Clinical and prognostic implications of atrial fibrillation in patients undergoing transcatheter aortic valve implantation

AIM: To study a cohort of consecutive patients under-going transcatheter aortic valve implantation (TAVI) and compare the outcomes of atrial fibrillation (AF) patients vs patients in sinus rhythm (SR). METHODS: All consecutive patients undergoing TAVI in our hospital were included. The AF group comprised patients in AF at the time of TAVI or with history of AF, and were compared with the SR group. Procedural, echocardiographic and follow-up variables were compared. Likewise, the CHA 2 DS 2-VASC stroke risk score and HAS-BLED bleeding risk score and antithrombotic treatment at discharge in AF patients were compared with that in SR patients. RESULTS: From a total of 34 patients undergoing TAVI, 17 (50%) were allocated to the AF group, of whom 15 (88%) were under chronic oral anticoagulation. Patients in the AF group were similar to those in the SR group except for a trend (P = 0.07) for a higher logistic EuroSCORE (28% vs 19%), and a higher prevalence of hypertension (82% vs 53%) and chronic renal failure (17% vs 0%). Risk of both stroke and bleeding was high in the AF group (mean CHA 2 DS 2-VASC 4.3, mean HAS-BLED 2.9). In the AF group, treatment at discharge included chronic oral anticoagulation in all except one case, and in association with an antiplatelet drug in 57% of patients. During a mean follow-up of 11 mo (maximum 32), there were only two strokes, none of them during the peri-procedural period: one in the AF group at 30 mo and one in the SR group at 3 mo. There were no statistical differences in procedural success, and clinical outcome (survival at 1 year 81% vs 74% in AF and SR groups, respectively, P = NS). CONCLUSION: Patients in AF undergoing TAVI show a trend to a higher surgical risk. However, in our cohort, patients in AF did not have a higher stroke rate compared to the SR group, and the prognosis was similar in both groups.     

Long-term outcome and risk factors associated with events in patients with atrial fibrillation treated with oral anticoagulants: The ASSAF-K registry

BackgroundOral anticoagulant therapy for atrial fibrillation (AF) has changed dramatically. Direct oral anticoagulant (DOAC) therapy is administered by general practitioners and specialists. However, the beneficial long-term effects and safety of DOACs have not been well investigated in real-world clinical practice.MethodsThe ASSAF-K (a study of the safety and efficacy of OAC therapy in the treatment of AF in Kanagawa), a prospective, multi-center, observational study, was conducted to clarify patient characteristics, status of OAC treatment, long-term outcomes, and adverse events, including cerebrovascular disease, bleeding, and death.ResultsA total of 4014 patients were enrolled (hospital: 2500 cases; clinic: 1514 cases). The number of patients in the final dataset was 3367 (mean age, 72.6 ± 10.0 years; males, 66.3 %). CHA₂DS₂-VASc and HAS-BLED scores were 3.0 ± 1.6 and 2.2 ± 1.0, respectively. The risk factors of the primary composite outcome (all-cause death, serious bleeding events, cerebral hemorrhage, and stroke) were higher age, lower body mass index, lower diastolic blood pressure, lower creatine clearance, history of heart failure, history of stroke, and medication of anti-platelet agents. The event-free rates of the primary composite outcome with DOACs, warfarin, and without OACs were 92.7 %, 88.0 %, and 87.4 %, respectively. The event rate of DOACs was significantly lower than that of warfarin [HR 0.63 (95 % CI 0.48–0.81)], and similar results were observed after adjustment for AF stroke risk score [HR 0.70 (95 % CI 0.54–0.90)]. Serious bleeding events tended to occur less frequently with DOACs compared with warfarin [unadjusted HR 0.53 (95 % CI 0.31–0.91), adjusted HR 0.61 (95 % CI 0.33–1.11)].ConclusionsThis multi-center registry demonstrated the long-term outcome in patients with AF treated with and without OACs and suggests that DOAC therapy is safe and beneficial in hospitals and clinics.     

