Lowest Risk Patients Research Articles

Clinical Outcomes, Costs, and Value of Surgery Among Older Patients with Colon Cancer at US News and World Report Ranked Versus Unranked Hospitals

BackgroundUS News and World Report (USNWR) hospital rankings influence patient choice of hospital, but their association with surgical outcomes remains ill-defined. We sought to characterize clinical outcomes and costs of surgery for colon cancer among USNWR top ranked and unranked hospitals.MethodsUsing Medicare Standard Analytic Files, patients aged ≥65 years undergoing surgery for colon cancer were identified. Hospitals were categorized as ‘ranked’ or ‘unranked’ based on USNWR cancer hospital rankings. One-to-one matching was performed between patients treated at ranked and unranked hospitals, and clinical outcomes and costs of surgery were compared.ResultsAmong 50 ranked and 2522 unranked hospitals, 13,650 patient pairs were compared. Overall, 30-day mortality was 2.13% in ranked hospitals versus 3.68% in unranked hospitals (p < 0.0001), and the overall paired cost difference was $8159 (p < 0.0001). As patient risk increased, 30-day mortality differences became larger, with the ranked hospitals having 30-day mortality of 7.59% versus 11.84% for unranked hospitals among the highest-risk patients (p < 0.0001). Overall paired cost differences also increased with increasing patient risk, with cost of care being $72,229 for ranked hospitals versus $56,512 for unranked hospitals among the highest-risk patients (difference = $14,394; p = 0.02). The difference in cost per 1% reduction in 30-day mortality was $9009 (95% confidence interval [CI] $6422–$11,597) for lowest-risk patients, which dropped to $3387 (95% CI $2656–$4119) for highest-risk patients (p < 0.0001).ConclusionTreatment at USNWR-ranked hospitals, particularly for higher-risk patients, was associated with better outcomes but higher-cost care. The benefit of being treated at highly ranked USNWR hospitals was most pronounced among high-risk patients.

Estimating benefit from dose dense adjuvant chemotherapy for early breast cancer in the PANTHER randomized phase 3 trial.

521 Background: Adjuvant dose dense chemotherapy for early breast cancer improves patient outcomes across all subgroups compared with standard interval treatment. However, the effect of dose dense treatment based on individual patient risk and over time, and the performance of the PREDICT model at this setting are not well-studied. Methods: This is an exploratory analysis from the phase 3 PANTHER trial (NCT00798070) that compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose dense (tDD EC/D, every 2 weeks) or standard interval schedule (FEC/D, every 3 weeks) to patients with high-risk resected early breast cancer. Dose tailoring in the experimental arm was performed according to a predefined algorithm based on hematologic and non-hematologic toxicity. We evaluated the performance of PREDICT in terms of calibration and discrimination in the entire cohort and subgroups of interest, conducted a subpopulation treatment effect pattern plot (STEPP) analysis and observed the relative treatment effect over time. Results: The intention-to-treat population consists of n=2003 randomized patients. Median follow-up was 10.3 years (interquartile range, 9.1 – 10.5 years). PREDICT consistently underestimated 5-year (absolute difference 1.4%) and 10-year overall survival (absolute difference 6.6%) in the entire population and across all subgroups, but mostly so in the highest risk patients where the difference between observed and predicted 10-year survival reached 20.4% for patients with tumors larger than 5 cm. Discriminatory accuracy was lower for 10-year than for 5-year survival (AUC 0.728 and 0.786, respectively), although the difference in model performance between the two treatment groups was small. In STEPP analysis, absolute benefit from tDD EC/D in the primary endpoint of breast cancer relapse free survival was stable across risk-defined overlapping subpopulations and ranged from 3.8% in the lowest risk patients to 3.6% in the highest risk ones. There was no evidence of differential treatment effect through time (pinteraction &gt;0.1 for all time-to-event endpoints). Conclusions: In this largely node-positive population, PREDICT consistently overestimated risk for death in all patient subgroups. We could not reliably identify any subgroup not benefiting from dose dense treatment, which should be the standard of care for primary resected high-risk breast cancer. Clinical trial information: NCT00798070 .

