Cardiac Index Research Articles

A new prehospital cardiac risk assessment index derived from vital signs by first contact emergency medical service, including prehospital oxygen saturation, for accurate prehospital triage of acute m

Abstract Background: Rapid and accurate triage is essential to improve the prognosis of patients with severe acute myocardial infarction (AMI). However, prehospital triage using vital signs, including prehospital oxygen saturation (SpO2), by first medical contact has not been evaluated. Purpose: The purpose of this study was to develop a new risk stratification index for AMI using vital signs including SpO2 for rapid and accurate prehospital triage. Methods: From January 2013 to June 2022, 3006 AMI patients who were directly transported by ambulance were enrolled from the Mie ACS registry. Based on observed risk relationships in 3,006 AMI patients, we developed and evaluated a prehospital cardiac risk assessment index (P-CRAI) using age, heart rate, and systolic blood pressure (SBP) and SpO2 to predict 30-day mortality: (heart rate×[age/10]2)/SBP＋1.1(100-SpO2). We also analyzed whether P-CRAI predicted the need for mechanical circulatory support (MCS) or ventilator use. Results: In the receiver operating characteristic (ROC) curve analysis, P-CRAI 38.1 has a sensitivity of 84.4%, specificity of 72.7%, and accuracy of 84.3% for predicting 30-day mortality, and P-CRAI was a strong predictor of 30-day mortality compared with the other indices and variables (Figure 1A). When divided into two groups with P-CRAI 38, Kaplan-Meier survival curves showed significant differences in 30-day survival between the high and low groups (83.7% vs. 98.7%, P<0.001, Figure 1B). P-CRAI≥38 was the strongest independent predictor of 30-day mortality with a hazard ratio of 7.64 compared to the other factors by multivariate Cox regression analysis. The spline curve of 30-day mortality by P-CRAI shows a correlation with prognosis (Figure 2A). In this study, we then used the bootstrap method to generate a calibration curve and validate P-CRAI. The results showed an excellent fit and that P-CRAI accurately estimated patient prognosis (Figure 2B). In addition, P-CRAI was a robust predictor of the very early events of death at 24 hours and MCS or ventilator use by ROC curve analysis. (c-statistic 0.835 and 0.726, respectively, P<0.01). Conclusion: The P-CRAI was found to be a useful tool for prehospital triage of AMI patients, accurately predicting 30-day mortality and the need for MCS.Figure 1.Figure 2.

Cardiac contractility index, a novel biomarker of incident heart failure amongst people with normal left ventricular ejection fraction in the UK Biobank

Abstract Background Cardiac contractility index (CCI) is a simple non-invasive measure of myocardial contractility defined by systolic blood pressure divided by indexed left ventricular end-systolic volume. Although left ventricular ejection fraction (LVEF) is essential for phenotyping patients with suspected heart failure (HF), it is load dependent and insensitive to subtle subclinical ventricular dysfunction. Left ventricular (LV) strain, although more sensitive at detecting subtle disturbances in myocardial function, also does not reflect loading conditions and dependency on image quality and inter-vendor variability limit widespread use. The ability of CCI to identify patients with subclinical left ventricular dysfunction at risk of developing HF is unknown. Purpose We aimed to: 1) explore the relationship between CCI with conventional imaging biomarkers of LV systolic dysfunction and 2) assess whether CCI could identify those at increased risk of incident HF in people without pre-existing left ventricular dysfunction in the UK Biobank imaging study. Methods We explored the relationship between CCI and laboratory and imaging biomarkers of systolic function, including LVEF and LV strain. Scatter plots were constructed for CCI with LVEF and LV strain. Pearson’s coefficients (r) and coefficient of determination (r2) were calculated to assess for correlations. People with sex-specific thresholds of abnormally low LVEF derived from within the same cohort (<48% for men, and <51% for women) were then excluded. CCI was then dichotomised as being high or low based its median value (4.4 mmHg/ml/m2). Age-sex adjusted Cox proportional hazards ratios (HR) with 95% CIs were estimated for the primary outcome of incident HF (derived from linked national digital registries) in addition to modelling with restricted cubic splines. Results We included 38,215 people (median age 55 years, 48% men). There was moderate correlation between CCI with LVEF (r=0.53 [0.53-0.54], R2=0.29; p<0.001), LV global circumferential strain (r=-0.50 [-0.50- -0.49], R2=0.25; p<0.001) and radial strain (r=-0.49 [0.48-0.50], R2=0.24; p<0.001), although was only weekly correlated with LV global longitudinal strain (r=-0.19 [-0.20- -0.18], R2=0.03; p<0.001) (Figure 1A). Using sex-specific thresholds 33,739 (88.3%) had a normal LVEF. During 195,584 person-years of follow-up (median 5.5 years), a total of 221 (0.7%) participants developed HF. Age-sex adjusted low CCI at baseline was associated with an increased risk of incident HF (adjusted HR 1.33 [1.01-1.75]; p=0.043). The association between CCI and incident HF was curvilinear (Figure 1B). Conclusions CCI identifies people with subclinical left ventricular systolic dysfunction at risk of developing incident heart failure.

