Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention of Recurrent Cardiovascular Events in a Real-World Cohort of Post-Acute Myocardial Infarction Patients.

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

Prognostic implications of statin intolerance in stable coronary artery disease patients with different levels of high-sensitive troponin.

BACKGROUND: The prognostic implication of statin in tolerance (SI) in those with stable CAD remains unclear. We hypothesized that SI is of higher prognostic significance in stable CAD patients with elevated high-sensitive cardiac troponin I (hs-cTnI). METHODS: A total of 952 stable CAD patients from the prospective Hong Kong CAD study who had complete clinical data, biomarker measurements and who were prescribed statin therapy were studied. RESULTS: We identified 13 (1.4%) and 125 (13.1%) patients with complete and partial SI, respectively. At baseline, patients with SI were more likely to have diabetes mellitus and a higher hs-cTnI level, but no difference in LDL-C level compared with those without SI. After 51 months of follow-up, patients with SI had a higher mean LDL-C level than those without SI. A total of 148 (15.5%) patients developed major adverse cardiovascular events (MACEs). Both SI (HR 1.52, 95% CI 1.06-2.19, P = 0.02) and elevated hs-cTnI (HR 3.18, 95% CI 2.07-4.89, P < 0.01) were independent predictors of a MACE in patients with stable CAD. When stratified by hs-cTnI level, SI independently predicted MACE-free survival only in those with elevated hs-cTnI (HR 1.51, 95% CI 1.01-2.24, P = 0.04). CONCLUSIONS: SI independently predicted MACE in patients with stable CAD and high hs-cTnI, but not in those with low hs-cTnI. Hs-cTnI may be used to stratify stable CAD patients who have SI for intensive lipid-lowering therapy using non-statin agents.

TIMI risk score for secondary prevention of recurrent cardiovascular events in a real-world cohort of post-non-ST-elevation myocardial infarction patients.

BACKGROUND: Patients who survive non-ST-elevation myocardial infarction (NSTEMI) are at heightened risk of recurrent cardiovascular events. Data on long-term secondary atherothrombotic risk stratification are limited. OBJECTIVES: To stratify post-NSTEMI patients for risk of recurrent cardiovascular events to maximise benefit from aggressive secondary prevention strategies using the TIMI Risk Score for Secondary Prevention (TRS 2°P) score in a real-world cohort of NSTEMI patients. METHODS AND RESULTS: This was a single-centre observational study of 891 post-NSTEMI patients (73.7 ± 12.7 years; male: 54.2%). The TRS 2°P is a nine-point risk stratification tool to predict cardiovascular events in patients with established cardiovascular disease. The primary outcome was a composite endpoint of cardiovascular death, non-fatal MI and non-fatal ischaemic stroke. After a median follow-up of 31 months (IQR: 11.4 - 60.2), 281 patients (31.5%) had developed a primary outcome (13.3%/year) including 196 cardiovascular deaths, 94 non-fatal MIs and 22 non-fatal strokes. The TRS 2°P score was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P score =0 was 1.6%, and increased progressively to 47.4% for those with a TRS 2°P score ≥6 (HR: 20.18, 95% CI: 4.85 to 84.05, p<0.001). Similar associations were also observed between the TRS 2°P score and cardiovascular death and MI (fatal and non-fatal), but not non-fatal ischaemic stroke. CONCLUSION: The TRS 2°P score stratified post-NSTEMI patients for risk of future cardiovascular events and potentially help guide the selection of more aggressive secondary prevention therapy.

Impact of provision of time in therapeutic range value on anticoagulation management in atrial fibrillation patients on warfarin.

