Killip scale reclassification according to lung ultrasound: Killip pLUS.

AIMS: The Killip scale remains a fundamental tool for prognostic assessment in ST-segment elevation myocardial infarction (STEMI) due to its simplicity and predictive value. Lung ultrasound (LUS) has emerged as a valuable adjunct for diagnosing and predicting outcomes in heart failure (HF) and STEMI patients, even those with subclinical congestion. We created a new classification (Killip pLUS), which reclassifies Killip I and II patients into an intermediate category (Killip I pLUS) based on LUS results. This category included Killip I patients and ≥1 positive zone (≥3 B-lines) and Killip II with 0 positive zones. We aimed to evaluate this new classification by comparing it with the Killip scale and a previous LUS-based reclassification scale (LUCK scale). METHODS AND RESULTS: Lung ultrasound was performed within 24 h of admission in a multicentre cohort of 373 patients admitted for STEMI. In-hospital mortality and major adverse cardiovascular events within one year after admission, comprising mortality or readmission for HF, acute coronary syndrome, or stroke, were analysed. When predicting in-hospital mortality, the global comparison of these three classifications was statistically significant: Killip pLUS area under the curve (AUC) 0.90 (95% CI 0.85-0.95) vs. Killip AUC 0.85 (95% CI 0.73-0.96) vs. LUCK 0.83 (95% CI 0.70-0.95), P = 0.024. To predict events during follow-up, the comparison between scales was also significant: Killip pLUS 0.77 (95% CI 0.71-0.85) vs. Killip 0.72 (95% CI 0.65-0.79) vs. LUCK 0.73 (95% CI 0.66-0.81), P = 0.033. CONCLUSION: The Killip pLUS scale provides enhanced risk stratification compared to the Killip and LUCK scales while preserving simplicity.

404-error "Disease not found": Unleashing the translational potential of -omics approaches beyond traditional disease classification in heart failure research.

The emergence of personalized medicine, facilitated by the progress in -omics technologies, has initiated a new era in medical diagnostics and treatment. This review examines the potential of -omics approaches in heart failure, a condition that has not yet fully capitalized on personalized strategies compared to other medical fields like cancer therapy. Here, we argue that integrating multi-omics technology with systems medicine approaches could fundamentally transform heart failure management, moving away from the traditional paradigm of 'one size fits all'. Our review examines how omics can enhance understanding of heart failure's molecular foundations and contribute to a more comprehensive disease classification. We draw attention to the current state of medical practice that only relies on clinical evidence and a number of standard laboratory tests. At the same time, we propose a shift towards a universal approach that uses quantitative data from multi-omics to unravel complex molecular interactions. The discussion centres around the potential of the transition as a means to enhance individual risk assessment and emphasizes management within clinical settings. While the use of omics in cardiovascular research is not recent, many past studies have focused only on a single omics approach. In order to achieve a better understanding of disease mechanisms, we explore more holistic approaches using genomics, transcriptomics, epigenomics, and proteomics. This review concludes with a call to action to adopt multi-omics in clinical trials and practice to pave the way for more personalized disease management and more effective heart failure interventions.

Independent and Added Value of Cardiopulmonary Exercise Testing to New York Heart Association Classification in Patients With Heart Failure.

PURPOSE: The objective of this study was to evaluate the independent and added value of a cardiopulmonary exercise test (CPX) to New York Heart Association (NYHA) functional analysis in patients with heart failure (HF) and ejection fraction (EF) <50%. METHODS: Patients (n = 613) with HF and EF < 50% underwent CPX and were followed for 28 ± 17 mo with respect to primary outcomes (death or heart transplantation). RESULTS: Mean patient age was 56 ± 12 yr, and 64% were male. Most patients were classified as NYHA class II (41%). The composite rate of primary outcomes was 12%; death occurred in 9%, and heart transplant in 4%. Independent predictors of primary outcomes were: EF (HR = 0.95: 95% CI, 0.92-0.98; P = .001) and NYHA (HR = 2.06: 95% CI, 1.54-2.75; P < .0001). When added to the model, peak oxygen uptake (V˙ O2peak ) was an independent predictor (HR = 0.90: 95% CI, 0.84-0.96; P = .001), as was the percentage of predicted V˙ O2peak (HR = 0.03: 95% CI, 0.007-0.147; P < .001), minute ventilation/carbon dioxide production slope (HR = 1.02: 95% CI, 1.01-1.04; P = .012), and CPX score (HR = 1.16: 95% CI, 1.06-1.27; P = .001). CONCLUSIONS: CPX variables were independent predictors of HF prognosis, even when controlled by NYHA functional class. Despite being independent predictors, the value added to NYHA classification was modest and lacked statistical significance.

