Publications by authors named "Koki Nakanishi"

93 Publications

Atrioventricular and Ventricular Functional Interdependence in Individuals Without Overt Cardiac Disease.

J Am Heart Assoc 2021 Nov 15:e021624. Epub 2021 Nov 15.

Department of Cardiovascular Medicine The University of Tokyo Japan.

Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that subclinical left ventricular dysfunction adversely affects LA/RV geometry and function even in a preclinical setting. This study aimed to investigate the atrioventricular and ventricular functional interdependence in a community-based cohort without overt cardiovascular disease. Methods and Results Left ventricular global longitudinal strain (LVGLS), RV free-wall longitudinal strain and LA phasic strain were assessed by speckle-tracking echocardiography in 1080 participants (600 men; 62±12 years) between 2014 and 2018. One hundred and forty-three participants (13.2%) had an abnormal LVGLS (>-18.6%). LA reservoir strain, conduit strain, and RV free-wall longitudinal strain were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (all <0.001). LA and RV dysfunction (LA reservoir strain<31.4% and RVLS>-19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS. Decreased LVGLS was associated with worse LA reservoir strain, conduit strain and RV free-wall longitudinal strain (standardized β=-0.20, -0.19 and 0.11 respectively, all <0.01) independent of cardiovascular risk factors. LA and/or RV dysfunction concomitant with abnormal LVGLS carried significantly increased risk of elevated B-type natriuretic peptide levels (>28.6 pg/mL for men and >44.4 pg/mL for women) compared with normal LVGLS (odds ratio, 2.01; =0.030). Conclusions LA/RV dysfunction was present in 20% individuals with abnormal LVGLS and multi-chamber impairment was associated with elevated B-type natriuretic peptide level, which may provide valuable insights for a better understanding of atrioventricular and ventricular interdependence and possibly heart failure preventive strategies.
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http://dx.doi.org/10.1161/JAHA.121.021624DOI Listing
November 2021

E-PASS scoring system serves as a predictor of short- and long-term outcomes in gastric cancer surgery.

Surg Today 2021 Oct 25. Epub 2021 Oct 25.

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan.

Purposes: This study aimed to evaluate the estimation of the physiological ability and surgical stress (E-PASS) scoring system for predicting the short- and long-term outcomes in gastric cancer (GC) surgery.

Methods: We analyzed a multi-institutional dataset to study patients who underwent gastrectomy with a curative intent between 2010 and 2014. This study evaluated the associations between the optimal E-PASS score cutoff value and the following outcomes: (1) the incidence of postoperative complications in stage I-III GC patients and (2) the prognosis in stage II-III GC patients.

Results: A total of 2495 GC patients were included. A cutoff value of 0.419 was determined using the ROC curve analysis. Postoperative complications were observed more frequently in the E-PASS-high group than that in the E-PASS-low group (30% vs. 17%, p < 0.0001). Among pStage II-III GC patients (n = 1009), the overall survival time of the E-PASS-high group was significantly shorter than that of the E-PASS-low group (hazard ratio 2.08; 95% confidence interval 1.64-2.65; p < 0.0001). A forest plot revealed that E-PASS-high was associated with a greater prognostic factor for overall survival in most subgroups.

Conclusions: The E-PASS scoring system may therefore be a useful predictor of the short- and long-term outcomes in patients with GC who have undergone radical gastrectomy.
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http://dx.doi.org/10.1007/s00595-021-02394-3DOI Listing
October 2021

Independent effect of visceral fat on left atrial phasic function in the general population.

Nutr Metab Cardiovasc Dis 2021 Nov 7;31(12):3426-3433. Epub 2021 Sep 7.

Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Background And Aims: Obesity increases the risk for atrial fibrillation (AF), although the impact of abdominal fat distribution on left atrial (LA) morphology and functional remodeling remains unclear. This study aimed to investigate whether increased abdominal adiposity is independently associated with impaired LA function and/or LA enlargement in a sample of the general population and to evaluate the role of adipokines in this association.

Methods And Results: The study cohort consisted of 527 participants (362 men; 57 ± 10 years) without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination and echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess LA phasic function including reservoir, conduit and pump strain. LA reservoir and conduit strain decreased with increasing VFA quartiles (both p < 0.05), whereas no significant differences were observed in LA volume index and pump strain. When stratified by SFA, there were no significant differences in LA size and function across the quartiles. In multivariable analysis, VFA was significantly associated with LA conduit strain independent of cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters (standardized β = -0.136, p = 0.019). VFA was correlated with serum adiponectin level (r = -0.51, p < 0.001), but there was no association between adiponectin level and three LA phasic strains.

Conclusion: In a sample of the general population, VFA accumulation was independently associated with worse LA conduit strain, which may be involved in the pathophysiological mechanism of obesity-related AF.
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http://dx.doi.org/10.1016/j.numecd.2021.08.044DOI Listing
November 2021

Deep learning model to detect significant aortic regurgitation using electrocardiography: Detection model for aortic regurgitation.

J Cardiol 2021 Sep 17. Epub 2021 Sep 17.

Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan.

Background: Aortic regurgitation (AR) is a common heart disease, with a relatively high prevalence of 4.9% in the Framingham Heart Study. Because the prevalence increases with advancing age, an upward shift in the age distribution may increase the burden of AR. To provide an effective screening method for AR, we developed a deep learning-based artificial intelligence algorithm for the diagnosis of significant AR using electrocardiography (ECG).

Methods: Our dataset comprised 29,859 paired data of ECG and echocardiography, including 412 AR cases, from January 2015 to December 2019. This dataset was divided into training, validation, and test datasets. We developed a multi-input neural network model, which comprised a two-dimensional convolutional neural network (2D-CNN) using raw ECG data and a fully connected deep neural network (FC-DNN) using ECG features, and compared its performance with the performances of a 2D-CNN model and other machine learning models. In addition, we used gradient-weighted class activation mapping (Grad-CAM) to identify which parts of ECG waveforms had the most effect on algorithm decision making.

Results: The area under the receiver operating characteristic curve of the multi-input model (0.802; 95% CI, 0.762-0.837) was significantly greater than that of the 2D-CNN model alone (0.734; 95% CI, 0.679-0.783; p<0.001) and those of other machine learning models. Grad-CAM demonstrated that the multi-input model tended to focus on the QRS complex in leads I and aVL when detecting AR.

