ANMCO Position paper: e-Health management in cardiovascular care pathways

Managing atrial fibrillation in the CRT patient: Controversy or consensus?

In this issue of the Circulation: Arrhythmia and Electrophysiology , Kurotobi et al1 determined the number of arrhythmogenic foci in atria provocable with isoproterenol infusion in patients with paroxysmal, persistent, and permanent atrial fibrillation (AF). The results show that persistent AF has more foci than paroxysmal AF. However, when AF persists for >12 months, the number of foci were reduced. The authors suggest that the increased number of foci probably is involved in the development of persistent AF. However, because this association is not observed for AF that persists for >12 months, the importance of these foci in AF maintenance remains unclear. Article see p 39 In ambulatory canine models, simultaneous sympathovagal discharges (rather than isolated sympathetic activation) are typical triggers of paroxysmal atrial tachycardia (AT) and AF.2,3⇓ These observations are explained by the late phase-3 early afterdepolarization (EAD), which depends on the coexistence of increased amplitude and duration of intracellular calcium (Cai) transient and the shortened action potential duration (APD).4,5⇓ Vagal stimulation shortens APD and therefore is needed to promote the late phase-3 EAD. In the Kurotobi study, however, arrhythmogenic foci were induced by isoproterenol alone, without the need of vagal stimulation or the use of parasympathomimetic agents. These results are different from that obtained in canine studies. The first possible explanation is that the pulmonary veins (PVs) naturally have shorter APDs with elevated (less negative) membrane potentials.6,7⇓ Rapid activation may further shorten the APD in the PVs.8 These changes are independent of the vagal tone. Jais et al9 reported the effective refractory periods of the PVs were shorter …

Oral Anticoagulation in Heart Failure with Atrial Fibrillation: Are We Taking the Right Steps Towards Guidelines?

Objective:to assess the diagnostic significance of atrial and brain natriuretic peptides for the detection of chronic heart failure in comorbid patients with atrial fibrillation and chronic obstructive pulmonary disease.Materials and methods:120 patients depending on the presence of chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and atrial fibrillation (AF) were divided into the following groups: I group (n=28) — patients with COPD without cardiovascular disease (CVD), II group — patients with CHF and COPD without AF (n=30), III group — patients with CHF and AF without COPD (n=33), IV group — patients with CHF, AF and COPD (n=29). Th e concentration of precursors of brain and atrial natriuretic peptides (NUP) (NT-proBNP and MR-proANP) was evaluated.Results:The level of NT-proBNP exceeded the reference values in all patients with CHF (I, II, III groups). In patients with CHF, AF and COPD the highest values of NT-proBNP concentrations were obtained, which were 2.2 times higher in the group of patients with CHF and COPD without AF (p=0.000) and 1.9 times higher in patients with CHF and AF without COPD (p=0.01). Comparative analysis of the MR-proANP level allowed to judge a higher concentration of this indicator in patients with CHF and COPD without COPD in comparison with the level of the marker in the groups of patients with CHF, AF and COPD (p=0.001), CHF and COPD without AF (p=0.000) and COPD without CVD (p=0.000).Conclusions:in patients with AF and COPD, the study of brain NUP NT-proBNP in connection with structural and functional changes of the right ventricle, against the background of existing cardiac arrhythmias and pulmonary pathology is preferable to determine the presence and severity of CHF. The elevated level of MR-proANP is of diagnostic value in patients with AF and CHF without COPD, due to the increased volume load on the Atria due to the presence of AF.

