The management of heart failure cardiogenic shock: an international RAND appropriateness panel.

BACKGROUND: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. METHODS: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1-3 as inappropriate, 4-6 as uncertain and as 7-9 appropriate). RESULTS: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. CONCLUSION: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.

Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation.

BACKGROUND: The efficacy and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. METHODS: We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. RESULTS: Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HRadj], 0.80 [95% CI, 0.73-0.88]; P<0.001), with a generally consistent effect across BMI (Ptrend across HRs, 0.48). NOACs also reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82-0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [Ptrend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HRadj, 0.91 [95% CI, 0.87-0.95]; P<0.001; death, HRadj, 0.91 [95% CI, 0.86-0.97]; P=0.003), these benefits were attenuated at higher BMI (Ptrend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW. CONCLUSIONS: The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.

Donor utilization in heart transplant with donation after circulatory death in the United States.

Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.

Waitlist and transplant outcomes in heart transplant candidates bridged with temporary endovascular right ventricular assist devices.

BACKGROUND: Advances in mechanical circulatory support and changes in allocation policy have shifted waitlisting practices for heart transplantation (HT) in the United States. This analysis reports waitlist and transplant outcomes among HT candidates bridged with temporary endovascular right ventricular assist devices (tRVADs). METHODS: Patients awaiting HT from 2008 to 2022 in the United Network of Organ Sharing registry were grouped by the presence of tRVAD while waitlisted and propensity matched. Waitlist outcomes were HT and a competing outcome of death/deterioration requiring waitlist inactivation. Competing-risks regression was used to model waitlist outcomes. Subanalyses were performed to compare waitlist outcomes among patients with durable and temporary left ventricular assist devices (LVADs) with and without concomitant tRVADs. One-year posttransplant mortality was estimated using Kaplan-Meier analysis. RESULTS: Of 41,507 HT candidates, 133 (0.3%) had tRVADs. After propensity matching, patients with tRVAD had a similar likelihood of HT and an elevated hazard for death/deterioration (hazard ratio 2.2, 95% confidence interval 1.4-3.2, p < 0.001) compared to those without tRVAD. Most patients with tRVAD (84%) had concomitant LVADs. tRVAD was associated with an elevated risk for deterioration/death among those with temporary LVADs but not durable LVADs. For patients undergoing HT, tRVAD was associated with an increased risk for 1-year mortality compared to propensity-matched recipients. CONCLUSIONS: Bridging with tRVAD is uncommon and primarily used in patients requiring biventricular support. tRVADs are associated with waitlist inactivation or death, particularly with concomitant temporary LVAD support. As temporary devices are increasingly used as a bridge to HT, outcomes of patients with tRVADs should inform future allocation policy, particularly for candidates with biventricular failure.

Right Ventricular Contractility and Pulmonary Arterial Coupling After Less Invasive Left Ventricular Assist Device Implantation.

Right ventricular failure contributes significantly to morbidity and mortality after left ventricular assist device implantation. Recent data suggest a less invasive strategy (LIS) via thoracotomy may be associated with less right ventricular failure than conventional median sternotomy (CMS). However, the impact of these approaches on load-independent right ventricular (RV) contractility and RV-pulmonary arterial (RV-PA) coupling remains uncertain. We hypothesized that the LIS approach would be associated with preserved RV contractility and improved RV-PA coupling compared with CMS. We performed a retrospective study of patients who underwent durable, centrifugal left ventricular assist device implantation and had paired hemodynamic assessments before and after implantation. RV contractility (end-systolic elastance [Ees]), RV afterload (pulmonary effective arterial elastance [Ea]), and RV-PA coupling (Ees/Ea) were determined using digitized RV pressure waveforms. Forty-two CMS and 21 LIS patients were identified. Preimplant measures of Ees, Ea, and Ees/Ea were similar between groups. After implantation, Ees declined significantly in the CMS group (0.60-0.40, p = 0.008) but not in the LIS group (0.67-0.58, p = 0.28). Coupling (Ees/Ea) was unchanged in CMS group (0.54-0.59, p = 0.80) but improved significantly in the LIS group (0.58-0.71, p = 0.008). LIS implantation techniques may better preserve RV contractility and improve RV-PA coupling compared with CMS.

