ABSTRACT
This study aims to develop a new heart failure with preserved ejection fraction (HFpEF) diagnostic algorithm tailored to Asian populations, addressing limitations of current diagnostic models. Existing HFpEF diagnostic algorithms primarily target patients with dyspnea and metabolic comorbidities, such as obesity, which are more prevalent in Western populations. However, in Asian countries, HFpEF cases are less frequently associated with obesity, leading to less prominent dyspnea and more noticeable symptoms such as fatigue. By incorporating exercise stress echocardiography and focusing on early-stage HFpEF, particularly in patients with symptoms beyond dyspnea, we seek to enable early diagnosis and intervention, ultimately extending healthy life expectancy and improving quality of life. The STOP-HFPEF (The Multicenter STudy On a Precise algorithm for diagnosis of Heart Failure with Preserved Ejection Fraction) study is a multicenter prospective observational investigation in Japan. Certified by the Japanese Society of Echocardiography, the study includes participants aged 20 and older who undergo exercise stress echocardiography. The primary goal is to develop a scoring model for diagnosing HFpEF in heart-failure stages A, B, and C. Secondary outcomes will assess the clinical utility of the new diagnostic score by comparing heart-failure incidence, cardiovascular events, and mortality rates.Study registration: Registered at the UMIN registry (UMIN000054565) on 1 July 2024.
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Activated arginine vasopressin (AVP) pathway worsens congestion in heart failure (HF), but its potential to relieve pulmonary congestion is also reported. The pathophysiological role and prognostic utility of AVP elevation in acute decompensated HF (ADHF) are poorly understood. We prospectively enrolled 52 hospitalized patients for ADHF to investigate the association between acute lung injury (ALI) in ADHF and AVP levels on admission. ALI was defined as respiratory failure leading to death, or requiring a respirator or a more than 12-h non-invasive intermittent positive pressure ventilation (NIPPV) support. In addition, we investigated the prognostic value of AVP levels on admission for cardiovascular death or recurrence of ADHF after discharge. ALI was documented in 7 patients (13.5%) during a median hospital stay of 14 days. And the patients with ALI demonstrated significantly higher AVP levels than those without (32.5 ± 21.6 vs. 6.4 ± 8.7 pg/ml, p = 0.018). Besides, the patients with ALI demonstrated significantly higher heart rates (HR) and lower E/e' on admission (HR: 127 ± 24 vs. 97 ± 28 bpm; E/e': 10.6 ± 3.7 vs. 17.4 ± 6.2, all p < 0.05, respectively). Of note, significant hemodilution assessed by hemoglobin and hematocrit values were observed in the patients with ALI 48 h after admission. A receiver operating characteristic curve analysis showed that higher than 7.2 pg/ml surrogate ALI in ADHF (AUC: 0.897, p = 0.001, Sensitivity: 85.7%, and Specificity: 77.8%). In contrast, increased AVP levels on admission could not predict cardiovascular events after discharge. Elevated AVP levels on admission are associated with ALI in ADHF but not cardiovascular events after discharge.
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The prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) is reported to be as worse as myocardial infarction with obstructive coronary arteries. However, its mechanical complications are still poorly understood. A 71-year-old woman developed MINOCA after ascending aortic replacement surgery. During treatment, the patient experienced cardiogenic shock due to a ventricular septal rupture (VSR). The introduction of Impella devices reduced the left-to-right shunt and improved the patient's hemodynamics. Finally, a scheduled surgical repair was performed under stable conditions. In this report, we focused on the pathophysiology of MINOCA-related VSR and discussed the effectiveness of Impella devices as a bridge to surgical repair and circulatory backup during the perioperative period.