Conclusions: The multi-input deep learning model using 12-lead ECG data could detect significant AR with modest predictive value.
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http://dx.doi.org/10.1016/j.jjcc.2021.08.029DOI Listing
September 2021

Prognostic impact of a microscopic positive margin in patients undergoing gastrectomy for gastric cancer: a propensity score‑matched analysis of a multi‑institutional dataset.

Surg Today 2021 Aug 26. Epub 2021 Aug 26.

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Purpose: We analyzed the effect of a microscopic positive margin on survival outcomes after gastrectomy for gastric cancer METHODS: We analyzed a multi-institutional dataset to study patients who underwent gastrectomy with curative intent between 2010 and 2014. We used propensity score matching to strictly balance the patients' oncological features, backgrounds, and postoperative treatment to compare the survival outcomes of those with microscopic positive margins and those with negative margins.

Results: Among 3029 patients, 32 (1.1%) had positive margins. After matching, we enrolled 128 patients in this retrospective analysis: 32 with a positive margin and 96 with a negative margin. The recurrence-free survival of the positive-margin group was significantly shorter than that of the negative-margin group (hazard ratio [HR], 1.62, 95% confidence interval, 1.00-2.63, p = 0.0485). Consistent results were observed for patients with pStages I-III disease (HR, 1.65, p = 0.0835), whereas the survival curves overlapped in those with pStage IV disease (HR, 1.29, p = 0.5934). The prevalence of overall recurrence in the positive-margin group was higher than that in the negative-margin group (75% vs 58%, p = 0.0917). This trend was consistent with locoregional recurrence (9% vs 3%) and distant recurrence (69% vs 55%).

Conclusions: The survival of patients after curative gastrectomy for gastric cancer was worse in those with microscopic positive margins than in those with negative margins.
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http://dx.doi.org/10.1007/s00595-021-02365-8DOI Listing
August 2021

Combined evaluation of right ventricular function using echocardiography in non-ischaemic dilated cardiomyopathy.

ESC Heart Fail 2021 10 4;8(5):3947-3956. Epub 2021 Aug 4.

Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan.

Aims: Although comprehensive assessment of right ventricular (RV) function using multiple echocardiographic parameters is recommended for management of patients with non-ischaemic dilated cardiomyopathy (DCM), it is unclear which RV parameters to combine. Additionally, normalization of RV parameters by estimated pulmonary artery systolic pressure (PASP), in consideration of RV-pulmonary artery coupling, may be clinically significant. The aim of our study was to elucidate the best combination of echocardiographic RV functional parameters, with or without indexing for PASP, to predict outcome in patients with heart failure with reduced ejection fraction secondary to DCM.

Methods And Results: We retrospectively analysed 109 DCM patients with left ventricular ejection fraction <40%. RV size was assessed by RV end-diastolic area (RVEDA) and RV end-systolic area (RVESA) from RV-focused apical four-chamber view. RV function was assessed by fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) and by RV longitudinal strain (RVLS) using two-dimensional speckle-tracking echocardiography. All functional parameters were also indexed for estimated PASP. Cox analyses were used to evaluate the association of RV morphology and functional parameters with 1 year outcome (composite of left ventricular assist device implantation and all-cause death). Area under the curve was used to compare prognostic values. Mean age was 44 ± 14 years, and 76 (69.7%) were men. Mean left ventricular ejection fraction was 21.9%, median RVEDA was 22.1 cm , FAC was 27.0%, TAPSE was 15.0 mm, and RVLS was -12.5%. Forty-one (37.6%) patients experienced the primary outcome. Multivariate Cox analysis revealed that RVEDA, RVESA, FAC, TAPSE, RVLS, FAC/PASP, and RVLS/PASP were independent predictors for primary outcome (all P < 0.05). However, normalization with PASP did not improve area under the curve for any RV functional parameters. When we evaluate hazard ratios according to the combination of two echocardiographic parameters of RV function, patients with impairment of both FAC (<27%) and RVLS (>-8.6%) had significantly higher hazard ratio than those with either impairment alone (11.3 vs. 3.4, P < 0.001); the other combinations did not improve prognostic value.

Conclusions: Normalizing echocardiographic RV parameters for PASP did not improve the prognostic values for our population. Meanwhile, combined evaluation of FAC and RVLS improved risk stratification in patients with heart failure with reduced ejection fraction secondary to DCM.
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http://dx.doi.org/10.1002/ehf2.13519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497345PMC
October 2021

Aging and myocardial strain.

J Med Ultrason (2001) 2021 Jul 23. Epub 2021 Jul 23.

Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Advanced age is widely recognized as a key risk factor for incident cardiovascular disease. The age-associated changes in cardiac properties alter the substrate on which cardiovascular disease is superimposed in various ways, and thus affect the development and manifestations of cardiovascular disease (CVD) in the elderly. However, it is still unclear whether age-related cardiac alteration is attributed to aging itself or whether it is secondary to other acquired cardiovascular risk factors. Understanding the association between aging and cardiac functional remodeling might provide insight into the pathogenesis of cardiovascular aging and may help inform possible preventive strategies for CVD in older individuals. Speckle-tracking echocardiography enables the objective and quantitative assessment of subtle myocardial alterations that are undetectable with conventional echocardiography, and has excellent feasibility and reproducibility. Left ventricular (LV) global longitudinal strain, a sensitive measure of LV systolic dysfunction, was found to be an independent risk factor for cardiovascular morbidity and mortality. More recently, deformation imaging has been employed to assess right ventricular (RV) and atrial performance, and impaired RV and atrial strain predict unfavorable outcomes in various clinical settings. This article reviews the association between aging and changes in myocardial strain values and describes future perspectives.
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http://dx.doi.org/10.1007/s10396-021-01115-0DOI Listing
July 2021

Deep Learning Algorithm to Detect Cardiac Sarcoidosis From Echocardiographic Movies.

Circ J 2021 Jun 26. Epub 2021 Jun 26.

Department of Cardiovascular Medicine, The University of Tokyo Hospital.