Comparative Outcomes of Sacubitril/Valsartan Use After Hospitalization for Heart Failure Among Medicare Beneficiaries Naïve to Renin-Angiotensin System Inhibitors.

Sacubitril/valsartan improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with angiotensin-converting enzyme inhibitors (ACEis). However, data on postdischarge outcomes in renin-angiotensin system inhibitor (RASi)-naïve patients are limited. We included Medicare beneficiaries aged ≥65 years who were hospitalized for HFrEF in the Get With The Guidelines-Heart Failure registry between October 2015 and June 2019, had part D prescription coverage, and were not on RASi therapy during the 6 months before hospital admission. We examined the associations between sacubitril/valsartan prescription at hospital discharge and outcomes at 30 days and 1 year after discharge using overlap-weighted median regression and Cox proportional hazards models. The end points included "home time" (defined as days alive and out of any health care institution), mortality, and rehospitalization. Among 3,572 patients with HFrEF and who are naïve to RASi therapy, at discharge, 290 (8.1%) were prescribed sacubitril/valsartan and 1,390 (38.9%) were prescribed ACEis and angiotensin receptor blockers. After adjusting for baseline characteristics, patients prescribed sacubitril/valsartan had a longer median home time (parameter estimate 27.0 days, 95% confidence interval [CI] 12.40 to 41.6, p <0.001) and lower all-cause mortality (hazard ratio [HR] 0.74, 95% CI 0.61 to 0.91, p = 0.004) at 1 year than patients not prescribed sacubitril/valsartan. The prescription of sacubitril/valsartan was not significantly associated with all-cause rehospitalization (HR 0.87, 95% CI 0.74 to 1.03, p = 0.10) or heart failure rehospitalization (HR 0.87, 95% CI 0.70 to 1.07, p = 0.19). In a restricted comparison of patients discharged on sacubitril/valsartan versus ACEis and angiotensin receptor blockers, there were no significant differences in the outcomes. In conclusion, in this contemporary population of RASi-naïve patients with HFrEF from routine clinical practice, compared with not initiating, the initiation of sacubitril/valsartan at discharge was associated with longer home time and improvements in overall survival.

Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF.

BACKGROUND: There is uncertainty surrounding the use of direct oral anticoagulants (DOACs) in patients with kidney dysfunction. METHODS: Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY [Randomized Evaluation of Long-term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), we performed an individual patient-level network meta-analysis to evaluate the safety and efficacy of DOACs versus warfarin across continuous creatinine clearance (CrCl). A multivariable Cox model including treatment-by-CrCl interaction with random effects was fitted to estimate hazard ratios for paired treatment strategies (standard-dose DOAC, lower-dose DOAC, and warfarin). Outcomes included stroke and systemic embolism (S/SE), major bleeding, intracranial hemorrhage (ICH), and death. RESULTS: Among 71 683 patients (mean age, 70.6±9.4 years; 37.3% female; median follow-up, 23.1 months), the mean CrCl was 75.5±30.5 mL/min. The incidence of S/SE, major bleeding, ICH, and death increased significantly with worsening kidney function. Across continuous CrCl values down to 25 mL/min, the hazard of major bleeding did not change for patients randomized to standard-dose DOACs compared with those randomized to warfarin (Pinteraction=0.61). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of ICH at CrCl values <122 mL/min, with a trend for increased safety with DOAC as CrCl decreased (6.2% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of S/SE with CrCl <87 mL/min, with a significant treatment-by-CrCl effect (4.8% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.01). The hazard of death was significantly lower with standard-dose DOACs for patients with CrCl <77 mL/min, with a trend toward increasing benefit with lower CrCl (2.1% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Use of lower-dose rather than standard-dose DOACs was not associated with a significant difference in incident bleeding or ICH in patients with reduced kidney function but was associated with a higher incidence4 of death and S/SE. CONCLUSIONS: Standard-dose DOACs are safer and more effective than warfarin down to a CrCl of at least 25 mL/min. Lower-dose DOACs do not significantly lower the incidence of bleeding or ICH compared with standard-dose DOACs but are associated with a higher incidence of S/SE and death. These findings support the use of standard-dose DOACs over warfarin in patients with kidney dysfunction.

