AHA_CF_etoc_Apr

Can be initiated early and safely in Patients stabilized after an acute HF decompensation event.

Risk of death and hospitalization more e ectively vs. Enalapril

QoL and functional capacity 2,3

ADHF: Acute decompensated heart failure; QoL: Quality of life 1. N Engl J Med. 2014 Sep 11;371(11):993-1004. 2. JAMA Cardiol. 2018 Jun 1;3(6):498-505.; 3. Front Cardiovasc Med.2021 Nov 11;8:754499.; 4. Eur J Heart Fail. 2019 Aug;21(8):998-1007.

April 2023 - Volume 16, Issue 4

In-Hospital Observation on Oral Diuretics After Treatment for Acute Decompensated Heart Failure:

Evaluating the Utility

Background: Following treatment for acute decompensated heart failure, in-hospital observation on oral diuretics (OOD) is recommended, assuming it provides actionable information on discharge diuretic dosing and thus reduces readmissions. Methods: In the Mechanisms of Diuretic Resistance (MDR) cohort, we analyzed in-hospital measures of diuretic response, provider’s decisions, and diuretic response ≈30 days postdischarge. In a Yale multicenter cohort, we assessed if in-hospital OOD was associated with 30-day readmission risk. The main objective of this study was to evaluate the utility of in-hospital OOD. Results: Of the 468 patients in the MDR cohort, 57% (N=265) underwent in-hospital OOD. During the OOD, weight change and net fluid balance correlated poorly with each other ( r =0.36). Discharge diuretic dosing was similar between patients who had increased, stable, or decreased weight (decreased discharge dose from OOD dose in 77% versus 72% versus 70%, respectively), net fluid status (decreased discharge dose from OOD dose in 100% versus 69% versus 74%, respectively), and urine output (decreased discharge dose from OOD dose in 69% versus 79% versus 72%, respectively) during the 24-hour OOD period ( P >0.27 for all). In participants returning at 30 days for formal quantification of outpatient diuretic response (n=98), outpatient and inpatient OOD natriuresis was poorly correlated ( r =0.26). In the Yale multicenter cohort (n=18 454 hospitalizations), OOD occurred in 55% and was not associated with 30-day hospital readmission (hazard ratio, 0.98 [95% CI, 0.93 – 1.05]; P =0.51). Conclusions: In-hospital OOD did not provide actionable information on diuretic response, was not associated with outpatient dose selection, did not predict subsequent outpatient diuretic response, and was not associated with lower readmission rate. Additional research is needed to replicate these findings and understand if these resources could be better allocated elsewhere.

April 2023 - Volume 16, Issue 4

Adverse Outcomes Associated With Interleukin-6 in Patients Recently Hospitalized for Heart Failure With Preserved Ejection Fraction

Background: Inflammation may play a role in the pathophysiology of heart failure with preserved ejection fraction. We examined whether circulating levels of interleukin-6 identify patients at greater risk of adverse outcomes following hospitalization with heart failure with preserved ejection fraction. Methods: We assessed relationships between interleukin-6 (IL-6) tertiles (T1-3) and all-cause death, cardiovascular death, and subsequent heart failure hospitalization (sHFH) in 286 patients recently hospitalized with heart failure with preserved ejection fraction. Associations between IL (interleukin)-6 and outcomes were examined in a Cox-regression model adjusted for risk factors including BNP (B-type natriuretic peptide). Biomarkers including hsCRP (high-sensitivity C reactive protein) were assessed. Results: The range of IL-6 (pg/mL) in each tertile was T1 (0.71 – 4.16), T2 (4.20 – 7.84), and T3 (7.9 – 236.32). Compared with T1, patients in the highest IL-6 tertile were more commonly male (56% versus 35%) and had higher crea tinine (117±45 versus 101±36 μmol/L), hsCRP (11.6 [4.9– 26.6]mg/L versus 2.3[1.1 – 4.2] mg/L). In univariable analysis, rates of all-cause death, cardiovascular death, and sHFH were higher in T3 versus T1. All-cause and cardiovascular death rates remained higher in T3 versus T1 after adjustment (P<0.001). One log unit increase in IL-6 was associated with higher risk of all-cause death (hazard ratio, 1.46 [1.17 – 1.81]), cardiovascular death (hazard ratio, 1.40 [1.10 – 1.77]), and sHFH (hazard ratio, 1.24 [1.01 – 1.51]) after adjustment. One log unit increase in hsCRP was associated with a higher risk of cardiovascular death and all-cause death before and after adjustment for other factors but was not associated with risk of sHFH before or after adjustment. Conclusions: In patients recently hospitalized with heart failure with preserved ejection fraction, IL-6 is an independent predictor of all-cause mortality, cardiovascular death, and sHFH after adjustment for risk factors including BNP. These findings are of particular relevance in the context of current anti – IL-6 drug development.