INTRODUCTION: The importance of time in therapeutic range (TTR) in patients prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF) cannot be overemphasised. AIM: To evaluate the impact of provision of TTR results during clinic visits on anticoagulation management. DESIGN: Single-centred, randomised controlled study. SETTING: Fifteen arrhythmia clinics in Hong Kong. PATIENTS: AF patients prescribed warfarin. INTERVENTIONS: Provision of TTR or no provision of TTR. MAIN OUTCOME MEASURES: A documented discussion between doctors and patients about switching warfarin to a non-vitamin K oral anticoagulant (NOAC). RESULTS: Four hundred and eighty one patients with AF prescribed warfarin were randomly assigned to (1) a TTR provision group or (2) control. Their mean age was 73.6±12.0 years and 60.7% were men. The mean CHA2DS2-VASc score was 3.2±1.6 and the mean HASBLED score was 1.7±1.2. The mean TTR was 63.9%±29.9%. At the index clinic visit, 71 of 481 patients (14.8%) had a documented discussion about switching warfarin to a NOAC. Patients with provision of TTR results were more likely to discuss switching warfarin to a NOAC than controls (19.1% vs 10.6%, P=0.03), especially those with a TTR <65% (35.2% vs 10.6%, P<0.001). A higher proportion of patients with provision of TTR results switched to a NOAC (5.9% vs 4.1%, P=0.49). CONCLUSIONS: The provision of TTR among patients on warfarin was associated with a discussion about switching from warfarin to a NOAC in those with TTR <65%, but did not result in actual switching to a NOAC, suggesting additional barriers.

Genetically deprived vitamin D exposure predisposes to atrial fibrillation.

AIMS: Low vitamin D level is associated with atrial fibrillation (AF) and may be implicated in its pathogenesis. METHODS AND RESULTS: We studied single nucleotide polymorphisms (SNPs) of vitamin D mechanistic pathways and serum 25-hydroxyvitamin D [25(OH)D] levels in an age- and gender-matched case-control study (controls without AF: mean age 68.6 ± 8.7 years, female 25%; n = 1019; with AF: mean age 69.7 ± 9.5 years, female 30%; n = 156) recruited from a Chinese clinical cohort of patients with stable coronary artery disease. Twelve SNPs involved in the vitamin D mechanistic pathways were studied [biosynthetic: rs4646536, rs10877012, rs3829251, rs1790349; activation: rs2060793, rs1993116; vitamin D-binding protein (VBP)/group-specific component (GC): rs4588, rs7041, rs2282679, rs1155563; and vitamin D receptor: rs1544410, rs10735810]. A genetic risk score (GRS) (0-8) was constructed from SNPs associated with serum 25(OH)D as a proxy to lifelong vitamin D-deficient state. All 4 SNPs involved in the VBP/GC were significantly associated with serum 25(OH)D (rs4588, P < 0.001; rs2282679, P < 0.001; rs7041, P = 0.011; rs1155563, P < 0.001; all other SNPs, P > 0.05). Vitamin D GRS (points 0-8) generated from these 4 SNPs was independently predictive of serum 25(OH)D [B = 0.54, 95% confidence interval (CI) 0.30-0.79; P < 0.001]. Genetically deprived vitamin D status as denoted by a low GRS (0-3) independently predicted an increased risk of AF, compared to a high GRS (4-8) (odds ratio = 1.848, 95% CI 1.217-2.805; P = 0.004). CONCLUSION: Genetically deprived vitamin D exposure predisposes to increased AF among patients with coronary artery disease. Whether VBP/GC may alter the risk of AF via alternative mechanisms warrants further studies.

Clinical Characteristics, Management, and Outcomes of Hospitalized Heart Failure in a Chinese Population-The Hong Kong Heart Failure Registry.