Análisis de los datos del Registro Español de Cirugía Cardiaca (RECC) 2021-2022

IntroductionSince February 8, 2021, the Spanish Society of Cardiovascular and Endovascular Surgery got under way the Spanish Registry of Cardiac Surgery (RECC), which is available for the different units of cardiovascular surgeons in our country. It is a tool that allows collect patient-level data of patients undergoing cardiac, vascular or endovascular surgery. After two years of development, we have carried out an analysis of the quality of the information obtained in order to acquire an overview of its content. MethodsThe information has been analyzed anonymously at patient, hospital and province level. For risk-adjusted mortality estimation, the EuroSCORE II preoperative risk estimation scale was used. ResultsA total of 7087 interventions have been included. Six thousand two hundred and sixty-seven were major cardiac surgeries: 53.9% valvular, 25.2% coronary artery bypass grafting, and 14.9% aortic procedures. The overall mortality was 5.0% and the risk-adjusted mortality rate was 0.88. The EuroSCORE II calibration in the overall sample was good in the lowest-risk patients, although it overestimated mortality in high-risk patients. ConclusionsRECC is a nationally defined clinical database in the field of cardiovascular surgery. RECC allows a patient-level data analysis in order to perform an accurate analysis of the volumen of activity, risk adjustment and results. Locally, it could be used as a tool to improve the quality of care and development of corrective programs.

Genomic determinants of outcome in acute lymphoblastic leukemia: A Children’s Oncology Group study.

10015 Background: While cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, half of relapses arise in those originally classified with standard risk (SR) disease. Methods: We performed genome/transcriptome sequencing of diagnostic and germline samples of children with SR (n=1381) B-ALL or high-risk (HR) B-ALL with favorable cytogenetics ( ETV6: RUNX1 or double trisomy (DT) of chromosomes (chr) 4+10; n=115) to identify predictors of relapse. We used a case-control study to analyze 439 patients who relapsed and 1057 who remained in complete remission for &gt; 5 years. Results: Genomic subtype was associated with relapse. Unbalanced ETV6:RUNX1 translocations were more common than balanced in relapse patients (OR=2.01, CI=1.25-3.20, P=0.002). Conversely, balanced TCF3:PBX1 translocations were more often associated with relapse than unbalanced in TCF3:PBX1 ALL (OR=0.11, CI=0.01-0.50, P=0.003). A striking finding was the high relapse rate in PAX5 altered ALL (57 of 116 cases (49%); OR=3.29, CI=2.16-5.01, P=3.49x10-8). The nature of the heterogeneous PAX5 driver alterations of this subtype influenced relapse risk, with internal PAX5 amplifications and biallelic PAX5 alterations associated with the highest risk. Specific chr gains influenced outcome in hyperdiploid ALL, with gain of chr 10 and disomy of chr 7 associated with favorable outcome (OR=0.27, CI=0.17-0.42, P=8.02x10-10, St Jude Children’s Research Hospital (SJCRH) validation cohort: OR=0.22, CI=0.05-0.80, P=0.009), while disomy of chr 10 and 17 and gain of chr 6 were enriched in patients that relapsed (OR=7.16, CI=2.63-21.51, P=2.19x10-5; SJCRH cohort: OR=21.32, CI=3.62-119.30, P=0.0004). Genomic alterations were also associated with relapse in a subtype-dependent manner, including alterations of INO80 in ETV6:RUNX1, IKZF1 and CREBBP in hyperdiploid, and FHIT in Ph-like ALL. Conclusions: Genetic subtype, aneuploidy patterns, and secondary genomic alterations influence risk of relapse in children otherwise classified with SR ALL, or HR ALL with favorable genetics. Comprehensive genomic analysis is required for optimal risk stratification and treatment allocation, and particularly to study reduction of therapy in the lowest risk patients. [Table: see text]

Drug therapies for stroke prevention.

Stroke is a major cause of mortality, morbidity and economic burden. Strokes can be thrombotic, embolic or haemorrhagic. The key risk factor for cardioembolic stroke is atrial fibrillation or flutter, and oral anticoagulation (OAC) is recommended in all but the lowest-risk patients with evidence of these arrhythmias. Risk factors for thrombotic stroke overlap strongly with those for other atherosclerotic cardiovascular diseases (ASCVDs). Antiplatelet therapy (APT) should be considered in patients with established ASCVD to reduce risk of cardiovascular events, including stroke. Intensification from single to dual APT or a combination of APT with low-dose OAC can reduce ischaemic stroke risk further, but increases bleeding risk. Blood pressure and lipid profile should be controlled appropriately to guideline targets. In patients with diabetes, good glycaemic control can reduce stroke risk. Inflammation is another emerging target for stroke prevention. Overall, comprehensive assessment and pharmacological modification of risk factors are central to stroke prevention.

