Left Ventricular Abnormalities Research Articles

Feature-based clustering of left ventricular strain curve for risk stratification in the general population

Abstract Objective Global left ventricular (LV) strain has been identified as an important predictor of adverse cardiovascular (CV) events. However, currently only the peak strain is used from the LV deformation curve, neglecting the temporal information hidden in all phases of cardiac cycle. Therefore, we employed unsupervised machine learning methods on time-series-derived features from LV strain to identify distinct clinical phenogroups associated with the risk of developing adverse events in the general population. Design and Method We prospectively studied 1185 community-dwelling individuals (mean age, 53.2 years; 51.3% women), in whom we acquired clinical and echocardiographic data including LV strain traces at baseline and collected CV events (n=116) on average 8.7 years later. We utilised Gaussian Mixture Model (GMM) on different features derived from LV strain curve, including slope during systole and early diastole, peak strain, slope during late diastole and the duration and height of diastasis (Figure, left panel). We evaluated the clinical significance of the clusters (k) by comparing the clinical characteristics and CV adverse outcome. Results Based on inertia and BIC scores the optimal number of clusters (k) was 4. The first two clusters had differences in heart rate, but had similar low CV risk profiles. Cluster 4 had the worst CV risk factors combination, and higher prevalence of LV remodelling and diastolic dysfunction (i.e. lowest e’ velocity and highest E/e’) compared to other clusters. Kaplan–Meier showed an increased cumulative incidence risk for all CV events across clusters (Figure, right panel). After adjustment for traditional risk factors, the risk was significantly higher in clusters 3 (HR: 1.28; 95% CI: 1.01-1.61; P=0.038) and 4 (HR: 1.20; 95% CI: 1.02-1.43; P=0.034) compared to the average population, while the risk of adverse events did not reach the significant level in subjects with an abnormal peak LV strain (<17%) (HR 1.12; P=0.66). Conclusion Unsupervised machine learning algorithm employed on features derived from time series LV strain curves identifies clinically meaningful clusters, and provides important prognostic information over the peak LV strain.

Structural and functional abnormalities of cardiac chambers in Barlow disease without significant mitral regurgitation

Abstract Background Limited and conflicting data have been reported on the existence of an early chamber remodelling in patients with Barlow disease (BD) without significant mitral regurgitation (MR). Purpose To explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities, evaluated by conventional and speckle-tracking echocardiography, in patients with BD and without significant MR; in addition, potential determinants of MR progression in these patients have been investigated. Methods We retrospectively identified consecutive patients with BD evaluated in two tertiary centers between 2010 and 2021. Only patients with MR graded from trivial to mild-to-moderate, as defined by an integrated multiparametric echocardiographic assessment, were selected. BD patients were matched with healthy controls with similar demographic characteristics and prevalence of cardiovascular risk factors, in a 1:1 ratio. A comprehensive echocardiographic evaluation, including LV and LA strain assessment by speckle-tracking analysis, was performed in all patients. Follow-up echocardiograms, when available, were reviewed in BD patients to evaluate the MR progression. Results A total of 231 patients with BD were included, of which 109 (56%) had trivial or mild MR and the remaining 122 (44%) had mild-to-moderate MR. As showed in Figure 1, patients with BD showed increased LV dimensions and indexed LV mass (LVMi), as compared with controls (all p<0.001); LV remodelling worsened with higher degree of MR (trivial-mild vs mild-to-moderate) and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Conversely, parameters of LV systolic performance, including LV strain, were similar to controls and between the two groups. In addition, BD patients had larger LA volumes and more impaired LA reservoir strain than controls (p<0.001), without differences in the latter according to MR severity. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi and LA volumes), and BD as independent correlate of LA reservoir strain. Progression to moderate-to-severe or greater MR was observed in 51 subjects (on 172 with available follow-up) after a median time of 38 (range: 24-68) months. On multivariable Cox regression analysis, LVMi (or alternatively eLVH), together with age, MR grade and the presence of mitral annular disjunction emerged as independent predictors of MR progression (Figure 2). Conclusions Patients with BD and no significant MR show an early LV and LA remodeling, together with a mild impairment of LA reservoir strain, but not of LV function. LV remodelling, and the presence of eLVH in particular, portends a higher risk of MR progression.Comparative echocardiographic analysisMultivariable Cox regression analyses