Randomized trial assessing worsening renal function with dapagliflozin addition in acute decompensated heart failure: ROAD-ADHF trial

Abstract Background Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has shown to reduce cardiovascular mortality in patients with chronic heart failure.1) In addition, DAPA can enhance diuresis in patients with acute decompensated heart failure (ADHF).2) However, there is little known how early initiation of DAPA might impact the worsening renal function (WRF) when combined with standard decongestive therapy for ADHF. Purpose We aimed to evaluate the impact of initiating DAPA within 24 hours after ADHF admission on WRF, compared to standard decongestive therapy with loop diuretics alone. Methods We enrolled consecutive ADHF patients with a left ventricular ejection fraction (LVEF) less than 50%. The patients were prospectively randomized to either the DAPA group who received DAPA at a dose of 10 mg once daily within 24 hours of admission or the conventional therapy group (CON group) who received loop diuretics alone. Furosemide, loop diuretic, dosage was adjusted by increase or decrease of 10 mg to maintain urine output between a 1-2 mL/kg/hour.3) The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥ 0.3 mg/dL from baseline within 7 days of admission.4) Additionally, right heart catheterization (RHC) was performed before discharge if the consent was obtained. Results From May 2021 to May 2023, we analyzed a total of 114 patients (56 in the DAPA group and 58 in the CON group). The mean age was 73 years, 35% were female, and the mean LVEF was 32.5%. There was no significant difference in the incidence of WRF between two groups (16.1% in the DAPA group vs. 12.1% in the CON group, P=0.54, Figure 1). The cumulative loop diuretics dose over 7 days was lower in the DAPA group than CON group (184 ± 9.64 mg vs. 214 ± 9.81 mg, P=0.03, Figure 2). RHC before discharge was performed in 54 patients (96.4%) in the DAPA group and in 54 (93.1%) in the CON group. There were no significant differences in the pulmonary artery wedge pressure, pulmonary artery pressure, right atrial pressure, and cardiac index by the thermodilution method or the Fick method between two groups. Conclusion This randomized prospective trial revealed the early initiation of DAPA within 24 hours of admission for ADHF reduced loop diuretic demand without inducing WRF compared to standard decongestive therapy.Figure 1Figure 2

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.

Higher myocardial mitochondrial ketone body oxidation capacity in human heart failure

Abstract Introduction/Purpose Recent studies suggest that the ketone bodies (KB) beta-hydroxybutyrate (HBA) and acetoacetate (ACA) are relevant substrates for myocardial energy metabolism in heart failure (HF). However, the amount of KB-dependent mitochondrial respiration in HF has not yet been quantified. High-resolution respirometry (HRR) is the gold-standard method for quantifying substrate-dependent mitochondrial oxidative capacity. Therefore, we aimed to evaluate the association between myocardial KB-dependent oxidative capacity and human HF using HRR. Methods The primary endpoint of this single-center prospective cohort study was KB-dependent and overall mitochondrial oxidative capacity in permeabilized myocardium. We used two different protocols for our measurements. In the first HRR protocol, conventional respirometry substrates including fatty acids, complex I- and complex II substrates were used to quantify the maximum coupled oxidative phosphorylation capacity (OXPHOS). Leak respiration was quantified using oligomycin to calculate the respiratory control ratio (RCR, state 3/state 4o), and leak control ratio (LCR, state 4o/state u). In the second protocol which was recently established by our working group, HBA and ACA were used as respirometry substrates to quantify KB-dependent respiration down to the enzyme level. The relative contribution of the KBs was obtained by comparing HBA- and ACA-derived respiration to OXPHOS. We applied both protocols to myocardial samples from individuals with advanced HF (HF group, catheter-acquired endomyocardial biopsies from non-ischemic HF patients or samples of explanted hearts collected during orthotopic heart transplantation surgery in end-stage heart failure patients) as well as previously heart transplanted individuals without current heart failure (Control group). Results Controls and HF had similar demographic characteristics, with comparable age distribution (mean±SD, 56.3±10.3 vs. 54.2±10.7 years, p=0.36), sex (68.75% vs. 66.67% male, p=0.87), or body mass index (25.0±5.8 vs. 29.0±10.6 kg/m2, p=0.08) and differed significantly in cardiac index (3.06±0.67 vs. 1.93±0.44) and ejection fraction (55.8±10.2 vs. 26.6±9.1) (both p<0.0001). The HF group exhibited lower OXPHOS and respiration for all substrate combinations tested (Fig. 1A). In contrast, KB-dependent respiration did not differ between HF and controls (Fig. 1B). The relative HBA-dependent respiration (Fig. 1C) and the relative and absolute ACA-dependent respiration (Fig. 1C and D) were higher in the HF group compared to controls. Mitochondrial uncoupling (LCR) (0.47±0.29 vs. 0.44±0.09 [AU], p=0.79) and coupling efficiency (RCR) (2.75±1.38 vs. 2.11±0.39 [AU], p=0.15) were not different between the groups. Conclusion These findings suggest that mitochondria in the failing heart can utilize KBs for OXPHOS to a greater extent and further hint towards KB metabolism as a potential therapeutic target for HF.

