Composite Endpoint Of All-cause Death Research Articles

Mini nutritional assessment is a predictor of mortality and morbidity in patients with pulmonary arterial hypertension

Abstract Background Malnutrition has been demonstrated as a predictor for unfavorable clinical outcomes in chronic heart failure, and may affect patients with pulmonary arterial hypertension (PAH). The Mini Nutritional Assessment (MNA) is a reliable indicator for nutritional status assessment, but its relationship with mortality risk and hospitalization in PAH patients has not yet been investigated. Purpose The study aimed to determine whether the MNA has prognostic value in stable patients with PAH. Methods A prospective multicenter study was performed. All patients completed the MNA at study entry in outpatient clinic or during planned hospitalization. The primary endpoint was all-cause mortality. Secondary end-point was the composite end-point of all cause death or PAH-related hospitalizations. Patients with malnutrition (MNA ≤17 points) or at risk of malnutrition (MNA 18-23,5 points) were considered as having abnormal nutritional status for statistical analysis. Results 182 PAH patients were included to the study (mean age 60 ± 17 years; 73% females; 57% idiopathic PAH). Abnormal nutritional status was identified in 68 (37%) patients. Median and the range of follow up period was 23 months and 0–32 months, respectively. 34 (18.7%) patients died, 53 (29.1%) were hospitalized due to PH, and 57 (31.3%) achieved the composite secondary end-point. Kaplan-Meier survival curves revealed significant differences in overall survival between patients with abnormal MNA and normal MNA, p <0.0001, and significant differences in composite risk of death and PAH-related hospitalization, p=0.02. In the multivariate Cox regression analysis including age, sex, and main risk factors (COMPERA 2.0 score, TAPSE/PASP, right atrial pressure, cardiac index, mix oxygen saturation), abnormal MNA remained significantly associated with all-cause mortality (HR 2.86 [95%CI: 1.29–6.38], p=0.01) and the composite end-point HR 2.39 [95% CI: 1.05–5.42], p=0.04) in PAH patients. Conclusions Using MNA as a routine screening tool allowed the detection of abnormal nutritional status in more than one third of PAH patients. Nutritional status assessed by the MNA was an independent predictor of all-cause death and the composite end-point of all-cause death and PAH-related hospitalization in patients with PAH.

The impact of the 2022 definition of pulmonary hypertension on long-term clinical outcomes in patients with heart failure with preserved ejection fraction

Abstract @ Backgrounds: In recent years, the definitions of pulmonary hypertension (PH) have been revised for early diagnosis and risk stratification of patients with PH. Using the 2015 definitions, the development of a precapillary component of PH in addition to a postcapillary PH was associated with right heart dysfunction and poor prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). However, the prognostic impact of revised definitions of PH in patients with HFpEF has not been fully evaluated. Purpose We investigated the impact of the 2018 and 2022 ESC/ERS definitions of PH on long-term clinical outcomes using data from a prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF). Methods A total of 250 patients hospitalised with acute HF who underwent right heart catheterisation after initial HF treatment were divided into PH categories according to the 2018 and 2022 definitions: isolated postcapillary PH (Ipc-PH), precapillary PH, combined postcapillary and precapillary PH (Cpc-PH), and unclassified PH. The incidence of the composite endpoint of all-cause death and HF rehospitalisation after discharge was compared across the PH categories. Results The overall prevalence of PH defined as a mPAP > 20 mmHg was 54%. Applying the 2022 definition, 42 patients (17%) were reclassified as either precapillary PH or Cpc-PH, resulting in a significant increase in the propotion of patients classified as having PH with a precapillary component (precapillary PH and Cpc-PH) compared with the 2018 definition (26% vs. 11%, p<0.0001). At a median follow-up of 822 days after discharge, PH with a precapillary component was associated with poor clinical outcomes according to the 2018 definition (Figure 1A), but according to the 2022 definition, clinical outcomes did not differ across the PH categories (Figure 1B). PVR ≥3 Wood units (WU) was a significant prognostic indicator, but there was no significant difference between the PVR 2-3 WU and PVR ≤2 WU categories (Figure 2). Conclusions The 2022 definition showed no association between PH classification and clinical outcomes. In patients with HFpEF, PVR ≥3 WU was identified as the key factor increasing the risk of all-cause death and HF hospitalisation.Figure 1Figure 2

Prognostic value of exercise tolerance and exercise-induced diastolic dysfunction in elderly patients referred for exercise stress echocardiography

