bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic profiling in new on-set non-ischemic dilated cardiomyopathy
Authors: Chen X , Kang Y U , Yang Z X , Zhang Q
Published: October 2024

Background

Dilated cardiomyopathy is known as the most common cardiomyopathy with no therapy directly targeted the pathogenesis. The metabolic is a promising tool for better understanding of the difference in metabolites between health and disease and offering therapeutic targets, but the understanding of the specific metabolic processes distinguishing new on-set DCM from normal individuals remains insufficient.

Aim

To investigate the targeted blood metabolic profiling distinctions between new on-set Dilated Cardiomyopathy (DCM) and normal group.

Methods

We analyzed 231 plasma metabolites by liquid chromatography ⁄ mass spectroscopy and gas chromatography ⁄ mass spectroscopy in 48 patients with new on-set DCM(the duration of DCM diagnosis was less than 6 month before enrollment) and 48 age-, sex- and body mass index-matched normal controls.

Results

Twenty-four metabolites were significantly different between DCM and control individuals when adjusted by sex, age and smoking [false discovery rate (FDR) < 0.05]. Plasma levels of guanidinoacetate, hypoxanthin were reduced while levels of 6-methyladenosine, 1-methyladenosine and others were increased in patients with DCM when compared to controls (figure 1), while Taurine, L-kynurenine and Methylmalonate were the most significant metabolites between the two groups (figure 2) .

Conclusions

Metabolic processes were strongly enhanced in DCM and may be used to distinguish new on-set DCM from normal individuals. And it identififies biologically active metabolites that could serve as markers of New-onset DCM and impart protective or harmful effects on cardiac structure and function.
Differences in clinical features of patients with heart failure and reduced, mildly reduced, and preserved ejection fraction in a contemporary cohort: is the clinical profile changing?
Authors: Anguita Gamez M , Gonzalez Manzanares R , Bonilla Palomas J L , Recio Mayoral A , Cequier Fillat A , Muniz Garcia J , Rodriguez Padial L , Romero Rodriguez N , Elola Somoza F J , Anguita Sanchez M
Published: October 2024

Introduction

Heart failure is a serious health problem and continues to have a high mortality and incidence of decompensations, despite advances in its management. The type of HF, defined by the LVEF value, has a great influence on treatment, since not all drugs and procedures have been shown to improve prognosis in the different subtypes of HF (reduced-HFrEF, mildly reduced-HFmrEF, and preserved-HFpEF). In addition, there are differences in clinical characteristics and comorbidities that may also influence these aspects, although the demographic and social changes that have occurred in recent years may have changed this perspective.

Purpose

To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical and demographic characteristics and comorbidities among the three subtypes of HF.

Methods

We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to the type of HF.

Results

Of the 1716 patients, 55.5% were HFrEF, 11.9% HFmrEF and 32.6% HFpEF. Figure 1 shows the main demographic and cardiovascular characteristics of the three subgroups. The median LVEFs were 30% (23-35), 45% (42-48) and 58% (53-65), respectively. Figure 2 shows the prevalence of major comorbidities. Patients with HFpEF were older and female in higher proportion, and presented a significantly higher prevalence of atrial fibrillation, valvular heart disease, obesity, hypertension, and anemia. Patients with HFrEF had a higher prevalence of coronary artery disease, smoking, admissions for HF in the previous year, and left bundle branch block. There were no differences between the three groups in the remaining comorbidities, including chronic kidney disease and chronic respiratory diseases. The characteristics of HFmrEF were intermediate between HFrEF and HFpEF (figures 1 and 2).

Conclusions

In our contemporary cohort of real-life HF patients, slight differences were observed between the 3 types of HF, particularly in relation to age, proportion of women, and prevalence of cardiac diseases. However, the prevalence of most of the major comorbidities did not show significant differences between the 3 groups, suggesting that a shift toward greater similarity in clinical characteristics between the 3 types of HF may be occurring.
Non-linear causal effects of kidney function on the risk of heart failure: a Mendelian randomization study
Authors: Liu J , Huang H , Lu X , He Y , Chen S , Wu W , Liang G , Zhou Y , Chen J , Tang N , Liu Y
Published: October 2024

Background

Kidney insufficiency is defined as the early stage of heart failure, but Mendelian randomization (MR) analyses based on several large heart failure cohorts suggest no linear causal effect between kidney function and heart failure (HF), inconsistent with observational studies evidence. However, whether there is a non-linear causal relationship between kidney function and HF has not been reported.

Methods and Results

Observational and non-linear MR analyses were performed using individual-level data from a UK Biobank cohort of white British ancestry subjects (N = 386,304). There were non-linear observational associations of between kidney function as assessed with estimated glomerular filtration rate (eGFR) and HF (P for nonlinear <0.001). Non-linear MR analyses showed a U-shaped association between genetically predicted eGFR values (both creatinine- and cystatin C-based eGFR) and the risk of HF (Quadratic P value < 0.05) and the risk of HF increased with both reduced and supranormal eGFR levels (β1 = -1.70E-05, P1-value = 0.004; β2 = 3.56E-06, P2-value = 0.004).

