Impact of Prior Ischemic Stroke on Outcomes in Patients With Heart Failure　- A Propensity-Matched Study.

BACKGROUND: Whether ischemic stroke per se, rather than older age or additional comorbidities, accounts for the adverse prognosis of heart failure (HF) is uncertain. The present study examineed the intrinsic association of ischemic stroke with outcomes in a propensity-matched cohort.Methods and Results:Of 1,351 patients hospitalized with HF, 388 (28.7%) had prior ischemic stroke. Using propensity score for prior ischemic stroke, estimated for each patient, a matched cohort of 379 pairs of HF patients with and without prior ischemic stroke, balanced on 32 baseline characteristics was assembled. At 30 days, prior ischemic stroke was associated with significantly higher risks of the combined endpoint of all-cause death or readmission (hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 1.38 to 2.65; P<0.001), all-cause death (HR: 2.08; 95% CI: 1.28 to 3.38; P=0.003), all-cause readmission (HR: 2.67; 95% CI: 1.78 to 4.01; P<0.001), and HF readmission (HR: 2.11; 95% CI: 1.19 to 3.72; P=0.010). Prior ischemic stroke was associated with a significantly higher risk of all 4 outcomes at both 6 months and 1 year. CONCLUSIONS: Prior ischemic stroke was a potent and persistent risk predictor of death and readmission among patients with HF after accounting for clinical characteristics.

Age-specific differences in non-cardiac comorbidities among elderly patients hospitalized with heart failure: a special focus on young-old, old-old, and oldest-old.

BACKGROUND: Despite the growing epidemic of heart failure (HF), there is limited data available to systematically compare non-cardiac comorbidities in the young-old, old-old, and oldest-old patients hospitalized for HF. The precise differences will add valuable information for better management of HF in elderly patients. METHODS: A total of 1053 patients aged 65 years or older hospitalized with HF were included in this study. Patients were compared among three age groups: (1) young-old: 65 to 74 years, (2) old-old: 75 to 84 years, and (3) oldest-old: ≥85 years. Clinical details of presentation, comorbidities, and prescribed medications were recorded. RESULTS: The mean age was 76.7 years and 12.7% were 85 years or older. Most elderly patients with HF (97.5%) had at least one of the non-cardiac comorbidities. The patterns of common non-cardiac comorbidities were different between the young-old and oldest-old group. The three most common non-cardiac comorbidities were anemia (53.6%), hyperlipidemia (45.9%), and diabetes (42.4%) in the young-old group, while anemia (73.1%), infection (58.2%), and chronic kidney disease (44.0%) in the oldest-old group. Polypharmacy was observed in 93.0% elderly patients with HF. Additionally, 29.2% patients were diagnosed with infection, and 67.0% patients were prescribed antibiotics. However, 60.4% patients were diagnosed with anemia with only 8.9% of them receiving iron repletion. CONCLUSIONS: Non-cardiac comorbidities are nearly universal in three groups but obviously differ by age, and inappropriate medications are very common in elderly patients with HF. Further treatment strategies should be focused on providing optimal medications for age-specific non-cardiac conditions.

Effect of Dialysis on Antiplatelet Drug Efficacy in Uremic Patients with Coronary Heart Disease.

BACKGROUND: Coronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease. METHODS: This study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation. RESULTS: The mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t= -1.278, P= 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P= 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel. CONCLUSION: Dialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

Blood Pressure Targets in the Hypertensive Elderly.

OBJECTIVE: Hypertension is an important risk factor of cardiovascular disease and increases mortality in the elderly. However, the available medical evidences are both inconsistent and insufficient regarding establishing credible and useful blood pressure (BP) targets in the hypertensive elderly. This review summarizes the existing evidences used for establishing optimal BP targets for this patient population and points out some data inconsistencies which have added to the uncertainty. DATA SOURCES: We conducted a search for the articles published in English in the PubMed database up to March 2017, with the keywords "hypertension," "elderly," "blood pressure," and "antihypertensive." STUDY SELECTION: Articles that related to BP targeting in the hypertensive elderly were selected for this review. RESULTS: The selected studies indicated that antihypertensive therapy can substantially reduce the risk of cardiovascular events and mortality, for a subset of the elderly (60 years or older) with systolic BP> 160 mmHg. Studies regarding more strict targets yielded mixed findings. For the very old and frail patients (80 years or older), there is a lack of evidence that optimal BP targets and intensive antihypertensives are helpful but in fact may be harmful. CONCLUSIONS: There are solid evidences that patients who are 60-80 years old and in good health have benefited from lowering their BP to below 150/90 mmHg. If well tolerated, the BP target can be further lowered to below 140/90 mmHg. However, for the very old and frail, individualized and careful assessment is crucial. Antihypertensive treatment should be cautious and the adverse effect of drugs requires close monitoring as such treatment can be counterproductive.