Abstract 18068: Isometric Handgrip Exercise Myocardial Perfusion Reserve Correlates With Coronary Microvascular Dysfunction and Abnormal Left Ventricular Strain: A Report From the Women’s Ischemia Syndrome Evaluation Pre-Heart Failure With Preserved Ejection Fraction Study

Background: Impaired coronary artery response to isometric handgrip exercise (IHE) has previously been demonstrated to reflect endothelial dysfunction, an important contributor to ischemia with no obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD). Stress perfusion cardiac magnetic resonance (CMR) imaging is typically performed with pharmacologic stress using myocardial perfusion reserve index (MPRI) as a measure of CMD. IHE-MPRI has not been comprehensively studied in patients with INOCA, who are at risk for heart failure with preserved ejection fraction (HFpEF). Hypothesis: IHE-MPRI is related to CMD measured by pharm-MPRI and left ventricular (LV) structural and functional abnormalities in INOCA patients at risk for HFpEF. Methods: Participants with INOCA underwent comprehensive CMR with first-pass perfusion with adenosine or regadenoson, rest, and IHE. MPRI was adjusted to rest rate-pressure product (RPP). Lack of a satisfactory IHE response (defined as increase in heart rate≥10 bpm or systolic blood pressure ≥10 mmHg) was excluded. CMR measures of LV structure, function, MPRI, T1 and T2 mapping were analyzed using commercial software, blinded to clinical data. Pearson correlations were performed. Results: Of the participants (n=44) with IHE-MPRI, mean age was 55±11 years, body mass index 27±7 kg/m 2 , and 98% female, 31% hypertension, 12.5% diabetes, 19% hyperlipidemia. IHE-MPRI adjusted for rest RPP significantly correlated positively with pharm-MPRI and inversely with time to peak strain, diastolic strain measures and myocardial T2 ( Figure ). IHE-MPRI was not related to resting or IHE heart rate, systolic strain, LV mass, volumes, mass-volume ratio, native T1 or extracellular volume. Conclusion: IHE-MPRI relates to CMD and LV strain among patients with INOCA. Measurement of IHE-MPRI may improve understanding of CMD and LV structural and functional abnormalities that may contribute to development of HFpEF.

Abstract 16126: Sex Differences in the Relationship Between Left Ventricular Global Longitudinal Strain and Abnormal Myocardial Flow Reserve in a Patient Population With Sleep Disordered Breathing

Introduction: Obstructive sleep apnea (OSA), a form of sleep disordered breathing (SDB), is associated with abnormal myocardial flow reserve (MFR), a precursor to heart failure with preserved ejection fraction (HFPEF). Sex differences have been reported in the prevalence of abnormal MFR and OSA. However, it is unknown if there are sex differences in the relationship between left ventricular (LV) global longitudinal strain (GLS) and abnormal MFR in a patient population with SDB. Methods: We compared LV GLS among patients in our institution who had sleep testing for obstructive sleep apnea (OSA), cardiac PET stress test and an echocardiogram between 2015 and 2019. We reprocessed the echocardiograms using a vendor neutral software to obtain the two-dimensional LV GLS. Results: Among the 148 participants, 59% were female. Compared with females, males had lower BMIs, a higher prevalence of prior myocardial infarction or revascularization, and a greater severity of nocturnal airway obstruction and hypoxia. Males also had a greater proportion with abnormal LV GLS (≥ -17). See Table. The prevalence of abnormal MFR (< 2.0) was higher among participants with abnormal LV GLS ( P = 0.031). This association was persistent among males but was lost among females (see Figure ). In age and sex adjusted logistic regression persons with abnormal LV GLS had 2X the odds of abnormal MFR (OR 2.3; 95% CI: 1.02 - 5.03). Among males, this association was significant (OR 4.8; 95%CI:1.5 - 13.7). No association observed among females. Formal interaction analyses did not meet statistical significance ( P int = 0.106). Conclusions: In this patient population with SDB, there was a significant association between LV GLS and abnormal MFR. The sex differences in the relationship may be due to differences in the severity of OSA and prevalence of ischemic heart disease. Future studies should clarify these relationships and elucidate the drivers of the sex disparities observed in these findings.