Conclusion

This study observed a non-linear U-shaped genetic relationship between eGFR and HF outcomes, indicating that both reduced and supranormal eGFR may be causally linked to a higher risk of HF.Central Illustration
Development and validation of a predicting model for risk of rehospitalization within 30 days in heart failure patients with preserved ejection fraction
Authors: Zhu Y L , Liu Z C , Huang H B , Wu M X , Zhang L L , Liao M , Zhao W J , He W F , Tan D , Zeng J P
Published: October 2024

Objective

This study aimed to develop and validate a predicting model for risk of rehospitalization within 30 days post discharge in patients diagnosed with Heart Failure with Preserved Ejection Fraction (HFpEF).

Methods

Clinical data of 9555 HFpEF patients registered in the heart failure registry from 2014 to 2022 at our hospital were analyzed. A total of 8160 patients (from 2014-2021) were designated as the training set, and 1395 patients (from 2022) as the validation set. A predictive model was established based on risk factors associated with 30-day rehospitalization due to heart failure identified by the Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression analysis. The model's stability was ensured through Bootstrap internal validation and Temporal validation external validation.

Results

LASSO and logistic regression analyses identified eight risk factors associated with increased risk of 30-day rehospitalization, including New York Heart Association (NYHA) classification, albumin, c-reactive protein, N-terminal pro b-type natriuretic peptide (NT-proBNP) divided by 100, anemia, pleural effusion, atrial fibrillation, and pulmonary hypertension. The established predictive model demonstrated good discriminative ability in the internal validation with an Area Under the Curve (AUC) value of 0.714, and a 95% confidence interval (CI) of 0.693-0.736 after 500 Bootstrap replicates. In the Temporal validation external validation, the model exhibited robust stability with an AUC value of 0.740 and a 95% CI of 0.693-0.781. When compared to analogous models from prior studies, present model showcased superior predictive accuracy in that both Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) values were positive and within their respective 95% confidence intervals (P-values <0.05).

Conclusion

This study successfully developed and validated a predictive model for 30-day rehospitalization due to heart failure in patients diagnosed with HFpEF. This model might allow the timely identification of high-risk HFpEF patients for 30-day rehospitalization due to heart failure and optimizes the patient management accordingly.
Phenotype of patients with severe aortic stenosis and small aortic annulus: how does it impact on hemodynamics and on transcatheter aortic valve implantation outcomes
Authors: Niro L , Danojevic S , De Raffele M , Ferrer-Sistach E , Teis A , Vilalta V , Fernandez-Nofrerias E , Carrillo-Suarez X , Bayes-Genis A , Delgado V
Published: October 2024

Background

Discordant grading of severe aortic stenosis can result from a tight aortic valve area (<1cm2) with a low transvalvular mean gradient (<40 mmHg). Small aortic annulus dimensions and low flow status may contribute to discordant grading of severe aortic stenosis. However, the frequency of patients with small aortic annulus and discordant grading, along with their characteristics and outcomes after intervention, remains unknown.

Purpose

To investigate the frequency of discordant grading severe aortic stenosis in patients with a small aortic annulus and to evaluate their clinical characteristics, as well as outcomes after transcatheter aortic valve implantation (TAVI).

Methods

Patients with an aortic annulus diameter < 23 mm determined by cardiac computed tomography who underwent TAVI between 2018 to 2023 were retrospectively evaluated. Patients were followed for the occurrence of the composite endpoint of of all-cause mortality, rehospitalizations for heart failure, non-fatal myocardial infarction, and non-fatal stroke.

Results

Among 230 patients with severe aortic stenosis and a small aortic annulus, 52 (23%) had discordant gradient (24 with low flow low gradient (LFLG) and 28 with normal flow low gradient (NFLG)) while 120 (52%) exhibited normal flow high gradient (NFHG) and 58 (25%) had low flow high gradient (LFHG). The majority of the patients were female (Table 1). Differences were noted among the three groups regarding aortic transvalvular gradients, stroke volume index and ejection fraction. During a median follow-up of 2 years, the composite endpoint occurred in 20% of the total cohort. Patients with discordant grading severe aortic stenosis experienced the worse outcome (Figure1).

Conclusions

Most patients with severe aortic stenosis and small annulus have high gradient and only 23% of patients presented discordant grading. Patients with discordant grading severe aortic stenosis showed worse outcomes, suggesting potential delays in referral due to challenges in diagnosing severe aortic stenosis among patients with small aortic annulus.Basal clinical characteristicsKaplan-Meier survival curves
Body fat or muscle underneath body mass index in heart failure patients: characteristics and prognostic values
Authors: Zhao Z , Kang Y , Chen X , Zhang X , Yang Z , Chen X , Zhang Q
Published: October 2024

Background

Body Mass Index (BMI) has been recognized as a prognosticator for heart failure (HF) in that higher BMI relates to lower mortality. However, limited data are available whether body composition underneath BMI would further differentiate patients with a better or worse outcome, especially in those with lower or normal BMI.

Purpose

To investigate the characteristics of body fat and body muscle in HF patient groups with different BMI, and their impact on prognosis.

Methods

Between July 2021 and July 2022, hospitalized HF patients who were suitable for the examination underwent body composition analysis by using bioelectrical analyses (BIA) in the stable state after decongestion therapy and before discharge. Percentage of body fat (PBF) and percentage of body muscle (PBM) were calculated by dividing the mass of body fat, or body muscle, respectively. Patients were divided into underweight (<18.5kg/m2), normal weight (20-24.9 kg/m2), overweight/obese (≥25kg/m2) based on BMI, who were followed for 180 days for all-cause death.

