RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites. METHODS: Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model. RESULTS: In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline (p < 0.001), betaine (p < 0.001), carnitine (p = 0.007), TMA (p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide (p < 0.001), indole-lactic acid (p = 0.038), 5-hydroxyindoleacetic acid (p < 0.0001) and 4-hydroxyphenyllactic acid (p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC (p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis (p = 0.42). CONCLUSIONS: Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications.

RESUMO

BACKGROUND: The region of adipose deposition is an important determinant in the outcomes of patients with heart failure (HF). However, the impact of regional adiposity on HF patients undergoing cardiac resynchronization therapy (CRT) remains unclear. METHODS: A retrospective cohort analysis was conducted on 95 patients from a single-center study, assessing post-CRT outcomes. Multi-slice body composition measurements of chest computed tomography before CRT placement were used for adipose quantification. Patients were stratified based on subcutaneous adiposity, intramuscular adiposity, and hepatic steatosis. RESULTS/CONCLUSION: Subcutaneous adiposity correlated with higher CRT response rates (44.4 % in subcutaneous adiposity vs 16.7 % in subcutaneous adipopenia, p = 0.009), while intramuscular adiposity was associated with increased pre-frailty (adjusted OR 14.17, 95 % CI 2.24-89.57, p = 0.005). The higher response to CRT in patients with subcutaneous adiposity may be secondary to preferred subcutaneous over ectopic adipose fat deposition, which is potentially protective against cardiomyocyte dysfunction. Thus, intramuscular adiposity could potentially serve as a prognostic tool for frailty in HF patients.

RESUMO

AIMS: To evaluate whether early-combination diuretic therapy guided by serial post-diuretic urine sodium concentration (UNa+) assessments in acute heart failure (AHF) facilitates safe and effective decongestion. METHODS: The Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment (DECONGEST) study is a pragmatic, 2-center, randomized, parallel-arm, open-label study aiming to enroll 104 patients with AHF and clinically evident fluid overload requiring treatment with intravenous loop diuretics. Patients are randomized to receive standard of care or a bundled approach comprising: (1) systematic post-diuretic UNa+ assessments until successful decongestion, defined as no remaining clinical signs of fluid overload with a post-diuretic UNa+ ≤ 80 mmol/L; (2) thrice-daily intravenous loop diuretic bolus therapy, with dosing according to estimated glomerular filtration rate; (3) upfront use of intravenous acetazolamide (500 mg once daily [OD]); and (4) full nephron blockade with high-dose oral chlorthalidone (100 mg OD) and intravenous canreonate (200 mg OD) for diuretic resistance, defined as persisting signs of fluid overload with a post-diuretic UNa+ ≤ 80 mmol/L. The primary endpoint of the DECONGEST study is a hierarchical composite of (1) survival at 30 days; (2) days alive and out of hospital or care facility up to 30 days; and (3) greater relative decrease in natriuretic peptide levels from baseline to day 30. CONCLUSION: The DECONGEST study aims to determine whether an intensive diuretic regimen focused on early combination therapy, guided by serial post-diuretic UNa+ assessments, safely enhances decongestion, warranting further evaluation in a larger trial powered for clinical events.

RESUMO

PURPOSE OF REVIEW: To review the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trends in cardiometabolic interventions. RECENT FINDINGS: Heart failure with preserved ejection fraction makes up approximately half of overall heart failure and is associated with significant morbidity, mortality, and overall burden on the healthcare system. It is a complex, heterogenous syndrome and clinical trials, to this point, have not revealed quite as many effective treatment options when compared to heart failure with reduced ejection fraction. Nevertheless, there is an expanding amount of data insight into the pathogenesis of this disease and the potential for newer therapies and management strategies. Heart failure with preserved ejection fraction pathology has been found to be linked to abnormal energetics, myocyte hypertrophy, cell signaling, inflammation, ischemia, and fibrosis. These mechanisms also intricately overlap with the significant comorbidities often associated with heart failure with preserved ejection fraction including, but not limited to, atrial fibrillation, chronic kidney disease, hypertension, obesity and coronary artery disease. Treatment of this disease, therefore, should focus on the management and strict regulation of these comorbidities by pharmacologic and nonpharmacologic means. In this review, a clinical update is provided reviewing the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trend in cardiometabolic interventions.