A machine learning approach to classifying New York Heart Association (NYHA) heart failure.

According to the European Society of Cardiology, globally the number of patients with heart failure nearly doubled from 33.5 million in 1990 to 64.3 million in 2017, and is further projected to increase dramatically in this decade, still remaining a leading cause of morbidity and mortality. One of the most frequently applied heart failure classification systems that physicians use is the New York Heart Association (NYHA) Functional Classification. Each NYHA class describes a patient's symptoms while performing physical activities, delivering a strong indicator of the heart performance. In each case, a NYHA class is individually determined routinely based on the subjective assessment of the treating physician. However, such diagnosis can suffer from bias, eventually affecting a valid assessment. To tackle this issue, we take advantage of the machine learning approach to develop a decision-tree, along with a set of decision rules, which can serve as additional blinded investigator tool to make unbiased assessment. On a dataset containing 434 observations, the supervised learning approach was initially employed to train a Decision Tree model. In the subsequent phase, ensemble learning techniques were utilized to develop both the Voting Classifier and the Random Forest model. The performance of all models was assessed using 10-fold cross-validation with stratification.The Decision Tree, Random Forest, and Voting Classifier models reported accuracies of 76.28%, 96.77%, and 99.54% respectively. The Voting Classifier led in classifying NYHA I and III with 98.7% and 100% accuracy. Both Random Forest and Voting Classifier flawlessly classified NYHA II at 100%. However, for NYHA IV, Random Forest achieved a perfect score, while the Voting Classifier reported 90%. The Decision Tree showed the least effectiveness among all the models tested. In our opinion, the results seem satisfactory in terms of their supporting role in clinical practice. In particular, the use of a machine learning tool could reduce or even eliminate the bias in the physician's assessment. In addition, future research should consider testing other variables in different datasets to gain a better understanding of the significant factors affecting heart failure.

Evaluation of the relationship between end-tidal carbon dioxide level and heart failure classification.

OBJECTIVE: Heart failure is a disease with cardiac dysfunction, and its morbidity and mortality are associated with the degree of dysfunction. The New York Heart Association classifies the heart failure stages based on the severity of symptoms and physical activity. End-tidal carbon dioxide refers to the level of carbon dioxide that a person exhales with each breath. End-tidal carbon dioxide levels can be used in many clinical conditions such as heart failure, asthma, and chronic obstructive pulmonary disease. The aim of the study was to reveal the relationship between end-tidal carbon dioxide levels and the New York Heart Association classification of heart failure stages. METHODS: This study was conducted at Kahramanmaras Sütçü Imam University Faculty of Medicine Adult Emergency Department between 01/03/2019 and 01/09/2019. A total of 80 patients who presented to the emergency department with a history of heart failure or were diagnosed with heart failure during admission were grouped according to the New York Heart Association classification of heart failure stages. The laboratory parameters, ejection fraction values, and end-tidal carbon dioxide levels of the patients were measured and recorded in the study forms. RESULTS: End-tidal carbon dioxide levels and ejection fraction values were found to be significantly lower in the stage 4 group compared to the other groups. Furthermore, pro-B-type natriuretic peptide (BNP) values were found to be significantly higher in stage 4 group compared to the other groups. CONCLUSION: It was concluded that end-tidal carbon dioxide levels could be used together with pro-BNP and ejection fraction values in determining the severity of heart failure.

