Heart Failure Outcomes Research Articles

Advanced Heart Failure Characteristics and Outcomes in Women and Men.

The epidemiology and pathophysiology of heart failure (HF) differ in women and men. Whether these differences extend to the subgroup of patients with advanced HF is not well defined. This is a retrospective cohort study of all adult Olmsted County, Minnesota residents with advanced HF (European Society of Cardiology criteria) from 2007 to 2017. Differences in survival and hospitalization risks in women and men following advanced HF development were examined using Cox proportional hazard regression and Andersen-Gill models, respectively. Of 936 individuals with advanced HF, 417 (44.6%) were women and 519 (55.4%) were men (self-reported sex). Time from development of HF to advanced HF was similar in women and men (median 3.2 versus 3.6 years). Women were older at diagnosis (mean age 79 versus 75 years), less often had coronary disease and hyperlipidemia, but more often had hypertension and depression (P<0.05 for each). Advanced HF with preserved ejection fraction was more prevalent in women than men (60% versus 30%, p<0.001). There were no differences in adjusted risks of all-cause mortality (hazard ratio [HR], 0.89 [95% CI, 0.77-1.03]), cardiovascular mortality (HR, 0.85 [95% CI, 0.70-1.02]), all-cause hospitalizations (HR, 1.04 [95% CI, 0.90-1.20]), or HF hospitalizations (HR, 0.91 [95% CI, 0.75-1.11]) between women and men. However, adjusted cardiovascular mortality was lower in women versus men with advanced HF with reduced ejection fraction (HR, 0.72 [95% CI, 0.56-0.93]). Women more often present with advanced HF with preserved ejection fraction and men with atherosclerotic disease and advanced HF with reduced ejection fraction. Despite these differences, survival and hospitalization risks are largely comparable in women and men with advanced HF.

Dapagliflozin Effects on Cardiac Deformation in HeartFailure and Secondary Clinical Outcome.

Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in the dapagliflozin group after 6months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P< 0.0001), indicating a significant difference between dapagliflozin and OMT. This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).

Right Ventricular-Pulmonary Arterial Coupling and Outcome in Heart Failure With Preserved Ejection Fraction.

Right ventricular-pulmonary artery coupling (RVPAC) refers to the relationship between right ventricular systolic force and afterload. The ratio of echocardiograph-derived tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) has been proposed as a noninvasive measurement of RVPAC and reported as an independent prognostic parameter of heart failure. However, it has not been adequately in detail evaluated in heart failure with preserved ejection fraction (HFpEF). We hypothesized that RVPAC may be used and proposed as an expression of key risk factors in patients with HFpEF. We retrospectively analyzed TAPSE/PASP of 648 HFpEF patients hospitalized in Chongqing Hospital of Traditional Chinese Medicine from January 1, 2016 to January 1, 2017. All eligible patients were followed up for 5 years. The correlation between TAPSE/SPAP index and clinical indicators and outcomes was evaluated. The final analysis included 414 patients. Nonsurvivors had significantly lower TAPSE, TAPSE/PASP and higher PASP compared with survivors (p < 0.0001). ROC curve analysis showed that the optimal cutoff of TAPSE, PASP, and RVPAC to predict all-cause death were 16.5 mm, 37.5 mmHg, and 0.45 mm/mmHg, respectively. In multivariate Cox regression analyses adjusted for gender showed a significant, independent association of the RVPAC with the composite endpoint of all-cause death or HF-related recurrent hospitalization (HR: 0.006; 95% CI 0.001-0.057, p < 0.001). RVPAC, defined by the ratio of TAPSE to PASP, is the expression of a key risk factor in HFpEF patients, which is independently associated with the composite endpoint of all-cause death or HF-related recurrent hospitalization.

