Network Analysis of Cardiac Remodeling by Primary Mitral Regurgitation Emphasizes the Role of Diastolic Function.

BACKGROUND: Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics. OBJECTIVES: The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data. METHODS: Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups. RESULTS: The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P < 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003). CONCLUSIONS: The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR.

Intersection Between Diabetes and Heart Failure: Is SGLT2i the "One Stone for Two Birds" Approach?

PURPOSE OF REVIEW: Diabetes mellitus (DM) is a major comorbidity of heart failure (HF). Comparing the similarities and differences in disease characteristics and treatment between the HF patients with and without DM, this review was to investigate whether and how the novel class of sodium-glucose transport protein 2 inhibitors (SGLT2i) would benefit both populations. RECENT FINDINGS: Despite the obviously different clinical profiles, patients of HF with reduced ejection fraction (HFrEF) should be treated the same with guideline directed medical therapy, irrespective of DM status. Upon the mounting evidence that supported its use in diabetic patients at high risk of HF, recent large clinical trials demonstrated that SGLT2i could further reduce HF hospitalization or cardiovascular mortality and improve quality of life in diabetic and non-diabetic HFrEF patients who were optimally managed. SGLT2i expands the foundation of HFrEF therapy. Whether it is equally effective in HF with preserved ejection fraction awaits more evidence.

Passive Prescription of Secondary Prevention Medical Therapy during Index Hospitalization for Acute Myocardial Infarction Is Prevalent and Associated with Adverse Clinical Outcomes.

Secondary prevention therapy reduces death and reinfarction after acute myocardial infarction (AMI), but it is underutilized in clinical practice. Mechanisms for this therapeutic gap are not well established. In this study, we have explored and evaluated the impact of passive continuation compared to active initiation of secondary prevention therapy for AMI during the index hospitalization. For this purpose, we have analyzed 1083 consecutive patients with AMI to a tertiary referral hospital in Hong Kong and assessed discharge prescription rates of secondary prevention therapies (aspirin, beta-blockers, statins, and ACEI/ARBs). Multivariate analysis was used to identify independent predictors of discharge medication, and Kaplan-Meier survival curve was used to evaluate 12-month survival. Overall, prescription rates of aspirin, beta-blocker, statin, and ACEI/ARBs on discharge were 94.8%, 64.5%, 83.5%, and 61.4%, respectively. Multivariate analysis showed that prior use of each therapy was an independent predictor of prescription of the same therapy on discharge: aspirin (odds ratio (OR) = 4.8, 95% CI = 1.9-12.3, P < 0.01), beta-blocker (OR = 2.5, 95% CI = 1.8-3.4, P < 0.01); statin (OR = 8.3, 95% CI = 0.4-15.7, P < 0.01), and ACEI/ARBs (OR = 2.9, 95% CI = 2.0-4.3, P < 0.01). Passive continuation of prior medication was associated with higher 1-year mortality rates than active initiation in treatment-naïve patients (aspirin (13.7% vs. 5.7%), beta-blockers (12.9% vs. 5.6%), and statins (11.0% vs. 4.6%); all P < 0.01). Overall, the use of secondary prevention medication for AMI was suboptimal. Our findings suggested that the practice of passive continuation of prior medication was prevalent and associated with adverse clinical outcomes compared to active initiation of secondary preventive therapies for acute myocardial infarction during the index hospitalization.

Discrepancy of Aortic Valve Area Measurements by Doppler vs. Biplane Stroke Volume Measurements and Utility of Combining the Different Areas in Aortic Valve Stenosis　- The Asian Valve Registry.

