bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of Trimetazidine on the left ventricular global longitudinal strain assessed by cardiac magnetic resonance in stable angina patients with previous myocardial infarction and left ventricular
Authors: Rustamova Y , Imanov G , Azizov V
Published: October 2024

Introduction

Trimetazidine (TMZ) is an anti-ischemic metabolic agent that is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris (SA). Global left ventricular (LV) systolic function is an important predictor of outcomes in patients after myocardial infarction (MI). Cardiac magnetic resonance (CMR) imaging has now evolved into a major tool for the evaluation of patients with LV dysfunction, providing precise measurements of ejection fraction (EF) and viability assessment but also now allowing assessment of global longitudinal strain (GLS) from standard cine CMR images. We hypothesized that the use of TMZ 80 mg as an anti-ischemic agent in patients with SA, history of MI, reduced EF and in the presence of viable myocardium may produce an early modification of GLS.

Methods

TRIM-AZ - was a non-interventional, prospective Azerbaijan study to analyze the capacity of short-term therapy with TMZ 80 mg on LV GLS evaluated by CMR in patients with previous MI. Patients with a confirmed diagnosis of heart failure (HF) with impaired LV systolic function and SA in the presence of viable myocardium were included. The treatment of all patients was optimized according to the latest ESC guidelines before entry in the study. Patients were randomized into two groups, one received TMZ 80 mg on top of guidelines directed medical therapies, and the other was the control group. A CMR as well as a transthoracic echography were performed for all patients at the inclusion visit and 8 weeks later.

Results

52 patients were included in the study, 30 patients in the TMZ group and 22 in the control group,. At baseline, the mean age was 62±7 years , 63% were smokers, 60% hypertensive, 60% diabetics, 48% had a family history of MI, 12% had typical symptoms of SA while 88% had atypical form (e.g. like shortness of breath). All patients received baseline therapy with ARNI/ACE-i, SGLT2 inhibitors, beta-blockers, MRA, ASA, and statin. 8 weeks after the initiation of TMZ, there were no significant changes in LVEF assessed both by Echo and CMR (29,8%±3,2% vs 30,1%±3,5% by echo in TMZ group; 31,3%±2,7% vs 31,6%±2,7% by echo in the control group; 25,9%±3,1% vs 26,9±4,1% by CMR in TMZ group; 26,9%±2,1% vs 30,1%±2,3% by CMR in the control group), however GLS was significantly improved in TMZ group (-9,9%±1,1% to -12,7%±1,2%, p=0,00), but not in control group (-9,3%±1,3% vs -10,3%±1,4% p=0,3). No adverse event related to TMZ use was reported during the study.

Conclusion

These findings suggest that the use of trimetazidine in patients with stable angina , previous MI and heart failure in the presence of viable myocardium could improve the left ventricular global longitudinal strain assessed by CMR.
No improvement in atrial arrhythmia rates in patients on baroreflex activation therapy
Authors: Pham V , Gan A , Fong M
Published: October 2024

Background

Atrial arrhythmias encompass a wide range of abnormal cardiac rhythms including atrial fibrillation, atrial flutter, and atrial tachycardia. Patients with heart failure with reduced ejection fraction (HFrEF) have increased risk of atrial arrhythmias, ultimately leading to increased morbidity. Baroreflex Activation Therapy (BAT) employs an implantable device to increase parasympathetic nervous system activity by stimulating the carotid baroreceptors thereby reducing afterload and heart failure symptoms. In our prior study, BAT therapy has been shown to reduce hospitalization rates in patients with HFrEF. However, the effects of BAT on atrial arrhythmia has never been studied.

Objective

In this study, we analyzed the effects of BAT on atrial arrhythmia rates in patients with HFrEF.

Methods

Patients with HFrEF with BAT therapy for at least 12-months at a hospital were retrospectively studied. Inclusion criteria includes implantable cardioverter-defibrillator (ICD) placement of at least 12-months pre- and post-BAT therapy. Additionally, patients diagnosed with atrial arrhythmias prior to the study timeline were excluded. Atrial arrhythmia rates 6 and 12-months pre-BAT therapy and 6 and 12-months post-BAT therapy were compared. Atrial arrhythmia episodes were recorded through ICD interrogation every 1-3 months in the clinic. Of the 31 identified patients on BAT therapy, 11 patients fit the inclusion criteria. For the 11 patients in the study, 3 identified as female and 8 identified as male, 6 identified as white, 4 identified as Hispanic, and 1 identified as African-American with a mean age of 59.8 ± 17.4 years. The average left ventricular ejection fraction pre-BAT therapy was 23.8 ± 10.8%.

Results

The mean average atrial arrhythmia rates for 6-month pre-BAT therapy and 6-month post-BAT therapy were 0.12/month ± 0.40 and 1.32/month ± 2.76 respectively (p=0.18), suggesting no differences in atrial arrhythmia rates at 6-months with BAT therapy. The mean average atrial arrhythmia rates for 12-month pre-BAT therapy and 12-month post-BAT therapy were 0.11/month ± 0.35 and 2.40/month ± 5.84 respectively (p=0.22), suggesting no differences in atrial arrhythmia rates at 12-months with BAT therapy.

Conclusion

Although BAT therapy has been shown to decrease hospitalization rates, BAT therapy is not associated with decreased atrial arrhythmia rates at 6 months and 12 months.
Prospective longitudinal evaluation of AI-ECG in newly diagnosed heart failure (PLANE-HF)
Authors: Alrumayh A , Kelshiker M A , Mansell J , Almonte M , Rainer R , Zahra A , Kallis C , Auton A , Plymen C , Sau A , Quint J , Bachtiger P , Peters N S
Published: October 2024

Background

* In the United Kingdom, there are one million people suffering from heart failure (HF), with more than 60,000 new cases annually (1).

