Lower LV Research Articles

Abstract 4121793: A Pressure-Volume Loops Approach Predicts Outcomes After Double Switch Operation For Congenitally Corrected Transposition Of The Great Arteries with Intact Ventricular Septum

Background: Double switch operation (DSO) for congenitally corrected transposition of the great arteries with intact ventricular septum (ccTGA) has a high rate of post-DSO LV dysfunction. Hypothesis: LV pressure-volume area (PVA), a surrogate of myocardial O 2 consumption, is a superior marker of LV preparedness and is associated with adverse outcomes after DSO. Aims: 1. Derive a mathematical relationship to estimate LV PVA (ePVA) from catheterization (pressure) and imaging (volumetric) data, using directly measured PVA (mPVA) as reference 2. Assess if lower ratio of LV ePVA to RV ePVA (as an internal control) is associated with adverse outcome after DSO. Methods: Aim 1: Using conductance catheter derived invasive subpulmonary LV PV loops, mPVA was recorded as the sum of stroke work (SW) and potential energy (PE). A mathematical relationship was established with standard catheterization/imaging data to estimate ePVA. Aim 2: In a retrospective cohort, LV:RV ePVA ratio was calculated as above, and along with standard clinical metrics, assessed for relationship with a composite outcome of ≥ moderate LV dysfunction, transplant, or death post-DSO. Results: Aim 1: In 20 PV loop studies in 18 pre-DSO patients, there was a strong linear correlation between measured and estimated SW and PE (R 2 > 0.9 and p<0.0001 for both). ePVA yielded high agreement and low bias compared to mPVA (mean bias 0.5±11%). Aim 2: Composite outcome occurred in 6/42 DSO patients (14%). LV:RV ePVA ratio (0.57 [0.49, 0.61] vs 0.90 [0.73, 1.1], p<0.001) and LV:RV pressure ratio (0.80 [0.77, 0.87] vs 1.13 [1.01, 1.23], p<0.001) were lower in those with adverse outcome. There were no differences in other pre-operative parameters. On time to event analysis, lower LV:RV ePVA ratio was the strongest determinant (HR 39, 95% CI 15-100; C Index 0.94), while lower LV:RV pressure ratio was the only other predictor (HR 24, 95% CI 13-42; C Index 0.88). In 8 patients with borderline pressure ratios of 0.77-0.88, ePVA ratio was an excellent discriminator - 3 patients with ePVA ratio of ≥0.67 had good outcomes, whereas 5 patients with ePVA ratio <0.67 had adverse outcomes. Conclusion: LV:RV ePVA ratio >0.67 is a strong and novel predictor of LV preparedness for DSO in patients with ccTGA.

Accuracy of mitral annular plane systolic excursion in diagnosing anthracycline-induced subclinical cardiotoxicity in patients with breast cancer - a retrospective cohort study

BackgroundThe mitral annular plane systolic excursion (MAPSE) is used to analyze the left ventricle longitudinal function. However, the accuracy of MAPSE in diagnosing oncological populations is unclear. In this study, we aimed to assess the accuracy of MAPSE in diagnosing subclinical cardiotoxicity in women with breast cancer undergoing anthracycline treatment.MethodsThis retrospective cohort study included echocardiographic assessments of patients with breast cancer who underwent anthracycline treatment as part of their therapeutic regimen. Assessments were performed before treatment, after administering the first dose of anthracycline, after completing anthracycline treatment, and 6 and 12 months after treatment. Left ventricular ejection fraction was calculated using the modified biplane Simpson method. The performances of MAPSE and global longitudinal strain (GLS) were analyzed using receiver operating characteristic (ROC) curves. Their accuracies were measured using the area under the ROC curves.ResultsSixty-one patients were included in this study. Of them, 8.2% presented cardiotoxicity 6 months after treatment completion. Patients with cardiotoxicity had lower LVEF (47% vs. 63%; p < 0.001), MAPSE (10.23 mm vs. 12.25 mm; p = 0.012), and LV GLS (16.13% vs. 19.05%; p = 0.005) values than those without. A 12% reduction in the GLS exhibited sensitivity, specificity, and overall accuracy of 80%, 70%, and 78%, respectively. A relative reduction of 15% in MAPSE exhibited a sensitivity, specificity, and accuracy of 80%, 77%, and 81.2%, respectively. An absolute MAPSE reduction of 2 mm exhibited a sensitivity, specificity, and accuracy of 80%, 73.21%, and 81.2%, respectively. No differences were observed between the ROC curves.ConclusionMAPSE showed similar accuracy to GLS in diagnosing subclinical cardiotoxicity in women with breast cancer undergoing anthracycline treatment.