低强度华法林抗凝治疗高出血风险房颤患者的有效性及安全性临床研究

目的：应用2010年欧洲心脏病学协会（ESC）房颤新指南提出的新的评分系统卒中危险评分（CHA2DS2-VASc）和首次推出的出血风险评分法（HAS-BLED）,观察CHA2DS2-VASc积分≥1分且HAS-BLED出血风险积分≥3分时,低强度华法林抗凝治疗高出血风险房颤患者的抗栓疗效和安全性。方法2011年1月至2012年1月我院非瓣膜性房颤患者99例,其CHA2DS2-VASc卒中危险评分≥1分且HAS-BLED出血风险积分≥3分。全部病例分成两组,标准强度华法林治疗组[2.0＜国际标准化比值（INR）≤3.0]和低强度华法林治疗组（1.6≤INR≤2.0）。观察两组患者的血栓栓塞率及出血发生率。结果卡方检验结果显示,两组患者的血栓栓塞率差异无统计学意义（P＞0.05）;标准强度华法林治疗组的出血发生率高于低强度华法林治疗组患者,差异有统计学意义（P＜0.05）。结论 CHA2DS2-VASc卒中危险评分≥1分且HAS-BLED出血风险积分≥3分的高出血风险的房颤患者可以采用低强度华法林抗凝,能有效减少血栓栓塞事件的发生,同时不增加严重出血事件,使用安全可靠。     

Clinical Outcomes Associated With Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulation in Atrial Fibrillation

ObjectivesThis study sought to investigate clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulants (DOACs) in patients with high-risk atrial fibrillation (AF).BackgroundLAAO has been shown to be noninferior to warfarin for stroke prevention in AF. However, anticoagulation with DOACs is now preferred over warfarin as thromboprophylaxis in AF.MethodsPatients with AF enrolled in the Amulet Observational Registry (n = 1,088) who had successful LAAO with the Amplatzer Amulet device (n = 1,078) were compared with a propensity score–matched control cohort of incident AF patients (n = 1,184) treated by DOACs identified from Danish national patient registries. Propensity score matching was based on the covariates of the CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65–74 years, sex category) and HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores for predicting stroke and bleeding. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium ≥3), or all-cause mortality, and follow-up was 2 years.ResultsAF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients treated with DOACs (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.49 to 0.67). Total events and event rates per 100 patient-years were (LAAO vs. DOACs) 256 vs. 461 and 14.5 vs. 25.7, respectively. The risk of ischemic stroke was comparable between groups (HR: 1.11; 95% CI: 0.71 to 1.75), while risk of major bleeding (HR: 0.62; 95% CI: 0.49 to 0.79) and all-cause mortality (HR: 0.53; 95% CI: 0.43 to 0.64) were significantly lower in patients treated with LAAO.ConclusionsAmong high-risk AF patients, LAAO in comparison with DOACs may have similar stroke prevention efficacy but lower risk of major bleeding and mortality.     

老年共病NVAF血栓形成高危患者出血评分相关因子分析

目的 通过对老年共病非瓣膜性房颤(nonvalvular atrial fibrillation,NVAF)患者血低密度脂蛋白胆固醇(LDL-C)与HAS-BLED出血评分的相关性分析,进而为该类患者的调脂及抗凝治疗提供理论依据.方法 根据纳入及排除标准,入选西安交通大学第二附属医院在2018.01～2020.06期间...     

Association Between β-Blockers and Outcomes in Heart Failure With Preserved Ejection Fraction: Current Insights From the SwedeHF Registry

