Systolic Function Research Articles

HIV is associated with subtle impairments in left ventricular function: insights from a large prospective cohort study of well-treated people with HIV

Abstract Background Human Immunodeficiency Virus (HIV) has become a treatable, chronic condition, but people with HIV still face an elevated risk of cardiovascular disease, including heart failure. Purpose To assess echocardiographic alterations in left ventricular (LV) function in a contemporary cohort of well-treated people with HIV compared to the general population. Methods We included 744 people with HIV frequency matched 1:1 on age and sex with controls from the general population. Both people with HIV and controls underwent echocardiography, physical examination, questionnaires and blood sampling according to similar study protocols. LV systolic dysfunction was defined as LV ejection fraction (LVEF) <50% or absolute global longitudinal strain (GLS) <16%. LV diastolic function was defined as abnormal if the following was true for half or more available parameters: (1) average E/e’>14, (2) septal e’ velocity < 7 cm/s or lateral e’ velocity <10cm/s, (3) tricuspid regurgitation velocity >2.8 m/s, (4) left atrial volume index >34ml/m2. Associations between HIV status and LV function were assessed using linear and logistic regression models adjusted for age, sex, smoking, hypertension, diabetes mellitus, total cholesterol and high-sensitivity C-reactive protein. Among people with HIV, the association between HIV-specific characteristics and LV function were assessed using logistic regression models with adjustment for the same potential confounders. Results Mean age was 53.4 years and 88% were male. For people with HIV, median time since HIV diagnosis was 18 years and 99% received antiretroviral therapy. People with HIV had lower adjusted mean absolute GLS [17.6 vs. 18.5%, p<0.001], E/A ratio [1.0 vs. 1.2, p<0.001] and average e’ [9.5 vs. 10.5 cm/s, p<0.001] than controls, while LVEF and E/e’ were not significantly different between people with HIV and controls (Figure 1). HIV was associated with impaired systolic function as assessed by GLS [odds ratio 1.70, 95% CI: 1.17-2.46, p=0.005], but not when assessed by LVEF [odds ratio 1.06, 95% CI: 0.78-1.45, p=0.69](Figure 2). Living with HIV was not associated with diastolic dysfunction compared to controls [odds ratio 0.97, 95% CI: 0.61-1.52, p=0.88], but longer HIV-duration was associated with higher odds of diastolic dysfunction among people with HIV (odds ratio 1.06, 95% CI: 1.02-1.10 per year, p=0.004). Current antiretroviral medication type, previous AIDS defining conditions, current CD4+ count and detectable viral load were not associated with LV dysfunction. Conclusion People with HIV show signs of early impairments in longitudinal LV systolic function compared to the general population. These subclinical changes may underlie the increased risk of heart failure observed in PWH.

Echocardiographic left and right ventricular strain reference values and their associated characteristics in a healthy adult population from the ELSA-Brasil Study

Abstract Background/Introduction Impaired left ventricular (LV) systolic function is a well-known predictor of cardiovascular morbidity and mortality. Global longitudinal strain (GLS) analysis has been shown a robust measure to detect early systolic dysfunction and a prognostic parameter beyond traditional echocardiographic systolic parameters. Standard reference values for echocardiography measures have been established by echocardiography societies. However, these data may not accurately represent diverse world populations. Purpose We aimed to describe, from a Brazilian multiethnic population, age and sex-specific reference values for left (LV) and right ventricles (RV) GLS in a sample free of cardiovascular disease and risk factors, and to describe the impact of these risk factors according to GLS distribution. Methods ELSA-Brasil is a prospective cohort to investigate cardiovascular disease and diabetes including 15,105 participants aged 35 to 74 years. A predefined representative randomly selected sample with echocardiographic exam was included. We categorized the sample in tertiles according to severity of LV and RV systolic function measured by GLS, and applied trend tests across ordered groups to illustrate the association between GLS and demographic characteristics and echocardiographic measures of cardiac structure and function. Results In the study population (n=527), the mean age was 50.2 years and 59% were women. The overall mean value of LVGLS was -19.0 ± 2.4%, while the mean value of RVFWLS was -28.35 ± 3.06%. Women had higher absolute values of LV and RV GLS compared to men. Conclusion Our study provided the reference ranges for LV and RV GLS in a large middle-aged healthy Brazilian sample, with sex-differences reflected on these values.Central FigureTable 1:Tertiles of LVGLS and RVFWLS

Improving time-efficiency and accuracy in echocardiography: real-time automated measurements of left ventricular global longitudinal strain using deep learning

Abstract Background Accurate quantification of left ventricular (LV) systolic function is fundamental in echocardiography. LV Global Longitudinal Strain (GLS) offers advantages over LV ejection fraction, being more sensitive, reproducible and offering better prognostic value. However, existing semi-automatic methods are time-consuming and heavily operator-dependent. Additionally, poor image quality and foreshortening decrease accuracy and reproducibility of GLS. As a result, these challenges lead to suboptimal efficiency and underutilization of GLS quantification in clinical practice. Purpose Our objective was to develop a deep learning (DL) application for real-time automated measurements of GLS, capable of providing tracking quality and foreshortening feedback during scanning. Subsequently, we aimed to validate the novel method in a prospective cohort study. Methods Deep learning networks were trained to identify apical views, identify timing of end-systole and end-diastole, conduct cardiac segmentation, estimate myocardial motion, assess LV length in each view for foreshortening detection, and present real-time visualization of tracking quality and GLS values for three cardiac cycles to the operator for review (Figure 1). The DL method was validated in a prospective cohort of 40 patients included regardless of image quality. Agreement with manual measurements obtained using semi-automatic software (EchoPAC version 204, GE HealthCare, Horten, Norway) was evaluated. Bland-Altman statistics and Pearson's correlation coefficient were used to evaluate agreement and correlation. Results Feasibility for real-time DL measurements of GLS was 98%, with one patient excluded due to poor image quality. There was good agreement (Bias 0.7%, LoA: -1.6 to 3.1%, figure 2) and excellent correlation (Pearson’s correlation coefficient of 0.93, p<0.001) between the real-time DL application and manual reference measurements for GLS. Using the DL application during scanning resulted in a 58% (95% CI 56%-61%) reduction in time required for scanning and post-processing to obtain GLS values, compared to using the semi-automatic method. Average time consumption was 2 minutes and 16 seconds for the DL method and 5 minutes and 27 seconds for the reference method. Conclusion Using deep learning, real-time fully automated measurement of GLS during scanning is feasible, time-saving, and provides good agreement with reference methods. Real-time measurements also offer the potential to reduce operator-related variability by integrating tools to provide image and tracking quality feedback to the user, ultimately benefiting patients.Application user interfaceAgreement between DL and reference