Atrial fibrillation and heart failure frequently coexist but the relative effect of atrial fibrillation on survival in people with heart failure, and vice versa, remains uncertain. We aimed to report contemporary estimates of mortality among people with atrial fibrillation and heart failure and analyse trends in mortality over time. We did a retrospective cohort study of adults aged 45 years or older in England, using primary care data from the Clinical Practice Research Datalink GOLD dataset and linked secondary care data (Hospital Episode Statistics and Office for National Statistics datasets), for a total follow-up period from Jan 1, 2000, to Dec 31, 2018. We recorded incident cases of heart failure and atrial fibrillation in primary or secondary care during the study period, as well as pre-existing cases at the study index date. Individuals were categorised as having both heart failure and atrial fibrillation, atrial fibrillation only, heart failure only, or neither condition, with heart failure and atrial fibrillation included in analyses as time-varying covariates. The primary outcome was all-cause mortality, as recorded in primary or secondary care. We report the incidence and hazard ratios for all-cause mortality by diagnosis status, median overall survival following diagnosis, and the cumulative probability of all-cause mortality from 3 months to 10 years of follow-up and by year of diagnosis to assess trends over time. Estimates of median survival and the cumulative probability of overall mortality were restricted to incident diagnoses during the study period, and calculated overall as well as by sex, age, and Index of Multiple Deprivation quintile. The cohort consisted of 2 381 941 people, including 100 132 initially diagnosed with heart failure only and 155 061 initially diagnosed with atrial fibrillation only by the study index date or during follow-up. By the end of follow-up, 74 470 people had been diagnosed with both conditions. 314 042 people died during follow-up, including 42 427 (57·0%) of those diagnosed with both heart failure and atrial fibrillation. In people diagnosed with both conditions during the study period (n=43 714), median overall survival was 3·15 years (95% CI 3·08-3·21), and the cumulative probability of mortality was 31·8% (95% CI 30·2-33·6) at 1 year, 61·4% (59·4-63·3) at 5 years, and 80·2% (78·3-82·1) at 10 years after both conditions had been diagnosed, representing significantly worse rates than for an initial diagnosis of either condition alone. Similarly, the risk-adjusted hazard of all-cause mortality was highest among people with both heart failure and atrial fibrillation. For the overall population, cumulative mortality probability estimates were unchanged over successive years of diagnosis for people with both heart failure and atrial fibrillation, while showing small improvements for people initially diagnosed with heart failure only (median reduction in 10-year cumulative probability of 3·8% [95% CI 1·4-6·1] between diagnosis years 2000 and 2008) or atrial fibrillation only (median reduction in 1-year cumulative mortality probability of 2·4% [0·5-4·2] between diagnosis years 2000 and 2017) and improvement over the long-term for people diagnosed with both conditions before age 65 years (median reduction in 10-year cumulative mortality probability of 14·5% [95% CI 3·8-25·2] between diagnosis years 2000 and 2008). For people with both conditions, median overall survival was significantly longer in the least deprived quintile (3·46 years [95% CI 3·31-3·59]; n=9275) than in the most deprived quintile (2·67 years [2·51-2·81]; n=6302). Median overall survival in each exposure group was similar between sexes after stratifying for age. Comorbid heart failure and atrial fibrillation was common and prognosis was poor, with no improvement in mortality estimates for diagnoses over time, and the worst survival in socially deprived groups. Wellcome Trust and the National Institute for Health and Care Research Collaboration for Leadership in Applied Health Research and Care Oxford.

Atrial fibrillation and congestive heart failure are risk factors for ischemic stroke usually attributed to cardiac embolism. To define potential alternative mechanisms, patients with atrial fibrillation and congestive heart failure were investigated by transcranial Doppler. Middle cerebral artery (MCA) blood flow velocities were analyzed in neurologically asymptomatic patients with nonvalvular (n = 10) and valvular (n = 13) atrial fibrillation, patients in normal sinus rhythm with congestive heart failure (n = 13), and control subjects (n = 11). Compared to patients in sinus rhythm with congestive heart failure and to control subjects, patients in both atrial fibrillation groups had significantly greater beat-to-beat variation in peak, mean, and diastolic velocities and in pulsatility index. Peak, mean, and diastolic MCA velocities in patients with atrial fibrillation and those with congestive heart failure were significantly less than those in control subjects. Patients with nonvalvular atrial fibrillation had a higher pulsatility index compared to each of the other three groups. These findings demonstrate substantial nonemboligenic alterations of the intracranial circulation associated with atrial fibrillation and congestive heart failure, and also provide an intracranial hemodynamic profile that may distinguish valvular from nonvalvular atrial fibrillation.

