bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogen microvascular dysfunction is associated with worse outcomes in heart transplantation
Authors: Abadie B , Besir B , Bhat P , Jacob M , Starling R , Ziada K , Tang W H , Jaber W
Published: October 2024

Background

Cardiac allograft vasculopathy (CAV) affects the health of both epicardial and microvascular blood vessels in heart transplants. Coronary microvascular dysfunction (CMD) has been associated with poor outcomes in the non-transplant population. Two patterns of microvascular dysfunction have been characterized, classical (low stress flow) and endogen (high rest flow). Whether these patterns of microvascular dysfunction are associated with outcomes in the transplant population has not been thoroughly evaluated.

Purpose

The purpose of the study was to assess the relationship between microvascular dysfunction and adverse outcomes in patients with heart transplants.

Methods

Patients with no history of angiographic CAV who underwent positron emission tomography myocardial perfusion imaging and were found to have normal perfusion (summed stress score = 0) were included in the study. Patients were then classified by microvascular dysfunction: normal (flow reserve ≥ 2.0) versus abnormal (flow reserve <2.0). Patients were further subclassified based on pattern of microvascular dysfunction, classical (stress myocardial flow <1.7 mL/min/g) and endogen (stress myocardial flow ≥1.7 mL/min/g). The two primary outcomes were all-cause mortality and a composite of death, heart failure hospitalization, acute coronary syndrome, and revascularization. Kaplan-Meier survival and Cox proportional regression were used to assess the relationship between microvascular function and outcomes.

Results

In total, 359 patients were enrolled in the study, of which 29 (8%) had classical CMD and 78 (22%) had endogen CMD. Patients with endogen CMD were more likely to be women (46%) compared to 31% for normal microvascular function and 24% for classical CMD. During a median follow up period of 2.0 years (Q1 1.7, Q3 2.3), 36 patients had an adverse event and 19 patients died. Endogen CMD was associated with a significantly higher risk of both the composite outcome, HR 2.30 (1.15 – 4.61), and all-cause mortality, 4.19 (1.64 – 10.73). Classical CMD was not associated with either the composite outcome, HR 0.88 (0.20 – 3.84) or death, HR 1.02 (0.12 – 8.33), however assessment of classical CMD was limited by small sample size.

Conclusions

Endogen-type CMD is associated with worse intermediate-term outcomes in transplant patients compared to normal microvascular function and classical-type CMD, although comparison to classical-type CMD was limited by small sample size.Table 1:DemographicsFigure 1:KM Survival Curves
Diagnosis of hypertrophic cardiomyopathy by artificial intelligence using standard transthoracic echocardiography
Authors: Karra N , Klempfner Y , Fiman M , Am-Shalom A , Arad M , Klempfner R , Schwammenthal E , Raanani E , Maor E
Published: October 2024

Introduction

Misdiagnosis of hypertrophic cardiomyopathy (HCM) is not uncommon among patients with left ventricular hypertrophy (LVH).

Purpose

We hypothesized that a convolutional neural network (CNN) could be trained to identify HCM patients among individuals with LVH using standard transthoracic echocardiography (TTE).

Methods

Echocardiographic reports of 121,767 unique patients linked to clinical data from the largest tertiary medical centre in the country (2007-2022) were reviewed. Patients with no septal hypertrophy were excluded. All HCM cases were retrieved from electronic medical records and were adjudicated by the authors. Data was then divided into 3 mutually exclusive cohorts: training (N=7,368), testing (N=2,456) and validation (2,456) cohorts. Deep learning models were used in order to train a model that identifies HCM patients. The model was based solely on parasternal long axis and apical four chamber views.

Results

Final study population included 12,281 patients who underwent a total of 27,242 echocardiography studies. There were 1535 (12%) patients with HCM. Mean age of study population was 72±14 and 7,943 (65%) were men. Overall, the model obtained 98.1% classification accuracy with an area under the curve of 0.851 in the independent test data (FIGURE) which could translate to sensitivity and specificity of 68% and 99%, respectively with positive and negative predictive values of 50% and 99%, respectively.

Conclusions

Applying artificial intelligence to the standard TTE can identify HCM patients with a reasonable accuracy. With further evaluation, this tool can be used to assist in HCM diagnosis.
Changes in echocardiographic and analytical parameters after iron replacement in stable heart failure patients. FER-STRAIN study
Authors: Benavent Garcia C , Romero Valero A , Garcia Suarez A , Del Rio Lopez M , Lledo Ortiz C , Izquierdo Hernandez A , Vicente Ibarra N , Moreno Martinez M , Garcia Honrubia A , Tamayo Obregon A , Castilla Cabanes E , Gomez Martinez M , Tormo Juarez P , Santos Martinez S , Morillas Blasco P
Published: October 2024

Background

Iron deficiency replacement with intravenous ferric carboxymaltose (FCM) has demonstrated to improve clinical and prognostic parameters in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Improvement of myocardial contractility is proposed as possible hypothesis and strain could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency.

