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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.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.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.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).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.

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. Summary SGLT2i expands the foundation of HFrEF therapy. Whether it is equally effective in HF with preserved ejection fraction awaits more evidence.

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

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/m(2), P-interaction = 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, P-interaction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (P-interaction = 0.003), whereby DM was associated with amore concentric left ventricular geometry in women than men. Women had lower quality of life than men (P 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.

Background: Little is known regarding the impact of socioeconomic factors on the use of evidence-based therapies and outcomes in patients with heart failure with reduced ejection fraction across Asia. Methods: We investigated the association of both patient-level (household income, education levels) and country-level (regional income level by World Bank classification, income disparity by Gini index) socioeconomic indicators on use of guideline-directed therapy and clinical outcomes (composite of 1-year mortality or HF hospitalization, quality of life) in the prospective multinational ASIAN-HF study (Asian Sudden Cardiac Death in Heart Failure). Results: Among 4540 patients (mean age: 60±13 years, 23% women) with heart failure with reduced ejection fraction, 39% lived in low-income regions; 34% in regions with high-income disparity (Gini ≥42.8%); 64.4% had low monthly household income (P interaction Conclusions: These findings highlight the importance of socioeconomic determinants among patients with heart failure in Asia and suggest that attention should be paid to address disparities in access to care among the poor and less educated, including those from wealthy regions. Registration: URL: https://clinicaltrials.gov ; Unique Identifier: NCT01633398.

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.

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

Background Data comparing outcomes in heart failure ( HF ) across Asia are limited. We examined regional variation in mortality among patients with HF enrolled in the ASIAN ‐HF (Asian Sudden Cardiac Death in Heart Failure) registry with separate analyses for those with reduced ejection fraction ( EF ; Methods and Results The ASIAN ‐ HF registry is a prospective longitudinal study. Participants with symptomatic HF were recruited from 46 secondary care centers in 3 Asian regions: South Asia (India), Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore), and Northeast Asia (South Korea, Japan, Taiwan, Hong Kong, China). Overall, 6480 patients aged >18 years with symptomatic HF were recruited (mean age: 61.6±13.3 years; 27% women; 81% with HF and reduced r EF ). The primary outcome was 1‐year all‐cause mortality. Striking regional variations in baseline characteristics and outcomes were observed. Regardless of HF type, Southeast Asians had the highest burden of comorbidities, particularly diabetes mellitus and chronic kidney disease, despite being younger than Northeast Asian participants. One‐year, crude, all‐cause mortality for the whole population was 9.6%, higher in patients with HF and reduced EF (10.6%) than in those with HF and preserved EF (5.4%). One‐year, all‐cause mortality was significantly higher in Southeast Asian patients (13.0%), compared with South Asian (7.5%) and Northeast Asian patients (7.4%; P Conclusions This first multinational prospective study shows that the outcomes in Asian patients with both HF and reduced or preserved EF are poor overall and worst in Southeast Asian patients. Region‐specific risk factors and gaps in guideline‐directed therapy should be addressed to potentially improve outcomes. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 01633398.

[Background]Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-relatedsymptoms 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. [Purpose] The purpose of this study was to clarify actual values for echocardiographic parameters related to severity of MR and determinant factors of MR-related symptoms. [Methods] Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by NYHA (≤ II or ≥ III). [Results]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 [Conclusions] 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. Determinant factors for mitral regurgita Model 1 Model 2 OR (95% CI) P-value OR (95% CI) P-value Age, per 1-y increment 1.03 (1.00-1.05) 0.035 1.02 (0.99-1.05) 0.053 Sex (female) 2.23 (1.20-4.16) 0.011 2.28 (1.31-3.98) 0.004 Hear rate, per 1 bpm increment 1.03 (1.00-1.05) 0.025 1.03 (1.01-1.05) 0.007 LVDs index, per 1 mm increment 0.99 (0.90-1.09) 0.90 EF, per 1% increment 0.95 (0.92-0.99) 0.019 0.96 (0.93-0.98) 40 mmHg 2.11 (0.97-4.57) 0.057 Hypertention 1.40 (0.75-2.63) 0.29

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

Impact of percutaneous coronary interventions (PCI) on health-related quality of life (HRQOL) is important but under-reported in elderly patients.To evaluate long-term health status in elderly patients who underwent PCI.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.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 P0.01). 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 P0.01).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.

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).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 (RMultichamber deformation imaging along with renal function and PASP could best predict adverse outcome in HFREF.

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

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.

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.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.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).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.