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PURPOSE: Renal circulation evaluation is essential in understanding the cardiorenal relationship in heart failure (HF), and there is a growing interest in imaging techniques that visualize renal circulation. This study aimed to assess the effectiveness of superb microvascular imaging (SMI) in evaluating renal circulation in HF patients. METHOD: The study included 71 HF patients undergoing cardiac catheterization. Prior to catheterization, renal ultrasound examinations were performed. A control group of 18 subjects without HF was also included. SMI was used to measure the vascular index (VI), which was calculated as the percentage of blood flow signal area in the region of interest. The intrarenal perfusion index (IRPI) was determined as a fluctuation index of VI, reflecting variations in the number of blood cells moving through renal tissue during the cardiac cycle. RESULTS: Using the upper 95% confidence interval of IRPI (0.6) from the control group, HF patients were classified into two groups. Patients with IRPI > 0.6 showed a more congestive profile. Right atrial pressure and biphasic or monophasic Doppler intrarenal flow pattern were independent determinants of IRPI > 0.6. In addition, IRPI remained a significant predictor of estimated glomerular filtration rate (eGFR). CONCLUSION: The parameter IRPI as variations in SMI signal during the cardiac cycle may be a useful evaluation method for renal perfusion impairment in HF.
Subject(s)
Heart Failure , Microvessels , Renal Circulation , Humans , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Female , Male , Middle Aged , Aged , Renal Circulation/physiology , Microvessels/diagnostic imaging , Microvessels/physiopathology , Kidney/diagnostic imaging , Kidney/blood supply , Kidney/physiopathology , Glomerular Filtration Rate , Microcirculation/physiologyABSTRACT
AIMS: Higher left ventricular (LV) ejection fraction (EF) is related to unfavourable prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The cause of this finding needs to be haemodynamically explained. Thus, we investigated this crucial issue from the perspective of LV-arterial (A) and right ventricular (RV)-pulmonary arterial (PA) coupling. METHODS AND RESULTS: Study patients were derived from our prospective cohort study of patients hospitalized due to acute decompensated HF and LVEF > 40%. We divided the 255 patients into three groups: HF with mildly reduced EF (HFmrEF), HFpEF with 50% ≤ LVEF < 60%, and HFpEF with LVEF ≥ 60%. We compared LV end-systolic elastance (Ees), effective arterial elastance (Ea), and Ees/Ea as a representative of LV-A coupling among groups and compared the ratio of tricuspid annular plane excursion to peak pulmonary arterial systolic pressure (TAPSE/PASP) as a representative of RV-PA coupling. All-cause death and readmission due to HF-free survival was worse in the group with a higher LVEF range. Ees/Ea was greater in HFpEF patients with LVEF ≥ 60% (2.12 ± 0.57) than in those with 50% ≤ LVEF < 60% (1.20 ± 0.14) and those with HFmrEF (0.82 ± 0.09) (P < 0.001). PASP was increased in the groups with higher LVEF; however, TAPSE/PASP did not differ among groups (n = 168, P = 0.17). In a multivariate Cox proportional hazard model, TAPSE/PASP but not PASP was significantly related to event-free survival independent of LVEF. CONCLUSION: HFpEF patients with higher LVEF have unfavourable prognosis and distinctive LV-A coupling: Ees/Ea is elevated up to 2.0 or more. Impaired RV-PA coupling also worsens prognosis in such patients. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000017725.
Subject(s)
Heart Failure , Pulmonary Artery , Stroke Volume , Humans , Heart Failure/physiopathology , Heart Failure/diagnostic imaging , Male , Female , Stroke Volume/physiology , Aged , Prospective Studies , Pulmonary Artery/physiopathology , Pulmonary Artery/diagnostic imaging , Prognosis , Cohort Studies , Middle Aged , Risk Assessment , EchocardiographyABSTRACT
Hemodialysis (HD)-induced myocardial stunning, characterized by transient left ventricular systolic dysfunction during HD, has been reported to be common and associated with a poor prognosis. However, the pathophysiology is not fully understood. We herein report a case of HD-induced myocardial stunning without obstructive coronary artery disease complicated by coronary microvascular dysfunction (CMD), suggesting that CMD plays a crucial role in the pathophysiology of this disease.