* Monitoring for declining left ventricular ejection fraction (LVEF) could optimise treatment approaches and avert healthcare episodes.

* Easy home-based tracking of cardiac function would be transformative.

* Previous studies have validated the capability of artificial intelligence-enabled electrocardiogram (AI-ECG) to correlated with changes in LVEF (2).

* We hypothesize that longitudinal changes in AI-ECG probability score is associated with changes in the left ventricular (LV) function.

Method

* A prospective multicentre longitudinal study recruiting newly diagnosed HF with reduced ejection fraction (HFrEF) cases to investigate application of AI-ECG using longitudinal single-lead ECG recordings via patient-administered smart ECG-stethoscope examination – Figure 1.

* A total of 36 patients were included in the analysis, with invitation to return for repeat echocardiography at 6-8 weeks.

* Adjusted logistic regression was performed to analyze changes in LVEF by 10% as the outcome variable, investigating the relationship with the trajectory of AI-ECG probability scores.

This study was approved by the UK Health Research Authority (reference 22/LO/0701).

Result

* Out of 36 patients, 19 patients had ischaemic and 17 had a non-ischaemic HF.

* The mean age was 56.3 years, 97.2% patients were male and 46.6% were White.

* 328 longitudinal single-lead ECGs were captured and used in the analysis.

* 12 (33.3%) patients had an increase of their LVEF by 10%; preceding AI-ECGs was predictive of this recovery (OR 1.36; 95% CI, 1.05 – 1.65, p value = 0.016 – Table 1)

Clinical Importance:

* Individualised predictions of deterioration and improvement

* Proactive medication adjustment

* Enhanced triage for echocardiography

Conclusion

* AI-ECG designed to identify left ventricular systolic dysfunction (LVSD) can predict changes in LVEF% among newly diagnosed HFrEF patients.

* Such results can place AI-ECG as a remote monitoring tool to track improvement or deterioration in patients’ LVEF%, which facilitate a proactive management and prevention strategies.
Presence of Atrial Fibrillation (AF) is a poor prognostic marker in patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Left Bundle Branch Block (LBBB)
Authors: Deshpande S , Masullo M , Petkar S
Published: October 2024

Background

Observational data indicate that between 20-30% of patients with HFrEF have LBBB. While numerous independent variables are implicated in the overall prognosis of these patients, this group of patients respond poorly to medical therapy. Presence of AF further impairs the functioning of the left ventricle by several mechanisms e.g., left atrial dilatation, decreased left ventricular filling, irregular cycle length, functional mitral regurgitation etc. Literature is sparse on the cumulative effect of AF in this group of patients.

Purpose

To assess the effect of AF on left ventricular ejection fraction (LVEF) and mortality in patients presenting with HFrEF and LBBB

Methods

Single centre, retrospective, observational study over 33 months (Jan 2021 – Sept 2023). Patients with HFrEF and LBBB (as defined by the European Society of Cardiology, 2021) identified from the heart failure database.

Results (Table)

N=80 Whole cohort: age 74.8 +/- 13.6 years (median:79, range 39-96); 57/80 (67.5%) males. Hypertension [41/80 (51.3%)] was most common comorbidity. Majority were on 3 drugs (23/80, 28.8%) of guideline directed medical therapy (GDMT) with ~1 in 4 patients [19/80 (23.8%)] on all 4 drugs. 32/80 (40.0%) were in AF, remainder in sinus rhythm (SR). Mean baseline LVEF: 21.8 +/- 8.4. Mean LVEF continued to be ≤35% (paired echocardiograms available in 50.0% patients) inspite of GDMT. The QRS duration continued to prolong on follow-up. Patients in AF were statistically significantly older, were less often on all 4 GDMT drugs (particularly sodium glucose transporter 2 inhibitors - SGLT2i’s), and were less likely to survive than those in SR. No difference in comorbid conditions or QRS prolongation on follow-up were seen between patients with AF versus SR. There was trend towards a larger increase in mean LVEF in patients with SR than AF.

Conclusions

In our experience, patients with HFrEF and LBBB continue to have a high mortality (45.0% at ~ 3 years) inspite of GDMT. AF is seen in a high percentage of patients (40.0%) in this cohort, worsening the prognosis further, with mortality nearly 3 times higher than those in SR. Aggressive management of patients with HFrEF and LBBB with, where indicated, early cardiac resynchronisation therapy (CRT) and more so, of those with AF (with +/- atrioventricular node ablation or left atrial ablation) should be considered at an early stage after diagnosis.Table
Prevalence and clinical significance of left ventricular thrombus discovered by pathological examination in explanted hearts of patients with end-stage cardiomyopathy
Authors: Puwanant S , Osotthanakorn T O , Bhumitrakul J B , Chantranuwat P C
Published: October 2024

Objective

We sought to determine the prevalence of anatomic LV thrombus detected by pathological examination of explanted hearts in patients with end-stage cardiomyopathy (CM) who have undergone heart transplantation, and to examine the relationship between anatomic LV thrombus missed by cardiac imaging and thromboembolic events.