Abstract 13286: Co-Morbidities Clustering According to Imaging Diagnostic Criteria in Cardiac Sarcoidosis

Background: Cardiac sarcoidosis (CS) diagnostic guidelines updated in 2006 and in 2017 now include imaging findings of left ventricular (LV) dysfunction (LV EF < 50%) on cardiac MRI and echocardiography as major diagnostic criterion. Limited data is available with regards to co-morbidities clustering in sarcoidosis and CS according to the 2017 updated guideline diagnostic criteria. Methods: A case control, single tertiary medical center study included 558 sarcoidosis patients with documented extracardiac sarcoidosis and completed electrocardiogram and/or cardiac MRI imaging. CS 2006 and 2017 diagnostic criteria and co-morbidity data were extracted from electronic charts and were available for comparison in 540 patients. Results: The total study population was composed of 52.7% (281/540) females, aged 58.9+/-12.6 years old, with diabetes mellitus (DM) present in 29.6% (160/540), HTN in 51.7% (279/540), CAD in 13.3% (72/540), moderate to severe aortic, mitral, or tricuspid valvular disease in 14.8% (80/540), ESRD in 2.4% (13/540), and COPD or asthma in 21.9% (118/540). There was a significant clustering of co-morbidities according to the imaging CS diagnostic criteria. Patients meeting the 2017 CS imaging criteria were found to be older (61.4+/-11.3 vs 58.8+/-12.8 years old in patients not meeting criteria, p=0.085), predominantly male (69.2%, (54/78) vs. 44.4%, (205/462), p<0.001), and demonstrated significantly increased prevalence of DM (39.7%, (31/78) vs. 27.9%, (129/462), p=0.034), and valvular disease (33.3%, (26/78) vs. 11.7%, (54/462), respectively, p<0.001). However, there were no statistically significant difference in the prevalence of HTN (60.3%, (47/78) vs. 50.2%, (232/462), p=0.101), ESRD (3.9%, (3/76) vs. 2.2%, (10/456), p=0.361), and COPD or asthma (19.2%, (15/78) vs. 22.3%, (103/462), p=0.544) in patients meeting 2017 CS criteria compared to those that did not. Conclusion: CS patients meeting 2017 imaging diagnostic criteria were found to have statistically significant clustering of the following co-morbidities: male gender, DM, and valvular disease. These findings underscore importance of comprehensive care in CS patients and warrant caution in assigning LV abnormalities observed on imaging solely to CS etiology.

Contribution of reduced skeletal muscle perfusion reserve to exercise intolerance in heart failure with preserved ejection fraction

BackgroundSkeletal muscle (SM)-associated mechanisms of exercise intolerance in HFpEF are insufficiently defined, and inadequate augmentation of SM blood flow during physical effort may be one of the contributors. Therefore, we sought to investigate the association of SM perfusion response to exertion with exercise capacity in this clinical condition. MethodsEchocardiography and SM microvascular perfusion by contrast-enhanced ultrasound were performed at rest and immediately post-exercise test in 77 HFpEF patients in NYHA class II and III, and in 25 subjects with normal exercise tolerance (stage B). Exercise reserve of cardiac function and SM perfusion was calculated by subtracting resting value from exercise value. ResultsIn addition to decreased cardiac functional reserve, HFpEF patients demonstrated significantly reduced SM perfusion reserve as compared to HF stage B, with the degree of impairment being greater in the subgroup with more profound left ventricular (LV) diastolic abnormalities (E/e’ > 15 and TRV > 2.8 m/s).SM perfusion reserve was significantly associated with exercise capacity (beta = 0.33; SE 0.11; p = 0.003), cardiac output reserve (beta = 0.24; SE 0.12; p = 0.039), resting E/e’ (beta = −0.33; SE 0.11; p = 0.006), and patient frailty expressed by the PRISMA 7 score (beta = −0.30; SE 0.11; p = 0.008). In multivariable analysis including clinical, demographic and cardiac functional variables, SM perfusion reserve was in addition to patient frailty, sex and LV longitudinal strain reserve among the independent correlates of exercise capacity. ConclusionsSM perfusion reserve is impaired in HFpEF, and is associated with reduced exercise capacity independent of clinical, demographic and “central” cardiac factors. This supports the need to consider the SM domain in patient management strategies in HFpEF.