Background: Because the early diagnosis of subclinical cardiac sarcoidosis (CS) remains difficult, we developed a deep learning algorithm to distinguish CS patients from healthy subjects using echocardiographic movies.Methods and Results:Among the patients who underwent echocardiography from January 2015 to December 2019, we chose 151 echocardiographic movies from 50 CS patients and 151 from 149 healthy subjects. We trained two 3D convolutional neural networks (3D-CNN) to identify CS patients using a dataset of 212 echocardiographic movies with and without a transfer learning method (Pretrained algorithm and Non-pretrained algorithm). On an independent set of 41 echocardiographic movies, the area under the receiver-operating characteristic curve (AUC) of the Pretrained algorithm was greater than that of Non-pretrained algorithm (0.842, 95% confidence interval (CI): 0.722-0.962 vs. 0.724, 95% CI: 0.566-0.882, P=0.253). The AUC from the interpretation of the same set of 41 echocardiographic movies by 5 cardiologists was not significantly different from that of the Pretrained algorithm (0.855, 95% CI: 0.735-0.975 vs. 0.842, 95% CI: 0.722-0.962, P=0.885). A sensitivity map demonstrated that the Pretrained algorithm focused on the area of the mitral valve.

Conclusions: A 3D-CNN with a transfer learning method may be a promising tool for detecting CS using an echocardiographic movie.
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http://dx.doi.org/10.1253/circj.CJ-21-0265DOI Listing
June 2021

Mitral Valvular Coaptation-Zone Area Is Associated with the Severity of Atherosclerosis Assessed by Cardio-Ankle Vascular Index.

Int Heart J 2021 May 15;62(3):552-558. Epub 2021 May 15.

Department of Clinical Laboratory, Graduate School of Medicine, The University of Tokyo.

Preservation of the mitral valve (MV) size is essential for valve function, and a reduced MV coaptation-zone area increases the risk of developing functional mitral regurgitation (FMR). We aimed to determine if the MV leaflet and coaptation-zone areas were associated with the severity of atherosclerosis assessed by cardio-ankle vascular index (CAVI) in patients with normal left ventricle (LV) systolic function and size by real-time 3D echocardiography (RT3DE).We performed RT3DE analysis in 66 patients with normal LV size and ejection fraction who underwent 2D echocardiography and CAVI. MV coaptation-zone areas were measured by custom 3D software and indexed by body surface area (BSA). The associations of clinical factors and mean CAVI with MV leaflet and coaptation-zone areas were evaluated by univariable and multivariable linear regression analyses.On univariable analysis, MV leaflet area/BSA was significantly associated with age (r = -0.335, P = 0.0069) and mean CAVI (r = -0.464, P < 0.001), and MV coaptation-zone area was significantly associated with age (r = -0.626, P < 0.001), hypertension (r = -0.626, P < 0.001), dyslipidemia (r = -0.626, P < 0.001), E/e' (r = -0.626, P < 0.001), and CAVI (r = -0.740, P < 0.001). On multivariable analysis, mean CAVI was independently associated only with MV leaflet area/BSA (standardized coefficient = -0.611, P < 0.001) and MV coaptation-zone area/BSA (standardized coefficient = -0.74, P < 0.001).In patients with normal LV systolic function and size, MV leaflet and coaptation-zone areas might be reduced according to advancing atherosclerosis. Patients with atherosclerosis might be at increased risk of developing FMR.
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http://dx.doi.org/10.1536/ihj.20-776DOI Listing
May 2021

Accurate Prediction of Prognosis After Radical Resection of Gastric Cancer by the Modified Systemic Inflammation Score; a Multicenter Dataset Analysis.

World J Surg 2021 08 1;45(8):2513-2520. Epub 2021 May 1.

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background: The presence of chronic inflammation and nutritional status in cancer patients affects its prognosis. There is a clinical need for a prognostic predictor that is objective and accurate, and that can be easily evaluated by preoperative screening. We evaluated the importance and usefulness of the preoperative modified systemic inflammation score (mSIS) to predict the long-term outcome of patients undergoing curative resection for gastric cancer (GC).

Methods: Of the 3571 patients who underwent curative resection for GC in nine institutions between January 2010 and December 2014, 1764 patients who met the inclusion criteria were included. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte-to-monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥ 4.0 g/dL and LMR ≥ 3.4), mSIS 1 (ALB < 4.0 g/dL or LMR < 3.4), and mSIS 2 (ALB < 4.0 g/dL and LMR < 3.4).

Results: Patients were categorized into preoperative mSIS 0 (n = 955), mSIS 1 (n = 584), and mSIS 2 (n = 225) groups. The overall survival times and the disease-free survival times of patients in preoperative mSIS 0,1 and 2 sequentially shortened (P < 0.0001), and mSIS 1 and 2 were identified as an independent prognostic factor (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.06-1.272, P = 0.0125 and HR 1.63, 95% CI 1.21-2.19, P = 0.0012). A stepwise increase in the prevalence of hematogenous recurrences was directly proportional to the mSIS. A forest plot revealed that mSIS 0,1 was associated with a greater risk of overall survival in most subgroups.

Conclusion: Preoperative mSIS can be easily calculated, and it is suggested that it is useful as a prognostic predictor of patients with different disease stages, for stratifying and evaluating clinical outcomes.
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http://dx.doi.org/10.1007/s00268-021-06138-9DOI Listing
August 2021

Risk factors including preoperative echocardiographic parameters for post-induction hypotension in general anesthesia.

J Cardiol 2021 09 8;78(3):230-236. Epub 2021 Apr 8.

Department of Anesthesiology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Severe hypotension immediately after induction of general anesthesia (post-induction hypotension) is a common complication and is associated with a poor postoperative outcome. We hypothesized that post-induction hypotension results from cardiac dysfunction which can be assessed by preoperative echocardiography.

Methods: We retrospectively enrolled 200 patients who had undergone elective surgery within 6 months after preoperative transthoracic echocardiography. The incidence of post-induction hypotension identified from anesthesia records was defined as a decrease in mean blood pressure to ≤50 mmHg after injection of induction anesthetics prior to surgery. Logistic regression analysis of patient characteristics and echocardiographic variables was used to identify the independent factors for post-induction hypotension.

Results: Post-induction hypotension was found in 63 of the 200 cases (incidence 32%). Independent risk factors for post-induction hypotension were the presence of a regional wall motion abnormality (RWMA) [odds ratio (OR), 6.65.; 95% confidence interval (CI), 1.76 - 25.10], an elevated E/e' (OR, 1.13; 95% CI, 1.00 - 1.28), female gender (OR, 3.61; 95% CI, 1.37 - 9.56), and the use of an angiotensin II receptor blocker (OR, 3.17; 95% CI, 1.12 - 8.96).

Conclusions: Assessment of RWMA and E/e' with preoperative transthoracic echocardiography might be helpful for stratification of patients at a risk of post-induction hypotension in general anesthesia.
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http://dx.doi.org/10.1016/j.jjcc.2021.03.010DOI Listing
September 2021

Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community.