Background Uncontrolled blood pressure (BP) is commonly observed in patients receiving antihypertensive agents. However, its relationship with early left ventricular (LV) dysfunction has not been elucidated. Methods This study enrolled 276 patients with treated hypertension and 85 healthy controls. The 140/90 mm Hg was used to define controlled (HT1 group, n=145) or uncontrolled BP (HT2 group, n=131) according to the concurrent guidelines. LV myocardial function was assessed by two-dimensional speckle tracking imaging, and the circumferential end-systolic wall stress (cESS)-corrected mid-wall fraction shortening (MWFS), systolic longitudinal (eLs-18), circumferential (eCs-18), and radial (eRs-18) strain were measured. Results Despite similar ejection fraction, the HT1 and HT2 groups displayed an overall reduction in the cESS-corrected MWFS (13.4±2.7 vs 11.7±1.7 vs 15.5±1.2), eLs-18 (15.6±2.8 vs 13.0±2.2 vs 17.4±2.8), eCs-18 (17.3±3.4 vs 14.1±2.7 vs 18.9±3.3), and eRs-18 (18.4±4.0 vs 14.8±3.1 vs 20.5±4.5) %·cm2/kdyne·10−2 when compared with the control group (all P

Cardiac contractility modulation (CCM) has been shown to be effective in improving symptoms and cardiac function in heart failure (HF). However, there is limited data on the role of CCM on long-term survival, which was explored in the present study.Forty-one consecutive HF patients with left ventricular ejection fraction (EF)40% received CCM and were followed for approximately 6 years. They were compared with another 41 HF patients who were enrolled into the HF registry in the same period, and had similar age, gender, EF and etiology of HF. The primary end-point was all cause-mortality. This was stratified by EF. Secondary end-points included HF hospitalization, cardiovascular death, and the composite outcome of death or heart failure hospitalization.The CCM and control groups were well balanced for demographic data, medications and baseline left ventricular EF (27 ± 6 vs 27 ± 7%, p=NS). The mean follow-up duration was 75 ± 19 months in the CCM group and 69 ± 17 months in the control group. All-cause mortality was lower in the CCM group than the control group (39% vs. 71%, respectively; Log-rank χ(2)=11.23, p=0.001). Of note, the improvement of all-cause mortality is more dramatic in patients with EF ≥ 25-40% (36% vs. 80%, Log-rank χ(2)=15.8, p0.001) than those with EF25% (50% vs. 56%, p=NS), CCM vs. control respectively. Similar results were shown for the benefit of CCM in the secondary endpoints of cardiovascular death, and the composite outcome of death or heart failure hospitalization. The occurrence of HF hospitalization showed no significant difference between CCM and control groups in the whole cohort (41% vs. 49%, p=NS), but was significantly lower with CCM in subjects with EF ≥ 25-40% at baseline (36% vs. 64%, Log-rank χ(2)=7.79, p=0.005).CCM resulted in significant improvement of long-term survival, in particular in those with EF ≥ 25-40%. A reduction in heart failure hospitalizations was also seen in this group of patients with less severely reduced EF.

AIMS Biventricular (BiV) pacing was superior to right ventricular apical (RVA) pacing at extended follow-up in the Pacing to Avoid Cardiac Enlargement (PACE) trial. Early pacing-induced systolic dyssynchrony (DYS) might be related to mid-term result. However, it remains unknown whether early pacing-induced DYS can predict long-term reduction of left ventricular (LV) systolic function. METHODS AND RESULTS Patients with standard pacing indications and normal LV ejection fraction (LVEF) were randomized either to BiV (n = 89) or RVA (n = 88) pacing. Seventy-four patients in the RVA group and 72 in the BiV pacing group completed follow-up longer than 2 years. Serial echocardiography was performed with DYS assessed by tissue Doppler imaging, and the early pacing-induced DYS was defined as >33 ms by using standard deviation of the time to peak systolic velocity (Dyssynchrony Index) in a 12-segment model of LV at 1 month. There were 46 (32%) patients having early pacing-induced DYS that was more prevalent in the RVA pacing group than that in the BiV pacing group (50.7 vs. 12.3%, χ(2) = 25.1, P < 0.001) despite the similar DYS between the two groups at baseline (30 ± 13 vs. 26 ± 11 ms, P = 0.051). At a median follow-up of 4.8 years, patients developing early DYS had lower LVEF (53.2 ± 9.4 vs. 60.9 ± 8.0%, P < 0.001) and larger LV end-systolic volume (40.3 ± 23.7 vs. 29.3 ± 13.4 mL, P < 0.001) than those without DYS. Significant EF reduction (defined as ≥5%) occurred in 71.7% (33 in 46) of patients with DYS, but only in 30% (30 in 100) in those without DYS (χ(2) = 22.4, P < 0.001). Further analysis showed that both DYS at 1 month [odds ratio (OR): 3.113, P = 0.013] and RVA pacing (OR: 7.873, P < 0.001) independently predicted the deterioration of LV systolic function with pacing period of 4.8 years. CONCLUSION Early pacing-induced DYS is a significant predictor of reduction of LV systolic function for long-term pacing, which could be prevented by BiV pacing at relatively long-period follow-up. CLINICAL TRIAL REGISTRATION Centre for Clinical Trials number, CUHK_CCT00037 (URL: http://www.cct.cuhk.edu.hk/Registry/publictrialrecord.aspx?trialid=CUHK_CCT00037).

a Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China b Division of Cardiology, Department ofMedicine and Therapeutics & Institute of VascularMedicine & Institute of InnovativeMedicine &Heart Education And Research Training (HEART) Center & Li Ka Shing Institute of Health Sciences & Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong c Department of Ultrasound, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China

Conventional right ventricular (RV) pacing can cause left ventricular (LV) dysfunction and even heart failure (HF) particularly if ventricular pacing is frequent.1 New onset HF has been observed in approximately one third of patients receiving RV pacing for acquired second- or third-degree atrioventricular block (AVB) after a median follow-up of nearly 8 years.2 An elegant study has shown recently that apparent pacing induced cardiomyopathy could occur even if the accumulative pacing percentage was

To understand the influence of myocardial bridging (MB) on left ventricular (LV) function, myocardial function was studied in patients with MB of the left anterior descending coronary artery (LAD) using three-dimensional speckle-tracking echocardiography (STE).Left anterior descending coronary artery MB was diagnosed by coronary angiography in 82 subjects. Patients were divided into three groups according to the percentage of systolic narrowing of the compressed segment: 30% to 49% was defined as group I (24 patients), 50% to 74% as group II (28 patients), and ≥75% as group III (30 patients). Thirty gender- and age-matched normal subjects were included as controls. Left ventricular myocardial deformation was estimated by three-dimensional STE.Left ventricular ejection fractions were normal in all patients, but diastolic function was impaired in groups II and III (E/E' ratio, 9 ± 3 and 10 ± 3, respectively). The amplitudes of longitudinal strain (LS) and area strain (AS) of the LAD territory was significantly reduced in groups II and III compared with controls and group I (LS, -15 ± 2% and -12 ± 1% vs -19 ± 2% and -18 ± 2%; AS, -22 ± 2% and -13 ± 2% vs -33 ± 4% and -33 ± 3%; P .0001), but the amplitudes of circumferential and radial strain showed no intergroup differences. Longitudinal strain and AS were significantly lower in patients with fractional flow reserve0.75 than in those with fractional flow reserve ≥ 0.75 (P .0001), with relative preservation of circumferential and radial strain. The severity of LAD compression was significantly associated with AS and LS of the LAD territory (r = -0.92 and r = -0.84, respectively, P .0001), but the correlations with circumferential and radial strain were modest (r = -0.36 and r = -0.32, respectively, P .05).With the increasing severity of systolic compression of the mural coronary artery, LV diastolic function and regional systolic deformation (AS and LS) of the MB perfusion territory were reduced. Three-dimensional STE can detect subtle myocardial dysfunction in patients with MB.