BackgroundWe studied the prognostic value of exercise tolerance and exercise-associated diastolic dysfunction (Ex-DD) in elderly patients referred for exercise stress echocardiography (ExE). MethodsA total of 674 patients ≥60 years who underwent ExE using the Bruce protocol between January 2017 and December 2020 were included in this study. The prognostic factors examined were exercise tolerance, quantified in metabolic equivalents of tasks (METs), and Ex-DD. Patients were followed for a composite endpoint of all-cause death and cardiovascular hospitalization. Results122 (18 %) patients had Ex-DD and had a higher incidence of the combined outcome (23 [19 %] vs. 47 [9 %], p = 0.001) compared to patients without Ex-DD. Patients were classified into the following groups: group A (no Ex-DD and METs≥8.5), group B (either Ex-DD or METs<8.5), and group C (both Ex-DD and METs<8.5). Group B did not show higher mortality (HR: 1.6, p = 0.475) or cardiovascular hospitalization (HR: 1.8, p = 0.08) compared to group A, but showed an increased risk for the combined outcome (HR: 1.9, p = 0.038). Group C was associated with higher mortality (HR: 4.8, p = 0.032), cardiovascular hospitalization (HR: 3.9, p < 0.001), and the combined outcome (HR: 4.0, p < 0.001) compared to group A. ConclusionsDecreased exercise capacity and Ex-DD were associated with poor outcomes, especially when both findings were present.

Relationship between the HeartMate Risk Score category on admission and outcome in patients with acute heart failure referred to a cardiac intensive care unit.

The HeartMate Risk Score (HMRS), a simple clinical prediction rule based on the patients' age, albumin, creatinine, and the international normalized ratio of the prothrombin time (PT-INR), is correlated with mortality in the cohort of left ventricular assist device (LVAD) recipients. However, in an aging society, an LAVD is indicated for only a small proportion of patients with acute heart failure (AHF), and whether the HMRS has prognostic implications for unselected patients with AHF is unknown. This study aimed to assess the prognostic value of HMRS categories on admission in patients with AHF. We analyzed 339 hospitalized patients with AHF who had albumin, creatinine, and the PT-INR recorded on admission. The patients were categorized as follows: the High group (HMRS > 2.48, n = 131), Mid group (HMRS of 1.58-2.48, n = 97) group, and Low group (HMRS < 1.58, n = 111). The endpoints of this study were all-cause death and readmission for heart failure (HF). During a median follow-up of 247days, 24 (18.3%) patients died in the High group, 7 (7.2%) died in the Mid group, and 8 (7.2%) died in the Low group. In a multivariable analysis adjusted for highly imbalanced baseline variables, a high HMRS was independently associated with survival, with a hazard ratio of 2.90 (95% confidence interval 1.42-5.96, P = 0.004). With regard to the composite endpoint of all-cause death and readmission for HF, the Mid group had a worse prognosis than the Low group, and the High group had the worst prognosis. A high HMRS on admission is associated with all-cause mortality and readmission for HF, and a mid-HMRS is associated with readmission for HF after AHF hospitalization. The HMRS may be a valid clinical tool to stratify the risk of adverse outcomes after hospitalization in unselected patients with AHF.

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

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

#1171 Effect of methoxy polyethylene glycol-epoetin beta on delaying dialysis in anemic patients with Stage 4-5 chronic kidney disease