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A population encounters a variety of environmental stresses, so the full source of its resilience can only be captured by collecting all the signatures of adaptation to the selection of the local environment in its population history. Based on the multiomic data of Arabidopsis thaliana, we constructed a database of phenotypic adaptations (p-adaptations) and gene expression (e-adaptations) adaptations in the population. Through the enrichment analysis of the identified adaptations, we inferred a likely scenario of adaptation that is consistent with the biological evidence from experimental work. We analyzed the dynamics of the allele frequencies at the 23,880 QTLs of 174 traits and 8,618 eQTLs of 1,829 genes with respect to the total SNPs in the genomes and identified 650 p-adaptations and 3,925 e-adaptations [false discovery rate (FDR) = 0.05]. The population underwent large-scale p-adaptations and e-adaptations along 4 lineages. Extremely cold winters and short summers prolonged seed dormancy and expanded the root system architecture. Low temperatures prolonged the growing season, and low light intensity required the increased chloroplast activity. The subtropical and humid environment enhanced phytohormone signaling pathways in response to the biotic and abiotic stresses. Exposure to heavy metals selected alleles for lower heavy metal uptake from soil, lower growth rate, lower resistance to bacteria, and higher expression of photosynthetic genes were selected. The p-adaptations are directly interpretable, while the coadapted gene expressions reflect the physiological requirements for the adaptation. The integration of this information characterizes when and where the population has experienced environmental stress and how the population responded at the molecular level.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Gene Frequency , Arabidopsis Proteins/genetics , Soil , PhenotypeABSTRACT
AIM: Adverse limb events after endovascular therapy (EVT) are a major concern. This study aimed to investigate the relationship between serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, a potentially potent indicator of atherosclerosis, and clinical outcomes after EVT in patients with lower extremity arterial disease (LEAD). METHODS: A total of 208 LEAD patients who underwent EVT and MDA-LDL measurements were retrospectively analyzed. Those with chronic limb-threatening ischemia (CLTI) were included in the CLTI subgroup (n=106). Patients were further categorized into the High or Low MDA-LDL groups according to the cut-off value calculated by receiver operating characteristic analysis. Major adverse limb events (MALE), a composite of cardiovascular death, limb-related death, major amputation, and target-limb revascularization, were evaluated. RESULTS: MALE occurred in 73 (35%) patients. The median follow-up interval was 17.4 months. The MDA-LDL cut-off values were 100.5 U/L (area under the curve [AUC] 0.651) in the overall population and 98.0 U/L (AUC 0.724) in the CLTI subgroup. Overall, the High MDA-LDL group showed significantly higher total cholesterol (189.7±37.5 mg/dL vs. 159.3±32.0 mg/dL, pï¼0.01), low-density lipoprotein cholesterol (114.3±29.7 mg/dL vs. 87.3±25.3 mg/dL, pï¼0.01), and triglyceride (166.9±91.1 mg/dL vs. 115.8±52.3 mg/dL, pï¼0.01) than the Low MDA-LDL group. Multivariate Cox regression analyses revealed that MDA-LDL and C-reactive protein were independent predictors of MALE. In the CLTI subgroup, MDA-LDL was an independent predictor of MALE. The High MDA-LDL group showed worse MALE-free survival rates than the Low MDA-LDL group in overall (pï¼0.01) and in the CLTI subgroup (p=0.01). CONCLUSIONS: Serum MDA-LDL level was associated with MALE after EVT.
Subject(s)
Endovascular Procedures , Peripheral Arterial Disease , Humans , Treatment Outcome , Malondialdehyde , Retrospective Studies , Peripheral Arterial Disease/surgery , Risk Factors , Lower Extremity/blood supply , Cholesterol, LDL , Endovascular Procedures/adverse effects , Ischemia/surgery , Limb SalvageABSTRACT
BACKGROUND: The number of patients with heart failure (HF) has increased, and it is crucial to prevent the development of HF in patients at risk of HF. The present study aimed to risk stratify patients in Stage A and B HF based on associations between exercise-induced changes in aortic stiffness and exercise tolerance.MethodsâandâResults: Patients in Stage A and B HF who performed a cardiopulmonary exercise test were enrolled in the study (n=106; median age 65.0 years [interquartile range 52.8-73.0 years]). Exercise tolerance was examined by the percentage of predicted peak oxygen consumption (%VÌO2peak). The ascending aortic pressure waveform was estimated non-invasively. Aortic stiffness was assessed using the augmentation index (AIx) and reflection magnitude (RM). Multivariable regression analysis showed that AIx measured both before and after exercise was significantly associated with %VÌO2peak (ß=-0.221 [P=0.049] and ß=-0.342 [P=0.003], respectively). When participants were divided into %VÌO2peak subgroups using a cut-off value of 60%, RM decreased immediately after exercise and remained lower 5 min after exercise in the group with preserved exercise tolerance, but recovered to baseline levels 5 min after exercise in the group with reduced exercise tolerance. CONCLUSIONS: Exercise-induced increases in aortic stiffness were associated with exercise tolerance in patients at risk of HF, suggesting that exercise-induced changes in aortic stiffness may be useful to stratify high-risk patients.