Solitus inversus dextrocardia, or mirror type dextrocardia, is a veryrare malposition with the prevalence around 0.1‰ and often presentsin Kartagener Syndrome [1,2]. Albeit a cardiac anomaly and hereditaryanatomicalvariation,solitusinversusdextrocardiaisanisolatedcardiacpositional anomaly and combining other congenital cardiac defects arequite uncommon in mirror-type dextrocardia, with the prevalence ofonly 3% [3], which is much lower when compared to solitus situsdextrocardia[4].Intheaccompanieddefects,hypertrophiccardiomyop-athy(HCM)isdefinitelyinfrequentandonlyseveralcaseshavebeenre-ported [5]. As a common hereditary cardiac disease, the occurrence ofHCM is supposed to be related to the mutation of genes encoding thesarcomere proteins[6]. Around5%ofpatients carry more than onemu-tation in patients with HCM in China [7]. We reported a case of mirror-type dextrocardia who developed HCM in adulthood exhibiting multi-ple genetic mutation related to sarcomere proteins.A 43-year-old nonsmoker male presented with repeated chest dis-comfort for more than 5 years and deteriorated for half a month. Hewas diagnosed as dextrocardia (mirror-image type) without detectingany other congenital cardiac anomaly at 6-year-old by an X-ray. In thefollowing 3 decades, his exercise ability was normal without recurrentrespiratory tract infections or sinusitis. At 38 years old, he developedcrushing retrosternal pain after physical exertion and was mitigated atrest. Physical examination showed that his blood pressure was 140/80 mm Hg without systolic murmur and the blood pressure differencebetweenlowerand upper extremitieswasless than20mmHg. Cardiacapex palpation was on the right 5th intercostal space in mid-clavicularline. Dextrocardia was demonstrated with cardiomegaly and normallungfieldontheX-ray(Fig.1).OnthestandardECG,rightaxisdeviationwas visible with positive QRS in aVR lead, inversion of all complex inlead I and dominant S waves in the chest leads (Fig. 2A). All thesesigns were normal after reversing limb leads and placing chest leadson the right except the hypertrophic sign of left ventricle (Fig. 2B).Transthoracicechocardiographyrevealedthatmirror-typedextrocardiawithsolitusinversus,atrioventricularconcordant,normalconnectionofventricular–arterial connection. Moreover, significant symmetric leftventricular hypertrophy (30 mm of the septum and 30 mm of the

Mitral and aortic valves are coupled via fibrous tissue. This coupling is considered to be important for cardiac function before and after mitral valve surgery. The relationship between mitral–aortic coupling and different types of mitral regurgitation (MR) is not completely understood. Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) was performed in 133 subjects: 30 normal subjects, 15 patients with Carpentier type I MR (annular dilatation and congenital cleft), 40 type II (mitral valve prolapse), 20 type IIIa (rheumatic) and 28 type IIIb (ischemic mitral regurgitation). Custom software was used to track mitral (MA) and aortic annuli (AoA) in 3D space throughout cardiac cycle, allowing measurement of changes in mitral and aortic valve morphology. Normal mitral–aortic coupling is characterized by reciprocal changes in the annular areas throughout cardiac cycle, with systolic reduction of the angle between the two annular planes. In Carpentier type II patients, not only MA but also AoA areas were increased (P

a Department of Intensive CareUnit, Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, The AffiliatedHospital of JiningMedical University, Shandong Province, China b Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong c Department of Radiology, The Affiliated Hospital of Jining Medical University, Shandong Province, China d Department of Pathology, The Affiliated Hospital of Jining Medical University, Shandong Province, China e Department of Ultrasonography, The Affiliated Hospital of Jining Medical University, Shandong Province, China f Department of Cardiac Surgery, The Affiliated Hospital of Jining Medical University, Shandong Province, China

Article history: Received 3 November 2015 Accepted 5 November 2015 Available online 10 November 2015 as possible from the right atrium as they could, the content see Fig. 2B; as the result, the right ventricular inflow tract was cleared. The histopathologic diagnosis was diffuse large B cell lymphoma (Fig. 2C,D). The patient died due to heart failure two weeks after the operation. Case 2: A 74-year-old man presented with dyspnea for 2 months.

Heart failure with preserved ejection fraction (HFpEF) is a global public health problem. Unfortunately, little is known about HFpEF across Asia.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.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.

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 P P 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.

Although transfemoral arterial approach (TFA) was the first developed method for coronary angiography and percutaneous coronary intervention (PCI), it has its own disadvantages, including the need for the bed rest for the requirement of puncture site compression after the procedure, vascular complications of local hematoma, psoas hematoma, arterio-venous fistula and pseudoaneurysm, as well as difficult access due to tortuous aorta or occlusion of femoral-iliac-aortic route [1–7]. Thus, to develop an alternative modality with easily approach, lesser vascular complications and comparable safety as the femoral arterial approach for PCI is of utmost importance. Transradial arterial approach (TRA) for coronary angiography and PCI is therefore developed as an alternative and even well-accepted first line approach. In fact, TRA which is a reasonably simple route of vascular access [8–10] for catheter-based coronary intervention, and has been developed for almost 20 years. As the safety and efficacy of this method has already been extensively discussed and validated for a long time by many clinical studies worldwide [8, 10], TRA is currently one of the most popular approaches, especially in Asia, for elective PCI [10–15]. Additionally, clinical studies have further proved that TRA is safe and efficacious in elective coronary angiographic study on an out-patient basis [15], elective left main coronary intervention [16], cerebral angiographic study, and vertebral or carotid stenting [17, 18]. Furthermore, while TRA for primary PCI is already a daily practice for hemodynamic stable patients in many medical centers of the world, in particular in Asia [19, 20], how to utilize the TRA for coronary intervention for acute ST-segment elevation myocardial Infarction (STEMI), non-STEMI and unstable angina with hemodynamic instability with the requirement of circulatory/mechanical support is an important issue that should be realized in our clinical practice.

