Citations

Introduction: Cardiovascular disease remains the leading cause of morbidity and mortality in patients with amyloid light chain (AL) amyloidosis. Current prognostic evaluation in AL cardiomyopathy (AL-CM) largely relies upon disparate proxy measurements to assess mortality. With respect to observed myocardial volume changes between systole and diastole, we describe a single measurement derived from cardiac MRI (CMR) to assess mortality of AL-CM. Methods: A cohort of 129 consecutive patients with AL-CM undergoing CMR with amyloid protocol from the years 2001 - 1997 was reviewed. Myocardial volume change at end systole and end diastole was assessed by disc summation with CMR. The myocardial function index (MFI) was calculated by consolidating blood pool and myocardial volume measures as confluent components of myocardial function utilizing operator tracings. The association of MFI and death was assessed with adjusted hazard ratios (HR) derived by a Cox model. Results: Data at time of CMR was reviewed. The mean age was 60 ±10; 68% subjects were female. Median survival from CMR was 47 months. Mean LVEF was assessed by echocardiography to be 55% ± 12. Mean calculated MFI was 19.8% ±7. Univariate analysis suggested MFI is strongly associated with death (HR 0.004; 95%CI 0.00002-0.0838; p = 0.0003). A multivariate analysis re-demonstrated the strong predictive value of MFI when controlled for age (HR 0.006; 95%CI 0.00003 - 0.1156; p = 0.0006). Conclusion: MFI strongly correlates with mortality in AL-CM. In contrast to previously described assessments of ventricular function (extracellular volume imaging, myocardial perfusion imaging, and myocardial contraction fraction), MFI is easily derived from CMR and considers blood pool and myocardial volumes as confluent components of myocardial function. Further studies are needed to assess MFI amongst patients with varying etiologies of heart failure.

Introduction: Recent studies showed post-operative atrial fibrillation (POAF) is associated with increased stroke risk - even approaching that of unprovoked AF. This raises the question of whether patients with POAF should receive anticoagulation. We aim to compare different anticoagulation strategies in patients with POAF after cardiac and non-cardiac surgeries. Methods: Using a large national administrative database (OptumLabs Data Warehouse), we identified 33,981 patients with POAF between 1/1/2013-9/30/2019. Patients were divided to four groups based on the initial treatment within 30 days of POAF: (1) no anticoagulation (N=28,807) (2) apixaban (N=2178) (3) rivaroxaban (N=1320) (4) warfarin (N=1676). Follow up started at the 30 th day after POAF to exclude patients who died shortly after surgery and minimize immortal time bias. The follow up continued until patients changed treatment strategies, insurance, or died. 1:1 propensity score matching was performed between each anticoagulant to no treatment to balance on 86 baseline characteristics. Results: The mean age was 71.1±11.2 yr; mean CHA 2 DS 2 -VASc was 4.1±1.8; 29.1% received cardiac surgeries; 15.2% received anticoagulation within 30 days of POAF. The event rate per 100 person years was 1.58 for stroke in no-anticoagulation group, and 1.29 for anticoagulation group; 2.86 for major bleeding in no-anticoagulation group and 4.50 for anticoagulation group. After matching, apixaban and rivaroxaban were associated with a lower risk of stroke, but a higher risk of major bleeding; warfarin was not associated with a lower risk of stroke, but a higher risk of major bleeding (Figure). The effect was consistent across subgroups, e.g., age and surgery type. Conclusions: In patients with POAF, the stroke rate was lower than what was typically observed in clinical AF. Treatment with apixaban and rivaroxaban immediately after POAF was associated with a reduced risk of stroke but an increased risk of major bleeding.