Left Ventricular Geometric Patterns in Newly Diagnosed Hypertension: An Echocardiographic Study

Objective: To investigate patterns of left ventricular (LV) geometric patterns in patients diagnosed with new-onset hypertension using transthoracic echocardiography. The LV diastolic function was also evaluated in these patients. Materials and Methods: The present study was a cross-sectional study that clinically evaluated patients diagnosed with new-onset hypertension at Burapha University Hospital. To classify LV geometric patterns, electrocardiogram, and transthoracic echocardiography to measure LV mass index and relative wall thickness were performed. Other relevant assessments were also conducted, including the diastolic function. Results: Fifty-five patients diagnosed with new-onset hypertension were enrolled, their mean age was 55.3 years, with a standard deviation of 11.8 years. Of all participants, 70.9% (95% CI 57.1 to 82.4) had concentric remodeling, 16.4% (95% CI 7.8 to 28.8) had concentric hypertrophy, 10.9% (95% CI 4.1 to 22.3) had normal geometry and 1.8% (95% CI 0.1 to 9.7) had eccentric hypertrophy. Of all participants, 81.8% were detected to have abnormal LV diastolic dysfunction. Abnormal relaxation pattern was the most common format. Conclusion: In the present study, approximately 10.9% of patients diagnosed with new-onset hypertension had normal LV geometry, whereas 89.1% had abnormal geometry in different patterns. Concentric remodeling was found to be the predominant abnormal geometrical format. Understanding LV geometric patterns helps clinicians stratify risk, predict prognosis, and make informed decisions about treatment strategies for these patients. Keywords: Hypertension; Left ventricular geometric pattern; Diastolic dysfunction

Echocardiographic Assessment of the Left Ventricle in Young Prehypertensive Nigerians.

Prehypertension is associated with an increased risk of cardiovascular morbidity and mortality. This risk could partly be explained by the early compromise in left ventricular (LV) structure and function. This study investigated the LV geometry and function in young black prehypertensive subjects. This cross-sectional descriptive study was conducted at the Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria. Echocardiography-derived LV geometry and function were assessed using standardized methods. Prehypertensive subjects had higher mean systolic blood pressure (BP) (130.78 ± 3.57 mmHg vs 111.42 ± 3.54 mmHg, P<0.001), diastolic BP (79.32 ± 4.13 mmHg vs 66.39 ± 4.42 mmHg, P<0.001), body mass index (BMI) (26.24 ± 3.45 kg/m2 vs 22.20 ± 2.21 kg/m2, P<0.001), waist circumference (WC) (86.93 ± 8.73 cm vs 76.73 ± 6.66 cm, P<0.001), fasting blood glucose (FBG) (93.84 ± 7.28 mg/dl vs 90.08 ± 6.26 mg/dl, P<0.001), and dyslipidemia (21.5% vs 6%. P<0.001) compared to normotensive subjects. LV mass index (LVMI) was greater in prehypertensive subjects compared to normotensive subjects {male (106.84 ± 12.34 g/m2 vs 76.07 ± 10.25 g/m2, P<0.001); female (92.06 ± 8.80 g/m2 vs 66.53 ± 7.21 g/m2, P<0.001)}, with abnormal LV geometry recorded in 17.5%. Linear regression analysis showed that waist circumference, systolic BP, serum creatinine level, and urea level were determinants of LVMI. The prevalence of LV diastolic dysfunction was higher in prehypertensive subjects than in normotensive subjects (14.5% vs. 0.5%, P<0.001), with systolic BP {odds ratio (OR) 0.928, confidence interval (CI) 0.834 - 0.969; P=0.016)} and diastolic BP (OR 0.832, CI 0.722 - 0.958; P=0.011) being independent predictors. This study showed that prehypertension in young Black subjects was associated with altered LV geometry and impaired diastolic function, and these changes demonstrated linear progression with increasing systolic BP.

LEFT VENTRICULAR GEOMETRY AMONG CHRONIC KIDNEY DISEASE PATIENTS: THE ROLE OF ANEMIA

BACKGROUND: Anaemia and abnormal left ventricular (LV) geometric pattern are common findings in Chronic Kidney disease (CKD) patients.&#x0D; OBJECTIVES: To assess LV geometric pattern and its relationship with anaemia among CKD patients.&#x0D; METHODS: A cross sectional study of 163 subjects (102 and 61 CKD subjects with and without anaemia respectively). Echocardiography determined the LV geometric pattern while packed cell volume (PCV) levels determined anaemia.&#x0D; RESULTS: The mean age of subjects with and without anaemia was 54.04 ± 14.47 and 54.92 ± 15.67 years respectively (p = 0.717) while the prevalence of LVH among the two groups was 68.8% and 57.9% respectively (p = 0.174). The most frequent LV geometry in both groups was concentric LVH (53.8% and 43.9% respectively). Prevalence of LV systolic dysfunction was 45%, higher among anaemic subjects (58(61.7%) vs 10(17.5%)) p &lt; 0.001. There was a strong negative correlation between PCV and left ventricular mass index (r = -0.345, p = 0.001) among anaemic subjects, but weak positive correlation among patients without anaemia (r = 0.001, p = 0.993).&#x0D; CONCLUSION: Anaemic CKD patients had a high prevalence of abnormal LV geometry with significant contribution from anaemia. Early management of anaemia may thus improve cardiovascular outcomes.

Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction.

Pseudomonas aeruginosa (P.a.) infection accounts for nearly 20% of all cases of hospital acquired pneumonia with mortality rates >30%. P.a. infection induces a robust inflammatory response, which ideally enhances bacterial clearance. Unfortunately, excessive inflammation can also have negative effects, and often leads to cardiac dysfunction with associated morbidity and mortality. However, it remains unclear how P.a. lung infection causes cardiac dysfunction. Using a murine pneumonia model, we found that P.a. infection of the lungs led to severe cardiac left ventricular dysfunction and electrical abnormalities. More specifically, we found that neutrophil recruitment and release of S100A8/A9 in the lungs activates the TLR4/RAGE signaling pathways, which in turn enhance systemic inflammation and subsequent cardiac dysfunction. Paradoxically, global deletion of S100A8/A9 did not improve but aggravated cardiac dysfunction and mortality likely due to uncontrolled bacterial burden in the lungs and heart. Our results indicate that P.a. infection induced release of S100A8/9 is double-edged, providing increased risk for cardiac dysfunction yet limiting P.a. growth.

Echocardiography Assessment of Left Ventricular Function in Extremely Preterm Infants, Born at Less Than 28 Weeks’ Gestation, With Bronchopulmonary Dysplasia and Systemic Hypertension

The survival of smaller and more immature premature infants has been associated with lifelong cardiorespiratory comorbidities. Infants with bronchopulmonary dysplasia (BPD) undergo routine screening echocardiography to evaluate for development of chronic pulmonary hypertension, a late manifestation of pulmonary vascular disease. Our aim was to evaluate left ventricular (LV) performance in infants with BPD and pulmonary vascular disease who developed systemic hypertension. We hypothesized that infants with hypertension were more likely to have impaired LV performance. We present a single-center cross-sectional study of premature infants born at less than 28 0/7weeks'gestational age with a clinical diagnosis of BPD. Infants were categorized by the systolic arterial pressure (SAP) at time of echocardiography as hypertensive (SAP ≥90mm Hg) or normotensive (SAP <90mm Hg). Sixty-four patients were included. Infants with hypertension showed altered LV diastolic function with prolonged tissue Doppler imaging-derived isovolumic relaxation time (54.2±5.1 vs 42.9±8.2, P<.001), lower E:A, and higher E:e'. Indices of left heart volume/pressure loading (left atrium:aorta and LV end-diastolic volume [6.1±2 vs 4.2±1.2, P<.001]) were also higher in the hypertensive group. Finally, infants in the hypertensive group had higher pulmonary vascular resistance index (4.42±1.1 vs 3.69±0.8, P=.004). We conclude that extremely preterm infants with BPD who develop systemic hypertension are at risk of abnormal LV diastolic dysfunction. Increased pulmonary vascular resistance index in the hypertensive group may relate to pulmonary venous hypertension secondary to LV dysfunction. This is an important consideration in this cohort when selecting the physiologically most appropriate treatment.

Echocardiographic Assessment in Patients Recovered from Acute COVID-19 Illness.