Impact of epicardial adipose tissue and atrial functional impairment in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

Abstract Background Recent studies outlined the additional prognostic value of atrial function in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). At the same time, increased epicardial adipose tissue (EAT) volumes have proven impact on atrial functional impairment in cardiovascular disease by nurturing adverse atrial remodelling. Purpose To explore the impact of increased EAT volumes as a potential pathomechanistic factor of atrial functional impairment in patients with severe AS undergoing TAVR. Methods 146 patients with severe AS underwent cardiac magnetic resonance (CMR) within 48h prior to TAVR between January 2017 and June 2021. Image analyses included myocardial volume quantification as well as CMR-feature-tracking derived strain. EAT volumes were manually delineated on short axis stacks in end-diastolic cardiac phases and indexed to body surface area. Functional and morphological parameters were compared between patients with high and low EAT volumes. Associations between morphological and functional parameters and EAT were tested using a multivariable linear regression model including patient specific parameters. Results After dichotomization at the median of 46.5ml/m2 total EAT volume, patients were assigned to high- and low-EAT groups accordingly. There was comparable age and body mass index and similar rates of co-morbidities such as hypertension, diabetes and atrial fibrillation in both groups. We observed a higher number of male patients in the high-EAT group (36 [53%] vs. 50 [72%], p=0.018). Regarding left and right ventricular dimensions and function, no differences could be shown. Left atrial (LA) end-systolic volumes were significantly higher in the high-EAT group (29.4ml/ml² [19.7-39.4] vs. 40.9ml/ml² [30.2-59.3], p=0.008), while there were no significant differences in end-diastolic volumes. Furthermore, LA reservoir strain was significantly lower in the high-EAT group compared to the low-EAT group (18.0% [11.7-21.0] vs. 11.8% [7.7-16.4], p=0.008) and was independently associated with higher EAT volumes (p=0.018) irrespective of cardiovascular risk factors and left ventricular (LV) systolic function in a multivariable regression model. Conclusion In patients with severe AS undergoing TAVR, increased EAT volumes are associated with both, morphological and functional changes of the atria. As impaired atrial function was previously shown to be an important predictor of mortality in TAVR patients, those results potentially render EAT as an additional pathomechanistic link between atrial remodelling and worse outcome in TAVR patients.

CD14 blockade preserves left ventricular structure and systolic function in a murine model of ST-elevation myocardial infarction

Abstract Background Cluster of differentiation-14 (CD14) facilitates the excessive pro-inflammatory monocyte-macrophage response to myocardial injury. Both acute and chronic infiltration of pro-inflammatory macrophages are implicated in the immunological progression of ischemic heart failure. However, investigation of clinically practicable strategies of CD14 blockade are yet to be reported. Purpose This fully blinded and randomised preclinical study evaluated the efficacy of a neutralising anti-CD14 antibody given at reperfusion in a murine model of reperfused ST-elevation myocardial infarction (STEMI) with key clinical features. Methods Large anterior STEMI was induced in 48 adult mice by left anterior descending coronary artery occlusion for 1 h prior to reperfusion and randomisation to receive anti-CD14 antibody, isotype control (IgG2a) or saline weekly for four weeks (independently blinded). Outcome measures included functional assessments by 9.4T cardiac magnetic resonance (CMR) imaging and ultra-high-resolution echocardiography at 21- and 28-days post-STEMI, respectively. Results Multi-plane short axis CMR at 21-days post-STEMI revealed greater left ventricular (LV) ejection fraction in the anti-CD14 antibody-treated group compared with saline- and isotype-treated controls (30±1 vs 19±1 and 20±1 %, respectively, p<0.001; Figure 1A). CMR also revealed reduced LV dilatation with anti-CD14-treatment compared to control groups (76±5 vs 102±8 and 107±7 µl EDV in saline- and isotype-treated controls, respectively, p<0.05). Parasternal long axis echocardiography at 28 days post-STEMI confirmed that anti-CD14 antibody treatment was associated with greater LV systolic function compared to saline and isotype controls (30±1 vs 24±1 and 25±2 % EF, respectively, p<0.05; Figure 1B). Preservation of LV end-diastolic (86±4 vs 111±6 and 101±5 µl, p<0.01) and end-systolic (61±3 vs 84±5 and 77±5 µl, p<0.01) volumes was also observed with anti-CD14 treatment. Global longitudinal strain (GLS) of the LV was also significantly greater at 28 days post-STEMI with anti-CD14 treatment relative to saline and isotype controls (-8.5±0.4 vs -6.8±0.3 and -6.6±0.4 %, respectively, p<0.05). Conclusion(s) The findings of this fully blinded and randomised preclinical study provide evidence of a clinically practicable strategy of CD14 blockade initiated at reperfusion to mitigate progressive LV systolic dysfunction and dilatation post-STEMI.Figure 1.Functional outcome measures

Cardiac structure and function in people with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs, however the extent of cardiac involvement in CF is yet to be determined. The remarkable therapeutic advancements with new highly effective CF transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. Purpose We aimed to explore the prevalence of abnormalities and potential subclinical alterations in cardiac structure and function in adults with CF compared to matched controls and investigate potential cardiovascular risk factors in people with CF (pwCF). Methods In this cross-sectional study, 104 adult pwCF in Denmark underwent clinical and echocardiographic examination. All participants were matched 1:1 with controls from the general population on age and sex. Uni- and multivariable linear regression models with adjustment for heart rate, FEV1, smoking status, hypertension and CF-related diabetes (CFRD) were used to test for differences in echocardiographic parameters between cases and controls. Abnormal cardiac function was defined as left ventricular ejection fraction (LVEF) <50%, left ventricular (LV) global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Uni- and multivariable logistic regression models adjusted for age, sex, homozygous genotype, FEV1/FVC, BMI, smoking status, CFRD, pancreatic insufficiency, hypertension, and ischemic heart disease were performed to assess associations between potential risk factors and cardiac dysfunction in CF. Forest plots were constructed to visually represent the findings. Results Of 104 pwCF, 44% were female, mean age was 34 years, 93% received CFTR modulator treatment, and 91% had mutations with only minimal CFTR function (mutation class I-III). The prevalence of abnormal cardiac function in pwCF was 44% versus 22% in controls. Compared to controls, pwCF were found to have smaller LV dimensions, worse LV diastolic function, and more impaired right ventricle (RV) as well as LV systolic function (Table). After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained impaired in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p=0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p=0.008, respectively) (Figure). Conclusion Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for potential risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were identified as factors associated with abnormal cardiac function in pwCF.Figure