Clinical, echocardiographic and haemodynamic predictors of morbidity and mortality in pulmonary hypertension: a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we aimed to evaluate the clinical, echocardiographic,haemodynamic and neurohumoral predictors of morbidity and mortality. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). ESC/ERS 2022 risk scoring model was used for risk predictions at baseline assessment. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age was 51.27 + 21.37 years, and 72 % of patients were female. Incident cases were noted in 65.9 % of overall group. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of overall patients, respectively. Background mono and dual targeted combinations, and sequential dual or triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. Baseline low-, intermediate- and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time was 867 (412-1667) days. Overall rates of mortality and CEP were 26 % and 39%, respectively. Prevalent versus incident cases were associated signifinatly lower mortality and CEP rates (p=0.028 and p=0.024, respectively). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. CHD-PAH compared with other groups was associated with a higher Kaplan-Meier (K-M) survival and CEP-free survival (p< 0.0001 and p=0.00023, respectively). Survival was associated with prevalent versus incident status, baseline functional class (FC) and six-minute walk distance (6MWD) in all subgroups (p<0.0001 for all), NT-brain natriuretic peptide and right atrial area in IPAH,CHD-PAH and CTD-PAH, and mixed venous O2 saturation % in IPAH and CHD-PAH (p varying from <0.0001 to 0.027). But, TAPSE / systolic pulmonary artery pressure ratio, right atrial-pulmonary capillary wedge pressure difference, pulmonary vascular resistance and its ratio to systemic vascular resistance, cardiac index were not related with survival. Baseline high versus intermediate /low risk was associated with a lower overall survival and CEP-free survival ( p=0.03 and p=0.003, respectively). Male sex [hazard ratio(HR):1.73;1.2-2,51,p = 0.004], 6MWD (p<0.001), FC III/IV (HR: 2.52;1.47-4.32, p<0.001) and baseline low-risk (HR:0.37;0.21-0.65, p<0.001) were independent predictors of mortality. Conclusions Our nation-wide data revealed current insights regarding the clinical, echocardiographic,haemodynamic and neurohumoral predictors of morbidity and mortality in PAH and group IV PH.

Echocardiographic insights redefining risk in pulmonary arterial hypertension: a focus on right atrial volume index for enhanced stratification

Abstract Introduction In Pulmonary arterial hypertension (PAH), the right atrium plays a critical role, and its size, determined by echocardiography, is crucial for risk stratification. Despite this, current guidelines still prioritize right atrial area (RAA) over the right atrial volume index (RAVI). This approach is contrary to the recommendations of international echocardiography societies since 2016, which advocate for the use of RAVI for a more accurate assessment. Purpose Identify the RAVI value corresponding to the RAA, in PAH risk stratification used in the 2022 ESC guidelines. Methods We conducted a retrospective analysis of all consecutive patients of a single-center, since 2002. Patient's echocardiograms were revised for simultaneous assessment of RAA and right atrial volume index (RAVI). Over an average follow-up of 6.7 years (SD 5.9), we recorded a cohort of 82 patients diagnosed with PAH. From this group, we excluded 27 patients with congenital etiologies, 14 due to the insufficient quality of echocardiographic data, and one patient identified as an extreme statistical outlier. A Pearson's correlation analysis was used to access the correlation between RAA and RAVI for PAH diagnosis. Results A total of 40 patients were included with a mean age at diagnosis of 48.85 years (SD 17.82), predominantly female (77.5 %). The most prevalent etiologies were idiopathic (32.5%) and connective tissue disease-associated PAH (27.5%). Clinical presentations included right heart failure signs in 30% of patients, rapid symptom progression in 12.5%, syncope history in 15% and 77.5% in WHO-FC III-IV. Average 6-MWD and NT-proBNP levels were 392,1 m (SD 120,2) and 1636,18 ng/L (SD 2576,14), respectively. Average hemodynamics parameters were right atrial pressure 7,39 mmHg (SD 4,940); cardiac index 2,28 L/min/m2 (SD 2,06); stroke volume index 3,38 mL/m2 (SD 3,92) and mixed venous oxygen saturation 65,68% (SD 10,86). Average echocardiographic parameters were RAA 20,14 cm2 (SD 4,80); TAPSE/sPAP 0,34 mm/mmHg (SD 0,18) and RAVI 37,78 mL/m2 (SD 13,67), with 10% of pericardial effusion. Statistical analysis revealed a strong and significant correlation between RAA and RAVI (r=0.82, 95% CI: 0.69-0.90, p<0.001). The derived linear relationship is expressed as "y=2.8*X -18". Therefore, an RAA value of 18 cm² translates to a RAVI of 32 mL/m², while an RAA of 26 cm² corresponds to a RAVI of 55 mL/m². Conclusion Our study supports a revision in HAP risk assessment guidelines, suggesting a shift to a more comprehensive approach using right atrial volume index (RAVI) measurements. We propose categorizing risk as low for RAVI < 32 mL/m², intermediate for RAVI between 32 and 55 mL/m², and high for RAVI > 55 mL/m². This recommendation aligns with the standards of international societies and is grounded in best clinical practices, considering that indexing measurements of the right atrium to body size potentially offers greater accuracy than absolute values.

The effects of targeting mild hypercapnia on right ventricular function after out-of-hospital cardiac arrest. A sub-study of the TAME trial.

