-produced antibodies . The conMultiple linear regression analysis using clinical variables  was performed to predict IgA, IgM, and total antibody values, which yielded three equations:2), r = 0.542, p < 0.001, and standard error of estimate = 776.67 ng/ml.IgA (ng/ml) = −15.805∗age (years) − 11.342∗eGFR (ml/min/1.73 m2) + 0.447∗UACR (mg/g), r = 0.461, p < 0.001, and standard error of estimate = 1394.90 ng/ml.IgM (ng/ml) = −10.861∗eGFR (ml/min/1.73 m2), r = 0.312, p = 0.016, and standard error of estimate = 2019.53 ng/ml.Total antibodies (ng/ml) = 6749.95 − 14.473∗eGFR  and eGFR, a marker of kidney damage. These negative correlations suggested that kidney damage tended to be more severe in patients with stronger B-cell-mediated immune responses. Moreover, multiple linear regression yielded three equations for predicting the concentrations of IgA, IgM, and total antibodies in the vitreous humor according to eGFR, suggesting possible associations between retinopathy and nephropathy during the development of DM –29. The The present study for the first time reported that local humoral immune response was involved in the pathogenesis of DR in T2DM, suggesting that the B cells might play an important role in the development and progression of DR. However, there were several limitations that should be acknowledged in the current study. Firstly, the sample size is not large and the study is not randomized which may lead to selection bias. Although significant differences have been observed using the included number of samples, population-based randomized studies with large sample sizes are needed to validate the results of the present study. Secondly, it would be more convincing if a group of diabetic patients without DR was added. However, during patient recruitment, very few T2DM patients without DR who met the inclusion criteria were referred to our clinic. Thirdly, the concentrations of antibodies in the serum samples were not analyzed. Although the previous studies have proven that the levels of plasma antibodies were increased in DR , 35, it This study showed that higher levels of IgA, IgM, and total antibodies produced by B cells were detected in the vitreous humor of T2DM patients with DR. There were low negative correlations between concentrations of IgA and IgM in the vitreous humor and eGFR, indicating a potential relationship between retinopathy and nephropathy in T2DM. Further investigations are needed to verify the functional roles of B cells in DR and other microvascular complications of diabetes.


Dear Editor,The causal link between inflammatory bowel disease (IBD) and chronic kidney disease (CKD) is not clear; therefore, we aimed to investigate the role of gut microbiota in decreasing renal function in patients with IBD. IBD is characterized by the disruption of host–microbe relationships, and dysbiosis and the metabolites produced by the dysbiotic intestinal microbiome may negatively influence the renal function.2 for a minimum of 3 months.To reveal the connection between UC and CKD, we performed 16S ribosomal DNA sequencing using ileocecal mucosal samples from nine patients with both UC and CKD, 29 UC patients with normal renal function, and 12 healthy individuals who had normal colonoscopy results Table . The patThe bacterial operational taxonomic units of patients in the UC + CKD group were decreased but were not significantly different from those of the UC or control group Figure >. CommunActinobacteria exhibited the highest relative abundance in the UC + CKD group  showed the highest relative abundance in the UC + CKD group  by at least twofold compared to that of the untreated control samples (Figure R. pickettii contributed to the inflammation seen in an UC in vitro assay resembling the intestinal conditions of UC patients.Among several species of the s Figure . This suR. pickettii (Figure Ralstonia‐treated kidney organoids presented markedly increased expression of KIM‐1 compared to the untreated control samples (Figure R. pickettii treated kidney organoids compared to the untreated control samples, indicating damage within the kidney tubules (Figure KIM‐1 and CYR61 in the R. pickettii treated organoids was statistically significant (Figure Ralstonia treatment, indicating that virulence factors such as endotoxins can provoke renal dysfunction through the gut–kidney axis.To model the gut–kidney axis, we utilized a co‐culture of Caco‐2 cells and kidney organoids in a transwell system; the kidney organoids were not directly exposed to i Figure . Kidney s Figure . On the s Figure . Furthert Figure , and thet Figure . It is iRalstonia was significantly higher in the UC + CKD group at both the genus and species levels. The relative abundance of Ralstonia was positively correlated with serum uric acid level and negatively correlated with eGFR. Ralstonia is an aerobic, gram‐negative, nonfermentable rod, and an opportunistic pathogen that causes infections in immunocompromised hosts. Intestinal R. pickettii is associated with the significant increase in endotoxin levels and worsened glucose intolerance in obesity.In this study, we found that the abundance of In vitro studies utilizing clinical isolates of R. pickettii from fecal culture samples might also validate our findings.The limitations of this study include its cross‐sectional nature, relatively small number of patients, and relatively high variability in the microbial composition of each group. Additional studies with larger sample sizes might be necessary to confirm the findings of the present study. In addition, the results of this study will be strengthened by comparing the current data with those for the microbiome of patients with Crohn's disease and CKD, and CKD patients without IBD. Further studies are required regarding potential confounding factors such as contamination in the 16S rRNA microbiome studies.R. pickettii was negatively correlated with renal function in individuals with UC and associated with kidney‐specific disruptive features especially under the inflamed colon, suggesting that R. pickettii might play an important role in the pathogenesis of CKD in UC.In conclusion, the present study demonstrates a change in the microbial community in patients with UC and decreased renal function. All authors declare no conflict of interest.Supporting informationClick here for additional data file.