Cause of death and excess mortality in patients with lower-risk myelodysplastic syndromes (MDS): A report from the European MDS registry.

Information on causes of death (CoDs) and the impact of myelodysplastic syndromes (MDS) on survival in patients with lower-risk MDS (LR-MDS) is limited. A better understanding of the relationship between disease characteristics, clinical interventions and CoDs may improve outcomes of patients with LR-MDS. We prospectively collected data on patients with LR-MDS in the European MDS registry from 2008 to 2019. Clinical, laboratory and CoDs data were obtained. To examine MDS-specific survival, relative survival (RS) was estimated using national life tables. Of 2396 evaluated subjects, 900 died (median overall survival [OS]: 4.7 years; median follow-up: 3.5 years). The most common CoDs were acute myeloid leukaemia/MDS (20.1%), infection (17.8%) and cardiovascular disease (CVD; 9.8%). Patients with isolated del(5q) and with red cell transfusion needed during the disease course, had a higher risk of fatal CVD. The 5-year OS was 47.3% and the 5-year RS was 59.6%, indicating that most patients died due to their underlying MDS. Older patients (aged >80 years) and the lowest-risk patients were more likely to die from competing causes. This study shows that MDS and its related complications play crucial role in the outcome of patients with LR-MDS.

Survey of current transplant center practices regarding COVID-19 vaccine mandates in the United States

An electronic survey canvassing current policies of transplant centers regarding a COVID-19 vaccine mandate for transplant candidates and living donors was distributed to clinicians at US solid organ transplant centers performing transplants from October 14, 2021–November 15, 2021. Responses were received from staff at 141 unique transplant centers. These respondents represented 56.4% of US transplant centers, and responding centers performed 78.5% of kidney transplants and 82.4% of liver transplants in the year prior to survey administration. Only 35.7% of centers reported implementing a vaccine mandate, while 60.7% reported that vaccination was not required. A minority (42%) of responding centers with a vaccine mandate for transplant candidates also mandated vaccination for living organ donors. Centers with a vaccine mandate most frequently cited clinical evidence supporting the efficacy of pre-transplant vaccination (82%) and stewardship obligations to ensure organs were transplanted into the lowest risk patients (64%). Centers without a vaccine mandate cited a variety of reasons including administrative, equity, and legal considerations for their decision. Transplant centers in the United States exhibit significant heterogeneity in COVID-19 vaccination mandate policies for transplant candidates. While all centers encourage vaccination, most centers have not mandated COVID-19 vaccination for candidates and living donors, citing administrative opposition, legal prohibitions, and concern about equity in access to transplants.

A qualitative exploration of decisions about dental recall intervals - Part 1: attitudes of NHS general dental practitioners to NICE guideline CG19 on the interval between oral health reviews

Introduction The National Institute for Health and Care Excellence (NICE) Guideline CG19 recommends that the intervals between oral health reviews should be tailored to patients' disease risk. However, evidence suggests that most patients still attend at six-monthly intervals.Aim To explore facilitators and barriers to the implementation of CG19 in general dental practice.Methods Semi-structured telephone interviews were conducted with 25 NHS general dental practitioners (GDPs) in Wales, UK. Transcripts were thematically analysed.Results Dentists described integrating information on clinical risk, patients' social and dental history, and professional judgement when making decisions about recall interval. Although most GDPs reported routinely using risk-based recall intervals, a number of barriers exist to recall intervals at the extremes of the NICE recommendations. Many practitioners were unwilling to extend recall intervals to 24 months, even for the lowest-risk patients. Conversely, dentists described how it could be challenging to secure the agreement of high-risk patients to three-month recalls. In addition, time and workload pressures, the need to meet contractual obligations, pressure from contracting organisations and the fear of litigation also influenced the implementation of risk-based recalls.Conclusions Although awareness of the NICE Guideline CG19 was high, there is a need to explore how risk-based recalls may be best supported through contractual mechanisms.