Cancer Screening in Patients with Heart Failure with Mildly Reduced and Reduced Ejection Fraction

Background: Heart failure with mildly reduced and reduced ejection fraction are associated with incident cancer. However, cancer screening is not routinely discussed in this population. This study aimed to describe the uptake and perception of cancer screening among patients with heart failure attending a specialised heart failure clinic in Australia. Methods: A prospective survey of consecutive ambulatory patients attending the clinic from 2022–2023 was performed. Included patients were eligible for recommended breast, cervical and/or bowel cancer screening according to Australian guidelines, had an ejection fraction of &lt;50% and no prior history of cancer. The primary endpoint was adherence to recommended cancer screening according to Australian guidelines. Perceptions towards cancer screening were also assessed and cancer screening rates were compared with those of the general Australian population. Results: Among the 200 included patients, there was low uptake of recommended breast, bowel and cervical cancer screening despite the availability of free national cancer screening programmes. Cancer screening rates among heart failure patients were lower than observed in the general Australian population. Patients were unaware of the association between cancer and heart failure and expressed interest in cancer screening participation. Conclusion: Future efforts should be targeted at improving education on cancer screening among patients and cardiovascular healthcare providers to improve overall health outcomes in heart failure.

Examining Heart Failure Outcomes Amid Housing Insecurity

How housing insecurity might affect patients with heart failure (HF) is not well characterized. Housing insecurity increases risks related to both communicable and noncommunicable diseases. For patients with HF, housing insecurity is likely to increase the risk for worse outcomes and rehospitalizations. We analyzed hospitalizations due to HF in the United States by using the 2020 National Inpatient Sample and Nationwide Readmissions Database to evaluate the impacts of housing insecurity on HF outcomes and hospital use. Individuals were identified as having housing insecurity by using diagnostic International Classification of Disease (ICD)-10 codes. Demographics and comorbidities were compared between patients with HF with and without housing insecurity. An adjusted logistic regression was performed to evaluate the relationships between housing insecurity and socioeconomic status on in-hospital mortality. Using a Cox proportional hazards model, patients with HF and without housing insecurity were evaluated for the risk of all-cause and HF-specific readmissions over time. Of the 1,003,270 hospitalizations for HF in the U.S. in 2020, 16,150 were identified as having housing insecurity (1.6%), and 987,120 were identified as having no housing insecurity (98.4%). The median age of patients with housing insecurity who were hospitalized for HF was 57, as compared to 73 in the population with no housing insecurity. A higher proportion of patients in the housing-insecurity group were Black (35% vs 20.1%) or Hispanic (11.1% vs 7.3%). Patients with housing insecurity were more likely to carry a diagnosis of alcohol-use disorder (15.2% vs 3.3%) or substance-use disorder (70.2% vs 17.8%) but were less likely to use tobacco (18.3% vs 28.7%). Patients with housing insecurity were over 4.5 times more likely to have Medicaid (52.4% vs 11.3%). Median length of stay did not differ between patients with housing insecurity vs those without it. Patients with housing insecurity were more likely to discharge against medical advice (11.4% vs 2.03%). After adjusting for patients' characteristics, housing insecurity was associated with lower in-hospital mortality rates (OR 0.60, 95% CI 0.39-0.92). Housing insecurity was associated with a higher risk of all-cause readmissions at 180 days (HR 1.13, 95% CI 1.12-1.14). However, there was no significant difference in the risk of HF-specific readmissions at 180 days (HR 1.07, 95% CI 0.998-1.14) CONCLUSIONS: Patients with HF and housing insecurity have distinct demographic characteristics. They are also more likely to be readmitted after their initial hospitalization when compared to those without housing insecurity. Identifying and addressing specific comorbid conditions for patients with housing insecurity who are hospitalized for HF may allow clinicians to provide more focused care, with the goal of preventing morbidity, mortality and unnecessary readmissions.

Systematic Review on the Role of IL-6 and IL-1β in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a leading cause of global morbidity and mortality, significantly driven by chronic inflammation. Interleukin-6 (IL-6) and interleukin-1β (IL-1β) are critical inflammatory cytokines implicated in CVD progression. This systematic review evaluates the roles of IL-6 and IL-1β in CVDs by synthesizing data from relevant studies to understand their impact on cardiovascular outcomes and identify potential therapeutic interventions. A comprehensive literature search was conducted using PubMed and Embase, covering studies from January 2014 to December 2024. Inclusion criteria encompassed studies investigating IL-6 and/or IL-1β in CVDs, including human and relevant animal models, and reporting clinical outcomes, molecular mechanisms, or therapeutic interventions. Data extraction and quality assessment were performed independently by two reviewers. Our review included 12 studies focusing on the roles of IL-6 and IL-1β in various CVDs. Elevated IL-6 levels were significantly associated with peripheral artery disease, myocardial infarction, and heart failure, while IL-1β levels were linked to worse outcomes in coronary artery disease and heart failure. Meta-analyses indicated a significant association between higher IL-6 and IL-1β levels and increased risk of adverse cardiovascular events. These findings suggest that targeting IL-6 and IL-1β could offer promising therapeutic strategies for reducing inflammation and improving cardiovascular outcomes.