The association between periodontal disease and coronary artery disease: insights from imaging, observational and genome-wide data

Abstract Background Periodontal disease is the sixth most common disease worldwide. It has been suggested that it may be a contributory risk factor for coronary artery disease (CAD). From a public health perspective, prevention of periodontal disease is relatively straightforward and cost-effective: daily brushing, flossing and, where applicable, smoking cessation. Purpose This study utilises imaging, longitudinal and genomic data to characterise the association between periodontal disease and CAD. Methods 481,915 individuals from the UK Biobank were included in this study, 18.9% (n = 91,022) of whom had self-reported periodontal disease. For the imaging analysis, a maximum of 59,019 had paired cardiovascular magnetic resonance (CMR) data. Multivariable linear regression models were constructed to examine the association of periodontal disease on CMR outcomes with LV end-diastolic volume, LV mass, LV mass:volume ratio (MVR), LV ejection fraction, LV global longitudinal strain and native T1 values considered as prognostically important phenotypes. The relationship between periodontal disease and incident CAD was assessed using Cox proportional hazards regression models. To examine the relationship of genetically-determined periodontal disease on CAD, a de novo GWAS for periodontal disease was performed and a genome-wide polygenic risk score (PRS) was constructed. Results Periodontal disease was associated with a significantly higher LV MVR (effect size = 0.00233, 95% confidence interval [CI] = 0.0006, 0.004) and significantly lower LV native global T1 value (effect size = -0.86 ms, 95% CI = -1.63, -0.09). The presence of periodontal disease was independently associated with a significantly increased hazard of incident CAD (HR = 1.09, 95% CI = 1.07, 1.13) at a median follow-up time of 13.8 years (Figure 1). Each standard deviation increase in the periodontal disease PRS was associated with increased odds of CAD (OR = 1.03, 95% CI = 1.02, 1.05) (Figure 2). Conclusion Using an integrated approach across imaging, observational and genomic data, periodontal disease is independently associated with biomarkers of subclinical remodelling as well as incident CAD. These findings highlight the potential importance of periodontal disease in the broader context of cardiovascular disease prevention.

Prognostic value of left atrial and ventricular strain in moderate atrial and ventricular secondary mitral regurgitation

Abstract Background Secondary mitral regurgitation (SMR) is associated with increased morbidity and mortality. In these patients, left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) have been proposed to improve risk stratification. However their prognostic value was shown to be inconsistent when considering the SMR etiology (i.e. atrial or ventricular), possibly due to be the influence of atrial fibrillation (AF) on these measures and specifically LARS. Moreover, data focusing on moderate SMR is lacking. Aim To investigate the prognostic value of LVGLS and LARS in patients with SMR stratified according to etiology, and to identify optimal threshold for both measures. Methods Patients (n=1061; age 68±11years , 59% male) with moderate SMR were retrospectively included and classified as ASMR or VSMR, and further subdivided into "sinus rhythm (SR) subgroup" (ASMR-SR: n=68 , VSMR-SR: n=435) or as "AF subgroup" (ASMR-AF: n=284 , VSMR-AF: n=274), if patients had history of AF. The endpoint was a composite of heart failure events and all-cause mortality. Threshold values for LVGLS and LARS were defined based on spline curve analysis. Results As compared to VSMR, ASMR patients were more frequently female (61% vs. 35%, p&amp;lt;0.001), had less comorbidities and were less symptomatic (i.e. NYHA functional class III-IV in 11% of ASMR vs. 24% of VSMR, p&amp;lt;0.001). For the echocardiographic characteristics, VSMR patients showed lower LV ejection fraction and LVGLS, as compared to ASMR patients. For both ASMR and VSMR, patients in the AF subgroups had larger LA volume index, lower LARS and more severe tricuspid regurgitation (Figure 1). During a median follow-up of 78 (IQR: 44-111) months, 27% of ASMR-SR, 37% of ASMR-AF, 50% of VSMR-SR and 72% of VSMR-AF group reached the combined endpoint. Separated multivariable cox regression analyses were performed in ASMR and VSMR patients (Table 1): for both etiologies, LARS and LVGLS were independently associated with the endpoint after correcting for other significant variables at the univariate analysis, including the SR or AF group and the interventions during follow-up. In addition, a stepwise addition of LVGLS and LARS to a basic model led to a significant difference in the likelihood ratio for both groups. The thresholds of LVGLS and LARS associated with an increased risk of the combined endpoint differed per etiology. For LVGLS the threshold was &amp;lt;16% for ASMR, and &amp;lt;12% for VSMR. When considering LARS assessment, different thresholds were identified according to the SR or AF group: &amp;lt;18% in ASMR-SR; &amp;lt;15% in ASMR-AF; &amp;lt;17% in VFMR-SR and &amp;lt;12% in VFMR-AF. Conclusion In moderate SMR patients, LVGLS and LARS are independently associated with outcomes both in ASMR and VSMR and could be considered to improve risk stratification. However, lower threshold for both parameters should be considered based on etiology and on the presence of AF.