Abstract Background The Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial found similar neurological outcomes between mild hypercapnia and normocapnia in resuscitated out-of- hospital cardiac arrest (OHCA) patients. Hypercapnic acidosis can cause pulmonary vasoconstriction and aggravate right ventricular dysfunction, which is common and associated with worsened outcomes after OHCA. Purpose We investigated the effects of targeting mild hypercapnia on right ventricular function. Methods Single-centre, pre-planned and prospective sub-study. Comatose OHCA patients were randomised to targeted mild hypercapnia (PaCO2 =6.7–7.3 kPa) or targeted normocapnia (PaCO 2 =4.7- 6.0 kPa) for 24 hours. Transthoracic echocardiography was performed at baseline, during intervention and 48 hours after randomisation. Serial right heart catherisation (RHC) was performed if available. Results A total of 137 patients were randomised, 111 were evaluated with echocardiography and 52 and 59 randomised to mild hypercapnia and normocapnia, respectively. 84 patients received RHC; 41 and 43 in the hypercapnia and normocapnia-group, respectively. Overall, the median age was 64 years, 80 % were male and median time to ROSC was 22 minutes. Baseline characteristics did not differ significantly between treatments groups (p >0.05). Targeting mild hypercapnia was associated with lower tidal volumes, respiratory frequencies and respiratory acidosis (P-group < 0.05). Positive end-expiratory pressure, right atrial pressure, pulmonary vascular resistance index and pulmonary capillary wedge pressure were similar between groups (P-group > 0.05). Median time to echocardiography after randomisation was 21 (IQR 14-23) and 17 (IQR 9-22) hours in the hypercapnia and normocapnia-group, respectively. Tricuspid annular plane systolic excursion (TAPSE) was similar between treatment-groups at baseline and higher in the hypercapnia-group during the intervention with a median of 21 mm (IQR 18-23) versus 16 mm (IQR 13-21), p = 0.002. S', fractional area change (FAC) and the ratio of TAPSE to the pulmonary artery systolic pressure (PASP) were all higher in the hypercapnia-group during the intervention. Overall, median left ventricular ejection fraction was 45 % (IQR 38-55) without treatment group differences (p=0.2). Both invasive and echocardiographic assessment found increased cardiac index and stroke volumes in the hypercapnia-group (p <0.05). Right ventricular stroke work index (RVSWI) was consistently higher in the hypercapnia-group throughout the intervention (P-group < 0.001), while the pulmonary artery pulsatility index did not differ (P-group >0.05). Conclusions In patients resuscitated from OHCA, targeting mild hypercapnia compared to normocapnia was associated with increased TAPSE, S', FAC, TAPSE:PASP, RVSWI and cardiac index. Contrary to our prior concern these results indicate improved right ventricular function while targeting mild hypercapnia.

Real-world evidence on pulmonary arterial hypertension: interim analysis from the Italian observational study INSPECTIO

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters

Effects of pulmonary hypertension targeted therapy on haemodynamics in pulmonary arterial hypertension associated with adult congenital heart disease: a meta-analysis

Abstract Background Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. There is growing evidence that PAH drugs lead to improved hemodynamics, exercise capacity, quality of life and survival in patients with PAH. Purpose The aim of this systematic review and meta-analysis is to evaluate the effects of pulmonary hypertension (PH) medical therapy on the haemodynamic parameters as well as exercise capacity in adult patients with PAH-CHD. Methods PubMed and the Cochrane Library databases have been systematically searched. Meta-analysis was conducted using STATA and Review Manager. Results Fourteen studies including 575 patients were analyzed. Pulmonary haemodynamics improved in patients receiving PH-targeted therapy. The weighted mean reduction in mean pulmonary arterial pressure (mPAP) was -5.8mmHg (I2=0%, 95% CI [–7.55, –4.06], p<0.001).The weighted mean reduction in right atrial pressure (RAP) was -5.81mmHg (I2=0%, 95% CI [-7.55, - 4,07], p<0.001). The weighted mean reduction in pulmonary vascular resistance (PVR) was 358.5dynes/sec/cm-5 (I2 51%, 95% CI [-566.55, -150.46] and p<0.001). Cardiac index was increased by 0.61L/min/m2 (I2=6%, 95% CI [0.23,1.00], p=0.002). Six-minute walking distance increased by 47.26m, (I2=0%, CI [38.36, 56.16], p<0.001). Conclusions PH-targeted therapy improves pulmonary haemodynamics and exercise capacity in adult patients with PAH-CHD.