What are the safe and optimal diastolic blood pressure (DBP) ranges among adults with treated systolic blood pressure (SBP) of less than 130 mm Hg?In this cohort study of 7515 patients from 2 randomized clinical trials who had treated SBP of less than 130 mm Hg, a DBP of less than 60 mm Hg was associated with increased cardiovascular risk and a DBP between 70 and 80 mm Hg was associated with lower cardiovascular risk.The findings suggest that a DBP of less than 60 mm Hg may be harmful and a DBP between 70 and 80 mm Hg is an optimal target for patients with treated SBP of less than 130 mm Hg; this topic merits further study. This cohort study evaluates whether diastolic blood pressure (BP) among adults with treated systolic BP of less than 130 mm Hg is associated with all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke. Extremely low diastolic blood pressure has been reported to be associated with increased adverse cardiovascular events ; however, current US guidelines recommend an intensive blood pressure target of less than 130/80 mm Hg without mentioning the lower limits of diastolic blood pressure.To evaluate whether there is a diastolic J-shape phenomenon for patients with an treated systolic blood pressure of less than 130 mm Hg and to explore the safe and optimal diastolic blood pressure ranges for this patient population.This cohort study analyzed outcome data of patients at high cardiovascular risk who were randomized to intensive or standard blood pressure control and achieved treated systolic blood pressure of less than 130 mm Hg in the Systolic Blood Pressure Intervention Trial (SPRINT) and Action to Control Cardiovascular Risk in Diabetes–Blood Pressure (ACCORD-BP) trial. Data were collected from October 2010 to August 2015 (SPRINT) and from September 1999 to June 2009 (ACCORD-BP). Data were analyzed from January to May 2020.Treated diastolic blood pressure, divided in intervals of less than 60, 60 to less than 70, 70 to less than 80, and 80 mm Hg and greater.The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. A composite cardiovascular outcome, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, was among the key secondary outcomes.P = .004), the composite cardiovascular outcome , nonfatal myocardial infarction , and nonfatal stroke .A total of 7515 patients  were included in this analysis. The nominally lowest risk was observed at a diastolic blood pressure between 70 and 80 mm Hg for the primary outcome, the composite cardiovascular outcome, nonfatal myocardial infarction, and cardiovascular death. A mean diastolic blood pressure of less than 60 mm Hg was associated with significantly increased risk of the primary outcome (hazard ratio [HR], 1.46; 95% CI, 1.13-1.90; This cohort study found that lowering diastolic blood pressure to less than 60 mm Hg was associated with increased risk of cardiovascular events in patients with high cardiovascular risk and an treated systolic blood pressure less than 130 mm Hg. The finding that a diastolic blood pressure value between 70 and 80 mm Hg was an optimum target for this patient population merits further study. Results of the Framingham Heart Study have shifted the emphasis on diastolic BP (DBP) to systolic BP (SBP) by showing that SBP was a more important risk factor for cardiovascular outcomes.2 This has generated debate and relative neglect of the role of DBP in cardiovascular risk estimation.3 Whether there is a diastolic J-shape phenomenon, meaning that both high and low DBP could increase cardiovascular risk, is among the most controversial issues.High blood pressure (BP) is among the most important modifiable risk factors for cardiovascular disease and death.4 Although there are studies showing linear associations between DBP and cardiovascular risk,6 more studies have reported a diastolic J-shape phenomenon.15 It seems certain that extremely low DBP is harmful. However, mainly driven by the Systolic Blood Pressure Intervention Trial (SPRINT) trial,16 which showed improved prognosis with intensive SBP lowering, the 2017 American Heart Association (AHA) Hypertension Guidelines17 recommend an intensive BP target of less than 130/80 mm Hg, with no recommendation on lower limits of DBP. Intensive SBP lowering could result in an excessive reduction of DBP, generating concern that the therapeutic harm-benefit equation will shift to harm considering the potential diastolic J-shape phenomenon. To avoid potential harm, the 2018 European Society of Cardiology (ESC) Hypertension Guidelines have recommended an optimal DBP target of between 70 and 80 mm Hg for patients with all risk levels.18 Given the great influence of the 2017 AHA guideline and the argument that the diastolic J-shape phenomenon only exists in the presence of high SBP ,19 it is critical to know whether the diastolic J-shape phenomenon exists in patients with SBP of less than 130 mm Hg and, if it does exist, what the safe and optimal DBP ranges are for this population.Debate on the diastolic J-shape phenomenon originated from an observation of low DBP and increased risk of death from myocardial infarction.16 and the Action to Control Cardiovascular Risk in Diabetes–Blood Pressure (ACCORD-BP)20 trials randomized 14 094 patients to intensive BP control  and standard BP control . The objectives of the present study were, first, to determine whether a diastolic J-shape phenomenon was evident with treated SBP of less than 130 mm Hg and, second, to investigate the safe and optimal DBP ranges in the presence of a guideline-recommended SBP of less than 130 mm Hg, using outcome data from SPRINT and ACCORD-BP.The SPRINTSTROBE) reporting guideline. The designs and outcomes of SPRINT16 and ACCORD-BP20 have been reported previously, and data were acquired from the National Heart, Lung, and Blood Institute BioLINCC Repository.21 In brief, SPRINT was a randomized, single-masked trial with 9361 patients at high cardiovascular risk randomized to an SBP target of either less than 140 mm Hg (the standard treatment group) or less than 120 mm Hg (the intensive treatment group) for a median of 3.26 years. Patients enrolled were aged 50 years or older with an SBP of 130 to 180 mm Hg with increased risk of cardiovascular disease but without diabetes or a history of stroke. Increased cardiovascular risk was defined by 1 or more of the following: clinical or subclinical cardiovascular disease other than stroke; chronic kidney disease, excluding polycystic kidney disease, with an estimated glomerular filtration rate (eGFR) between 20 and less than 60 mL/min/1.73 m2 of body surface area, as calculated by the 4 variable Modification of Diet in Renal Disease equation; a 10-year risk of cardiovascular disease of 15% or greater on the basis of the Framingham risk score; or age 75 years or older.16 In the ACCORD-BP trial, 4733 patients were randomly assigned to either intensive  or standard  BP control for a median of 4.7 years. Patients enrolled were aged 40 to 79 years with type 2 diabetes