Backgroundβ-Blockers have an uncertain effect in heart failure with a preserved ejection fraction of 50% or higher (heart failure with preserved ejection fraction [HFpEF]).Methods and ResultsWe included patients with HFpEF from the Swedish Heart Failure Registry (SwedeHF) enrolled from 2011 through 2018. In a 2:1 propensity-score matched analysis (β-blocker use vs nonuse), we assessed the primary outcome first HF hospitalization, the coprimary outcome cardiovascular (CV) death, and the secondary outcomes of all-cause hospitalization and all-cause death. We performed intention-to-treat and a per-protocol consistency analyses. There were a total of 14,434 patients (median age 79 years, IQR 71–85 years, 51% women); 80% were treated with a β-blocker at baseline. Treated patients were younger and had higher rates of atrial fibrillation and coronary artery disease, and higher N-terminal pro-B-type natriuretic peptide levels. In the 4412:2206 patient matched cohort, at 5 years, 42% (95% CI 40%–44%) vs 44% (95% CI 41%–47%) had a HF admission and 38% (IQR 36%–40%) vs 40% (IQR 36%–42%) died from CV causes. In the intention-to-treat analysis, β-blocker use was not associated with HF admissions (hazard ratio 0.95 [95% CI 0.87–1.05, P = .31]) or CV death (hazard ratio 0.94 [95% CI 0.85–1.03, P = .19]). In the subgroup analyses, men seemed to have a more favorable association between β-blockers and outcomes than did women. There were no associations between β-blocker use and secondary outcomes.ConclusionsIn patients with HFpEF, β-blocker use is common but not associated with changes in HF hospitalization or cardiovascular mortality. In the absence of a strong rational and randomized control trials the case for β-blockers in HFpEF remains inconclusive.Bullet points● The effect of β-blockers with heart failure with preserved ejection fraction of 50% or greater is uncertain.● In a propensity score–matched heart failure with preserved ejection fraction analysis in the SwedeHF registry, β-blockers were not associated with a change in risk for heart failure admissions or cardiovascular deaths.Lay summaryThe optimal treatment for heart failure with a preserved pump function remains unknown. Despite the lack of scientific studies, β-blockers are very commonly used. When matching patients with a similar risk profile in a large heart failure registry, the use of β-blockers for the treatment of heart failure with a preserved pump function was not associated with any changes in heart failure hospital admissions or cardiovascular death.     

Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study)

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 +/- 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 +/- 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip's classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI.     

Hyponatremia and long-term outcomes in chronic heart failure--an observational study from the Duke Databank for Cardiovascular Diseases

BackgroundHyponatremia is a well known predictor of short-term outcomes in heart failure (HF); however, its impact on long-term survival in HF patients with systolic dysfunction is not well established.Methods and ResultsUsing the Duke Databank for Cardiovascular Diseases, we identified 1,045 patients with HF and systolic dysfunction undergoing cardiac catheterization from January 2000 through December 2008. The effect of hyponatremia as independent predictor of all-cause death and cardiovascular death/rehospitalization was examined using a multivariable Cox proportional regression model. Hyponatremia was present in 107/1,045 patients (10.2%). Hyponatremic patients were older, more likely to be anemic, with higher heart rate and levels of blood urea nitrogen, lower blood pressure, and more severe HF. Using an unadjusted analysis, hyponatremia was associated with higher risk of all-cause death (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.44–2.49; P < .0001) and of cardiovascular death/rehospitalization (HR 1.40, 95% CI 1.11–1.77; P = .005) at 4.5 years. When entered into a multivariable Cox model, hyponatremia remained significant for all-cause death (HR 1.42, 95% CI 1.07–1.88) and for cardiovascular death/rehospitalization (HR 1.45, 95% CI 1.14–1.86).ConclusionsHyponatremia is relatively common in HF patients with LV dysfunction and is independently associated with increased risk of all-cause mortality and cardiovascular mortality/rehospitalization.     

Prognostic implications of adherence to oral anticoagulants among patients with atrial fibrillation: Insights from MISOAC-AF trial

ObjectivesTo explore the implications of adherence to oral anticoagulants (OACs) on all-cause mortality and cardiovascular outcomes in patients with atrial fibrillation (AF).MethodsThis post-hoc analysis of the MISOAC-AF trial included recently hospitalized patients with AF. Adherence to OACs was assessed by the proportion of days covered (PDC). Good adherence was defined as PDC >80 %. Cox regression models were used to associate PDC with clinical outcomes of all-cause death, cardiovascular death (CVD), stroke, and bleeding. A sub-analysis was performed among adherent patients to compare outcomes between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs).ResultsDuring a median 31-month follow-up, 778 cardiac patients with comorbid AF who had been prescribed OACs upon hospital discharge were studied. The mean PDC was 0.78; 66 % of patients had good adherence (>80 %) which was associated with lower risk of all-cause death [adjusted hazard ratio (aHR): 0.64; 95 % confidence interval (CI): 0.46 to 0.84, p < 0.001] and CVD (aHR: 0.70; 95 % CI: 0.50 to 0.97, p = 0.03). The risk of stroke and major or non-major bleeding did not differ by adherence status. Among adherent patients to OACs, VKA use was associated with higher rates of all-cause death (p < 0.001), CVD (p < 0.001), and stroke (p = 0.01); no differences were found regarding major or non-major bleeding risk.ConclusionsIn recently hospitalized patients with AF, good adherence to OACs was associated with a reduced risk of all-cause death and CVD. The rates of stroke or bleeding events were not significantly different. VKAs were associated with more adverse events compared to DOACs.     