Usefulness of preoperative NT-proBNP for prediction of acute heart failure, perioperative myocardial infarction/injury and mortality after non-cardiac surgery

Abstract Background Predicting cardiac complications after non-cardiac surgery is challenging. Purpose to determine the predictive accuracy of N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP) and, to assess the utility of existing NT-proBNP cutoffs of the 2021 ESC Guidelines for the diagnosis of acute and chronic heart failure for prediction of postoperative acute heart failure (pAHF), perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery. Methods we prospectively determined preoperative NT-proBNP concentrations in consecutive patients at high cardiac risk undergoing inpatient non-cardiac surgery. Uni- and multivariable regression models were constructed to test the association between NT-proBNP concentrations and the outcomes (pAHF, PMI, 30-day and one-year mortality), using NT-proBNP as a continuous variable. We further stratified NT-proBNP into 5 categories according to guidelines (<125 pg/ml, 125 to 299pg/ml, 300 to 900 pg/ml, 901 to 1800pg/ml and >1800 pg/ml). Receiver operating characteristic curves were constructed to determine the predictive value of NT-proBNP. Results Among the 2,334 cases included, pAHF occurred in 83 (3.6%), PMI in 381 (17%), 45 (2.5%) patients died within 30 days and 179 (10%) within one year. After adjusting for confounders, NT-proBNP concentrations were independent predictors of pAHF (adjusted hazard ratio [aHR] 1.8 [95%CI, 1.5-2.1], p<0.001), PMI (aHR 1.3 [95%CI, 1.2-1.4],p<0.001) and 30 day/one year mortality (aHR 1.6[95%CI, 1.3-2.0], p<0.001)/aHR 1.5 [95%CI 1.4-1.7], p<0.001). By quintiles, higher the NT-proBNP levels were strongly associated with adverse outcome (Figure). Accuracy of preoperative NT-proBNP for prediction of pAHF was excellent (area under the curve [AUC] 0.825) and better than accuracy of the Revised Cardiac Risk Index score (AUC 0.692, p<0.001), whereas accuracy of NT-proBNP for prediction of PMI (AUC 0.654) and mortality (AUC 0.787) was only moderate. Conclusion NT-proBNP concentrations are independent predictors of pAHF, PMI and short and long-term mortality following non-cardiac surgery. Stratifying NT-proBNP concentrations using current recommended cut-offs could help to further determine the magnitude of the risk, mainly of pAHF.

Frailty and MECKI score in predicting mortality in advanced heart failure

Abstract Background Physical frailty (PF), characterized by decreased physiological reserves and increased vulnerability to stressors, has emerged as a significant predictor of adverse outcomes in heart failure (HF). The MECKI (Metabolic Exercise Cardiac Kidney Index) score, a composite index derived from cardiopulmonary exercise testing parameters and renal function, has shown promise in predicting outcomes in HF patients. Purpose The aim of the study is to evaluate the independent prognostic role of the MECKI score and PF on mortality in patients with advanced heart failure (AHF). Methods Ninety-one patients with AHF were enrolled, including 42 on the heart transplant waiting list, 10 undergoing evaluation for listing, and 49 removed from the list due to transplant contraindications or reaching age limits. All patients included in the study were on medically optimized therapy. MECKI score assessment was conducted upon enrollment, along with hematological and biochemical evaluations including creatinine, hemoglobin, Na+, and NT-pro-BNP levels. Patients also underwent echocardiography assessing ejection fraction (EF), TAPSE, Inferior Vena Cava (IVC) diameters, and PASP. Additionally, all patients performed the 6-minute walk test (6MWT) and cardiopulmonary exercise testing with assessment of VO2max and VE/VCO2. Frailty was assessed based on modified Fried criteria. Results The mean age was 56.5±11.2 years. Mean NYHA class was 2.7±0.6, EF was 28.8±7.6, TAPSE was 17.5±4.2, and NT-proBNP was 2912.2±3249.0. Mean VO2max was 12.0±3.5 ml/kg/min, and mean distance walked during 6MWT was 278.8±137.2 meters. Mean frailty score was 3.2±1.2 while mean MECKI score was 15.2±14,2. During a mean follow-up of 32.0±15.3 months, there were 21 deaths, 15 patients received heart transplants, and 1 patient underwent LVAD implantation. Stratified data for mortality showed statistically significant differences in deceased patients compared to survivors regarding NYHA class (3.2±0.3 vs 2.6±0.7; p<0.001), Frailty Index (4.4±0.7 vs 2.7±1.13; p<0.001), NT-proBNP (5425.0±2863.0 vs 1731.0±1618.0; p<0.001), VE/VCO2 (42.7±12.3 vs 35.0±9.1; p<0.003), and MECKI score (29.4±15.2 vs 11.2±11.2; p<0.001). Linear regression analysis demonstrated a significant positive correlation for Frailty Index and MECKI score with age, NYHA class, VE/VCO2, IVC, and NT-proBNP, while showing a negative correlation with TAPSE, VO2max, and 6-minute walk test. Cox regression analysis on mortality demonstrated the predictive role of Frailty (HR=2.121; 95%CI=1.017-4.421; p=0.045) and MECKI score (HR=1.043; 95%CI=1.009-1.079; p=0.014) independently from age, sex, NYHA class, NT-proBNP, EF, TAPSE, VO2max, 6MWT, and IVC diameter. ROC curves demonstrated an AUC of 0.896 for MECKI score and mortality, and 0.884 for Frailty Index and mortality. Conclusions The MECKI score and physical frailty are both valid independent predictors of mortality in patients with advanced heart failure.