Abstract Background and Aims The optimal hemoglobin (Hb) target for treating anemia in pre-dialysis chronic kidney disease (CKD) remains controversial. This study investigates the efficacy and safety of methoxy polyethylene glycol-epoetin beta, in delaying the initiation of kidney replacement therapy (KRT), all-cause mortality, CKD progression, and quality of life in stage 4-5 CKD patients. It compares outcomes between patients targeting an Hb level of 10.5-11.5 g/dL versus 8.5-9.5 g/dL. Method This was a single-center, open-label, parallel-group randomized controlled trial. Patients with estimated glomerular filtration rates (eGFR) of 8-15 ml/min/1.73 m2, who had not yet started dialysis, were randomized into two groups based on different Hb targets (Group A: 10.5-11.5 g/dL, Group B: 8.5-9.5 g/dL). Methoxy polyethylene glycol-epoetin beta (MIRCERA®) was prescribed by a pre-specified protocol to achieve these Hb targets. Iron supplements were administered to maintain transferrin saturation &amp;gt;20% or serum ferritin &amp;gt;200 ng/ml. Primary outcomes included a composite of all-cause death and KRT initiation, with secondary outcomes encompassing eGFR slope, hospitalization incidence, blood transfusion necessity, and quality of life measured by the 36-Item Short Form Health Survey (SF-36). Results A total of 62 participants were randomized. The mean age was 64.0 years (SD ±16.0), with 51.6% being female. The mean estimated Glomerular Filtration Rate (eGFR) at enrollment was 12.1 ml/min/1.73 m2 (SD ±3.1). Group A had a significantly higher time-averaged Hemoglobin (Hb) level (10.5 g/dL, SD ±1.2) compared to 8.5 g/dL (SD ±0.9) in the control group (p &amp;lt; 0.001). There was no significant difference in the composite endpoint of all-cause death and Kidney Replacement Therapy (KRT) initiation between the two groups (Hazard Ratio [HR] 0.69; 95% Confidence Interval [CI] 0.32-1.50; p = 0.35, as shown in the Figure). The eGFR slope was similar in both groups (−2.54 vs. −2.53 ml/min/1.73 m2 per year, p = 0.9). Time-averaged ferritin, transferrin saturation, blood pressure, and dietary sodium/protein intake showed no significant differences. Participants in the lower Hb target group required more blood transfusions (11 vs 1 unit, Incidence Rate Ratio [IRR] = 0.075, 95% CI 0.002-0.517, p = 0.001). Rates of hospital admissions, and changes in SF-36 quality of life domains were comparable between the groups, as detailed in the Table. Conclusion The study indicates that using methoxy polyethylene glycol-epoetin beta to maintain a higher Hb target in anemic patients with stage 4-5 CKD does not significantly alter the rate of all-cause mortality, the initiation of KRT, and rate of eGFR decline compared to a lower Hb target. However, a higher Hb target may reduce the need for blood transfusions without adversely affecting the progression of CKD, hospitalization rates, or quality of life. These findings suggest that while higher Hb targets may not dramatically alter key clinical outcomes, they could offer benefits in reducing transfusion requirements, thus providing a more nuanced approach to managing anemia in late-stage CKD.

Abstract 1060: Association Of Inflammation And Cholesterol With Long-term Clinical Outcomes After In-stent Restenosis Revascularization

Background: Among patients with coronary artery disease, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is at least as strong a predictor of future cardiovascular events as is residual risk assessed by low-density lipoprotein cholesterol (LDL-C). Objectives: To evaluate the relationships between relative importance of hsCRP and LDL-C as determinants of clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions. Methods: Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. Quartiles of increasing hsCRP and LDL-C were assessed as predictors of clinical outcomes after adjustment for covariates. Patients were then categorized as four predefined residual risk groups according to hsCRP (≥2 mg/L vs. &lt;2mg/L) and LDL-C levels (≥70mg/dL vs. &lt;70mg/dL). Results: During a median follow-up of 36 months, 436 MACEs occurred. Baseline hsCRP was significantly associated with MACE (highest versus lowest quartile; adjusted hazard ratio [aHR], 1.90 [95% CI, 1.39-2.59]; P&lt;0.001). By contrast, the baseline LDL-C quartile was not associated with MACE (highest versus lowest quartile; aHR, 0.93 [95% CI, 0.71- 1.22]; P=0.59). Compared with patients without residual risk (hsCRP &lt;2 mg/L and LDL-C &lt;70 mg/dL), participants with both residual inflammatory and LDL-C risk (hsCRP ≥2 mg/L and LDL-C ≥70 mg/dL) (aHR, 1.39 [95% CI, 1.06-1.83]; P=0.02) and those with residual inflammatory risk only (hsCRP ≥2 mg/L and LDL-C &lt;70 mg/dL) (aHR, 1.34 [95% CI, 1.01-1.72]; P=0.04) had significantly higher risks of MACE. Conclusions: In the current cohort of patients after ISR PCI, inflammation assessed by hsCRP predicted higher risk of adverse clinical outcomes, whereas the level of LDL-C was not associated with prognosis.