and hemoglobin A1c concentrations of 7.5% or more  with history of cardiovascular disease or individuals aged 55 to 79 years with anatomical evidence of significant atherosclerosis, albuminuria, left ventricular hypertrophy, or at least 2 risk factors for cardiovascular disease.20 In SPRINT, targeting a SBP of less 120 mm Hg vs less than 140 mm Hg resulted in 25% reduction of adverse cardiovascular events.16 The results of ACCORD-BP showed no difference in the composite cardiovascular outcome but did find a decrease of stroke.20 The studies were approved by the institutional review board at each participating site, and written informed consent was obtained from all participants. The present study protocol was approved by medical ethics committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences. For this post hoc analysis, patients who did not have any recorded BP after randomization or had missing key covariates were excluded.This cohort study was reported in adherence to the Strengthening the Reporting of Observational Studies in Epidemiology . A mean of 3 subsequent BP measurements was recorded as baseline and follow-up BP. BPs were measured after 5 minutes of rest in both SPRINT and ACCORD-BP.23 BP measurements were scheduled at baseline, monthly for the first 3 months, and every 3 months thereafter in SPRINT. In the intensive group in ACCORD-BP, BP measurements were scheduled at baseline, every month for the first 4 months, and every 2 months thereafter; in the standard treatment group, BP measurements were scheduled at baseline, month 1, month 4, and every 4 months thereafter. For the present analysis, the treated SBP, DBP, and pulse pressure (PP) for each patient were computed by taking the mean of their BP measurement from month 3 to the last reading.In the SPRINTThe primary outcome of this analysis was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary outcomes included the individual components of the primary outcome, cardiovascular death, and a composite cardiovascular outcome including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.2 test for categorical data. HRs for all outcomes were analyzed by DBP category and tested for differences using Cox regression, adjusting for study, study group , and baseline patient characteristics . History of cardiovascular disease was defined as history of myocardial infarction, stroke, acute coronary syndrome, coronary artery bypass grafting or percutaneous coronary intervention, other revascularization , left ventricular hypertrophy, ankle brachial index of 0.9 or less, and at least 50% stenosis of artery. The association between mean achieved DBP and DBP changes from baseline as continuous variables with SBP of less than 130 mm Hg was also analyzed with restricted cubic splines that allow exploration of nonlinear associations.24 Likelihood-ratio test was used to assess whether the association was really nonlinear. To avoid potential reverse associations, we excluded patients with any primary or secondary events within 30 days after randomization. In addition, sensitivity analyses were conducted by excluding patients with mean achieved SBP of less than 110 mm Hg, by additional adjustment of baseline PP as a categorical variable (≥60 mm Hg or not) and baseline DBP in the Cox regression model, and by additional adjustment of baseline PP (≥60 mm Hg or not), baseline SBP, and achieved SBP in the Cox regression model. We also analyzed the association of intensive vs standard BP control with cardiovascular and mortality outcomes in a subgroup of patients with baseline DBP of less than 60 mm Hg in the ACCORD-BP and SPRINT trials separately. All analyses were done with SPSS statistical software version 20.0 (IBM Corp) and RStudio version 1.2.5033 . A 2-tailed P < .05 was considered statistically significant.Due to the similarity of the study design and study population, we combined data from the SPRINT and ACCORD-BP trials. To avoid potential bias by combining data from 2 different studies, we also analyzed data from the 2 trials separately. Patients with achieved SBP of less than 130 mm Hg were selected and divided into subgroups on the basis of their mean achieved DBP at the following cutoffs: less than 60, 60 to less than 70, 70 to less than 80, and at least 80 mm Hg, with 70 to less than 80 mm Hg as the reference . Groups were tested for differences using 1-way analysis of variance for continuous data and the χP < .001), had lower mean (SD) BMI , had lower mean (SD) baseline DBP , had higher mean (SD) baseline SBP , had lower mean (SD) LDL-C levels , had higher mean (SD) glycemic levels , were less likely to currently use tobacco , and more likely to have a history of cardiovascular disease . Full clinical and demographic characteristics grouped by treated DBP are presented in the In SPRINT and ACCORD-BP trials, we included 7515 patients (mean [SD] age 65.6 [8.7] years) with 4553 (60.6%) men . Most paP = .004), cardiovascular outcome , nonfatal myocardial infarction , and nonfatal stroke  was observed at DBP of less than 60 mm Hg. No significant associations were observed between achieved DBP of 80 mm Hg or greater and the primary outcome , all-cause death , nonfatal myocardial infarction , cardiovascular outcome , and cardiovascular death .The adjusted HRs for primary and secondary outcomes in different DBP groups are presented in To test the robustness of our results, we conducted sensitivity analyses. First, with analysis of data from SPRINT and ACCORD-BP trials separately, similar results were observed  (eTable 3 in the P = .003), all-cause death (P = .001), and nonfatal myocardial infarction (P = .049) were observed. Similarly, nonlinear associations between DBP change from baseline as a continuous variable and all-cause death (P = .006), nonfatal stroke (P = .02) and cardiovascular death (P = .03) were observed , nonfatal myocardial infarction, and cardiovascular death in this population.16 the 2017 AHA guidelines recommend an intensive BP target of less than 130/80 mm Hg without mentioning the lower limit of DBP.17 However, aggressively lowering SBP could result in a substantial reduction of DBP, counteracting the benefits of lowering SBP. Secondary analyses of SPRINT data showed that an excessively low achieved DBP was associated with a 25% increase in cardiovascular risk and even greater risk among patients with preexisting cardiovascular disease or chronic kidney disease.25 The linear association between DBP and outcomes reported in a previous meta-analysis was only observed at a DBP value of greater than 75 mm Hg,5 which might not have been low enough to observe the diastolic J-shape phenomenon. A post hoc analysis of the SPRINT study reported that even in the lowest DBP quintile , intensive BP lowering was associated with reduced risk of cardiovascular events  and all-cause death .26 However, the lowest quintile in the post hoc analysis of SPRINT may not have been low enough to reveal the potential hazardous