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

BackgroundCoronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF.Methods and ResultsWe assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization.ConclusionsIn this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.     

The Relationship Between Valproate and Lamotrigine/Levetiracetam Use and Prognosis in Patients With Epilepsy and Heart Failure: A Danish Register-Based Study

ObjectiveTo compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF.MethodsThis was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA. A Cox regression model was used to compute crude and adjusted hazard ratios for the outcome, using an intention-to-treat approach. Average treatment effects (eg, 1-year absolute risks), risk differences and the ratio of risks were computed using the G-formula based on a Cox regression model for the outcomes at the end of the follow-up period.ResultsWe included 1345 subjects in the study population. VPA users (n = 696), when compared to LTG/LEV users (n = 649), had an increased hazard of mortality due to HF (hazard ratio [HR] 2.39; 95% CI 1.02–5.60) and to all-cause mortality (HR 1.37; 95% CI 1.01–1.85) in both crude and adjusted analyses. The 1-year absolute risks for all-cause mortality were 29% (95% CI 25%–33%) and 22% (95% CI 18%–26%) for VPA and LTG/LEV users. For mortality due to HF, 1-year absolute risks were 5% (95% CI 3%–7%) and 2% (95% CI 1%–4%) for VPA and LTG/LEV users. The average risk ratio, with LTG/LEV as the reference group, was 1.31 (95% CI 1.02–1.71) for all-cause mortality and 2.35 (95% CI 1.11–5.76) for HF mortality.ConclusionIn older people with HF and epilepsy, treatment with VPA was associated with a higher risk of all-cause and HF mortality compared to treatment with LTG and LEV.     

Prognostic Significance of Newly Diagnosed Atrial Fibrillation After Acute Myocardial Infarction: A Study of 184,980 Medicare Patients

We aimed to determine whether newly diagnosed atrial fibrillation (AF) predicted cardiovascular events and death after myocardial infarction (AMI) in a large nationwide cohort of patients. All Medicare beneficiaries aged >65 years who were discharged alive after a diagnosis of AMI between January 1, 2007 and December 31, 2008 were identified. Main exposure was a diagnosis of AF during admission or within 90 days after discharge. Primary outcome was a composite of recurrent AMI, stroke and all-cause mortality. Secondary outcomes were each of recurrent AMI, stroke and all-cause mortality. We used Cox proportional hazards regression to assess the relationship between AF and time-to-event outcomes with follow up ending at 3 years. Of 184,980 patients, 9.1 % had AF; 40.6 % were male; 82.8 % were non-Hispanic whites. Mean age was 79.1 ± 8.1 years. Overall, 15.7 % had subsequent AMI, 5.7 % had stroke and 43.9 % died during a mean follow up of 26.4 months. AF was associated with a significantly increased risk of the primary outcome (Hazard ratio (HR) = 1.10; 95 % confidence interval (CI): 1.07–1.12). AF was also separately associated with significantly increased risk of recurrent AMI (HR = 1.09; 95 % CI: 1.04–1.14), stroke (HR = 1.29; 95 % CI: 1.21–1.37), and death (HR = 1.09; 95 % CI: 1.06–1.12). Neither age, race nor sex modified the effects of AF on primary or secondary outcomes. In conclusion, AF is a significant predictor of adverse cardiovascular outcomes and mortality after AMI. Further studies are needed to understand mechanisms by which AF alters outcomes in survivors of AMI.     

Characteristics and outcomes of patients with a history of cancer recruited to heart failure trials

Aims

Heart failure (HF) therapy trials usually exclude cancer patients. We examined the association between cancer history and outcomes in trial participants with HF and reduced (HFrEF) or preserved ejection fraction (HFpEF).