Results

127 consecutive patients with obtained data were finally enrolled (60±15 years, 70% males), including 20 (15.75%) underweight, 75 (59.06%) normal weight, and 32 (25.19%) overweight/obese. As shown in Table 1, As shown in Table 1, the body fat mass and muscle mass varied with BMI, though they showed a different rate of change. Compared with patients with normal weight, the fat and muscle mass in those overweight/obese was 81.8% and 12.4% higher; whereas it was 39.2%, and 23.1% lower in those underweight, respectively. As results, the overweight/obesity group had a higher PBF, but a lower percentage of PBM. Consequently, the overweight/obesity group had a higher PBF, a lower PBM and a decreased muscle mass/fat mass ratio (MFR); conversely, the underweight group had a lower PBF, a higher PBM and an increased MFR. During 180-day follow-up, 17 (13.4%) died for all cause. By Cox regression analysis, MFR independently predict all-cause death (HR, 1.273, 95% CI: 1.056-1.534, p=0.011) after adjusted for age, BMI, ejection fraction and NT-proBNP. Of note, in patients with normal weight, Receiver Operating Characteristic (ROC) curve analysis suggested the capability of MFR (AUC=0.780, p=0.003) as well as its superiority over BMI in association with all-cause mortality (Figure 1).

Conclusions

The change of body fat or muscle mass with BMI displayed a different rate in HF patients, so that the MFR was higher in underweight but lower in overweight/obese when compared to normal weight group. Apart from BMI, MFR emerged as a predictor of mortality, in particular in patients with normal weight.
Prognostic impact of systemic immune-inflammation index in patients with acute decompensated heart failure with preserved ejection fraction -PURSUIT-HFpEF Registry-
Authors: Kokubu Y , 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

Systemic inflammation has been implicated in the pathophysiology of heart failure with preserved ejection fraction. Several studies have shown that systemic immune-inflammation index (SII), a novel index based on platelets, neutrophils, and lymphocytes, predicts poor prognosis in patients with cardiovascular disease. However, it remains to be elucidated whether SII could have predictive value in patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF).

Purpose

This study is designed to investigate the association of SII at admission or discharge with poor clinical outcome in patients with ADHF-HFpEF.

Methods

Patients’ data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for ADHF-HFpEF in a city. Laboratory data and body weight measurements were performed just before discharge. We analyzed 966 patients (mean age: 81 years old, male: 45%) after exclusion of patients on dialysis, missing follow-up data, or missing data to calculate SII. SII was calculated as follows: SII = platelet count × neutrophil count / lymphocyte count on admission and at discharge. The primary endpoint was the composite of all-cause death and rehospitalization for worsening heart failure.

Results

During a mean follow-up period of 1.8±1.3 years, the primary endpoint was observed in 435 patients (259 patients died and 176 patients underwent rehospitalization for worsening heart failure). In multivariate Cox analysis, high SII at discharge (> 536×109 determined by receiver operating characteristic curve analysis (AUC: 0.564 [0.526-0.602]) was significantly independently associated with not only the primary endpoint (hazard ratio 1.28 [1.04-1.57], p=0.020) but also all-cause death ((hazard ratio 1.39 [1.06-1.81], p=0.018) after adjustment for major confounders such as age, gender, body mass index, NYHA class, systolic blood pressure, heart rate and laboratory data including NT-proBNP and CRP. However, high SII on admission was not significantly associated with primary endpoint after multivariate adjustment. Kaplan-Meier analysis revealed that patients with high SII at discharge had significantly greater risk of both the primary endpoint (56% vs 43%, p<0.001) and all-cause mortality than those with low SII (36% vs 24%, p<0.001).

Conclusion

Systemic immune-inflammation index at discharge, but not on admission, would be associated with post-discharge poor outcome in patients with acute decompensated heart failure with preserved ejection fraction.
The association between circulating B cell count and clinical outcomes in patients with heart failure
Authors: Kobayashi Y , Otaki Y , Watanabe T , Tachibana S , Sato J , Hashimoto N , Wanezaki M , Kutsuzawa D , Kato S , Tamura H , Nishiyama S , Takahashi H , Arimoto T , Watanabe M
Published: October 2024

Background

Despite advances in treatments, heart failure (HF) is still an growing health problem associated with a high mortality rate. In recent years, researchers have increasingly focused on the association between HF and the immune system. However, there have been only a few reports concerning the association between B cells and heart failure. The aim of the present study was to identify alterations in lymphocyte subset counts and examine whether lymphocyte subset counts are associated with clinical outcomes in patients with HF.

Methods and Results

We evaluated lymphocyte subset count, including CD3+ T cells, CD19+ B cells and CD56+ natural killer cells in consecutive 395 patients with HF. All patients were divided into three groups according to CD19+ B cell counts tertiles. First tertile group showed higher inflammation and higher prevalence of malnutrition compared to other groups. There were 79 all-cause deaths and 119 HF-related events during the median follow-up period of 374 days. We found that each lymphocyte subsets decreased with advancing New York Heart Association functional class. The receiver operating characteristics curve analysis demonstrated that the area under the curve of CD19+ B cell count for all-cause mortality was the greatest among lymphocyte subset counts. Kaplan-Meier analysis showed that patients with lowest tertile group had the highest rates of all-cause deaths and HF-related events than in other groups. Multivariate Cox proportional hazard regression analysis demonstrated that CD19+ B cell count was significantly associated with all-cause mortality and HF-related events after adjustment for confounding risk factors.