Clinical value of anti-DSG2 antibodies in arrhythmogenic right ventricular cardiomyopathy: a real-life experience

Abstract Background/Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease leading to ventricular arrhythmias and heart failure. The diagnosis is challenging and currently based on a set of clinical criteria with limited sensitivity and specificity. Anti-desmoglein-2 (DSG2) antibodies were previously found in patients diagnosed with ARVC, while they were absent in both healthy controls and athletes. Purpose The study aimed to evaluate the diagnostic value of anti-DSG2 antibodies by comparing their concentration in patients with ARVC and other right ventricular diseases. Additionally, the prognostic value of the biomarker was assessed. Methods A cohort of 101 patients with a definite diagnosis of ARVC according to the 2010 Task Force criteria was enrolled (64 males, mean age 47 ± 16 years). The control group included patients with Ebstein anomaly and Eisenmenger syndrome (16 and 21 subjects, respectively). Anti-DSG2 antibody concentration was assessed using enzyme-linked immunosorbent assay (ELISA). After that, an ARVC cohort was followed for 3.9 ± 1.6 years for the occurrence of the primary endpoint of cardiac death or heart transplantation (HTx) and major arrhythmic events (MAEs) defined as ventricular fibrillation, sustained ventricular tachycardia (sVT) or appropriate implantable cardioverter-defibrillator intervention. Results The median anti-DSG2 antibody concentration presented as ELISA optical density (OD) reached 1.36 [0.54-2.15] in the ARVC cohort, while it was 0.4 [0.34-0.54] in Ebstein anomaly group and 0.36 [0.28-0.58] in the Eisenmenger syndrome group. There was a significant difference in antibody levels between ARVC and both control groups (p < 0.001, Figure 1). The cutoff value for the diagnosis of ARVC was 0.774, with 72.3% sensitivity and 100% specificity (AUC = 0.823). After dividing the ARVC cohort according to the designated cutoff point, the anti-DSG2-positive subgroup was significantly younger (44.5 ± 15.4 vs. 52.8 ± 15.5 years, p = 0.017) and more likely to have a history of sVT (68.5% vs. 46.4%, p = 0.041). There was no difference regarding sex, presence of PKP2 or DSG2 mutations, previous sports activities, history of sudden cardiac arrest or syncope, right ventricular dimensions and systolic function, left ventricular ejection fraction and heart failure symptoms. This threshold was not predictive for the primary endpoint and MAEs. However, a more stringent cutoff value for anti-DSG2 level (1.021) was found to predict death or HTx (HR [95% CI] 4.56 [1.05-19.76], p = 0.026, Figure 2). Conclusions The concentration of anti-DSG2 antibodies is significantly higher in ARVC compared to other right ventricular diseases. A high antibody level is prognostic for death or HTx in ARVC.Figure 1Figure 2

Fenofibrate modulates cardiac energy metabolism in moderate-severe aortic stenosis: a mechanistic double-blinded randomised controlled MR trial

Abstract Background Aortic stenosis (AS) is associated with impaired cardiac metabolism and high-energy phosphate production which can further exacerbate the progression to HF. Myocardial lipid accumulation and reduced production of high-energy phosphates have important implications for both systolic and diastolic heart function in AS. Peroxisome proliferator-activated receptor alpha (PPAR-alpha agonist, has the potential to optimise cardiac substrate metabolism, thereby, may be effective in improving cardiac dysfunction and functional capacity in AS. Methods In this prospective, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe asymptomatic AS (n=72) were randomly assigned to Fenofibrate 200 mg daily or matching placebo for 6 months in 4:1 fashion. Of the total 72 participants, 59 received Fenofibrate and 13 received placebo. All subjects underwent cardiac magnetic resonance (CMR) and exercise testing at 0 and 6 months, with follow-up data available in 47 patients. The primary end point was change in myocardial triglyceride content (MTG) determined by proton magnetic resonance spectroscopy (1H-MRS). Secondary outcome measures included change in cardiac energetics (PCr/ATP) determined by phosphorus magnetic resonance spectroscopy (31P-MRS), left ventricular strain determined by myocardial tagging and exercise capacity i.e. peak VO2 assessment via cardiopulmonary exercise testing. Results Cardiac energetics (PCr/ATP) showed statistically significant improvement in the Fenofibrate group (0.14 ± 0.48; CI: - 0.03, 0.30; p=0.05) vs placebo group (0.11 ± 0.75; CI -0.42, 0.65; p=0.64). There was also significant reduction in MTG in the Fenofibrate group (mean change -0.40 ± 0.97; 95% CI -0.74, -0.06; p=0.02). MTG content also reduced in the placebo group (mean change -0.41 ± 0.26, 95% CI -1.10, 0.18, p 0.13), but the reduction was not statistically significant. Though no significant changes were seen in the systolic function parameters, there was a significant improvement in diastolic function in the fenofibrate group only (peak diastolic longitudinal strain rate 9.6, 95% CI: 1.13, 18.1; p = 0.02). Peak VO2 did not show any significant improvement in either group. Conclusions Fenofibrate works as a metabolic modulator upregulating fatty acid metabolism in pressure overload AS hearts. Such modulation is associated with an improvement in cardiac energetics and diastolic function in moderate-severe AS.Main results from baseline to 6 monthsBaseline demographic and CMR parameters