Multimorbidity has become the norm worldwide as populations age. It remains, however, infrequently researched. This study evaluated factors associated with multimorbidity in a predominantly Chinese hypertensive population. We included all adult patients prescribed their first antihypertensive agents in the entire public sector in Hong Kong from a validated database. Multimorbidity was defined as having one or more medical conditions (cardiovascular diseases; respiratory diseases; diabetes or impaired fasting glucose; renal disease) in addition to hypertension. We studied the prevalence of multimorbidity and performed multinomial regression analyses to evaluate factors independently associated with multimorbidity. 223,286 hypertensive patients (average age of 59.9 years, SD 17.6) were included. The prevalence of having 0, 1 and ≥ 2 additional conditions was 59.6%, 32.8% and 7.5%, respectively. The most common conditions were cardiovascular disease (24.2%) and diabetes (23.0%), followed by respiratory disorders (14.6%) and renal disease (10.9%). Older age (>50 years), male sex, lower household income, receipt of social security allowance and suboptimal blood pressure control (>140 mmHg or >90 mmHg; >130 mmHg or >80 mmHg for diabetes patients; AOR = 3.38-4.49) were significantly associated with multimorbidity. There exists a synergistic effect among these variables as older (≥ 70 years), male patients receiving security allowance had substantially higher prevalence of multimorbidity (19.9% vs 7.5% among all patients). Multimorbidity is very common in hypertensive patients and its prevalence increased markedly with the presence of risk factors identified in this study. Hypertensive patients with multimorbidities should receive more meticulous clinical care as their blood pressure control tends to be poorer.

Right ventricular (RV) pacing may affect myocardial perfusion and coronary blood flow; however, it remains unknown whether this is related to systolic dyssynchrony induced by RV pacing. This prospective study was aimed to assess the relationship between dyssynchrony and the changes of coronary blood flow.Seventy patients with sinus node dysfunction were prospectively enrolled. Coronary flow was evaluated by measuring diastolic velocity time integral (VTI) and duration at the distal-portion of left anterior descending coronary artery (LAD) with transthoracic echocardiography at baseline and follow-up. Systolic dyssynchrony was assessed with tissue Doppler imaging by time standard deviation to peak systolic velocity of 12 left ventricular segments (Ts-SD, cutoff value ≥ 33 ms).Adequate data for analysis was available from 65 patients. At follow-up (mean follow up time: 127 ± 45 days), LAD velocity-time integral (LAD-VTI: 12.1 ± 4.2 vs. 10.7 ± 4.6 cm, p0.001) was decreased and there was deterioration of left ventricular systolic function (left ventricular ejection fraction: 65 ± 7% vs. 62 ± 7%). However, these changes were only detected in those with RV pacing induced systolic dyssynchrony. Significant reduction of LAD-VTI (defined as ≥ 5%) occurred in 34 (52%) patients which was more prevalent in those with pacing-induced systolic dyssynchrony than those without (85.3% versus 16.1%, χ(2)=31.1, p0.001). Though similar at baseline, LAD-VTI was significantly lower in the dyssynchrony group at follow up (p0.001). Cox-regression analysis showed that pacing-inducing systolic dyssynchrony [hazard ratio (HR): 3.62, p=0.009] and higher accumulative pacing percentage (HR: 1.02, p=0.002) were independently associated with reduction of LAD-VTI. ROC curve demonstrated that accumulative pacing percentage ≥ 35% was 97% sensitive and 84% specific in revealing significant reduction (area under the curve: 0.961, p0.001).RV pacing induced dyssynchrony is associated with reduced coronary flow and this may account for, in part, the deleterious effect of RV pacing on ventricular function over time.