<i>Circulation: Arrhythmia and Electrophysiology</i> Editors’ Picks

Pitfall in the anticoagulant therapy in patients with paroxysmal atrial fibrillation and heart failure

Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction. We studied Framingham Heart Study participants with new-onset AF or HF between 1980 and 2012. Among 1737 individuals with new AF (mean age, 75±12 years; 48% women), more than one third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79±11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HF with preserved ejection fraction (multivariable-adjusted hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.48-3.70; no AF as referent) versus HF with reduced ejection fraction (HR, 1.32; 95% CI, 0.83-2.10), with a trend toward difference between HF subtypes (P for difference=0.06). Prevalent HF was associated with incident AF (HR, 2.18; 95% CI, 1.26-3.76; no HF as referent). The presence of both AF and HF portended greater mortality risk compared with neither condition, particularly among individuals with new HF with reduced ejection fraction and prevalent AF (HR, 2.72; 95% CI, 2.12-3.48) compared with new HF with preserved ejection fraction and prevalent AF (HR, 1.83; 95% CI, 1.41-2.37; P for difference=0.02). AF occurs in more than half of individuals with HF, and HF occurs in more than one third of individuals with AF. AF precedes and follows HF with both preserved and reduced ejection fraction, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted.

Recurrent orthostatic syncope due to left atrial and left ventricular collapse after a continuous-flow left ventricular assist device implantation

Background: Heart failure is a leading health problem with over 500,000 new cases and 275,000 deaths annually in the United States. Recent reports indicate that atrial fibrillation (AF) is linked to various forms of ventricular dysfunction (VD). Over 2 million Americans have AF, which is more prevalent in people over 65 years of age. However, the molecular “cause and effect” relationship between AF and VD has not been elucidated. We hypothesize that abrogation of nuclear erythroid-2 like factor-2 (Nrf2), a master antioxidant transcriptional regulator, induces atrial remodeling and fibrillation on aging. Methods: Age and sex matched WT and Nrf2-/- mice were used in this study. Atrial mass, remodeling, antioxidants and molecular redox signaling were studied at 2 and &gt;20 months of age. Echocardiography, immunoblotting, quantitative real-time PCR and immunofluorescence (fibrosis) analyses were performed in the atrial tissue. Results: At 2 months of age, WT and Nrf2-/- mice had comparable levels of ROS in the atrium. On aging, the ROS levels were significantly increased in atria of Nrf2- null when compared to wild-type (WT) mice at 20 months of age. While decreased Nrf2-antioxidant signaling in response to increased ROS generation in atria of Nrf2- null mice was observed, ventricular function appeared to be normal at 20 months of age. However, upon endurance exercise stress (EES), hypertrophy markers including ANF, BNF, PLN and SERCA2A were significantly (p&lt;0.05) altered in Nrf2- null when compared to age-matched WT mice. Further, activation of fibrotic process was evident in the Nrf2- null mouse atrium as indicated by significantly (p&lt;0.05) increased markers of tissue remodeling (i.e. MMP2/9) on aging. These results indicating an early onset of atrial hypertrophy/remodeling due to age-induced oxidative stress, which cause AF in Nrf2- null mice. Age-dependent decline in Nrf2 and sustained progression of AF could lead to ventricular dysfunction and heart failure. Conclusion: Our findings indicate that atria are primary targets to age-associated oxidative stress and exhibit fibrosis, which promotes atrial fibrillation and remodeling. Thus, activation of Nrf2 signaling to prevent oxidative stress could be a potential therapeutic target for AF.

This paper aims to provide guidance for clinicians, based on the evidence available regarding the clinical effectiveness and health economics of the self management of oral anticoagulation therapy by patients....

Introduction: Heart Failure (HF) has shared genetic architecture with its risk factors, including atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). The risk prediction performance of polygenic risk scores (PRS) for those HF risk factors and HF itself over an established risk equation warrants investigation. Methods: Within the Atherosclerosis Risk in Communities (ARIC) study, six PRSs were constructed for AF, BMI, CHD, SBP, T2D, and HF by summing the product of pre-computed weights from genome-wide association studies and SNP allele dosages in European and African Americans separately. The association between PRSs and incident HF was assessed using cox proportional hazard models, and the 10-, 20-, and 30-year risk prediction performance of PRS over the ARIC HF risk equation was assessed using C-statistics. Associations between AF PRS and HF subtypes, echocardiographic measures, and 4,877 proteins were examined. Results: Over 30 years follow-up, 1,922 (22%) and 735 (29%) HF cases developed in 8,624 European (mean age=54.2, 52% female) and 2,525 African (mean age=53.3, 61% female) Americans. The PRSs for AF and HF were associated with incident HF in both European and African Americans (P&lt;0.05). The AF PRS showed the greatest effect on HF risk in European (HR=1.47, 95% CI: 1.41 to 1.53) and African (HR=1.29, 95% CI: 1.20 to 1.39) Americans. Addition of AF PRS to the ARIC HF risk equation significantly improved the C-statistics for 10-year risk prediction in European (ΔC=0.017, 95% CI: 0.009 to 0.026) and African (ΔC=0.015, 95% CI: 0.004 to 0.026) Americans. The AF PRS was further associated with HF with reduced (HR=1.45, 95% CI: 1.29 to 1.64) and preserved (HR=1.49, 95% CI: 1.34 to 1.66) ejection fraction, and higher left atrial volume index (P=1.67х10 -4 ). Protein analyses revealed that 61 proteins were associated with AF PRS, where NT-proBNP and Coagulation factor X showed the strongest positive and negative associations respectively. Conclusions: The PRS of AF was associated with incident HF, and had significant incremental value over an established HF risk prediction equation. These findings suggest that PRS may be useful in identifying individuals with high risk of HF.