Pulmonary transit time is a predictor of outcomes in heart failure: a cardiovascular magnetic resonance first-pass perfusion study

BackgroundPulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure.MethodsWe recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves.ResultsPatients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08–1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02–1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP.ConclusionsPTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.

2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II

BackgroundThe REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, “responders” (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified. ObjectivesThis study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt. MethodsThe study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status. ResultsIn 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]). ConclusionsAt 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033)

Physical Heart Failure Symptom Clusters Predictive of Delay in Seeking Treatment.

Recent research has focused on the relationship between heart failure (HF) symptom clusters and outcomes, including mortality, hospitalization, functional status, and quality of life. No known studies to date have explored the role of physical HF symptom clusters and delays in seeking treatment. Describe physical symptom clusters in a population of HF patients and determine if a specific cluster is predictive of delay in seeking treatment for HF symptoms. We analyzed combined data from two studies (n = 406) collected during acute HF hospitalization. The Heart Failure Somatic Awareness Scale quantified physical HF symptoms. Delay, measured in days, was collected from the medical record and confirmed by interview. Hierarchical agglomerative clustering techniques determined physical HF symptom clusters. Hierarchical multiple regression analysis was computed to explore predictors of delay. Participants were primarily White, male sex older adults. Three physical HF symptom clusters were identified: discordant, edema-related symptoms, and dyspnea-related symptoms. Hierarchical multiple regression analysis revealed in Step 1 that age was a significant predictor of delay. Our findings provide valuable insight into the role of physical symptom clusters on delay in persons with HF. Through agglomerative hierarchical clustering techniques, we found three physical HF symptom clusters that were then used to determine differences in cluster membership by demographic and clinical variables. Significant age differences were noted by cluster membership with youngest older adults in a discordant symptom cluster.

Geographical variation in patient characteristics and outcomes in heart failure with mildly reduced and preserved ejection fraction.

Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF. We conducted an individual patient analysis of five clinical trials enrolling patients with HFpEF or HFmrEF from North America (NA), Latin America (LA), Western Europe (WE), Central/Eastern Europe and Russia (CEER), and Asia-Pacific (AP). We compared regions using descriptive statistics and multivariable regression models. Among the 19 959 patients included, 4066 (23.1%) had HFmrEF and 15 353 (76.9%) HFpEF. Regardless of HF phenotype, patients from WE were oldest, and those in CEER youngest. LA had the largest portion of females and NA most black patients. Obesity and diabetes were most prevalent in NA and hypertension and coronary heart disease most common in CEER. Self-reported health status varied strikingly and was the worst in NA and best in AP. Among patients with HFmrEF, rates of the primary composite endpoint (cardiovascular death or HF hospitalization) were: NA 12.56 per 100 patient-years (/100py), AP 11.67/100py, CEER 10.12/100py, LA 8.90/100py, and WE 8.43/100py, driven by differences in the rate of HF hospitalization. The corresponding values in HFpEF were 11.47/100py, 7.80/100py, 5.47/100py, 5.92/100py, and 7.80/100py, respectively. There is substantial geographic variation in patient characteristics, treatment and outcomes among patients with HFpEF and HFmrEF. These findings have implications for interpretation and generalizability of trial results, design and conduct of future trials, and optimization of care for these patients.

Even a low comorbidity burden predicts poor outcome in chronic heart failure.