Purpose

Evaluate the effect of iron deficiency replacement with FCM in the strain of both ventricles in patients with stable HFrEF.

Methods

We performed an observational, analytical, longitudinal and prospective study that included 73 patients with stable HFrEF who presented iron deficiency without anemia defined as serum ferritin <100 ug/L or between 100 and 300 ug/L if the transferrin saturation was <20%. They were randomized 2:1 to iron replacement with FCM or control group. A central core lab, blinded to the treatment/control groups performed 3D echocardiograms and strain analysis. Analytical parameters and biomarkers were determined basal and four weeks after the randomization.

Results

Mean age of the study population was 70 years old, 77% were male, 75% had high blood pressure, 70% dyslipidemia and 41% diabetes. Of the total, 51 patients were assigned to the replacement group and 22 patients to the control group. Mean left ventricular ejection fraction (LVEF) was 33%, without basal differences between both groups. Four weeks after the randomization, a significant improvement of LVEF of 2.47±2.32% (p=0.018) was observed in the replacement group, as well as in the left ventricle global longitudinal strain (LV-GLS) of -0.96±2.08% (p=0.006). In blood tests, a significant improvement of ferritin (130.9±111.98mg/L, p<0.000), hemoglobin (0.3±0.7g/dL, p=0.027) and medium corpuscular volume (1.7±2.16fL, p=0.005), and also an increase of the biomarker myeloperoxidase (40.16±138.36pmol/L, p=0.02) were detected in the treatment group. Nevertheless, these changes were not observed in the control group.

Conclusions

In patients with stable HFrEF replacement of iron deficiency with FCM is associated with an improvement of myocardial contractility, of LVEF measured by 3D and LV-GLS.Variation of parametersLV-GLS before and after FCM
Predictors of Right vEntricular Failure aftER LVAD implantation: PREFER LVAD study
Authors: Mandoli G E , Foli S , Pastore M C , Landra F , Ghionzoli N , Martini L , Bernazzali S , Maccherini M , Valente S , Cameli M
Published: October 2024

Introduction

The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed.

Purpose

To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation.

Materials and Methods

We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome.

Results

The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure.

Conclusions

A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.
Cancer survivorship - heart failure risk factor or potentiator?
Authors: Wong J , Huynh Q , Soh C , Smith J , Marwick T
Published: October 2024

Introduction

An emerging challenge in cancer survivorship is the increased incidence of heart failure (HF) in long term adult survivors. This has been attributed to shared risk factors found between cancer and HF, cancer treatment-related cardiac dysfunction (CTRCD) and cancer itself. However, determining the magnitude and interplay of these risks can refine the process of risk-stratifying which survivors are most vulnerable to the development of HF.

Objective

This study investigates the relationship between traditional HF risk factors and subclinical HF (Stage B/SBHF) in adult cancer survivors compared to non-cancer controls.

Methods

102 adult survivors ≥10 years post cardiotoxic cancer treatment were prospectively recruited. All participants were evaluated with clinical review and echocardiography for presence of SBHF. SBHF was defined as the presence of left ventricular hypertrophy, abnormal global longitudinal strain (GLS) or diastolic dysfunction. Participants were matched to non-cancer controls by traditional HF risk factors - hypertension (HTN), type-2 diabetes (T2DM), obesity and age. Participants were excluded if they were symptomatic, had a prior history of HF or moderate/severe valvular regurgitation.

Results

Approximately 50% of cancer survivors did not have any of the 3 main HF risk factors (HTN, T2DM, obesity). The mean ARIC-HF 4-year risk score in cancer survivors was 3.1% [1.8, 5.6]. When matched by HF risk factors (HTN, T2DM, obesity and age), there was no difference in SBHF prevalence and GLS between cancer survivors (38%, -18.7%) and non-cancer controls (43%, -18.7%, (SBHF p=0.53%, GLS p=0.92%). However, the association between HF risk factors and impaired GLS (<-16%) was stronger in cancer survivors compared to non-cancer controls (Table 1).