Subject(s)
Heart Failure , Vascular Stiffness , Humans , Middle Aged , Aged , Exercise Tolerance , Exercise Test , ExerciseABSTRACT
AIMS: Newly introduced drugs for heart failure (HF) have been reported to improve the prognosis of HF with preserved ejection fraction (HFpEF) in the lower range of left ventricular ejection fraction (LVEF). We hypothesized that a higher LVEF is related to an unfavourable prognosis in patients with HFpEF. METHODS AND RESULTS: We tested this hypothesis by analysing the data from a prospective multicentre cohort study in 255 patients admitted to the hospital due to decompensated HF (LVEF > 40% at discharge). The primary endpoint of this study was a composite outcome of all-cause death and readmission due to HF, and the secondary endpoint was readmission due to HF. LVEF and the mitral E/e' ratio were measured using echocardiography. In multicovariate parametric survival time analysis, LVEF [hazard ratio (HR) = 1.046 per 1% increase, P = 0.001], concurrent atrial fibrillation (AF) (HR = 3.203, P < 0.001), and E/e' (HR = 1.083 per 1.0 increase, P < 0.001) were significantly correlated with the primary endpoint. In addition to these covariates, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use was significantly correlated with the secondary endpoint (HR = 0.451, P = 0.008). Diagnostic performance plot analysis demonstrated that the discrimination threshold value for LVEF that could identify patients prone to reaching the primary endpoint was ≥57.2%. The prevalence of AF or E/e' ratio did not differ significantly between patients with LVEF ≥ 58% and with 40% < LVEF < 58%. CONCLUSION: A higher LVEF is independently related to poor prognosis in patients with HFpEF, in addition to concurrent AF and an elevated E/e' ratio. ACEI/ARB use, in contrast, was associated with improved prognosis, especially with regard to readmission due to HF. CLINICAL TRIAL REGISTRATION: https://www.umin.ac.jp/ctr/index.htm. UNIQUE IDENTIFIER: UMIN000017725.
Subject(s)
Heart Failure , Ventricular Function, Left , Humans , Stroke Volume , Cohort Studies , Prospective Studies , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , PrognosisABSTRACT
AIM: To investigate the effect of left ventricular ejection fraction (LVEF) on the behavior of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with heart failure and type 2 diabetes mellitus with the use of canagliflozin compared to glimepiride. METHODS: Patients (nâ¯=â¯233) from the CANDLE trial were randomly assigned to either the add-on canagliflozin (nâ¯=â¯113) or glimepiride treatment groups (nâ¯=â¯120). The patients were followed-up for 24â¯weeks. The NT-proBNP levels were measured at baseline and after 24â¯weeks. The LVEF was determined at baseline. RESULTS: There was a significant relationship between the baseline NT-proBNP level (X1) and the change in NT-proBNP levels from baseline to 24â¯weeks (Y) in the canagliflozin group (Yâ¯=â¯-0.533â¯×â¯X1â¯+â¯178; râ¯=â¯-0.860, pâ¯<â¯0.001). However, this relationship was not observed in the glimepiride group (pâ¯=â¯0.428). The baseline LVEF (X2) correlated with Y with a marginal significance in the canagliflozin group (Yâ¯=â¯7.72â¯×â¯X2-549; râ¯=â¯0.192, pâ¯=â¯0.054), but no relationship was observed in the glimepiride group. In the canagliflozin group, bivariate regression analysis showed a significant correlation between Y, X1, and X2; Yâ¯=â¯-0.567â¯×â¯X1-6.04â¯×â¯X2â¯+â¯542 (Râ¯=â¯0.871, pâ¯<â¯0.001). The partial regression coefficients of X1 (pâ¯<â¯0.001) and X2 (pâ¯=â¯0.006) significantly explained the variance in Y. The correlation coefficient for X2 was negative. There was a significant relationship between the logarithmically transformed NT-proBNP [ln(NT-proBNP)] at baseline (X1') and the change in ln(NT-proBNP) values from baseline to 24â¯weeks (Y'), a surrogate of the rate of change in NT-proBNP levels, in the canagliflozin group (Y'â¯=â¯-0.18â¯×â¯X1'â¯+â¯0.93; râ¯=â¯0.450, pâ¯=â¯0.001). CONCLUSIONS: The baseline NT-proBNP level significantly affected the extent and the rate of its decrease by canagliflozin. The reduction in NT-proBNP levels by canagliflozin was prominent in patients with a higher LVEF at baseline. However, its confounding effect of LVEF on canagliflozin treatment was not recognized without adjusting for the NT-proBNP level at baseline.