Patients with heart failure (HF) often have multiple cardiovascular risk factors (CVRF) and comorbidities (CMB). We evaluated the impact of additive CMB and CVRF in HF prognosis. We retrospectively analyzed ambulatory patients with systolic dysfunction between January 2012 and May 2018. Follow-up: until January 2021. Endpoint: all-cause death. CVRF analyzed: Arterial hypertension, Diabetes mellitus and smoking. CMB evaluated: coronary artery disease, non-coronary atherosclerotic disease, respiratory disease, dementia, anemia, chronic kidney disease, inflammatory/autoimmune disease, active cancer and atrial fibrillation. Classification according to the number of CVRF and/or CMB: < 2 and ≥ 2. The independent prognostic impact of CVRF/CMB burden was assessed with multivariate Cox-regression. Most patients had ≥ 2 CMB (67.9%). Regarding CVRF, 14.9% presented none, 40.2% had one and 32.1% had two. During a median 49-month follow-up, 419 (49.1%) patients died. Mortality was higher among patients with ≥2 CVRF (56.1 vs 43.4% in those with <2) and in those with ≥2 CMB (57.7 vs 31.0%). While patients with one CMB had similar mortality than those with none. Patients with ≥2 CMB had higher long-term mortality risk: HR=2.47 (95% CI: 1.95-3.14). In patients with ≥2CVRF: HR of dying = 1.39 (1.14- 1.70). When taken together there was a clear survival disadvantage for patients with ≥ 2 CVRF/CMB - adjusted HR: 2.20 (1.45-3.34). The presence of only 2 CVRF/CMB more than doubles the patients´ risk of dying. CVRF and CMB should be assessed as part of routine patient management.

Analysis of the significance of echocardiographic signs of right ventricular dysfunction for predicting the outcome of heart failure with reduced left ventricular ejection fraction

Objective: to determine the ultrasound signs of right heart dysfunction, which increase the prognostic value of the recommended parameters of left ventricular (LV) dysfunction in patients with heart failure with reduced ejection fraction (HFrEF).Materials and methods. The prospective study included 79 patients with HFrEF LV with clinical manifestations of chronic heart failure functional class III according to the New York Heart Association (HF NYHA Class III) in 52 patients (65.8%) and HF NYHA Class IV in 27 (34.1%). The primary end point was death during a follow-up period of up to 3 years while waiting for heart transplantation.Results. Overall mortality was 33 patients (41.7%), 17 (21.5%) during the 1st year of follow-up. Regression analysis revealed the following independent ultrasound predictors of poor prognosis: LV ejection fraction on 3D-echocardiography (3DE LVEF), p = 0.014; global longitudinal strain of the LV (GLS LV), p = 0.010, and of the interventricular septum basal segment (IVSLS BS), p = 0.012; mean longitudinal strain of the basal segment of the right ventricle free wall (FWLS BS RV), p = 0.003. Changes in the configuration and dilatation of the LV cavity, an increase in LV end-diastolic pressure, impaired contractility, and strain of the LV myocardium can affect the function of the right ventricle (RV) through the common interventricular septum (IVS). Dilatation of the RV due to an increase in the end diastolic area (RV EDA) of more than 30 cm2 (p = 0.012) and end systolic area (RV ESA) of more than 25 cm2 (p = 0.001), an increase in the volume of the right atrium (3DE AKI) of more than 100 ml (p = 0.036), and a decrease in the % inspiratory collapse of the inferior vena cava (% IVC) less than 30% (p = 0.005) demonstrated a prognostic significance in the observed patients. A decrease in the deformation properties of the pancreas due to the longitudinal component and impaired strain of the basal segment makes a greater contribution to RV dysfunction (FWLS BS, % &lt; -15% (p &lt; 0.001)).Conclusions. RV dysfunction in patients with HFrEF is an unfavorable prognostic factor, independently associated with existing LV dysfunction. The most significant ultrasound sign for surveillance prediction of patients with LV HFrEF and RV dysfunction are indicators of ventricular myocardial deformation. Remodeling of the right chambers and dysfunction of the RV is a trigger for the separation of the RV and pulmonary artery, which ultimately leads to adverse outcomes.

