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.

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.

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.

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.

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.

Long-term clinical outcomes after fatty liver screening in patients undergoing coronary angiogram: A prospective cohort study.

UNLABELLED: There is ongoing debate on whether screening for nonalcoholic fatty liver disease (NAFLD) is worthwhile in high-risk groups. Because of shared risk factors, NAFLD is highly prevalent in patients with coronary artery disease. We aimed to test the hypothesis that NAFLD screening in patients requiring coronary angiogram would identify high-risk patients and predict long-term clinical outcomes. This was a prospective cohort study. NAFLD screening was performed by abdominal ultrasonography before coronary angiogram in 612 consecutive patients. At baseline, 356 (58.2%) patients had NAFLD. NAFLD patients, compared with those without, were more likely to have >50% stenosis in one or more coronary arteries (84.6% vs. 64.1%; P < 0.001) and therefore require percutaneous coronary intervention (68.3% vs. 43.4%; P < 0.001). During 3,679 patient-years of follow-up, 47 (13.2%) NAFLD patients and 59 (23.0%) patients without NAFLD died (age- and sex-adjusted hazard ratio [aHR]: 0.36; 95% confidence interval [CI]: 0.18-0.70; P = 0.003). Composite cardiovascular outcomes (cardiovascular deaths, nonfatal myocardial infarction, heart failure, or secondary interventions) were similar between groups (36.5% vs. 37.1%; aHR, 0.90; 95% CI: 0.69-1.18). Older age and diabetes were the only independent factors associated with cardiovascular events. Only 2 patients, both in the NAFLD group, died of primary liver cancer. No other patients developed liver-related complications. CONCLUSION: In patients with clinical indications for coronary angiogram, the presence of NAFLD is associated with coronary artery stenosis and need for coronary intervention, but not increased mortality or cardiovascular complications. Liver cancer and cirrhotic complications are rare. Our data do not support NAFLD screening in this patient group at present, but studies with a longer duration of follow-up are needed.

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.

Regional and ethnic differences among patients with heart failure in Asia: the Asian sudden cardiac death in heart failure registry.

AIMS: To characterize regional and ethnic differences in heart failure (HF) across Asia. METHODS AND RESULTS: We prospectively studied 5276 patients with stable HF and reduced ejection fraction (≤40%) from 11 Asian regions (China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, and Thailand). Mean age was 59.6 ± 13.1 years, 78.2% were men, and mean body mass index was 24.9 ± 5.1 kg/m2. Majority (64%) of patients had two or more comorbid conditions such as hypertension (51.9%), coronary artery disease (CAD, 50.2%), or diabetes (40.4%). The prevalence of CAD was highest in Southeast Asians (58.8 vs. 38.2% in Northeast Asians). Compared with Chinese ethnicity, Malays (adjusted odds ratio [OR] 1.97, 95% CI 1.63-2.38) and Indians (OR 1.44, 95% CI 1.24-1.68) had higher odds of CAD, whereas Koreans (OR 0.38, 95% CI 0.29-0.50) and Japanese (OR 0.44, 95% CI 0.36-0.55) had lower odds. The prevalence of hypertension and diabetes was highest in Southeast Asians (64.2 and 49.3%, respectively) and high-income regions (59.7 and 46.2%, respectively). There was significant interaction between ethnicity and region, where the adjusted odds were 3.95 (95% CI 2.51-6.21) for hypertension and 4.91 (95% CI 3.07-7.87) for diabetes among Indians from high- vs. low-income regions; and 2.60 (95% CI 1.66-4.06) for hypertension and 2.62 (95% CI 1.73-3.97) for diabetes among Malays from high- vs. low-income regions. CONCLUSIONS: These first prospective multi-national data from Asia highlight the significant heterogeneity among Asian patients with stable HF, and the important influence of both ethnicity and regional income level on patient characteristics. CLINICALTRIALSGOV IDENTIFIER: NCT01633398.

Feasibility Study of Transthoracic Echocardiography for Coronary Slow Flow Phenomenon Evaluation: Validation by Coronary Angiography.