Impacts of the SYNTAX score I, II and SYNTAX score II 2020 on left main revascularization

Patients with left main coronary artery disease (LMCAD) with a high SYNTAX score (SS) were excluded from randomized studies that comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to compare PCI and CABG in the real-world practice and investigate the impact of SS I, SS II, and SS II 2020 on clinical outcomes. In total, 292 Patients with LMCAD (173 PCI, 119 CABG) treated between 2017 and 2021 were enrolled. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, stroke, or myocardial infarction (MI). The mean SS I was high in both groups (PCI vs. CABG: 31.64 ± 11.45 vs. 32.62 ± 11.75, p = 0.660). The primary outcome occurred in 28 patients (16.2%) in the PCI group and in 19 patients (16.0%) in the CABG group without significant difference [adjusted hazard ratio, 95% CI = 0.98 (0.51–1.90), p = 0.97] over the follow-up period (26.9 ± 17.7 months). No significant difference was observed in all-cause mortality (11.6% vs. 11.8%, p = 0.93) or stroke rates (3.5% vs. 5.0%, p = 0.51) between groups. However, PCI was associated with higher MI (4.6% vs. 0.8%, p < 0.05) and revascularization rates (26% vs. 5.9%, p < 0.001). Prognostic value of the SS I, SS II and SS II 2020 on the primary outcome was not relevant in the PCI group. Among patients with LMCAD, PCI and CABG did not significantly differ in the composite endpoint of all-cause death, stroke, and MI. These results support the potential expansion of PCI indications in LMCAD management for whom are ineligible for CABG with complex coronary artery disease.

β-blockers may be detrimental in frail patients with heart failure with preserved ejection fraction.

The effectiveness of β-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of β-blocker and prognosis according to the status of frailty. We compared prognosis between HFpEF patients with and without β-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831). Among 1159 patients enrolled in the analysis (median age, 81.4years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of β-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5. Use of β-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of β-blockers in HFpEF patients with frailty may need careful attention.

Heart failure 'the cancer of the heart': the prognostic role of the HLM score.

The multi-systemic effects of heart failure (HF) resemble the spread observed during cancer. We propose a new score, named HLM, analogous to the TNM classification used in oncology, to assess the prognosis of HF. HLM refers to H: heart damage, L: lung involvement, and M: systemic multiorgan involvement. The aim was to compare the HLM score to the conventional New York Heart Association (NYHA) classification, American College of Cardiology/American Heart Association (ACC/AHA) stages, and left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients. We performed a multicentre, observational, prospective study of consecutive patients admitted for HF. Heart, lung, and other organ function parameters were collected. Each patient was classified according to the HLM score, NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography. The follow-up period was 12months. The primary endpoint was a composite of all-cause death and rehospitalization due to HF. A total of 1720 patients who completed the 12month follow-up period have been enrolled in the study. 520 (30.2%) patients experienced the composite endpoint of all-cause death and rehospitalization due to HF. 540 (31.4%) patients were female. The mean age of the study population was 70.5±12.9. The mean LVEF at admission was 42.5±13%. Regarding the population distribution across the spectrum of HLM score stages, 373 (21.7%) patients were included in the HLM-1, 507 (29.5%) in the HLM-2, 587 (34.1%) in the HLM-3, and 253 (14.7%) in the HLM-4. HLM was the most accurate score to predict the primary endpoint at 12months. The area under the receiver operating characteristic curve (AUC) was greater for the HLM score compared with the NYHA classification, ACC/AHA stages, or LVEF, regarding the composite endpoint (HLM=0.645; NYHA=0.580; ACC/AHA=0.589; LVEF=0.572). The AUC of the HLM score was significantly better compared with the LVEF (P=0.002), ACC/AHA (P=0.029), and NYHA (P=0.009) AUC. The HLM score has a greater prognostic power compared with the NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography in terms of the composite endpoint of all-cause death and rehospitalization due to HF at 12months of follow-up.

Prognostic role of fragility detection in a heart failure clinic using the vulnerable elderls survey scale 13 (VES-13) and a multimodality assessment