Methods and results

We combined PARADIGM-HF and ATMOSPHERE, which enrolled HFrEF patients (n = 15 415) and we pooled HFpEF patients (ejection fraction ≥45%) enrolled in PARAGON-HF and CHARM-Preserved (n = 7363). The associations between cancer history, cardiovascular (CV) death, HF hospitalization, non-CV and all-cause death in these trials were examined. Incident cancer diagnoses during these trials were also measured. There were 658 (4.3%) and 624 (8.5%) patients with a cancer history in the HFrEF and HFpEF trials, respectively. HFrEF patients with a cancer history had a higher risk of HF hospitalization (adjusted hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.07–1.52, p = 0.007) and non-CV death (adjusted HR 1.57; 95% CI 1.16–2.12, p = 0.003) than those without. The risks of other outcomes were similar. There were no differences in the risk of any outcome in HFpEF patients with and without a cancer history. Adjusting for age and sex, the incidence of new cancer in the HFrEF and HFpEF trials was 1.09 (95% CI 0.83–1.36) and 1.07 (95% CI 0.81–1.32) per 100 person-years, respectively.

Conclusions

Although participants in HFrEF trials with a cancer history had higher risks of HF hospitalization and non-CV death than those without, the risks of CV and all-cause death were similar. Outcomes in HFpEF patients with and without a cancer history were similar. Incident cancer diagnoses were similar in HFrEF and HFpEF trials.     

Cardiovascular Outcomes with SGLT-2 inhibitors in patients with heart failure with or without type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials

Background and aimsWe conducted a systematic review and meta-analysis of all the randomized controlled trials (RCTs) with SGLT-2 inhibitors (SGLT-2i) in patients with known heart failure (HF) with or without type 2 diabetes (T2DM), that have studied the outcomes of cardiovascular (CV) death, hospitalization due to HF (HHF), and composite of CV death or HHF.MethodsA systematic search in PubMed, Embase and Cochrane Library database were made up till November 20, 2020 using specific keywords. RCTs that qualified underwent a meta-analysis by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio (HR) using both random- and fixed-effects model.ResultsThis meta-analysis of 9 RCTs (N = 19,741) have found a significant 26% relative risk reduction in composite of CV death or HHF (HR 0.74; 95% CI, 0.69–0.79; p < 0.001) with SGLT-2i in patients with HF. The meta-analysis of 8 RCTs (N = 16,460) also showed a significant reduction in CV death (HR 0.86; 95% CI, 0.78–0.95; p = 0.003) and HHF (HR 0.68; 95% CI, 0.62–0.74; p < 0.001) outcomes with SGLT-2i in patients with HF. Subgroup analysis stratified on baseline ejection fraction (EF) showed a similar benefit in the composite of CV death or HHF in patients with HF with reduced EF (HFrEF) or preserved EF (HFpEF).ConclusionsSGLT-2i significantly reduces the composite of CV death or HHF, CV death, and HHF in patients with HF. Although subgroup analysis suggested an insignificant P_heterogenity for these outcomes irrespective of the types of HF, however, reduction in both CV death and HHF were more pronounced in patients with HFrEF.     

Atrial fibrillation in patients with severe aortic stenosis

BackgroundThere has been no previous report evaluating the long impact of atrial fibrillation (AF) on the clinical outcomes stratified by the initial management [conservative or aortic valve replacement (AVR)] strategies of severe aortic stenosis (AS).MethodsWe analyzed 3815 patients with severe AS enrolled in the CURRENT AS registry. Patients with AF were defined as those having a history of AF when severe AS was found on the index echocardiography. The primary outcome measure was a composite of aortic valve–related death or hospitalization for heart failure.ResultsThe cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with AF than in those without AF (44.2 % versus 33.2 %, HR 1.54, 95 % CI 1.35–1.76). After adjusting for confounders, the risk of AF relative to no AF remained significant (HR 1.34, 95 % CI 1.16–1.56). The magnitude of excess adjusted risk of AF for the primary outcome measure was greater in the initial AVR stratum (N = 1197, HR 1.95, 95 % CI 1.36–2.78) than in the conservative stratum (N = 2618, HR 1.26, 95 % CI 1.08–1.47) with a significant interaction (p = 0.04). In patients with AF, there was a significant excess adjusted risk of paroxysmal AF (N = 254) relative to chronic AF (N = 528) for the primary outcome measure (HR 1.34, 95 % CI 1.01–1.78).ConclusionsIn patients with severe AS, concomitant AF was independently associated with worse clinical outcomes regardless of the initial management strategies. In those patients with conservative strategy, paroxysmal AF is stronger risk factor than chronic AF.     