Conclusion

We for the first time demonstrated that the CD19+ B cell count was significantly associated with severity and clinical outcomes of HF.Kaplan-Meiyer curveforest plot
Comprehensive stress echocardiography uncovers the heterogenity of phenotypes in non-ischemic heart failure with abnormal ejection fraction
Authors: Kalakauskaite L , Karaliute G , Balkeviciene L , Celutkiene J , Ciampi Q , Cortigiani L , Wierzsbowka-Drabik K , Zagatina A , Djordjevic-Dikic A , Manganelli F , Boshchenko A , Borguezan-Daros C , Arbucci R , Pellikka P A , Picano E
Published: October 2024

Background

Heart failure (HF) with abnormal left ventricular (LV) ejection fraction (EF) manifests in multiple phenotypes, each presenting distinct and potentially actionable therapeutic targets. This study aimed to assess the potential of the ABCDE+ stress echocardiography (SE) protocol in uncovering different phenotypes of non-ischemic HF.

Methods

With a retrospective analysis of prospectively acquired data, we identified 265 patients (mean age: 65.7±12.6 years; 154 males, 59.9%) with non-ischemic HF with EF<50% (mean =41.4±7.5) enrolled by 23 certified laboratories between 2021 and 2023. Ischemic origin was excluded based on data of angiography and medical history. ABCDE-SE was evaluated with exercise (n=98, 37.0%), dobutamine (n=50, 18.9%), or vasodilators (n=117, 44.1%). The protocol consisted of several steps: A assessed regional wall motion abnormality (RWMA); B evaluated number of B-lines; C measured left ventricular contractile reserve; Step D with coronary flow velocity reserve (CFVR) in the left anterior descending artery (LAD) was completed in 102 patients (38.5%); step E assessed heart rate reserve. Additionally, step F (evaluated in 188 patients at rest and 107 at peak stress) noted the presence of rest or stress-induced moderate-to-severe secondary mitral regurgitation. The SE response was graded on a scale from 0 (all steps normal) to 5 (all ABCDE+ steps abnormal).

Results

The mean ABCDE score was 1.5±1.2, ranging from 0 (n=59, 22.3%) to 5 (n=2, 0.8%) (see distribution of scores in Figure 1A). Abnormal results were observed in 21 subjects (7.9%) for A, 86 (32.5 %) for B, 147 (55.5%) for C, 42/102 (41.2%) for D, and 101 (38.1%) for E steps. Step F was abnormal in 22/188 (11.8%) at rest and in 16/107 (14.9%) at peak stress. The predominant "solitary phenotypes" (only one step abnormal) were impaired LV contractile function phenotype (step C in 47, 51.1%) followed by chronotropic insufficiency (step E in 17, 18.5%) and congestive phenotype (step B in 17, 18.5%) (see Figure 1B). The most frequent combined phenotype was BCE – congestive phenotype with impaired ventricular and heart rate reserves (28 [62.2%]). Notably, 38 patients (14.3%) demonstrated improved regional contractility, while 27 patients (10.2%) showed new regional wall motion abnormality (see Table).

Conclusion

Non-ischemic HF patients with abnormal EF exhibit a broad spectrum of phenotypes. Impaired left ventricular contractility, interstitial congestion, and chronotropic insufficiency are the most frequent abnormalities detected by ABCDE-SE. Up to one-quarter of such patients demonstrate normal SE results. This comprehensive approach paves the way for personalized, SE-guided therapy.
Right ventricular pulmonary artery uncoupling independently associated with 5 year outcome following AHF hospitalisation
Authors: Berrill M , John I , Fluck D , Sharma P , Baltabaeva A
Published: October 2024

Background

Right ventricular pulmonary artery (RV-PA) uncoupling is associated with poor outcome across a range of conditions, but its role in acute heart failure (AHF) remains incompletely investigated.

Purpose

To investigate if RV-PA uncoupling is independently associated with mortality following hospitalisation for AHF.

Methods

418 patients were recruited. 391/418 (93.5%) had measurable TAPSE and SPAP and were followed up for 5 years to assess for all-cause mortality. Patients were recruited if they displayed signs and symptoms of AHF, had point-of-care brain-natriuretic peptide >100pg/ml and had evidence of HF on TTE. We identified a study-specific cut-off for TAPSE/SPAP of 0.24mm/mmHg on ROC analysis and performed univariate analysis to assess for an association with outcome. 30 covariates encompassing comorbidities, medications, echo parameters and observations were assessed and logistic regression analysis performed including variables associated with outcome.

Results

Patient average age at presentation was 79 years, 53.3% were male, 55.5% had hypertension, 30.7% had diabetes and 36.8% had CAD with a mean LVEF of 42.6% and BNP of 1363pg/ml. The mean TAPSE was 15.6mm and SPAP of 52.5mmHg. The average TAPSE/SPAP was 0.34mm/mmHg. 252/391 (64.5%) presented with TAPSE/SPAP <0.24mm/mmHg. These individuals were at higher risk of 5-year mortality compared to >0.24mm/mmHg: HR 1.94 (95% CI 1.49-2.54 [p<0.0001]), which persisted when adjusted for significant covariates – HR 1.35 (95% CI 1.02-1.80 [p<0.0395]).