Methods and results

A total of consecutive 148 explanted hearts from patients (44 years; 80% were men) undergoing heart transplantation were examined. The most common etiology of end-stage heart failure was dilated CM (53%). Of 148 explanted hearts, LV thrombus was present in 19 patients/hearts (13%). Excluding patients with ischemic CM (n=7), LV thrombus was present in 8 DCMs (9%), 1 genetic associated with LV noncompaction (100%), 2 hypertrophic CM (25%), and 1 arrhythmogenic CM (14%). None of patients with cardiac sarcoidosis (n=5) had LV thrombus. Of these patients, 11 (58%) received anticoagulants with favorable numbers of time in therapeutic range. No patient in the cohort had history of thromboembolic event before heart transplantation. Only 11 patients (26 %) with pathological evidence of LV thrombus had LV thrombus detected by previous echocardiograms (median time difference from echocardiogram to heart transplantation = 170 days). Six of 19 patients with anatomic LV thrombus had undergone cardiac MRI; LV thrombus had been detected in 2 patients (33%). The most common site of missed LV thrombus was LV cavity (where thrombi did not attach to any particular LV endocardial surface) followed by LV apex (Figure).

Conclusion

The prevalence of LV thrombus found by pathological examination in end-stage heart diseases was 13 % despite anticoagulation in most patients. However, the presence of these thrombi did not cause any serious thromboembolic events. Anatomic LV thrombi were missed by echocardiography/cardiac MRI in approximately 70% of patients. Genetic associated LV noncompaction and HCM were the most 2 prevalent CMs with anatomic thrombi, while none of patients with cardiac sarcoidosis had evidence of LV thrombus. Further study in thromboembolic milieu involving endocardial surface in specific type of CM may be needed.
Temporal trends and prognostic significance of heart failure after acute myocardial infarction
Authors: Sim D S , Ahn Y K , Kim H S , Rha S W , Cha K S , Park J S , Chae J K , Joo S J , Choi D J , Hur S H , Kim D I , Oh S K , Hwang J Y , Bae J H , Jeong M H
Published: October 2024

Background

There are limited and conflicting data regarding the incidence and prognostic impact of in-hospital heart failure (HF) complicating acute myocardial infarction (MI). The aim of this study was to examine temporal trends in the incidence and outcomes of systolic HF after acute MI in a large national cohort in South Korea.

Methods

The nationwide Korea Acute Myocardial Infarction Registry records baseline characteristics, treatments, and outcome of consecutive patients with acute MI admitted to hospitals capable of primary percutaneous coronary intervention (PCI) in South Korea. Systolic HF was defined as an ejection fraction ≤40% by echocardiography at admission. This study included 68,123 patients admitted for index acute MI between 2005 and 2020 (phase 1: 2005-2007, n=14,735; phase 2: 2008-2011, n=24,656; phase 3: 2012-2015, n=13,104; phase 4: 2016-2020, n=15,628).

Results

In all patients, the incidence of HF declined from 19.4% in phase 1 to 14.1% in phase 4 (p<0.001). This decrease was more pronounced in patients with ST-segment elevation MI (STEMI, from 20.9% to 15.8%) compared to those with non-ST-segment elevation MI (NSTEMI, from 17.9% to 12.3%). The use of PCI and of statins at discharge increased from 86% to 91.2% and from 75.1% to 92.2%, respectively (p<0.001 for all). Previous history of MI increased from 8.4% to 10.4% (p<0.001) whereas previous history of HF and stroke decreased from 6.3% to 1.3% and from 17.4% to 6.4%, respectively (p<0.001). The median symptom-to-door time decreased from 3.5 hours to 2.1 hours for STEMI and from 6.3 hours to 5.5 hours for NSTEMI (p<0.001). The median door-to-balloon time decreased from 107 min to 64 min for STEMI and from 26 hours to 14 hours for NSTEMI (p<0.001). The in-hospital and 12-month mortality rates for all patients decreased over the years from 5.0% to 3.3% and from 7.6% to 6.1%, respectively (p<0.001). However, in those who developed HF during the index MI, no significant declining trends were observed in in-hospital mortality (phase 1: 8.8%, phase 2: 7.95%, phase 3: 8.3%, phase 4: 7.3%, p=0.123) and 12-month mortality (phase 1: 15.4%, phase 2: 12.6%, phase 3: 19.4%, phase 4: 15.2%, p=0.270). Independent predictors of developing in-hospital HF were age >75 years, body mass index <18.5 kg/m2, symptom-to-door and door-to-balloon times, systolic blood pressure <100 mmHg at presentation, heart rate >90 min at presentation, presence of atrial fibrillation or diabetes, and previous history of MI, HF or stroke.

Conclusions

A marked reduction was found in the incidence of HF after acute MI between 2005 and 2020 in South Korea. However, in-hospital and 12-month mortality rates in HF patients remain unchanged, warranting intensive post-MI management with more aggressive efforts for secondary prevention.
Global myocardial work index is an independent predictor of functional capacity on 6-minute walk test in stable non-ischaemic cardiomyopathy
Authors: Chen H H L , Bhat A , Chen R , Fernandez F , Gan C H , Negishi K , Tan T C
Published: October 2024

Background

Reduction in 6-minute walk test distance (6MWD) in heart failure (HF) is associated with impaired quality of life and adverse cardiovascular outcomes. Myocardial work (MW) indices are novel non-invasive measures of left ventricular (LV) function which characterise myocardial contractile efficiency and energy utility.

Purpose

We aim to assess the predictive capacity of MW indices for functional capacity in stable non-ischaemic cardiomyopathy (NICM).