Rationale and design of the PACIFIC-PRESERVED (PhenomApping, ClassIFication and Innovation for Cardiac dysfunction in patients with heart failure and PRESERVED left ventricular ejection fraction) study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that is poorly defined, reflecting an incomplete understanding of its pathophysiology. AIM: To redefine the phenotypic spectrum of HFpEF. METHODS: The PACIFIC-PRESERVED study is a prospective multicentre cohort study designed to perform multidimensional deep phenotyping of patients diagnosed with HFpEF (left ventricular ejection fraction≥50%), patients with heart failure with reduced ejection fraction (left ventricular ejection fraction≤40%) and subjects without overt heart failure (3:2:1 ratio). The study proposes prospective investigations in patients during a 1-day hospital stay: physical examination; electrocardiogram; performance-based tests; blood samples; cardiac magnetic resonance imaging; transthoracic echocardiography (rest and low-level exercise); myocardial shear wave elastography; chest computed tomography; and non-invasive measurement of arterial stiffness. Dyspnoea, depression, general health and quality of life will be assessed by dedicated questionnaires. A biobank will be established. After the hospital stay, patients are asked to wear a connected garment (with digital sensors) to collect electrocardiography, pulmonary and activity variables in real-life conditions (for up to 14 days). Data will be centralized for machine-learning-based analyses, with the aim of reclassifying HFpEF into more distinct subgroups, improving understanding of the disease mechanisms and identifying new biological pathways and molecular targets. The study will also serve as a platform to enable the development of innovative technologies and strategies for the diagnosis and stratification of patients with HFpEF. CONCLUSIONS: PACIFIC-PRESERVED is a prospective multicentre phenomapping study, using novel analytical techniques, which will provide a unique data resource to better define HFpEF and identify new clinically meaningful subgroups of patients.

Prevalencia, caracterización y pronóstico de pacientes con sospecha de insuficiencia cardíaca en atención primaria de salud en Chile / Characterization and prognosis of patients with suspected heart failure at primary health care institutions in Chile

Introducción: La insuficiencia cardíaca (IC) tiene alta morbilidad y mortalidad. Su diagnóstico temprano en atención primaria de salud (APS) es un reto dada la baja especificidad de sus criterios clínicos y las limitaciones en acceso a técnicas diagnósticas. Objetivo: Analizar la prevalencia de IC, subtipos y pronóstico de pacientes con disnea y/o edema de extremidades inferiores que consultan en APS. Metodología: Se trata de un estudio prospectivo de 340 pacientes en APS, sin diagnóstico previo de IC. Se realizó una evaluación clínica, electrocardiograma, NT-proBNP "point-of-care", ecocardiografía con interpretación telemática por cardiólogos. Utilizando los algoritmos HFA-PEFF y H2FPEF se clasificaron los pacientes como :1) IC con fracción de eyección (FE) reducida (ICFER); 2) IC con FE preservada (ICFEP) y 3) pacientes sin diagnóstico de IC. Se efectuó un análisis de sobrevida de los diferentes grupos. Resultados: La prevalencia de ICFER fue 8%, ICFEP por HFA-PEFF 42% y por H2FPEF 8%. Los algoritmos sugieren efectuar un estudio complementario en el 47% con HFA-PEFF y 76% con H2FPEF (p<0.05). La sobrevida global a 36 meses fue 90±2% y cardiovascular 95±1%. Usando HFA-PEFF, los pacientes con IC tuvieron menor sobrevida que aquellos sin IC (HR 2.3, IC95% 1.14.9; p=0.029). No hubo diferencias de mortalidad con H2FPEF. Conclusiones: En pacientes de APS que consultan por disnea y/o edema de extremidades inferiores sometidos a evaluación con NT-proBNP y ecocardiografía, se observó una prevalencia de IC de hasta 50%, 8% de ICFER y 42% de ICFEP. La caracterización de IC utilizando HFA-PEFF está asociada al pronóstico vital.

Background: Heart failure (HF) is a condition associated with high morbidity and mortality. Its early diagnosis in primary health care (PHC) represents a substantial challenge, considering its non-specific clinical manifestations and the limitations on timely access to diagnostic techniques. Objective: To evaluate the prevalence of HF, characterize subtypes and determine the prognosis of patients consulting in PHC for dyspnea Edema of the lower extremities. Methods: Prospective study in 340 patients who consulted in PHC, without previous diagnosis of HF. Clinical evaluation, electrocardiogram, NT-proBNP point-ofcare and echocardiography with telematic interpretation by cardiologists were performed. Using the HFA-PEFF and H2FPEF algorithms patients were classified as: 1) HF with reduced ejection fraction (HFREF); 2) HF with preserved ejection fraction (HFPEF) and 3) No HF. Actuarial survival analyses were performed. Results: We observed a prevalence of HFREF of 8%, high probability of HFPEF by HFA-PEFF in 42% and by H2FPEF in 8%. Intermediate probability of HFPEF, requiring complementary study, was observed in 47% of patients with HFA-PEFF and 76% of patients with H2FPEF (p<0.05). Overall survival at 36 months was 90±2% and cardiovascular survival at 36 months was 95±1%. Using HFA-PEFF, patients with HF presented lower overall survival compared to patients with no HF (HR 2.3, 95%CI 1.1-4.9; p=0.029). We did not observe mortality differences with H2FPEF. Conclusions: In patients consulting for dyspnea and/or lower extremity edema at PHC and undergoing evaluation with NT-proBNP and echocardiography, we observed a HF prevalence of 50%. HF classification through HFA-PEFF was associated with lower survival rates.

