Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.
Ontology highlight
ABSTRACT:
SUBMITTER: Sayour NV
PROVIDER: S-EPMC11023004 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
Publications
Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.
Sayour Nabil V NV Paál Ágnes M ÁM Ameri Pietro P Meijers Wouter C WC Minotti Giorgio G Andreadou Ioanna I Lombardo Antonella A Camilli Massimiliano M Drexel Heinz H Grove Erik Lerkevang EL Dan Gheorghe Andrei GA Ivanescu Andreea A Semb Anne Grete AG Savarese Gianluigi G Dobrev Dobromir D Crea Filippo F Kaski Juan-Carlos JC de Boer Rudolf A RA Ferdinandy Péter P Varga Zoltán V ZV
European heart journal 20240401 14
Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of thi ...[more]
Similar Datasets
Project description:BACKGROUND:Heart failure (HF) is a clinical syndrome where diagnostic certainty varies. The prognosis of individuals with some clinical features of HF, but without the fully overt syndrome, is unclear. Therefore, we sought to evaluate their natural history. METHODS AND RESULTS:Between 1990 and 2009, all suspected HF cases in the Framingham Heart Study were adjudicated into 3 groups reflecting varying diagnostic certainty: definite (meeting HF diagnostic criteria; n = 479), possible (meeting HF criteria but with an alternative explanation for findings; n = 135), and probable (insufficient criteria for definite HF; n = 121) HF. Age-and-sex-matched individuals (n = 1112) without HF or cardiovascular disease (CVD) were controls. Using multivariable-adjusted Cox regression, we compared the possible/probable HF groups with controls regarding risk of incident definite HF, coronary heart disease (CHD), other CVD or death; and with definite HF regarding risk of latter three outcomes. During follow-up (mean 8.6 years), ~90% of individuals with possible, probable and definite HF experienced CVD events or died. Compared with controls, those with possible or probable HF experienced higher hazards for definite HF, CHD, other CVD and death (hazards ratios [HR] 1.35-9.31; p<0.05). The possible/probable groups did not differ from the definite HF group for risk of any outcome. Compared with the possible HF group, the probable HF group had a higher propensity for definite HF (HR 1.64, with a higher proportion of ischemic HF) but lower risk of death (HR 0.69). CONCLUSIONS:Individuals meeting partial criteria for HF are at a substantial risk for progression to HF, CVD, and mortality.
| S-EPMC7147998 | biostudies-literature
Project description:Heart failure is a common entity encountered in healthcare with a vast socioeconomic impact. Recent advances in pharmacotherapy have led to the development of novel therapies with mortality benefits, improvement in heart failure symptoms and hospitalizations. This article is intended to explore those newer pharmacotherapies and summarize the evidence behind guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). It has been several years since any significant advances in pharmacotherapy of heart failure have resulted in survival benefit. Angiotensin-neprilysin inhibitors through the PARADIGM-HF and PIONEER-HF trials have shown mortality benefits and a reduction in heart failure hospitalizations and are considered landmark trials in heart failure. Vericiguat is an oral guanylate cyclase stimulator that through the recent VICTORIA trial showed a 10% relative difference in death from cardiovascular cause or hospitalization for heart failure. The sodium-glucose transport protein 2 (SGLT2) inhibitors are another class of medications that have shown promise in the treatment of patients with HFrEF and diabetes mellitus. The CANVAS and EMPA-REG OUTCOME trials showed the potential benefit of SGLT2 inhibitors on cardiovascular mortality, DECLARE-TIMI 58 trial showed that treatment with dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure to a greater extent in patients with reduced ejection fraction (EF). Although novel pharmacotherapy is the current focus of intense research, there have been numerous studies on potential benefit of iron supplementation in ferropenic patients with heart failure. Another rapidly expanding area of research in the realm of heart failure is precision medicine and its impact on the development, progression, and treatment of heart failure. The field of heart failure is dynamic and with the influx of data from recent and ongoing trials, newer therapies with morbidity and mortality benefits in HFrEF are now available, nonetheless, much work is still needed.