BACKGROUND: The aortic valve area index (AVAI) in aortic stenosis (AS) is measured by echocardiography with a continuity equation using the stroke volume index by Doppler (SVIDoppler) or biplane Simpson (SVIBiplane) method. AVAIDopplerand AVAIBiplaneoften show discrepancy due to differences between SVIDopplerand SVIBiplane. The degree of discrepancy and utility of combined AVAIs have not been investigated in a large population of AS patients, and the characteristics of subjects with larger discrepancies are unknown.Methods and Results:We studied 820 patients with significant AS (AVADoppler<1.5 cm2) enrolled in the Asian Valve Registry, a prospective multicenter registry at 12 Asian centers. All-cause death and aortic valve replacement were defined as events. SVIDopplerwas significantly larger than SVIBiplane(49±11 vs. 39±11 mL/m2, P<0.01) and AVAIDopplerwas larger than AVAIBiplane(0.51±0.15 vs. 0.41±0.14 cm2/m2, P<0.01). An increase in (AVAIDoppler- AVAIBiplane) correlated with shorter height, lower weight, older age, smaller left ventricular (LV) diameter and increased velocity of ejection flow at the LV outflow tract. Severe AS by AVAIDoppleror AVAIBiplaneenabled prediction of events, and combining these AVAIs improved the predictive value of each. CONCLUSIONS: Discrepancy in AVAI by Doppler vs. biplane method was significantly more pronounced with increased LV outflow tract flow velocity, shorter height, lower weight, older age and smaller LV cavity dimensions. Combining the AVAIs enabled mutual and incremental value in predicting events.

Changes of echocardiographic parameters in primary mitral regurgitation and determinants of symptom: an assessment from the Asian Valve Registry data.

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2 (severe) (p < 0.001), LV end-diastolic diameter: 51.2, 54.5, 58.1 mm (p < 0.001), and LV mass index: 101, 109, 123 g/m2 (p < 0.001)]. Regarding moderate and severe MR, 70 patients (10.4%) were symptomatic. In multivariable analysis, for being symptomatic in moderate and severe MR patients, LV mass index (odds ratio [OR] per 10 g/m2 increment; 1.09; 95% confidence interval [CI]: 1.005-1.18, p = 0.040), ejection fraction (OR per 1% increment; 0.96, 95%CI: 0.93-0.98, p < 0.001), female gender (OR 2.28; 95% CI: 1.31-3.98, p = 0.004), and heart rate (OR per 1 bpm increment; 1.03; 95%CI: 1.01-1.05, p = 0.007) were independent factors. LV and LA parameters on echocardiography worsened as MR severity progressed. Larger LV mass index and lower ejection fraction were independent determinant factors for MR-related symptoms. We should also pay attention to LV hypertrophy in patients with primary MR.

Heart failure with preserved ejection fraction in Asia.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a global public health problem. Unfortunately, little is known about HFpEF across Asia. METHODS AND RESULTS: We prospectively studied clinical characteristics, echocardiographic parameters and outcomes in 1204 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions, grouped as Northeast Asia (Hong Kong, Taiwan, China, Japan, Korea, n = 543), South Asia (India, n = 252), and Southeast Asia (Malaysia, Thailand, Singapore, Indonesia, Philippines, n = 409). Mean age was 68 ±12 years (37% were < 65 years) and 50% were women. Seventy per cent of patients had ≥2 co-morbidities, most commonly hypertension (71%), followed by anaemia (57%), chronic kidney disease (50%), diabetes (45%), coronary artery disease (29%), atrial fibrillation (29%) and obesity (26%). Southeast Asian patients had the highest prevalence of all co-morbidities except atrial fibrillation, South Asians had the lowest prevalence of all co-morbidities except anaemia and obesity, and Northeast Asians had more atrial fibrillation. Left ventricular hypertrophy and concentric remodelling were most prominent among Southeast and South Asians, respectively (P < 0.001). Overall, 12.1% of patients died or were hospitalized for heart failure within 1 year. Southeast Asians were at higher risk for adverse outcomes, independent of co-morbidity burden and cardiac geometry. CONCLUSION: These first prospective multinational data from Asia show that HFpEF affects relatively young patients with a high burden of co-morbidities. Regional differences in types of co-morbidities, cardiac remodelling and outcomes of HFpEF across Asia have important implications for public health measures and global HFpEF trial design.

Impact of diabetes and sex in heart failure with reduced ejection fraction patients from the ASIAN-HF registry.