Ventricular interaction and clinical outcomes in patients undergoing transcatheter tricuspid valve repair

Abstract Background Excessive volume overload of the right ventricle (RV) due to tricuspid regurgitation (TR) can cause a leftward shift of the interventricular septum and changes left ventricular (LV) geometry, which leads to decreases LV distensibility and results in cardiac output. This unfavorable ventricular interaction might have prognostic impacts of patients undergoing transcatheter tricuspid valve repair (TTVr). Purpose We investigated the association between the ventricular interaction and clinical outcomes in patients undergoing TTVr. Methods We retrospectively assessed 304 patients who underwent TTVr. The ventricular interaction was assessed using LV eccentricity index which was defined as LV antero-posterior dimension / LV septo-lateral dimension at end-diastole in the parasternal short-axis view (Figure 1). Increased ventricular interaction was defined as LV eccentricity index ≥1.2. The primary outcome was a composite of all-cause mortality and heart failure hospitalization within one year after TTVr. Results The mean LV eccentricity index at baseline was 1.23 ± 0.20, and 168 of 304 patients (55.3%) had increased ventricular interaction. Patients with increased ventricular interaction were more likely to have massive or torrential TR, reduced RV function, larger RV areas, and lower cardiac index. Increased ventricular interaction at baseline was associated with an increased risk of the composite outcome (HR 2.14; 95%CI 1.36–3.37; p=0.001; Figure 2A), which was consistent after adjusting for age, male sex, renal function, LV ejection fraction, RV function, and residual TR. Echocardiography at baseline showed that 83 of 168 patients (49.4%) with increased ventricular interaction at baseline had an improvement in the ventricular interaction (i.e., LV eccentricity index ≥1.2 at baseline but <1.2 at discharge), which was associated with a lower risk of the composite outcome than persisted ventricular interaction (i.e., LV eccentricity index ≥1.2 at both baseline and discharge) (Figure 2B), irrespectively of baseline characteristics and residual TR. Smaller RV area and residual TR ≤2+ were related to the improved ventricular interaction. Conclusion Ventricular interaction, defined as LV eccentricity index ≥1.2, is associated with an increased risk of clinical outcomes after TTVr. However, the post-procedural improvement in ventricular interaction after TTVr may be linked to better prognosis.Figure 1Figure 2

Elective endovascular reperfusion therapies in intermediate-high risk pulmonary embolism after PERT assesment

Abstract Background The ideal management of patients with intermediate-high risk (IHR) pulmonary embolism (PE) is still unknown. A multidisciplinary approach by Pulmonary Embolism Response Teams (PERT) in combination with the advent of endovascular therapies sounds promising. Purpose Evaluate in-hospital events of elective endovascular reperfussion therapies in selected IHR PE patients after PERT assesment in a single center initial experience. Methods Analysis of consecutive patients with PE admitted from Jan/2017 to Jan/2024. The in-hospital evolution of an elective invasive strategy defined by an institutional PERT (since April/2021) in IHR PE patients was compared against the current standard of care (isolated anticoagulation and reperfusion only after hemodynamic collapse). Patients with limitations of therapeutic efforts due to comorbidities were excluded. Results 361 patients with PE were treated with 76 (21.1%) stratified as IHR. After excluding 14 patients due to limitations of therapeutic efforts (78±9.4 years; 64.3% active cancer), 62 were included for analysis. An elective endovascular treatment was performed in 20 (31.3%) patients; these were younger and with fewer comorbidities. However, they had more tachypnea, greater central distribution of thrombotic burden and signs of right ventricle overload assessed by flattening of the interventricular septum. Baseline characteristics, clinical presentation and management are described in table 1. Within the invasive group, endovascular reperfusion was performed with local thrombolysis (70%), aspiration thrombectomy (15%) or their combination (15%). During hemodynamic evaluation, hidden shock was detected in 42.9% (6/14), with improvements in cardiac index observed after reperfusion therapy (n=8; 2.1 vs. 2.5). Improvement was also observed in pulmonary artery systolic pressure (n=14, 56.9 vs. 37.1mmHg; p<0.001) and right ventricular function (n=15, TAPSE 16 vs. 22mm; p<0.001). Compared with the current standard of care, an elective invasive approach was associated with a shorter hospital stay (6.5 vs. 9 days; p=0.02), less hemodynamic collapse (0% vs. 19.1%; p=0.04), need for mechanical ventilation (0% vs. 19.1%; p=0.04) and in-hospital mortality (0% vs. 21.4%; p=0.04) without differences in the incidence of major bleeding (Fig 1). After multivariate logistic regression analysis, the mortality benefit persisted in favor of an invasive strategy (p=0.014). Conclusions An "elective" invasive strategy in selected patients with IHR PE after PERT assessment was safe and resulted in less major in-hospital cardiovascular events in a single-center initial experience. Although these results should be taken with caution given the limitations of this study (single-center, small observational sample), they are in line with recent reports and are the focus of ongoing large randomized clinical trials.Table 1

Hemodynamic monitoring during weaning from mechanical ventilation in critically ill pediatric patients: a prospective observational study