Methods

We prospectively recruited consecutive patients with stable NICM from our HF service from January 2021 to December 2023. All patients received optimal guideline direct therapy (OGDT) for 3-months before undergoing a comprehensive transthoracic echocardiogram and functional assessment with 6-minute walk test (6MWT). We excluded patients with prior cardiac surgery, severe airways disease, valvular heart disease, and those in atrial fibrillation (AF) or had mechanical limitations to their mobility at time of 6MWT. We collected demographic, clinical, and echocardiographic factors to identify the determinates of reduced 6MWD defined as <300 metres.

Results

Of 249-patients included (69.9% male; age 57.3±16.5yrs), 65-patients had reduced 6MWD. They were significantly older (62.3±17.2 vs 55.5±16.0yrs, p=0.005), had shorter height (166.3±10.3 vs 171.3±9.8cm, p=0.001), higher prevalence of AF history (39.1 vs 21.4%, p=0.001), lower LV-ejection-fraction (38.1±13.3 vs 43.3±10.2%, p=0.001), lower LV-global-longitudinal-strain (LV-GLS; 10.5±4.4 vs 12.7±3.9%, p<0.001), lower global-work-index (GWI; 943±487 vs 1230±455mmHg%, p<0.001), lower global-constructive-work (GCW; 1286±561 vs 1590±494mmHg%, p<0.001), lower global-work-efficiency (GE; 81.2±9.9 vs 85.4±8.1mmHg%, p=0.04), larger indexed left atrial volume (LAV; 45.0±18.4 vs 40.1±24.5ml/m2, p=0.038), higher E/e’ ratio (14.6±8.9 vs 11.8±6.0, p=0.003), and lower right-ventricular-free-wall-strain (RV-FWS; 19.2±6.7 vs 21.8±6.4, p=0.008; Table 1.). On receiver-operating-characteristics-curve analysis, GWI best predicted 6MWD reduction (Figure 1; AUC 0.68) compared to GCW, GE, LVEF and LVGLS (AUC: 0.62, 0.40, 0.62, and 0.62 respectively). Accounting for covariates, our multiple regression was run to predict 6MWD from age, height, AF history, LAV, E/e’, GWI and RV-FWS. These variables statistically significantly predicted 6MWD, F(4,239)=23.5, p<0.001, R2=0.34). With each 100mmHg% rise in GWI being independently associated with a 6.5m increase in 6MWD.

Conclusion

GWI was independently associated with 6MWD in our cohort of NICM patients on OGDT. MW indices provide some mechanistic insights into exercise capacity in patients with NICM.Table 1.Baseline CharacteristicsFigure 1.ROC of GWI Discriminating 6MWD
Up-titration of Guideline Directed Medical Therapy (GDMT) and the occurrence of side effects in Heart Failure with reduced Ejection Fraction (HFrEF)
Authors: Panagiotides N , Weidenhammer A , Arfsten H , Prausmueller S , Spinka G , Bartko P , Goliasch G , Huelsmann M , Pavo N
Published: October 2024

Background

The ESC Guidelines recommend early, full-dose use of heart failure (HF) medications to enhance survival, but real-world application often faces delays and inconsistencies. Clinicians often fear side effects during up-titration to the recommended target dose (TD), i.e. hypotension, bradycardia, renal impairment, and hyperkalemia (HK). The dependency of side effects during dose escalation from the severity of HF remains unclear.

Purpose

This study aimed to evaluate the relationship between the occurrence of side effects during up-titration of HF medication and HF severity reflected by N-terminal pro B-type natriuretic peptide (NT-proBNP).

Methods

425 patients with HFrEF and a complete data set of patient characteristics, medications and laboratory values at baseline (BL), 2 months (2M), and 6 months (6M) were included from our outpatient HF unit's prospective registry. Significant side effects were defined as: systolic blood pressure (SBP) <90mmHg, heart rate (HR) <50 beats per minute (bpm), potassium (K) >5.0mmol/l or K >5,5mmol/l and estimated glomerular filtration rate (eGFR) <30ml/min/1.73m2. Patients were categorized into three risk groups based on their NT-proBNP levels, i.e. low-risk with NT-proBNP <1000pg/ml, medium-risk with NT-proBNP 1000-2000pg/ml or high-risk with NT-proBNP >2000pg/ml. The occurrence of side effects was recorded and the development compared among the HF risk groups.

Results

Figure 1 shows up-titration of HF medication. Mean daily dosages of betablockers (BB), mineralocorticoid receptor antagonists (MRA) and renin-angiotensin-system inhibitors (RASi) increased significantly during follow-up (BL vs 2M and BL vs 6M, p<0.001 for all). The majority of patients received ≥50% of the recommended TDs at 6M (89% for BB, 83% for MRA, 88% for RASi and 91% for total mean TDs ≥50%), and the achieved daily dosages at 6M were largely comparable across the HF risk groups at 6M, except for RASi (p=0.030).

Figure 2 depicts the side effects. Side effects developed almost exclusively at short-term within 2M except for lower SBP (Figure 2A). Newly developed side effects occurring after up-titration (2B) were even more rare and predominantly occurred within the highest NT-proBNP group. The occurrence of hypotension and bradycardia was infrequent and comparable within the HF risk groups. Renal dysfunction (at 6M p=0,041) and HK occurred predominantly in higher risk patients (HK at 2M p=0,001 and at 6M p<0,001).