BACKGROUND: Epidemiological data for heart failure (HF) in the Chinese population is scarce. In this study, we described the clinical characteristics and outcomes of new-onset HF in our population. METHODS AND RESULTS: We conducted a retrospective, observational study on consecutive Chinese patients hospitalized for new-onset HF between 2005 and 2012 in our center. A total of 1940 patients (mean age, 78.2 ± 11.8 years, 54.2% female) were identified. The rate of new HF hospitalization was 0.59 per 1000 population. The most prevalent comorbidities were hypertension (69.8%) and coronary artery disease (29.3%), and 52.3% had HF with preserved ejection fraction (HFpEF). The all-cause mortality was 19.5% at 1 year, 32.1% at 2 years, and 54% at 5 years. Cardiovascular mortality was 7.2% at 1 year, 11.8% at 2 years, and 20.7% at 5 years. No difference in all-cause mortality or cardiovascular mortality was observed between those with HF with reduced ejection fraction than HFpEF. CONCLUSIONS: Our patients with new-onset HF shared similar clinical characteristics with the Caucasian population. The prognosis was poor with high all-cause mortality for both HFpEF and HF with reduced ejection fraction.

Ischaemic stroke in patients with atrial fibrillation with chronic kidney disease undergoing peritoneal dialysis.

AIMS: Little is known about the ischaemic stroke risk and benefit of warfarin therapy for stroke prevention in chronic kidney disease (CKD) patients on peritoneal dialysis (PD) with concomitant atrial fibrillation (AF). Our objective was to determine the risk of ischaemic stroke in a 'real-world' cohort of PD patients with AF, and clinical benefit or harm of aspirin and warfarin. METHODS AND RESULTS: This is a single-centred observational study of Chinese patients with non-valvular AF. Hospitalizations with ischaemic stroke and intracranial haemorrhage (ICH) were recorded. Of 9810 patients from a hospital-based AF registry, 271 CKD patients on PD with AF (76.8 ± 12.5 years, CHA2DS2-VASc: 3.69 ± 1.83, and HAS-BLED: 2.07 ± 0.97) were identified. Amongst these PD patients, 24.7% received warfarin; 31.7% received aspirin; and 43.5% received no antithrombotic therapy. Amongst patients with no antithrombotic therapy, annual incidence of ischaemic stroke in PD patients was comparable with those non-CKD counterparts (9.32 vs. 9.30%/year). Similar to non-CKD patients, annual incidence of ischaemic stroke increased with increasing CHA2DS2-VASc score (CHA2DS2-VASc = 0-1: 5.76 vs. 5.70%/year, P = 1.00; and CHA2DS2-VASc ≥ 2: 10.80 vs. 9.94%/year, P = 0.78). Amongst PD patients, warfarin therapy was associated with lower risk of ischaemic stroke compared with aspirin [Hazard ratio (HR): 0.16, 95% confidence interval (CI): 0.04-0.66, P = 0.01] and no therapy (HR: 0.19, 95% CI: 0.06-0.65, P = 0.01), but not associated with a higher risk of ICH. CONCLUSION: In CKD patients on PD with AF, who had similar ischaemic stroke risk as non-CKD counterparts, warfarin therapy is associated with reduction in risk of ischaemic stroke without a higher risk of ICH.

Ischemic stroke and intracranial hemorrhage with aspirin, dabigatran, and warfarin: impact of quality of anticoagulation control.

BACKGROUND AND PURPOSE: Little is known about the impact of quality of anticoagulation control, as reflected by time in therapeutic range (TTR), on the effectiveness and safety of warfarin therapy in Chinese patients with atrial fibrillation. We investigated the risks of ischemic stroke and intracranial hemorrhage (ICH) in relation to warfarin at various TTRs in a real-world cohort of Chinese patients with atrial fibrillation receiving warfarin and compared with those on dabigatran, aspirin, and no therapy. METHODS: This is an observational study. RESULTS: Of 8754 Chinese patients with atrial fibrillation and CHA2DS2-VASc ≥1 (79.5±9.2 years; CHA2DS2-VASc, 4.1±1.5; and Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly (>65 years), Drugs/Alcohol Concomitantly [HAS-BLED], 2.2±0.9), 16.3% received warfarin, 41.1% aspirin, 4.5% dabigatran, and 38.1% received no therapy. The incidence of ischemic stroke was highest in patients with no therapy (10.38%/y), followed by patients on aspirin (7.95%/y). The incidence of stroke decreased progressively with increasing TTR quartiles (<17.9%, 17.9%-38.8%, 38.8%-56.2%, and >56.2%) from 7.34%/y (first quartile) to 3.10%/y (fourth quartile). Patients on dabigatran had the lowest incidence of stroke among all groups (2.24%/y). The incidence of ICH was lowest in patients on dabigatran (0.32%/y) compared with those on warfarin (0.90%/y), aspirin (0.80%/y), and no therapy (0.53%/y). ICH incidence decreased with increasing TTR from 1.37%/y (first quartile) to 0.74%/y (fourth quartile). CONCLUSIONS: In Chinese patients with atrial fibrillation, the benefits of warfarin therapy for stroke prevention and ICH risk are closely dependent on the quality of anticoagulation, as reflected by TTR. Even at the top TTR quartile, warfarin was associated with a higher stroke and ICH risk than dabigatran.