Coronavirus (COVID-19) infections have spread rapidly worldwide and posed an immense public health problem. COVID-19 infection can affect the cardiovascular system both acutely and in patients followed up some period after COVID-19 infection. The aim of this study was to evaluate left ventricular (LV) and right ventricular (RV) function by echocardiography in COVID-19 recovered patients (hospitalized and non-hospitalized). Forty-two patients who recovered from COVID-19 but had ongoing symptoms were included in this retrospective observational cross-sectional study. Patients were followed-up at a median time of 112 days from confirmed COVID-19 diagnosis and a comprehensive echocardiogram was performed. COVID-19 patients were age- and sex-matched to healthy controls. Traditional TTE parameters and advanced echocardiographic parameters including two-dimensional LV global longitudinal strain (GLS) and RV free wall strain (FWS) were measured. LV volumes and LV ejection fraction were similar in COVID-19 patients and controls; however, LV GLS was significantly worse in the COVID-19 group (p = 0.002). Similarly, RV volumes and traditional RV function parameters were similar, but RV FWS (p = 0.009) and RV global strain (p = 0.015) were reduced. Alterations in LV and RV strain were observed in both hospitalized and non-hospitalized patients. In the subset of COVID-19 patients without any co-morbidities (n = 30), LV GLS remained reduced compared to controls. According to multivariate analysis, COVID-19 infection was the only independent determinant of reduced LV GLS (p = 0.012), while COVID-19 infection, diastolic blood pressure, and RV fractional area change were determinants of RV FWS. In this observational study, prior COVID-19 infection demonstrated LV dysfunction in patients with persistent symptoms. Abnormal LV strain was evident in both hospitalized and non-hospitalized patients, suggesting that these changes are independent of the severity of COVID-19 infection at presentation. The use of LV GLS in COVID-19 patients could have potential clinical utility to support the indication for cardiac magnetic resonance imaging in patients with possible COVID-19 related myocarditis. Future longitudinal studies are needed to evaluate its correlation with adverse cardiovascular events.

Subclinical Left Ventricular Dysfunction and Ventricular Arrhythmias in Older Adults With Normal Ejection Fraction.

Background Premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) are known to be associated with reduced left ventricular (LV) ejection fraction and adverse outcomes in patients with structural heart disease. The relationship between subclinical LV dysfunction and ventricular arrhythmias in the general population is not established. Methods and Results Participants in the SAFARIS (Subclinical Atrial Fibrillation and Risk of Ischemic Stroke) study with normal left ventricular ejection fraction (n=503; mean age 77 years, 63% women) underwent 14-day electrocardiographic monitoring and 2-dimensional echocardiography. Frequent PVCs were defined as PVCs >500 per 24 hours and NSVT as ≥4 consecutive ventricular ectopic beats. Reduced LV global longitudinal strain (GLS) was used as an indicator of subclinical LV dysfunction. Seventy-six participants (15.1%) had PVCs >500/d, 117 (23.3%) had NSVT episodes. LV GLS was significantly reduced in both frequent PVCs and NSVT groups (P<0.01). In multivariable analyses, lower LV GLS was associated with frequent PVCs (adjusted odds ratio [aOR], 1.19 [95% CI, 1.09-1.30 per unit reduction]; P<0.001) and NSVT (aOR, 1.09 [95% CI, 1.01-1.17]; P=0.036) independently of established risk factors and other echocardiographic parameters. Abnormal LV GLS (>-15.8%) carried a 2-fold increase in risk of ventricular arrhythmias (aOR, 2.18, P=0.029 for PVCs; aOR, 2.09, P=0.026 for NSVT). Conclusions PVCs and NSVT episodes were frequent in this community-based elderly cohort with normal left ventricular ejection fraction and were independently associated with lower LV GLS. The association between LV dysfunction and ventricular arrhythmias is present at an early, subclinical stage, an observation that carries possible preventative implications.

Association of insulin use with LV remodeling and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: assessed by cardiac MRI

BackgroundInsulin is commonly used in type 2 diabetes mellitus (T2DM) to achieve glycemic control. However, recent evidence showed that insulin use is associated with poor outcomes in the context of heart failure (HF). Since heart failure with reduced ejection fraction (HFrEF) accounts for approximately 50% of cases in the general HF population, we aimed to evaluate the effect of insulin treatment on left ventricular (LV) remodeling and contractility abnormalities in a HFrEF cohort and assess whether insulin was a predictor of adverse outcomes in this entity.MethodsA total of 377 HFrEF patients who underwent cardiac MRI were included and divided according to diabetes status and the need for insulin treatment. LV structural and functional indices, as well as systolic strains, were measured. The determinants of impaired myocardial strains were assessed using linear regression analysis. The associated endpoints were determined using a multivariable Cox proportional hazards model.ResultsT2DM patients on insulin displayed a higher indexed LV end-diastolic volume and LV mass than those with T2DM not on insulin or those without T2DM, despite similar LV ejection fractions, accompanied by a higher three-dimensional spherical index (P < 0.01). Worse longitudinal and circumferential peak systolic strain was shown to occur in T2DM patients on insulin (P < 0.01). Insulin treatment was independently associated with impaired magnitudes of systolic strain. The median follow-up duration was 32.4 months (IQR, 15.6–43.2 months). Insulin treatment remained consistently associated with poor outcomes after adjustment for established confounders, with an adjusted hazard ratio of 3.11; (95% CI, 1.45–6.87; P = 0.009) in the overall cohort and 2.16 (95% CI, 1.08–4.59; P = 0.030) in the diabetes cohort.ConclusionsInsulin may further lead to adverse LV remodeling and contractile dysfunction in the context of HFrEF with T2DM. Considerable care should be taken when treating HFrEF patients with insulin.