effect, given that only 39.0% of patients achieved an treated DBP of less than 60 mm Hg in the lowest DBP quintile  in SPRINT  was associated with increased risk of cardiovascular events. However, many studies reporting the diastolic J-shape phenomenon32 also reported that a DBP of less than 60 mm Hg was associated with increased risk of cardiovascular events. Therefore, the present study’s findings  emphasized the need and provided an important hypothesis for future studies aiming to explore the lower boundary of DBP targets in this population.The biological plausibility for this phenomenon or the diastolic J-shape phenomenon has been proposed.Reverse causality has always been a concern regarding diastolic J-shape phenomena in observational studies. Because the present study is a secondary analysis of randomized clinical trial data, reverse causality is inevitably a concern. However, we used all appropriate measures to minimize the possibility of reverse causality, including excluding patients with outcomes occurring within 30 days after randomization, adjusting age and comorbid conditions, and conducting a series of sensitivity analyses. Similar results from these sensitivity analyses implied that the findings of the present study were unlikely to be simply an effect of reverse causality. However, due to the nature of retrospective observational studies, neither this study nor previous similar studies could establish a causal relationship between low DBP and risk of outcomes. Results of the present study only serve as a caution regarding lowering DBP to less than 60 mm Hg and as an important hypothesis to be tested in future prospective studies regarding safe and optimal DBP ranges.This study has limitations and strengths. First, the present study is a post hoc analysis of previous randomized clinical trials; therefore, the possibilities of reverse causality and unidentified confounding cannot be completely ruled out, although the sensitivity analyses and adjustments we did could have mitigated these possibilities. Second, lacking biomarkers of tissue injury, such as cardiac troponin, we were unable to reveal potential mechanism of the association of low achieved DBP and cardiovascular risk. Third, there were only 476 patients (6.3%) in the subgroup with DBPs of 80 mm Hg or greater, which might lead to the observed insignificant association of DBP with all outcomes in this subgroup. Therefore, results in this DBP group should be interpreted with caution, especially the outcome of nonfatal stroke. Fourth, our findings were generated from a cohort with high cardiovascular risk; therefore, it may not apply to the general population. The strengths of present study include its large sample size, its racially diverse population, and the use of mean treated BP rather than baseline BP or BP from observational studies, which are often affected by comorbid conditions.In this study, lowering DBP to less than 60 mm Hg was associated with increased risk of cardiovascular events in patients with high cardiovascular risk and an treated SBP of less than 130 mm Hg. The finding that a DBP value between 70 and 80 mm Hg was an optimal target for this patient population merits consideration and further study.


Ticagrelor is a drug widely used in patients with acute coronary syndromes (ACS) that specifically increases the plasma level of adenosine, which is likely to cause atrial fibrillation (AF). Therefore, in this study we aimed to investigate the electrocardiographic and echocardiographic predictors of AF development after P2Y12 receptor antagonists in ACS patients.This cross-sectional study included 831 patients with ACS . Patients were divided into ticagrelor (n = 410) and clopidogrel (n = 421) groups. P wave properties including P wave dispersion and atrial electromechanical conduction properties were measured as AF predictors with surface ECG and tissue Doppler imaging.Baseline characteristics such as age, sex, heart rate, blood pressure, and laboratory parameters were almost the same in the ticagrelor and clopidogrel groups. The statistical analysis showed no significant difference in P wave dispersion (PWD) between ticagrelor and clopidogrel groups . Subgroups analysis according to ACS types also showed no significant difference in PWD . In addition, we did not find significant difference in atrial electromechanical delay (EMD) with tissue Doppler imaging .In conclusion, we did not find any difference in detailed electrocardiographic and echocardiographic parameters as AF predictors between ticagrelor and clopidogrel groups in patients with ACS. Acute coronary syndromes (ACS) are one of the major causes of mortality and morbidity worldwide. Current guidelines recommend dual antiplatelet therapy in patients with ACS . Ticagrelor, one of the relatively new drugs used in ACS, is a reversible and direct-acting oral antagonist of adenosine diphosphate receptor P2Y12, and it was found superior over clopidogrel in the PLATO trial [3]. Although the benefit of ticagrelor has been attributed mostly to its faster, greater, and more consistent P2Y12 inhibition compared to clopidogrel, continuity of growing benefits of ticagrelor and its effect on reduction of cardiovascular mortality in the PLATO trial make it different from other P2Y12-ADP receptor blockers [3–5]. These differences led to the hypothesis that ticagrelor has pleiotropic properties and nonplatelet directed mechanisms of action. These effects of ticagrelor have been mostly attributed to increased half-life and plasma concentration of adenosine .Adenosine is a purine nucleoside primarily produced by endothelial cells [8] and it has a number of effects, such as coronary vasodilatation [9], inhibition of platelet aggregation [10], modulation of inflammation [11], reduced ischemia/reperfusion injury , and reduced atrioventricular conduction [14]. Besides some positive effects, it is also known that adenosine has the potential to cause atrial fibrillation (AF) [15–17]. In addition, there is a case report in the literature suggesting that ticagrelor could cause AF, a possible mechanism of which is increased plasma adenosine level [18]. However, there are no studies in the literature investigating the risk of AF in patients treated with ticagrelor. In this study, we aimed to determine whether ticagrelor predisposes to AF in ACS patients by using surrogate electro and echocardiographic parameters.This cross-sectional study was conducted between January 2016 and February 2017 on patients diagnosed with ACS, which consists of ST elevated myocardial infarction (STEMI) and non-ST elevated myocardial infarction (NSTEMI). STEMI is defined as having a typical angina that lasts 20 min or longer and with STEMI criteria in ECG [2]. Non-ST-elevation myocardial infarction is defined as a rise in troponin level (troponin-I > 0.06 ng/mL) with typical chest pain without STEMI criteria in ECG [1]. The treatment of the patients was arranged in line with the European Society