Characteristics and outcomes for patients with heart failure diagnosed according to the universal definition and classification of heart failure. Data from a single-center registry.

BACKGROUND: There are no data on the characteristics and outcomes for patients with heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction diagnosed according to the universal definition and classification of HF. AIMS: We used the universal HF definition to compare baseline characteristics, hospital readmission and mortality rates in individuals with HFrEF, HFmrEF, and HFpEF diagnosed retrospectively. RESULTS: The study was designed as a single-center retrospective analysis of all consecutive 40732 hospital admissions between 2013 and 2021 in a tertiary department of cardiology. All patients with HF, defined according to the universal definition and classification of HF, were identified. The study included 8471 patients with a mean age of 65.1 (12.8) years, of whom 2823 (33.3%) were females. Most individuals had a prior diagnosis of HF (76.3%) and elevated N-terminal pro-B-type natriuretic peptide levels (99.0%) with a median of 1548 (629-3786) pg/ml. Mean ejection fraction (EF) was 36.2 (14.9)%. The median follow-up was 39.1 (18.1-70.5) months. The most frequent type of HF was HFrEF (n = 4947; 58.4%), followed by HFpEF (n = 1138; 28.2%) and HFmrEF (n = 2386; 13.4%). Urgent HF readmissions and all-cause deaths were highest in HFrEF (40.8% and 42.7%), followed by HFmrEF (25.4% and 31.5%) and HFpEF (15.2% and 23.8%, respectively). CONCLUSIONS: The highest rates of urgent HF readmissions and all-cause mortality were observed in patients with HFrEF, followed by HFmrEF and HFpEF. In all HF groups, the all-cause mortality rate was higher than the rates of urgent HF readmission.

Insuficiencia cardíaca secundaria a cardiopatías congénitas y adquiridas en edades pediátricas / Heart Failure Secondary to Congenital and Acquired Heart Disease in the Pediatric Age Group

Introducción: Las cardiopatías congénitas son causa frecuente de insuficiencia cardíaca mientras las cardiopatías adquiridas resultan menos frecuentes. La expresión clínica difiere en gran manera de la población adulta y representa la emergencia cardiovascular más frecuente en pediatría. El diagnóstico es completamente clínico, y el tratamiento está encaminado a corregir la causa que la origina. Objetivo: Actualizar conceptos, fisiopatología, manifestaciones clínicas, y tratamiento de la insuficiencia cardíaca en pediatría. Métodos: Se revisaron las bases de datos Medline, PubMed, SciELO y plataforma Springerlink, disponibles desde Infomed; desde el año 2000 hasta 2020, en idioma español e inglés. Análisis y síntesis de la información: La insuficiencia cardíaca es un síndrome clínico resultado de disfunción ventricular, sobrecarga de presión o volumen, independiente o en combinación, que conlleva a signos y síntomas característicos. La identificación de su causa, el diagnóstico precoz y el tratamiento oportuno mejoraran el pronóstico de los pacientes aquejados. Conclusiones: La insuficiencia cardíaca en edad pediátrica representa una compleja afección de causas multifactoriales. El diagnóstico puede hacerse con el método clínico, complementándose con los diferentes exámenes. El tratamiento médico farmacológico o no, se encamina a tratar la causa, además de nuevas terapias en desarrollo prometedoras en el futuro(AU)