Abstract Background Fragility has repeatedly proved to play a significant prognostic role in HF patients. We recently reported that the Vulnerable Elderls Survey scale 13 (VES-13) was useful and even showed a higher sensitivity for detecting fragility in outpatients with heart failure (HF) than a multimodality assessment used for many years in our Heart Failure Clinic. Concordance between VES-13 and the multimodality assessment was superior to 80%, but Cohen’s Kappa did not reach the suitable level of 0.70. Purpose To assess which of the two approaches (VES-13 scale and a multimodality assessment that includes Barthel index, OARS scale, Pfeiffer test, and abbreviated Yesavage Geriatric Depression Scale of 4 items [GDS]) is superior from the prognostic point of view. Methods Nurses fulfilled the scales with the patients at their first visit. Patients with a scoring ≥3 in the VES-13 scale and the presence of one of the predefined criteria in the multimodality assessment (Barthel &amp;lt;90; OARS score &amp;lt;10 in women and &amp;lt;6 in men; Pfeiffer Test score &amp;gt;3 ± 1, depending on educational level; one positive depression response in abbreviated GDS; and age &amp;gt;85 years or nobody to turn to for help) were considered to have fragility for the purpose of the study. All-cause mortality and the composite of all-cause death or HF hospitalization were the analysed end-points. Results From March 2021 to December 2021, 172 patients were evaluated with the two fragility screening modalities (mean age 69.1 ± 11.4 years, 64% men, 42.4% from ischaemic aetiology, 66.9%/26.2% in NYHA class II/III, LVEF 40.3% ± 13.9). VES-13 identified 68 (39.5%) patients with fragility, while the multimodality assessment detected 61 (35.5%) patients. During a mean follow-up of 15.8 ± 4.8 months, 22 patients (12.8%) died, 18 (10.5%) had at least one HF hospitalization and 37 suffered the composite end-point of all-cause death or HF hospitalization (21.5%). In Cox regression analyses fragility detected by both approaches showed similar prognostic value for all-cause mortality (HR 2.89 [1.24-6.77], p=0.014) using the multimodality approach vs. (HR 2.89 [1.21-6.89], p=0.017) using the VES-13 scale. However, fragility detected by the VES-13 scale revealed to be a more powerful prognostic tool for the composite end-point (HR 2.90 [1.49-5.64], p=0.002) than the multimodality approach (HR 1.47 [0.77-2.81], p=0.248). Conclusions Fragility detected both by the VES-13 and by a multimodality approach showed similar prognostic role for all-cause mortality, but VES-13 showed a higher stratification capacity for the composite end-point of all-cause death or HF hospitalization. Nevertheless neither of the two approaches is actually a prognostic tool. It is necessary to perform a complete geriatric assessment to identify the grade of fragility, the possible prognostic impact and the best intervention to improve outcomes and quality of life.

Anatomical, functional and prognostic correlates of resting coronary flow velocity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical significance of baseline peak diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery (LAD) has not been investigated yet in patients with hypertrophic cardiomyopathy (HCM). Aim To assess the anatomical, functional and prognostic correlates of baseline LAD CFV in HCM. Methods 384 consecutive adult HCM patients (age=52+15 years, 164 [43%] females) with no known coronary artery disease from 8 centers in 5 countries were prospectively analyzed. All patients underwent comprehensive transthoracic echocardiography including CFV measurement with pulse wave Doppler in the mid-distal LAD. All patients had preserved left ventricular (LV) function. LV force was calculated as (peak instantaneous LV outflow tract gradient+systolic blood pressure)/LV end-systolic volume. Patients were followed for a median of 50 months (IQ range 18-97 months), the outcome measure was a composite endpoint of all-cause death and acute heart failure. Results The mean CFV was 36±11 cm/s. CFV was positively correlated with LV maximal wall thickness (r=0.375, p&amp;lt;0.001), LV maximal septal thickness (r=0.320, p&amp;lt;0.001), resting LV outflow tract gradient (r=0.274, p&amp;lt;0.001), LV force (r=0.227, p&amp;lt;0.001), mean E/e’ (r=0.479, p&amp;lt;0.001) and heart rate (r=0.221, p&amp;lt;0.001). During follow-up, 54 events occurred (33 all-cause deaths and 21 acute heart failures). Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (&amp;gt;31 cm/s) to predict the composite endpoint. Patients with CFV &amp;gt;31 cm/s had a significantly worse 10-year event-free survival compared to those with CFV ≤31 cm/s, see Figure. Conclusion Higher resting LAD CFV is associated with greater LV wall thickness, higher LV outflow tract gradient, faster heart rate and more elevated left ventricular filling pressures in HCM. Elevated resting CFV may indicate a coronary microcirculation dysfunction either primary or secondary to anatomical (septal hypertrophy), functional (increased myocardial oxygen demand), or autonomic (increased sympathetic drive) determinants. Whatever the underlying endotype, high resting CFV is related to worse prognosis in the long term.Figure.

Acute changes of right ventricular longitudinal strain after transcatheter edge-to-edge repair in patients with functional mitral regurgitation