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Humans , Ventricular Function, Left , Stroke Volume , Canagliflozin , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Heart Failure/drug therapy , Natriuretic Peptide, Brain , Peptide Fragments , BiomarkersABSTRACT
An 81-year-old man with chronic pancreatitis was being treated with a protease inhibitor. He developed an acute exacerbation of chronic pancreatitis and dyspnea. Contrast-enhanced computed tomography showed disruption of the main pancreatic duct, a cystic lesion connecting the mediastinum to the main pancreatic duct, and left pleural effusion. We diagnosed a pancreatic pseudocyst, mediastinal pancreatic pseudocyst, and pancreatic pleural effusion. Endoscopic retrograde pancreatography showed leakage of contrast medium from the pancreatic body; furthermore, a cystic cavity extending to the mediastinum through a pancreatic duct fistula was visualized. An endoscopic transpapillary nasopancreatic drainage tube was placed in the cystic cavity. Computed tomography showed that the mediastinal pseudocyst and pleural effusion had disappeared. Endoscopic transpapillary pancreatic duct drainage may be useful when a connection between the main pancreatic duct and a mediastinal pseudocyst is confirmed by imaging.
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A 75-year-old man receiving treatment for necrotizing pancreatitis developed septic disseminated intravascular coagulation and acute coronary syndrome (ACS). During percutaneous coronary intervention (PCI), a large amount of fresh thrombi appeared after balloon dilatation for the ACS-culprit lesion. Given the low plasma antithrombin (AT) activity and poorly prolonged activated clotting time (ACT), we suspected that acquired AT deficiency-related heparin resistance (HR) was responsible for the thrombus formation. Administration of AT gamma markedly improved ACT, and we successfully completed PCI. We suggest that AT gamma be considered a treatment option for AT deficiency-related HR and subsequent intraprocedural thrombotic events.
Subject(s)
Percutaneous Coronary Intervention , Thrombosis , Male , Humans , Aged , Heparin/therapeutic use , Percutaneous Coronary Intervention/adverse effects , Anticoagulants , Thrombosis/drug therapy , Thrombosis/etiology , Antithrombins/therapeutic use , Dietary SupplementsABSTRACT
Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. MethodsâandâResults: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with left ventricular ejection fraction (LVEF) ≤50% were excluded. CTRCD was defined as a ≥10% decline in LVEF and LVEF <50% after chemotherapy. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. CTRCD was observed in 36 patients (22%). Mean LVEF and global longitudinal strain (GLS) were lower, left ventricular mass index was higher, and ASA was smaller in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (hazard ratio [HR] per 1% decrease 1.20; 95% confidence interval [CI] 1.07-1.35) and ASA (HR per 1° increase 0.97; 95% CI 0.95-0.99) were identified as independent determinants of CTRCD. An integrated discrimination improvement evaluation confirmed the significant incremental value of ASA for developing CTRCD. Conclusions: Smaller ASA was an independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.