AIMS: To examine sex differences in clinical characteristics, echocardiographic features, quality of life and 1-year death or heart failure (HF) hospitalization outcomes in patients with/without diabetes mellitus (DM). METHODS AND RESULTS: Utilizing the Asian Sudden Cardiac Death in HF (ASIAN-HF) registry, 5255 patients (mean age 59.6 ± 13.1, 78% men) with symptomatic HF with reduced ejection fraction (HFrEF) were stratified by DM status to address the research aims. Despite similar prevalence of DM between Asian men (43%) and women (42%), the odds of DM increased at lower body mass index in women vs. men (≥ 23 vs. ≥ 27.5 kg/m2 , Pinteraction = 0.014). DM was more strongly related to chronic kidney disease in women vs. men [adjusted odds ratio (OR) 1.85, 95% confidence interval (CI) 1.33-2.57 vs. OR 1.32, 95% CI 1.11-1.56, Pinteraction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (Pinteraction = 0.003), whereby DM was associated with a more concentric left ventricular geometry in women than men. Women had lower quality of life than men (P < 0.001), in both DM and non-DM groups. DM was associated with worse composite outcomes at 1 year in women vs. men [hazard ratio (HR) 1.79, 95% CI 1.24-2.60 vs. HR 1.32, 95% CI 1.12-1.56; Pinteraction = 0.005). CONCLUSIONS: Asian women with HFrEF were more likely to have DM despite a lean body mass index, a greater burden of chronic kidney disease and more concentric left ventricular geometry, compared to men. Furthermore, DM confers worse quality of life, irrespective of sex, and a greater risk of adverse outcomes in women than men. These data underscore the need for sex-specific approaches to diabetes in patients with HF.

Sustained 3-Year Benefits in Quality of Life After Percutaneous Coronary Interventions in the Elderly: A Prospective Cohort Study.

BACKGROUND: Impact of percutaneous coronary interventions (PCI) on health-related quality of life (HRQOL) is important but under-reported in elderly patients. OBJECTIVES: To evaluate long-term health status in elderly patients who underwent PCI. METHODS: Consecutive patients who underwent PCI at a university-affiliated hospital from September 2009 to June 2012 were prospectively enrolled with HRQOL assessment at baseline (up to 2 weeks before PCI) and at 6-, 12-, and 36-month follow-up using the EuroQol five-dimensional questionnaire descriptive profile and visual analogue scale (VAS). Minimally important benefit (MIB) in HRQOL was defined as greater than half an SD improvement in the baseline VAS score. RESULTS: Of 1957 patients, 49.9%, 29.1%, and 21.0% were aged younger than 65 years, 65 to 74 years, and 75 years and older, respectively. Mean VAS scores at baseline (50.1 ± 20.5 vs. 51.6 ± 20.5 vs. 52.6 ± 21.8; P = 0.09) and at 36 months (72.9 ± 14.0 vs. 72.8 ± 16.1 vs. 72.0 ± 14.8; P = 0.77) were similar between the three age groups, respectively. MIB at 36 months was observed in 65.7%, 61.9%, and 61.2% of patients in each age group, respectively. Proportion of patients aged 75 years and older reporting problems in pain/discomfort and self-care reduced from 91.2% and 24.8% at baseline to 41.4% and 10.1% at 36 months, respectively (both P < 0.01). Independent predictors of MIB in HRQOL at 36 months in patients 75 years and older included poor baseline HRQOL, MIB at 6 months, and presentation with myocardial infarction (all P < 0.01). CONCLUSIONS: Elderly patients experienced sustained long-term improvement in quality of life comparable with younger patients after PCI. Our findings suggest that age per se should not deter against revascularization because of sustained benefit in HRQOL.

Prevalence, clinical correlates, and outcomes of anaemia in multi-ethnic Asian patients with heart failure with reduced ejection fraction.

AIMS: Recent international heart failure (HF) guidelines recognize anaemia as an important comorbidity contributing to poor outcomes in HF, based on data mainly from Western populations. We sought to determine the prevalence, clinical correlates, and prognostic impact of anaemia in patients with HF with reduced ejection fraction across Asia. METHODS AND RESULTS: We prospectively studied 3886 Asian patients (60 ± 13 years, 21% women) with HF (ejection fraction ≤40%) from 11 regions in the Asian Sudden Cardiac Death in Heart Failure study. Anaemia was defined as haemoglobin <13 g/dL (men) and <12 g/dL (women). Ethnic groups included Chinese (33.0%), Indian (26.2%), Malay (15.1%), Japanese/Korean (20.2%), and others (5.6%). Overall, anaemia was present in 41%, with a wide range across ethnicities (33-54%). Indian ethnicity, older age, diabetes, and chronic kidney disease were independently associated with higher odds of anaemia (all P < 0.001). Ethnicity modified the association of chronic kidney disease with anaemia (Pinteraction  = 0.045), with the highest adjusted odds among Japanese/Koreans [2.86; 95% confidence interval (CI) 1.96-4.20]. Anaemic patients had lower Kansas City Cardiomyopathy Questionnaire scores (P < 0.001) and higher risk of all-cause mortality and HF hospitalization at 1 year (hazard ratio = 1.28, 95% CI 1.08-1.50) compared with non-anaemic patients. The prognostic impact of anaemia was modified by ethnicity (Pinteraction  = 0.02), with the greatest hazard ratio in Japanese/Koreans (1.82; 95% CI 1.14-2.91). CONCLUSIONS: Anaemia is present in a third to more than half of Asian patients with HF and adversely impacts quality of life and survival. Ethnic differences exist wherein prevalence is highest among Indians, and survival is most severely impacted by anaemia in Japanese/Koreans.