Sex differences related changes in cardiac structure and function after ST-segment elevation myocardial infarction

Abstract Background Sex disparities in presentation, treatment, and outcomes after ST-segment Elevation Myocardial Infarction (STEMI) are well recognized. However, little is known about sex related changes in cardiac structure and function following a STEMI in this contemporary era of early PCI. Purpose To compare sex differences in change of echocardiographic parameters of structure and function following a first-time STEMI. Methods This echocardiographic study involved 380 non-diabetic first-time STEMI patients. Structural and functional parameters were evaluated during initial hospitalization (median 1 day after presentation) and at 4-months. Adverse remodelling was defined as a 20% increase in left ventricular end-diastolic volume (LVEDV) at 4 months compared to the hospitalisation echo. Functional parameters included left ventricular ejection fraction (LVEF) and wall motion score index (WMSI). According to current guidelines, eccentric hypertrophy was defined as left ventricular mass index (LVMI) &amp;gt;95 g/m2 for women and &amp;gt;115 g/m2 for men with a relative wall thickness (RWT) ≤0.42; concentric hypertrophy was defined as LVMI &amp;gt;95 g/m2 for women and &amp;gt;115 g/m2 for men with RWT &amp;gt;0.42. The different patterns in geometry were assessed at 4-months. Results Among 380 patients, comprising 285 males and 95 females, females had a higher prevalence of hypertension (42% vs. 25.6%, p=0.004), lower hemoglobin levels (8.40 mmol/l vs. 9.10, p&amp;lt;0.001), and higher plasma NT-proBNP concentrations upon admission (132 ng/L vs 67, p&amp;lt;0.001) and after 24 hours (1322 ng/l vs 784, p&amp;lt;0.001). During the initial echocardiogram conducted upon hospitalization, as well as during the echocardiogram at 4 months, women had significantly lower LV diameters, LV volumes, LV mass, LAVI and wall thickness compared to man. However, during both evaluations women showed higher E/e’ ratio’s and LVEF. The change in echocardiographic variables between both timepoints did not differ significantly between sexes. Furthermore, no significant difference in LV geometry patterns (eccentric or concentric) were observed between sexes and adverse LV remodelling was similar between both groups at approximately 22-23% (p=0.991). Conclusions Although differences exist between sexes in patient characteristics and individual echocardiographic parameters, no disparity is observed in geometry patterns, adverse LV remodelling, or the change in echocardiographic parameters after STEMI.

Right ventricular-pulmonary artery coupling assessed by two-dimensional strain predicts in- hospital complications in takotsubo syndrome

Abstract Background and purpose Takotsubo syndrome (TTS) may lead to serious in-hospital complications. Our study aims to investigate the prognostic impact of right ventricular-to-pulmonary artery (RV-PA) coupling in patients with TTS. Methods Consecutive TTS patients were prospectively enrolled. RV function was evaluated by RV global longitudinal strain (RVGLS) and RV free wall strain (RVFWS) and RV-PA coupling was measured as the ratio of either tricuspid annular plane systolic excursion (TAPSE), RVGLS or RVFWS to pulmonary artery systolic pressure (PASP). Data about in-hospital complications (defined as acute heart failure, life-threatening arrhythmias and death from any cause) were collected. Results A total of 80 patients were analysed (71±11 years, female 77.5%) and in-hospital complications occurred in 33 (41%). Patients who experienced in-hospital complications had lower LV ejection fraction (LVEF), lower TAPSE/PASP, RVFWS/PASP and RVGLS/PASP and higher left atrial volume indexed (LAVi) values. LVEF (OR 0.913, 95% CI [0.858–0.971], p=0.004) and RVGLS/PASP (OR 0.098, 95% CI [0.012–0.788], p= 0.029) were independent predictors of in-hospital complications. Receiver operating characteristics (ROC) curve analysis showed an area under the curve (AUC) of 0.696 (95% CI [0.57–0.82], p= 0.002) of RVGLS/PASP for the prediction of in-hospital complications. A cut-off value of RVGLS/PASP of ≤ 0.48 %/mmHg showed a sensitivity and specificity of 75% and 60%, and allowed to identify 24% of patients who experienced in-hospital complications despite a preserved LVEF (≥50%). Conclusion RV-PA coupling assessed by RVGLS/PASP may help identifying TTS patients at higher risk of cardiovascular complications with an additional prognostic value to LVEF alone.

Lung Structure and Longitudinal Change in Cardiac Structure and Function: The MESA COPD Study.

Lung structure and cardiac structure and function are associated cross-sectionally. The classic literature suggests relationships of airways disease to cor pulmonale and emphysema to reduced cardiac output (CO) but longitudinal data are lacking. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease (COPD) Study was a multi-center longitudinal COPD case-control study of participants 50-79 years with ≥10 pack-years smoking without clinical cardiovascular disease. Segmental airway wall area (WA) and percent emphysema were measured on computed tomography. Right and left ventricle (RV, LV) parameters were assessed on magnetic resonance imaging (MRI) in exams six years apart. Longitudinal and period cross-sectional associations were evaluated with mixed models adjusted for demographics, body size, and smoking. The 187 participants with repeated MRI were 67±7 years old; 42% had COPD; 22% currently smoked; and the race/ethnicity distribution was 54% white, 30% Black, 14% Hispanic, and 3% Asian. Greater WA at enrollment was associated with longitudinal increase in RV mass (3.5 g per 10mm2 WA, 95% CI: 1.1, 5.9). Greater percent emphysema was associated with stably lower LV end diastolic volume (-7.8 mL per 5% emphysema, 95% CI: -10.3, -3.0) and CO (-0.2 L·min-1 per 5% emphysema, 95% CI: -0.4, -0.1). Cardiac associations varied by lung structure over six years in this multi-ethnic study. Greater WA at enrollment was associated with longitudinal increases in RV mass; whereas greater percent emphysema was associated with stable decrements in LV filling and CO.