The role of urine chloride in acute heart failure

In our retrospective study, we aimed to investigate the relationship between urinary chloride (uCl−) and selected clinical and laboratory biomarkers, renal function, and patient outcomes in the acute heart failure (AHF) population. We divided 248 adult patients (≥ 18 years) with AHF into two groups: low uCl− (< 115 mmol/L) and high uCl−. The mean age of the patient group was 70.2 ± 12.6, and 182 patients were male (73.4%). Clinical endpoints included in-hospital mortality, one-year mortality, and a composite endpoint of one-year mortality and rehospitalization for heart failure. Patients were followed up for at least one year. Relevant clinical and baseline biomarker data were collected, including markers concerning inflammation, liver and kidney function, perfusion and congestion, iron status, cardiac remodeling, gasometry, renin and aldosterone. Low uCl− was associated with worse in-hospital outcomes, including higher in-hospital mortality (7.7% vs. 1.4%, p = 0.014), the need for inotropic support (20.19% vs. 2.08%, p ≤ 0.001), worsening of HF during therapy (17.31% vs. 4.86%, p ≤ 0.001), and the need for treatment in an intensive cardiac care unit (33.65% vs. 15.28%, p ≤ 0.001). Low uCl− was a significant predictor of one-year mortality (40.4% vs. 16.7%, p < 0.05) and the composite outcome (HR 2.42, 95% CI 1.43–4.08, p < 0.001). In the multivariable analysis, uCl− was independently associated with the risk of one-year mortality (HR 0.92, 95% CI 0.87–0.98, p < 0.05) and the composite outcome (HR 0.95, 95% CI 0.92–0.99, p < 0.05). Our findings suggest that low uCl− is a marker of more advanced heart failure, activation of the renin–angiotensin–aldosterone system and is related to worse one-year outcomes.

Hypertension and Heart Failure: From Pathophysiology to Treatment.

Hypertension represents one of the primary and most common risk factors leading to the development of heart failure (HF) across the entire spectrum of left ventricular ejection fraction. A large body of evidence has demonstrated that adequate blood pressure (BP) control can reduce cardiovascular events, including the development of HF. Although the pathophysiological and epidemiological role of hypertension in the development of HF is well and largely known, some critical issues still deserve to be clarified, including BP targets, particularly in HF patients. Indeed, the management of hypertension in HF relies on the extrapolation of findings from high-risk hypertensive patients in the general population and not from specifically designed studies in HF populations. In patients with hypertension and HF with reduced ejection fraction (HFrEF), it is recommended to combine drugs with documented outcome benefits and BP-lowering effects. In patients with HF with preserved EF (HFpEF), a therapeutic strategy with all major antihypertensive drug classes is recommended. Besides commonly used antihypertensive drugs, different evidence suggests that other drugs recommended in HF for the beneficial effect on cardiovascular outcomes exert advantageous blood pressure-lowering actions. In this regard, type 2 sodium glucose transporter inhibitors (SGLT2i) have been shown to induce BP-lowering actions that favorably affect cardiac afterload, ventricular arterial coupling, cardiac efficiency, and cardiac reverse remodeling. More recently, it has been demonstrated that finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces new-onset HF and improves other HF outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of a history of HF. Other proposed agents, such as endothelin receptor antagonists, have provided contrasting results in the management of hypertension and HF. A novel, promising strategy could be represented by small interfering RNA, whose actions are under investigation in ongoing clinical trials.

Temporal evolution of anxiety and depression in chronic heart failure and its association with clinical outcome

BackgroundAlthough anxiety and depression have been associated with adverse outcomes in chronic heart failure (HF), data on temporal evolution of these symptoms are scarce. We aimed to investigate the association between repeatedly measured depression and anxiety symptoms and clinical outcome in chronic HF patients. MethodsIn this prospective observational study, outpatients with chronic HF were included and followed-up for a maximum of 2.5 years. The hospital anxiety and depression scale (HADS) questionnaire was conducted every six months. The primary endpoint was a composite of HF hospitalization, cardiovascular death, heart transplantation and left ventricular assist device (LVAD) implantation. Cox and joint models were used to investigate the association between the HADS score and the endpoint. ResultsA total of 362 patients filled out a median (25th–75th percentile) of 3 [2–4] questionnaires each. Mean ± SD age was 63 ± 13 years, 72% were men. Anxiety scores remained relatively stable leading up to the endpoint, while depression scores increased. Higher baseline depression scores were significantly associated with the endpoint (hazard ratio [HR] 1.68 and 95% confidence interval [CI] 1.19–2.36 per log(score+1), p = 0.003), while higher baseline anxiety scores did not reach statistical significance (HR [95% CI] 1.34 [0.99–1.83], p = 0.061). When repeatedly measured, both higher anxiety (HR [95% CI] 1.57[1.07–2.30], p = 0.022) and depression (HR [95% CI] 2.04 [1.39–3.06], p < 0.001) scores were significantly associated with the endpoint. ConclusionSerial measurements of depression and anxiety symptoms identify chronic HF patients with increased risk of adverse clinical outcomes. Screening for both disorders should be considered in clinical practice.