OBJECTIVE: This study aimed to assess echocardiography parameters in CSFP evaluation. METHODS: This study enrolled 79 consecutive patients with CSFP validated by coronary angiography and control individuals with normal coronary flow. Coronary flow rates were determined by corrected CTFC. Clinical and coronary angiography data and coronary parameters assessed by echocardiography using the CFI were recorded. RESULTS: Baseline characteristics were similar between the two groups. Patients with CSFP were predominantly males, with higher BMI values, weights and triglyceride levels (p < 0.05), but lower platelet counts (p < 0.05). Conventional echocardiography parameters were similar in the two groups. However, echocardiographic measurements of the LAD, including PDV, MDV, PDP, MDP and VTI, in the CSFP group were lower compared with control values (p < 0.05). BMI was positively correlated with CSFP. LAD's CTFC showed strong inverse correlations with PDV, MDV, PDP, and MDP in CSFP groups. ROC curve analysis revealed that coronary artery flow-related parameters occupied more than half of the AUC. CONCLUSIONS: CSFP could be identified with the help of echocardiography.

Uncontrolled blood pressure as an independent risk factor of early impaired left ventricular systolic function in treated hypertension.

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 (εLs-18), circumferential (εCs-18), and radial (εRs-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), εLs-18 (15.6±2.8 vs 13.0±2.2 vs 17.4±2.8), εCs-18 (17.3±3.4 vs 14.1±2.7 vs 18.9±3.3), and εRs-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<.001). The changes were more obvious in the HT2 group, regardless of LV hypertrophy. Reductions in the cESS-corrected MWFS and εLs-18 were seen in 68 (25%) and 52 (19%) patients, respectively. Uncontrolled BP were 4.365 times (95% CI 2.203-8.648, P<.001) and 3.928 times (1.851-8.337, P<.001) more likely to be associated with the changes. CONCLUSIONS: Uncontrolled BP in hypertensive patients is associated with further reduction in LV myocardial function detected by advanced echocardiographic techniques, which cannot be explained by the increase in afterload. It might be regarded as a composite risk factor for earlier and faster development of clinical heart failure, therefore, a simplified treatment target.

Ticagrelor versus clopidogrel in Asian patients with acute coronary syndrome: A retrospective analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial.

BACKGROUND: In the PLATO trial, ticagrelor was superior to clopidogrel in reducing cardiovascular events among patients with acute coronary syndrome (ACS) at the expense of increased nonfatal bleeding. Because Asian patients, when compared with non-Asian patients, are believed to be more susceptible to bleeding, we evaluated the effects of ticagrelor compared with clopidogrel in Asian (n=1,106) and non-Asian (n=17,515) patients with acute coronary syndrome enrolled in the PLATO study. METHODS AND RESULTS: Interaction between Asian/non-Asian and primary efficacy end point (a composite of vascular death, myocardial infarction, and stroke) and net clinical benefit (composite of primary efficacy end point and coronary artery bypass graft [CABG] surgery or non-CABG-related major bleeding) were evaluated with a Cox proportional hazards model. Baseline demographics and comorbidities were different between Asians and non-Asians. The overall cardiovascular event rates were higher in Asians, but bleeding rates were similar. Despite these observed differences, the effects of ticagrelor versus clopidogrel were not significantly different between Asians and non-Asians with respect to the primary efficacy outcome (hazard ratio for Asians vs non-Asians, 0.84 [95% CI 0.61-1.17] vs 0.85 [95% CI 0.77-0.93], P=.974), net clinical benefit (0.85 [95% CI 0.65-1.11] vs 0.93 [95% CI 0.86-0.99], P=.521), or individual efficacy end points. There was no significant interaction for bleeding (PLATO major bleeding, 1.02 [95% CI 0.70-1.49] vs 1.04 [95% CI 0.95-1.14], P=.938) and other related adverse events with ticagrelor compared with clopidogrel between Asians and non-Asians. CONCLUSIONS: We observed consistency of effects in Asian patients receiving ticagrelor and clopidogrel in the PLATO study. The relatively modest number of Asian patients in this analysis supports further investigation of larger cohorts to confirm our observations.