Conclusion

Our investigation indicates that cancer survivorship alone may not directly contribute to the development of SBHF. However, it appears to exert a synergistic influence when coupled with established risk factors such as HTN, T2DM or obesity, potentially exacerbating the progression of SBHF.Table 1:HF risk factors & abnormal GLS
Residual congestion in acute decompensated heart failure: A novel approach through microvascular imaging of renal circulation
Authors: Kayama K , Kikuchi S , Sugimoto T , Seo Y
Published: October 2024

Background

In patients admitted for acute decompensated heart failure (ADHF), residual congestion at discharge is associated with adverse clinical outcomes. Traditionally, the extent of congestion has been inferred from central venous pressure, but it has also been highlighted that this is insufficient for a comprehensive evaluation of residual congestion. On the other hand, renal congestion is an important finding of organ congestion, and Superb Microvascular Imaging (SMI), a technique that reveals minute flow details, is promising for assessing renal circulation. We hypothesized that in patients with ADHF, assessment of renal circulation using SMI may be superior to conventional methods in assessing residual congestion.

Methods

In this prospective study, we enrolled 45 consecutive patients admitted with ADHF. We performed comprehensive evaluations including blood tests, echocardiography, and renal ultrasonography using SMI. The vascular index (VI), as measured by SMI, was calculated as the percentage of blood flow signal area in the region of interest. Subsequently, we calculated the intra-renal perfusion index (IRPI), representing cyclic variation in VI, as (maximum VI - minimum VI) within one cardiac cycle, divided by the maximum VI (Figure). Brain Natriuretic Peptide (BNP) levels were utilized to evaluate the state of decongestion.

Results

At discharge, the mean IRPI was 0.61±0.04, while the median BNP levels were 204.9 pg/ml (interquartile range: 102.7, 428.2). Patients exhibiting elevated log BNP levels at discharge (>2.31, based on median value) displayed significantly higher IRPI values [0.61(0.49, 0.86) vs 0.53(0.35, 0.59), p=0.02] and were older (80.8±8.5 vs 70.3±14.9 years, p=0.010). However, no significant differences were observed regarding laboratory parameters including hematocrit and creatinine levels, as well as echocardiographic parameters such as ejection fraction, E/e' ratio, and estimated right atrial pressure (RAP). Moreover, at discharge, creatinine levels (p=0.56) and estimated RAP (p=0.06) exhibited no significant correlation with IRPI.

Conclusion

Renal circulation evaluated by SMI may serve as a useful indicator of the extent of residual congestion at discharge compared to blood tests and echocardiographic estimates of right atrial pressure in patients admitted for ADHF.
Current echocardiographic indices for right ventricular function are inadequate to predict patient outcomes in chronic tricuspid regurgitation
Authors: Lee K , Wright E , Liu S , Bourg C , Moreau K , Bonds K , Oger E , Donal E , Vannan M
Published: October 2024

Background/Introduction

The presence of chronic tricuspid regurgitation (TR) can lead to pseudo-normalization of right ventricular (RV) functional indices on transthoracic echocardiography (TTE). Thus, the current cutoffs for RV free wall strain (FWS), functional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) (1) are not optimal for the volume overload associated with TR (2).

Purpose

We aimed to evaluate the sensitivity and specificity of the current cutoffs for RV FWS (>-23%), FAC (<35%), and TAPSE (<17 mm) in predicting adverse patient outcomes in a multi-centric population with chronic TR. We also evaluated whether interventricular septal shape was correlated with patient outcomes and aimed to develop cutoffs for this novel index.

Methods

We studied 753 patients (mean age 70.3 ± 15.0 years, 42.5% male) with >mild, medically managed TR who presented to our centers between 2018 and 2023. We measured TR grade (3), RV size, RV FWS, FAC, TAPSE, and eccentricity index (EI) for each patient (Figure 1). We subsequently tracked time to cardiac-related hospitalization or death, whichever came first. Using receiver operating characteristics (ROC), we estimated the area-under-the-curve (AUC) for RV FWS, FAC, and TAPSE as well as systolic and diastolic EI in predicting adverse patient outcomes. We used the modified Youden index (4) to analyze the current cutoffs for RV FWS, FAC, and TAPSE and specify novel cutoffs for all indices (including systolic and diastolic EI).

Results

Over a mean follow-up of 52 ± 16 months, there were 282 hospitalizations and 146 deaths across the 753 patients. AUC values for RV FWS, FAC, and TAPSE in predicting adverse clinical outcomes were 0.54, 0.62, and 0.54, respectively (p < 0.05 each, Figure 2A). Systolic and diastolic EI had the highest AUC (0.86 each, p < 0.0001) and were equivalent to one another in predicting adverse outcomes (Z-score = 0.0471, p = 0.9624) (Figure 2B). Sensitivity and specificity for the current cutoffs for RV FWS, FAC, and TAPSE are shown in Figure 2C. Using maximized Youden indices, the proposed cutoffs for normal RV FWS, FAC, TAPSE, systolic EI, and diastolic EI in chronic TR were ≤-24%, ≥38%, ≥22 mm, <1.3, and <1.3, respectively, which are all notably higher than the currently cutoffs (Figure 2C).