Cardiac structure and function in patients with chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is common and strongly associated with cardiovascular disease, but the pathophysiology has not been fully elucidated. Purpose We aimed to investigate cardiac structure and function in patients with COPD compared to a matched general population. Methods In a prospective cohort study, 796 patients with COPD were included and matched 1:2 on age and sex with controls from a general population study. All participants underwent an examination program including echocardiography. Standardized linear regression coefficients were used to compare cardiac structure and function in patients with COPD vs. controls. Impaired left ventricular (LV) function was defined as a left ventricular ejection fraction (LVEF) <50%, or global longitudinal strain (GLS) <16% (numerical). Impaired right ventricular (RV) function was defined as tricuspid annular plane systolic excursion (TAPSE) <1.7 cm. Diastolic dysfunction was defined as having at least two of the following parameters: E/e’ >14, septal e’ velocity <7cm/s, or lateral e’ velocity <10 cm/s, left atrial volume index (LAVi) >34 mL/m2, or tricuspid regurgitation velocity (TRV) >2.8 m/s. Logistic regression was used to assess associations between having COPD and systolic and diastolic dysfunction. Results Mean age was 70.2 ± 8.3 years and 52% were females. COPD patients had a mean forced expiratory volume in 1 second (FEV1) of 49.4 ± 18.8% predicted. At baseline, 43% of the patients with COPD had hypertension and 10% had diabetes (DM). Additionally, 57% with COPD had cardiovascular disease at baseline, including 12% with ischemic heart disease (IHD), 15% with atrial fibrillation (AF), 6% with heart failure, and 5% with a previous ischemic stroke. Patients with COPD had impaired measures of cardiac structure and function including a lower GLS (COPD vs. controls: 16.3 vs. 19.2%), lower TAPSE (2.3 vs. 2.6 cm), larger LAVi (29.0 vs. 24.7 mL/m2), and higher TRV (2.7 vs. 2.3 m/s), p for all associations <0.001. (See figure). Patients with COPD had a significantly higher prevalence of impaired LV systolic function (OR for GLS <16%: 8.18, 95% CI(6.04; 11.1), p <0.001), impaired RV systolic function (OR for TAPSE <1.7 cm: 2.77, 95% CI(1.63; 4.69), p <0.001), and LV diastolic dysfunction (OR for diastolic dysfunction grade I or higher: 4.00, 95% CI(3.12; 5.13), p <0.001) after adjustment for age, sex, hypertension, smoking, DM, IHD, AF, and lower density lipoprotein. (See figure). Conclusion Patients with COPD had significantly impaired LV and RV systolic function as well as impaired diastolic function compared with individuals from the general population. These findings underscore the importance of recognizing and addressing cardiovascular comorbidities in COPD.

Exercise Doppler echocardiography to detect early changes in the right ventricular-pulmonary circulation unit after pulmonary embolism

Abstract Introduction After pulmonary embolism (PE), patients frequently complain about reduced exercise capacity and dyspnea on exertion, even without pulmonary hypertension (PH). The underlying condition is often chronic thromboembolic disease, which is caused by residual pulmonary obstruction with preserved resting pulmonary haemodynamics. The symptoms are the consequences of the increased dead space ventilation, exercise-induced PH and right ventricular (RV) dysfunction. We aimed to assess the pathologic differences in the echocardiographic parameters of the RV- pulmonary circulation unit among patients with previous PE and the healthy control group. Furthermore, an objective was to compare the hemodynamic response to stress after different treatment strategies (thrombolysis vs. heparin administration). Methods 21 patients after PE (mean age 58,5±12,1 years; 53% men) have been included in the study. All of them were effectively anticoagulated for at least three months, and none had any signs of PH on echocardiography at rest. The control group included 20 healthy volunteers (mean age 56,9±11,5 years; 55% men). Each patient underwent resting and exercise stress echocardiography on a semi-recumbent bicycle ergometer according to a standardised protocol until the maximally tolerated workload. Echocardiography was performed at rest, at 50 Watt workload and during peak stress. The measurements focused on the RV's systolic function (TAPSE), the estimated pulmonary artery systolic pressure (PASP), and the Doppler measurements in the RV and left ventricular outflow tracts. Pulmonary vascular resistance (PVR) and RV-pulmonary artery coupling (RV-PA) were calculated from the echocardiographic parameters. Results The post-PE group had significantly higher PASP (39,2 ±16,6 vs. 27,7±12,5 mmHg; p<0,05) and PVR (1,5±0,4 vs. 1,1±0,3 Wood Units; p<0,05) at peak stress, than the controls. 55% of post-PE patients remained symptomatic, but there were no significant differences between the symptomatic and asymptomatic groups regarding TAPSE, PASP, RV-PA coupling and PVR. 30% of post-PE patients had thrombolysis. In the patients where thrombolysis was performed, the coupling at peak stress was significantly higher than in heparin-treated patients (1,4±0,1 vs 0,9±0,4 mm/mmHg, p<0,05). Conclusion Post-PE patients without resting PH have higher PVR and PASP than the healthy control group, even after at least 3 months of adequate therapy. Post-PE patients treated with thrombolysis may have more preserved RV-PA coupling than the heparin-treated patients.

The condition of myocardium reserves score from a cloud-based analytics platform of Holter ECG data indicates better cardiometabolic function in heart failure

Abstract Introduction Cardiometabolic dysregulation, particularly type 2 diabetes mellitus (T2DM), is associated with subtle myocardial pathologies, even in individuals without known cardiovascular disease. These subclinical changes, often undetectable by standard electrocardiogram (ECG) analytics, can offer valuable insights into the relationship between metabolic health and cardiac function. Novel ECG markers, developed through machine learning and artificial intelligence (AI), may provide the sensitivity needed to detect such changes. Aim This study aims to evaluate novel composite cardiac parameters from an analytics platform in the context of heart failure (HF), seeking to understand their relationship to cardiometabolic dysregulation. Methods Data from the MyoVasc study, a prospective cohort on HF, were analysed. Participants underwent extensive clinical phenotyping, including a Holter ECG assessment. Holter ECG data was processed based on machine learning and AI models on a cloud-based analytics platform (Cardiolyse, Helsinki, Finland), generating both traditional and proprietary ECG, and heart rate variability cardiac health markers. LASSO-penalized logistic regression adjusted for sex and age was performed to select the marker most strongly associated with T2DM. The identified marker was then evaluated in relation to cardiac function and structure as well as HF-related outcome. Results A total of 953 subjects (mean±SD age 64.6±10.5 years; 35.7% women) were included in the analyses. Symptomatic HF stage C/D was present in 54.8% (n=522) of subjects and diabetes mellitus in 22.4% (n=213). The Condition of Myocardium Reserves Score (CMRS) was the novel composite cardiac parameter selected based on its relationship with T2DM. In a Poisson regression model with robust variance adjusted for sex and age, a lower score was associated with T2DM (Prevalence ratio per SD 1.24, 95% confidence interval [1.14;1.36], P=0.0002). In multivariable linear regressions adjusted for traditional cardiovascular risk factors, comorbidities, and medication, a higher CMRS was associated with better global longitudinal strain (β per SD –0.82 [–1.11;–0.53], P<0.0001), diastolic function (left ventricular E/e’; β per SD –0.04 [–0.06;–0.01], P=0.0059) and systolic function (LV ejection fraction; β per SD 2.06 [1.46;2.67], P<0.0001). A lower CMRS independently predicted all-cause death (Hazard ratio per SD 1.25 [1.09;1.45], P=0.0020) and worsening of HF (HR per SD 1.44 [1.21;1.72], P<0.0001) in Cox regression analysis adjusted for the same confounders. Conclusion The Condition of Myocardium Reserves Score exhibited a strong association with cardiometabolic dysregulation. A higher CMRS indicated preserved cardiac function, while a lower score independently predicted increased risk of all-cause death and worsening HF. This novel score offers potential as a non-invasive tool for assessing cardiometabolic health and stratifying risk in patients with HF.