Development of a Model for the Pediatric Survival After Veno-Arterial Extracorporeal Membrane Oxygenation Score: The Pedi-SAVE Score.

Pediatric cardiac extracorporeal membrane oxygenation (ECMO) patients have high mortality rates. The purpose of our study was to develop and validate the Pediatric Survival After Veno-arterial ECMO (Pedi-SAVE) score for predicting survival at hospital discharge after pediatric cardiac veno-arterial (VA) ECMO. We used data for pediatric cardiac VA-ECMO patients from the Extracorporeal Life Support Organization registry (1/1/2001-12/31/2015). Development and validation cohorts were created using 2:1 random sampling. Predictors of survival to develop pre- and postcannulation models were selected using multivariable logistic regression and random forest models. ß-coefficients were standardized to create the Pedi-SAVE score. Of 10,091 pediatric cardiac VA-ECMO patients, 4,996 (50%) survived to hospital discharge. Pre- and postcannulation Pedi-SAVE scores predicted that the lowest risk patients have a 65% and 74% chance of survival at hospital discharge, respectively, compared to 33% and 22% in the highest risk patients. In the validation cohort, pre- and postcannulation Pedi-SAVE scores had c-statistics of 0.64 and 0.71, respectively. Precannulation factors associated with survival included: nonsingle ventricle congenital heart disease, older age, white race, lower STAT mortality category, higher pH, not requiring acid-buffer administration, <2 cardiac procedures, and indication for VA-ECMO other than failure to wean from cardiopulmonary bypass. Postcannulation, additional factors associated with survival included: lower ECMO pump flows at 24 hours and lack of complications. The Pedi-SAVE score is a novel validated tool to predict survival at hospital discharge for pediatric cardiac VA-ECMO patients, and is an important advancement in risk adjustment and benchmarking for this population.

Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital

ObjectivesCOVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal...

Doing less, accomplishing more for childhood acute lymphoblastic leukaemia (ALL).

With survival rates of childhood acute lymphoblastic leukaemia (ALL) reaching 90%, the inevitable question is, can we do less? Risk-stratified ALL therapy has led to a low (10%) cumulative risk of relapse (CIR), leading some to question the value of routine, scheduled follow-up and blood counts. In a population-based ALL study from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) registry, Jensen et al1 reported that scheduled follow-up diagnosed only 49% of relapses. Surprisingly, relapses diagnosed during scheduled visits did not fare better (5-year overall survival 63% compared to 72% for relapses detected by extra visits; hazard ratio 0·95). The authors concluded that after completing ALL therapy, scheduled visits yielded no extra benefit. However, this conclusion should be interpreted with caution. Jensen et al. excluded those who underwent haematopoietic stem cell transplantation (HSCT). Also excluded were 262 of 600 (44%) cases of relapses that had occurred during therapy. Patients who were post-HSCT or with relapsed leukaemia had a significantly higher risk of relapse and complications. While Jensen et al. studied only the most feared complications, that is relapse and secondary malignancies, scheduled visits enabled screening for potential severe chronic health conditions (CHCs) and school coping issues. Why did patients, who were diagnosed with relapse during scheduled visits, counter-intuitively, have poorer outcomes? We suggest that they had poorer outcomes because they had significantly higher risk factors.1 Specifically, their median time to relapse was signficantly shorter at 39 months (vs 45 months; P = 0·009). In addition, they had an increased incidence of isolated bone marrow relapse (P = 0·02). Thus, scheduled visits picked up higher risk relapses, which was, in fact, advantageous. To diagnose one subclinical relapse, Jensen et al. calculated that as many as 1269 blood tests had to be done.1 This calculation remained theoretical and biased; all scheduled patients diagnosed with symptoms and signs of relapse were excluded. Such exclusion unnecessarily disadvantaged against scheduled visits. In fact, all patients had scheduled visits; extra visits were additional. Equally important, 58 of 130 (45%) patients who were diagnosed with relapse during extra visits suffered symptoms for >2 weeks. Such delays in diagnosis were of equal concern. After more than 2 years of treatment, the value of a scheduled visit goes beyond just diagnosing relapse alone. The Children’s Cancer Survivor Study2 reported that severe CHCs occurred in 21% of survivors of ALL. However, in risk-stratified standard risk (SR) patients, these severe CHCs were reduced to 11%. Yet, despite this reduction, compared to their siblings, ALL SR survivors experienced increased severe CHC [relative risk (RR) 1·9]. Compared to the general population, this increase in CHC was not associated with increased mortality. In four groups of ALL survivors: (1) relapsed ALL; (2) SCT; (3) cranial or total body irradiation; and (4) high-risk patients, an increased risk of severe CHC and neurocognitive impairment remained.2 We have reported that ALL survivors, especially those treated with cranial radiotherapy, had increased chronic inflammation and accelerated ageing.3 Arguably, to better manage severe CHC, these patients need more, not fewer, scheduled visits and care. For decades, the key concern of both doctors and patients is relapse. Relapse can be catastrophic; it means a resistant disease requiring more intensive therapies with increased morbidity and mortality. Recently, cell-based therapy such as chimeric antigen receptor T-cell therapy against CD19 (CAR-T CD19) cured 50% of B-lymphoblastic leukaemia in second relapse.4 With more effective therapy, relapse may be salvageable. To, carefully, do less and not lose hard-fought gains, we need to choose who can be safely followed up less frequently. From the minimal residual disease-stratified Malaysia-Singapore ALL 2003 experience,5 after completing therapy, the lowest risk patients (Malaysia-Singapore 2003 SR) had only 1·7% CIR (Table I). Similarly, after completing NOPHO ALL 2008 therapy,1 the CIR was only 3·4%. The choice is clear: low-risk ALL patients, treated using reduced intensity protocols without cranial radiotherapy, can be followed less. The authors thank Dr Edwynn Chiew and Mr Chen ZW for providing the updated data on MS2003. All the authors contributed to the writing of the paper. Yeoh AE received speaker fee from Amgen (2020). The other authors have no conflicts of interest.