| S-EPMC8039644 | biostudies-literature
Project description:Abstract Background This study aimed to assess the prescribing patterns of evidence‐based pharmacotherapy and their association with clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in Thailand. Methods A retrospective cohort study of patients with HFrEF was conducted. Treatment with a β‐blocker and renin–angiotensin system inhibitors (RASIs) with or without mineralocorticoid receptor antagonists (MRAs) at discharge was regarded as guideline‐directed medical therapy (GDMT). All others were considered non‐GDMT. The primary endpoint was the composite of all‐cause mortality or heart failure (HF) rehospitalization. Inverse‐probability‐treatment‐weighted adjusted Cox proportional hazard models were used to examine the treatment effects. Results In total, 653 patients with HFrEF (mean age 64.1 ± 14.3 years; 55.9% male) were included. GDMT with β‐blockers and RASIs with or without MRAs was prescribed at a rate of 35.4%. During a median of 1‐year follow‐up, 167 patients (27.5%) had a composite event, 81 patients (13.3%) had all‐cause mortality, and 109 patients (18.0%) had HF rehospitalization. Patients treated with GDMT at discharge showed significantly lower rates of the primary endpoint (adjusted hazard ratio [HR] 0.63; 95% CI 0.44–0.89; p = 0.009) compared with patients who did not receive GDMT. The use of GDMT was also associated with a significantly lower risk of all‐cause mortality (adjusted HR 0.59; 95% CI 0.36–0.98; p = 0.045) and HF rehospitalization (adjusted HR 0.65; 95% CI 0.43–0.96; p = 0.031). Conclusions For HFrEF treatment, GDMT initiation at hospital discharge was associated with a significantly reduced risk of all‐cause mortality and HF rehospitalization. Nevertheless, prescribing GDMT remains underused, and it could be encouraged to improve HF outcomes in real‐world settings. Discharge medication profiles in the overall cohort. (A) Standard medication profiles at discharge and (B) pharmacotherapy treatment patterns for heart failure with reduced ejection fraction at discharge. Highlights The initiation of heart failure with reduced ejection fraction (HFrEF) pharmacotherapies at discharge was associated with a significantly reduced risk of all‐cause mortality and heart failure rehospitalization. Evidence‐based HFrEF pharmacotherapy remains underused in real‐world settings. The present findings highlight the need to encourage the use of evidence‐based pharmacotherapy for HFrEF to improve long‐term outcomes.
| S-EPMC10249177 | biostudies-literature
Project description:Heart failure (HF) is a life-threatening cardiac syndrome characterized by high morbidity and mortality, but current anti-heart failure therapies have limited efficacy, necessitating the urgent development of new treatment drugs. Exogenous ketone supplementation helps prevent heart failure development in HF models, but therapeutic ketosis in failing hearts has not been systematically elucidated, limiting the use of ketones to treat HF. Here, we summarize current evidence supporting ketotherapy in HF, emphasizing ketone metabolism in the failing heart, metabolic and non-metabolic therapeutic effects, and mechanisms of ketotherapy in HF, involving the dynamics within the mitochondria. We also discuss clinical strategies for therapeutic ketosis, aiming to deepen the understanding of the characteristics of ketone metabolism, including mitochondrial involvement, and its clinical therapeutic potential in HF.
| S-EPMC11540999 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is a worldwide major health burden and heart failure (HF) is the most common cardiovascular (CV) complication in affected patients. Therefore, identifying the best pharmacological approach for glycemic control, which is also useful to prevent and ameliorate the prognosis of HF, represents a crucial issue. Currently, the choice is between the new drugs sodium/glucose co-transporter 2 inhibitors that have consistently shown in large CV outcome trials (CVOTs) to reduce the risk of HF-related outcomes in T2DM, and metformin, an old medicament that might end up relegated to the background while exerting interesting protective effects on multiple organs among which include heart failure. When compared with other antihyperglycemic medications, metformin has been demonstrated to be safe and to lower morbidity and mortality for HF, even if these results are difficult to interpret as they emerged mainly from observational studies. Meta-analyses of randomized controlled clinical trials have not produced positive results on the risk or clinical course of HF and sadly, large CV outcome trials are lacking. The point of force of metformin with respect to new diabetic drugs is the amount of data from experimental investigations that, for more than twenty years, still continues to provide mechanistic explanations of the several favorable actions in heart failure such as, the improvement of the myocardial energy metabolic status by modulation of glucose and lipid metabolism, the attenuation of oxidative stress and inflammation, and the inhibition of myocardial cell apoptosis, leading to reduced cardiac remodeling and preserved left ventricular function. In the hope that specific large-scale trials will be carried out to definitively establish the metformin benefit in terms of HF failure outcomes, we reviewed the literature in this field, summarizing the available evidence from experimental and clinical studies reporting on effects in heart metabolism, function, and structure, and the prominent pathophysiological mechanisms involved.