Biologically active adrenomedullin as a marker for residual congestion and early rehospitalization in patients hospitalized for acute heart failure: Data from STRONG-HF.

Biologically active adrenomedullin (bio-ADM) is a promising marker of residual congestion. The STRONG-HF trial showed that high-intensity care (HIC) of guideline-directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio-ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated. We measured plasma bio-ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio-ADM correlated with most signs of congestion, with the exception of rales. Changes in bio-ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma -0.24; p = 0.0001). Patients in the highest tertile of baseline bio-ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180-day all-cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42-3.22) and 180-day HF rehospitalization (HR 2.33, 95% CI 1.38-3.94). Areas under the receiver-operating characteristic curves were 0.5977 (95% CI 0.5561-0.6393), 0.5800 (95% CI 0.5356-0.6243), and 0.6159 (95% CI 0.5711-0.6607) for bio-ADM, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their combination, respectively, suggesting that both bio-ADM and NT-proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio-ADM and NT-proBNP than NT-proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio-ADM concentration (interaction p = 0.37). In contrast to NT-proBNP, the 90-day change in bio-ADM did not differ significantly between HIC and usual care. Bio-ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio-ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT-proBNP.

Peripheral artery disease, chronic kidney disease, and recurrent admissions for acute decompensated heart failure: The ARIC study

Background and aimsPeripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known. MethodsSince 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m2 [stage 3a or worse]). ResultsFrom 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29–2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14–3.40); p-interaction = 0.8. ConclusionAmong patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population.

Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

Killip scale reclassification according to lung ultrasound: Killip pLUS.

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). 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. The Killip pLUS scale provides enhanced risk stratification compared to the Killip and LUCK scales while preserving simplicity.

Gender differences in Clinical Characteristics and Outcomes of Heart Failure with Reduced Ejection Fraction

Background and Objectives: Studies evaluating gender differences and outcomes in heart failure with reduced ejection fraction are limited in Iraq. The aim of this study was to assess the clinical characteristics, risk factors, outcomes and severity of heart failure with reduced ejection fraction in both genders. Patients and Methods: This is a prospective cohort study of 117 patients aged more than 18 years who had been admitted to the Hawler Cardiac Center or medical ward with heart failure with reduced ejection fraction for the period from December 2021 till 30th of October 2022. The clinical characteristics, severity of left ventricular systolic dysfunction and the outcomes over three months were compared between women and men. Results: One hundred seventeen patients were included in the study, 61 (52.1%) patients were male and 56 (47.9%) were female with male to female ration (1.09:1), p-value (0.017). Women presented with higher incidence of moderate left ventricular systolic dysfunction 36(64.2%), obesity 43 (76.8%) p-value=0.017*, dyslipidemia 27 (48.2%) p-value=0.038, pulmonary hypertension 4 (7.1%), atrial fibrillation 15(26.8%) and high cardiac hospitalization 12 (21.4%), while men have high incidence severe left ventricular systolic dysfunction 33(54.1% ) p-value=0.046, smoking 42 (68.9%); p-value &lt;0.001 and ST-segment elevation myocardial infarction 28 (45.9%) p-value &lt;0.001. the p-values off all above findings are less than &lt;0.05 respectively Conclusions: There are major differences in risk factors, clinical presentation and outcomes between both genders. The majority of women presented with moderate left ventricular systolic dysfunction and higher rate of cardiac hospitalization while men presented with severe left systolic dysfunction associated with high incidence of ST-elevation myocardial infarction.