Sinus rhythm maintenance and the changes of echocardiographic parameters in patients with late persistent atrial fibrillation at 6 months after direct current cardioversion

Abstract Background Late persistent non-valvular atrial fibrillation (AF), with a duration of its episode ≥90 days and up to 12 months, is considered a distinct persistent AF entity, which might possess substantial differences as compared to its early persistent pattern (up to 3 months) in terms of myocardial remodeling and its reversibility after cardioversion. Purpose To study the changes of echocardiographic parameters in patients with non-valvular late persistent AF with respect to sinus rhythm (SR) maintenance at 6 months after successful direct current cardioversion (DCCV). Methods The cohort single-center study enrolled 59 late persistent AF patients, who underwent a successful elective DCCV. At 6-months follow-up, patients were subdivided into the groups regarding SR maintenance: 32 (54 %%) patients with a maintained SR (G1), and 27 (46 %) patients with a failure to maintain SR (G2). The parameters of myocardial remodeling and function were evaluated by transthoracic (TTE) and transesophageal echocardiography (TEE) baseline (by TTE and TEE) and at 6-months follow-up (by TTE). Results TTE data from G1 patients, in contrast to G2, suggested better baseline status of left heart chambers, particularly the lower diameter of left atrium (LA), left ventricular (LV) end-diastolic and end-systolic volumes and higher LV systolic function (by LV ejection fraction [EF]). According to the TEE data, G2 (vs. G1) was characterized by more prevalent cases of LA spontaneous (echo) contrast (41 % vs. 15 %, respectively; p=0,042) and LA appendage flow velocity ≤40 cm/s (82 % vs. 53 %, respectively; p=0,022). At 6-months follow-up TTE, G1 patients, as opposed to G2, demonstrated a better profile of echocardiographic parameters, namely a lower LA diameter, LA and right atrium (RA) volumes, along with less advanced LV remodeling and higher LV EF. TTE data from G1 at 6-months follow-up after DCCV suggested the reverse remodeling of both atria, namely the decrease of LA diameter, LA volume and its index (Fig. 1), as well as RA volume and its index. Moreover, G2 demonstrated a decline in LV systolic function, in particular the rise of LV end-systolic volume and decrease of LV EF (Fig. 2), as compared to G1. Furthermore, at 6-months follow-up, G2 patients presented with more advanced severity of PH and tricuspid regurgitation, in comparison with G1. Conclusions Late persistent AF patients with a SR maintenance at 6-months follow-up after successful DCCV presented a better baseline profile of myocardial remodeling and systolic function. The SR maintenance at 6-months follow-up after DCCV was associated with the reverse remodeling of left heart chambers (LA and LV) and RA. On the contrary, a failure to maintain SR in late persistent AF patients was associated with a deterioration in LV systolic function, and more advanced PH and tricuspid regurgitation.

Prognostic value of combined myocardial performance index in patients with acute ST-elevation myocardial infarction

Abstract Background Myocardial performance index (MPI) also known as Tei index is a unique echocardiographic parameter which can estimate both systolic and diastolic performances of left and right ventricles. We previously suggested the echocardiographic parameter combined MPI (CMPI) as a new predictor of the prognosis of acute ST-elevation myocardial infarction (STEMI). The CMPI is the sum of left ventricular (LV) MPI and right ventricular (RV) MPI (CMPI = LV MPI + RV MPI). We supposed that CMPI might be a better predictor in STEMI, because it reflects both ventricular systolic and diastolic functions. Objectives The purpose of this study is to assess the prognostic value of a new echocardiographic parameter CMPI in STEMI patients calculated in acute phase. Methods 240 STEMI patients who underwent primary PCI have been included in the study. Echocardiography (EchoCG) was performed, and LV MPI and RV MPI were assessed within 24 hours after the symptom onset, prior to primary PCI. The MPI was calculated as the sum of isovolumic contraction time (ICT) and isovolumic relaxation time (IRT), divided by the ejection time (ET): MPI = (ICT + IRP) / ET. 50 % of the patients had anterior STEMI. 30 patients (12.5%) had concomitant RV myocardial infarction (MI). Patients were divided into two groups: Group 1 – CMPI > 0.9 (110 patients), Group 2 – CMPI ≤ 0.9 (130 patients). Baseline demographic and clinical characteristics were similar in both groups. Also, there were no differences in LV MI localization and concomitant RV MI between the groups. Primary endpoints were in-hospital and the one-year cardiovascular mortality rates. The secondary endpoint was the one-year heart failure hospitalization rate. Results In Group 1 the in-hospital mortality rate was 9.1%, and 3.1% in Group 2 (p = 0.0489). One-year cardiovascular mortality rate was 12.7% in and 5.4%, respectively (p = 0.0465). One-year heart failure hospitalization was also significantly lower in Group 2 (22.7% vs. 12.3%, p = 0.0332). Conclusion CMPI can be offered as a new predictor for the in-hospital and one-year cardiovascular mortality and one-year heart failure hospitalization rate in patients with acute STEMI.