ADAMTS-1 expression in rat myocardium after ischemic preconditioning: age-associated differences.

BACKGROUND: It has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning. METHODS: Sixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated. RESULTS: ADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats. CONCLUSIONS: Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.

[Ischemia preconditioning attenuated myocardial ischemia via upregulating the expression of adiponectin in rat].

OBJECTIVE: To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model. METHOD: Infarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats. RESULT: Infarct size was smaller in IPC than in MI rats (20% ± 2% vs. 31% ± 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area (P < 0.05). Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 ± 0.47 vs. 10.90 ± 1.74; 6 h: 8.18 ± 1.41 vs. 10.98 ± 1.74; 12 h: 6.97 ± 1.02 vs. 9.31 ± 0.96, P < 0.05). CONCLUSION: IPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponectin may play a critical role in the protective effect of IPC.

[Effect of ischemia preconditioning on pro- and anti- angiogenic molecule expression and functional arteries formation].

OBJECTIVE: to observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis. METHODS: rat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area. RESULTS: VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group (P < 0.05). Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P < 0.05). CONCLUSION: IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.

Electrophysiologic characteristics and radiofrequency ablation of focal atrial tachycardia arising from non-coronary sinuses of Valsalva in the aorta.

OBJECTIVES: Focal atrial tachycardia (AT) arising from non-coronary cusp (NCC) is very rare, and the experience in catheter ablation of this kind of tachycardia remains limited. This study describes the electrophysiologic characteristics and radiofrequency ablation of AT arising from NCC. METHODS AND RESULTS: The study population consisted of five consecutive patients (three females and two males; age 37-68 years) with AT arising from NCC. The morphology of P waves was described as positive, negative, isoelectric, or biphasic (positive-negative or negative-positive). The atrial mapping was performed during tachycardia to define the earliest atrial activation site. Mean tachycardia cycle length of AT in five patients was 363 +/- 44 ms. P-wave morphology was predominantly upright or biphasic in lead II, III, and aVF, inverted in aVR. Positive P-wave morphology was seen in lead aVL in all five patients. The precordial leads were negative-positive in V(1) and V(2), negative-positive or positive in lead V(3)-V(5), and positive in lead V(6). All the five patients underwent successful radiofrequency ablation within NCC. During a follow up of > 3 months, no patient presented with a recurrence. CONCLUSIONS: This study demonstrated that mapping and ablation of focal AT arising from NCC is safe and effective. When earliest activation was recorded in the proximal electrode of the His-bundle catheter, but radiofrequency ablation in this region cannot successfully eliminated the tachycardia, the AT should be considered to arise from NCC especially when P-wave morphology was initially negative with a late positive component in right precordial leads, upright or biphasic in inferior leads.

Pharmacokinetics of rapamycin-eluting stents in miniswine coronary model.

BACKGROUND: The results of clinical trials of rapamycin-eluting stents reduce restenosis have been quite promising. The main purpose of this study was to characterize the in vivo pharmacokinetics of high dose rapamycin (Rapa)-eluting stents in a miniswine coronary model. METHODS: Ten miniswines underwent placement of 18 high dose Rapa-eluting stents in the left anterior descending and right coronary arteries. At the planned times of the 1.5th, 12th, 24th hour, 3th, 7th and 28th day, the animals (n = 1, 1, 2, 2, 2, and 2, respectively) were euthanized after completion of coronary angiography. Blood samples were obtained at 0, 10, 20, 30 minutes; 1, 2, 6, 24 hours; and 3, 7, 28 days to determine systemic Rapa levels. Rapa levels in whole blood, arterial wall, heart, renal and liver tissues were determined by high-performance liquid chromatography/mass spectroscopy. RESULTS: Peak whole blood concentration (Cmax), time to peak concentration (tmax), elimination half-life (t1/2beta), area under the curve (AUC), and apparent systemic clearance (Cl/F) were (10.91 +/- 1.28) ng/ml, (2.0 +/- 0.2) hours, (7.25 +/- 0.63) hours, (1.15 +/- 0.11) ng x h x ml(-1), and (180 +/- 12) ml x h(-1) x kg(-1), respectively. More than 95% Rapa detected is localized in the coronary artery surrounding the stent and heart. CONCLUSION: Stent-based delivery of Rapa via a copolymer stent is feasible and safe. This strategy holds promise for the prevention of stent restenosis.