Abstract Background Transcatheter edge-to-edge repair (TEER) is a valid therapeutic option in symptomatic patients with severe secondary mitral valve regurgitation (SMR) at high surgical risk. While right ventricular (RV) dysfunction is a predictor of poor outcomes in this context, TEER may lead to an improvement of RV function which portends a better outcome. Purpose The aim of this study was to investigate acute change in RV function and its prognostic implication after successful TEER in patients with severe SMR. Methods Patients with severe SMR who underwent TEER from 2013 to 2021 at our center were retrospectively screened. Only patients with successful procedure (MR ≤ grade 2) and adequate echocardiographic images for longitudinal strain assessment were enrolled. RV function was estimated at baseline and pre-discharge by echocardiographic evaluation; RV global longitudinal strain (RVGLS) and RV free wall longitudinal strain (RVFWLS) were assessed before and after TEER. Longitudinal strain improvement was defined as an increase of post procedural strain greater than median value variation. Population was then divided in two groups based on RVGLS significant improvement. The primary outcome was a composite of all-cause death, heart transplantation (HT) and left ventricular assist device (LVAD) implantation during follow-up, assessed with Kaplan-Maier curves and compared by log-rank test. Results A total of 61 patients were included. Mean age was 70±10 years, 89% patients were symptomatic with NYHA class 3-4, mean furosemide daily dose was 200±146 mg. Pre-TEER median left ventricle ejection fraction (LVEF) was 29% [IQR, 26; 35%], RV fractional area change (FAC) was 32% [IQR 26; 37%] and tricuspid anulus plan systolic excursion (TAPSE) was 17 mm [IQR 14; 20 mm]. Median RVGLS and RVFWLS at baseline were respectively -11% [IQR -13; -9%] and -14% [IQR -17; -11%]. After TEER a significant variation of RVGLS and RVFWLS was observed (RVGLS: -13% [IQR -15; -10%] p 0.012; RVFWLS: -16% [-19; - 13%] p 0.001). Moreover, a significant reduction in estimated systolic pulmonary artery pressure (sPAP) between baseline (45 mmHg [IQR 35; 55mmHg]) and post TEER (40 mmHg [IQR 30;45 mmHg] p &amp;lt;0.001) was observed. Median improvement of RVGLS was 1.3%. After mean follow up time of 55±7 months event rate for the combined primary endpoint was numerically lower in the improved RVGLS group, although the difference was not statistically significant (p 0.243). Interestingly, rate of HT was significantly lower in RVGLS-improved group (p 0.032). Conclusions This study showed significant pre-discharge improvement of RV longitudinal strain in patient with severe SMR after successful TEER. At follow-up this improvement did not affect the outcome in terms of freedom from composite endpoint of all-cause death, HT or LVAD implantation but events were numerically lower in patients with strain improvement. Further data on larger population are needed to confirm our observations.Table 1,2Figure 1,2

Invasive Hemodynamic and Vasoreactivity Testing with Inhaled Iloprost in Children with Pulmonary Arterial Hypertension Associated with Congenital Heart Defects

Objective: Invasive hemodynamic evaluation and acute vasoreactivity testing are recommended in the diagnosis of pulmonary arterial hypertension (PAH), but their clinical role in children with PAH associated with congenital heart defects (CHD) is unclear. This study aims to investigate acute hemodynamic responses to inhaled iloprost, and its role in prognosis in children with PAH-CHD. Methods: A retrospective analysis was conducted on 83 pediatric patients with PAH-CHD in whom invasive hemodynamics were evaluated before and after a single inhaled dose of iloprost at a single center between 2010 and 2022. Details of the CHD corrective operation, medical treatment, and outcome for each patient were obtained via medical records or telephone contact. A composite endpoint of all-cause death, admission for worsening heart failure during follow-up, and event-free survival was defined, and risk factors associated with this composite endpoint were analyzed. Results: The patient age was (11.3 ± 4.6) years, and 60 (72.3%) were female. Fifty-nine (71.1%) patients were diagnosed with Eisenmenger syndrome. After iloprost inhalation, mean pulmonary artery pressure decreased from (78.2 ± 11.5) to (72.3 ± 13.2) mmHg (P &lt; 0.001), and pulmonary vascular resistance index (PVRI) decreased from (18.0 ± 7.9) to (14.5 ± 8.1) WU·m2 (P &lt; 0.001). A total of 38 (45.8%) patients had a positive response, defined as a PVRI decrease &gt;25% with stable systemic pressure. Thirty-seven (44.6%) patients underwent a corrective CHD operation at a median of 24 d after hemodynamic evaluation. Nine patients died, and 15 met the composite endpoint during a follow-up period of 5.4 (3.8, 8.8) years. Five-year event-free survival estimates were 96.7% (95% confidence interval: 90.3%–100%) in patients with a positive response, and 82.8% (95% confidence interval: 71.7%–94.5%) in patients with a non-positive response (log-rank P = 0.012). A positive PVRI response and higher pulmonary arterial oxygen saturation after iloprost inhalation, lower baseline brain natriuretic peptide, and PAH-targeted therapy at follow-up were significantly associated with a favorable clinical outcome. A positive acute vasoreactivity testing response and PAH-targeted therapy at follow-up were independent predictors of outcome in multivariate Cox analysis. Conclusions: Acute inhalation of iloprost can lead to a significant decrease in hemodynamic parameters. Responsiveness to inhaled iloprost is associated with better outcomes and can be a valuable predictor of outcomes.