Coronary microvascular dysfunction as assessed by cardiac MRI and its association with aerobic exercise capacity in dilated cardiomyopathy

Abstract Background Dilated cardiomyopathy (DCM) has a poor prognosis. Aerobic exercise capacity (peak VO2) is an independent predictor of mortality but the central mechanisms contributing to exercise intolerance in DCM are unknown. Purpose To characterise myocardial perfusion reserve (MPR) and determine if cardiovascular magnetic resonance (CMR) measures of structure, function and microvascular function are associated with aerobic exercise capacity in DCM. Methods Single centre, prospective, case-control comparison of adults with DCM and matched controls. Adenosine-stress perfusion CMR to assess cardiac structure, function and quantitative perfusion, and cardiopulmonary exercise testing (CPET) to determine peak VO2, was performed. Controls were propensity matched based on age, sex, body mass index and diabetes status, and between group comparison was adjusted for other key clinical characteristics (CMR: ethnicity and systolic blood pressure; CPET: ethnicity, systolic blood pressure, smoking history and lung disease). Comparison of perfusion in segments with and without late gadolinium enhancement was performed using mixed effects linear regression taking into account individual patient segmental perfusion. Pre-specified multivariable linear regression, including key clinical and cardiac variables, was undertaken in patients with DCM to identify independent associations with percentage predicted peak VO2, which incorporates age, sex, height and weight. Results Sixty-six patients with DCM (median age 61 years, 71% male) were matched to 66 controls (median age 59 years, 71% male). The DCM group had greater left ventricular (LV) end-diastolic and end-systolic volumes, lower systolic and diastolic function, and had more focal and diffuse fibrosis compared to controls (Table 1). There was lower rest (0.58±0.14 versus 0.65±0.17 mL/min/g; P=0.033) and stress (1.53±0.49 versus 2.01±0.60 mL/g/min; P<0.001) myocardial blood flow, and lower MPR (2.69±0.84 versus 3.15±0.84 mL/g/min; P=0.002) in the DCM group. In DCM patients, mixed effects linear regression demonstrated lower rest (adjusted mean 0.54(95% CI 0.50-0.57) versus 0.58(0.55-0.62) mL/g/min; P<0.001) and stress MBF (1.38(1.25-1.51) versus 1.55(1.43-1.67) mL/g/min; P<0.001) in segments with LGE compared to segments without LGE, but there was no difference in MPR (2.71(2.47-2.96) versus 2.76(2.55-2.97) mL/g/min; P=0.496). DCM patients had markedly lower peak VO2 (19.8±5.5 versus 25.2±7.3 mL/kg/min; P<0.001). Multivariable linear regression demonstrated that LV ejection fraction, extracellular volume fraction and MPR, but not LV mass, were independently associated with percentage predicted peak VO2 in DCM (R squared=0.531, P<0.001; Table 2). Conclusions DCM patients have lower rest and stress myocardial blood flow and lower MPR compared to controls. In DCM, MPR, LV ejection fraction and fibrosis are independently associated with aerobic exercise capacity.

Left ventricular volume as a predictor of exercise capacity and functional independence in individuals with preserved ejection fraction

Abstract Background Cardiorespiratory fitness (CRF) is vital for independent living and is a powerful prognostic marker. Increased left ventricular (LV) volume has been linked with high CRF in athletes, but its utility as a diagnostic marker of low CRF across the entire health-disease continuum has yet to be tested. Methods This multi-center international cohort from Australia and Belgium examined the relationship between ventricular size on resting echocardiography and CRF (peakVO2 from cardiopulmonary exercise testing [CPET] or CPET with simultaneous echocardiography) in individuals with preserved LV ejection fraction (≥50%). LV end-diastolic volume (LVEDV) and LVEDV indexed to body surface area (LVEDVi) were tested as predictors of very low CRF (CRF associated with functional disability - peakVO2 < 1100ml or <18 ml/kg/min) and compared against other candidate measures of systolic and diastolic cardiac function that have been associated with heart disease. Thresholds for absolute and indexed LVEDV which best distinguished between lower and higher CRF status were identified. Results 2876 individuals (251 healthy non-athletes, 309 elite endurance athletes, 1969 individuals with unexplained dyspnea, 347 individuals with heart failure with preserved ejection fraction) were included. For the entire cohort, LVEDV had the strongest univariate association with peakVO2 (R2 = 0.45, standardized [std] β 0.67, p< 0.001) and, remained the strongest independent predictor of peakVO2 after adjusting for age, sex and body mass index (std β 0.44, p < 0.001). The relationship between LVEDV and VO2peak differed based on health/disease status (Figure 1). LVEDV demonstrated the greatest diagnostic capability in identifying functional disability (LVEDV AUC 0.72; LVEDVi AUC 0.71, Figure 2), outperforming ejection fraction, diastolic velocities, atrial volumes and pulmonary artery pressure estimates. The probability of achieving a peak VO2 below the threshold required for functional independence was highest for smaller ventricular volumes with LVEDV and LVEDVi of 88ml and 57 ml/m2 proving the optimal cut-points, respectively. Conclusions A small LVEDV is associated with a higher probability of poor exercise capacity, failure to achieve the peak VO2 required for functional independence and is the strongest independent echocardiographic predictor of CRF across the health-disease continuum.Figure 1.Ventricular Size and CRFFigure 2.Predictors of CRF status

High-intensity exercise-related sudden cardiac death in hypertrophy cardiomyopathy

Abstract Background Whether exercise provokes sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is uncertain. Current European guidelines recommend against high-intensity exercise in individuals with high SCD risk or obstructive physiology. Purpose We investigated the factors associated with exercise-related SCD in HCM. Methods We retrospectively analyzed of 2,844 consecutive patients with HCM who underwent evaluation between 2005 and 2023 at a high-volume tertiary center. SCD events were defined as a composite of aborted SCD, appropriate implantable cardioverter-defibrillator (ICD) shock, and SCD. Among 80 first SCD events (2.8%), 75 events had a description of the physical activity at the time of the event. Patients were classified into two groups according to physical activity level at the time of the SCD event. Group 1 included patients with high-intensity exercise-related SCD events, defined as happening during or immediately after high-intensity exercise or physical activity, while Group 2 included patients with SCD events happening at rest or during light or moderate physical activity. Results The 75 first SCD events included 44 aborted SCD, 22 appropriate ICD shocks, and 9 SCD. Median age at SCD event was 54 (IQR 39.5–62.5) years and 60 (80%) were men. Patients in Group 1 (n=14) were younger than patients in Group 2 (n=61) (23.5 [IQR 16–48] vs. 55 [IQR 44–64] years, p<0.001), and most patients in group 1 (92.9%) were under the age of 60 years. Patients in Group 1 had slightly smaller left ventricular (LV) end-diastolic dimension and had higher ESC SCD risk scores (3.6 [IQR 2.5–6.7] vs. 2.4 [IQR 1.7–4.8], p=0.044) than patients in Group 2; however, there were no significant differences in the proportion of high-risk patients (28.6% vs. 14.8%, p=0.396) or patients with AHA major SCD risk factors (57.1% vs. 55.7%, p=0.999). Otherwise, there were no significant differences in the presence of obstructive physiology, apical HCM, and apical aneurysm, LV systolic and diastolic function, and comorbidities between the two groups. Furthermore, of the 29 patients who underwent genetic testing, there was no difference in the proportion of patients with pathogenic sarcomeric variants according to exercise-related SCD (50.0% vs. 65.2%, p=0.683). To note, there was a non-significant tendency towards higher proportion of thin filament variants in Group 1 than Group 2 among those with pathogenic sarcomeric variants (100% [3/3] vs 26.7% [4/15], p=0.084). Conclusions Most high-intensity exercise-related SCD events happened under the age of 60. The ESC SCD risk score was higher in patients with high-intensity exercise-related SCD events, although the SCD risk categories or AHA risk factors could not discriminate patients at higher risk of events. These results suggest that exercise recommendations should not be based on SCD risk category, presence of obstruction, or degree of LV hypertrophy.