Ivabradine in Severe Aortic Stenosis with Poor Left Ventricular Ejection Fraction.

Patients with severe aortic stenosis (AS) and left ventricular systolic dysfunction pose a significant challenge to the managing physician. Conventional pharmacological therapy for systolic heart failure has not been proven beneficial in this setting. Ivabradine, a selective current inhibitor, decreases the spontaneous firing rate of sinoatrial nodal cells, thereby reducing the heart rate, and has been shown to reduce a composite end-point of heart failure hospitalization and mortality in patients with impaired left ventricular function. Herein are reported details of the hemodynamic effects and clinical outcome of ivabradine treatment in an 86-year-old man with severe AS and severe left ventricular systolic function.

Slow Heart Rate Predicts New Occurrence of Atrial Fibrillation.

BACKGROUND: This study aims to investigate the relation between baseline heart rate and new occurrence of AF in patients with mild symptoms. METHODS: Patients without pre-existing AF or structural heart disease who underwent 24-hour electrocardiogram (ECG) monitoring for palpitations, dizziness or syncope were followed up for new-onset AF. RESULTS: 428 patients (mean age 66.6±10.2 years, 43.7% male) were classified according to the average heart rate into four quartiles (1(st) quartile: <63 beat per minute (bpm); 2(nd) quartile: 63-70 bpm; 3(rd) quartile 70-77 bpm; and 4(th) quartile: >77 bpm). There were no significant differences in gender, prevalence of diabetes, hypertension, left ventricular ejection fraction, or medications but a higher prevalence of coronary artery disease was noted among patients in the lower quartiles of average heart rate. After a mean follow-up of 5.8±1.8 years, 60 patients (14.0%) developed new-onset AF. The annual incidence of new-onset AF was highest amongst those at the lowest quartile of average heart rate (9.39%/year) as compared to those amongst other quartiles. Cox regression analysis revealed that increasing age, decreasing quartile of average heart rate, and the use of calcium channel blocker were associated with increased risk of new-onset AF. CONCLUSIONS: Average heart rate predicts new AF.

Transcatheter aortic valve implantation without balloon predilatation: not always feasible.

Balloon predilatation has been regarded as an essential step before implanting the self-expandable prosthesis during transcatheter aortic valve implantation (TAVI). Recent evidence showed that without balloon predilatation, an implantation success rate of >95% could be achieved. We report two cases in which balloon predilatation was not performed initially during TAVI but eventually required it to facilitate device crossing and implantation. They illustrated the importance of case selection and alerted us the potential limitation in performing TAVI without balloon predilatation.

Difficulties with horizontal aortic root in transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) emerged to be a viable treatment option for failing bioprosthesis in the aortic position. Transfemoral approach is the most common access route for TAVI and associated with most favorable clinical outcome. However, in the presence of unfavorable aortic root anatomy, TAVI via transfemoral approach provides inadequate support for device manipulation during valve positioning, particularly performed for the indication of severe aortic regurgitation. We report our experience on TAVI utilizing CoreValve for a patient with regurgitant failing bioprosthesis with horizontal aortic root where we encountered difficulties during implantation and retrieval of valve delivery system.