Outcomes of patients with atrial fibrillation and ischemic stroke while on oral anticoagulation.

AIMS: The prognosis of patients with atrial fibrillation (AF) and ischemic stroke while taking oral anticoagulation is poorly understood. This study aimed to characterize the outcomes of patients following a stroke event while on oral anticoagulation. METHODS AND RESULTS: Individual participant data from five pivotal randomized trials of antithrombotic therapy in AF were used to assess the outcomes of patients with a post-randomization ischemic stroke while on study medication (warfarin, standard-, or lower-dose direct oral anticoagulant regimen) during trial follow-up. The primary outcome was recurrent ischemic stroke after the first post-randomization ischemic stroke. The primary analysis included 1163 patients with a first post-randomization ischemic stroke while on study medication (median age 73 years, 39.3% female, 35.4% history of stroke before trial enrollment). During a median continued follow-up of 337 days, 74 patients had a recurrent ischemic stroke [cumulative incidence at 1 year: 7.0%, 95% confidence interval (CI) 5.2%-8.7%]. The cumulative incidence of mortality at 3 months after stroke was 12.4% (95% CI 10.5%-14.4%). Consistent results for the incidence of recurrent ischemic stroke at 1 year were obtained in an analysis accounting for the competing risk of death (6.2%, 95% CI 4.8%-7.9%) and in a landmark analysis excluding the first 2 weeks after the index stroke and only including patients without permanent study drug discontinuation since then (6.8%, 95% CI 4.6%-8.9%). CONCLUSION: Patients with AF and ischemic stroke while on oral anticoagulation are at increased risk of recurrent ischemic stroke and death. These patients currently have an unmet medical need.

Characteristics, therapies, and outcomes of In-Hospital vs Out-of-Hospital cardiac arrest in patients presenting to cardiac intensive care units: From the critical care Cardiology trials network (CCCTN).

BACKGROUND: Cardiac arrest (CA) is a common reason for admission to the cardiac intensive care unit (CICU), though the relative burden of morbidity, mortality, and resource use between admissions with in-hospital (IH) and out-of-hospital (OH) CA is unknown. We compared characteristics, care patterns, and outcomes of admissions to contemporary CICUs after IHCA or OHCA. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of tertiary CICUs in the US and Canada. Participating centers contributed data from consecutive admissions during 2-month annual snapshots from 2017 to 2021. We analyzed characteristics and outcomes of admissions by IHCA vs OHCA. RESULTS: We analyzed 2,075 admissions across 29 centers (50.3% IHCA, 49.7% OHCA). Admissions with IHCA were older (median 66 vs 62 years), more commonly had coronary disease (38.3% vs 29.7%), atrial fibrillation (26.7% vs 15.6%), and heart failure (36.3% vs 22.1%), and were less commonly comatose on CICU arrival (34.2% vs 71.7%), p < 0.001 for all. IHCA admissions had lower lactate (median 4.3 vs 5.9) but greater utilization of invasive hemodynamics (34.3% vs 23.6%), mechanical circulatory support (28.4% vs 16.8%), and renal replacement therapy (15.5% vs 9.4%); p < 0.001 for all. Comatose IHCA patients underwent targeted temperature management less frequently than OHCA patients (63.3% vs 84.9%, p < 0.001). IHCA admissions had lower unadjusted CICU (30.8% vs 39.0%, p < 0.001) and in-hospital mortality (36.1% vs 44.1%, p < 0.001). CONCLUSION: Despite a greater burden of comorbidities, CICU admissions after IHCA have lower lactate, greater invasive therapy utilization, and lower crude mortality than admissions after OHCA.

The Road Not Yet Traveled: Distinction in Critical Care Cardiology through the Advanced Heart Failure and Transplant Cardiology Training Pathway.