Assuntos

Insuficiência Cardíaca , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/epidemiologia , Volume Sistólico/fisiologia

RESUMO

AIMS: Pathophysiology and prognostic implications of right ventricle (RV) dysfunction in heart failure are complex and incompletely elucidated. Cardiac magnetic resonance imaging (CMR) is the reference standard for RV quantification, but its clinical implications in non-ischaemic cardiomyopathy (NICM), in the context of myocardial fibrosis and functional mitral regurgitation are not well defined. We evaluated predictors, prognostic impact, and thresholds for defining significant RV dysfunction in NICM. METHODS AND RESULTS: NICM patients (n = 624) undergoing CMR assessment during 2002-2017 were retrospectively studied. CMR's quantification of right ventricular ejection fraction (RVEF) was evaluated against the primary outcome of all-cause mortality, heart transplant, and/or left ventricular assist device implantation in threshold and multivariable analyses. Mean RVEF was 43 ± 13%, and factors associated with reduced RVEF were male sex, New York Heart Association (NYHA) class III-IV, right bundle branch block, lower left ventricular ejection fraction, higher mitral regurgitant fraction (MR-RF) and right ventricle size in NICM. RVEF per 5% increase was independently associated with the primary endpoint hazards ratio (95% confidence interval) 0.80 (0.73-0.88), P < 0.001. RVEF ≤40% was the optimal threshold associated with worse prognosis, regardless of late gadolinium enhancement (LGE) or MR-RF quantification. On the other hand, higher LGE was associated with primary endpoint in patients with RVEF ≤40% only, while risk associated with MR-RF was significant dampened after adjusting for RVEF. CONCLUSION: RVEF provides powerful risk stratification, with RVEF ≤40% defining significant RV dysfunction associated with adverse outcomes in NICM. The integration of quantitative CMR measurements for RVEF, LGE, and MR-RF provides comprehensive NICM risk prognostication.

RESUMO

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

RESUMO

BACKGROUND: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. METHODS: Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. RESULTS: Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] µmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. CONCLUSIONS: Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Assuntos

Plaquetas , Eritritol , Glucose , Voluntários Saudáveis , Agregação Plaquetária , Trombose , Humanos , Eritritol/sangue , Eritritol/administração & dosagem , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Masculino , Trombose/sangue , Trombose/induzido quimicamente , Trombose/prevenção & controle , Estudos Prospectivos , Agregação Plaquetária/efeitos dos fármacos , Feminino , Adulto , Adoçantes não Calóricos/administração & dosagem , Adoçantes não Calóricos/efeitos adversos , Adulto Jovem , Fator Plaquetário 4/sangue , Espectrometria de Massas em Tandem , Pessoa de Meia-Idade , Serotonina/sangue , Edulcorantes/administração & dosagem , Testes de Função Plaquetária

RESUMO

Obesity is a common comorbidity among patients with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), with the strongest pathophysiologic link of obesity being seen for HFpEF. Lifestyle measures are the cornerstone of weight loss management, but sustainability is a challenge, and there are limited efficacy data in the heart failure (HF) population. Bariatric surgery has moderate efficacy and safety data for patients with preoperative HF or left ventricular dysfunction and has been associated with reductions in HF hospitalizations and medium-term mortality. Antiobesity medications historically carried concerns for cardiovascular adverse effects, but the safety and weight loss efficacy seen in general population trials of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide/GLP-1 agonists are highly encouraging. Although there are safety concerns regarding GLP-1 agonists in advanced HFrEF, trials of the GLP-1 agonist semaglutide for treatment of obesity have confirmed safety and efficacy in patients with HFpEF.

Assuntos

Cirurgia Bariátrica , Insuficiência Cardíaca , Obesidade , Redução de Peso , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Obesidade/complicações , Obesidade/terapia , Volume Sistólico/fisiologia , Fármacos Antiobesidade/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico

RESUMO

OBJECTIVE: To determine the pathophysiologic and prognostic meaning of patient self-reported sodium intake in heart failure (HF) with preserved ejection fraction (HFpEF). METHODS: This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial of patients enrolled in the Americas. Tertiles of baseline self-reported sodium intake were used to assess the relationship between self-reported sodium intake and clinical presentation/outcome and interactions with treatment effect of spironolactone. RESULTS: Self-reported sodium intake of 1748 patients with HFpEF included in TOPCAT were divided according to tertiles of sodium intake (47% low, 35% moderate, and 18% high sodium intake). After covariate adjustment, lower self-reported sodium intake was associated with higher risk of HF hospital admission (P=.009). Patients with lower sodium intake had higher E-wave velocity, left ventricular end diastolic volume, and estimated plasma volume (P<.001). Lower sodium intake was associated with a larger treatment effect of spironolactone on HF hospitalizations (hazard ratio, 0.69; 95% CI, 0.53 to 0.91) vs the highest tertile (hazard ratio, 1.37; 95% CI, 0.79 to 2.38; interaction P=.030). In addition, linear mixed models indicated larger reductions in blood pressure, dyspnea, and edema (all interaction P<.001) in patients with lower sodium intake receiving spironolactone. CONCLUSION: Low self-reported sodium level in HFpEF is associated with higher risk of HF hospital admissions and may indicate a sodium-vulnerable state; patients should not be falsely reassured that they are in a lower risk category despite greater adherence to medical recommendations.

RESUMO

BACKGROUND: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). METHODS: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. RESULTS: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. CONCLUSIONS: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF. REGISTRATION: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.

Assuntos

Betaína , Carnitina , Colina , Microbioma Gastrointestinal , Insuficiência Cardíaca , Metilaminas , Humanos , Metilaminas/sangue , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/sangue , Microbioma Gastrointestinal/fisiologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Incidência , Colina/sangue , Carnitina/análogos & derivados , Carnitina/sangue , Betaína/sangue , Betaína/análogos & derivados , Estados Unidos/epidemiologia , Fatores de Risco , Biomarcadores/sangue , Idoso de 80 Anos ou mais

RESUMO

The beneficial impacts of metabolic surgery (MS) on patients with heart failure (HF) are incompletely characterized. We aimed to describe the cardiac and metabolic effects of MS in patients with HF and hypothesized that patients with HF would experience both improved metabolic and HF profiles using glycemic control and diuretic dependency as surrogate markers. In this single-center, university-affiliated academic study in the United States, a review of 2,342 hospital records of patients who underwent MS (2017 to 2023) identified 63 patients with a medical history of HF. Preoperative characteristics, 30-day outcomes, and up to 2-year biometric and metabolic outcomes, medication usage, and emergency department utilization were collected. At 24 months, mean body mass index change was -16 kg/m2 (p <0.001) that corresponded to a mean percentage total body weight loss of 29% (p <0.001). Weight loss was accompanied by significant reductions in hemoglobin A1c (p <0.001) and a 65% decrease in diuretic use at 24 months after surgery (p <0.001). Similarly, emergency visits for cardiac conditions (p = 0.06) and intravenous diuresis (p = 0.07) trended favorably at 1 year after surgery compared with 1 year before surgery but were not statistically significant. In conclusion, in patients with HF who were carefully selected, MS appears to provide significant reduction in oral diuretic dependency, and metabolic improvements with trends toward lower rates of emergency department utilization.

Assuntos

Diuréticos , Insuficiência Cardíaca , Humanos , Feminino , Masculino , Diuréticos/uso terapêutico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Redução de Peso , Hemoglobinas Glicadas/metabolismo , Resultado do Tratamento , Índice de Massa Corporal , Serviço Hospitalar de Emergência/estatística & dados numéricos