Conclusions

Up-titration of HF medications is highly feasible, particularly in low- and medium-risk patients. Despite rare side effects such as hyperkalemia and renal impairment, up-titration remains unimpeded, especially in patients with NT-proBNP levels below 2000pg/ml. These findings emphasize the safety of up-titration in HF.
Prognostic role of right ventricular-pulmonary artery coupling assessed by TAPSE/PASP ratio in patients with heart failure and mildly reduced ejection fraction
Authors: Ono M , Suzuki A , Yoshida A , Minami Y , Kikuchi N , Hattori H , Shiga T , Ashihara K , Yamaguchi J
Published: October 2024

Background

The development of right ventricular (RV)-pulmonary arterial (PA) coupling has resulted in a novel and comprehensive index for evaluating RV function in relation to the underlying RV afterload. In patients with heart failure (HF), it is acknowledged that RV-PA uncoupling are features that are associated with poor outcome. The RV-PA coupling index can be readily assessed non-invasively using the ratio of two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). However, few studies have defined the prognostic impact of the TAPSE/PASP ratio in patients with HF and mildly reduced EF (HFmrEF).

Methods

From the prospective cohort study of 1,410 hospitalized HF patients (age 68+/-15, men 62%) between August 2015 and September 2019, this study enrolled 191 HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41–49%) patients whose TAPSE and PASP were measured during hospitalization and discharged alive. We studied the prognostic impact of TAPSE/PASP ratio on HFmrEF patients using by cut-off value obtained from receiver operating characteristic (ROC) analysis. The primary and secondary endpoints was defined as the all-cause death and HF re-hospitalization after discharge, respectively.

Results

During median follow-up of 38 [23–52] months, 48 patients (25%) died. The deceased patients had a significantly older (median 75 vs. 71 years, p<0.05), higher rate of ischemic heart disease (50% vs. 23%, p<0.05), elevated brain natriuretic peptide levels (325 vs. 159 pg/ml, p<0.05) and lower rate of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (65% vs. 80%, p<0.05) at discharge. In the ROC analysis, the cut-off value of TAPSE/PASP ratio for mortality was 0.46. Patients with TAPSE/PASP ≤0.46 had a significantly higher all-cause mortality (log-rank p<0.05) and had a tendency of higher rate of HF re-hospitalization than patients with TAPSE/PASP >0.46 (log-rank p=0.06) (Figure). Using multivariate analysis, the lower TAPSE/PASP ratio had an independent predictive value of prognosis in patients with HFmrEF (hazard ratio 2.16, 95% confidence interval; 1.08–3.92, p<0.05) (Table).

Conclusion

The TAPSE/PASP ratio has a significant prognostic value in patients with HFmrEF. The RV-PA uncoupling assessed by TAPSE/PASP ratio might be useful for risk assessment in patients with HFmrEF.
Impact of various iron deficiency definitions on mortality risk in chronic heart failure across the spectrum of left ventricular ejection fraction spectrum
Authors: Mohamed A , Daniel Moelager Christensen D M C , Milan Mohammad M M , Christian Torp-Pedersen C T P , Lars Koeber L K , Emil Loldrup Fosboel E L F , Tor Biering-Soerensen T B S , Morten Lock M L , Mariam Elmegaard Malik M E M , Nina Nouhravesh N N , Charlotte Anderrson C A , Morten Schou M S , Gunnar Gislason G G
Published: October 2024

Introduction

Iron deficiency (ID) is prevalent in chronic heart failure (HF) but lacks a consensus definition.

Purpose

This study evaluates the prevalence of ID and its association with all-cause mortality and first hospitalization for HF, using current European Society of Cardiology (ESC) guidelines, transferrin saturation (TSAT) <20%, ferritin <100 ng/ml, and serum iron ≤13 μmol/L as ID criteria.

Methods and Results

Of 8587 new-onset HF patients registered in the Danish Heart Failure Registry from April 2003 to July 2021, we found varying ID prevalence (35.4% to 67%) based on different definitions. In heart failure with reduced ejection fraction (HFrEF) patients, irrespective of anemia, ID defined by TSAT <20% and serum iron ≤13 μmol/L was associated with all-cause mortality (non-anemic, HR: 1.42, 95% CI:1.22-1.64 and HR: 1.25, 95% CI: 1.1-1.43; anemic, HR: 1.22, 95% CI: 1.1-1.35 and HR: 1.26, 95% CI: 1.12-1.41, respectively) and first HF hospitalization (non-anemic, HR:1.41, 95% CI:1.23-1.62, HR: 1.33, 95% CI: 1.18-1.51; anemic, HR:1.27, 95% CI:1.12-1.45 and HR: 1.26, 95% CI:1.09-1.45, respectively). ID per ESC guidelines was only associated to mortality in non-anemic HFrEF (HR: 1.24, 95% CI:1.09-1.42) and first HF hospitalization in HFrEF, irrespective of anemia (non- anemic, HR:1.24, 95% CI:1.09-1.42; anemic, HR:1.35, 95% CI:1.2-1.52). No association was observed between the various definitions and outcomes in patients with heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction.

Conclusion

ID, when defined by TSAT <20% or serum iron ≤13 μmol/L, is associated with increased mortality and first hospitalization in HFrEF patients, regardless of anemia. Conversely, ID as per ESC guidelines is associated with mortality in non-anemic HFrEF patients and first hospitalization in HFrEF, irrespective of anemia status.Figure 1:Forest plot mortalityFigure 2:Forest plot hospitalization
Obesity paradox exists in super elderly patients with heart failure
Authors: Tachibana T , Kubota Y , Nishino T , Kato K , Iwade Y , Hayashi D , Watanabe Y , Matsuda J , Miyachi H , Tara S , Tokita Y , Iwasaki Y , Asai K
Published: October 2024

Background

Aging and obesity are two global concerns in public health. As obesity is associated with several metabolic disorders, it is a well-known risk factor of heart failure (HF). However, several studies have suggested that obesity may have paradoxical survival benefits in patients with HF. Therefore, the aim of this study was to investigate whether the obesity paradox exists in super elderly patients with HF in Japan.