Conclusions

Given the pseudo-normalization of RV FWS, FAC, and TAPSE in chronic TR, waiting to intervene until these values become "abnormal" (per the current cutoffs) may in fact be too late. Our data suggest that the new cutoffs are needed to identify compensated RV function in the setting of TR. Moreover, interventricular septal shape (assessed via EI) predicts adverse patient outcomes with greater accuracy than conventional indices and should perhaps be incorporated in clinical decision-making.Figure 1.Eccentricity MeasurementFigure 2.ROC Curves for RV Indices
An elevated mPAP over CO slope by exercise echocardiography predicts outcome in unexplained dyspnea
Authors: Falter M , Bekhuis Y , Hoedemakers S , Moura-Ferreira S , Coosemans S , L'hoyes W , Pauwels R , Milani M , Delpire B , Jasaityte R , Stassen J , Herbots L , Claessen G , Verwerft J
Published: October 2024

Background

Exercise pulmonary hypertension, defined by a slope of mean pulmonary artery pressure (mPAP) over cardiac output (CO) >3 mmHg/L/min, measured by invasive exercise hemodynamics, is associated with worse event-free survival in patients with unexplained dyspnea. Whether non-invasive techniques yield similar results has yet to be tested.

Purpose

To investigate the prognostic value of an mPAP/CO slope > 3 mmHg/L/min determined by exercise echocardiography in suspected heart failure with preserved ejection fraction (HFpEF).

Methods

This prospective cohort study included patients with unexplained dyspnea defined as dyspnea with an ejection fraction ≥50%. Patients with more than mild valvular heart disease, more than mild pulmonary disease, a history of heart failure, and myocardial or pericardial disease were excluded. A positive HFpEF score was defined as either an HFA-PEFF score of ≥5, including the diastolic stress test and exercise tricuspid regurgitation velocity, or a H2FPEF score of ≥6. The mPAP and CO were obtained by Doppler echocardiography. The primary outcome was the composite endpoint of unplanned cardiovascular hospitalisation (CVH) or all-cause mortality.

Results

Among the 1922 patients studied (median age 66 [56 to 74] years, 48% women), 39% (n=721) had exercise pulmonary hypertension. After a median follow-up of 14 (10-34) months; 57(3%) patients died and 235 (12%) had at least 1 unplanned CVH. A mPAP/CO slope >3 mmHg/L/min predicted death or unplanned CVH with an odds ratio of 1.51(1.11-2.07) when adjusted for age, sex and pulmonary pressures at rest (Figure 1). The mPAP/CO slope had incremental prognostic value irrespective of whether patients had a positive HFpEF score or not (increase in χ² from 19 to 29; p =0.002) (Figure 2).

Conclusion

Exercise pulmonary hypertension determined by exercise echocardiography is prognostically relevant as it predicts death and unplanned CVH in patients with unexplained dyspnea. These findings were independent of age, sex, pulmonary hypertension at rest and both the HFpEF scores with the diastolic stress test included.KM exPHTKM exPHT and HFpEF score
Anemia and 4 cavities myocardial strain in acute heart failure
Authors: Soulat-Dufour L , Djebnoune H , Lang S , Ederhy S , Adavane-Scheuble S , Chauvet-Droit M , Arnaud C , Lebos P , Fagnen P , David N , Jullien S , Gerard M , Boccara F , Cohen A
Published: October 2024

Background

Anemia is a frequent comorbidity in heart failure (HF) in elderly patients. Few data are available concerning the correlation between anemia and echocardiographic morphologic, functional and hemodynamic markers in acute HF.

Purpose

The aim of the study was to evaluate 4 cavities myocardial strain in elderly patients hospitalized with acute HF and to evaluate the influence of the presence of concomitant anemia.

Methods

One hundred and seven patients aged 70 years or older, hospitalized for acute HF were prospectively analyzed. Left ventricle longitudinal strain (LVGLS), left atrial (LA) reservoir, right atrial (RA) reservoir and right ventricle (RV) free wall strain were measured using speckle tracking transthoracic echocardiography (TTE) at admission. The population was divided into 2 groups, with (N = 47) or without (N = 60) of anemia.

Results

Mean age was 81.2 ± 6.6 years; 67 (62.6%) patients were men. Anemia was documented in 60 (56.1%) patients. Patients with anemia, compared to those without anemia, had more frequently history of hypertension, diabetes, renal insufficiency, and iron deficiency (Table 1). Patients with anemia, compared to those without anemia, had higher indexed cardiac output, LV ejection fraction and tricuspid annular plane systolic excursion, TAPSE (Table 1). Myocardial strain analysis found that patients with anemia, compared to those without anemia, had significantly higher LVGLS, LA and RA reservoir strain (Figure 1).