BackgroundCardiovascular dysfunction is a significant factor contributing to weaning failure in mechanically ventilated children. Understanding the cardiopulmonary pathophysiological changes that occur during weaning is a prerequisite for the early recognition of weaning failure of cardiovascular origin. This study aimed to assess the effect of weaning trials on central hemodynamics and to identify the indices predictive of cardiac-related weaning failure.MethodsThis prospective observational study was conducted in the Pediatric Intensive Care Unit (PICU) and included mechanically ventilated patients aged between 2 and 30 months who were on minimal ventilatory settings and ready for weaning. Patients who were hemodynamically unstable, diagnosed with neuromuscular diseases, or diagnosed with cardiac diseases were excluded. Hemodynamic parameters were evaluated during weaning from ventilation via echocardiography and noninvasive cardiometry during pressure support (PS) ventilation and at the end of the spontaneous breathing trial (SBT).ResultsThe study included 50 patients, comprising 30 males (60%) and 20 females (40%) with ages ranging from 2 to 30 months. Echocardiography revealed a significant increase in the cardiac index (CI), tricuspid annular plane systolic excursion (TAPSE), and the E/A ratio at the end of SBT. Moreover, right ventricular systolic pressure (RVSP) significantly decreased. Noninvasive cardiometry revealed a significant increase in the index of contractility (ICON) and CI at the end of SBT (p-value = 0.023 and < 0.001, respectively). Of the 12 (25%) patients who failed their first extubation trial, they exhibited a significantly lower CI and TAPSE (p values = 0.001 and 0.001, respectively).ConclusionThis study identified that weaning from mechanical ventilation in children is associated with hemodynamic changes, which can impact weaning success and reveal potential ventricular dysfunction. Bedside echocardiography was found to detect cardiac dysfunctions during weaning, and noninvasive cardiometry was considered a reliable tool that supports echocardiography for detecting changing trends in CI in PICUs. However, accurate values should be confirmed by echocardiography.

The Predictive Value of Perioperative Inflammatory Indexes in Major Arterial Surgical Revascularization from Leriche Syndrome

Objectives: The role of inflammation in the pathophysiology of atherosclerosis is extensive. Our study aims to assess the predictive role of inflammatory indexes regarding in-hospital mortality in major vascular surgery of Leriche syndrome as a convenient, low-cost, and noninvasive prognostic marker to optimize the patient’s perioperative course. Methods: Our retrospective single-center study enrolled consecutive patients diagnosed with aortoiliac occlusive disease, Leriche syndrome, who underwent elective major vascular surgery between 2017 and 2023 in a tertiary cardiovascular center. Preoperative, postoperative, and day-one after-surgery data, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, and monocyte–lymphocyte ratio, were studied to the endpoint, in-hospital death. We also tested the delta values of the indexes to the endpoint. The indexes were compared to the Revised Cardiac Risk Index (RCRI) and Vascular Surgery Group Cardiac Risk Index (VSG-CRI) for outcome prediction. Results: The tested inflammatory indexes significantly increased from the preoperative to postoperative and, further, to the day-one settings. Preoperative AISI (p = 0.040) emerged as the only independent risk factor regarding in-hospital death occurrence in Leriche patients who underwent major revascularization surgery. While RCRI did not significantly predict the endpoint (AUC = 0.698, p = 0.057), VSG-CRI (AUC = 0.864, p = 0.001) presented the best result in ROC analysis. Postoperative NLR (AUC = 0.758, p = 0.006) was next, followed by NLR postoperative–preoperative (_Preop-_Postop) delta value (AUC = 0.725, p = 0.004), postoperative SIRI (AUC = 0.716, p = 0.016), SIRI_Preop-_Postop delta value (AUC = 0.712, p = 0.016), postoperative SII (AUC = 0.692, p = 0.032), and SII_Preop-_Postop delta value (AUC = 0.631, p = 0.030). Conclusions: Inflammatory indexes are valuable tools for assessing perioperative risk in major vascular surgery, enhancing the value of the already validated risk scores.

STATE OF HAEMODYNAMICS AND OXYGEN BUDGET IN THE PERIOPERATIVE PERIOD IN PATIENTS WITH OSTEOARTHRITIS AND CONCOMITANT CARDIAC PATHOLOGY DURING TOTAL HIP ARTHROPLASTY SURGERY DEPENDING ON THE TYPE OF SURGICAL ACCESS