Cardiovasc Diabetol 2021 01 21;20(1):22. Epub 2021 Jan 21.

Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Background: Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease.

Methods: We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR < 1.5), presence of insulin resistance (HOMA-IR ≥ 1.5) and diabetes mellitus (DM). Multivariable logistic regression models were conducted to evaluate the association between abnormal glucose metabolism and impaired LVGLS (> - 16.65%).

Results: Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e' ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (- 17.6 ± 2.6% vs. - 19.7 ± 3.1%, p < 0.05). The prevalence of impaired LVGLS was higher in abnormal HOMA-IR group compared with normal HOMA-IR group (42.4% vs. 14.0%) and similar to that of DM (48.9%). In multivariable analyses, glycemic abnormalities were significantly associated with impaired LVGLS, independent of traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters [adjusted odds ratio (OR) 2.38, p = 0.007 for abnormal HOMA-IR; adjusted OR 3.02, p = 0.003 for DM]. The independent association persisted even after adjustment for waist circumference as a marker of abdominal adiposity. Sub-group analyses stratified by body mass index showed significant association between abnormal HOMA-IR and impaired LVGLS in normal weight individuals (adjusted OR 4.59, p = 0.001), but not in overweight/obese individuals (adjusted OR 1.62, p = 0.300).

Conclusions: In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.
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http://dx.doi.org/10.1186/s12933-020-01201-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818760PMC
January 2021

Relation of Body Mass Index to Adverse Right Ventricular Mechanics.

Am J Cardiol 2021 04 29;144:137-142. Epub 2020 Dec 29.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Although higher body mass index (BMI) is associated with adverse left ventricular morphology and functional remodeling, its possible association with right ventricular (RV) dysfunction has not been extensively evaluated. RV free wall longitudinal strain (RVLS) is emerging as an important tool to detect early RV dysfunction. This study aimed to investigate the independent effect of increased BMI on RVLS in a large sample of the general population without overt cardiac disease. We examined 1,085 participants (603 men, mean age 62 years) who voluntarily underwent an extensive cardiovascular health check-up. This included laboratory tests and speckle-tracking echocardiography to assess RVLS. The association between BMI and RVLS was determined by logistic regression analyses. The prevalence of abnormal RVLS (>-19.2%) was greatest in obese individuals (29.7%), followed by overweight (16.3%), and normal weight (10.6%, p <0.001). In multivariable analyses, BMI was significantly associated with abnormal RVLS (adjusted odds ratio [OR] = 1.07 per 1 kg/m, p = 0.033) independent of traditional cardiovascular risk factors, pertinent laboratory and echocardiographic parameters including RV size and pulmonary artery systolic pressure. In subgroup analyses, BMI was significantly associated with abnormal RVLS in men (adjusted OR 1.10 per 1 kg/m, p = 0.032) and younger (<65 years) participants (adjusted OR 1.13 per 1 kg/m, p = 0.011), but not in women and the elderly. In a sample of the general population, higher BMI was independently associated with subclinical RV dysfunction. Furthermore, an increased BMI may carry different risk for impaired RVLS depending on the age and sex.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.069DOI Listing
April 2021

Short-term outcomes of gastrectomy after neoadjuvant chemotherapy for clinical stage III gastric cancer: propensity score-matched analysis of a multi-institutional database.

Surg Today 2021 May 10;51(5):821-828. Epub 2020 Nov 10.

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65Tsurumai‑cho, Showa‑ku, Nagoya, Japan.

Purpose: Preoperative chemotherapy for gastric cancer may be effective from the standpoint of compliance, although there is insufficient evidence of its efficacy. We analyzed a multicenter database to clarify whether preoperative chemotherapy influenced the short-term outcomes of gastrectomy.

Methods: We analyzed, retrospectively, 3571 patients who underwent gastrectomy between January, 2010 and December, 2014. Patients with clinical stage-III gastric adenocarcinoma were divided into a neoadjuvant chemotherapy (NAC) group and a non-NAC group. We performed propensity-matched comparative analysis to stratify the groups according to age, sex, tumor region, tumor type, preoperative stage, procedure, lymph node dissection, and tumor differentiation. Preoperative blood data, surgical findings, and postoperative complications were analyzed.

Results: Analysis of the matched NAC (n = 64) and non-NAC (n = 128) groups revealed that the preoperative values of neutrophils, platelets, and Hb were significantly lower in the NAC group. Blood loss during surgery was significantly higher, surgical times were longer, and the rate of repeat surgery was significantly lower in the NAC group; however, the rates of rehospitalization did not differ between the groups and mortality was 0% in both groups. Postoperative complications were not significantly different between the groups.

Conclusions: NAC did not increase the complication rate of gastrectomy for gastric cancer.
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http://dx.doi.org/10.1007/s00595-020-02179-0DOI Listing
May 2021

Subclinical Hypothyroidism as an Independent Determinant of Left Atrial Dysfunction in the General Population.

J Clin Endocrinol Metab 2021 03;106(4):e1859-e1867

Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Purpose: Although subclinical hypothyroidism (SCH) is a common clinical entity and carries independent risk for incident heart failure (HF), its possible association with subclinical cardiac dysfunction is unclear. Left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic strain can unmask subclinical left heart abnormalities and are excellent predictors for HF. This study aimed to investigate the association between the presence of SCH and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease.

Methods: We examined 1078 participants who voluntarily underwent extensive cardiovascular health check-ups, including laboratory tests and 2-dimensional speckle-tracking echocardiography to assess LVGLS and LA reservoir, conduit, and pump strain. SCH was defined as an elevated serum thyroid-stimulating hormone level with normal concentration of free thyroxine.

Results: Mean age was 62 ± 12 years, and 56% were men. Seventy-eight (7.2%) participants exhibited SCH. Individuals with SCH had significantly reduced LA reservoir (37.1 ± 6.6% vs 39.1 ± 6.6%; P = 0.011) and conduit strain (17.3 ± 6.3% vs 19.3 ± 6.6%; P = 0.012) compared with those with euthyroidism, whereas there was no significant difference in left ventricular ejection fraction, LA volume index, LVGLS, and LA pump strain between the 2 groups. In multivariable analyses, SCH remained associated with impaired LA reservoir strain, independent of age, traditional cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters. including LVGLS (standardized β -0.054; P = 0.032).