Introduction: Watchman has been increasingly used in AF patients who have difficulties taking anticoagulation, but the RCTs only compared Watchman to warfarin. There was also a signal of increased ischemic stroke with Watchman in comparison to warfarin in RCTs, which made some clinicians question the fundamental premise that Watchman can reduce stroke. We aimed to compare Watchman to no anticoagulation in a large national cohort of patients in the US. Methods: We identified AF patients treated with Watchman (N=7,309) or no anticoagulation (N=1,234,543) between 2015-2017 from the OptumLabs Data Warehouse, which is the first to link private insurance, Medicare Advantage, and Medicare Fee-for-Service records at patient level longitudinally. One-to-one propensity score matching was used to balance patients on demographics and medical history. The primary outcomes were ischemic stroke or systemic embolism (hereafter referred to as stroke) and major bleeding. Secondary outcomes included all-cause mortality and intracranial bleeding. Results: In the unmatched cohort, the mean age was 76.6±6.4 yr in the Watchman group and 76.6 ±8.5 yr in the no anticoagulation group, but Watchman patients were more likely to have a history of bleeding (44.9% vs 13.7%) and intracranial bleeding (9.5% vs 2.6%). After matching, the two groups were similar on 18 baseline characteristics. Watchman was associated with a lower risk of stroke and mortality, but a higher risk of major bleeding and a similar risk of intracranial bleeding. The associations were largely consistent across subgroups, including those with relative contraindications to anticoagulation (Figure). Conclusions: In AF patients who had difficulties taking anticoagulation, Watchman offers an alternative approach to reduce stroke and mortality. The results provide important evidence to inform clinical decision making in the absence of RCTs, since 40% of AF patients in routine practice are not on anticoagulation.

Abstract Background We have demonstrated that a neural network is able to predict a person’s age from the electrocardiogram (ECG) [artificial intelligence (AI) ECG age]. However, some discrepancies were observed between ECG-derived and chronological ages. We assessed whether the difference between AI ECG and chronological age (Age-Gap) represents biological ageing and predicts long-term outcomes. Methods and results We previously developed a convolutional neural network to predict chronological age from ECGs. In this study, we used the network to analyse standard digital 12-lead ECGs in a cohort of 25 144 subjects ≥30 years who had primary care outpatient visits from 1997 to 2003. Subjects with coronary artery disease, stroke, and atrial fibrillation were excluded. We tested whether Age-Gap was correlated with total and cardiovascular mortality. Of 25 144 subjects tested (54% females, 95% Caucasian) followed for 12.4 ± 5.3 years, the mean chronological age was 53.7 ± 11.6 years and ECG-derived age was 54.6 ± 11 years (R2 = 0.79, P < 0.0001). The mean Age-Gap was small at 0.88 ± 7.4 years. Compared to those whose ECG-derived age was within 1 standard deviation (SD) of their chronological age, patients with Age-Gap ≥1 SD had higher all-cause and cardiovascular disease (CVD) mortality. Conversely, subjects whose Age-Gap was ≤1 SD had lower all-cause and CVD mortality. Results were unchanged after adjusting for CVD risk factors and other survival influencing factors. Conclusion The difference between AI ECG and chronological age is an independent predictor of all-cause and cardiovascular mortality. Discrepancies between these possibly reflect disease independent biological ageing.

Objectives Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions. Methods Data were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region. Results GDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AF-death score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions. Conclusions In patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions. Trial registration number ClinicalTrials.gov Registry NCT00412984 and NCT00262600.