of Cardiology guidelines. Patients were given 180 mg ticagrelor as the loading dose in the ticagrelor group. Angiotensin converting enzyme inhibitors, beta blockers, and statins were started in all patients without contraindication within the first 24 h after diagnosis. Patients were treated with percutaneous coronary intervention . Patients who needed coronary bypass surgery were not included in the study. The other exclusion criteria were as follows: atrial infarction diagnostic criteria described by Liu et al. [19], a history of AF, use of antiarrhythmic drug other than beta-blockers, renal dysfunction (creatinine >1.5 mg/dL), severe valvular heart disease, permanent pacemaker, cerebrovascular disease, and the need for mechanical ventilation. The study was conducted following the principles of the Declaration of Helsinki for Human Research and approved by the institutional ethics committee.Electro-echocardiographic evaluation was performed on patients who had been treated for a median of 2.5 days. A 12-lead surface ECG was obtained from all study participants nearly 2 h after the last dose of the clopidogrel/ticagrelor in the supine position before discharge and analyses were done with this ECG [20]. The point at which the first atrial deflection crossed the isoelectric line was defined as the beginning of the P wave and the return to baseline was considered as the end of the P wave.  Pmax and Pmin durations were measured for all patients in all 12 leads on the ECG. The difference between Pmax and Pmin durations on the ECG was defined as P wave dispersion (PWD) [21]. The laboratory tests included complete blood count, fasting glucose level, lipid profile, troponin level, liver, kidney, and thyroid function tests. The weight and height of the participants were measured, and the body mass index (BMI) (kg/m2) was calculated using the following formula: BMI = weight/(height)2. Echocardiographic examination and evaluation of patients were performed using Philips Healthcare iE33 xMATRIX Echocardiography  with an S5–1 transducer before discharge. Examinations were performed by a single experienced cardiologist who was blinded to the patients and their characteristics. Evaluation of the patients was performed in the left lateral decubitus position. A continuous one-lead ECG was obtained during all examinations. The average of three consecutive beats was used to calculate the associated parameters. M-mode echocardiography was used in the parasternal long-axis view to measure basic echocardiographic parameters, such as the left atrium (LA), left ventricular (LV) end-systolic and end-diastolic dimensions, LV ejection fraction (EF), and diastolic LV septal and posterior wall thickness. Electromechanical properties of the atria were determined by tissue Doppler imaging. Before the study, the Nyquist limit was adjusted to 15–20 cm/s and the monitor sweep speed was set at 50–100 mm/s to optimize the spectral display myocardial velocities. The pulsed doppler sample volume was placed at the LV lateral and septal mitral annulus, and subsequently at the septal mitral annulus and right ventricular tricuspid annulus in apical four chamber view. Atrial electromechanical delay (EMD) was considered as the time interval from the onset of P wave on ECG to the beginning of “A”-wave in tissue Doppler (PA). PA interval, which was measured from the lateral mitral, septal mitral, and tricuspid annulus was called PA lateral, PA septum, and PA tricuspid, respectively. PA intervals between the lateral and right ventricular annulus were accepted as interatrial EMD, the difference between the septal and tricuspid PA intervals as right intraatrial EMD, and the difference between the lateral and septal PA intervals as left intraatrial EMD. The data were analyzed using SPSS 18.0 statistics package . Normally distributed continuous variables were expressed as means ± standard deviation, while continuous variables with a nonnormal distribution were expressed as median and interquartile ranges (IQR). Student’s t-test or the Mann–Whitney U test were used to compare the means or medians of groups, respectively. Categorical data were expressed as proportions and compared using the chi-square test. The relationship between antiplatelet types and P wave duration, PWD, PR interval, P wave axis, and EMD values was assessed by ANCOVA analysis by removing the effects of confounding factors that were significant in the antiplatelet and ACS types. P-values less than 0.05 were considered statistically significant.A total of 1036 patients were assessed with a diagnosis of ACS. Eighty-eight patients were excluded because of the atrial infarction criteria and 45 patients due to the history of AF. After exclusion of the patients with renal dysfunction (creatinine >1.5 mg/dL), severe valvular heart disease, permanent pacemaker, cerebrovascular disease, and the need for mechanical ventilation, 831 patients remained for further analysis. STEMI was found in 486 (58.5%) and NSTEMI in 345 (41.5%) patients. All patients were divided into two groups according to receiving ticagrelor  or clopidogrel . The rate of patients diagnosed with STEMI in the ticagrelor group was found to be higher than in the clopidogrel group . Table 1 summarizes the patients’ baseline characteristics. The groups had no significant differences in terms of age, sex, BMI, heart rate, blood pressure, creatinine, alanine amino transferase, hemoglobin, thyroid-stimulating hormone levels, LA diameter, and LVEF. As shown in Table 1, LDL, HDL, and 24th hour troponin levels were significantly higher in the ticagrelor group. In the analysis of total population data, there was no statistically significant difference in PWD between ticagrelor and clopidogrel groups  (Table 2). The other electrocardiographic predictors of AF, such as PR interval and P wave axis, also showed no significant difference . Subgroups analysis according to ACS types also showed no significant difference in PWD . Echocardiographic parameters are shown in Table 2. Like electrocardiographic parameters, we did not find any differences in echocardiographic predictors. There was no statistically significant difference in left intraatrial EMD, right intraatrial EMD, and interatrial EMD between the groups . In addition, there was no statistically significant difference in echocardiographic predictors of AF in the subgroups according to ACS types. The mean interatrial EMD values of ticagrelor and clopidogrel groups were found as 24.53 ± 3.74 ms and 24.86 ± 3.33 ms in NSTEMI (P = 0.644) and as 23.98 ± 2.82 ms versus 24.23 ± 3.16 ms (P = 0.493) in STEMI subgroup (P = 0.493).The relationship between antiplatelet types and P wave duration, PWD and EMD values, was evaluated by ANCOVA analysis by removing the effects of confounding factors  that were found to be significant between the antiplatelet groups and the ACS subgroups. When the effects of confounding factors were removed, there was no significant relationship between