Methods

A total of 4,292 patients from our hospital HF registry were divided into four age subgroups: (A) less than 65, (B) elderly 65-74, (C) high elderly 75-84, (D) super elderly ≥85. The primary endpoint was the all-cause death within 1-year after discharge.

Results

At baseline, the proportion of men in each group was 42-76%, the mean left ventricular ejection fraction was 49-61%, the average of N-terminal pro-B-type natriuretic peptide was 1972-2944 pg/ml, and the mean body mass index (BMI) ranged 21-25 kg/m2. Patients with higher BMI were more common in the younger age group, while those with lower BMI were more common in the older age group. Cubic spline curves of Cox proportional hazard regression models demonstrated an inverse relationship between BMI and mortality (Fig. 1). Lower BMI was associated with higher all-cause mortality in all ages, although this association was attenuated at the young age, and pre-obesity (25–29.9 kg/m2) was associated with the greatest survival benefit. Meanwhile, the impact of underweight (<18.5 kg/m2) was stronger super elderly subjects, a one-unit increase in BMI was associated with a 10.3% decrease in the hazard ratio of death (P=0.021). Kaplan-Meier curves for all-cause mortality also showed that lower BMI was associated with higher all-cause mortality in all groups, and the differences were statistically significant in Groups B, C, and D (Fig. 2).

Conclusion

Our study suggested the existence of the obesity paradox among HF patients in super elderly. Mildly overweight may be beneficial at old age with HF.
Clinical outcomes of patients with heart failure with improved ejection fraction after acute MI: a multicenter prospective study from the COREA-AMI Registry
Authors: Seung J , Kim J J , Kim Y R , Hwang B Y , Chang K Y
Published: October 2024

Background

The 2021 Universal Definition of Heart Failure introduce a new classification, heart failure with improved ejection fraction (HFimpEF). As yet, little is known about the long-term clinical outcomes of patients with HFimpEF after acute myocardial infarction (AMI).

Methods

From a multicenter, prospective cohort of AMI patients undergoing PCI, patients with an initial echocardiogram at the time of PCI and at least one follow-up echocardiogram one month to two years after the initial event were considered for analysis. HFimpEF was defined as initial left ventricular ejection fraction (LVEF)≤40% and at least one follow-up LVEF>40% with an increase of ≥10% from baseline. Persistent HFrEF was defined as LVEF ≤40% without interval improvement. Patients with LVEF>40% were defined as having preserved LVEF. The primary endpoint was all-cause mortality.

Results

In total, 3038 patients with repeated echocardiogram measurements were selected for initial analysis. 187 patients were identified as having HFimpEF, 190 patients had persistent HFrEF, 631 patients had HFmrEF, and 2030 patients had preserved EF. Kaplan-Meier analysis revealed that HFimpEF was associated with improved survival compared to chronic HFrEF, but inferior to preserved LVEF (log-rank p<0.001). Even after multivariate Cox regression analysis was done to account for confounding variables, HFimpEF was associated with reduced mortality compared to persistent HFrEF (HR 0.49, 95% CI 0.31-0.78). Compared to patients with preserved LVEF, HFimpEF patients had a tendency toward higher mortality, but did not reach statistical significance (HR 1.18, 95% CI 0.80-1.76).

Conclusion

HFimpEF is associated with decreased all-cause mortality compared to persistent HFrEF in patients with AMI.
Multiple comorbidities are associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not moderate-severe frailty -PURSUIT-HFpEF Registry-
Authors: Kondo T , Watanabe T , Yamada T , Seo M , Yano M , Hayashi T , Nakagawa A , Nakagawa Y , Yasumura Y , Sotomi Y , Okada K , Hikoso S , Nakatani D , Fukunami M , Sakata Y
Published: October 2024

Background

A variety of comorbidities are frequently observed and represent a major problem in the management of patients with heart failure. Frailty is a strong predictor of poor clinical outcome in patients with heart failure, which may be partially attributable to the presence of multiple comorbidities. However, it remains to be clarified whether frailty is prognostically useful in relation to multiple comorbidities in patients with acute decompensated heart failure and preserved ejection fraction (ADHF-HFpEF).

Purpose

The purpose of this study is to investigate the relationship between frailty, multiple comorbidities and prognosis in patients with ADHF-HFpEF.

Methods

We prospectively studied 1028 patients with ADHF-HFpEF. Frailty was assessed using Clinical Frailty Scale (CFS). Multiple comorbidities were defined as the presence of 4 or more factors from the following 11 groups: diabetes, obesity, lung disease, anemia, renal dysfunction, electrolyte disorder, dyslipidemia, depression, hypertension, stroke and cancer. The primary outcome of this study was the composite endpoint of all-cause mortality and rehospitalization for worsening heart failure.

Results

During a mean follow-up period of 1.6±1.3 years, 454 patients underwent primary outcome. CFS (p<0.001) and the number of comorbidities (p=0.006) were significantly independently associated with primary outcome after multivariate adjustment. Kaplan-Meier analysis revealed that patients with multiple comorbidities had significantly higher risk for primary outcome than those without multiple comorbidities in the group with non-frailty (defined as CFS of 1 or 2, p=0.019) and mild frailty (CFS of 3 or 4, p=0.036). However, there was no significant difference in the group with moderate or greater frailty (CFS of 5 or more) in patients with ADHF-HFpEF.