Management and clinical outcome of myocardial infarction in Kosovo: A cross-sectional study.

Myocardial infarction (MI) is a major cause of mortality worldwide, irrespective of its presentation as non-ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). The objective of this study was to assess national results of management and clinical outcome of acute MI patients in Kosovo. This cross-sectional descriptive study, conducted at the Clinic of Cardiology of the University Clinical Center of Kosovo, in Prishtina, included all patients hospitalized with acute MI over a period of 7 years (2014-2020). The primary outcome of the study was in-hospital mortality. Among 7353 admitted patients with acute MI (mean age 63 ± 12 years, 29% female) and according to the final diagnosis, 4436 (59.4%) patients had STEMI, and 2987 (40.6%) NSTEMI. More patients with STEMI received primary percutaneous intervention (PPCI) than those with NSTEMI (50% vs. 41%, p < 0.001). In-hospital mortality was higher in no PPCI patients compared to PPCI both in NSTEMI (10.7% vs. 2.6%, p < 0.001) and STEMI (20.9% vs. 6.8%, p < 0.001). Age ≥65 years [0.399 (0.267-0.597), p ˂ 0.001], hemoglobin level [0.889 (0.815-0.970), p = 0.008], STEMI [0.491 (0.343-0.704), p ˂ 0.001], lack of PPCI [2.636 (1.798-3.866), p ˂ 0.001], cardiogenic shock [0.002 (0.001-0.006), p < 0.001], reduced left ventricular ejection fraction (LV EF) [0.966 (0.951-0.980), p < 0.001], and heart rate at admission [1.009 (1.000-1.017), p = 0.047], independently predicted mortality. In STEMI, cardiogenic shock (p ˂ 0.001), lack of PPCI (p = 0.006), female gender (p = 0.01), and low LV EF (p = 0.04) predicted mortality but age ≥65 years (p = 0.02), female gender (p = 0.02), low LV EF (p = 0.007), and low hemoglobin (p = 0.04) predicted mortality in NSTEMI. Between 2014 and 2020, half of patients with acute MI were not treated with PPCI, who had high mortality, particularly when presenting with STEMI. Age, cardiogenic shock, anemia, low LV EF, STEMI and no PPCI independently predicted mortality. Cardiogenic shock and lack of PPCI independently predicted mortality, only in STEMI.

Use of strain imaging to detect subtle myocardial involvement in post COVID-19 patients: An Indian perspective

BackgroundThe study assessed Global longitudinal strain imaging (GLS) to detect subtle myocardial dysfunction among patients clinically recovered from COVID-19. MethodsAll patients (n = 101 76 % males, mean age 55.45 ± 11.14 years), and controls (n = 30), underwent clinical assessment and echocardiography, including GLS assessment. ResultsThe prevalence of diabetes mellitus, hypertension and dyslipidemia was comparable amongst patients and controls. The average GLS was significantly lesser in post COVID patients (−16.21 ± 1.96 vs −18.49 ± 1.64 respectively, p = 0.004) and significantly higher proportion of post COVID patients had GLS > -18 % (43 % vs 22.58 % respectively, p = 0.001) as compared to controls. The RV free wall longitudinal strain (RVFLS) was also lower in the patient group (22.35 ± 4.69 vs 24.19 ± 4.11, p = 0.004) and 21.7 % post COVID-19 patients had pathological RV FWLS (> −20 %) vs controls (6.6 %).Average GLS was significantly lesser in severe post COVID patients (viz −14.25 ± 1.92 vs −16.63 ± 1.61 vs −17.63 ± 1.91, p < 0.0001, respectively among severe, moderate and mild COVID-19 patients. On performing regression analysis, severity of COVID-19 (OR 7.762) was a significant predictor of impaired GLS. ConclusionDespite normal global LVEF, post COVID-19 recovered patients had significantly lower LV GLS and RV FWLS with severe COVID-19 infection, regardless of having a clinical recovery. This study reiterates the importance of speckle tracking echocardiography as an important imaging modality for detection of subclinical myocardial dysfunction in the post COVID-19 recovered patients.

Hypertension and Left Ventricular Strain in Pediatric Chronic Kidney Disease.