Conclusion

TAPSE/SPAP ratio is an independent predictor of mortality in patients admitted with AHF. Our cut-off, a lower value than others have suggested in the literature for chronic conditions such as pulmonary hypertension, could identify those at risk of poor outcome in the acute setting. This may offer an exciting therapeutic target and help risk stratify patients. These results should focus the attention of those managing AHF patients onto the RV, pulmonary pressures and their interrelationship. It is time we moved beyond the LVEF.
Prognostic impact of secondary prevention medical therapy in patients with Takotsubo cardiomyopathy: a Bayesian network meta-analysis
Authors: Zaka A , Mutahar D , Gupta A , Kovoor J , Stretton B , Bacchi S , Mridha N
Published: October 2024

Background

Takotsubo cardiomyopathy (TTC) is a form of transient left ventricular systolic dysfunction without evidence of complicated coronary artery disease. Although initially considered a benign condition, recent studies have demonstrated a significant risk of acute phase complications and a mortality rate between 1-8%. Efficacy of medical therapy in secondary prevention of all-cause mortality and TTC recurrence is not well established. We performed a systematic review and network meta-analysis to evaluate prognostic impact of secondary prevention medical therapy in patients with TTC.

Methods

PubMed, MEDLINE, EMBASE, CENTRAL, and Web of Science were searched up to January 6, 2024. Eligible studies included multivariable-adjusted or propensity matched studies of patients receiving medical therapy with B-blockers (BB), renin–angiotensin–aldosterone system (RAAS) inhibitors, aspirin and statins after an index presentation with TTC. The primary outcome was all-cause mortality at any time point. Secondary outcome was TTC recurrence. Random-effect hierarchical Bayesian meta-analyses was performed.

Results

We identified 15 observational studies. TTC mortality was reported in 435 (4.4%) out of 9735 patients. Mean age was 70.2 ± 4 years and 8858 patients (91.5%) were females. There were no differences in all-cause mortality when comparing BB versus control (OR 0.83; 95% CI 0.47 to 1.47, p=0.52); BB versus RAAS inhibitors (OR 1.03; 95% CI 0.61-1.63), BB versus aspirin (OR 1.02; 95% CI 0.471-2.25) and BB versus statins (OR 0.871; 95% 0.432-1.75). No significant differences were also observed for TTC recurrence.

Conclusion

This network meta-analysis found no significant difference in all-cause mortality or recurrence rates in Takotsubo cardiomyopathy with the use of secondary prevention medical therapies, including beta-blockers, RAAS inhibitors, aspirin, and statins
Combination of diuretics to overcome diuretic resistance in acute heart failure: systematic review and updated network meta-analysis
Authors: Cunha I , Jairo Nunes J T N , Edimar Bocchi E A B
Published: October 2024

Background

Diuretic resistance in acute heart failure (AHF) presents a significant therapeutic challenge. While randomized clinical trials (RCTs) have compared various diuretics against furosemide, direct comparisons among these therapies are lacking. This network meta-analysis aims to fill this knowledge gap.

Purpose

To evaluate the efficacy and safety of various diuretic combination therapies in overcoming diuretic resistance in acute heart failure patients.

Methods

We conducted a systematic review and network meta-analysis of RCTs from January 2000 to December 2023. These RCTs included hospitalized AHF patients with evidence of diuretic resistance. We applied a frequentist random effects model to perform a network meta-analysis combining a total of 11 diuretic strategies compared with low-dose furosemide (reference group). Primary outcomes were urine output and weight loss at 72 hours. Secondary outcomes included cardiovascular mortality and heart failure hospitalization. The safety endpoint was the incidence of acute kidney injury across different diuretic strategies.

Results

Empagliflozin and high-dose furosemide showed the highest increase in urine output (SMDs: 363.94, P-score=0.64; and 306.31, P-score=0.68). For weight loss, hydrochlorothiazide led to the greatest losses (SMD: 1.33; P-score=0.20), followed by tolvaptan + furosemide low-dose (SMD: 0.85; P-score=0.43). Dapagliflozin ranked best for reducing heart failure hospitalizations (OR 0.15; P-score=0.94), and empagliflozin had the highest rank for mortality reduction (OR 0.31; P-score=0.91) but without statistical significance for mortality. Empagliflozin also showed a better safety profile (OR: 0.74; 95% CI: 0.32 to 1.71 P-score=0.87), (Figure 1 and 2).

Conclusion

Our findings indicate that SGLT2 inhibitors are a promising therapeutic avenue to mitigate the challenges of diuretic resistance in AHF, demonstrating potential benefits in enhancing urine output, reducing hospitalization rates, and maintaining favourable safety profile.Network and forest plots for U.O/ weightNetwork and forest plots for HHF/ AKI
Guideline-directed medical therapy titration for heart failure with ischaemic aetiology and its effect on cardiac remodelling and cardiovascular mortality-from a real world perspective
Authors: Bonini J , Zuin M , Vilei F , De Pietri M , Guidi Colombi G , Tezze R , Sarti A , Guardigli G , Fucili A
Published: October 2024

Background

Contemporary Heart Failure (HF) pharmacological treatment has been reshaped by several landmark trials in recent years, and available evidence strongly encourages treatment up-titration to target doses. Recent literature regarding treatment sequencing demonstrated positive effects of up-titration on major outcomes regardless of HF aetiology.