Introduction: Congenital heart disease is a frequent cause of heart failure while acquired heart disease is less frequent. The clinical expression differs greatly from the adult population and represents the most frequent cardiovascular emergency in pediatrics. Diagnosis is completely clinical and treatment is aimed at correcting the cause. Objective: To update concepts, pathophysiology, clinical manifestations and treatment of heart failure in pediatrics. Methods: The databases Medline, PubMed, SciELO and Springerlink platform, available from Infomed, were reviewed from 2000 to 2020, in Spanish and English. Analysis and synthesis of the information: Heart failure is a clinical syndrome resulting from ventricular dysfunction, pressure or volume overload, independently or in combination, leading to characteristic signs and symptoms. Identification of its cause, early diagnosis and timely treatment improve the prognosis of afflicted patients. Conclusions: Heart failure in pediatric age represented a complex condition with multifactorial causes. The diagnosis can be made with the clinical method, complemented with different examinations. Pharmacological or non-pharmacological medical treatment is aimed at treating the cause, in addition to promising new therapies under development in the future(AU)

Malnutrition outweighs the effect of the obesity paradox.

BACKGROUND: High body mass index (BMI) is paradoxically associated with better outcome in patients with heart failure (HF). The effects of malnutrition on this phenomenon across the whole spectrum of HF have not yet been studied. METHODS: In this observational study, patients were classified by guideline diagnostic criteria to one of three heart failure subtypes: reduced (HFrEF), mildy reduced (HFmrEF), and preserved ejection fraction (HFpEF). Data were retrieved from the Viennese-community healthcare provider network between 2010 and 2020. The relationship between BMI, nutritional status reflected by the prognostic nutritional index (PNI), and survival was assessed. Patients were classified by the presence (PNI < 45) or absence (PNI ≥ 45) of malnutrition. RESULTS: Of the 11 995 patients enrolled, 6916 (58%) were classified as HFpEF, 2809 (23%) HFmrEF, and 2270 HFrEF (19%). Median age was 70 years (IQR 61-77), and 67% of patients were men. During a median follow-up time of 44 months (IQR 19-76), 3718 (31%) of patients died. After adjustment for potential confounders, BMI per IQR increase was independently associated with better survival (adj. hazard ratio [HR]: 0.91 [CI 0.86-0.97], P = 0.005), this association remained significant after additional adjustment for HF type (adj. HR: 0.92 [CI 0.86-0.98], P = 0.011). PNI was available in 10 005 patients and lowest in HFrEF patients. PNI was independently associated with improved survival (adj. HR: 0.96 [CI 0.95-0.97], P < 0.001); additional adjustment for HF type yielded similar results (adj. HR: 0.96 [CI 0.96-0.97], P < 0.001). Although obese patients experienced a 30% risk reduction, malnutrition at least doubled the risk for death with 1.8- to 2.5-fold higher hazards for patients with poor nutritional status compared with normal weight well-nourished patients. CONCLUSIONS: The obesity paradox seems to be an inherent characteristic of HF regardless of phenotype and nutritional status. Yet malnutrition significantly changes trajectory of outcome with regard to BMI alone: obese patients with malnutrition have a considerably worse outcome compared with their well-nourished counterparts, outweighing protective effects of high BMI alone. In this context, routine recommendation towards weight loss in patients with obesity and HF should generally be made with caution and focus should be shifted on nutritional status.

Phenomapping a Novel Classification System for Patients With Destination Therapy Left Ventricular Assist Devices.

Patients with continuous flow destination therapy (DT) left ventricular assist devices (LVAD) comprise a heterogeneous population. We hypothesized that phenotypic clustering of individuals with DT LVADs by their implantation characteristics will be associated with different long-term risk profiles. We analyzed 5,999 patients with continuous flow DT LVADs in Interagency Registry for Mechanically Assisted Circulatory Support using 18 continuous variable baseline characteristics. We Z-transformed the variables and applied a Gaussian finite mixture model to perform unsupervised clustering resulting in identification of 4 phenogroups. Survival analyses considered the competing risk for cumulative incidence of transplant or the composite end point of death or heart transplant where appropriate. Phenogroup 1 (n = 1,163, 19%) was older (71 years) and primarily white (81%). Phenogroups 2 (n = 648, 11%) and 3 (n = 3,671, 61%) were of intermediate age (70 and 62 years), weight (85 and 87 kg), and ventricular size. Phenogroup 4 (n = 517, 9%) was younger (40 years), heavier (108 kg), and more racially diverse. The cumulative incidence of death, heart transplant, bleeding, LVAD malfunction, and LVAD thrombosis differed among phenogroups. The highest incidence of death and the lowest rate of heart transplant was seen in phenogroup 1 (p <0.001). For adverse outcomes, phenogroup 4 had the lowest incidence of bleeding, whereas LVAD device thrombosis and malfunction were lowest in phenogroup 1 (p <0.001 for all). Finally, the incidence of stroke, infection, and renal dysfunction were not statistically different. In conclusion, the present unsupervised machine learning analysis identified 4 phenogroups with different rates of adverse outcomes and these findings underscore the influence of phenotypic heterogeneity on post-LVAD implantation outcomes.