High-sensitivity C-reactive protein is associated with cardiac dysfunction and morbidity in a community-based cohort

Abstract Background Inflammation is increasingly recognized as a risk factor for cardiac morbidity in the general population. Biomarkers like high-sensitivity C-reactive protein (hs-CRP) can aid in the detection of adverse systemic inflammation. The relationship between hs-CRP and cardiac structure and function is therefore a target of interest. Purpose The purpose of this study was to investigate the association of inflammation with cardiac structure and function in individuals free of overt cardiac disease. In addition, we examined if hs-CRP provided prognostic information regarding incident heart failure and myocardial infarction independent of echocardiographic measures. Methods In a community-based cohort study, participants were randomly selected for invitation from the Capital Region of Denmark. Echocardiography was performed on all the participants and measures of cardiac structure and function were obtained by blinded investigators. Participants with a history of cardiac disease were excluded from the analysis. Associations between log-transformed hs-CRP and echocardiographic measures were analyzed through uni- and multivariable linear regressions. Results A total of 3,379 individuals were included. Mean age was 55 years, 42% were female and the median hs-CRP was 1.13 (interquartile range: 0.65 - 1.47) mg/L. In the univariable analyses, increasing levels of hs-CRP were associated with worse left ventricular (LV) function including LV ejection fraction, global longitudinal strain (GLS), worse diastolic function (E/e’), worse right heart function (tricuspid regurgitation (TR) velocity and tricuspid annular plane systolic excursion (TAPSE)) and higher left ventricular (LV) mass index (p < 0.001 for all measures) (figure). When adjusting for sex, age, physical activity, smoking status, body mass index, blood pressure, hypercholesterolemia, diabetes, hypertension, creatinine, and heart rate, only LVEF (p < 0.001), GLS, (p < 0.001), E/e’ (p = 0.027), TAPSE (p = 0.008) and peak TR velocity (p = 0.015) remained significantly associated with increasing hs-CRP levels. In multivariable Cox regression adjusting for clinical characteristics and echocardiographic measures including LV ejection fraction, LV mass index, E/e’, TAPSE and GLS, higher hs-CRP was significantly associated with both heart failure and myocardial infarction (table) (HR for heart failure: 1.30, 95% CI: 1.03–1.66 p = 0.030; HR for acute myocardial infarction: 1.40, 95% CI: 1.04 – 1.89, p = 0.028, per doubling of hs-CRP). We did not find any interactions between hs-CRP and outcome among different types of echocardiographic phenotypes. Conclusion In the general population, higher levels of hs-CRP were associated with declining systolic, diastolic and right heart function. The associations persisted when adjusting for clinical characteristics. In addition, hs-CRP was associated with cardiac events independent of cardiac function as assessed by echocardiography.Linear regression splinesCox regressions

Interleukin 6 in asymptomatic patients with nonsevere aortic valve stenosis: a post-hoc study of the SEAS trial

Abstract Background Inflammation plays a pivotal role in the pathogenesis of aortic valve stenosis (AS) through cytokine-mediated valve calcification. Studies of explanted valves found associations of an elevated pro-inflammatory cytokine, Interleukin 6 (IL-6), with increased postoperative mortality. However, limited knowledge exists regarding the prognostic value of elevated circulating IL-6 in asymptomatic patients with nonsevere AS. Purpose To investigate the hypothesis that elevated plasma IL-6 concentration ≥7 pg/mL (above the upper limit of normal 95th percentile) correlates with more severe AS and a higher risk of adverse outcomes in asymptomatic patients with nonsevere AS. Methods We analyzed data of 1574 asymptomatic patients who had mild-to-moderate AS, preserved systolic and kidney function, no overt cardiovascular diseases, and an event-free follow-up one year after enrollment in the randomized Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. We ascertained the correlation of year-0 and year-1 IL-6 levels with echocardiographic AS severity, defined as moderate-severe AS in the presence of ≥2 measurements at year-0: aortic valve area <1 cm², mean pressure gradient ≥40 mmHg, maximal transaortic velocity ≥4 m/s, and velocity ratio <0.25. Multivariable regression examined correlations between IL-6 at year-0 and clinical variables. Cox proportional hazard models and competing risk analyses examined associations of elevated IL-6 at year-1 and 4-year risk of the primary composite endpoint of major cardiovascular events (MACE) comprising the first event of cardiovascular death, aortic valve replacement, hospitalization with heart failure, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or ischemic stroke. Results At year-0, among 1574 patients with a mean (SD) age of 67.5 (9.7) years, 629 (40.0%) were women, 263 (16.7%) had moderate-severe AS, and 194 (12.3%) had elevated IL-6. The median relative IL-6 change from year-0 to year-1 was 1.0 (IQR, 0.8-1.4) across AS-severity groups (P=0.12) (Figure 1). In adjusted models, IL-6 at year-0 did not correlate with AS-severity (P=0.30). In mild AS, an elevated IL-6 at year-1 was associated with an increased 4-year MACE risk (HR 1.40; 95% CI, 1.02-1.92; p=0.04) in adjusted Cox regression analyses (Figure 2A). In sensitivity analyses, the annual IL-6 increase >50% combined with normal IL-6 was associated with an increased 4-year MACE-risk of HR 1.48 (95% CI, 1.10-2.00; P=0.009) in patients with mild AS and 1.82 (95% CI, 0.68-1.74; P=0.73) in patients with moderate-severe AS (all P for interaction>0.25) (Figure 2C-D). Conclusion In asymptomatic patients with nonsevere AS, circulating IL-6 remains stable within the reference range in 7 out of 8 patients during a 1-year follow-up, regardless of AS severity. An elevated IL-6 was associated with a 1.4-fold increased 4-year MACE-risk in patients with mild AS, suggesting its possible role as an early risk marker.Figure 1Figure 2