Aspirin for Primary Prevention of Cardiovascular Events

BackgroundThe efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.ObjectivesThe purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.MethodsRandomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.ResultsA total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.ConclusionsAspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.     

Impact of Pre-Existing and New-Onset Atrial Fibrillation on Outcomes After Transcatheter Aortic Valve Replacement

ObjectivesThis study sought to evaluate impact of new-onset and pre-existing atrial fibrillation (AF) on transcatheter aortic valve replacement (TAVR) long-term outcomes compared with patients without AF.BackgroundPre-existing and new-onset AF in patients undergoing TAVR are associated with poor outcomes.MethodsThe study identified 72,660 patients ≥65 years of age who underwent nonapical TAVR between 2014 and 2016 using Medicare inpatient claims. History of AF was defined by diagnoses on claims during the 3 years preceding the TAVR, and new-onset AF was defined as occurrence of AF during the TAVR admission or within 30 days after TAVR in a patient without prior history of AF. Outcomes included all-cause mortality, and readmission for bleeding, stroke, and heart failure (HF).ResultsOverall, 40.7% had pre-existing AF (n = 29,563) and 6.8% experienced new-onset AF (n = 2,948) after TAVR. Mean age was 81.3, 82.4, and 83.8 years in patients with no AF, pre-existing, and new-onset AF, respectively. Pre-existing AF patients had the highest burden of comorbidities. After follow-up of 73,732 person-years, mortality was higher with new-onset AF compared with pre-existing and no AF (29.7, 22.6, and 12.8 per 100 person-years, respectively; p < 0.001). After adjusting for patient characteristics and hospital TAVR volume, new-onset AF remained associated with higher mortality compared with no AF (adjusted hazard ratio: 2.068, 95% confidence interval [CI]: 1.92 to 2.20; p < 0.01) and pre-existing AF (adjusted hazard ratio: 1.35; 95% CI: 1.26 to 1.45; p < 0.01). In competing risk analysis, new-onset AF was associated with higher risk of bleeding (subdistribution hazard ratio [sHR]: 1.66; 95% CI: 1.48 to 1.86; p < 0.01), stroke (sHR: 1.92; 95% CI: 1.63 to 2.26; p < 0.01), and HF (sHR: 1.98; 95% CI: 1.81 to 2.16; p < 0.01) compared with pre-existing AF.ConclusionsIn patients undergoing TAVR, new-onset AF is associated with increased risk of mortality and bleeding, stroke, and HF hospitalizations compared with pre-existing AF or no AF.     

Elevated pulmonary artery pressure by Doppler echocardiography predicts hospitalization for heart failure and mortality in ambulatory stable coronary artery disease: the Heart and Soul Study.