Application of the RIETE score to identify low-risk patients with pulmonary embolism: From the COMMAND VTE Registry

BackgroundThe RIETE score could be specifically useful for identification of low-risk pulmonary embolism (PE) patients for home treatment. However, the external validation of the RIETE score has been limited. MethodsThe COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). The current study population consisted of 1479 patients with acute PE, who were divided into 2 groups; RIETE scores of 0 (N = 260) and ≥ 1 (N = 1219). ResultsThe cumulative 10-day and 30-day incidences of a composite endpoint of all-cause death, recurrent PE, or major bleeding were lower in patients with the RIETE score of 0 than in those with the RIETE score of ≥1 (10-day: 0.4 % vs. 6.7 %, P < 0.001, and 30-day: 0.4 % vs. 10.0 %, P < 0.001). The area under the receiver-operating characteristic curve (AUC) in the RIETE score for the 10-day composite endpoint showed numerically better predictive ability than that in the sPESI score (0.77 vs. 0.73, P = 0.07), and the AUC in the RIETE score for the 30-day composite endpoint showed significantly better predictive ability than that in the sPESI score (0.77 vs. 0.71, P = 0.003). ConclusionsThe RIETE score was well validated in the current large real-world registry. The RIETE score of 0 could identify patients with reasonably low risks of the 10-day and 30-day composite endpoint of all-cause death, recurrent PE, or major bleeding.

Implications of ventricular arrhythmia after cardiac resynchronization therapy

Conflicting data are available on whether ventricular arrhythmia (VA) or shock therapy increases mortality. Although cardiac resynchronization therapy (CRT) reduces the risk of VA, little is known about the prognostic value of VA among patients with CRT devices. The purpose of this study was to evaluate the implications of VA as a prognostic marker for CRT. We investigated 330 CRT patients within 1 year after CRT device implantation. The primary endpoint was the composite endpoint of all-cause death or hospitalization for heart failure. Forty-three patients had VA events. These patients had a significantly higher risk of the primary endpoint, even among CRT responders (P = .009). Fast VA compared to slow VA was associated with an increased risk of the primary endpoint (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.06-4.34; P = .035). Shock therapy was not associated with a primary endpoint (shock therapy vs antitachycardia pacing: HR 1.49; 95% CI 0.73-3.03; P = .269). The patients with VA had a lower prevalence of response to CRT (23 [53%] vs 202 [70%]; P = .031) and longer left ventricular paced conduction time (174 ± 23 ms vs 143 ± 36 ms; P = .003) than the patients without VA. VA occurrence within 1 year was related to paced electrical delay and poor response to CRT. VA could be associated with poor prognosis among CRT patients.

Procollagen type 1 N-terminal propeptide is associated with adverse outcome in acute chest pain of suspected coronary origin.

Extracellular matrix (ECM) is an integral player in the pathophysiology of a variety of cardiac diseases. Cardiac ECM is composed mainly of collagen, of which type 1 is the most abundant with procollagen type 1 N-terminal Propeptide (P1NP) as a formation marker. P1NP is associated with mortality in the general population, however, its role in myocardial infarction (MI) is still uncertain, and P1NP has not been investigated in acute chest pain. The objective of the current study was to assess the role of P1NP in undifferentiated acute chest pain of suspected coronary origin. 813 patients from the Risk in Acute Coronary Syndromes study were included. This was a single-center study investigating biomarkers in consecutively enrolled patients with acute chest pain of suspected coronary origin, with a follow-up for up to 7 years. Outcome measures were a composite endpoint of all-cause death, new MI or stroke, as well as its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. In multivariable Cox regression analysis, quartiles of P1NP were significantly associated with the composite endpoint at 1 year of follow-up with a hazard ratio for Q4 of 1.82 (95% CI, 1.12-2.98). There was no other significant association with outcomes at any time points. P1NP was found to be an independent biomarker significantly associated with adverse clinical outcome at one year in patients admitted to hospital for acute chest pain of suspected coronary origin. This is the first report in the literature on the prognostic value of P1NP in this clinical setting. NCT00521976.

Current opinion in quantitative lung ultrasound for the nephrologist.