Conclusion

Anemia is common in elderly patients with decompensated HF. Patients suffering from both anemia and acute HF exhibited significantly higher myocardial strain (except free wall RV strain), suggesting a possible compensatory mechanism. Further investigations are necessary to understand the pathophysiologic links between HF, anemia and myocardial strain as well as their implications for prognosis.
Right ventricular to pulmonary artery coupling credicts poor outcomes after interatrial shunting in heart failure
Authors: Bakhshaliyev N , Kilicaslan B , Paitazoglou C , Bergmann M , Anker S D , Mahfoud F , Pfister R , Kilic T , Bartunek J , Ozdemir R
Published: October 2024

Background

Left atrial decompression is under investigation for heart failure (HF) with the potential to improve symptoms and potentially clinical outcomes. However, heterogeneous outcomes have been observed in randomized controlled studies.

Purpose

This study aimed to explore whether right ventricular (RV) -pulmonary artery (PA) coupling, as assessed from the tricuspid annular plane systolic excursion (TAPSE) /systolic PA pressure ratio, can be useful in predicting outcomes after implantation of the interatrial shunting device.

Methods

A total of 106 HF patients, n=62 with reduced ejection fraction (HFrEF), n=44 with preserved ejection fraction (HFpEF), were prospectively enrolled in the PRELIEVE registry with the Atrial Flow Regulator (AFR) implantation. Serious adverse events included cardiovascular mortality and HF worsening (W).

Results

Serious adverse events (SAEs) occurred in a total of 19 (18%) patients. There were no differences in baseline comorbidities, KCCQ scores, the 6-minute walking distance between patients with and without SAEs (Table). Patients with SAEs showed higher systolic pulmonary arterial pressure, NT-proBNP, serum creatinine and lower TAPSE/PASP ratio. Incidence of SAEs was higher in patients within the first TAPSE/PASP vs the third tertile (59% vs 12%, p=0.026), respectively. A TAPSE/PASP of <0.55 was identified to bear the most optimal sensitivity to predict the event (AUC=0.683, CI95% (0.533-0.833).

Conclusion

The reduced TAPSE/PASP ratio was associated with higher rates of serious adverse events in patients with heart failure undergoing controlled inter-atrial shunting. The hypothesis generating finding that reduced RV-PA coupling may identify potential clinical non-responders to left atrial decompression should be further prospectively validated.
Mortality based right ventricle functional echocardiographic cutoffs in patients with compared to without tricuspid regurgitation
Authors: Zornitzki L , Freund O , Frydman S , Rozenbaum Z , Granot Y , Banai S , Topilsky Y
Published: October 2024

Introduction

Tricuspid-annular-plane-systolic-excursion (TAPSE) and peak-lateral-tricuspid-annular-systolic-velocity (S’) are frequently used echocardiographic indices of right-ventricle (RV) function. Tricuspid regurgitation (TR) is present in 70-90% of the general population, and while trivial or mild TR may not have prognostic implications, several studies have demonstrated that ≥moderate TR is an independent predictor of adverse outcomes, and that increasing TR severity incurs an increased risk of mortality. The abnormality thresholds for TAPSE and S' are based on published mean and standard deviation data obtained from healthy adults, but not on outcome data. The effect of significant TR on the abnormality threshold of TAPSE and S’ prime is currently unknown.

Purpose

We aimed to re-examine the abnormality thresholds for TAPSE and S' based on their association with mortality in consecutive patients, stratified to with, or without, significant tricuspid regurgitation (TR).

Methods

We performed a retrospective analysis of consecutive patients undergoing echocardiography between 2011-2021 in a large tertiary center. TR was assessed using a semi-quantitative method. Cut-off values associated with excess mortality were assessed using spline curves in univariate, and multivariate Cox logistic regression analyses.

Results

A total of 24717 subjects were included in the current analysis with a median (interquartile range) follow up of 1321 (581-1902) days. 1143 (4.6%) subjects had clinically significant (≥moderate) TR. In the entire cohort, TAPSE<20.9 mm and S’ <10.9 cm/s were associated with excess mortality. In sub-group analysis, among subjects with significant TR, TAPSE<18.0 mm and S'<10.0 cm/s was the cutoff associated with excess mortality, while subjects without TR had a higher cutoff of TAPSE<21.5 mm and S'<10.9 cm/s. In a multivariate model adjusted for the presence of TR and baseline characteristics, TAPSE<20.9 mm (HR 1.20, 95% CI 1.14-1.27; p<0.001) and S’<10.9 cm/s (HR 1.07, 95% CI 1.01-1.13; p=0.015) were independent predictors for mortality. A sensitivity analysis, which included 14,664 patients with additional echocardiographic indices, demonstrated that low TAPSE remained an independent predictor of mortality (aOR=1.15; 95% CI: 1.07-1.24; p<0.001)