| S-EPMC8698925 | biostudies-literature
Project description:Study objectiveHalf of patients with heart failure have preserved ejection fraction (HFpEF). Over the years, guidelines have recommended or advised against various therapies for HFpEF management. However, there is limited evidence on the trends in utilization of the various medications. The aim of this study was to examine the trends in the use of pharmacotherapies among patients with HFpEF from 2008 through 2020.DesignRetrospective cohort study of patients with HFpEF used MarketScan® Commercial and Medicare Supplemental Databases (2007-2020).ParticipantsPatients with HFpEF.Outcome measuresUtilization rates for angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), aldosterone receptor antagonists (ARAs), diuretics, β-blockers, calcium channel blockers (CCBs), phosphodiesterase 5 inhibitors (PDE5Is), nitrates, digoxin, and sodium glucose cotransporter-2 inhibitors (SGLT2i) within 90 days of the first HFpEF diagnosis.ResultsWe identified 156,730 patients with HFpEF (mean [SD] age, 73 [13.4] years; 57 % females). From 2008 to 2020, we found increased utilization rates for ARNIs (0.02 % vs. 0.17 % of all patients, p < 0.01), ARBs (14.3 % vs. 18.6 %, p < 0.01), ARAs (7.0 % vs. 8.4 %, p < 0.01), CCBs (30.6 % vs. 33.4 %, p < 0.01), and SGLT2i (0.001 % vs. 0.021 %, p < 0.01). By contrast, the utilization of ACEIs (30.4 % vs. 20.5 %, p < 0.01), digoxin (9.5 % vs. 2.4 %, p < 0.01), nitrates (10.7 % vs. 4.9 %, p < 0.01), diuretics (54.1 % vs. 50.4 %, p = 0.20), and β-blockers (52.6 % vs. 51.7 %, p < 0.01) decreased, while utilization rates of PDE5Is remained stable (1.5 % vs. 1.1 %, p = 0.90) .ConclusionsDuring the 13-year study period, the utilization of ARNIs, ARBs, ARAs, CCBs, and SGLT2i increased while the utilization of digoxin, nitrates, diuretics, and β-blockers decreased among patients with HFpEF.
| S-EPMC10946036 | biostudies-literature
Project description:AimsTemporal conversions among ejection fraction (EF) classes can occur across the heart failure (HF) spectrum reflecting amended structural and functional outcomes unaccounted for by current taxonomy. This retrospective study aims to investigate the differences in serum laboratory values, guideline-directed medical therapy (GDMT), and co-morbidity burden across EF conversion groups.Methods and resultsHeart failure patients at least 18-year-old who obtained at least two echocardiograms between January 2018 and January 2020 were identified using ICD-10 codes. Analysis of variance, chi-square tests, and analysis of means for proportions were used as appropriate to identify associations with class conversion groups. A total of 874 patients who underwent 1748 echocardiograms on unique visits were categorized according to initial EF as HF with preserved EF (HFpEF) (n = 531, 61%), HF with mildly reduced or midrange EF (HFmrEF) (n = 132, 15%), or HF with reduced EF (HFrEF) (n = 211, 24%). In accordance with follow-up EF, class conversions were categorized into HF with improved EF (HFiEF) (n = 143, 16%), HF with worsened EF (HFwEF) (n = 171, 20%), or HF with stable EF (HFsEF) (n = 560, 64%). The average age was 75 ± 13 years old; 54% were male, 85% were Caucasian, 11% were African American, and 4% other. The mean time between EF assessments was 208.6 ± 170.2 days. Serum sodium levels were greater in HFwEF (139 ± 3 mmol/L) when compared with HFsEF (138 ± 4 mmol/L) (P = 0.05). Pro-BNP levels were higher in HFiEF (12 150 ± 19 554 pg/mL) versus HFsEF (6671 ± 10 525 pg/mL) (P = 0.007). Angiotensin receptor-neprilysin inhibitors (ARNI) were more frequently ordered on index visit in HFiEF (P = 0.03), but no other significant differences in GDMT were identified. Despite similar Elixhauser Co-morbidity Measure (ECM) scores, ECM categorical analysis revealed that HFwEF was more likely to have an established diagnosis of depression (P = 0.03) and a spectrum of psychiatric illnesses (P = 0.03) on preliminary visit. HFsEF was less likely to have an established diagnosis of blood loss anaemia (P = 0.04). Metastatic cancer was more likely to have been diagnosed in HFiEF and less likely in HFsEF (P = 0.002).ConclusionsDespite similar ECM scores, EF class conversion groups demonstrated salient differences in average serum sodium and pro-BNP levels. Inpatient ARNI orders, psychiatric, hematologic, and oncologic co-morbidity patterns were also significantly different. Findings demonstrate blood-based biomarker patterns and targetable co-morbid conditions which may play a role in future EF class conversion. Dedicated studies evaluating measurements related to GDMT dose-titration, quality of life, and functionality are the next steps in this field of HF.