Mechanical wave velocities by clutter filter wave imaging detects myocardial dysfunction in acute coronary syndrome

Abstract Background/introduction Mechanical waves within the myocardium arising from physiologic events in the cardiac cycle such as the atrial kick (AK), mitral valve closure (MVC) and aortic valve closure (AVC) offer insight to tissue stiffness and can be measured by high frame rate echocardiography. Purpose To investigate the feasibility of measuring mechanical wave velocities in the left ventricle by clutter filter wave imaging (CFWI) and its potential for detecting regional myocardial dysfunction in patients with acute coronary syndrome. Methods We examined 60 patients (66±9 years of age, 72% male) with acute coronary syndrome by high frame rate echocardiography after revascularisation, imaging the left ventricle from the parasternal long axis view and three apical projections. Intrinsic mechanical waves generated by the AK, MVC and AVC were analysed off-line by CFWI of all walls using custom software (PyMWI) on 2000 frames of in-phase and quadrature component data per view extracted from a Vivid E95 scanner. Results We analysed a total number of 2372 waves recorded with a frame rate of 1180 (1134-1199) frames per second. The feasibility for measuring AK waves was high in all regions (mean 89%), but lower for the MVC and AVC waves with significant variability between regions (mean 44% and 46%, respectively; p<0.001). Feasibility declined from basal to apical segments for all waves (p=0.0001). Mean mechanical wave velocity was slowest for the AK wave at 2.5 (2.0-3.0) m/s, faster for the AVC wave at 5.1 (3.5-6.3) m/s and fastest for the MVC wave at 6.6 (4.9-8.6) m/s (p=0.0001). Basal AK wave velocity was faster in patients with basal wall motion abnormalities compared to those without (2.7 vs. 2.0 m/s, p=0.0004) and could detect the presence of wall motion abnormalities adjusting for age, gender and parameters of diastolic function (univariable OR 3.4, 95% CI 1.5-7.7, p<0.01; multivariable OR 4.4, 95% CI 1.4-14.1, p=0.01). Basal AK wave velocity detected wall motion abnormalities with an AUC of 0.78 with cut-off speeds of 2.3 m/s and 3.0 m/s, both correctly classifying 73% of cases (sensitivity/specificity 81%/68% and 43%/89%, respectively). Mechanical wave velocities of other waves and in other regions were not consistently and only weakly associated with echocardiographic parameters of systolic and diastolic function. Conclusion(s) Mechanical wave velocities by CFWI detects myocardial dysfunction in acute coronary syndrome. Elevated basal AK wave velocity was independently associated with myocardial dysfunction where AK wave velocity ≥2.3 m/s provided a good sensitivity and ≥3.0 m/s a good specificity for detecting regional wall motion abnormalities. The feasibility of measuring the AK wave was good, whereas MVC and AVC waves had lower feasibility and were inadequate for assessment of myocardial function. Feasibility variations between AK and MVC/AVC waves suggest differences in wave propagation dynamics or intrinsic wave properties.Illustration Clutter Filter Wave ImagingRisk of myocardial dysfunction

Myocardial injury and heart failure biomarkers in acute intermittent porphyria

Abstract Background Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by the defect in the hydroxymethylbilane synthase gene, encoding the third enzyme in heme biosynthesis pathway. The main symptoms include abdominal pain, vomiting, paralysis, confusion. Exacerbation of AIP may manifest with elevation of blood pressure and tachycardia due to hyperactivity of sympathetic nervous system. Data regarding cardiac function in AIP are scarce. Purpose The aim of this study was to assess the myocardial injury and heart failure biomarkers during AIP exacerbations and remission. Methods This cohort prospective study encompassed patients at the age 18-65 years who had at least one exacerbation of AIP in their lifetime. Patients examined during the AIP exacerbations were reassessed in the remission phase. The concentrations of sodium, troponin T, CK-MB mass, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and metoxycatecholamines in blood were assessed. Blood pressure was measured with 24-hour ABPM. Echocardiography was performed according to the current recommendations. Results The total number of 70 patients with AIP were enrolled to the study (April 2019 - March 2023). We assessed 36 patients in both phases of disease, mean age 37 years (21-63), 75% females. The median of prior AIP exacerbations was 8. During the exacerbations a significant increase in the concentrations of NT-proBNP (250 [97 ; 501] vs. 89 [48 ; 140] pg/mL, p<0.001), metanephrine (49.0 [37.8 ; 61.2] vs. 41.4 [36.8 ; 53.3] pg/mL, p=0.009) and normetanephrine (169.8 [118.2 ; 327.2] vs. 93.2 [78.1 ; 120.9] pg/mL, p<0.001) was observed. Conversely, sodium concentrations decreased (136 [133 ; 140] vs. 140 [139 ; 142] mmol/L, p<0.001). There were no significant differences in the values of troponin (5.4 [4.0 ; 11.3] vs. 5.6 [3.7 ; 9.5] ng/L, p=0.445), CK-MB mass (1.88 [0.84 ; 2.64] vs. 1.21 [0.83 ; 2.80] ng/mL, p=0.80). In the acute phases of AIP the levels of NT-proBNP were correlated negatively with the values of sodium concentrations (r=-0.36, p=0.032) and positively with average systolic blood pressure (r=0.32, p=0.06). Echocardiography showed an increase in left ventricular (LV) mass indices in some patients hospitalized due to AIP symptoms. Sodium concentrations correlated negatively with these changes (r=-0.36, p=0.032). LV ejection fraction was slightly higher during AIP exacerbations. There were no significant differences in other parameters of LV systolic and diastolic function. Conclusions During acute intermittent porphyria (AIP) exacerbations there is an increase in the concentrations of NT-proBNP and catecholamines in blood. In most patients the levels of markers of myocardial injury, such as troponin and CK-MB mass, do not differ significantly between phases of disease. During AIP exacerbations some patients experience an increase in LV mass which may be associated with hyponatremia. In most cases cardiac function do not change significantly.Frequency of abnormal laboratory resultsResults of echocardiography