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During the process of range expansion, populations encounter a variety of environments. They respond to the local environments by modifying their mutually interacting traits. Common approaches of landscape analysis include first focusing on the genes that undergo diversifying selection or directional selection in response to environmental variation. To understand the whole history of populations, it is ideal to capture the history of their range expansion with reference to the series of surrounding environments and to infer the multitrait coadaptation. To this end, we propose a complementary approach; it is an exploratory analysis using up-to-date methods that integrate population genetic features and features of selection on multiple traits. First, we conduct correspondence analysis of site frequency spectra, traits, and environments with auxiliary information of population-specific fixation index (F ST). This visualizes the structure and the ages of populations and helps infer the history of range expansion, encountered environmental changes, and selection on multiple traits. Next, we further investigate the inferred history using an admixture graph that describes the population split and admixture. Finally, principal component analysis of the selection on edge-by-trait (SET) matrix identifies multitrait coadaptation and the associated edges of the admixture graph. We introduce a newly defined factor loadings of environmental variables in order to identify the environmental factors that caused the coadaptation. A numerical simulation of one-dimensional stepping-stone population expansion showed that the exploratory analysis reconstructed the pattern of the environmental selection that was missed by analysis of individual traits. Analysis of a public dataset of natural populations of black cottonwood in northwestern America identified the first principal component (PC) coadaptation of photosynthesis- vs growth-related traits responding to the geographical clines of temperature and day length. The second PC coadaptation of volume-related traits suggested that soil condition was a limiting factor for aboveground environmental selection.
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Genetic stock identification (GSI) is a major management tool of Pacific salmon (Oncorhynchus Spp.) that has provided rich genetic baseline data of allozymes, microsatellites, and single-nucleotide polymorphisms (SNPs) across the Pacific Rim. Here, we analyzed published data sets for adult chum salmon (Oncorhynchus keta), namely 10 microsatellites, 53 SNPs, and a mitochondrial DNA locus (mtDNA3, control region, and NADH-3 combined) in samples from 495 locations in the same distribution range (n = 61,813). TreeMix analysis of the microsatellite loci identified the greatest convergence toward Japanese/Korean populations and suggested two admixture events from Japan/Korea to Russia and the Alaskan Peninsula. The SNPs had been purposively collected from rapidly evolving genes to increase the power of GSI. The largest expected heterozygosity was observed in Japanese/Korean populations for microsatellites, whereas it was largest in Western Alaskan populations for SNPs, reflecting the SNP discovery process. A regression of SNP population structures on those of microsatellites indicated the selection of the SNP loci according to deviations from the predicted structures. Specifically, we matched the sampling locations of the SNPs with those of the microsatellites and performed regression analyses of SNP allele frequencies on a 2-dimensional scaling (MDS) of matched locations obtained from microsatellite pairwise F ST values. The MDS first axis indicated a latitudinal cline in American and Russian populations, whereas the second axis showed differentiation of Japanese/Korean populations. The top five outlier SNPs included mtDNA3, U502241 (unknown), GnRH373, ras1362, and TCP178, which were identified by principal component analysis. We summarized the functions of 53 nuclear genes surrounding SNPs and the mtDNA3 locus by referring to a gene database system and propose how they may influence the fitness of chum salmon.
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Populations are shaped by their history. It is crucial to interpret population structure in an evolutionary context. Pairwise FST measures population structure, whereas population-specific FST measures deviation from the ancestral population. To understand the current population structure and a population's history of range expansion, we propose a representation method that overlays population-specific FST estimates on a sampling location map, and on an unrooted neighbor-joining tree and a multi-dimensional scaling plot inferred from a pairwise FST distance matrix. We examined the usefulness of our procedure using simulations that mimicked population colonization from an ancestral population and by analyzing published human, Atlantic cod, and wild poplar data. Our results demonstrated that population-specific FST values identify the source population and trace the evolutionary history of its derived populations. Conversely, pairwise FST values represent the current population structure. By integrating the results of both estimators, we obtained a new picture of the population structure that incorporates evolutionary history. The generalized least squares estimate of genome-wide population-specific FST indicated that the wild poplar population expanded its distribution to the north, where daylight hours are long in summer, to coastal areas with abundant rainfall, and to the south where summers are dry. Genomic data highlight the power of the bias-corrected moment estimators of FST, whether global, pairwise, or population-specific, that provide unbiased estimates of FST. All FST moment estimators described in this paper have reasonable processing times and are useful in population genomics studies.