| S-EPMC9288751 | biostudies-literature
Project description:AimsEvidence on the risk factors for incident heart failure in Asia has been limited. We sought to identify the risk factors for pre-heart failure or symptomatic heart failure, based on N-terminal pro-B-type natriuretic peptide (NT-proBNP), in the Japanese general population.MethodsWe performed a retrospective cohort study based on the Circulatory Risk in Communities Study involving 5335 Japanese individuals whose NT-proBNP levels were measured between 2010 and 2015. Of these, 2768 people aged between 30 and 69 years who undertook annual cardiovascular risk surveys at least once between 1990 and 2000 were retrospectively eligible to be participants in this study. We performed multivariable logistic regression analyses to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-heart failure or symptomatic heart failure defined as NT-proBNP >400 pg/mL or as having a diagnosis of heart failure and taking medication for heart failure for several cardiovascular risk factors (body mass index, blood pressure, diabetes mellitus, total cholesterol, triglyceride, smoking status, drinking status).ResultsWe identified 85 cases of heart failure. The multivariable ORs (95% CIs) were 5.70 (2.70-12.0) for body mass index of 27-29.9 kg/m2 and 5.91 (2.19-16.0) for ≥30 kg/m2 compared with 21-22.9 kg/m2 ; 2.49(1.01-6.13) for systolic blood pressure of ≥160 mmHg vs. <130 mmHg; 2.87(1.23-6.68) for diastolic blood pressure of ≥100 mmHg vs. <80 mmHg; 5.16(2.14-12.4) for diabetes vs. non-diabetes; and 2.24 (0.92-5.49) for current smokers of ≥20 cigarettes/day vs. never smokers. The multivariable ORs (95% CIs) of the number of risk factors, defined as the sum of four risk factors (obesity, hypertension, diabetes, and current smoker) was 6.80 (3.69-12.5) for ≥2 risk factors vs. no risk factors.ConclusionsThe accumulation of these risk factors was associated with a graded higher risk of pre-heart failure or symptomatic heart failure.
| S-EPMC9871651 | biostudies-literature
Project description:AimsMany European healthcare providers struggle to adopt multidisciplinary, integrated care pathways for people with heart failure (HF) as recommended by the European Society of Cardiology. PRO-HF (Program to Optimize Heart Failure Patient Pathways) was developed to help clinicians identify strengths, gaps, and shortcomings in their HF pathways and support tailored interventions to optimize pathways and enhance patient care. We report initial findings from baseline assessments of HF pathway characteristics and challenges from 10 hospitals in six European countries (France, Ireland, Portugal, Spain, The Netherlands, and United Kingdom).Methods and resultsBaseline assessments were holistic appraisals of full HF services to calibrate current status and development needs and assist management teams in prioritizing improvement projects. Assessments were performed using a comprehensive checklist of measures covering the HF patient journey from diagnosis to ongoing follow-up. These included a digital survey sent to full HF care teams and one-to-one interviews. The digital survey focused on four key areas (HF outpatient clinic; remote patient management; efficient device implantation and inpatient pathways; and network maximization) and 16 dimensions of excellence. Priority areas and themes for action identified in baseline assessments were (i) provision of HF specialist care; (ii) data capture and analysis; (iii) institutional care protocols; (iv) hospital-wide strategies; and (v) multidisciplinary teams (MDTs). Suboptimal specialist care of emergency inpatients was an issue at all hospitals and prioritized at 8/10. Availability and accessibility of data on patients, activities, and outcomes was an issue at all hospitals and prioritized by 4/10. A lack of clear protocols, templates, and tools for some HF activities created variability in patient care (e.g., HF specialist consultations, diagnostic testing, follow-up appointments, medications, and device eligibility) and inefficient use of clinician time. This made it difficult to initiate new technologies (e.g., remote patient monitoring) due to the risk of overburdening staff. MDTs were frequently understaffed. Multiple interventions were identified to address gaps and shortcomings that could be tailored to specific needs of individual hospitals (e.g., inpatient pathway optimization, creation/optimization of HF outpatient clinics, development of an HF performance dashboard, enhancement of protocol adherence, streamlining cardiac resynchronisation therapy pathways, and MDT coordination).ConclusionsPRO-HF provides a valuable opportunity to identify gaps and significant shortcomings in HF pathways in European hospitals. Preliminary findings from hospitals that have initiated suggested changes to address these challenges are encouraging, though longer-term follow-up from more hospitals is needed to confirm the impact of PRO-HF on HF pathway optimization and patient care.
| S-EPMC11424341 | biostudies-literature
Project description:During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.
| S-EPMC7041880 | biostudies-literature