Summary. Aim. To compare the hemodynamic status and oxygen budget in patients with osteoarthritis and comorbid cardiac pathology during total hip arthroplasty, based on the type of surgical approach used. Materials and Methods. The study analyzed the treatment outcomes of 90 patients with stage 3-4 osteoarthritis of the hip who underwent total cemented hip arthroplasty. All patients were divided into two groups according to the surgical approach (traditional posterior or modified posterior). The study was conducted at the following stages: before surgery, immediately after surgery, 24 hours post-surgery, and one week after surgery. The following parameters were recorded: hemodynamic parameters (heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and central venous pressure) and oxygen budget parameters (hemoglobin (Hb), lactate, hematocrit (Ht), oxygen saturation of hemoglobin in arterial and venous blood (SaO2 and SvO2), partial pressure of oxygen in arterial and venous blood (paO2 and pvO2)). Based on these data, the following indices were calculated: left ventricular ejection fraction (LVEF), cardiac index (CI); oxygen content in arterial and venous blood (CaO2 and CvO2), arteriovenous oxygen content difference (C(a-v)O2), oxygen transport (TO2), oxygen consumption (VO2); systemic perfusion pressure (SPP), blood flow power (BFP), oxygen reserve (OR), and circulatory reserve (CR). Results. The use of the modified posterior approach positively influenced hemodynamic parameters. After the surgery and on the 7th day post-surgery, SPP was significantly lower with the modified posterior approach. The CI was also significantly affected by the modified posterior approach. Throughout the study, except for the first stage, CI was significantly higher when using the modified posterior approach. LVEF increased significantly with both approaches, but on the 7th day post-surgery, it was significantly higher in the second group. BFP did not statistically differ between the two groups throughout the study, but its energy efficiency was lower, primarily due to the arteriovenous oxygen content difference (C(a-v)O2). C(a-v)O2 was the same before surgery for both approaches. At subsequent stages of the study, the differences between the groups increased, and on the 7th day, they were the most significant, with C(a-v)O2 being lower after using the modified posterior approach. The energy efficiency of blood flow was assessed by calculating OR and CR. Both indicators were significantly higher during the study, except at the preoperative stage, when using the modified posterior approach. Conclusions. Our study clearly demonstrates the benefits of implementing the modified posterior approach in total hip arthroplasty for patients with osteoarthritis and comorbid cardiac pathology. This approach improves hemodynamic and oxygen budget parameters compared to the traditional approach, which can significantly impact treatment outcomes for patients with cardiac comorbidity and reduce the number of postoperative complications.

Fluid Overload Modifies Hemodynamic Impact of CRRT: Evidence of a Covert Cardiorenal Syndrome?

Fluid overload (FO) in critically ill children correlates with higher morbidity and mortality rates. Continuous renal replacement therapy (CRRT) is commonly employed to manage FO. In adults, both FO and CRRT adversely affect myocardial function. It remains unclear if children experience similar cardiovascular effects. Observational single-center study on children (<18 years) receiving CRRT at Texas Children's Hospital from 11/2019 to 3/2021. Excluded were those with end-stage renal disease, pacemakers, extracorporeal membrane oxygenation, ventricular assist devices, apheresis, or without an arterial line. Electrocardiometry (ICON® Osypka Medical GmbH (Berlin, Germany)) which is non-invasive and utilizes bioimpedance, was applied to obtain hemodynamic data over the first 48 hours of CRRT. Our aim was to identify how FO >15% affects hemodynamics in children receiving CRRT. Seventeen children, median age 43 months (IQR 12-124), were included. The median FO at CRRT initiation was 14.4% (2.4%-25.6%), with 9 (53%) patients having FO >15%. Differences were noted in systemic vascular resistance index (1277 [IQR 1088-1666] vs. 1030 [IQR 868-1181] dyne*s/m2/cm5, P < 0.01), and cardiac index (3.90 [IQR 3.23-4.75] vs. 5.68 [IQR 4.65-6.32] L/min/m2, P < 0.01), with no differences in heart rate or mean arterial pressure between children with and without FO. FO affects the hemodynamic profile of children on CRRT, with those having FO >15% showing higher SVRI and lower CI, despite HR and MAP remaining unchanged. Our study illustrates the feasibility and utility of electrocardiometry in these patients, suggesting future research employ this technology to further explore the hemodynamic effects of dialysis in children.

Normalization of Electrocardiogram-Derived Cardiac Risk Indices: A Scoping Review of the Open-Access Literature

Normalization of Electrocardiogram-Derived Cardiac Risk Indices: A Scoping Review of the Open-Access Literature

Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study

Chronic kidney disease (CKD) affects ~10% of the population and cardiovascular disease is its commonest complication. Despite treatment, patient outcomes remain poor and newer therapies are urgently needed. Here, we investigated the systemic and renal effects of apelin in CKD. In a randomized, double-blind, placebo-controlled, crossover study, 24 subjects (12 patients with CKD and 12 matched healthy subjects) received pyroglutamated apelin-13 ([Pyr1]apelin-13, 1 nmol/min and 30 nmol/min) or matched placebo on two separate visits. Systemic and renal hemodynamics were monitored throughout. The co-primary endpoints were change in systemic vascular resistance index and renal blood flow. Secondary endpoints were change in blood pressure, cardiac output, pulse wave velocity, glomerular filtration rate, natriuresis, free water clearance and urinary protein excretion. In both health and CKD, 30 nmol/min [Pyr1]apelin-13 reduced mean arterial pressure by ~4%, systemic vascular resistance by ~12%, and increased cardiac index by ~10%, compared to placebo (p < 0.05 for all). Both doses of [Pyr1]apelin-13 increased renal blood flow by ~15%, natriuresis by ~20% and free water clearance by ~10%, compared to placebo (p < 0.05 for all). In patients with chronic kidney disease only, glomerular filtration rate fell by ~10%, effective filtration fraction by ~5% and proteinuria by ~25% (p < 0.01 for all). Apelin has short-term cardiovascular and renal benefits in CKD. If maintained longer-term, these should improve patient outcomes. Clinical trials of long-acting oral apelin agonists are justified in CKD and other conditions with impaired salt and water balance. Registration number at www.clinicalTrials.gov: NCT03956576. Funded by Kidney Research UK.