Prioritizing cervical cancer screening services during the COVID-19 pandemic: Response of an academic medical center and a public safety net hospital in California

The expeditious diagnosis and treatment of high-grade cervical precancers are fundamental to cervical cancer prevention. However, during the COVID-19 pandemic healthcare systems have at times restricted in-person visits to those deemed urgent. Professional societies provided some guidance to clinicians regarding ways in which traditional cervical cancer screening might be modified, but many gaps remained. To address these gaps, leaders of screening programs at an academic medical center and an urban safety net hospital in California formed a rapid-action committee to provide guidance to its practitioners. Patients were divided into 6 categories corresponding to various stages in the screening process and ranked by risk of underlying high-grade cervical precancer and cancer. Tiers corresponding to the intensity of the local pandemic were constructed, and clinical delays were lengthened for the lowest-risk patients as tiers escalated. The final product was a management grid designed to escalate and de-escalate with changes in the local epidemiology of the COVID-19 pandemic. While this effort resulted in substantial delays in clinical screening services as mandated by the healthcare systems, the population effects of delaying on both cervical cancer outcomes as well as the beneficial effects related to decreasing transmission of severe acute respiratory coronavirus 2 have yet to be elucidated.

Aneuploidy and loss of heterozygosity as risk markers for malignant transformation in oral mucosa.

The ability to predict malignant transformation in oral potentially malignant disorders would inform targeted treatment, provide prognostic information and allow secondary prevention. DNA ploidy and loss of heterozygosity assays are already in clinical use, and loss of heterozygosity has been used in prospective clinical trials. This review appraises published evidence of predictive ability and explores interpretation of heterogeneous studies, with different diagnostic methods, criteria and intention. Both methods have a sound biological foundation and have predictive value independent of dysplasia grading and clinical parameters. The application of these two techniques cannot be directly compared because of differences in expression of results and application to populations of different risk. Predicting malignant transformation accurately on an individual patient basis is not yet possible with either technique. However, they are valuable applications to stratify patients for inclusion in trials, identify the lowest risk patients and exclude risk when biopsy results are indeterminate for dysplasia.

Patient-Reported Outcomes and Long-Term Nonadherence to Aromatase Inhibitors.