Purpose

We investigated a contemporary Heart Failure with Reduced Ejection Fraction (HFrEF) patient cohort and ischaemic aetiology and sought to understand the effects both in terms of echocardiographic remodelling and upon mortality for cardiovascular (CV) causes of contemporary ESC guideline-directed medical therapy (GDMT) on a real-world level.

Methods

We retrospectively analysed data of consecutive patients with HFrEF and ischaemic genesis followed in our tertiary HF clinic between January 2019 and January 2022. Eligible patients were stratified into two groups: patients treated or not with full doses of ESC GDMT [including angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i)].

Results

Overall, 203 patients (mean age 70.1±12.3 years, 165 males) were included into the analysis. Over a mean follow-up of 1223±221.2 days, 115 (56.6) patients achieved the full recommended doses of each drug. Patients with an unsuccessful up-titration had higher end-diastolic volume at transthoracic echocardiography (p for difference at first and second follow-up <0.001; figure 1, panel A), lower left ventricular ejection fraction (40.1±4.3% vs 44.3±7.8 and 38.7±4.9% vs 42.3±5.6% at the first and second follow-up, respectively) and higher CV mortality rates compared to those treated with the maximal doses (figure 1, panel B).

Conclusions

Up-titration of pharmacotherapy in our real-world cohort of patients with HFrEF and ischaemic aetiology demonstrated a positive effect both on pivotal echocardiographic parameters and on CV mortality. Our data suggest that timely identification and referral of patients with coronary artery disease who fail to achieve complete positive remodelling after an acute event (or during chronic disease course) for HF contemporary treatment implementation should be envisaged.Figure 1
A personalized, 3D printed, polymeric elastic support device for the prevention of post-MI cardiac remodeling
Authors: Nachman D , Alamore R , Aliev E , Shtraikh S , Horesh A , Rokach Y , Salman S , Abu-Rbo K , Mansour N , Ben Dori E , Cohn D , Amir O
Published: October 2024

Introduction

Myocardial remodeling and dilatation following myocardial infarction (MI) initiates a vicious cycle leading to heart failure (HF). The anatomy and pathophysiology of every patient is unique. We have developed a 3D printed, biopolymer based personalized Elastic Support Device, that is 3D printed based on patient’s imaging, aiming to restore cardiac physiology. This study aimed to assess the device on rat MI model.

Materials and Methods

MI was induced in 24 Sprague Dawley rats by permanently ligating the mid LAD artery via midline sternotomy cut. Twelve animals underwent immediate implantation of the elastic support device that was pre-printed from animal specific 3D echocardiography. The animals were followed up with echocardiography at days -2, 7, 14, 28. The animals were sacrificed at day 28, cardiac tissue and plasma were taken for further histological and biochemical analysis.

Results and discussion

Mortality was similar at both groups (5 vs 4 in the device and control groups respectively). Ejection fraction reduced in both groups from a baseline of 61.9±8.9% to 47.5±12.7%. Left Ventricular End Diastolic Diameter increased from baseline to day 28 in the control (7.0±0.56mm vs 7.7±1mm) but not the device group (6.87±0.2mm vs 6.93±1.1mm, p<0.05). Parameters of diastolic function such as E/E’ were similar in both groups throughout the follow-up. Mason’s Trichrome stained cardiac sections revealed improved infarct size at the device group (7.4±1.9% vs. 10.6±2.8%) and lower overall cardiac fibrosis.

Conclusion

In this preliminary small animal model study, the capability to 3D print and implant an imaging based, personalized, 3D printed elastic support device. The cardiac diastolic function was not impaired, and no safety issues were noticed. Furthermore, cardiac dilatation was prevented, and infarct size was reduced.Trial design and results
Endomyocardial biopsy in patients with myocarditis - still justified in the CMR era? A single-centre experience
Authors: Seuthe K , Pfister R , Pennig L , Mons U , Klingel K , Ten Freyhaus H
Published: October 2024

Background

Endomyocardial biopsy (EMB) is still considered the diagnostic gold standard for myocarditis. However, in the past decades, cardiac magnetic resonance (CMR) was established as a non-invasive tool supporting the diagnosis of myocarditis. Furthermore, there is often reluctance in performing EMB due to rare but potentially severe complications. We therefore sought to identify patient subgroups that could potentially derive benefits from EMB. This involved a comprehensive analysis of the diagnostic and therapeutic outcomes resulting from the procedure at our centre.

Methods

In this retrospective single-centre study, data of all patients presenting with (peri-) myocarditis between 01/2016 and 06/2023 at our tertiary care centre were included. Frequency of histological confirmation of acute myocarditis and histology leading to immunosuppressive therapy were analysed according to patient risks. Prespecified risk factors were (i) LV-EF ≤30%, (ii) presence of severe arrhythmias (VF, VT, high grade AV-block) or (iii) pre-existing autoimmune disease. Furthermore, the subgroup of recurrent myocarditis cases was analysed separately.