Conclusion

TAPSE and S’ thresholds associated with excess mortality are higher than those previously reported in healthy adults. The TAPSE and S' cutoffs associated with excess mortality were lower in patients with significant TR compared to patients without, suggesting that a personalized approach for their interpretation is needed.Central illustration
Effects of Sacubitril/Valsartan on all-cause hospitalizations in heart failure: participant-level pooled analysis of PARADIGM-HF and PARAGON-HF
Authors: Lu H , Claggett B L , Packer M , Lam C S P , Swedberg K , Rouleau J , Zile M R , Lefkowitz M , Desai A S , Jhund P , Mcmurray J J V , Solomon S D , Vaduganathan M
Published: October 2024

Background

Sacubitril/valsartan is indicated to reduce the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with chronic HF. However, many of these patients are older and have multiple comorbidities that increase the risk of hospitalizations other than HF, yet the effects of sacubitril/valsartan on hospitalizations of any cause have not been well described.

Methods

PARADIGM-HF and PARAGON-HF were phase-3, global multicenter randomized clinical trials that evaluated sacubitril/valsartan versus enalapril (in PARADIGM-HF) or valsartan (in PARAGON-HF) across the spectrum of left ventricular ejection fraction (LVEF; ≤40% in PARADIGM-HF and ≥45% in PARAGON-HF). We pooled individual participant-level data from these 2 trials to examine the effects of sacubitril/valsartan on time-to-first investigator-reported all-cause and cause-specific hospitalization using Cox proportional hazards models, stratified by geographic region and trial. We additionally examined heterogeneity in treatment response by LVEF.

Results

Over 2.8 years median follow-up, among 13,194 participants in the pooled PARADIGM-HF/PARAGON-HF, sacubitril/valsartan significantly reduced the risk of all-cause hospitalizations compared with renin-angiotensin system inhibitor (HR 0.92; 95% CI 0.88-0.97; P=0.002); Figure 1 Panel A. The absolute risk reduction (ARR) was 2.1 per 100 patient-years corresponding to a number-needed-to-treat (NNT) of 48 patient-years of treatment exposure to prevent 1 all-cause hospitalization. Reductions in overall hospitalizations among patients with identifiable causes (N=5,783) seemed to be primarily driven by lower rates of cardiac and pulmonary hospitalizations associated with sacubitril/valsartan. Patients treated with sacubitril/valsartan did not have a higher rate of composite non-cardiac hospitalizations (Figure 1 Panel B). Similarly, sacubitril/valsartan reduced the risk of the composite of all-cause hospitalization or all-cause mortality (HR 0.92; 95% CI 0.87-0.96; P<0.001), with an ARR of 2.5 per 100 patients-years and an NNT of 40 patient-years. For all-cause hospitalization, we observed significant heterogeneity by LVEF as a continuous measure (Pinteraction=0.027); treatment effects were most apparent in those with an LVEF below 60% (HR 0.91 95% CI 0.86-0.96; Figure 2).

Conclusions

In a pooled analysis of >13,000 patients with chronic HF, sacubitril/valsartan reduced hospitalization for any reason with benefits most apparent among those with an LVEF below normal.
The effects of SGLT2 inhibitors on right ventricle functions in heart failure patients: update meta-analysis of the current literature
Authors: Cinar T , Saylik F , Cicek V C , Pay L , Khachatryan A , Alejandro J , Erdem A , Hayiroglu M I
Published: October 2024

Background

There is some discrepancy in the present studies concerning the effect of sodium-glucose cotransporter type 2 (SGLT2) inhibitors on right ventricular (RV) functions in heart failure (HF) patients. The current meta-analysis was focused on determining the impact of SGLT2 inhibitors on RV functions in such individuals.

Methods

Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were utilized to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The Robin-I risk of bias algorithm was used to assess the bias risks of randomized studies.

Results

This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT-2 inhibitors had substantially lower systolic pulmonary artery pressure (sPAP) and higher TAPSE values (mean difference (MD) = 1.30 [0.78;1.82], p =0.002 and MD =-5.39 [-7.88; -2.89], p=0.003, respectively). There was no significant difference in RVS’ values between follow-up and baseline (MD=1.38 [-1.35;3.80], p=0.169). However, as compared to the baseline period, fractional area contraction (FAC) values were substantially larger at the end of the follow-up period (MD=5.40 [3.74;7.07], p=0.015).

Conclusion

To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2 inhibitors on RV function in HF patients. Our findings suggest that SGLT2 inhibitors may improve RV performance in HF patients.
Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF Stress Trial
Authors: Backhaus S J , Schulz A , Lange T , Schmidt-Schweda L S , Hellenkamp K , Evertz R , Kowallick J T , Kutty S , Hasenfus G , Schuster A
Published: October 2024

Background

With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests.