RESUMO

BACKGROUND: Skeletal muscle mass (SMM) plays a crucial role in risk assessment in transcatheter aortic valve replacement (TAVR) candidates, yet it remains underutilized. Traditional methods focus on weakness or performance but omit SMM. This study compared traditional and novel markers of sarcopenia and frailty in terms of their ability to predict adverse outcomes post-TAVR. METHODS: Three risk models were evaluated for the composite outcome of perioperative complications, 1-year rehospitalization, or 1-year mortality: (1) sarcopenia by combining low muscle mass (LMM) and weakness/performance assessed by hand grip strength or gait speed; (2) frailty by an Adapted Green score; and (3) frailty by the Green-SMI score incorporating LMM by multilevel opportunistic pre-TAVR thoracic CT segmentation. RESULTS: In this study we included 184 eligible patients from January to December of 2018, (96.7%) of which were balloon expandable valves. The three risk models identified 22.8% patients as sarcopenic, 63.6% as frail by the Adapted Green score, and 53.8% as frail by the Green-SMI score. There were higher rates of the composite outcome in patients with sarcopenia (54.8%) and frailty (41.9% with the Adapted Green and 50.5% with the Green-SMI score) compared to their nonsarcopenic (30.3%) and nonfrail counterparts (25.4% with the Adapted Green and 18.8% with the Green-SMI score). Sarcopenia and frailty by Green-SMI, but not by the Adapted Green, were associated with higher risks of the composite outcome on multivariable adjustment (HR 2.2 [95% CI: 1.25-4.02], P = .007 and HR 3.4 [95% CI: 1.75-6.65], P < .001, respectively). CONCLUSIONS: The integration of preoperative CT-based SMM to a frailty score significantly improves the prediction of adverse outcomes in patients undergoing TAVR.

Assuntos

Estenose da Valva Aórtica , Fragilidade , Sarcopenia , Substituição da Valva Aórtica Transcateter , Humanos , Sarcopenia/epidemiologia , Sarcopenia/complicações , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Masculino , Feminino , Fragilidade/complicações , Fragilidade/epidemiologia , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Idoso de 80 Anos ou mais , Medição de Risco/métodos , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Força da Mão , Velocidade de Caminhada , Fatores de Risco , Músculo Esquelético

RESUMO

Chronic kidney disease (CKD) and heart failure are often co-existing conditions due to a shared pathophysiological process involving neurohormonal activation and hemodynamic maladaptation. A wide range of pharmaceutical and interventional tools are available to patients with CKD, consisting of traditional ones with decades of experience and newer emerging therapies that are rapidly reshaping the landscape of medical care for this population. Management of patients with heart failure and CKD requires a stepwise approach based on renal function and the clinical phenotype of heart failure. This is often challenging due to altered drug pharmacokinetics interactions with various degrees of kidney function and frequent adverse effects from the therapy that lead to poor patient tolerance. Despite a great body of clinical evidence and guidelines that have offered various treatment options for patients with heart failure and CKD, respectively, patients with CKD are still underrepresented in heart failure clinical trials, especially for those with advanced CKD and end-stage renal disease (ESRD). Future studies are needed to better understand the generalizability of these therapeutic options among heart failures with different stages of CKD.

Assuntos

Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Gerenciamento Clínico

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DbCM) increases risk of overt heart failure in individuals with diabetes mellitus. Racial and ethnic differences in DbCM remain unexplored. OBJECTIVES: The authors sought to identify racial and ethnic differences among individuals with type 2 diabetes mellitus, structural heart disease, and impaired exercise capacity. METHODS: The ARISE-HF (Aldolase Reductase Inhibitor for Stabilization of Exercise Capacity in Heart Failure) trial is assessing the efficacy of an aldose reductase inhibitor for exercise capacity preservation in 691 persons with DbCM. Baseline characteristics, echocardiographic parameters, and functional capacity were analyzed and stratified by race and ethnicity. RESULTS: The mean age of the study participants was 67.4 years; 50% were women. Black and Hispanic patients had lower use of diabetes mellitus treatments. Black patients had poorer baseline ventricular function and more impaired global longitudinal strain. Overall, health status was preserved, based on Kansas City Cardiomyopathy Questionnaire scores, but reduced exercise capacity was present as evidenced by reduced Physical Activity Scale for the Elderly (PASE) scores. When stratified by race and ethnicity and compared with the entire cohort, Black patients had poorer health status, more reduced physical activity, and a greater impairment in exercise capacity during cardiopulmonary exercise testing, whereas Hispanic patients also displayed compromised cardiopulmonary exercise testing functional capacity. White patients demonstrated higher physical activity and functional capacity. CONCLUSIONS: Racial and ethnic differences exist in baseline characteristics of persons affected by DbCM, with Black and Hispanic study participants demonstrating higher risk features. These insights inform the need to address differences in the population with DbCM. (Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy [ARISE-HF]; NCT04083339).