Conclusions: In an unselected community-based cohort, individuals with SCH had significantly impaired LA phasic function. This association may be involved in the higher incidence of HF in subjects with SCH.
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http://dx.doi.org/10.1210/clinem/dgaa730DOI Listing
March 2021

Are there gender differences in the association between body mass index and left ventricular diastolic function? A clinical observational study in the Japanese general population.

Echocardiography 2020 11 21;37(11):1749-1756. Epub 2020 Sep 21.

Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan.

Background: Increased body mass index (BMI) is a major risk factor for heart failure with preserved ejection fraction (HFpEF), and HFpEF is more prevalent in elderly females than males. We hypothesized that there may be gender differences in the association between BMI and echocardiographic left ventricular (LV) diastolic parameters.

Methods: We enrolled 456 subjects (243 males) without overt cardiac diseases, all of whom underwent a health checkup. Early (E) and late (A) diastolic transmitral flow velocity, early diastolic mitral annular velocity (e'), and left atrial (LA) volume index were measured by echocardiography to assess LV diastolic function. To examine gender differences in the association between BMI and LV diastolic function, we analyzed the interaction effects of gender on the association between BMI and echocardiographic LV diastolic parameters.

Results: Although there were significant gender differences in the association between BMI and E/A and e' in the crude model (interaction effect 0.037 and 0.173, respectively; P = .006 and .022, respectively), these differences were not statistically significant after adjustment for factors related to LV diastolic function. On the other hand, there were significant associations between BMI and LV diastolic parameters in each gender, even after adjustment.

Conclusions: Our findings suggest there is no gender difference in the association between BMI and echocardiographic LV diastolic parameters. However, the association between BMI and LV diastolic parameters was significant in both genders. Controlling body weight might be beneficial for both women and men to prevent progression of LV diastolic dysfunction and development of HFpEF.
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http://dx.doi.org/10.1111/echo.14866DOI Listing
November 2020

Carotid intima-media thickness and subclinical left heart dysfunction in the general population.

Atherosclerosis 2020 07 15;305:42-49. Epub 2020 Jun 15.

Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Background And Aims: Although carotid intima-media thickness (IMT) is an established marker of atherosclerosis and carries independent risk for cardiovascular disease, its possible association with subclinical cardiac dysfunction has not been extensively evaluated. Left ventricular global longitudinal strain (LVGLS) and peak left atrial longitudinal systolic strain (PALS) can detect subclinical left heart dysfunction. This study aimed to investigate the association between carotid IMT and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease.

Methods: We examined 1161 participants who underwent extensive cardiovascular examination. Ultrasonography of common carotid artery was performed for the measurement of maximal carotid IMT. LVGLS and PALS were assessed by 2-dimensional speckle-tracking echocardiography.

Results: Mean age was 62 ± 12 years, and 56% were male. The prevalence of abnormal LVGLS (>-18.6%) and PALS (<31.4%) was greatest in the upper quartile of carotid IMT (both p < 0.001). In multivariable analyses, carotid IMT was associated with abnormal LVGLS (adjusted odds ratio = 1.33 per 1SD increase of IMT, p = 0.003) as well as PALS (adjusted odds ratio = 1.33 per 1SD increase of IMT, p = 0.005) independent of traditional cardiovascular risk factors, echocardiographic parameters including LV ejection fraction, LV mass index and diastolic dysfunction, and pertinent laboratory parameters. The independent association between carotid IMT and PALS persisted even after adjustment for LVGLS.

Conclusions: Participants with increased IMT had significantly impaired LV and LA function in an unselected community-based cohort. This association may be involved in the higher incidence of cardiovascular disease in individuals with increased carotid IMT.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.05.019DOI Listing
July 2020

Sex-specific difference in the association between arterial stiffness and subclinical left ventricular dysfunction.

Eur Heart J Cardiovasc Imaging 2021 06;22(7):817-823

Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Aims: Increased arterial stiffness is one of the key mechanisms of heart failure with preserved ejection fraction (HFpEF). However, the possible association between arterial stiffness and subclinical left ventricular (LV) dysfunction and its sex-specific difference remains unclarified. LV strain is emerging as a highly sensitive tool to unmask early LV abnormalities.

Methods And Results: We examined 1155 participants free of overt cardiovascular disease who underwent extensive cardiovascular examination. Speckle-tracking echocardiography was employed to assess LV global longitudinal strain (LVGLS) and circumferential strain (GCS), and arterial stiffness was assessed by cardio-ankle vascular index (CAVI). Mean age was 62 ± 12 years, and 56% were men. CAVI as continuous variable was associated with abnormal LVGLS (>-18.6%) independent of cardiovascular risk factors and echocardiographic parameters [adjusted odds ratio (OR) 1.23, P = 0.027] but not with LVGCS. In sex-stratified analysis, more pronounced association between quartiles of CAVI and abnormal LVGLS was observed in women than in men (unadjusted OR = 6.43 in women and 2.46 in men for upper quartile vs. lower quartile; both P < 0.01). CAVI was significantly associated with abnormal LVGLS independent of cardiovascular risk factors in both sexes. However, after further adjustment for LV mass index and diastolic parameters, the independent association persisted only in women (adjusted OR 1.67, P = 0.007), but not in men (adjusted OR 1.14, P = 0.227).

Conclusion: Increased arterial stiffness was independently associated with decreased LVGLS even without overt cardiovascular disease; a sex-specific pattern exists in the alteration of vascular-ventricular coupling, which might partially explain the greater susceptibility to HFpEF in women.
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http://dx.doi.org/10.1093/ehjci/jeaa156DOI Listing
June 2021

Association of arterial stiffness with left atrial structure and phasic function: a community-based cohort study.

J Hypertens 2020 06;38(6):1140-1148

Department of Cardiovascular Medicine.

Objectives: Increased arterial stiffness is currently recognized as an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study aimed to investigate the association of arterial stiffness with left atrial (LA) volume and phasic function in a community-based cohort.

Methods: We included 1156 participants without overt cardiovascular disease who underwent extensive cardiovascular examination. Arterial stiffness was evaluated by cardio-ankle vascular index (CAVI). Speckle-tracking echocardiography was employed to evaluate LA phasic function including reservoir, conduit, and pump strain as well as left ventricular global longitudinal strain (LVGLS).