Left ventricular structural abnormalities in the assessment of diastolic function in the elderly: source of discrepancies between the 2009 and 2016 criteria.

Diastolic dysfunction (DD) is routinely evaluated in echocardiography to support diagnosis, prognostication, and management of heart failure, a condition highly prevalent in elderly patients. Clinical guidelines were published in 2009, and updated in 2016, pursuing to standardize and improve DD categorization. We aimed to assess the concordance of DD between these two documents in an elderly population and to investigate how left ventricular structural abnormalities (LVSA) impact the reclassification. To evaluate this we analyzed the 308 consecutive transthoracic echocardiograms in patients older than 60 years (70.4 ± 7.7 years-old, 59% women) that fulfilled the inclusion criteria out of the 1438 echocardiograms performed in a tertiary hospital. We found that the prevalence of DD was lower according to the 2016 criteria (64% vs. 91%; p < 0.001), with 207 (67.2%) patients changing category, indicating poor agreement between the guidelines (kappa = 0.21). There were 188 (61%) patients with LVSA, which drove most of the reclassifications in 2016 Grade I DD cases. The prevalence of elevated filling pressures by Doppler halved in this elderly population using the updated recommendations (20.9% vs. 39.2%; p < 0.001). In conclusion the prevalence of DD was lower applying the 2016 guidelines, with a poor agreement with 2009 guidelines in all DD grades. The role of LVSA in reclassifications was particularly evident in Grade I DD, while Doppler parameters drove reclassifications among the more severe grades. If not properly addressed, these discrepancies may undermine the reliance on DD as a diagnostic and prognostic tool, particularly in an elderly population at a higher risk of heart failure.

Diastolic function in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by clustered age-independent concentric left ventricular (LV) geometry, geometry-independent systolic dysfunction and age and heart rate-independent diastolic dysfunction. Concentric LV geometry is always associated with echocardiographic markers of abnormal LV relaxation and increased myocardial stiffness, two hallmarks of diastolic dysfunction. Non-haemodynamic mechanisms such as metabolic and electrolyte abnormalities, activation of biological pathways and chronic exposure to cytokine cascade and the myocardial macrophage system also impact myocardial structure and impair the architecture of the myocardial scaffold, producing and increasing reactive fibrosis and altering myocardial distensibility. This review addresses the pathophysiology of diastole in CKD and its relations with cardiac mechanics, haemodynamic loading, structural conditions, non-haemodynamic factors and metabolic characteristics. The three mechanisms of diastole will be examined: elastic recoil, active relaxation and passive distensibility and filling. Based on current evidence, we briefly provide methods for quantification of diastolic function and discuss whether diastolic dysfunction represents a distinct characteristic in CKD or a proxy of the severity of the cardiovascular condition, with the potential to be predicted by the general cardiovascular phenotype. Finally, the review discusses assessment of diastolic function in the context of CKD, with special emphasis on end-stage kidney disease, to indicate whether and when in-depth measurements might be helpful for clinical decision making in this context.

Difficulties in Diagnosing Fabry Disease in Patients with Unexplained Left Ventricular Hypertrophy (LVH): Is the Novel GLA Gene Mutation a Pathogenic Mutation or Polymorphism?