Heart failure clinical care analysis uncovers risk reduction opportunities for preserved ejection fraction subtype.

Heart failure (HF) has no cure and, for HF with preserved ejection fraction (HFpEF), no life-extending treatments. Defining the clinical epidemiology of HF could facilitate earlier identification of high-risk individuals. We define the clinical epidemiology of HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]), identified among 2.7 million individuals receiving routine clinical care. Differences in patterns and rates of accumulation of comorbidities, frequency of hospitalization, use of specialty care, were defined for each HF subtype. Among 28,156 HF cases, 8322 (30%) were HFpEF and 11,677 (42%) were HFrEF. HFpEF was the more prevalent subtype among older women. 177 Phenotypes differentially associated with HFpEF versus HFrEF. HFrEF was more frequently associated with diagnoses related to ischemic cardiac injury while HFpEF was associated more with non-cardiac comorbidities and HF symptoms. These comorbidity patterns were frequently present 3 years prior to a HFpEF diagnosis. HF subtypes demonstrated distinct patterns of clinical co-morbidities and disease progression. For HFpEF, these comorbidities were often non-cardiac and manifested prior to the onset of a HF diagnosis. Recognizing these comorbidity patterns, along the care continuum, may present a window of opportunity to identify individuals at risk for developing incident HFpEF.

Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial.

BACKGROUND: Previous studies have suggested that haemodynamic-guided management using an implantable pulmonary artery pressure monitor reduces heart failure hospitalisations in patients with moderately symptomatic (New York Heart Association [NYHA] functional class III) chronic heart failure and a hospitalisation in the past year, irrespective of ejection fraction. It is unclear if these benefits extend to patients with mild (NYHA functional class II) or severe (NYHA functional class IV) symptoms of heart failure or to patients with elevated natriuretic peptides without a recent heart failure hospitalisation. This trial was designed to evaluate whether haemodynamic-guided management using remote pulmonary artery pressure monitoring could reduce heart failure events and mortality in patients with heart failure across the spectrum of symptom severity (NYHA funational class II-IV), including those with elevated natriuretic peptides but without a recent heart failure hospitalisation. METHODS: The randomised arm of the haemodynamic-GUIDEed management of Heart Failure (GUIDE-HF) trial was a multicentre, single-blind study at 118 centres in the USA and Canada. Following successful implantation of a pulmonary artery pressure monitor, patients with all ejection fractions, NYHA functional class II-IV chronic heart failure, and either a recent heart failure hospitalisation or elevated natriuretic peptides (based on a-priori thresholds) were randomly assigned (1:1) to either haemodynamic-guided heart failure management based on pulmonary artery pressure or a usual care control group. Patients were masked to their study group assignment. Investigators were aware of treatment assignment but did not have access to pulmonary artery pressure data for control patients. The primary endpoint was a composite of all-cause mortality and total heart failure events (heart failure hospitalisations and urgent heart failure hospital visits) at 12 months assessed in all randomly assigned patients. Safety was assessed in all patients. A pre-COVID-19 impact analysis for the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT03387813. FINDINGS: Between March 15, 2018, and Dec 20, 2019, 1022 patients were enrolled, with 1000 patients implanted successfully, and follow-up was completed on Jan 8, 2021. There were 253 primary endpoint events (0·563 per patient-year) among 497 patients in the haemodynamic-guided management group (treatment group) and 289 (0·640 per patient-year) in 503 patients in the control group (hazard ratio [HR] 0·88, 95% CI 0·74-1·05; p=0·16). A prespecified COVID-19 sensitivity analysis using a time-dependent variable to compare events before COVID-19 and during the pandemic suggested a treatment interaction (pinteraction=0·11) due to a change in the primary endpoint event rate during the pandemic phase of the trial, warranting a pre-COVID-19 impact analysis. In the pre-COVID-19 impact analysis, there were 177 primary events (0·553 per patient-year) in the intervention group and 224 events (0·682 per patient-year) in the control group (HR 0·81, 95% CI 0·66-1·00; p=0·049). This difference in primary events almost disappeared during COVID-19, with a 21% decrease in the control group (0·536 per patient-year) relative to pre-COVID-19, virtually no change in the treatment group (0·597 per patient-year), and no difference between groups (HR 1·11, 95% CI 0·80-1·55; p=0·53). The cumulative incidence of heart failure events was not reduced by haemodynamic-guided management (0·85, 0·70-1·03; p=0·096) in the overall study analysis but was significantly decreased in the pre-COVID-19 impact analysis (0·76, 0·61-0·95; p=0·014). 1014 (99%) of 1022 patients had freedom from device or system-related complications. INTERPRETATION: Haemodynamic-guided management of heart failure did not result in a lower composite endpoint rate of mortality and total heart failure events compared with the control group in the overall study analysis. However, a pre-COVID-19 impact analysis indicated a possible benefit of haemodynamic-guided management on the primary outcome in the pre-COVID-19 period, primarily driven by a lower heart failure hospitalisation rate compared with the control group. FUNDING: Abbott.