Results

A total of 150 consecutive patients (36.7 ± 15.5 years, 77.3% male) were included in this study. 26/150 patients had a documented EF ≤30%, 13/150 an EF >30% with another risk factor and 111/150 an EF>30% without another risk factor. EMB was performed in 21/26 patients with EF ≤30% (80.7%), in 7/13 patients with EF >30% and another risk factors (53.8%) and in 16/111 (14%) patients without risk factors. EMB led to the initiation of immunosuppressive therapy in 11/28 patients with risk factors (39.3%) and in none of the patients without risk factors (0/16, 0%, p=0.003)(figure 1). With respect to the subgroup of patients presenting with recurrent myocarditis (n=10), no specific therapy was performed.

Conclusion

Due to a high therapeutic yield for initiation of immunosuppressive therapy in non-infectious myocarditis, performing EMB should be considered in all high-risk patients. In patients without clinical risk factors including cases of recurrent or relapsing myocarditis no specific therapy was initiated.
Rationale and study design of the international randomized control trial MYocarditis THerapy with Steroids: the MYTHS trial
Authors: Ammirati E , Conti N , Frea S , Uribarri A , Grosu A , Loffredo F , Corsi D , Tomasoni D , Cappelli F , Marini M , Garascia A , Van De Heyning C M , Crespo-Leiro M , Adler E D , Potena L
Published: October 2024

Background

Immunosuppression is generally suggested in patients with specific subtypes of acute myocarditis, such as eosinophilic myocarditis or giant cell myocarditis or associated with systemic autoimmune disorders. In contrast, no specific treatment for most acute myocarditis complicated by acute heart failure (HF) or cardiogenic shock is recommended beyond the management of acute HF and supportive therapy. Nevertheless, large registries commonly reported using corticosteroids in severe forms without data supporting this strategy.

Purpose

To assess the safety and efficacy of high-dose pulse intravenous (IV) corticosteroid therapy to treat patients with complicated/fulminant acute myocarditis based on clinical suspicion.

Methods

An international pragmatic investigator-initiated single-blinded randomized controlled trial that screens patients between 18 and 70 years admitted to the hospital for suspected acute myocarditis (cardiac symptoms onset within three weeks) complicated by acute HF/cardiogenic shock and left ventricular (LV) ejection fraction<41% without significant LV dilation is ongoing. Patients are randomized in a 1:1 ratio to pulsed IV methylprednisolone (1 g) in saline solution (250 mL) daily for three days or placebo (saline without methylprednisolone) on top of standard therapy and maximal supportive care. A final diagnosis of myocarditis is confirmed by histology or cardiac magnetic resonance imaging. A population of 288 patients has been planned to assess a reduction in the probability of reaching the primary endpoint from 25% in the placebo arm to 12% in the methylprednisolone arm with a power of 0.80 (Figure). The main analysis will be conducted on an intention-to-treat basis.

Results

The primary efficacy endpoint of the trial is defined as the time from randomization to the first event occurring within 6 months, including all-cause death, heart transplantation, or long-term LV assist device implant, or need for an upgrading of the temporary mechanical circulatory support (t-MCS), or ventricular tachycardia (VT)/fibrillation (VF) treated with direct current (DC) shock, or first rehospitalization due to HF or VT/VF, or advanced atrioventricular block. The safety endpoints include a composite of potential complications that can occur, including serious infections, acute gastrointestinal bleeding, and other complications that can be related to corticosteroid therapy or prolonged stay on t-MCS. There are 32 active centers, and 48 patients have been randomized since December 2021. The trial is expected to be completed by the end of 2028.

Conclusion

The results of the MYTHS trial can define the role of IV methylprednisolone in the initial treatment of patients with complicated forms of acute myocarditis that currently have an unacceptably high mortality rate.
Identifying prognostic factors in patients with cardiogenic shock undergoing VA-ECMO treatment: insights from ECLS-SHOCK using machine learning
Authors: Kresoja K P , Zweymer U , Akin I , Rassaf T , Mahabadi A A , Lehmann R , Eitel I , Graf T , Schuster A , Skurk C , Lurz P , Schneider S , Desch S , Freund A , Thiele H
Published: October 2024

Background/Introduction

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been shown to reduce short-term mortality in patients with acute myocardial infarction complicated by cardiogenic shock. However, whether some patients might benefit from VA-ECMO remains to be cleared.

Purpose

To identify the impact of VA-ECMO therapy on outcomes by leveraging the potential of machine learning.

Methods

The ECLS-SHOCK trial is a randomized controlled trial where patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early VA-ECMO plus usual medical treatment or usual medical treatment alone. The primary outcome was death from any cause at 30 days. Extreme gradient boosting (XGBoost) was used to develop a model for the prediction of 30-day all-cause mortality and to assess the influence of VA-ECMO on outcomes.

Results

Overall, 209 patients were randomized to the VA-ECMO and 208 to control. Baseline characteristics between groups were well balanced (median age 63 years, 81% male, 67% presenting with ST-segment elevation myocardial infarction).

At 30-days 100 patients in the VA-ECMO and 102 in the control group were dead. The final XGBoost model contained 27 variables and the 10 most influential variables are shown in Fig. 1. On derivation the model predicted mortality with an AUC of 1.00 and on validation with an AUC of 0.80 (95% CI 0.71 to 0.89), with a sensitivity of 95% (95% CI 88% to 100%) and a specificity of 55% (40% to 69%), resulting in a positive predictive value of 65% and a negative predictive value of 92% at a Youden-derived cut-off. Importantly, neither the VA-ECMO therapy nor its complications were among the most influential factors of the model with a relative importance of 1.1% for VA-ECMO therapy and 0.25% for peripheral vascular complications and bleeding complications even being discarded by the model.