Incremental prognostic value of multichamber deformation imaging and renal function status to predict adverse outcome in heart failure with reduced ejection fraction.

AIMS: Deformation imaging, particularly of left-sided heart, is fast becoming an essential tool in clinical cardiology. However, data are scant regarding the value of biventricular and bi-atrial deformation in association with comorbidities in heart failure with reduced left ventricular ejection fraction (HFREF). METHODS AND RESULTS: Forty-nine subjects (72 ± 13 years; 28 male) with HFREF and 14 age-matched controls underwent deformation imaging including LV global longitudinal strain (LVGLS%), right ventricular strain (RVS%), and left atrial reservoir strain (LARS%). Standard echo parameters included LVEF%, E/E' ratio, and pulmonary artery systolic pressure (PASP). Mean ± SD of LVEF, LVGLS%, and RVS% were 31% ± 8%, 7% ± 3%, and 17% ± 7%, respectively, and were significantly lower compared with controls (all P < .0001). Over a follow-up period of 4.2 years, 24% of patients died and 48% had a composite outcome of death and heart failure hospitalization. In the logistic regression model, taking the composite of death and heart failure hospitalization as a dichotomous variable, RVS%, E/E' ratio, and PASP were the only significant univariate predictors of adverse outcome (R2  = .68, all P < .05). In the multivariate model, however, only PASP predicted adverse outcome. PASP also had the largest AUC (0.8) in the ROC analysis. A creatinine level of >88 µmol/L (SCREAT) and a cutoff value of LA reservoir strain (LARS %) at <16.7% provided the best sensitivity (86%) and specificity (40%) with an odds ratio of 3.8. In the Kaplan-Meier survival estimate, LARS%-SCREAT predicted all-cause mortality and HF hospitalization. CONCLUSION: Multichamber deformation imaging along with renal function and PASP could best predict adverse outcome in HFREF.

Comparison between characteristics of severe and very severe aortic stenosis.

OBJECTIVES: Patients with very severe aortic stenosis (AS) have extremely poor clinical outcomes even if they are asymptomatic compared to those with severe AS, but the clinical and echocardiographic characteristics of patients with very severe AS remain unclear. METHODS: The Asian Valve Registry is a prospective, multicenter, multinational registry for the study and identification of the incidence, natural course, clinical outcomes, and prognostic factors for patients with significant AS at 9 centers in Asian countries. Severe AS was observed in 367 of 1066 patients with AS, and 212 were classified as very severe AS, defined as a peak aortic valve velocity ≥5.0 m/s or a mean aortic valve gradient ≥60 mm Hg. RESULTS: The prevalence of NYHA functional class II-IV among patients with very severe AS was significantly higher than that among patients with severe AS (67.9% vs 51.5%, P < .001). As for echocardiographic parameters, it was noteworthy that left ventricular mass index (LVMI) and left atrial volume index (LAVI) for patients with very severe AS were significantly larger than those for patients with severe AS (LVMI: 145.1 ± 36.4 g/m2 vs 119.2 ± 32.1 g/m2 , P < .0001; LAVI: 56.1 ± 24.6 mL/m2 vs 49.8 ± 22.6 mL/m2 , P = .002). Moreover, multivariate logistic regression analysis showed that LVMI was the only independently associated with NYHA functional class II-IV in patients with very severe AS. CONCLUSIONS: Our findings may well have clinical implications for better management of patients with AS and lead to better understanding of poor outcomes for patients with very severe AS.

Patients with ST-segment elevation of myocardial infarction miss out on early reperfusion: when to undergo delayed revascularization.