Immediate results of bifurcational stenting assessed with optical coherence tomography.

BACKGROUND: A tubular stent may adapt with difficulty to coronary bifurcation lesions (CBLs). METHODS: Time domain or frequency domain (FD) optical coherence tomography (OCT) was performed to assess strut apposition immediately after stent implantation across four segments inside the bifurcation, in a consecutive series of patients. OCT pullbacks were performed in the main vessel (MV). RESULTS: A total of 13,142 struts in 45 CBL in 41 patients were assessed. Strut malapposition was significantly more frequent in the half bifurcation facing the side-branch (SB) ostium (42.9%) than in the proximal segment of the bifurcation 11.8%, half bifurcation opposite the SB 6.7%, or the distal segment 5.7% (all P < 0.0001). Lesions (n = 15) treated with stenting of both MV and SB had a total higher rate of malapposition than those (n = 30) treated with stenting of the MV only (17.6% vs. 9.5%; P = 0.0014). In latter group, lesions treated with FD-OCT-guided stent implantation (n = 13) presented a lower rate of malapposition than those treated with conventional angiographic-guided stent implantation (n = 17) (7.1% vs. 17.5%; P = 0.005). CONCLUSIONS: In CBL, strut malapposition is particularly high at the SB ostium. However, a strategy of stenting MV only with adjunctive FD-OCT guidance is associated with lower rates of malapposition.

Real-world experience of MitraClip for treatment of severe mitral regurgitation.

BACKGROUND: Percutaneous edge-to-edge mitral valve repair with the MitraClip(®) was shown to be a safe and feasible alternative compared to conventional surgical mitral valve repair. Herein is reported our experience on MitraClip(®) for high-risk surgical candidates with severe mitral regurgitation (MR). METHODS AND RESULTS: Patients with severe MR (3 or 4+) and high operative risk were considered for MitraClip(®) implantation. Device success was defined as placement of 1 or more MitraClips(®) with reduction of MR to ≤2+. Patients were followed up clinically and with echocardiography at 1 year. A total of 27 patients with severe MR (age, 74±12 years; 17 male; logistic EuroSCORE, 27±12; left ventricular ejection fraction, 40±17%) were treated. Fifty-six percent of MR was degenerative and 44% was functional. Device success was 93% with 14 patients receiving 2 clips. MR severity was reduced from 3.5±0.5 to 1.7±0.8 (P<0.001); New York Heart Association class improved from 3.1±0.4 to 2.0±0.8 (P<0.001). In 45% of functional and in 29% of degenerative MR patients, to avoid mitral stenosis, additional MitraClip(®) implantation was not attempted, with resultant transmitral mean gradient of 4.9±1.6mmHg vs. 3.1±1.4mmHg, respectively (P=0.01). CONCLUSIONS: MitraClip(®) was shown to be an effective and safe treatment for patients with both functional and degenerative MR. Inability to obtain a greater reduction of MR was the consequence of borderline transmitral gradient requiring a compromise to avoid mitral stenosis, particularly in the functional MR patients.

Edge-to-edge percutaneous repair of severe mitral regurgitation--state-of-the-art for Mitraclip® implantation.

MitraClip® therapy is a percutaneous edge-to-edge plication of the mitral leaflets, mimicking the Alfieri surgical technique. MitraClip® implantation is a safe procedure, and survival outcomes in high-surgical-risk patients are superior to historical controls. Despite these results, questions remain concerning long-term efficacy and durability. The MitraClip® device has been studied in a safety and feasibility trial in the USA, a randomized pivotal trial against surgical mitral valve repair. Moreover, MitraClip® now has over 2 years of CE-mark approval and a rapidly expanding clinical experience in Europe, primarily in patients at high risk for surgery. A dedicated multidisciplinary team is necessary, as well as thoughtful patient selection, familiarity with the technical aspects of the procedure, including transesophageal ultrasound imaging and post-procedure monitoring. Currently available clinical data and procedural steps are herein reviewed. Because the MitraClip® procedure is still relatively new, continued investigation is required to further better define the patient populations that will benefit most.