Results: CAVI was negatively correlated with reservoir and conduit strain (r = -0.37 and -0.45, both P < 0.001), whereas weakly, but positively correlated with LA volume index and pump strain (r = 0.12 and 0.09, both P < 0.01). In multivariable analysis, CAVI was significantly associated with reservoir and conduit strain independent of traditional cardiovascular risk factors and LV morphology and function including LVGLS (standardized β = -0.22 and -0.27, respectively, both P < 0.001), whereas there was no independent association with LA volume index and pump strain. In the categorical analysis, the abnormal CAVI (≥9.0) carried the significant risk of impaired reservoir and conduit strain (adjusted odds ratio = 2.61 and 3.73 vs. normal CAVI, both P < 0.01) in a fully adjusted model including laboratory and echocardiographic parameters.

Conclusion: Arterial stiffness was independently associated with LA phasic function, even in the absence of overt cardiovascular disease, which may explain the higher incidence of atrial fibrillation in individuals with increased arterial stiffness.
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http://dx.doi.org/10.1097/HJH.0000000000002367DOI Listing
June 2020

Is the measurement of drain amylase content useful for predicting pancreas-related complications after gastrectomy with systematic lymphadenectomy?

World J Gastroenterol 2020 Apr;26(14):1594-1600

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

Many studies investigating postoperative pancreatic fistula (POPF) after gastrectomy, including studies measuring drain amylase content (D-AMY) as a predictive factor have been reported. This article reviews previous studies and looks to the future of measuring D-AMY in patients after gastrectomy. The causes of pancreatic fluid leakage are; the parenchymal and/or thermal injury to the pancreas, and blunt injury to the pancreas by compression and retraction. Measurement of D-AMY to predict POPF has become common in clinical practice after pancreatic surgery and was later extended to the gastric surgery. Several studies have reported associations between D-AMY and POPF after gastrectomy, and the high value of D-AMY on postoperative day (POD) 1 was an independent risk factor. To improve both sensitivity and specificity, attempts have been made to enhance the predictive accuracy of factors on POD 1 as well as on POD 3 as combined markers. Although several studies have shown a high predictive ability of POPF, it has not necessarily been exploited in clinical practice. Many problems remain unresolved; ideal timing for measurement, optimal cut-off value, and means of intervention after prediction. Prospective clinical trial could be imperative in order to develop D-AMY measurement in common clinical practice for gastric surgery.
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http://dx.doi.org/10.3748/wjg.v26.i14.1594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167417PMC
April 2020

Serum uric acid level and subclinical left ventricular dysfunction: a community-based cohort study.

ESC Heart Fail 2020 06 6;7(3):1031-1038. Epub 2020 Apr 6.

Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Aims: Although serum uric acid (SUA) level is correlated with oxidative stress and serves as a marker of poor prognosis in heart failure patients, its possible association with subclinical left ventricular (LV) dysfunction has not been evaluated. This study aimed to investigate the association between SUA and subclinical LV dysfunction in a sample of a general population without overt cardiac disease.

Methods And Results: We examined 1175 participants who underwent extensive cardiovascular health check-up including laboratory tests and speckle-tracking echocardiography to assess LV global longitudinal strain (GLS). The association of SUA concentration, as a continuous variable and a categorical variable using quartiles, with the presence of abnormal LVGLS was assessed. Mean age was 62 ± 12 years, and 656 (56%) were male participants. Mean SUA was 5.6 ± 1.3 mg/dL (25th-75th percentile, 4.6-6.5 mg/dL). The prevalence of abnormal LVGLS (greater than -18.6%) was greatest in the upper quartile of SUA. In multivariable analysis, SUA as a continuous variable was significantly associated with abnormal LVGLS [adjusted odds ratio (OR), 1.26 per 1 mg/dL; P = 0.008] independent of traditional cardiovascular risk factors, pertinent laboratory parameters and echocardiographic measures, and medications. In the categorical analysis, the upper quartile of SUA was independently associated with abnormal LVGLS in a fully adjusted model (adjusted OR, 2.28 vs. lowest quartile; P = 0.020).

Conclusions: In a sample of the general population, an elevated SUA was independently associated with subclinical LV dysfunction. Assessment of LVGLS may add important prognostic information in individuals with elevated SUA, even in the absence of overt cardiac disease.
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http://dx.doi.org/10.1002/ehf2.12691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261553PMC
June 2020

Comparison Between Healthcare-Associated and Community-Acquired Infective Endocarditis at Tertiary Care Hospitals in Japan.

Circ J 2020 03 5;84(4):670-676. Epub 2020 Mar 5.

Department of Cardiovascular Medicine, The University of Tokyo.

Background: Healthcare-associated infective endocarditis (HAIE) has become increasingly recognized worldwide because the underlying patient conditions are completely different from those of community-acquired infective endocarditis (CIE). However, data on HAIE in the Japanese population is lacking. We sought to clarify the patient characteristics and prognosis of HAIE in a Japanese population.Methods and Results:A retrospective study was conducted in 158 patients who were diagnosed with infective endocarditis, 53 of whom (33.5%) were classified as HAIE. Compared with patients with CIE, those with HAIE were older (median age 72 vs. 61 years; P=0.0002) and received surgical treatment less frequently (41.5% vs. 62.9%; P=0.01). Regarding causative microorganisms, staphylococci,including methicillin-resistant pathogens, were more common in patients with HAIE (32.1% vs. 14.3%; P=0.01). Patients with HAIE had higher in-hospital mortality (32.1% vs. 4.8%; P<0.0001) and Kaplan-Meier analysis showed worse prognosis for patients with HAIE than CIE (P<0.0001, log-rank test). On multivariate Cox analysis, HAIE (hazard ratio 3.26; 95% confidence interval 1.49-7.14), age ≥60 years, surgical treatment, stroke, and heart failure were independently associated with mortality.

Conclusions: HAIE has different clinical characteristics and causative microorganisms, as well as worse prognosis, than CIE. Preventive strategies, and the prompt and appropriate identification of HAIE may improve the outcome of infective endocarditis.
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http://dx.doi.org/10.1253/circj.CJ-19-0887DOI Listing
March 2020

Importance of surgical expertise in septal myectomy for obstructive hypertrophic cardiomyopathy.

Gen Thorac Cardiovasc Surg 2020 Oct 27;68(10):1094-1100. Epub 2020 Feb 27.

Department of Surgery, Division of Cardiothoracic Surgery, Columbia University Medical Center, 177 Fort Washington Ave, New York, NY, USA.