OBJECTIVES: We compared the predictive ability of tricuspid regurgitation (TR) and end-diastolic pulmonary regurgitation (EDPR) gradients in outpatients with coronary artery disease. BACKGROUND: The TR and EDPR gradients, in conjunction with right atrial pressure, provide Doppler estimates of pulmonary artery systolic and diastolic pressures. We hypothesized that increases in TR or EDPR gradients in stable coronary artery disease would predict heart failure (HF) hospitalization or cardiovascular (CV) death. METHODS: We measured TR and EDPR gradients in 717 adults with completed outcome adjudications who were recruited for the Heart and Soul Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for HF hospitalization, CV death, all-cause death, and the combined end point. Multivariate adjustments were made for age, gender, race, history of CV or pulmonary disease, functional class, and left ventricular ejection fraction. RESULTS: There were 63 HF hospitalizations, 19 CV deaths, and 86 all-cause deaths at the 3-year follow-up. There were 466 measurable EDPR gradients and 573 measurable TR gradients. Age-adjusted ORs for EDPR >5 mm Hg predicted HF hospitalization (2.7, 95% CI 1.3 to 5.5, p = 0.006), all-cause death (2.5, 95% CI 1.4 to 4.4, p = 0.002), and HF hospitalization or CV death (2.7, 95% CI 1.4 to 5.2, p = 0.004). Age-adjusted OR for TR >30 mm Hg predicted HF hospitalization (3.4, 95% CI 1.9 to 6.2, p < 0.0001) and HF hospitalization or CV death (3.0, 95% CI 1.7 to 5.3, p = 0.0001). Multivariate adjusted OR per 5-mm Hg incremental increases in EDPR predicted HF hospitalization or CV death (1.9, 95% CI 1.01 to 3.6, p = 0.046) and all-cause death (1.7, 95% CI 1.05 to 2.8, p = 0.03). Multivariate adjusted OR per 10-mm Hg incremental increases in TR predicted HF hospitalization or CV death (1.6, 95% CI 1.1 to 2.4, p = 0.008). CONCLUSIONS: Increases in EDPR or TR gradients predict HF hospitalization or CV death among ambulatory adults with coronary artery disease.     

Can we predict stroke in atrial fibrillation?

Stroke prevention with appropriate thromboprophylaxis still remains central to the management of atrial fibrillation (AF). Nonetheless, stroke risk in AF is not homogeneous, but despite stroke risk in AF being a continuum, prior stroke risk stratification schema have been used to 'artificially' categorise patients into low, moderate and high risk stroke strata, so that the patients at highest risk can be identified for warfarin therapy. Data from recent large cohort studies show that by being more inclusive, rather than exclusive, of common stroke risk factors in the assessment of the risk for stroke and thromboembolism in AF patients, we can be so much better in assessing stroke risk, and in optimising thromboprophylaxis with the resultant reduction in stroke and mortality. Thus, there has been a recent paradigm shift towards getting better at identifying the 'truly low risk' patients with AF who do not even need antithrombotic therapy, whilst those with one or more stroke risk factors can be treated with oral anticoagulation, whether as well-controlled warfarin or one or the new oral anticoagulant drugs. The new European guidelines on AF have evolved to deemphasise the artificial low/moderate/high risk strata (as they were not very predictive of thromboembolism, anyway) and stressed a risk factor based approach (within the CHA(2) DS(2)-VASc score) given that stroke risk is a continuum. Those categorised as 'low risk' using the CHA(2) DS(2)-VASc score are 'truly low risk' for thromboembolism, and the CHA(2) DS(2)-VASc score performs as good as-and possibly better--than the CHADS(2) score in predicting those at 'high risk'. Indeed, those patients with a CHA(2) DS(2)-VASc score = 0 are 'truly low risk' so that no antithrombotic therapy is preferred, whilst in those with a CHA(2) DS(2)-VASc score of 1 or more, oral anticoagulation is recommended or preferred. Given that guidelines should be applicable for >80% of the time, for >80% of the patients, this stroke risk assessment approach covers the majority of the patients we commonly seen in everyday clinical practice, and considers the common stroke risk factors seen in these patients. The European guidelines also do stress that antithrombotic therapy is necessary in all patients with AF unless they are age <65 years and truly low risk. Indeed, some patients with 'female gender' only as a single risk factor (but still CHA(2) DS(2)-VASc score of 1, due to gender) do not need anticoagulation, especially if they fulfil the criterion of "age <65 and lone AF, and very low risk". In the European and Canadian guidelines, bleeding risk assessment is also emphasised, and the simple validated HAS-BLED score is recommended. A HAS-BLED score of ≥ 3 represents a sufficiently high risk such that caution and/or regular review of a patient is needed. It also makes the clinician think of correctable common bleeding risk factors, and the availability of such a score allows an informed assessment of bleeding risk in AF patients, when antithrombotic therapy is being initiated.     

Impact of Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction

BackgroundFew studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance.Methods and ResultsPatients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m² in men and >33 mL/m² in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00–26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26–9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09–3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone.ConclusionsThese data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.