Conclusion(s)

Multiple comorbidities would be associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not in patients with moderate or greater frailty.Multiple comorbidities and MACE risk
Global and national insights into the decline of hypertrophic cardiomyopathy as a cause of sudden death in the young
Authors: Nelson D , Rowe S , Ha F , Lim H , Playford D , Strange G , Ellims A , Semsarian C , La Gerche A , Paratz E
Published: October 2024

Background & Objective

Hypertrophic cardiomyopathy (HCM) has been reported as a leading cause of sudden cardiac death (SCD) in the young but appears less common in contemporary cohorts of young SCD. This research aimed to determine if HCM is a common cause of SCD in the young and whether this has changed over time.

Methods

We analysed three national databases, the National Echo Database Australia (NEDA), Centre for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) and the National Coronial Information System of Australia (NCIS) to determine incidence of SCD due to HCM in ≤ 35 years old from 1999-2017. Sub-analyses assessed for differences in sex and obstructive and non-obstructive HCM phenotypes.

Results

NEDA: Of 40,738 individual echocardiograms 2005-2017, 868 (2.13%) exhibited the HCM phenotype. 982 patients died ≤ 35 years, of which 4 deaths were attributable to HCM (0.4%). CDC-WONDER: 41% reduction in HCM related mortality/million people across 1999-2016 (p<.0001). Similar reduction was seen when stratified for age, sex and non-obstructive/obstructive HCM phenotype. NCIS: 36% reduction in HCM-related SCD was observed between 2001-2010 and 2011-2016 periods (p=.049).

Conclusions

HCM rarely causes SCD and accounts for <5% of SCD in the young. Rates of HCM-related SCD have been decreasing over the last two decades. Improved survival likely relates to improved case detection and medical management.Abstract Figure
Masked hypotension in patients with heart failure
Authors: Li Z , Qiu Z E P I N G , Jin W E I
Published: October 2024

Background

Hypotension limits the up-titration of guideline-directed medical therapies (GDMTs) and correlates with poor prognosis in patients with heart failure. The value of ambulatory blood pressure monitoring (ABPM) in heart failure patients and its association with GDMTs optimization and clinical outcomes were undetermined.

Methods

REM-HF (Risk Evaluation and Management in Heart Failure) is a multicenter, prospective observational cohort. Our study screened patients from REM-HF who were hospitalized for incident HF and newly initiated GDMTs between April 2018 and December 2022. Eligible participants conducted a 24-hour ABPM before discharge and were followed-up as the cohort routine. GDMTs target dose achievement and dose trajectories were assessed at 3-month visit. The primary outcome was a composite of all-cause mortality and heart failure readmission.

Results

On adjusted restricted cubic spline analysis, office SBP demonstrated a U-shape relationship with the primary outcome (P for nonlinearity=0.003), while 24-hour SBP was linear (P for nonlinearity=0.338). The risk-related threshold of ambulatory and office systolic hypotension was defined as corresponding SBP < 120 mmHg accordingly. Combining these two measurements together, we described three blood pressure status as sustained hypotension (s-hypo, both SBP < 120 mmHg), masked hypotension (m-hypo, 24h SBP < 120 mmHg while office SBP ≥ 120mmHg), and non-hypotension (n-hypo). Among the 491 patients included, 124 (25.3%), 151 (30.8%) and 216 (44.0%) had s-hypo, m-hypo, and n-hypo, respectively. The m-hypo group showed similar clinical features as the s-hypo subjects, including more serious left ventricle remodeling and worse cardiac function. After the GDMTs dose titration, either patients with s-hypo or m-hypo were as unlikely to achieve target dose as the non-hypotensives (OR for s-hypo 0.42, 95%CI 0.19-0.95, P=0.038; OR for m-hypo 0.39, 95%CI 0.19-0.80, P=0.011). During a median follow-up of 693 days, the adjusted risk of primary outcome was higher in the s-hypo group and m-hypo group compared with the non-hypo group (HR for s-hypo 2.47, 95%CI 1.54-3.96, P<0.001; HR for m-hypo 1.68, 95%CI 1.06-2.65, P=0.027). No significant differences were found in target dose achievement and clinical outcomes between the s-hypo and m-hypo groups.

Conclusion

Masked systolic hypotension can occur in nearly one-third of new-onset HF patients. Patients with m-hypo and s-hypo exhibit similar clinical characteristics, both associated with GDMTs intolerance and adverse outcomes, suggesting m-hypo deserves recognition as a discrete entity. ABPM provides a more comprehensive view of patients’ blood pressure status by identifying this population.
Prevalence and outcomes of American Heart Association stages of heart failure in an adult brazilian population of the ELSA-Brasil study
Authors: Pianca E G , Heidemann Junior A , Santos A B S , Bittencourt M S , Ribeiro A L P , Lotufo P A , Duncan B B , Foppa M
Published: October 2024

Aims

Heart failure (HF) has a major impact on public health, affecting up to 2% of adult population. HF staging is helpful in capturing pre-clinical disease and its progression to advanced stages. We aimed to determine the prevalence and mortality of HF stages in the participants of a Brazilian adult cohort.

Methods

The ELSA-Brasil cohort comprises 15,105 adult public servants from 6 Brazilian capitals. In the initial evaluation of the study (2008-2010), ELSA carried out interviews and clinical, laboratory, and cardiovascular ancillary tests. In this analysis, we included participants who had electrocardiogram and echocardiogram performed at baseline visit, and additional information regarding risk factors and functional capacity.