Virtual histology findings and effects of varying doses of atorvastatin on coronary plaque volume and composition in statin-naive patients: the VENUS study.

BACKGROUND: While statin induces plaque regression, its effects, particularly with different doses on plaque virtual histology composition, remain unknown. METHODS AND RESULTS: In this prospective, randomized, double-blinded study, 40 consecutive statin-naive patients with stable angina requiring percutaneous coronary intervention (PCI) were randomized to 2 arms (20 patients each) receiving 6 months of atorvastatin 10 mg or 40 mg daily. The primary end-point was (VH-IVUS) changes from baseline to 6 months, as assessed by a core laboratory. Fifty-four VH-IVUS lesions were analyzed from the 10 mg group and 57 from the 40 mg group. Overall, plaque volume was reduced by 4.28% (-5.10±14.93 mm(3), P<0.001), absolute VH-IVUS fibrous volume by 10.54% (-4.87±10.74 mm(3), P<0.001), and relative percentage fibrous component by 3.29±7.84% (P<0.001), while relative percentage dense calcium increased by 1.50±3.08% (P<0.001), and necrotic core by 3.19±7.82% (P<0.001). Beneficial changes were more substantial in the higher dose (40 mg) group, with significantly more percentage plaque volume regression (-1.50±3.85% vs. 0.38±4.05% increase in the 10 mg group, P=0.014), less relative percentage necrotic core expansion (1.68±7.57% vs. 4.78±7.82% in the 10 mg group, P=0.037), and without occurrence of major adverse cardiac events (vs. 6 patients in the 10 mg group, P=0.020). CONCLUSIONS: In statin-naive patients requiring PCI, 6 months of atorvastatin induced a significant percentage of plaque volume reduction and substantial modification of VH-IVUS composition. In addition, these effects appeared to vary with different doses of atorvastatin, showing significantly better limitation of relative percentage necrotic core expansion at a higher dose.

Chronic Medication Use and Factors Associated With Polypharmacy Among Outpatient Pediatric Patients.

OBJECTIVE: This study aimed to determine the prevalence and predictors of chronic polypharmacy among pediatric patients in an outpatient setting. METHODS: We conducted a review of medications dispensed to patients from an outpatient pediatric facility during a 12-month period. Patients who received chronic medications (≥30 days' supply), which contained at least 1 active pharmaceutical ingredient were included in the study. Descriptive analysis was used to determine prevalence of polypharmacy while predictive factors for polypharmacy were evaluated using logistic regression. RESULTS: Our study included 3920 patients (median age, 9.9 years; IQR, 9.4) and 16,401 medications. The median number of chronic medications used among our study cohort was 2.0 (IQR, 1) with polypharmacy identified in 309 (7.9%) patients. Predictors for polypharmacy were age and the use of certain therapeutic class of medications. Patients 12 to <19 years old (OR, 6.95; 95% CI, 4.1-10.1) were more likely to require ≥5 concurrent medications compared with patients younger than 2 years of age. Use of calcium supplements (OR, 21.2; 95% CI, 11.3-39.6), Vitamin D analogues (OR, 14.3; 95% CI, 8.0-25.8), and systemic glucocorticoids (OR, 18.8; 95% CI, 10.7-33.2) were also highly associated with polypharmacy. CONCLUSIONS: Adolescents and children with chronic medical conditions who require prolonged systemic glucocorticoids, calcium, and Vitamin D supplements are at higher risk of incurring long-term polypharmacy. This subgroup of pediatric patients may be more vulnerable to the occurrence of negative outcomes resulting from the use of multiple chronic medications.