As the acuity, complexity, and illness severity of patients admitted to cardiac intensive care units have increased, the need to recognize critical care cardiology (CCC) as a dedicated subspecialty in cardiovascular disease has received increasing support. Differing viewpoints exist regarding the optimal pathway for CCC training. Currently, all proposed CCC training pathways involve permutations of individual training years culminating in subspecialty certification across multiple disciplines; however, there are significant disadvantages to these training paradigms. We propose an innovative, pragmatic approach to CCC training through tailored subspecialty training in advanced heart failure and transplant cardiology (AHFTC), using elective time to enrich AHFTC training with skills and experiences necessary to become a highly skilled critical care cardiologist. The completion of this pathway would lead to completion of AHFTC training with a novel designation: distinction in critical care cardiology.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex.

BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data. METHODS: We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex. RESULTS: A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin. CONCLUSIONS: Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.

End-of-life care in the cardiac intensive care unit: a contemporary view from the Critical Care Cardiology Trials Network (CCCTN) Registry.

AIMS: Increases in life expectancy, comorbidities, and survival with complex cardiovascular conditions have changed the clinical profile of the patients in cardiac intensive care units (CICUs). In this environment, palliative care (PC) services are increasingly important. However, scarce information is available about the delivery of PC in CICUs. METHODS AND RESULTS: The Critical Care Cardiology Trials Network (CCCTN) Registry is a network of tertiary care CICUs in North America. Between 2017 and 2020, up to 26 centres contributed an annual 2-month snapshot of all consecutive medical CICU admissions. We captured code status at admission and the decision for comfort measures only (CMO) before all deaths in the CICU. Of 13 422 patients, 10% died in the CICU and 2.6% were discharged to palliative hospice. Of patients who died in the CICU, 68% were CMO at death. In the CMO group, only 13% were do not resuscitate/do not intubate at admission. The median time from CICU admission to CMO decision was 3.4 days (25th-75th percentiles: 1.2-7.7) and ≥7 days in 27%. Time from CMO decision to death was <24 h in 88%, with a median of 3.8 h (25th-75th 1.0-10.3). Before a CMO decision, 78% received mechanical ventilation and 26% mechanical circulatory support. A PC provider team participated in the care of 41% of patients who died. CONCLUSIONS: In a contemporary CICU registry, comfort measures preceded death in two-thirds of cases, frequently without PC involvement. The high utilization of advanced intensive care unit therapies and lengthy times to a CMO decision highlight a potential opportunity for early engagement of PC teams in CICU.

Clinical trajectory of patients with a worsening heart failure event and reduced ventricular ejection fraction.

BACKGROUND: Recent data suggest that patients with heart failure with reduced ejection fraction (HFrEF) and worsening heart failure (WHF) have potential for greater benefit from newer HF therapies. We investigated characteristics and outcomes of patients with HFrEF and WHF by severity of left ventricular dysfunction. METHODS: We identified patients with chronic symptomatic HFrEF (left ventricular ejection fraction [LVEF] ≤35%) and evidence of WHF (emergency department visit or hospitalization for acute HF within 12 months of index echocardiogram) treated at Duke University between 1/2009 and 12/2018. Patients were stratified by LVEF≤25% or 26% to35%. Cox models were used to estimate cause-specific hazard ratios and 5-year event incidence of death and hospitalization across the range of LVEF. RESULTS: Of 2823 patients with HFrEF and WHF, 1620 (57.4%) had an LVEF≤25% and 1203 (42.6%) had an LVEF 26% to35%. Compared to patients with LVEF 26% to35%, those with LVEF≤25% were younger and more commonly men with a lower cardiovascular comorbidity burden. Patients with LVEF≤25% were less commonly on beta blockers (85.9% vs 90.5%) but more commonly treated with mineralocorticoid receptor antagonists (49.3% vs 41.1%) and implantable defibrillators (41.3% vs 28.2%). Patients with LVEF≤25% had significantly higher hazards for death (HR 1.24 [95% CI 1.11 - 1.38]), all-cause hospitalization (HR 1.21 [95% CI 1.10 - 1.33]), and HF hospitalization (HR 1.25 [95% CI 1.1 - 1.38]) through 5-years. CONCLUSIONS: More than half of patients with chronic HFrEF and WHF have severe LV dysfunction. Important differences in comorbidities, HF therapies, and outcomes exist between those with LVEF≤25% and those with LVEF 26% to35%.

Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction.

OBJECTIVE: Atrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF. METHODS/RESULTS: The prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1-3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06-1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality. CONCLUSIONS: In stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF. TRIAL REGISTRATION NUMBER: ClinicalTrials: NCT01866904.

De Novo vs Acute-on-Chronic Presentations of Heart Failure-Related Cardiogenic Shock: Insights from the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown. METHODS AND RESULTS: We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P < 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P < 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P < 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02). CONCLUSIONS: Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation.

Termination Based on Event Accrual in Per Protocol Versus Intention to Treat in the ROCKET AF Trial.

Background In event-driven clinical trials, study termination is based on accrual of a target number of primary efficacy events. For noninferiority trials in which superiority is conditionally examined, the ideal cohort in which to track event accrual is unclear. We used data from the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial to determine the effect of primary efficacy-event tracking in the per-protocol cohort during the on-treatment period versus the intention-to-treat (ITT) cohort during the ITT period. Methods and Results ROCKET AF was terminated after accruing 429 primary efficacy events (stroke or systemic embolism) in the per-protocol cohort during the on-treatment period for noninferiority. We identified the date on which 429 events occurred in the ITT cohort during the ITT period. We performed noninferiority and superiority analyses based on hypothetical study termination on this date. ROCKET AF would have terminated 226 days earlier if events were tracked during the ITT period. Similar to the main trial findings, rivaroxaban would have met noninferiority versus warfarin for the primary efficacy end point (hazard ratio [HR], 0.77; 95% CI, 0.62-0.96; P<0.001). In contrast to the main trial findings, rivaroxaban would have met superiority for the primary efficacy end point (HR, 0.82; 95% CI, 0.68-0.99; P=0.038). In both termination scenarios, rivaroxaban was associated with a lower risk of intracranial hemorrhage and similar risk of other safety end points. Conclusions Clinical trial termination based on event accrual in the ITT cohort versus the per-protocol cohort may have important implications on trial results depending on rates of study drug discontinuation and event rates off treatment.

Management and Outcomes of Cardiogenic Shock in Cardiac ICUs With Versus Without Shock Teams.

BACKGROUND: Single-center studies suggest that implementation of multidisciplinary cardiogenic shock (CS) teams is associated with improved CS survival. OBJECTIVES: The aim was to characterize practice patterns and outcomes in the management of CS across multiple centers with versus without shock teams. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of cardiac intensive care units (CICUs) in North America. All consecutive medical admissions to each CICU (n = 24) were captured during annual 2-month collection periods (2017-2019; n = 6,872). Shock management and CICU mortality among centers with versus without shock teams were compared using inverse probability weighting. RESULTS: Ten of the 24 centers had shock teams. Among 1,242 CS admissions, 44% were at shock team centers. The groups were well-balanced with respect to demographics, shock etiology, Sequential Organ Failure Assessment score, biochemical markers of end organ dysfunction, and invasive hemodynamics. Centers with shock teams used more pulmonary artery catheters (60% vs 49%; adjusted odds ratio [OR]: 1.86; 95% CI: 1.47-2.35; P < 0.001), less overall mechanical circulatory support (MCS) (35% vs 43%; adjusted OR: 0.74; 95% CI: 0.59-0.95; P = 0.016), and more advanced types of MCS (53% vs 43% of all MCS; adjusted OR: 1.73; 95% CI: 1.19-2.51; P = 0.005) rather than intra-aortic balloon pumps. The presence of a shock team was independently associated with lower CICU mortality (23% vs 29%; adjusted OR: 0.72; 95% CI: 0.55-0.94; P = 0.016). CONCLUSIONS: In this multicenter observational study, centers with shock teams were more likely to obtain invasive hemodynamics, use advanced types of MCS, and have lower risk-adjusted mortality. A standardized multidisciplinary shock team approach may improve outcomes in CS.