Conclusion

In patients with acute myocardial infarction complicated by cardiogenic shock the influence of VA-ECMO therapy on 30-day mortality, even when investigated with complex machine learning models, is negligibly low.
Levosimendan in patients with cardiogenic shock refractory to dobutamine weaning
Authors: Zeitouni M , Dorvillius E , Sulman D , Procopi N , Beaupre F , Devos P , Barthelemy O , Rouanet S , Ferrante A , Chommeloux J , Hekimian G , Kerneis M , Silvain J , Montalescot G
Published: October 2024

Background

The role of Levosimendan in managing cardiogenic shock remains the subject of debate.

Objective

This study examines the use and effects of Levosimendan when combined with dobutamine in patient’s refractory to dobutamine weaning.

Methods

This retrospective study included patients with cardiogenic shock admitted between January 1st, 2010, and October 31st, 2022. After initial dobutamine weaning failure, we compared patients who were treated with dobutamine alone versus those for whom Levosimendan was added in top of dobutamine. The primary outcome was successful inotrope withdrawal, defined as survival without catecholamine support, transplant, or definitive ventricular assist device at 30 days. Secondary outcomes included all-cause mortality at 30 and 90 days. Data analysis used inverse probability weighting according to propensity score.

Results

Among 349 patients with cardiogenic shock and failure to withdraw dobutamine, Levosimendan was used on top of dobutamine in 114 patients, and another try of dobutamine alone was made in 235 patients. At 30 days, successful inotrope withdrawal occurred in 46 (43.4%) patients with Levosimendan and dobutamine versus 24 (10.5%) patients of the dobutamine only group (weighted OR 4.99 [2.65 - 9.38]; p<0.001), with similar results at 90 days (weighted OR 6.16 [3.22-11.78]; p<0.001). Levosimendan + dobutamine was associated with lower 30-day mortality (weighted OR 0.47 [0.26-0.84]; p=0.01), with no difference at 90 days (weighted OR= 0.67 [0.39-1.14]; p=0.14).

Conclusion

Adding Levosimendan to dobutamine may improve inotrope withdrawal success and reduce 30-day mortality in patients with initial weaning failure, especially in those without project of cardiac assistance or transplant.
Comparing outcomes in cardiogenic shock patients with ischemic versus nonischemic cardiomyopathy: A nationwide retrospective observational study
Authors: Gupta S , Thakkar A , Carter K , Choi J , Saravia S , Mahmood K
Published: October 2024

Introduction

Ischemic and non-ischemic cardiomyopathy are common causes of heart failure. In our study, we compare the in-hospital outcomes between these two groups of patients with cardiogenic shock.

Methods

Data was obtained from the Nationwide Inpatient Sample database between January 2016 to December 2020. The study included all adult patients who were in cardiogenic shock and either ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM). The primary outcome was inpatient mortality. Secondary outcomes were cardiac arrest, arrhythmias, acute respiratory failure, and acute renal failure, as well as the need for ventilators, dialysis, and ECMO.

Results

Among 168,591 adult patients who had cardiogenic shock during their hospitalization, 72,538 patients had either ischemic cardiomyopathy or nonischemic cardiomyopathy. Among them, 31,854 (43.9%) had ischemic cardiomyopathy (ICM) vs 40,684 (56.1%) who had nonischemic cardiomyopathy (NICM). Patients with NICM had higher in-patient mortality (24.6% vs 26.1, aOR: 1.12; 95% CI: 1.08-1.16, p<0.001); when adjusted for age, sex, race, and Charlson comorbidity index. Furthermore, patients with NICM also had a higher risk of respiratory failure (54.1% vs 53.8%, aOR:1.11, 95% CI: 1.07-1.14, p<0.001) and required more life-saving treatments like pressors (1.6% vs 0.7%, aOR: 1.14; 95% CI: 1.10-1.20, p< 0.001) and dialysis (12.7.1% vs 11.3%, aOR:1.20, 95% CI: 1.14-1.26, p<0.001).

However, these patients with NICM had a lower risk of cardiac arrest (7.2% vs 7.8%, aOR: 0.88; 95% CI: 0.84-0.94, p< 0.001) and ventricular arrhythmias (29.5% vs 32.2%, aOR: 0.82; 95% CI: 0.80-0.86, p<0.001) as well as lower ECMO utilization (2.5 vs 2.1, aOR:0.82; 95% CI: 0.73-0.92, p <0.001) and blood transfusions (9.8% vs 11.7%, aOR:0.839; 95% CI: 0.80-0.88, p< 0.001). There was no significant difference in the ventilator use between the 2 groups (40.3% vs 39.7%, aOR:1.01, 95% CI: 0.97-1.04, p=0.714).

Conclusion

The findings of this study underscore the higher in-patient mortality among patients with non-ischemic cardiomyopathy (NICM) presenting with cardiogenic shock. These results emphasize the need for tailored treatment approaches targeting NICM-CS, warranting dedicated diagnostic and therapeutic strategies to improve prognosis in this vulnerable patient subset.Odd's ratios for NICM-CS vs ICM-CS