Volume overload mediates worse cardiovascular outcomes in patients with end-stage kidney disease (ESKD) on hemodialysis (HD), leading to increased acute care utilization. Understanding the presence of pulmonary congestion, which is often clinically silent, could be instrumental in predicting acute care needs and mitigating risks through appropriate therapy. This review provides an overview of the existing literature on lung ultrasound in ESKD patients. Quantitative lung ultrasound predicts adverse cardiovascular outcomes in ESKD patients on HD. The largest randomized controlled trial of a lung ultrasound-guided ultrafiltration strategy demonstrated control of pulmonary congestion without an increased risk of intradialytic hypotension, arrhythmia, or access thrombosis. Despite this, the study was negative in the incidence of the primary composite endpoint of all-cause death, nonfatal myocardial infarction, and decompensated heart failure. A post hoc analysis showed promise with reductions in recurrent acute care utilization and cardiovascular events. Recent research has focused on simplification of the 28-zone lung ultrasound, and abbreviated protocols have been shown to retain prognostic ability. Lung ultrasound is a valuable tool for nephrologists to diagnose and manage pulmonary congestion. However, its optimal integration with other hemodynamic parameters to formulate effective management strategies remains elusive. Future studies should address these gaps and find solutions to the training inadequacies in clinician-performed ultrasound.

Association between lipoprotein(a) and long-term outcomes after percutaneous coronary intervention for lesions with in-stent restenosis

ObjectivesThis study aimed to evaluate the association between increased lipoprotein (a) [Lp(a)] and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). BackgroundElevated Lp(a) is demonstrated to be associated with recurrent ischemic events after PCI. However, the impact of Lp(a) in patients with ISR remains undetermined. MethodsBetween January 2017 and December 2018, a total of 2086 patients who underwent PCI for ISR were consecutively enrolled. Patients were categorized as elevated group (> 30 mg/dL, n=834) and non-elevated group (≤ 30 mg/dL, n=1252) according to baseline Lp(a) levels. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. ResultsDuring a median follow-up of 36 months, the primary outcome occurred in 202 of 1252 patients (26.7%) in the elevated Lp(a) group and 237 of 834 patients (21.8%) in the non-elevated Lp(a) group (adjusted hazard ratio: 1.31; 95% confidence interval: 1.08-1.58; P = 0.007), driven by higher rate of all-cause death (4.1% vs. 2.5%, P = 0.002 by Log-rank test; aHR: 1.77; 95% CI: 1.07-2.94; P = 0.03) and repeat revascularization (22.3% vs. 19.5%, P = 0.04 by Log-rank test; aHR: 1.18; 95% CI: 0.94-1.49; P = 0.16). Adding continuous or categorical Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification, and integrated discrimination. The results were consistent across subgroups. ConclusionsIn the current cohort of patients who underwent PCI for ISR, elevated Lp(a) at baseline is associated with higher risk of long-term MACE.

Prognostic value of right ventricular longitudinal strain in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair.

To evaluate the prognostic impact of pre-procedural right ventricular longitudinal strain (RVLS) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge repair (TEER) in comparison with conventional echocardiographic parameters of RV function. This is a retrospective study including 142 patients with SMR undergoing TEER at two Italian centres. At 1-year follow-up 45 patients reached the composite endpoint of all-cause death or heart failure hospitalization. The best cut-off value of RV free-wall longitudinal strain (RVFWLS) to predict outcome was -18% [sensitivity 72%, specificity of 71%, area under curve (AUC) 0.78, P < 0.001], whereas the best cut-off value of RV global longitudinal strain (RVGLS) was -15% (sensitivity 56%, specificity 76%, AUC 0.69, P < 0.001). Prognostic performance was suboptimal for tricuspid annular plane systolic excursion, Doppler tissue imaging-derived tricuspid lateral annular systolic velocity and fractional area change (FAC). Cumulative survival free from events was lower in patients with RVFWLS ≥ -18% vs. RVFWLS < -18% (44.0% vs. 85.4%; < 0.001) as well as in patients with RVGLS ≥ -15% vs. RVGLS < -15% (54.9% vs. 81.7%; P < 0.001). At multivariable analysis FAC, RVGLS and RVFWLS were independent predictors of events. The identified cut-off of RVFWLS and RVGLS both resulted independently associated with outcomes. RVLS is a useful and reliable tool to identify patients with SMR undergoing TEER at high risk of mortality and HF hospitalization, on top of other clinical and echocardiographic parameters, with RVFWLS offering the best prognostic performance.