Objective: In 2011, a multidisciplinary hypertrophic cardiomyopathy (HCM) program with a dedicated myectomy surgeon was implemented at our institution. We hypothesized that a dedicated approach allows better identification and management of mitral regurgitation (MR) during septal myectomy (SM) for obstructive HCM with significant mitral regurgitation.

Methods: Between 2006 and 2018, 181 patients had SM at our institution. This study consists of 53 patients with preoperative moderate or greater MR associated with systolic anterior motion who underwent isolated SM with or without mitral intervention. Patients were divided into those who underwent SM by a dedicated myectomy surgeon (group D, n = 31) or by a non-dedicated surgeon (group ND, n = 22). Primary outcome of interest was rate of mitral valve replacement (MVR) at SM. Secondary outcomes include in-hospital mortality, need for permanent pacemaker, mitral valve reoperation, and residual MR and left ventricular outflow tract gradient on postoperative echocardiography.

Results: 12 patients (55%) had a concomitant MVR during septal myectomy in group ND compared to 2 patients (6%) in group D (p < 0.01). Among patients who did not undergo MVR, patients in group D less commonly had residual MR than patients in ND after SM (p < 0.01). Group D had 100% survival with NYHA class I in 94% patients at follow-up visit (p = 0.01). Reoperation for MVR was required in four patients in group ND vs. none in group D (p < 0.01).

Conclusions: A dedicated surgeon is able to spare the mitral valve in patients undergoing SM. This study emphasizes the importance of surgical expertise in this cohort.
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http://dx.doi.org/10.1007/s11748-020-01320-7DOI Listing
October 2020

Propensity-score-matched analysis of a multi-institutional dataset to compare postoperative complications between Billroth I and Roux-en-Y reconstructions after distal gastrectomy.

Gastric Cancer 2020 07 17;23(4):734-745. Epub 2020 Feb 17.

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background: Few well-controlled studies have compared postoperative complications between Billroth I (B-I) and Roux-en-Y (R-Y). The aim of the present study was to compare the incidence of overall and severe postoperative complications by reconstruction method after distal gastrectomy.

Methods: We performed a multi-institutional dataset study of patients who underwent distal gastrectomy with B-I or R-Y reconstruction from 2010 to 2014. Using propensity scores to strictly balance the significant variables, we compared postoperative complications between the techniques.

Results: After matching, we enrolled 1014 patients (n = 507 in each group). The incidence of postoperative complications in the R-Y group was significantly higher vs the B-I group (29% vs 17%, P < 0.0001). The incidence of intra-abdominal abscess (4.3% vs 1.8%, P = 0.0177), bowel obstruction (2.6% vs 0.6%, P = 0.0203), and delayed gastric emptying (5.3% vs 1.0%, P < 0.0001) in the R-Y group was significantly higher vs the B-I group, respectively; we saw no significant difference in leakage (3.4% vs 4.1%, P = 0.5084). The incidence of grade ≥ III severe postoperative complications in the R-Y group was significantly higher vs the B-I group (13% vs 7.1%, P = 0.0013). Multivariable analysis showed that R-Y reconstruction was a strong independent risk factor for overall postoperative complications (odds ratio 1.58, P = 0.0044) and grade ≥ III severe postoperative complications (odds ratio 1.75, P = 0.0127). A forest plot revealed that R-Y reconstruction was associated with a greater risk of both overall and grade ≥ III severe postoperative complications in any subgroups.

Conclusions: R-Y reconstruction was associated with increasing overall postoperative complications, as well as severe postoperative complications.
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http://dx.doi.org/10.1007/s10120-020-01048-6DOI Listing
July 2020

Influence of visceral adiposity accumulation on adverse left and right ventricular mechanics in the community.

Eur J Prev Cardiol 2020 12 3;27(18):2006-2015. Epub 2019 Dec 3.

Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Aims: Obesity carries significant risk for unfavorable ventricular remodeling and subsequent heart failure (HF) development, although the association between abdominal fat distribution and subclinical ventricular dysfunction is unclear. This study aimed to compare the subcutaneous and visceral abdominal adiposity with the risk of decreased ventricular strain.

Methods: We included 340 participants without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination, and speckle-tracking echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess left ventricular global longitudinal strain (LVGLS) and right ventricular free-wall longitudinal strain (RVLS).

Results: Mean age was 56 ± 9 years, and 244 of the participants (72%) were male. The mean LVGLS and RVLS were -19.1 ± 3.0% and -25.0 ± 4.1%, respectively. Both VFA and SFA correlated with LVGLS ( = 0.46 and  = 0.15, both  < 0.01) and RVLS ( = 0.38 and  = 0.12, both  < 0.05), demonstrating a stronger correlation between VFA and ventricular strain. Multivariable analysis showed that VFA was significantly associated with LVGLS and RVLS, independent of traditional cardiovascular risk factors as well as pertinent laboratory and echocardiographic parameters (both  < 0.05), whereas SFA was not. Serum adiponectin level was correlated with LVGLS ( = -0.34,  < 0.001) and RVLS ( = -0.25,  < 0.001), although it lost statistical significance following multivariable adjustment.

Conclusion: In a sample of the general population, VFA, but not SFA, accumulation was significantly associated with decreased LV and RV strain, an association that may be involved in the increased risk of HF in obese individuals.
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http://dx.doi.org/10.1177/2047487319891286DOI Listing
December 2020

Cognitive Decline Over Time in Patients With Systolic Heart Failure: Insights From WARCEF.

JACC Heart Fail 2019 12;7(12):1042-1053

Columbia University Medical Center, New York, NY. Electronic address:

Objectives: This study sought to characterize cognitive decline (CD) over time and its predictors in patients with systolic heart failure (HF).

Background: Despite the high prevalence of CD and its impact on mortality, predictors of CD in HF have not been established.

Methods: This study investigated CD in the WARCEF (Warfarin versus Aspirin in Reduced Ejection Fraction) trial, which performed yearly Mini-Mental State Examinations (MMSE) (higher scores indicate better cognitive function; e.g., normal score: 24 or higher). A longitudinal time-varying analysis was performed among pertinent covariates, including baseline MMSE and MMSE scores during follow-up, analyzed both as a continuous variable and a 2-point decrease. To account for a loss to follow-up, data at the baseline and at the 12-month visit were analyzed separately (sensitivity analysis).