Left ventricular global longitudinal strain (LV GLS) on echocardiography is a sensitive yet clinically significant marker of myocardial dysfunction. Reduced LV GLS is prevalent in adults with chronic kidney disease and hypertension and is associated with adverse cardiovascular outcomes. It may be a biomarker of chronic kidney disease-associated myocardial dysfunction in children, but data are limited. Our objective was to describe LV GLS in the CKiD study (Chronic Kidney Disease in Children) and to examine the association between blood pressure (BP) and reduced LV GLS. A single apical 4-chamber view was used to estimate LV GLS. Our main analyses examined the association of clinic BP with the absolute value of LV GLS and LV GLS dichotomized at 16. Sensitivity analyses using 24-hour ambulatory BP monitoring data were also performed. Generalized estimating equations were used to account for within-person correlation and to estimate robust SEs for 95% CIs. Covariates in adjusted models included: age, sex, race, estimated glomerular filtration rate, urine protein, hemoglobin, left ventricular hypertrophy, and the use of renin-angiotensin system inhibitors. LV GLS was measured in 962 person-visits. A total of 77 assessments had an LV GLS <16. In adjusted models, both clinic systolic BP (odds ratio, 1.02 [95% CI, 1.01-1.03]) and diastolic BP (odds ratio, 1.02 [95% CI, 1.00-1.03]) percentiles were associated with LV GLS <16. Having awake or nighttime diastolic BP hypertension on ambulatory BP monitoring was significantly associated with a lower absolute value of LV GLS. Office systolic and diastolic hypertension was associated with diminished LV GLS. Only diastolic hypertension detected on ambulatory BP monitoring was associated with lower LV GLS.

In Search of Optimal Criteria for Iron Deficiency in CHF Patients. Post-hoc Analysis of the Study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)".

Comparative analysis of clinical, anamnestic, and laboratory and instrumental data of patients with chronic heart failure (CHF) and iron deficiency (ID) diagnosed according to the AHA/ESC/RSC criteria, and CHF patients diagnosed with ID based on decreased transferrin saturation (TSAT) ≤19.8% or serum iron (Fe) ≤13 μmol/l. An additional analysis of the ID-CHF-RF study was performed. The analyzed population included 498 patients (198 women) with CHF. In addition to the ID criteria provided by the protocol (AHA/ESC/RSC criteria: ferritin &lt;100 μg/l or ferritin from 100 to 299 μg/l and TSAT&lt;20%), concentrations of ID biomarkers were assessed, which showed high sensitivity and specificity for the diagnosis of ID compared to the morphological picture of the bone marrow (TSAT&lt;19.8% or Fe ≤13 μmol/l). Subgroups of patients with ID determined only by the AHA/ESC/RSC criteria, only by the TSAT≤19.8% and Fe ≤13 μmol/l criteria, and by both were analyzed. ID diagnosed by the AHA/ESC/RSC criteria was found in 83.1% of patients. The TSAT ≤19.8% and Fe ≤13 μmol/l criteria revealed ID in 74.5% of patients. In 341 patients (76.8%), ID was diagnosed using both criteria. Patients with ID diagnosed by the TSAT≤19.8% and Fe≤13 μmol/l criteria, compared with patients with ID diagnosed by the AHA/ESC/RKO criteria, had a 50% lower Fe (9.8 μmol/l vs. 19.4 μmol/l) and a higher incidence of anemia (43.3% vs. 23.3%) and diabetes mellitus (DM) (36.7% and 24.7%). Also, these patients had higher values of body mass index (BMI) and NT-proBNP concentration (2317 [1305;9092] vs. 1691 [709;3856] pg/ml), and lower LV EF values (41.5 [29.0;54.5]% vs. 45.0 [34.0;54.0]%), respectively. The most severe course of CHF and the greatest changes in laboratory tests associated with ID and anemia were observed in patients with ID determined by two criteria. Patients in this group were older, with a higher BMI, more frequent presence of atrial fibrillation, and higher NT-proBNP (4182 [1854;9341] pg/ml). Patients with isolated low ferritin are characterized by less severe clinical and functional impairment compared to patients with low TSAT or Fe. At the same time, patients with ferritin higher than 300 μg/l and low TSAT and/or Fe were characterized by very severe CHF and a low functional status, although this may not be related with ID. Thus, the use of the ferritin-based criteria of ID may lead to overdiagnosis of ID in some patients and, at the same time, miss some of the most "severe" patients who likely require the ID correction. Patients with ID who show a decrease in all three parameters are likely to benefit most from Fe supplementation. It is advisable to perform additional studies on the effect of Fe supplements on the course and prognosis of the disease in this cohort of patients.

Longitudinal assessment of systolic anterior motion of the mitral valve in cats with hypertrophic cardiomyopathy.

The proportion of cats with hypertrophic cardiomyopathy (HCM) that lose systolic anterior motion of the mitral valve (SAM) in the long term is unknown. Cats with HCM will lose SAM in the long term. Loss of SAM will be associated with greater age, longer scan-interval, and alteredleft ventricular (LV) dimensions. Sixty unsedated cats with HCM, not receiving beta blockers or pimobendan. A retrospective cohort study from 2 referral centers. Cats were eligible if they had been diagnosed with HCM and had a repeat echocardiogram ≥1 year later. Clinical and echocardiographic data of the left heart variables were collected. Thirty-eight cats had SAM at the initial scan. After a median follow-up time of 2.1 years (range: 1.0-5.9), 7 cats had lost SAM (18%) and 5 cats (23%) gained SAM. On follow-up, cats with SAM at the initial scan had a larger left atrium (P = .037), lower left atrial fractional shortening (P = .014), greater LV internal diameter in end-systole (P = .002), and lower LV fractional shortening (P < .001). Four cats with SAM developed congestive heart failure. There were no new cases of congestive heart failure or change in left heart variables in cats without SAM at the initial scan. The gain or loss of SAM was not associated with age or time between scans. Similar proportions of cats gained or lost SAM. Cats with SAM at baseline had more evidence of disease progression than cats without SAM.