The HF stages were defined based on AHA guidelines criteria as follow: Stage 0 was defined as a healthy individual with no risk factors for heart failure. Stage A (at risk for HF) included those without cardiac structural or functional abnormality but with any of the following conditions: systemic hypertension; diabetes mellitus, obesity, history of myocardial revascularization, history of rheumatic fever, and seropositivity for Chagas’ disease. Stage B (pre-HF) was defined as asymptomatic participants with history of myocardial infarction or any major abnormalities on ECG or echocardiogram. Stage C (symptomatic HF) included participants with a clinical history of HF, or HF symptoms in the presence of structural heart disease (defined as in Pre-HF stage). Considering the community-dwelling profile of the sample, we did not expect to have advanced heart failure patients in our sample.

Results

We included the 3,267 participants (61±9 years; 53% women) with baseline data. Prevalences of HF stages were stage 0: 938 (29%) A: 1,385 (42%), B: 651 (28%) and C: 293 (9%), with different distribution between sexes (p<0.001). Older participants had higher prevalences of stages B and C (p<0.001), with the prevalence of stage C increasing from 1.8% at 35-44 years to 12.2% at 65-74 years. After 12 years of follow-up, total mortality rates of HF stages were Stage 0: 4%; A:10%. B: 16%, and C: 26%, and respective Cox proportional hazard ratios [95% CI] adjusted for age and sex were A: 1.94 [1.3-2.8], B:2.78 [1.9-4.1], and C: 5.39 [3.6-8.1] compared to stage 0.

Conclusions

The prevalence of HF in Brazilians reflects what is described in international literature, with a large proportion of individuals in pre-symptomatic stages. A notable shift in the sample toward pre-symptomatic and symptomatic HF occurred gradually and persistently across the age span studied. Mortality rates increase incrementally across the HF stages. This information is important for understanding and planning health policies for this syndrome.
A U-shaped relationship between LVEF and the risk of heart failure hospitalization: a large hospital-based cohort study
Authors: Chang H C , Sung S H
Published: October 2024

Background

Left ventricular ejection fraction (LVEF) is a frequently used metric for quantifying left ventricular function. Previous studies found a U-shaped relationship between LVEF and long-term survival. However, the association between the spectrum of LVEF and heart failure (HF) hospitalization remains unclear.

Purpose

We aim to investigate the distribution of HF hospitalizations across the spectrum of LVEF using a large hospital-based cohort.

Methods

Consecutive participants who underwent echocardiography (2002-2021) in a tertiary medical center in Taiwan were included. LVEF was measured by echocardiography using biplane Simpson’s method and was categorized into intervals of 5% from <20% to ≥70%. The study outcome was HF hospitalization by linking to the National Health Insurance Registry Database. Cox proportional hazards regression was used for analyses with adjustment for age, sex, hypertension, diabetes, hyperlipidemia, coronary artery disease, and history of HF. We used restricted cubic splines to demonstrate the distribution of HF hospitalizations across the spectrum of LVEF.

Results

94,762 participants (age 59.7 ± 18.1, men 51.4%) were included. Adjusted hazard ratios (HR) for HF hospitalizations showed a U-shaped relationship between LVEF and the risk of incident HF hospitalization with a nadir of risk at LVEF of 60-70%. (Figure) Compared with the reference group (LVEF: 60-65%), subjects with LVEF> 70% had an HR of 1.49 (95% confidence interval [CI]: 1.21-1.84), and those with LVEF of 50-55% had an HR of 1.93 (95% CI: 1.68-2.22). Similar results with a nadir at 60-70% could be observed irrespective of different age groups defined by the World Health Organization (WHO), sex, with or without hypertension or diabetes.

Conclusions

A U-shaped relationship between LVEF and the risk of incident HF hospitalization can be observed, with a nadir at LVEF of 60-70%. LVEF ≥ 70% may be defined as supranormal LVEF that necessitates further HF treatment.Figure
Kidney status and events preceding death in heart failure: A real world data study on 18,456 patients with heart failure
Authors: Zahir D , Elmegaard M E , Garred C G , Jhund P , Petrie M , Mcmurray J , Kober L K , Schou M S
Published: October 2024

Background

Despite advancements in heart failure (HF) management, kidney dysfunction remains a significant clinical challenge, and is associated with higher mortality rates and other adverse outcomes. However, there are few studies of kidney events preceding death in patients with HF in the real world.

Methods

Using registry-based data, the prevalence of kidney events preceding death in patients with HF over the period 2014-2018 in Denmark. All deaths in patients with a diagnosis of HF within the previous 10 years were included. Kidney events occurring during within 1 year of death compromised of: acute kidney injury, chronic renal replacement therapy, sustained eGFR<15 mL/min/1.73 m2, or renal transplantation. The prevalence of kidney events preceding death was calculated and different subgroups were compared.

Results

Among the 18,586 HF patients who died, a total of 3107 (16.7%) experienced kidney events during within 1 year of death. The prevalence of HF patients with kidney events before death was 15.5% for acute kidney injury, 5.8% for chronic renal replacement therapy, 7.4% for an eGFR<15 mL/min/1.73 m2, and 0.18% for renal transplantation (see Figure 1). Acute kidney injury episodes were frequently observed in the last month before death (7.5%) (Figure 2). Age-specific analysis revealed a higher proportion of deaths associated with kidney dysfunction in patients under the age of 65 years compared to those aged 80 years and above (24.3% vs 13.4%). Furthermore, male sex, death in-hospital, reduced pre-existing kidney function, a higher degree of frailty, and lower educational status were associated with higher frequency of death associated with kidney dysfunction.

Conclusion

In this real-world study, a significant proportion of deaths among HF patients were associated with kidney dysfunction, particularly with acute kidney injury. Further research and awareness of renal complications are necessary to improve outcomes in this population.