Subject(s)
Biological Evolution , Genetics, Population , Genetic Variation , Genomics , HumansABSTRACT
Background: Risk stratification of normal-flow, low-gradient (NFLG) severe aortic stenosis (SAS) with preserved left ventricular (LV) ejection fraction (EF) remains unclear. MethodsâandâResults: Of 289 consecutive patients diagnosed with SAS by aortic valve area <1.0 cm2, 66 with NFLG-SAS (stroke volume index >35 mL/m2, mean pressure gradient <40 mmHg, LVEF ≥50%) were enrolled in this study; patients with bicuspid aortic valve, acute coronary syndrome, hemodialysis, or a history of aortic valve replacement (AVR) were excluded. Adverse events (AEs) were defined as cardiovascular death, hospitalization for heart failure, and deteriorating condition requiring AVR. Factors associated with AEs were investigated using a Cox proportional hazards model. Over a median of 675 days of follow-up, 25 AEs were recorded: 4 cardiovascular deaths, 12 hospitalizations for heart failure, and 9 patients requiring AVR. In addition, there were 14 events of progression to high-gradient SAS. Multivariable analysis showed significant associations between AEs and the presence of symptoms (hazard ratio [HR] 10.276; 95% confidence interval [CI] 3.724-28.357; P<0.001), LV hypertrophy (LV mass index >115 and >95 mg/m2 for males and females, respectively; HR 3.257; 95% CI 1.172-9.050; P=0.024), and tricuspid regurgitation (TR) velocity (HR 2.761; 95% CI 1.246-6.118; P=0.012). Conclusions: The presence of symptoms, LV hypertrophy, and high TR velocity could be reliable prognostic indicators and may require watchful waiting for timely AVR in patients with NFLG-SAS.
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BACKGROUND: A few studies to evaluate an incidence of bradyarrhythmia in patients with hypertrophic cardiomyopathy (HCM) have been reported. METHODS: We enrolled 161 patients with HCM to evaluate their bradyarrhythmia risk, especially the risk of patients who were at risk for sudden cardiac death (SCD) and eligible for implantation of an implantable cardiac defibrillator (ICD). We defined symptomatic bradyarrhythmia requiring a pacing therapy as a bradyarrhythmia event and collected the data on an occurrence of the event after the time of diagnosis of HCM. The incidence of bradyarrhythmia events was compared between patients with ICD indications (ICD-candidate group) and those without (non-ICD-candidate group). Furthermore, we investigated the associated factors with bradyarrhythmia events using a Cox proportional-hazards model. RESULTS: During 5.5 ± 4.4 years follow-up, bradyarrhythmia events occurred in 8% (13 patients) of whole patients, and in 15% of the ICD-candidate group (n = 74). In contrast, only 2 events (2%) occurred in the non-ICD-candidate group. The incidence of bradyarrhythmia in the ICD-candidate group was significantly higher than that in the non-ICD-candidate group (log-rank p = 0.015). In the ICD-candidate group, a Cox proportional-hazards model demonstrated that lower heart rate at the time of diagnosis (HR: 1.072, 95%CI: 1.012 to 1.135, p = 0.018), and an eligibility of ICD implantation for secondary prevention of SCD (HR: 9.092, 95%CI: 2.644 to 31.258, p < 0.001) were significantly associated with future bradyarrhythmia. CONCLUSIONS: HCM patients with eligibility for ICD implantation, especially for secondary prevention of SCD, more frequently suffered from bradyarrhythmia events.