antiplatelet use and AF predictors (P > 0.05).From the date of treatment initiation, subgroup analysis was performed in 66 (16.09%) patients with side effects  related to ticagrelor. There was no significant difference in terms of AF predictors in patients with side effects related to ticagrelor when compared to the group receiving clopidogrel or ticagrelor without side effects. PWD was 38.79 ± 12.28 ms in patients receiving ticagrelor that had side effects, while this value was 41.44 ± 13.17 ms in patients without side effects (P = 0.279) and 40.34 ± 13.14 ms in clopidogrel group (P = 0.657). Interatrial EMD was 24.23 ± 2.79 ms in patients receiving ticagrelor and had side effects, while this value was 24.18 ± 3.21 ms in patients without side effects (P = 0.998) and 24.35 ± 3.01 ms in clopidogrel group (P = 0.990).Our study was designed to find out whether ticagrelor could change AF predictors. We did not find a statistically significant difference in PWD, interatrial and intraatrial EMD durations between ticagrelor and clopidogrel groups in patients with ACS.IKAdo. In addition to that, adenosine has other effects that may promote arrhythmogenesis. Adenosine has sympathoexcitatory effects mediated through baroreflex activation and chemoreceptor stimulation [30]. Adenosine can also hyperpolarize dormant pulmonary vein myocytes and increase excitability, as well as trigger pulmonary vein ectopy . It has been shown that ticagrelor increases plasma adenosine levels as early as six hours after the loading dose in patients with ACS [33]. Therefore, the main point of our study was to determine whether additional increase in adenosine, which is caused by ticagrelor, would increase the susceptibility to AF. In ACS patients, AF is seen at a high rate (approximately 10%) compared to the normal population, and this increase has been associated with long-term increased morbidity and mortality . AF development in patients with ACS is mostly attributed to ischemia and decreased atrial perfusion, increased left ventricular end-diastolic pressure, increased left atrial pressure, diastolic dysfunction, and autonomic regulatory disturbances [24]. In addition, recently, inflammation and neurohumoral factors have been shown to be associated with AF development in patients with ACS [24]. In our study, there were no significant differences between the groups in parameters that could affect the development of AF such as LA diameter, systolic and diastolic functions of LV. Furthermore, patients with atrial infarction criteria on ECG were excluded from the study to reduce the possible confounding effects of atrial ischemia [19]. Apart from the normal course of ACS, there is a case report indicating that ticagrelor, which increases plasma concentration of adenosine, may cause AF [18]. PLATO trial and some case reports have shown that ticagrelor causes bradyarrhythmias, such as atrioventricular block and sinus node pause . The most probable mechanism for these bradycardic events appears to be increasing plasma concentration of adenosine. Besides the bradycardic effects of adenosine, it is known that intravenous adenosine administration could cause spontaneous AF [15]. Moreover, endogenous production of adenosine during metabolic stress conditions has been suggested as a trigger of AF . Although the mechanism is not clearly understood, this phenomenon is thought to be mediated by adenosine’s effects on shortening atrial action potential duration and refractoriness [30]. Because adenosine has little effect on atrial conduction velocity, the net effect of adenosine, therefore, is to shorten the wavelength of activation, thereby potentiating AF. This cellular electrophysiological effect is mediated by its specific G protein-coupled adenosine A1 receptor and this ligand activates the heterotrimeric protein Gi/o, which then activates the inward rectifying K+ current, It has been shown that PWD and Pmax are predictors of AF [34]. Normal value for PWD is defined as 29 ± 9 ms in the literature, while a PWD > 40 ms leads to atrial tachyarrhythmias . Rosiak et al. also demonstrated that PWD is predictive of AF in STEMI patients and that a value of >25 ms is associated with increased risk for AF [36]. In our study, PWD was 40.98 ± 12 in the ticagrelor group and 40.06 ± 12 in the clopidogrel group, and no statistical difference was found between the two groups. PWD value determined in our study is higher than the PWD values in non-ACS patients in the literature, but the patient groups show some differences. In particular, the high value of PWD may explain the fact that since our patient group included ACS patients, additional comorbidities were common and LVEF was lower than other studies in the literature. Thus, Ding et al. found that patients with cardiac resynchronization therapy had high PWD values and showed a decrease in PWD when EF was improved [37]. Besides electrocardiographic parameters, we also looked at echocardiographic parameters, which were shown to predict AF . Likewise, in electrocardiographic analysis, there was no statistical difference between the interatrial, right and left intraatrial electro-mechanic delays that were measured by TDI between ticagrelor and clopidogrel groups.  Although recent investigations have shown that dyspnea is caused by direct P2Y12-inhibitory effect on the central nervous system, in our study patients with side effects due to ticagrelor were also considered as subgroups due to probably increased adenosine levels than those without side effects [40]. However, subgroup analyses for AF predictors showed no significant difference in patients with or without side effects [20]. To the best of our knowledge, this is the first study investigating the association between ticagrelor and AF predictors. Nevertheless, the lack of follow-up in terms of future arrhythmic episodes is among the major limitations of our study. Reliable methods for detecting AF could be used, such as long-term rhythm monitoring. In addition, the lack of difference between the ticagrelor and clopidogrel groups in terms of AF predictors may be attributed to several causes. For example, possible atrial structural disturbances due to ACS and having multiple risk factors may have masked potential effects of adenosine on AF development. There were also some differences in frequency of ACS types and troponin levels in the two study groups. Furthermore, the increase in adenosine level caused by ticagrelor might not be sufficient to alter the AF predictors we have investigated. It has also been shown in the literature that adenosine causes AF in a dose-dependent AF [14].In conclusion, in this study, we found that there was no significant difference in electro-echocardiographic AF predictors such as PWD and EMD in ACS patients who received ticagrelor or clopidogrel. In addition, there was no difference even in patients with side effects, suggesting that the possible increase in adenosine level did not lead to AF susceptibility.