Methods

The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e’>8) who underwent simultaneous rest and exercise-stress echocardiography and RHC. HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15mmHg stress: ≥25mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e’). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH).

Results

The final study population included 68 patients (HFpEF n=34 and NCD n=34) of which 23 reached the clinical endpoint, 1 Patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p<0.001) compared to patients with a score ≤4. LA compliance at rest outperformed E/e’ (AUC 0.78 vs 0.87, p=0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p=0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p<0.001) irrespective of concomitant atrial fibrillation.

Conclusions

LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.
Disease-modifying treatments in transthyretin amyloid cardiomyopathy: a meta-analysis of randomized controlled trials
Authors: Tsai C H , Kao T W , Lin Y H
Published: October 2024

Background and Aims

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and life-threatening disease. With advancements in pharmacology, numerous novel medications are currently under investigation. However, the effects of these treatments on long-term outcomes remain elusive and inconclusive.

Methods

PubMed, MEDLINE, Embase, and the Cochrane Library were searched for literature inclusion until January 2024. Only phase 3, high-quality, randomized controlled trials related to ATTR-CM were considered for enrolment. Endpoints included all-cause mortality, six-minute walk distance, Kansas City Cardiomyopathy Questionnaire–Overall Summary Score, and serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels. A random-effects model was applied for meta-analysis.

Results

Three landmark trials (ATTR-ACT, APOLLO-B, ATTRibute-CM) comprising 866 patients with ATTR-CM were pooled. 66.6% of the subjects were administered with medical treatment. Consistent improvements in all-cause mortality (P=0.001), 6-minute walk distance (P=0.045), Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (P<0.001), and serum NTproBNP level (P=0.002) were present by medical treatment. At 12 months, only NT-proBNP showed significant improvement in the pooled analysis of the APOLLO-B and ATTRibute-CM results. At 30 months, the pooled analysis of ATTR-ACT and ATTRibute-CM demonstrated significantly better all-cause mortality and KCCQ scores in patients received mediation.

Conclusions

Disease-modifying Treatments is associated with better survival, functional capacity, quality of life, and NTproBNP level in patients with ATTR-CM. Extended follow-up duration might be needed to demonstrate efficacies.
Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)
Authors: Pastore M C , Stefanini A , Mandoli G E , Piu P , Iuliano M A , Diviggiano E E , Carli L , Marchese A , Pecere A , Martini L , Cavigli L , Focardi M A , D'ascenzi F , Valente S , Cameli M
Published: October 2024

Background

Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE).

Methods

This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints.

Results

Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT.

Conclusions

This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.
Effect of Dapagliflozin on health-related quality of life in patients with heart failure: a meta-analysis of Randomized Controlled Trials
Authors: De Souza M , Rodrigues Defante M L , Martins Prizao V , Consendey Martins O , Morais B , Ximenes Mendes B , Muniz J
Published: October 2024

Introduction

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces the risk of cardiovascular mortality and hospitalization for heart failure among individuals with chronic heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF). The effect of dapagliflozin on symptoms, physical capacity and quality of life is still unclear in this population.

Purpose

To investigate the effects of dapagliflozin on symptoms and health-related quality of life improvement in patients with chronic heart failure.

Methods

We systematically searched PubMed, Embase and Cochrane Central databases for randomized controlled trials (RCTs) comparing dapagliflozin to placebo in patients with chronic heart failure. We pooled mean differences (MD) and 95% confidence intervals (CI) with a random-effects model for continuous outcomes. Subgroup analyses were performed by reduced or preserved ejection fraction (EF). The outcomes analyzed were change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score and six-minute walk test (6MWT).

Results

Five RCTs with 6,238 patients were included. Of these, 5,410 (86.7%) presented a reduced EF and 2,724 (43.65%) had diabetes. There was a statistical significant improvement in total symptoms score (KCCQ-TSS) (MD=3.08; 95% CI 2.14-4.02; p<0.00001; I2=0%; Fig.1A) and in physical limitation score (KCCQ-PLS) (MD=3.91; 95% CI 1.66-6.17; p=0.0007; I2=0%; Fig1B) when dapagliflozin was compared to placebo. Subgroup analyses showed that the KCCQ-TSS score were significant higher in patients treated with dapagliflozin when compared to placebo in HFrEF (MD= 2.98; 95% CI 1.96-.99; p<0.00001; I2=0%; Fig1A) and HFpEF group (MD=3.73; 95% CI 1.16-6.30; p=0.004; I2=0%; Fig1A). The KCCQ-PLS score had a significant increase after dapagliflozin treatment when compared to placebo in participants with HFrEF (MD=4.36; 95% CI 0.72-8.00; p=0.02; I2=0%; Fig1B) and HFpEF (MD=3.64; 95% CI 0.76-6.51; p=0.01; I2=0%; Fig1B). There was no significant difference in 6MWT in dapagliflozin versus placebo group (MD=5.78; 95% CI -0.48-12.03; p=0.07; I2=0%; Fig.2).