Results: A total of 1,846 patients were included. In linear regression, MMSE decrease was independently associated with higher baseline MMSE score (p < 0.0001), older age (p < 0.0001), nonwhite race/ethnicity (p < 0.0001), and lower education (p < 0.0001). In logistic regression, CD was independently associated with higher baseline MMSE scores (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.07 to 1.20]; p < 0.001), older age (OR: 1.37; 95% CI: 1.24 to 1.50; p < 0.001), nonwhite race/ethnicity (OR: 2.32; 95% CI: 1.72 to 3.13 for black; OR: 1.94; 95% CI: 1.40 to 2.69 for Hispanic vs. white; p < 0.001), lower education (p < 0.001), and New York Heart Association functional class II or higher (p = 0.03). Warfarin and other medications were not associated with CD. Similar trends were seen in the sensitivity analysis (n = 1,439).

Conclusions: CD in HF is predicted by baseline cognitive status, demographic variables, and NYHA functional class. The possibility of intervening on some of its predictors suggests the need for the frequent assessment of cognitive function in patients with HF. (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF]; NCT00041938).
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http://dx.doi.org/10.1016/j.jchf.2019.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944056PMC
December 2019

Effect of Body Weight Change on Blood Pressure in a Japanese General Population with a Body Mass Index ≥ 22 kg/m.

Int Heart J 2019 Nov 15;60(6):1381-1386. Epub 2019 Nov 15.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.

The association between changes in body weight and blood pressure (BP) in overweight people in the general population still remains unclear. We sought to clarify the effect of body weight change on BP using a community-based cohort. We studied 1,170 overweight subjects with a body mass index (BMI) ≥ 22 kg/m who underwent health check-ups. Among the study subjects, 175 (15%) were categorized in the weight loss group (weight loss ≥ 5%), 869 (74%) in the weight stable group, and 126 (11%) in the weight gain group (weight gain ≥ 5%). There were no significant differences in baseline BP between the 3 groups. In the weight loss group, systolic and diastolic BP, and the rates of stage 2 (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) and stage 1 hypertension (130 mmHg≤ systolic BP < 140 mmHg or 80 mmHg≤ diastolic BP < 90 mmHg) decreased. In contrast, in the weight gain group, systolic and diastolic BP and the rate of stage 2 hypertension increased. Subgroup analysis showed that the correlation between change in body weight and BP was seen in each subgroup according to age, sex, and BMI. The results of the present study suggest the significance of body weight control for BP control in subjects with BMI ≥ 22 kg/m.
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http://dx.doi.org/10.1536/ihj.19-314DOI Listing
November 2019

Dietary Saturated Fat Promotes Arrhythmia by Activating NOX2 (NADPH Oxidase 2).

Circ Arrhythm Electrophysiol 2019 11 31;12(11):e007573. Epub 2019 Oct 31.

Department of Medicine (L.C.J., U.M.R.A., E.Y.W., M.V.R., K.R.L., K.N., S.H., U.B.P., J.P.M.).

Background: Obesity and diets high in saturated fat increase the risk of arrhythmias and sudden cardiac death. However, the molecular mechanisms are not well understood. We hypothesized that an increase in dietary saturated fat could lead to abnormalities of calcium homeostasis and heart rhythm by a NOX2 (NADPH oxidase 2)-dependent mechanism.

Methods: We investigated this hypothesis by feeding mice high-fat diets. In vivo heart rhythm telemetry, optical mapping, and isolated cardiac myocyte imaging were used to quantify arrhythmias, repolarization, calcium transients, and intracellular calcium sparks.

Results: We found that saturated fat activates NOX (NADPH oxidase), whereas polyunsaturated fat does not. The high saturated fat diet increased repolarization heterogeneity and ventricular tachycardia inducibility in perfused hearts. Pharmacological inhibition or genetic deletion of NOX2 prevented arrhythmogenic abnormalities in vivo during high statured fat diet and resulted in less inducible ventricular tachycardia. High saturated fat diet activates CaMK (Ca/calmodulin-dependent protein kinase) in the heart, which contributes to abnormal calcium handling, promoting arrhythmia.

Conclusions: We conclude that NOX2 deletion or pharmacological inhibition prevents the arrhythmogenic effects of a high saturated fat diet, in part mediated by activation of CaMK. This work reveals a molecular mechanism linking cardiac metabolism to arrhythmia and suggests that NOX2 inhibitors could be a novel therapy for heart rhythm abnormalities caused by cardiac lipid overload.
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http://dx.doi.org/10.1161/CIRCEP.119.007573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004280PMC
November 2019

Alteration of Cardiac Performance and Serum B-Type Natriuretic Peptide Level in Healthy Aging.

J Am Coll Cardiol 2019 10;74(14):1789-1800

Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.

Background: The impact of aging on cardiac function is not fully elucidated. Speckle-tracking echocardiography can unmask subclinical cardiac dysfunction.

Objectives: This study investigated the impact of healthy aging on left ventricular (LV), right ventricular (RV), and left atrial (LA) performance and their relationship with serum B-type natriuretic peptide (BNP) levels in a sample of the general population without prevalent cardiovascular risk factors and structural heart disease.

Methods: Speckle-tracking echocardiography was performed to assess LV global longitudinal strain (LVGLS), RV free wall strain, and LA phasic strain in 481 normal weight healthy participants who underwent extensive cardiovascular examination. Elevated BNP was defined as BNP >37.82 pg/ml for men and >50.86 pg/ml for women, which was the 90th percentile of BNP value distribution in the study population.

Results: Mean age was 60 ± 12 years (range: 24 to 86 years), and 46% of the participants were men. The earliest alteration of age-related cardiac performance was observed in LA reservoir and conduit strain starting from decade 5, followed by elevated E/e' from decade 6. LVGLS decreased starting from decade 7, whereas there were no significant differences in RV strain, LV ejection fraction, or LV mass index across the decades. In the multivariable linear regression analyses, age was an independent predictor of decreased LVGLS (standardized β = 0.21; p < 0.001) and decreased LA phasic strain (standardized β = -0.40 and -0.61 for reservoir and conduit strain; both p < 0.001). Age and LA strain were significantly associated with elevated BNP values (adjusted odds ratios: 1.10 and 0.93; both p < 0.05, respectively), independent of ventricular morphology and function.

Conclusions: Decreases in LA reservoir and conduit strain are the earliest markers of age-related cardiac remodeling, and LA reservoir strain is an independent predictor of elevated serum BNP level, with both possibly being markers of increased risk of heart failure in older adults.
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http://dx.doi.org/10.1016/j.jacc.2019.07.080DOI Listing
October 2019
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