OBJECTIVE: There are still a high proportion of patients with ST-segment elevation myocardial infarction (STEMI) missing out early reperfusion even in the primary percutaneous coronary intervention (PCI) era. Most of them are stable latecomers, but the optimal time to undergo delayed PCI for stable ones remains controversial. METHODS: We investigated all STEMI patients who underwent delayed PCI (2-28 days after STEMI) during 2007-2010 in Beijing and excluded patients with hemodynamic instability. The primary outcome was major adverse cardiovascular events (MACEs). RESULTS: This study finally enrolled 5,417 STEMI patients and assigned them into three groups according to individual delayed time (Early group, 55.9%; Medium group, 35.4%; Late group, 8.7%). During 1-year follow-up, MACEs occurred in 319 patients. The incidence of MACEs were respectively 7.1%, 5.6% and 6.7% among three groups. The Medium group had less recurrent myocardial infarction plus cardiac death (hazard ratio, 0.525; 95% confidence interval, 0.294-0.938, P = 0.030) than Late group and less repeat revascularization (hazard ratio, 0.640; 95% confidence interval, 0.463-0.883, P = 0.007) than Early group in pairwise comparisons. We depicted the incidence of major adverse cardiovascular event (MACE) by delayed time as a quadratic curve and found the bottom appeared at day 14. CONCLUSIONS: The delayed PCI time varied in the real-world practice, but undergoing operations on the second week after STEMI had greater survival benefit and less adverse events for whom without early reperfusion and hemodynamic instability.

Disparity Between Indications for and Utilization of Implantable Cardioverter Defibrillators in Asian Patients With Heart Failure.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are lifesaving devices for patients with heart failure (HF) and reduced ejection fraction. However, utilization and determinants of ICD insertion in Asia are poorly defined. We determined the utilization, associations of ICD uptake, patient-perceived barriers to device therapy and, impact of ICDs on mortality in Asian patients with HF. METHODS AND RESULTS: Using the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, 5276 patients with symptomatic HF and reduced ejection fraction (HFrEF) from 11 Asian regions and across 3 income regions (high: Hong Kong, Japan, Korea, Singapore, and Taiwan; middle: China, Malaysia, and Thailand; and low: India, Indonesia, and Philippines) were studied. ICD utilization, clinical characteristics, as well as device perception and knowledge, were assessed at baseline among ICD-eligible patients (EF ≤35% and New York Heart Association Class II-III). Patients were followed for the primary outcome of all-cause mortality. Among 3240 ICD-eligible patients (mean age 58.9±12.9 years, 79.1% men), 389 (12%) were ICD recipients. Utilization varied across Asia (from 1.5% in Indonesia to 52.5% in Japan) with a trend toward greater uptake in regions with government reimbursement for ICDs and lower out-of-pocket healthcare expenditure. ICD (versus non-ICD) recipients were more likely to be older (63±11 versus 58±13 year; P<0.001), have tertiary (versus ≤primary) education (34.9% versus 18.1%; P<0.001) and be residing in a high (versus low) income region (64.5% versus 36.5%; P<0.001). Among 2000 ICD nonrecipients surveyed, 55% were either unaware of the benefits of, or needed more information on, device therapy. ICD implantation reduced risks of all-cause mortality (hazard ratio, 0.71; 95% confidence interval, 0.52-0.97) and sudden cardiac deaths (hazard ratio, 0.33; 95% confidence interval, 0.14-0.79) over a median follow-up of 417 days. CONCLUSIONS: ICDs reduce mortality risk, yet utilization in Asia is low; with disparity across geographic regions and socioeconomic status. Better patient education and targeted healthcare reforms in extending ICD reimbursement may improve access. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT01633398. Unique identifier: NCT01633398.

Efficacy and safety of instantaneous wave-free ratio in patients undergoing coronary revascularisation: protocol for a systematic review.