Incidence, definition, diagnosis, and management of the cardiac resynchronization therapy nonresponder.

PURPOSE OF REVIEW: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with mild-to-severe heart failure. However, up to 40% of CRT recipients are nonresponders. This review addresses important aspects with regard to the identification and management of CRT nonresponders. RECENT FINDINGS: Mid-term clinical or echocardiographic nonresponse is associated with worse clinical outcomes during the extended follow-up. A number of predictors are indicative of CRT response, which include patient characteristics, electrical determinants, and imaging techniques from preimplant to postimplant period, and can be grouped as modifiable and nonmodifiable contributors to treatment response. Advanced age, male sex, ischemic cause, end-stage heart failure, inadequate electrical delay, and absence of mechanical dyssynchrony are regarded as unfavorable but nonmodifiable factors, for which considering underutilization of CRT by refining patient selection is reasonable. On the contrary, more efforts should be made to optimize patient management by correcting those modifiable factors, such as suboptimal medical therapy, uncontrolled atrial fibrillation, left ventricular lead dislodgement or inappropriate location, loss of biventricular capture, and lack of device optimization. SUMMARY: Proper management and careful selection of CRT recipients will transform a proportion of treatment nonresponders into responders, which is vital to improve patients' outcome.

Deterioration of left ventricular systolic function in extended Pacing to Avoid Cardiac Enlargement (PACE) trial: the predictive value of early systolic dyssynchrony.

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).

Noncardiac comorbidities in heart failure with preserved ejection fraction - commonly ignored fact.

It has been well described that many patients with heart failure (HF) have a normal left ventricular ejection fraction. This entity has been termed "heart failure with preserved ejection fraction (HFPEF)". Significant advances have been made in understanding the clinical characteristics of HFPEF over the past 2 decades on the basis of large HF registries and randomized clinical trials. However, most multicenter clinical trials that investigated medical therapies in HFPEF have yielded disappointing results. HFPEF being a clinical syndrome involving multiple organ systems may be a potential explanation for treatment failure. In this review we discuss the prevalence of noncardiac comorbidities in HFPEF patients as well as their effect on the prognosis of HFPEF.

How low should we target the LDL goal to improve survival for acute coronary syndrome patients in Hong Kong?

BACKGROUND: Utilization of lipid-lowering agents has been associated with improved long-term outcomes in acute coronary syndrome (ACS) patients. However, updated data regarding local use and outcomes was lacking. METHODS: We retrospectively reviewed 696 hospitalized patients in the local ACS registry of Prince of Wales Hospital during 1 January 2008 to 31 December 2009 with data retrieved using computerized clinical records of all patients. RESULTS: Among the 402 MI patients included, 104 (25.9 %) were not prescribed with statins at discharge. Percutaneous coronary intervention (PCI) not performed or planned during hospitalization (OR: 0.324, p = 0.001) and latest lower LDL-C level before discharge (OR: 0.221 for an increment of 1 mmol/L, p = 0.009) were significant independent predictors of the absence of statin prescriptions at discharge. A significantly lower all-cause mortality rate (14.4 % vs 51.7 %, p < 0.001), fewer total hospitalizations (p < 0.001) and fewer hospitalizations due to cardiovascular problems (p < 0.001) were observed in patients discharged with statins. LDL-C goal attainment of < 2.6 mmol/L resulted in a significant reduction in mortality (10.8 % vs 24.2 %, p = 0.001), but not for goal attainment of < 1.8 mmol/L. Significant difference in survival existed only when LDL-C cut-off values were above 2.4 mmol/L. CONCLUSIONS: This study revealed the under-utilization of statin therapy in eligible MI patients at discharge and unsatisfactory percentages of LDL-C goal attainment, and also reassured the role of low LDL-C reduction to < 2.6 mmol/L in the management of MI. However, the current study did not show that the lower LDL-C reduction improved survival of ACS patients. Further research should be conducted to assess the necessity of aggressive LDL-C reduction to < 1.8 mmol/L in local patients.