Increased preload and echocardiographic assessment of diastolic function.

Echocardiographic diastolic parameters are used to diagnose and monitor increased left ventricular filling pressure (LVFP) and we hypothesized that increased loading conditions cause increased E/e'. Our aim was to assess the effect of preload augmentation on diastolic parameters among both healthy subjects and subjects with known cardiac disease. We included 129 subjects merged from two cohorts; one dialysis cohort (n=47) and one infusion cohort (n=82). Echocardiography was performed immediately before and after hemodialysis (HD) or saline infusion, under low and high loading conditions. Elevated LVFP was defined as septal E/e'≥15 and/or lateral E/e'≥13 at high-loading conditions. The population was divided according to elevated LVFP (n=31) and normal LVFP (n=98). The load difference for the population was 972±460mL, with no differences in load difference between elevated and normal LVFP (p NS). The subjects with elevated LVFP were older (63±11 vs. 46±16 years, p<.001), and had lower LV ejection fraction (50±14vs. 59±8.1%, p<.01). After augmented preload, EDV increased in the normal LVFP group (p<.01) but remained unchanged in the elevated LVFP group (p NS). Both E and e' increased among the subjects with normal LVFP, whereas E/e' remained unchanged (∆E/e' +.1 [-.5-1.2]), p NS). Among the subjects with elevated, LVFP we observed increased E but not e', resulting in significantly increased E/e' (∆ average E/e' +2.4 [0-4.0], p<.01). Augmented preload does not seem to affect E/e' among subjects with normal LVFP, whereas E/e' seems to increase significantly among subjects with elevated LVFP.

The Relative Apical Sparing Strain Pattern in Severe Aortic Valve Stenosis: A Marker of Adverse Cardiac Remodeling.

The presence of a relative apical sparing (RAS) echocardiographic strain pattern raises a suspicion of underlying cardiac amyloidosis (CA). However, it is also increasingly observed in patients with aortic stenosis (AS). We aimed to evaluate the prevalence, dynamics, and clinical characteristics of the RAS strain pattern in severe AS patients who had been referred for surgical aortic valve replacement (SAVR). A total of 77 patients with severe AS and without CA were included with a mean age of 70 (62-73) years, 58% female, a mean aortic valve area index of 0.45 ± 0.1 cm2/m2, and a mean gradient of 54.9 (45-70) mmHg. An RAS strain pattern was detected in 14 (18%) patients. RAS-positive patients had a significantly higher LV mass index (125 ± 28 g/m2 vs. 91 ± 32, p = 0.001), a lower LV ejection fraction (62 ± 12 vs. 68 ± 13, p = 0.040), and lower global longitudinal strain (-14.9 ± 3 vs. -18.7 ± 5%, p = 0.002). RAS strain pattern-positive patients also had higher B-type natriuretic peptide (409 (161-961) vs. 119 (66-245) pg/L, p = 0.032) and high-sensitivity troponin I (15 (13-29) vs. 9 (5-18) pg/L, p = 0.026) levels. Detection of an RAS strain pattern was strongly associated with increased LV mass index (OR 1.03, 95% CI 1.01-1.06, p < 0.001). The RAS strain pattern had resolved in all patients by 3 months after SAVR. Our findings suggest that the RAS strain pattern can be present in patients with severe AS without evidence of CA. The presence of an RAS strain pattern is associated with adverse LV remodeling, and it resolves after SAVR.

Poor cardiac output reserve in pulmonary arterial hypertension is associated with right ventricular stiffness and impaired interventricular dependence.

Pulmonary arterial hypertension (PAH) is characterised by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (P-V) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH. RV P-V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index (CI) during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance (E ed)) and ventricular interdependence (left ventricular transmural pressure (LVTMP)) were compared at matched exercise stages. Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 mL·m-2; p=0.0001), with higher associated exercise afterload (effective arterial elastance (E a) 1.76 versus 0.90 mmHg·mL-1; p<0.0001), RV stiffness (E ed 0.68 versus 0.26 mmHg·mL-1; p=0.003) and right-sided pressures (right atrial pressure 14 versus 8 mmHg; p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg; p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling. Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiological PAH differences unapparent at rest.

Phase I dose escalation and pharmacokinetics clinical trial of mitoxantrone hydrochloride liposome in children with relapsed and refractory solid tumors.