Conclusions

Dapagliflozin improves health-related quality of life by reducing symptoms and physical limitation in patients with HFrEF and HFpEF.
Predictors of hypercontractile heart phenotype in patients with chronic coronary syndromes
Authors: Wang Y , Cerracchio E , Ciampi Q , Cortigiani L , Zagatina A , Kasprzak J D , Wierzbowska-Drabik K , Boshchenko A , Gaibazzi N , Djordjevic-Dikic A , Pitino A , Tripepi G L , Citro R , Pellikka P A , Picano E
Published: October 2024

Background

Hypercontractile phenotype of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS), but its clinical recognition remains elusive.

Purpose

To assess the clinical variables associated with the hypercontractile phenotype of the LV, identified with supernormal values of an index of LV contractility such as LV force, also known as ventricular elastance.

Methods

In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65± 11.1 years, 2974 males, 58%) with CCS referred for resting transthoracic echocardiography with technically successful volumetric echocardiography in 17 accredited laboratories. We measured systolic blood pressure (SBP) with a cuff sphygmomanometer. We assessed semi-quantitatively wall motion score index (WMSI), and quantitatively LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and cardiac output (CO = SV*heart rate).Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Odds ratios (ORs) with the corresponding 95% conﬁdence interval (CI) were estimated.

Results

For all the studied patients, EF was 59±11%. Force was 4.51±2.11 mmHg/ml, with reference sextile = 3.50-4.26 mmHg/ml, lowest sextile (Group 1) <2.60 mmHg/ml and highest sextile (Group 6) > 6.36 mmHg/ml. The correlation between the log of EF and the log of Force was significant with linear regression (r = 0.73, p < 0.001). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC (Table). By multivariable logistic regression model, the highest sextile of force was associated with age > 71 years (OR 4.35, 95% CI 3.06-6.18, p < 0.001), female sex (OR 4.48, 95% CI 3.62-5.54, p < 0.001), absence of beta-blocker therapy (OR 1.56, 95% CI 1.27-1.91), rest SBP> 159 mmHg (OR 6.86, 95% CI 5.03-9.35, p < 0.001), high heart rate (OR 1.03, 95% CI 1.02-1.04, p < 0.001), absence of prior MI (OR 1.31, 95% CI 1-1.72, p = 0.049), and higher LV EF at rest (OR 1.24, 95% CI 1.22-1.26, p < 0.001).

Conclusions

A hypercontractile phenotype of the LV with high force is associated with a small heart, reduced SV, and higher arterial elastance. It was clinically associated with advanced age, female sex, history of hypertension, absence of beta-blocker therapy, and high resting SBP.
Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial
Authors: Yu Y L , Gonzalez A , Hansen T W , Verdonschot J A J , Ahmed F , Petutschnigg J , Heymans S , Girerd N , Clark A L , Cleland J G , Zannad F , Diez J , Mischak H , Ferreira J P , Staessen J A
Published: October 2024

Background

Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) detects many sequenced peptides, for >70% derived from collagens.

Purpose

UPP and serum fibrosis markers were analysed together in patients at risk of HF with as objective to generate insights into the antifibrotic action of spironolactone.

Methods

In the open-label HOMAGE trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/d and followed for 9 months (n=290; 23.8% women; median age: 73 years). UPP was done by capillary electrophoresis coupled with mass spectrometry; 1498 urinary peptides with detectable signal in ≥30% of patients were analysed. Serum markers of COL1A1 synthesis (PICP and PICP/CITP) were measured. After rank normalisation of the biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted models. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher Z transform.

Results

Among all the urinary peptides, only the changes in collagen fragments remained significantly different (p<0.05) between randomisation groups after accounting for baseline levels, covariables and multiple testing. Compared to the control group, spironolactone reduced 16 of 27 collagen-derived urinary peptides. From baseline to 9 months, serum PICP and the PICP/CITP ratio decreased from 79.0 to 75.4 µg/L and from 21.3 to 18.3, respectively (p≤0.0129), reflecting decreased COL1A1 synthesis. Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and the serum fibrosis markers.

Conclusions

Spironolactone downregulated urinary collagen-derived peptides, probably by shrinking the body-wide pool of collagens. Spironolactone did not affect the interaction between urinary and serum fibrosis markers, suggesting that collagen scaffolding is maintained, thereby explaining why some urinary collagen fragments increased. Combining urinary and serum fibrosis biomarkers opens new avenues for discovery of antifibrotic drugs and refines insight in the action of antifibrotic drugs.Figure 1Figure 2