Anesthetic management of pregnant women with Fontan circulation remains challenging. There are few reports that describe the anesthetic management of cesarean section after Fontan surgery. Here, we present a case of successful epidural anesthesia in a woman with Fontan circulation who required emergency cesarean section.2 of 35 mmHg, PO2 of 55.5 mmHg, and hemoglobin of 16.3 g/dL. Her blood coagulation parameters were within normal limits except for a high fibrinogen concentration (4.55 g/L).A 29-year-old woman at gestational week 28 was scheduled for emergency cesarean section because of fetal distress. Her past medical history was significant for congenital transposition of the great arteries that had been treated by Fontan surgery 26 years earlier. Her postoperative course had been uneventful and she had reached a near normal level of activity with no arrhythmias or thrombotic complications. On presentation, her oxygen saturation was approximately 84% and she had digital clubbing. Arterial blood gas analysis showed a PCOThe diagnosis was pregnancy requiring emergency cesarean section because of fetal distress.Before anesthesia, a radial artery line was established for continuous measurement of blood pressure. An air pressure pump was placed on the patient's lower limbs and a low-dose dobutamine infusion was started. Next, epidural anesthesia was successfully performed at L2–3. Five milliliters of 2% lidocaine followed by 10 mL of 0.75% ropivacaine were injected. Dobutamine was infused to maintain a target blood pressure of 100–120/60–70 mmHg.The procedure was uneventful with the patient maintaining a stable heart rate of 80 to 90 beats/min and an oxygen saturation of 90% to 94%. A male infant weighing 840 g was delivered. The Apgar score was 9 at 1 and 5 minutes. The patient was transferred to the intensive care unit for 20 hours of monitoring and discharged 9 days later. The neonate was discharged after 2 months of specialist neonatal treatment.Epidural anesthesia may be used in women with Fontan circulation undergoing emergency cesarean section. Knowledge of the physiology of the heart lesion and that of pregnancy are critical to the outcome. The surgical outcome and long-term survival rate have also improved.,3 However, pregnant women who have undergone Fontan surgery are still likely to need cesarean section. The anesthetic management of pregnant patients with Fontan circulation remains challenging. The success of anesthesia directly affects the prognosis. Saito et al recently reported on a woman with Fontan circulation who underwent emergency cesarean section under general anesthesia, while Mathney and Beilin reported successful use of epidural anesthesia for elective cesarean delivery in a woman in a similar situation. However, there is no detailed information in the literature on whether or not epidural anesthesia is feasible in an emergent situation. Here we describe a successful case of epidural anesthesia for emergency cesarean section in a woman with Fontan circulation.In 1971, Fontan and Baudet described a surgical technique for successful palliation of patients with tricuspid atresia. Subsequently, this technique has been applied to treat most functional single ventricles.22 partial pressure of 35 mmHg, an O2 partial pressure of 55.5 mmHg, and a hemoglobin level of 16.3 g/dL. Her blood coagulation parameters were within normal limits, except for a high fibrinogen level of 4.55 g/L. During her hospital stay, she received intensive monitoring and anticoagulation therapy with low-molecular-weight heparin (LMWH).This case was reviewed by the Ethical Committee Board of First Affiliated Hospital, Zhejiang University School of Medicine (No: 2018-186) and Informed consent was obtained from the patient for publication of her case. A 29-year-old woman  with a pregnancy of 24 weeks and 5 days was admitted because of a decrease in diastolic umbilical artery blood flow and suspected fetal distress. Her past medical history was significant for congenital heart disease  that had been treated by modified Fontan surgery 26 years earlier. After corrective cardiac surgery, the right atrium was connected directly to the pulmonary artery and the right ventricle was combined with the left as a functional single ventricle through a large ventricular septal defect. She had fared well postoperatively with a near normal level of activity (New York Heart Association class I–II) and no arrhythmias or thrombotic complications. Her oxygen saturation was about 84% with a nasal catheter supplying oxygen at a flow rate of 2 L/min. Digital clubbing was noted. Doppler echocardiography showed the complicated congenital aortic transposition of Fontan surgery, that is, right atrial and pulmonary artery bridge blood flow and a large ventricular septal defect suggesting a functional single ventricle, with no significant increase in pulmonary artery pressure. Arterial blood gas analysis showed a COAt gestational week 28, the patient suddenly developed signs of threatened preterm delivery, and monitoring showed a decreased diastolic umbilical artery blood flow and fetal distress. Given her cardiac status and concern regarding the potential for hemodynamic disturbance during vaginal delivery, the decision was taken to perform an emergent cesarean delivery in a cardiothoracic operating theater with immediate availability of cardiopulmonary bypass.When transferred to the operating room, she received oxygen at a flow rate of 5 L/min via a mask. A radial artery was cannulated for monitoring of arterial blood pressure (BP) and central venous access was established to measure central venous pressure (CVP). On admission, her BP was 112/64 mmHg, her