10047 Background: Compared with solvent-based mitoxantrone, mitoxantrone hydrochloride liposome has been found to reduce bone marrow toxicity. This open-label, muti-center, single-arm phase I clinical trial aims to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in pediatric with solid tumors. Methods: The study was divided into Phase Ia and Ib. Phase Ia was the dose escalation study, with a "3+3" design. Patients received mitoxantrone hydrochloride liposome at three dose levels (16 mg/m2, 20mg/m2, 24mg/m2, d1) in combination with irinotecan (50mg/m2, d1-5) and vincristine (1.5mg/m2, d1) every 3 weeks. Pharmacokinetic studies were conducted simultaneously. The primary endpoint of Phase Ia was the maximum tolerated dose (MTD). In phase Ib, patients received the combination therapy of mitoxantrone hydrochloride liposome at the MTD dose. The primary endpoint of Phase Ib was the incidence and severity of hematological adverse events. Secondary endpoints in both phases included objective response rate (ORR), pharmacokinetic (PK) parameters, and others. Results: From October 2022 to January 2024, a total of 51 pediatric patients with relapsed and refractory solid tumors were enrolled, 28 patients in Phase Ia and 23 patients in Phase Ib. The median age was 10.0 years (range: 3, 21). All Patients could be evaluated for toxicity and 40 for efficacy. The MTD of mitoxantrone hydrochloride liposome was determined to be 24mg/m2. The results of pharmacokinetic analysis were not returned. Highest incidence of hematological and non-hematological adverse events (AEs) were anaemia (88.2%), diarrhea (84.3%). The newly found or aggravated TnIUtra, BNP value abnormality and lower LV function after medication were 4 (11.8%), 5 (14.3%) and 0 (0.0%), respectively. The overall ORR and DCR were 50.0% (95% CI: 33.8% - 66.2%) and 90.0% (95% CI: 76.3% -97.2%). 13 patients (25.0%) treated with mitoxantrone hydrochloride liposome combination regimen received the opportunity of surgery. Conclusions: The mitoxantrone hydrochloride liposome combination regimen has demonstrated an acceptable toxicity profile and promising clinical efficacy in pediatric patients with solid tumors, especially in sarcomas. Clinical trial information: NCT05620862 .

Prevalence and predictors of mitral annular disjunction and ventricular ectopy in mitral valve prolapse

BackgroundMitral annular disjunction (MAD) is associated with ventricular arrhythmia in mitral valve prolapse (MVP). The proportional risk from MAD and other predictors of ventricular arrhythmia in MVP has not been well characterized. ObjectiveThis study aimed to identify predictors of complex or frequent ventricular ectopy (cfVE) in MVP and to quantify risk of cfVE and mortality in MVP with MAD. MethodsWe studied 632 adult patients with MVP on transthoracic echocardiography at the University of North Carolina Medical Center from 2016 to 2019 (median age, 64 [interquartile range, 52–74] years; 52.7% female; 16.3% African American). Resting and ambulatory electrocardiograms were used to identify cfVE. ResultsMAD was present in 94 (14.9%) patients. Independent associations of MAD were bileaflet prolapse (odds ratio [95% CI], 4.25 [2.47–7.33]; P < .0001), myxomatous valve (2.17 [1.27–3.71]; P = .005), absence of hypertension (2.00 [1.21–3.32]; P = .007), electrocardiogram inferior or lateral lead T-wave inversion (2.07 [1.23–3.48]; P = .006), and female sex (1.99 [1.21–3.25]; P = .006). cfVE was frequent with MAD (39 [41.5%] vs 93 [17.3%] without; P < .0001). Independent cfVE predictors were MAD (hazard ratio [95% CI], 2.23 [1.47–3.36]; P = .0001), bileaflet prolapse (1.86 [1.25–2.76]; P = .002), heart failure (1.79 [1.16–2.77]; P = .009), lower left ventricular ejection fraction (0.14 [0.03–0.61]; P = .009), coronary artery disease (1.60 [1.05–2.43]; P = .03), and inferior or lateral lead T-wave inversion (1.51 [1.03–2.22]; P = .03). After a median of 40 (33–48) months, there was increased mortality with MAD (P = .04). ConclusionMAD in MVP is associated with bileaflet or myxomatous MVP, absence of hypertension, T-wave inversion, and female sex. There is increased cfVE and mortality with MAD, highlighting the need for closer follow-up of these patients.

HAEMODYNAMIC FORCES ANALYSIS IN PATIENTS WITH PARAVALVULAR REGURGITATION AFTER TAVR: A PROPENSITY–SCORE MATCHED RETROSPECTIVE STUDY

Abstract Background Paravalvular regurgitation (PVR) after TAVR is a frequent complication, but its direct quantification and grading with conventional echocardiography is still limited by several factors. LV remodeling has still a role in the evaluation of PVR and its pathophysiology. Hemodynamic forces (HDF) analysis has emerged as a new tool to evaluate LV cardiac function in addiction to ejection fraction (EF) and global longitudinal strain (GLS). Aim of the study: To evaluate the difference in pre– and post–TAVR HDF in patients with preserved EF, using a propensity–matched analysis comparing patients with more than mild PVR to patients with mild or no PVR. Medis Ultrasound Suite software has been used for the estimation of HDF in order to differentiate earlier LV function modification between the two groups and its relationship with clinical outcomes. Material and Methods 25 patients from two European high–volume centers with more than mild PVR and coupled pre– and post–TAVR echocardiographic evaluation available for HDF analysis were retrospectively included, paired 1:2 with 50 patients, matched for characteristics that may influence HDF analysis and with mild or none PVR. Clinical outcome was a composite of heart failure (HF) valve–related hospitalization and worsening HF at 1 year. Results No significative differences were found at baseline clinical and echocardiography evaluation between the two groups: median age was 83 years, mean LVEF was 61%. Post–procedural echocardiographic evaluation was performed at 34 days after TAVR (IQR 5 – 50). Patients with significant PVR had higher LV end–diastolic volume (p = 0.044), lower endocardial GLS (p = 0.07) and lower LV diastolic apex–base longitudinal forces (LVD Apex–Base) (p = 0.045). The difference between LVD Apex–base pre– and post–TAVR was significantly lower in the significant PVR group (–0.8 vs 0.3%, p = 0.021). At Cox regression analysis, LV longitudinal force (LVLF) Ratio turned out to be predictive of clinical outcome (HR 1.11, 95CI 1.02 – 1.20, p = 0.017) in the overall population. Conclusion HDF analysis seems to be superior to conventional echocardiographic values of left ventricular cardiac function to detect the early effects of LV volume overload in patients with significant PVR after TAVR. Furthermore, in the overall population, LVLF Ratio predicts clinical outcomes and could be a promising new index to better evaluate the development of heart failure in patients with AS undergoing TAVR.