Background: Atrial fibrillation (AF), mitral regurgitation (MR), and left ventricular (LV) ejection fraction have a complex interplay. We evaluated the role of AF in patients with heart failure and moderate-to-severe or severe secondary MR enrolled in the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and its impact on mechanisms and outcomes with the MitraClip. Methods: Patients in the COAPT trial were stratified by the presence (n=327) or absence (n=287) of a history of AF and by assignment to treatment group. Clinical, echocardiographic, and outcome measures were assessed. The primary outcome was the composite rate of death or heart failure hospitalization at 24 months. Results: Patients with history of AF were older and more often male. They had a higher LV ejection fraction, larger left atrial volumes and mitral valve orifice areas, smaller LV volumes, and similar MR severity. Patients with AF compared with those without a history of AF had a higher unadjusted (hazard ratio [HR], 1.32 [95% CI, 1.06–1.64], P =0.01) and adjusted (HR, 1.30 [1.03–1.64], P =0.03) 2-year rate of the primary outcome. Treatment with the MitraClip compared with guideline-directed medical therapy alone reduced death or heart failure hospitalization in both those with (HR, 0.61 [0.46–0.82]) and without (HR, 0.46 [0.33–0.66]) a history of AF ( P int =0.18). Treatment with the MitraClip was associated with a lower risk of stroke in patients with a history of AF (HR, 0.18 [0.04–0.86]) but not in those without a history of AF (HR, 1.64 [0.58–4.62]; P int =0.02). Conclusions: In the COAPT trial, patients with a history of AF had larger left atrial and mitral valve orifice areas with higher LV ejection fraction and smaller LV volumes, suggesting an atrial mechanism contribution to functional MR. Despite the worse prognosis of heart failure patients with a history of AF, MR reduction with the MitraClip still afforded substantial clinical benefits. Treatment with MitraClip was associated with a lower risk of stroke in patients with a history of AF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01626079.

Abstract Aims There are limited contemporary data on the use of initial fibrinolysis in ST-segment elevation myocardial infarction cardiogenic shock (STEMI-CS). This study sought to compare the outcomes of STEMI-CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI). Methods Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (&gt;18 years) STEMI-CS admissions receiving pre-hospital/in-hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI-CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in-hospital mortality, development of non-cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do-not-resuscitate status. Results During 2009–2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non-White, with lower co-morbidity, and admitted on weekends and to small rural hospitals (all P &lt; 0.001). In the fibrinolysis group, 95.3%, 77.4%, and 15.7% received angiography, PCI, and coronary artery bypass grafting, respectively. The fibrinolysis group had higher rates of haemorrhagic complications (13.5% vs. 9.9%; P &lt; 0.001). The fibrinolysis group had comparable all-cause in-hospital mortality [logistic regression analysis: 28.8% vs. 28.5%; propensity-matched analysis: 30.8% vs. 30.3%; adjusted odds ratio 0.97 (95% confidence interval 0.90–1.05); P = 0.50]. The fibrinolysis group had comparable rates of acute organ failure, hospital length of stay, rates of palliative care referrals, do-not-resuscitate status use, and lesser hospitalization costs. Conclusions The use of initial fibrinolysis had comparable in-hospital mortality than those receiving PPCI in STEMI-CS in the contemporary era in this large national observational study.

Stem cell and regenerative approaches that might rejuvenate the heart have immense intuitive appeal for the public and scientific communities. Hopes were fueled by initial findings from preclinical models that suggested that easily obtained bone marrow cells might have significant reparative capabilities; however, after initial encouraging pre-clinical and early clinical findings, the realities of clinical development have placed a damper on the field. Clinical trials were often designed to detect exceptionally large treatment effects with modest patient numbers with subsequent disappointing results. First generation approaches were likely overly simplistic and relied on a relatively primitive understanding of regenerative mechanisms and capabilities. Nonetheless, the field continues to move forward and novel cell derivatives, platforms, and cell/device combinations, coupled with a better understanding of the mechanisms that lead to regenerative capabilities in more primitive models and modifications in clinical trial design suggest a brighter future.

Abstract The concept that cell-based repair of myocardial injury might be possible was introduced almost two decades ago; however, the field of cardiovascular reparative medicine has been criticized as translation to clinically effective approaches has been slow. The recent retraction of a series of papers has further impacted perception of this area of research. As researchers, clinicians, and teachers in this field, we felt it incumbent to critically appraise the current state of cardiac cell repair, determine what can be learned from past mistakes, and formulate best practices for future work. This special communication summarizes an introspective assessment of what has fallen short, how to prevent similar issues, and how the field might best move forward in the service of science and patients.