heart rate was 73 beats/min. and her CVP was 13 mmHg. After an air pressure pump was placed on her lower limbs for intermittent driving of blood, a low-dose dobutamine infusion (1–3 μg/kg min) was initiated. After evaluation, epidural puncture was performed at L2–3. Five milliliters of 2% lidocaine followed by 0.75% ropivacaine (10 mL) were slowly injected into the epidural space. Ten minutes after anesthesia, a male infant weighing 840 g was delivered with 1-minute and 5-minute Apgar scores of 9. After delivery, a low-dose continuous infusion of phenylephrine and alprostadil was administered. Her hemodynamic status was stable throughout the procedure . Her respiration was stable at a rate of 16–20 breaths/min via an oxygen mask with an oxygen saturation of 90% to 94%. Postoperatively, she was transferred to the intensive care unit for 20 hours of monitoring and was discharged 9 days later. The neonate was discharged after 2 months of specialist neonatal treatment.3 Since then, the surgical outcome and long-term survival of patients with complex congenital heart disease have improved dramatically.,3 Nowadays, an increasing number of women are reaching childbearing age post-Fontan repair. These women are usually counseled by their physicians to terminate a pregnancy because of delivery-related factors that cannot be controlled. Despite the progress made in terms of anesthetic technique and the anesthetic agents available, management of women with Fontan circulation in the peripartum period remains challenging for anesthesiologists. A thorough understanding of the physiology of the partially corrected heart lesion and the impact of the physiologic changes of pregnancy is critical to successful management of cesarean section in these women. We have presented a case of successful epidural anesthesia for emergency cesarean section in a woman with Fontan circulation. The operation was uneventful, and both the mother and neonate were discharged after an uneventful postoperative course.Taking into account the anatomic characteristics of the human pulmonary circulation, Fontan and Baudet devised a surgical technique for successful palliation of patients with tricuspid atresia in 1971. Moreover, pregnant patients with Fontan circulation face volume overload and hypercoagulation, both of which require additional specialist treatment.,9 Such factors add to the difficulty of perioperative anesthetic management in these women. With the advent of routine preventive anticoagulation therapy, intravertebral anesthesia  may no longer be the best choice in emergent situations. However, in the present case, prompt cessation of LMWH paved the way for an epidural block. More than 12 hours had elapsed since the last dose of LMWH and the patient's blood coagulation parameters were within normal range, so epidural block was reconsidered. Nevertheless, to minimize the risk of intravertebral hemorrhage or hematoma, the epidural puncture was performed by an experienced anesthesiologist and LMWH was restarted 12 hours postoperatively.Fontan surgery, also known as a pulmonary collateral procedure, is performed through the right atrium and pulmonary artery. The difference in pressure between the vena cava and left atrium produces a pressure gradient (right atrium - pulmonary artery - pulmonary vein - left atrium) that promotes perfusion of the pulmonary vascular bed with venous blood. The procedure is palliative rather than curative, but in many cases can result in normal or near-normal pump function and body growth. The common complications after a Fontan procedure include heart failure, arrhythmia, and thrombosis. Therefore, we used a low-dose dobutamine infusion intraoperatively to maintain a BP of 100–120/60–70 mmHg and a heart rate of 80 to 90 beats/min, thereby increasing hemodynamic performance.In the presence of mixed venous blood, severe hypoxia may lead to marginal myocardial function and loss of compensation, resulting in circulatory collapse. The key to preventing lethal hypoxia and stabilizing hemodynamic status in a patient with Fontan circulation is to ensure the pressure gradient between the vena cava and left atrium. General anesthesia provides a secure airway but usually requires mechanical ventilation, which increases the mean intrathoracic pressure and pulmonary vascular resistance and decreases the venous return and pulmonary blood flow, thereby decreasing oxygenation in a patient with Fontan circulation. However, epidural block allows spontaneous breathing, which produces a low intrathoracic pressure and may be a more suitable technique in such patients, even in emergent situations. We performed an epidural block in our patient to ensure stable pulmonary vascular resistance and oxygenation with adequate intraoperative volume load and peripheral vascular resistance. It is also essential to maintain sinus rhythm and myocardial contractility for preservation of cardiac function and to maintain the pressure gradient.4Epidural block may be helpful in women with Fontan circulation undergoing cesarean section, even in emergent situations. However, a thorough understanding of the physiology of Fontan circulation is essential for successful perioperative management. It is critical to maintain hemodynamic stability and ensure an appropriate BP gradient. Finally, management of such patients requires multidisciplinary collaboration between clinicians who are familiar with congenital heart disease, including cardiologists, obstetricians, and cardiac anesthetists.www.editage.com) for English language editing.We would like to thank Editage (Conceptualization: Yong-Xing Yao.Writing – original draft: Pin Wu.Writing – review & editing: Sheng-Mei Zhu.