Inter-season training effects on cardiovascular health in American-style football players

BackgroundRecent studies on American-style football (ASF) athletes raised questions about the impact of training on the cardiovascular phenotype, particularly among linemen players who engage mostly in static exercise during competition and who exhibit concentric cardiac remodeling, often considered maladaptive. We aimed to examine the cardiovascular adaptation to the inter-season mixed-team training program among ASF players.MethodsA prospective, longitudinal, cohort study was conducted among competitive male ASF players from the University of Montreal before and after an inter-season training, which lasted 7 months. This program includes, for all players, combined dynamic and static exercises. Clinical and echocardiographic examinations were performed at both steps. Left atrial (LA) and ventricular (LV) morphological and functional changes were assessed using a multiparametric echocardiographic approach (2D and 3D-echo, Doppler, and speckle tracking). Two-way ANOVA was performed to analyze the impacts of time and field position (linemen versus non-linemen).ResultsFifty-nine players (20 linemen and 39 non-linemen) were included. At baseline, linemen had higher blood pressure (65% were prehypertensive and 10% were hypertensive), thicker LV walls, lower LV systolic and diastolic functions, lower LA-reservoir and conduit functions than non-linemen. After training, linemen significantly reduced weight (Δ-3.4%, P < 0.001) and systolic blood pressure (Δ-4.5%, P < 0.001), whereas non-linemen maintained their weight and significantly increased their systolic (Δ+4.2%, P = 0.037) and diastolic (Δ+16%, P < 0.001) blood pressure ). Mixed training was associated with significant increases in 2D-LA volume (P < 0.001), 3D-LV end-diastolic volume (P < 0.001), 3D-LV mass (P < 0.001), and an improvement in LV systolic function, independently of the field position. Non-linemen remodeled their LV in a more concentric fashion and showed reductions in LV diastolic and LA reservoir functions.ConclusionsOur study underscored the influence of field position on cardiovascular adaptation among university-level ASF players, and emphasized the potential of inter-season training to modulate cardiovascular risk factors, particularly among linemen.

ANTIHYPERTENSIVE DRUGS IN CHRONIC HEART FAILURE IN THE CZECH REPUBLIC, FOCUSING ON BETA-BLOCKERS

Objective: Hypertension is a very common comorbidity in patients with heart failure. Beta-blockers (BB) are the first choice drug together with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF), reducing morbidity and mortality. Design and method: Data were collected in the FARmacology and NeuroHumoral Activation Registry (FAR NHL). Patients with chronic heart failure with left ventricular ejection fraction (LVEF) &lt; 50% for at least one month were included. Results: 1,100 patients with a mean age of 65 years, 80.8% male, were included. The mean systolic blood pressure was 128.0 mm Hg, mean diastolic blood pressure was 80.0 mm Hg. Of all patients, 20% received low dose of beta-blocker (LD), 57% medium dose (MD) and 17% high dose (HD), 6.2% did not receive BB. The higher the blood pressure (LD 124/ 77; MD 129/ 80; HD 132/ 82 mm Hg; p &lt; 0.001), LV EF (LD 29.5; MD 30.5; HD 32.0%; p = 0.003), creatinine clearance (LD 78.7; MD 87.8; HD 91.1 ml/min; p = 0.001) or weight of the patients, the higher the BB dose they received (LD 83.2; MD 88.7; HD 93.5 kg; p &lt; 0.001). The lower the NT-proBNP, the higher the BB dose patients received (LD 767; MD 456; HD 314 pg/ml; p &lt; 0.001). The presence of atrial fibrillation (AF) did not affect the BB dose. Patients with AF were more likely to be treated with digoxin or a combination of digoxin and BB than patients without AF (p &lt; 0.001). Conclusions: According to FAR NHL registry, almost 94% of patients with HFrEF receive BB. A total of 17% of patients take the target dose of BB. If a patient has BB, he/she is treated with the recommended preparation in more than 99% of cases. The more severe the disease, as reflected by lower BP, creatinine clearance, LV EF, weight or higher NT-proBNP, the lower the dose of beta-blockers the patient receives and tolerates.