Management of heart failure with preserved ejection fraction in a local public hospital in Hong Kong.

BACKGROUND: Heart failure (HF) is one of the most debilitating chronic illnesses. The prevalence is expected to increase due to aging population. The current study aimed to examine the management of heart failure with preserved ejection fraction (HFpEF) including drug use pattern, direct medical cost and humanistic outcome in a local public hospital in Hong Kong. METHODS: The current study adopted the retrospective observational study design. Subjects were recruited from the Heart Failure Registry of the Prince of Wales Hospital in Hong Kong between 2006 and 2008 and completed the Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 3 designated time-points conferred eligibility. Patients with significant valvular disorder were excluded. Each patient's medical record was reviewed for 12 months after the date of admission. Heart failure related admissions, clinic visits, cardiovascular drugs, laboratory tests and diagnostic tests were documented. Costs and MLHFQ scores in patients with or without hypertension, diabetes and renal impairment were compared. RESULTS: A total of 73 HFpEF patients were included. It was found that loop diuretics (93.1%, 78.1%) was the most frequently used agent for HFpEF management in both in-patient and out-patient settings. The mean 1-year direct medical cost was USD$ 19969 (1 US $ = 7.8 HK$), with in-patient ward care contributing to the largest proportion (72.2%) of the total cost. Patients with diabetes or renal impairment were associated with a higher cost of HFpEF management. Significant difference was found in the renal impairment group (median cost: USD$ 24604.2 versus USD$ 12706.8 in no impairment group, p = 0.023). The MLHFQ scores of the subjects improved significantly during the study period (p < 0.0005). CONCLUSIONS: The cost of management of HFpEF was enormous and further increased in the presence of comorbidities.

miR-29b as a therapeutic agent for angiotensin II-induced cardiac fibrosis by targeting TGF-ß/Smad3 signaling.

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)-ß1 coding sequence region, thereby inhibiting TGF-ß/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-ß/Smad3 pathway.

Effect of paricalcitol on left ventricular mass and function in CKD--the OPERA trial.

Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 µg) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function. Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo). Changes in LV volume, ejection fraction, tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 µg one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD.

Latent transforming growth factor-ß1 protects against bleomycin-induced lung injury in mice.

Transforming growth factor (TGF)-ß1 is a potent mediator known to induce lung fibrosis. However, the role of latent TGF-ß1 in lung inflammation and fibrosis is unclear. To investigate the role of circulating latent TGF-ß1 in bleomycin-induced lung injury, lung disease was induced in keratin-5 promoter-driven TGF-ß1(wt) transgenic (Tg) mice by bleomycin. The role of latent TGF-ß1 in pulmonary inflammation and fibrosis was examined at Days 7 and 28 after administration of bleomycin. Compared with littermate wild-type (WT) mice, TGF-ß1(wt) Tg mice had over twofold-higher levels of latent TGF-ß1 in both plasma and lung tissue, and were protected from bleomycin-induced pulmonary inflammation, such as up-regulation of IL-1ß, TNF-α, and macrophage chemotactic protein-1, and infiltration of CD3(+) T cells and F4/80(+) macrophages. In addition, the severity of lung fibrosis with massive collagen matrix accumulation was markedly reduced in TGF-ß1(wt) Tg mice. These protective effects were associated with higher levels of Smad7 and inactivation of both NF-κB and TGF-ß/Smad3 signaling pathways, in addition to an increase in forkhead box P3 (Foxp3)-dependent regulatory T cells, but inhibition of T helper 17-mediated lung injury. In summary, mice overexpressing latent TGF-ß1 are protected from bleomycin-induced lung injury. Triggering the Smad7 negative feedback mechanism to inhibit both NF-κB and TGF-ß/Smad signaling pathways, and enhancing the regulatory T cell response to counter-regulate T helper 17-mediated lung injury, are potential mechanisms by which latent TGF-ß1 protects against bleomycin-induced lung injury.