(1) Background: Atrial fibrillation (AF) is the most common arrhythmia causing an increased risk of mortality and morbidity. It is classified into paroxysmal and non-paroxysmal AF depending on the duration and frequency of the episodes. (2) Aims: Our goal was to investigate and compare the clinical profiles, risk of co-morbidities, the use of oral anticoagulation, and outcomes of patients with paroxysmal and non-paroxysmal AF in inpatient and outpatient settings. (3) Methods: Data were extracted from 28 different hospitals and centers in Jordan with a total of 2160 patients enrolled in the study using an observational non-interventional study model. The clinical features and the use of oral anticoagulants were compared in patients with paroxysmal and non-paroxysmal AF. (4) Results: Paroxysmal AF was documented in 35.6% (769) of the patients and non-paroxysmal types in 63.9% (1380); in addition, the type of AF was unknown in 11 (0.5%) patients. Our results showed that non-paroxysmal AF patients tend to be older with more co-morbidities and higher CHA2DS2-VASC and HAS-BLED scores. They also have higher rates of hypertension and diabetes. Anticoagulant, antiarrhythmic, and diuretic agents, overall, were used more in non-paroxysmal AF than paroxysmal AF. Hospital admissions were also more frequent in non-paroxysmal AF due to various factors, some of which are heart failure, bleeding risk, and COPD. (5) Conclusions: Non-paroxysmal AF is more common among Jordanian AF patients. The prevalence of comorbidities and the use of different types of therapies, especially anticoagulants, were higher in these patients.

Background: Atrial fibrillation (AF) can be associated with reductions in left ventricular ejection fraction (LVEF) that improve upon conversion of AF to sinus rhythm. Such LVEF changes during AF may be due to LVEF measurement error from beat-to-beat variations related to AF itself. More precise artificial intelligence (AI)-enhanced LVEF assessment could help distinguish between such LVEF “pseudo-reduction” during AF and true cardiomyopathy, thus potentially preventing unnecessary downstream workup and treatment. Methods: Using a transthoracic echocardiogram database at a large academic medical center, we identified all patients whose LVEF fell below 50% while in AF who had subsequent LVEF recovery to over 50% within 90 days after converting from AF to sinus rhythm. For echocardiograms in AF, we compared the clinically assessed LVEF with AI-enhanced LVEF assessment by EchoNet-Dynamic, a validated deep learning algorithm. Results: In our cohort of 84 patients, the mean age was 74 years old, 36.9% were female, and 26.2% non-White. The mean LVEF recovery was 19.3% (95% CI 17.1-21.5%) after converting from AF to sinus rhythm with a mean duration of 27.4 days between the AF and sinus rhythm echocardiograms (Figure 1). For AF echocardiograms, the LVEF when reassessed by deep learning was 8.4% (6.3-10.5%) higher than the original clinical read, resulting in 30.3% of patients being reclassified as no longer having a reduced LVEF less than 50% while in AF. Among these patients with LVEF reductions during AF, 27.4% and 19.0% were given a new or worsened heart failure with reduced ejection fraction (HFrEF) diagnosis, 15.5% underwent ischemic testing, and 17.9% were started on new HFrEF medications. Discussion: LVEF reductions during AF can lead to new HFrEF diagnosis, workup, and treatment. However, such LVEF reductions may be temporary and partially explained by undermeasurement of LVEF during AF. AI-enhanced LVEF assessment may help reduce such measurement errors during AF and thereby prevent overdiagnosis of HFrEF. Further research is needed to understand the clinical significance of true but temporary LVEF reductions during AF.