INTRODUCTION: Effective selection of coronary lesions for revascularisation is pivotal in the management of symptoms and adverse outcomes in patients with coronary artery disease. Recently, instantaneous 'wave-free' ratio (iFR) has been proposed as a new diagnostic index for assessing the severity of coronary stenoses without the need of pharmacological vasodilation. Evidence of the effectiveness of iFR-guided revascularisation is emerging and a systematic review is warranted. METHODS AND ANALYSIS: This is a protocol for a systematic review of randomised controlled trials and controlled observational studies. Electronic sources including MEDLINE via Ovid, Embase, Cochrane databases and ClinicalTrials.gov will be searched for potentially eligible studies investigating the effects of iFR-guided strategy in patients undergoing coronary revascularisation. Studies will be selected against transparent eligibility criteria and data will be extracted using a prestandardised data collection form by two independent authors. Risk of bias in included studies and overall quality of evidence will be assessed using validated methodological tools. Meta-analysis will be performed using the Review Manager software. Our systematic review will be performed according to the guidance from the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. ETHICS AND DISSEMINATION: Ethics approval is not required. Results of the systematic review will be disseminated as conference proceedings and peer-reviewed journal publication. TRIAL REGISTRATION NUMBER: This protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017065460.

Tetramethylpyrazine suppresses angiotensin II-induced soluble epoxide hydrolase expression in coronary endothelium via anti-ER stress mechanism.

Activation of soluble epoxide hydrolase (sEH) is associated with endothelial dysfunction in hypertension, though the underlying mechanisms are inadequately understood and the role of endoplasmic reticulum (ER) stress is yet to be studied in detail. Tetramethylpyrazine (TMP), a major bioactive ingredient of Chinese herb Chuanxiong, is well-known for its cardiovascular benefits. Nevertheless, whether TMP may protect vascular endothelium from ER stress and whether regulation of sEH is involved remain unknown. This study aimed at investigating the role of ER stress in angiotensin-II (Ang-II)-induced sEH dysregulation and elucidating the significance of ER stress regulation in the vasoprotective effect of TMP. Porcine primary coronary artery endothelial cells (PCECs) were used for western blot, ELISA, and reverse-transcription PCR analysis. Porcine coronary arteries were assessed in a myograph for endothelial dilator function. Ang-II induced expression of ER stress molecules in PCECs meanwhile enhanced sEH expression and decreased 11,12-EET. Exposure of PCECs to the chemical ER stress inducer tunicamycin also increased sEH expression. Inhibition of ER stress suppressed sEH upregulation, resulting in an increase of 11,12-EET. The impairment of endothelium-dependent vasorelaxation induced by Ang-II or tunicamycin was ameliorated by inhibitors of ER stress or sEH. TMP showed comparable inhibitory effect to ER stress inhibitors on the expression of ER stress molecules, the dysregulation of sEH/EET, and the impairment of endothelial dilator function. We demonstrated that ER stress mediates Ang-II-induced sEH upregulation in coronary endothelium. TMP has potent anti-ER stress capacity through which TMP normalizes sEH expression and confers protective effect against Ang-II on endothelial function of coronary arteries.

Risk of aortic aneurysm and dissection in patients with autosomal-dominant polycystic kidney disease: a nationwide population-based cohort study.

Although cardiovascular complications are the most common cause of death in patients with autosomal-dominant polycystic kidney disease (ADPKD), the incidence and risk of aortic aneurysm and dissection (AAD) in ADPKD remains unclear due to limited data and insufficient cases. We utilized the data from Taiwan National Health Insurance Research Database (NHIRD) to do a population-based cohort study (1997-2008). After excluding those patients with age <18 years old and initially concomitant diagnoses of end-stage renal disease and AAD, a total of 2076 ADPKD patients were selected from 1,000,000 of general population. Additionally, the non-ADPKD group was set up as comparison group in 1:10 ratio after matching with age, gender, income and urbanization (n=20760). The result showed that ADPKD group had higher frequency of comorbidities than non-ADPKD group. The frequency of AAD in ADPKD was significantly higher than in general population (0.92% v.s. 0.11%, p<0.0001). Of them, 58% of AAD were acute aortic dissection. In addition, Kaplan-Meier analysis demonstrated that cumulative incidence of AAD was remarkably higher in the ADPKD than non-ADPKD group (p<0.001). The mean time period from ADPKD diagnosis to AAD occurrence was 4.02±3.16 years. After adjusting for age, gender and comorbidities, the ADPKD patients had up to 5.49-fold greater risk for AAD occurrence as compared to non-ADPKD counterparts (95% CI 2.86-10.52, p<0.0001). Particularly, those patients with co-existing ADPKD and hypertension had very high risk for future development of AAD. In conclusion, the risk of AAD significantly increases in patients with ADPKD as compared with those of general population.