Nonadherence to aromatase inhibitors (AIs) is common and increases risk of breast cancer (BC) recurrence. We analyzed factors associated with nonadherence among patients enrolled in S1105, a randomized trial of text messaging. At enrollment, patients were required to have been on an adjuvant AI for at least 30 days and were asked about financial, medication, and demographic factors. They completed patient-reported outcomes (PROs) representing pain (Brief Pain Inventory), endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms), and beliefs about medications (Treatment Satisfaction Questionnaire for Medicine; Brief Medication Questionnaire). Our primary endpoint was AI nonadherence at 36 months, defined as urine AI metabolite assay of less than 10 ng/mL or no submitted specimen. We evaluated the association between individual baseline characteristics and nonadherence with logistic regression. A composite risk score reflecting the number of statistically significant baseline characteristics was examined. We analyzed data from 702 patients; median age was 60.9 years. Overall, 35.9% patients were nonadherent at 36 months. Younger patients (younger than age 65 years) were more nonadherent (38.8% vs 28.6%, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.05 to 2.16; P = .02). Fourteen baseline PRO scales were each statistically significantly associated with nonadherence. In a composite risk model categorized into quartile levels, each increase in risk level was associated with a 46.5% increase in the odds of nonadherence (OR = 1.47, 95% CI =1.26 to 1.70; P < .001). The highest-risk patients were more than 3 times more likely to be nonadherent than the lowest-risk patients (OR = 3.14, 95% CI = 1.97 to 5.02; P < .001). The presence of multiple baseline PRO-specified risk factors was statistically significantly associated with AI nonadherence. The use of these assessments can help identify patients for targeted interventions to improve adherence.

An Exploratory Study of Goals of Care Conversations Initiated with Seriously Ill Veterans in the Emergency Room.

Background: Emergency department (ED) visits are common for older patients with chronic, life-limiting illnesses and may offer a valuable opportunity for clinicians to initiate proactive goals of care conversations (GoCC) to ensure end-of-life care that aligns with the patients' values, goals, and preferences. Objectives: The purpose of this study is to assess whether GoCC are occurring with patients in Department of Veteran Affairs (VA) EDs, to characterize these patients' goals of care and life-sustaining treatment (LST) decisions, and to examine the extent to which palliative or hospice consultations occur following the ED visit. Design: We conducted a cross-sectional retrospective study using health record data. Settings/Subjects: A total of 10,780 patients receiving care in VA, whose first GoCC occurred during an ED visit. Results: Of the patients in the study, approximately half were at least 70 years of age, three-quarters were white, and half had multiple serious disease comorbidities. The percentage of patients who desired cardiopulmonary resuscitation was lower among the highest risk (i.e., of hospitalization and death) patients (64% vs. 51%). The percentage of patients wanting other LSTs (e.g., mechanical ventilation) was higher among the lowest risk patients; and the percentage of patients requesting limits to LSTs was highest among higher risk patients. Eighteen percent of patients had a palliative or hospice care consult within three months of their ED visit. Conclusions: In this study, we verified that GoCC are being initiated in the ED with Veterans at differing stages in their illness trajectory and that higher proportions of higher risk patients preferred to limit LSTs.

An outlook on biomarkers in cardiogenic shock.

Cardiogenic shock is a severe complication with mortality rates of ∼50% that requires a rapid and complex management to aid and identify the highest and lowest risk patients. To that end, novel cardiogenic shock biomarkers are needed to improve risk stratification and to personalize therapy. Established biomarkers such as BNP, NT-proBNP, ST2, and troponins provide insufficient predictive value in cardiogenic shock. More recent biomarkers, including DPP3, adrenomedullin, angiopoietin 2, and the CS4P score are gaining momentum. DPP3 showed early prediction of refractory status and survival in cardiogenic shock. The CS4P score is based on the levels of liver fatty acid-binding protein (L-FABP), beta-2-microglobulin (B2M), fructose-bisphosphate aldolase B (ALDOB), and SerpinG1 (IC1). These proteins are not cardiac-specific but reflect multiorgan dysfunction, systemic inflammation, and immune activation. The CS4P improved reclassification of 32% of patients compared with the CardShock risk score. A new wave of research focused on novel proteomic and molecular techniques, is providing new candidates that promise to aid clinical decision-making and patient stratification in cardiogenic shock. The CS4P score is emerging as the most robust, yet it requires prospective validation in cardiogenic shock patients managed with circulatory and ventricular assist devices.