April 2023 - Volume 16, Issue 4

Outcomes of Combined Heart and Kidney Transplantation Under the New Heart Allocation Policy: A United Organ Network for Organ Sharing Database Analysis

Background: The impact of the new heart allocation policy, which prioritizes acutely ill patients on temporary mechanical circulatory support and provides broader sharing of donor organs, on patient and graft survival in combined heart and kidney transplantation (HKT) is unknown. Methods: In the United Network for Organ Sharing data, patients were divided in groups before and after the policy change (OLD, January 1, 2015 to October 17, 2018, N=533; and NEW, October 18, 2018 to December 31, 2020, N=370). Propensity score matching was performed utilizing recipient characteristics (283 pairs). The median follow-up was 1099 days. Results: The annual volume of HKT increased approximately 2-fold during this period (N=117 in 2015 and N=237 in 2020), predominantly among patients not on hemodialysis at time of transplantation. Ischemic times for heart (OLD, 2.94 versus NEW, 3.37 hours; P<0.001) and kidney grafts (14.1 versus 16.0 hours; P<0.001) were longer under the new policy, as was the travel distance (47 versus 183 miles; P<0.001). In the matched cohort, 1-year overall survival (OLD, 91.1% versus NEW, 84.8%; P<0.001), and freedom from heart and kidney graft failure rate were worse under the new policy. Patients not on hemodialysis at time of HKT demonstrated worse survival and a higher risk of kidney graft failure under the new policy compared with the old policy. In multivariate Cox proportional-hazards analysis, the new policy was associated with an increased risk of mortality (hazard ratio, 1.81; P=0.007), and graft failure among HKT recipients (heart, hazard ratio, 1.81; P=0.007; and kidney, hazard ratio, 1.83; P=0.002). Conclusions: The new heart allocation policy was associated with worse overall survival and decreased freedom from heart and kidney graft failure in HKT recipients

April 2023 - Volume 16, Issue 4

Exposure to Arterial Hyperoxia During Extracorporeal Membrane Oxygenator Support and Mortality in Patients With Cardiogenic Shock

Background: Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator (ECMO) support. We examined hyperoxia in the Extracorporeal Life Support Organization Registry among patients receiving venoarterial ECMO for cardiogenic shock. Methods: We included Extracorporeal Life Support Organization Registry patients from 2010 to 2020 who received venoarterial ECMO for cardiogenic shock, excluding extracorporeal CPR. Patients were grouped based on PaO2 after 24 hours of ECMO: normoxia (PaO2 60 – 150 mmHg), mild hyperoxia (PaO2 151 – 300 mmHg), and severe hyperoxia (PaO2 >300 mmHg). In-hospital mortality was evaluated using multivariable logistic regression. Results: Among 9959 patients, 3005 (30.2%) patients had mild hyperoxia and 1972 (19.8%) had severe hyperoxia. In-hospital mortality increased across groups: normoxia, 47.8%; mild hyperoxia, 55.6% (adjusted odds ratio, 1.37 [95% CI, 1.23 – 1.53]; P<0.001); severe hyperoxia, 65.4% (adjusted odds ratio, 2.20 [95% CI, 1.92 – 2.52]; P<0.001). A higher PaO2 was incrementally associated with increased in-hospital mortality (adjusted odds ratio, 1.14 per 50 mmHg higher [95% CI, 1.12 – 1.16]; P<0.001). Patients with a higher PaO2 had increased in-hospital mortality in each subgroup and when stratified by ventilator settings, airway pressures, acid-base status, and other clinical variables. In the random forest model, PaO2 was the second strongest predictor of in-hospital mortality, after older age. Conclusions: Exposure to hyperoxia during venoarterial ECMO support for cardiogenic shock is strongly associated with increased in-hospital mortality, independent from hemodynamic and ventilatory status. Until clinical trial data are available, we suggest targeting a normal PaO2 and avoiding hyperoxia in CS patients receiving venoarterial ECMO

April 2023 - Volume 16, Issue 4

Predictive Modeling to Assess Pretest Probability of Transthyretin Gene Variants Based on Demographic Information

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a morbid condition, though recent advances in diagnosis and therapy stand to change its natural history. Patients’ TTR genotype may guide family screening as more treatments and preventive strategies become available. An efficient, intuitive means of determining pretest genetic risk may better inform patients/clinicians when pursuing genetic testing. Methods: This is a cohort study of 767 consecutive patients diagnosed with ATTR-CM who underwent genetic testing. Classification and regression trees (CART) analysis created a decision tree assessing likelihood of carrying a pathologic TTR gene variant. Age, sex, and race were used as independent variables. Logistic regression was also performed to model probability of pathologic TTR genotype. The primary outcome was the decision tree’s accuracy in 2 separate institutions’ ATTR -CM registry. Results: In our study cohort, 208 patients (27.1%) had ATTRv. Race has served most efficiently as the root node followed by age and sex in a CART algorithm, and showed 88.2% accuracy (75.3% sensitivity, 93.9% specificity) in the validation cohort. The odds of having a TTR gene variant were greater in Black patients compared with non-Black patients (OR, 34.6 [95% CI, 20.5 – 58.3]; P<0.001). Non-Black patients with ATTR CM aged 69 years and older had <4% risk of having a predisposing mutation. Conclusions: This CART algorithm incorporating age, sex, and race was able to determine which patients with ATTR CM have pathogenic TTR mutations with high specificity. Non-Black patients diagnosed at age 69 years or older with ATTR-CM have a low likelihood to have ATTRv