Challenges and opportunity in the era of quantitative echocardiography.

The advancement of echocardiography in the past two decades is more than downsizing of the machines and improvement of image quality, but introduction of new imaging modalities leading to the ability of performing quantitative analysis. This function is greatly facilitated by the integration of echo machines with high performance computers, software programming and establishment of workstation for offline analysis. Today, echo examination is more than estimation of ejection fraction (EF) and patterns of left ventricular (LV) diastolic dysfunction. Echosonographers are facing a large number of quantitative parameters for interpretation. In newer imaging modalities such as tissue Doppler imaging, speckle tracking, 3-dimensional echocardiography and 3D-transoesophageal echocardiography, quantitative echocardiographic assessment has important roles. These have brought many opportunities but also challenges in our echo practice.

Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury.

Despite increasing knowledge of the significance of calcium-activated potassium (KCa) and canonical transient receptor potential (TRPC) channels in endothelial physiology, no studies so far have investigated the link between these two distinct types of channels in the control of vascular tone in pathological conditions. We previously demonstrated that hypoxia-reoxygenation (H-R) inhibits endothelial KCa and TRPC3 channels in porcine coronary arteries (PCAs). The present study further investigated whether modulation of TRPC3 is involved in H-R-induced KCa channel inhibition and associated vasodilatory dysfunction using approaches of wire myography, whole-cell voltage-clamp, and coimmunoprecipitation. Pharmacological inhibition or siRNA silencing of TRPC3 significantly suppressed bradykinin-induced intermediate- and small-conductance KCa (IKCa and SKCa) currents in endothelial cells of PCAs (PCAECs). TRPC3 protein exists in physical association with neither IKCa nor SKCa. In H-R-exposed PCAECs, the response of IKCa and SKCa to bradykinin-stimulation and to TRPC3-inhibition was markedly weakened. Activation of TRPC3 channels restored H-R-suppressed KCa currents in association with an improved endothelium-derived hyperpolarizing factor (EDHF)-type vasorelaxation. We conclude that inhibition of TRPC3 channels contributes to H-R-induced suppression of KCa channel activity, which serves as a mechanism underlying coronary endothelial dysfunction in ischemia-reperfusion (I-R) injury and renders TRPC3 a potential target for endothelial protection in I-R conditions.

Clinical, humanistic, and economic outcomes between drug-eluting stent (DES) and bare metal stent (BMS): 18-month follow-up study.

BACKGROUND: Percutaneous coronary intervention (PCI) is one of the most performed interventions for ischemic heart diseases. In Hong Kong, the total number of patient discharges and deaths for ischemic heart diseases in 2009 was 33,363, including 4,360 deaths. There are over 5,000 cases of PCI yearly. This study aimed to compare clinical, economic, and humanistic outcomes among patients receiving drug-eluting stent (DES) or bare metal stent (BMS) in Hong Kong. METHODS: Patients who received stent implantation between September 15, 2009 and October 11, 2010 in Prince of Wales Hospital, Hong Kong, were recruited and followed for 18 months. Occurrence of major adverse cardiac events (cardiac death, non-fatal MI, TLR and TVR) was employed as the clinical outcome measurements. Improvement in quality-of-life by stent interventions was measured as quality-adjusted life-year (QALY). EQ-5D questionnaire was adopted to assess the QALY gained. Cost-utility analysis and cost-effectiveness analysis for BMS and DES were employed as the economic outcome measurement. RESULTS: Six hundred and eighty-four patients (DES = 402; BMS = 282) were included. From 0-18 months, TLR rate (2.7% vs 3.5%, p = .549) and TVR rate (3.7% vs 6.4%, p = .111) were lower in the DES group, but without statistical significance. EQ VAS (71.06 ± 14.56 vs 71.07 ± 16.57, p = .998) and utility score (0.81 ± 0.17 vs 0.78 ± 0.16, p = .162) were comparable between DES and BMS group. Overall, the cost per QALY gained was HKD + 1,178,100 and ICER was HKD + 187,000 (1USD = 7.8 HKD). CONCLUSIONS: No significant difference in TVR, TLR rates, EQ VAS, and utility score was found between the DES and BMS group. The higher cost of index procedure for the DES group was found to be partly offset by reduced cost of follow-up, offering cost-effectiveness in ACS patients, predominantly in STEMI patients. DES was recommended for STEMI patients.