Value of Exercise Stress Echocardiography in Children with Hypertrophic Cardiomyopathy

Exercise stress echocardiography (ESE) is a valuable diagnostic and prognostic tool in adults with hypertrophic cardiomyopathy (HCM). Inducible and resting left ventricular outflow tract gradients are important predictors of heart failure. However, there are minimal data on the utility of this modality in children. Retrospective review of all pediatric HCM patients who underwent ESE at Boston Children's Hospital (January 2007-June 2018) was carried out. Patients were assigned to one of three categories based on left ventricular outflow tract gradients: group 1: <30mm Hg at rest and exercise; group 2: <30mm Hg at rest and ≥30mm Hg with exercise; and group 3: ≥ 30mm Hg at rest and exercise. Records were reviewed for earliest occurrence of composite endpoint of any one of the following: cardiac syncope, chest pain, nonsustained and sustained ventricular tachycardia, aborted cardiac arrest, heart failure class≥II, or HCM-related death/transplantation. A total of 91 children (67% males) with median age 12years (6-24years) at first ESE and median left ventricle wall thickness of 20mm formed the cohort. Median follow-up duration was 3years. During ESE, only one child experienced an event and was resuscitated. Of the 91 children, 25 were classified as group 1, 40 as group 2, and 26 as group 3. Twenty-six patients met the composite endpoint, including two heart transplant, one aborted cardiac arrest, and one sudden cardiac death. Group 3 patients had a 5 times higher risk of developing symptoms and/or serious clinical outcome at any age (hazard ratio=5.18; 95% CI, [1.39-19.2]; P=.014). During our short follow-up time, group 2 patients had a higher risk of outcome, but this did not achieve statistical significance (hazard ratio=1.95; 95% CI, [0.5-7.6]; P=.33). In this large series of pediatric patients with HCM, ESE can be performed safely and served as an effective tool to identify the lowest risk patients for cardiac outcome.

Systolic Blood Pressure in Heart Failure With Preserved Ejection Fraction Treated With Sacubitril/Valsartan

BackgroundGuidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data. ObjectivesThis study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan. MethodsUsing 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro−B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects. ResultsAverage age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex. ConclusionsBaseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Predicting risk of cardiovascular events 1 to 3 years post-myocardial infarction using a global registry.

BackgroundRisk prediction tools are lacking for patients with stable disease some years after myocardial infarction (MI).HypothesisA practical long‐term cardiovascular risk index can be developed.MethodsThe long‐Term rIsk, Clinical manaGement and healthcare Resource utilization of stable coronary artery dISease in post‐myocardial infarction patients prospective global registry enrolled patients 1 to 3 years post‐MI (369 centers; 25 countries), all with ≥1 risk factor (age ≥65 years, diabetes mellitus requiring medication, second prior MI, multivessel coronary artery disease, or chronic non‐end‐stage kidney disease [CKD]). Self‐reported health was assessed with EuroQoL‐5 dimensions. Multivariable Poisson regression models were used to determine key predictors of the primary composite outcome (MI, unstable angina with urgent revascularization [UA], stroke, or all‐cause death) over 2 years.ResultsThe primary outcome occurred in 621 (6.9%) of 9027 eligible patients: death 295 (3.3%), MI 195 (2.2%), UA 103 (1.1%), and stroke 58 (0.6%). All events accrued linearly. In a multivariable model, 11 significant predictors of primary outcome (age ≥65 years, diabetes, second prior MI, CKD, history of major bleed, peripheral arterial disease, heart failure, cardiovascular hospitalization (prior 6 months), medical management (index MI), on diuretic, and poor self‐reported health) were identified and combined into a user‐friendly risk index. Compared with lowest‐risk patients, those in the top 16% had a rate ratio of 6.9 for the primary composite, and 18.7 for all‐cause death (overall c‐statistic; 0.686, and 0.768, respectively). External validation was performed using the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events registry (c‐statistic; 0.748, and 0.849, respectively).ConclusionsIn patients >1‐year post‐MI, recurrent cardiovascular events and deaths accrue linearly. A simple risk index can stratify patients, potentially helping to guide management.

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients.

Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n=1,021) and validated in the remainder (n=3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC>35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P<0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index=0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index=0.71) and OS (C-index=0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.