Assuntos

Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Humanos , Feminino , Masculino , Cardiomiopatias Diabéticas/etnologia , Cardiomiopatias Diabéticas/epidemiologia , Idoso , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Tolerância ao Exercício/fisiologia , Hispânico ou Latino/estatística & dados numéricos , Negro ou Afro-Americano , Ecocardiografia , Teste de Esforço , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico

RESUMO

Purpose of review: The purpose of this review is to discuss myocardial recovery in heart failure with reduced ejection fraction (HFrEF) and to summarize the contemporary insights regarding heart failure with improved ejection fraction (HFimpEF). Recent findings: Improvement in left ventricular ejection fraction (LVEF ≥ 40%) with improved prognosis can be achieved in one out of three (10-40%) patients with HFrEF treated with guideline-directed medical therapy. Clinical predictors include non-ischemic etiology of HFrEF, less abnormal blood or imaging biomarkers, and lack of specific pathogenic genetic variants. However, a subset of patients may ultimately relapse, suggesting that many patients are merely in remission rather than having fully recovered. Summary: Patients with HFimpEF have improved prognosis but nonetheless remain at risk of relapse and long-term adverse events. Future studies will hopefully chart the natural history of HFimpEF and identify clinical predictors such as blood or novel imaging biomarkers that distinguish subgroups of patients based on differential trajectory and prognosis.

RESUMO

Background: Reduced cardiac energy is a hallmark feature of heart failure and is common in cardiac amyloidosis (CA) and can be aggravated by the presence of iron deficiency. Methods: Retrospective analysis of a single tertiary care center CA registry. Prevalence of iron deficiency was determined based on two definitions: (1) Classic definition, ferritin < 100 µg/L irrespective of transferin saturation (TSAT) or ferritin between 100 and 300 µg/L with a TSAT < 20%, and (2) TSAT-based definition, TSAT < 20%. Results: Out of a total of 393 CA patients who had a full set of iron indices (44% light chain [AL]-CA, 50% transthyretin [ATTR]-CA, remainder other or unspecified CA subtype), 56% had iron deficiency according to the classic definition and 58% according to the TSAT definition, with similar prevalence in AL-CA vs ATTR-CA (p = .135). Per both definitions 58% had anemia. Only the TSAT-based definition was associated with worse functional status (p = .039) and worse cardiac function. CA patients with a TSAT < 20% illustrated features of more pronounced right ventricular (RV) failure including lower TAPSE on echocardiography, lower RV ejection fraction and RV stroke volume index on CMR, increased right-sided filling pressures, lower pulmonary artery pulsatility index, and higher RAP/PCWP ratio by right heart catheterization. Neither the classic nor the TSAT-based definition was associated with a higher risk of all-cause mortality after covariate adjustment. Conclusion: Iron deficiency is common in cardiac amyloidosis and, when identified with a TSAT < 20%, is associated with worse functional status and more pronounced RV disease, but not with a higher risk of all-cause mortality.

RESUMO

The accessibility of the retina with the use of non-invasive and relatively low-cost ophthalmic imaging techniques and analytics provides a unique opportunity to improve the detection, diagnosis and monitoring of systemic diseases. The National Heart, Lung, and Blood Institute conducted a workshop in October 2022 to examine this concept. On the basis of the discussions at that workshop, this Roadmap describes current knowledge gaps and new research opportunities to evaluate the relationships between the eye (in particular, retinal biomarkers) and the risk of cardiovascular diseases, including coronary artery disease, heart failure, stroke, hypertension and vascular dementia. Identified gaps include the need to simplify and standardize the capture of high-quality images of the eye by non-ophthalmic health workers and to conduct longitudinal studies using multidisciplinary networks of diverse at-risk populations with improved implementation and methods to protect participant and dataset privacy. Other gaps include improving the measurement of structural and functional retinal biomarkers, determining the relationship between microvascular and macrovascular risk factors, improving multimodal imaging 'pipelines', and integrating advanced imaging with 'omics', lifestyle factors, primary care data and radiological reports, by using artificial intelligence technology to improve the identification of individual-level risk. Future research on retinal microvascular disease and retinal biomarkers might additionally provide insights into the temporal development of microvascular disease across other systemic vascular beds.

RESUMO

AIMS: The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved. METHODS AND RESULTS: We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular-pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660-0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656-0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference -0.072, 95% CI -0.123 to -0.020, p = 0.006, and -0.043, 95% CI -0.067 to -0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all). CONCLUSIONS: Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.