Association Between Diagnosis Code Expansion and Changes in 30-Day Risk-Adjusted Outcomes for Cardiovascular Diseases.

BACKGROUND In January 2011, Centers for Medicare and Medicaid Services expanded the number of inpatient diagnosis codes from 9 to 25, which may influence comorbidity counts and risk-adjusted outcome rates for studies spanning January 2011. This study examines the association between (1) limiting versus not limiting diagnosis codes after 2011, (2) using inpatient-only versus inpatient and outpatient data, and (3) using logistic regression versus the Centers for Medicare and Medicaid Services risk-standardized methodology and changes in risk-adjusted outcomes. METHODS AND RESULTS Using 100% Medicare inpatient and outpatient files between January 2009 and December 2013, we created 2 cohorts of fee-for-service beneficiaries aged ≥65 years. The acute myocardial infarction cohort and the heart failure cohort had 578 728 and 1 595 069 hospitalizations, respectively. We calculate comorbidities using (1) inpatient-only limited diagnoses, (2) inpatient-only unlimited diagnoses, (3) inpatient and outpatient limited diagnoses, and (4) inpatient and outpatient unlimited diagnoses. Across both cohorts, International Classification of Diseases, Ninth Revision (ICD-9) diagnoses and hierarchical condition categories increased after 2011. When outpatient data were included, there were no significant differences in risk-adjusted readmission rates using logistic regression or the Centers for Medicare and Medicaid Services risk standardization. A difference-in-differences analysis of risk-adjusted readmission trends before versus after 2011 found that no significant differences between limited and unlimited models for either cohort. CONCLUSIONS For studies that span 2011, researchers should consider limiting the number of inpatient diagnosis codes to 9 and/or including outpatient data to minimize the impact of the code expansion on comorbidity counts. However, the 2011 code expansion does not appear to significantly affect risk-adjusted readmission rate estimates using either logistic or risk-standardization models or when using or excluding outpatient data.

Classification of Heart Failure According to Ejection Fraction: JACC Review Topic of the Week.

The recent U.S. Food and Drug Administration expanded indication for sacubitril/valsartan introduces a new potential taxonomy for heart failure, with no reference to "preserved" ejection fraction but referring to "below normal" ejection fraction as those most likely to benefit. This review summarizes the evolution of nomenclature in heart failure and examines evidence showing that patients with ejection fraction in the "mid range" may benefit from neurohormonal blockade similar to those with more severely reduced (<40%) ejection fraction. Furthermore, prominent sex differences have been observed wherein the benefit of neurohormonal blockade appears to extend to a higher ejection fraction range in women compared to men. Based on emerging evidence, revised nomenclature is proposed defining heart failure with "reduced" (<40%), "mildly reduced," and "normal" (≥55% in men, ≥60% in women) ejection fraction. Such nomenclature signals consideration of potentially beneficial therapies in the largest group of patients with reduced or mildly reduced ejection fraction.

SGLT2 inhibitors: What role do they play in heart failure with reduced ejection fraction?

ABSTRACT: Sodium-glucose cotransporter-2 (SGLT2) inhibitors can decrease risk for heart failure in patients with type 2 diabetes and can decrease risk of major cardiovascular events in patients with heart failure (HF) and diabetes. Specific SGLT2 inhibitors can also decrease major cardiovascular events in patients with HF only.