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value.Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation.Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Loss of miR-29 is associated with cardiac fibrosis. This study examined the role and therapeutic potential of miR-29 in mouse model of hypertension induced by angiotensin II (AngII). By using microRNA microarray, in situ hybridization, and real-time polymerase chain reaction, we found that AngII-induced cardiac fibrosis in the hypertensive heart and in cultured cardiac fibroblasts were associated with downregulation of miR-29a-c via a Smad3-dependent mechanism. In vitro knockdown of miR-29b enhanced but overexpression of miR-29b inhibited AngII-induced fibrosis, revealing a protective role of miR-29b in cardiac fibrosis in response to AngII. This was further demonstrated in vivo by the ability of overexpressing miR-29b in the mouse heart to prevent AngII-mediated cardiac fibrosis and cardiac dysfunction. Importantly, we also found that restored miR-29b in the established hypertensive heart was capable of blocking progressive cardiac fibrosis and improving cardiac dysfunction, demonstrating a therapeutic potential of miR-29b for chronic heart disease. Further studies revealed that targeting the transforming growth factor (TGF)-β1 coding sequence region, thereby inhibiting TGF-β/Smad3 signaling, could be a new mechanism by which miR-29b inhibited AngII-induced cardiac fibrosis. In conclusion, miR-29b plays a protective role in AngII-mediated cardiac remodeling and may be a therapeutic agent for cardiac fibrosis by targeting the TGF-β/Smad3 pathway.

Cardiac auscultation by stethoscope is widely used but limited by low sensitivity and accuracy. Phonocardiogram was developed in an attempt to provide quantitative and qualitative information of heart sounds and murmurs by transforming acoustic signal into visual wavelet. Although phonocardiogram provides objective heart sound information and holds diagnostic potentials of different heart problems, its examination procedure is time-consuming and it requires specially trained technicians to operate the device. Acoustic cardiography (AUDICOR, Inovise Medical, Inc., Portland, OR, USA) is a major recent advance in the evolution of cardiac auscultation technology. The technique is more efficient and less operator-dependent. It synchronizes cardiac auscultation with ECG recording and provides a comprehensive assessment of both mechanical and electronic function of the heart. The application of acoustic cardiography is far beyond auscultation only. It generates various parameters which have been proven to correlate with gold standards in heart failure diagnosis and ischemic heart disease detection. Its application can be extended to other diseases, including LV hypertrophy, constrictive pericarditis, sleep apnea and ventricular fibrillation. The newly developed ambulatory acoustic cardiography is potentially used in heart failure follow-up in both home and hospital setting. This review comprehensively summarizes acoustic cardiographic research, including the most recent development.

Purpose: Current clinical guidelines recommend that ultrafiltration (UF) should be reserved for use in patients with Acute Decompensated Heart Failure (ADHF) who are unresponsive or resistant to diuretics. However, its efficacy and safety remain unknown. We systematically reviewed the available randomized data on the efficacy and safety of UF in ADHF. Methods: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in January 2013 to identify Randomized Controlled Trials (RCTs) evaluating UF in ADHF patients. Outcomes of interest included net fluid loss, net weight loss, all-cause mortality, all-cause rehospitalization and adverse events. A random-effects model was used to calculate mean differences (MDs) and odds ratios (ORs) for continuous and dichotomous data, respectively, with 95% Confidence Intervals (CIs). Statistical heterogeneity was assessed by I2 statistic (25% ≤ 50% ≤ 75% for low, moderate and high heterogeneity, respectively). Results: Eleven studies enrolling 614 participants were included in systematic review and data of ten (n=604) studies were meta-analyzed. A total of 302 (50%) participants were randomized to UF. Comparison arms consisted of intravenous diuretics (6 studies), no treatment (2 studies) and unspecified conventional therapy (2 studies; "standard HF therapies" and "conventional management"). Compared to control, treatment of UF was associated with significant net fluid loss (MD 1.43, 95% CI 0.51-2.35, P=0.002) and net weight loss (MD 1.64, 95% CI 0.04-3.24, P=0.04), with moderate to substantial statistical heterogeneity across studies (I2=50% and 70%, respectively). There were no significant differences in all-cause mortality (OR 1.08, 95% CI 0.63-1.86, P=0.77) or all-cause rehospitalization (OR 0.89, 95% CI 0.39-2.00, P=0.77). Analysis of adverse events was inconclusive since only one study reported event numbers. Conclusions: Our meta-analysis shows that the use of UF is effective in reducing fluid and body weight, with no significant benefit in mortality or rehospitalization. Available randomized evidence on the effects of UF in ADHF is limited and underpowered. Data from well-conducted randomized clinical studies of adequate power are much needed to establish the role of UF in ADHF patients for whom conventional HF treatment is unsuccessful or contraindicated.