Epidemiology of Heart Failure: A Contemporary Perspective.

Designated as an emerging epidemic in 1997, heart failure (HF) remains a major clinical and public health problem. This review focuses on the most recent studies identified by searching the Medline database for publications with the subject headings HF, epidemiology, prevalence, incidence, trends between 2010 and present. Publications relevant to epidemiology and population sciences were retained for discussion in this review after reviewing abstracts for relevance to these topics. Studies of the epidemiology of HF over the past decade have improved our understanding of the HF syndrome and of its complexity. Data suggest that the incidence of HF is mostly flat or declining but that the burden of mortality and hospitalization remains mostly unabated despite significant ongoing efforts to treat and manage HF. The evolution of the case mix of HF continues to be characterized by an increasing proportion of cases with preserved ejection fraction, for which established effective treatments are mostly lacking. Major disparities in the occurrence, presentation, and outcome of HF persist particularly among younger Black men and women. These disturbing trends reflect the complexity of the HF syndrome, the insufficient mechanistic understanding of its various manifestations and presentations and the challenges of its management as a chronic disease, often integrated within a context of aging and multimorbidity. Emerging risk factors including omics science offer the promise of discovering new mechanistic pathways that lead to HF. Holistic management approaches must recognize HF as a syndemic and foster the implementation of multidisciplinary approaches to address major contributors to the persisting burden of HF including multimorbidity, aging, and social determinants of health.

Comparison of New York Heart Association Class and Patient-Reported Outcomes for Heart Failure With Reduced Ejection Fraction.

Importance: It is unclear how New York Heart Association (NYHA) functional class compares with patient-reported outcomes among patients with heart failure (HF) in contemporary US clinical practice. Objective: To characterize longitudinal changes and concordance between NYHA class and the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS), and their associations with clinical outcomes. Design, Setting, and Participants: This cohort study included 2872 US outpatients with chronic HF with reduced ejection fraction across 145 practices enrolled in the CHAMP-HF registry between December 2015 and October 2017. All patients had complete NYHA class and KCCQ-OS data at baseline and 12 months. Longitudinal changes and correlations between the 2 measure were examined. Multivariable models landmarked at 12 months evaluated associations between improvement in NYHA and KCCQ-OS from baseline to 12 months with clinical outcomes occurring from months 12 through 24. Statistical analyses were performed from March to August 2020. Exposure: Change in health status, as defined by 12-month change in NYHA class or KCCQ-OS. Main Outcomes and Measures: All-cause mortality, HF hospitalization, and mortality or HF hospitalization. Results: In total, 2872 patients were included in this analysis (median [interquartile range] age, 68 [59-75] years; 872 [30.4%] were women; and 2156 [75.1%] were of White race). At baseline, 312 patients (10.9%) were NYHA class I, 1710 patients (59.5%) were class II, 804 patients (28.0%) were class III, and 46 patients (1.6%) were class IV. For KCCQ-OS, 1131 patients (39.4%) scored 75 to 100 (best health status), 967 patients (33.7%) scored 50 to 74, 612 patients (21.3%) scored 25 to 49, and 162 patients (5.6%) scored 0 to 24 (worst health status). At 12 months, 1002 patients (34.9%) had a change in NYHA class (599 [20.9%] with improvement; 403 [14.0%] with worsening) and 2158 patients (75.1%) had a change of 5 or more points in KCCQ-OS (1388 [48.3%] with improvement; 770 [26.8%] with worsening). The most common trajectory for NYHA class was no change (1870 [65.1%]), and the most common trajectory for KCCQ-OS was an improvement of at least 10 points (1047 [36.5%]). After adjustment, improvement in NYHA class was not associated with subsequent clinical outcomes, whereas an improvement of 5 or more points in KCCQ-OS was independently associated with decreased mortality (hazard ratio, 0.59; 95% CI, 0.44-0.80; P < .001) and mortality or HF hospitalization (hazard ratio, 0.73; 95% CI, 0.59-0.89; P = .002). Conclusions and Relevance: Findings of this cohort study suggest that, in contemporary US clinical practice, compared with NYHA class, KCCQ-OS is more sensitive to clinically meaningful changes in health status over time. Changes in KCCQ-OS may have more prognostic value than changes in NYHA class.