Fabry disease (FD) is an X-linked, lysosomal glycosphingolipid storage disorder that occurs very rarely. Cardiac involvement may comprise of left ventricular hypertrophy (LVH), arrhythmias, conduction abnormalities, heart failure and valvular abnormalities. The goal of this study was to conduct gene analysis for FD in patients suffering from unexplained LVH. 120 patients over the age of 30 who were diagnosed by echocardiography with idiopathic LVH were included in the study. Patients with severe hypertension, intermediate valve disease such as moderate aortic stenosis, known FD, and a family history of autosomal dominant hypertrophic cardiomyopathy were excluded from the study. GLA gene mutations were studied by Sanger sequence analysis in all patients. Of the 120 total patients included in this study, 69 were female (58%) and 51 were male (42%). The mean age was 60.3 ± 15.7. GLA gene mutations were detected in three male patients. The detected mutations are as follows: NM_000169.2:IVS6-10G>A (c.1000-10G>A), NM_000169.2:c.937G>T (p.D313Y) (p.Asp313Tyr) and NM_000169.2:c.941A>T (p.K314M) (p.Lys314Met). Early diagnosis is of vital importance in FD, which can be treated with enzyme replacement. Genetic screening in patients diagnosed with idiopathic LVH by echocardiography is important in the early diagnosis and treatment of FD. Patients over 30 years of age with idiopathic LVH should be screened for FD. Various new polymorphisms can be detected in genetic screening. Identifying new polymorphisms is important for knowing the true mutations in FD.

Dark papillary muscles sign: a novel prognostic marker for cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background the prognostic role of left ventricular (LV) papillary muscle abnormalities in patients with preserved LV systolic ejection fraction (LVEF) is unknown. Aim to evaluate the prevalence and the clinical and prognostic impact of papillary muscle abnormalities by CMR in patients with ventricular arrhythmias, preserved LVEF with no cardiac disease. Methods 391 patients with &amp;gt;500/24h premature ventricular complexes and/or with non-sustained ventricular tachycardia (NSVT), preserved LVEF and no cardiac disease, were enrolled. Different features of LV papillary muscles were considered: supernumerary muscles, papillary thickness, the attachment, late gadolinium enhancement (LGE). The end-systolic hypointensity was defined when its measured signal intensity (SI) was lower than the SI of the septum in early post-contrast cine CMR images. Dark-Paps was defined when both the main papillary muscles had systolic hypointensity. Mitral valve prolapse, mitral annular disjunction (MAD), myocardial LGE were considered. The outcome of hard cardiac events was define as a composite of cardiac death, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) shock, sustained ventricular tachycardia (lasting ≥30 s at ≥100 beats/min). Results Dark-Paps was found in 79 (20%) patients and was more frequent in females. It was associated with higher prevalence of mitral valve prolapse and MAD. During a median follow-up of 2534 days, 22 hard cardiac events occurred. At Kaplan-Meier curve (Figure) analysis patients with Dark-Paps were at higher risk of events than those without (p&amp;lt;0.0001). Dark-Paps was significantly associated with hard cardiac events in all the multivariate models performed. Dark-Paps improved prognostic estimation when added to NSVT (p = 0.0006), to LGE (p = 0.005) and to a model including NSVT+LGE (p = 0.014). Dark-Paps allowed a significant net reclassification when added to NSVT (NRI 0.30, p =0.03), to LGE (NRI 0.25, p =0.04), and to NSVT + LGE (NRI 0.32, p =0.02). Conclusions Dark-Paps sign could be considered a novel imaging prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction.

Impact of sex on severity assessment and cardiac remodeling in primary mitral regurgitation due to valve prolapse

Abstract Funding Acknowledgements Type of funding sources: None. Background It is well known that left ventricular(LV) dimensions are influenced by body size and sex. However, current guidelines for primary mitral regurgitation(MR) valve disease propose echocardiographic cut-off values for MR quantitative parameters (effective orifice regurgitant area(EROA), regurgitant volume(RegVol)) and left heart remodeling (LV end-systolic diameter[ESD], indexed LA volume[indLAV]) which are not sex-specific. Purpose Therefore we aimed at evaluating how MR severity and cardiac remodeling are influenced by sex. Methods We retrospectively evaluated 470 patients (27% women, median age 63 [IQR: 53–71] years) with chronic significant (at least moderate to severe) primary MR due to valve prolapse who underwent transthoracic echocardiographic(Echo) and cardiac magnetic resonance imaging(CMR) in 3 tertiary centers between 2005 and 2022. The relationship between MR quantification, cardiac remodeling and sex was evaluated. Results Women were older than men (p&amp;lt;0.001), had higher NYHA functional class (p = 0.035), larger Echo-indLAV (p = 0.003), higher right ventricle systolic peak pressure (p = 0.032), and more symptoms-triggered MV intervention (p = 0.029). However, both EROA (p&amp;lt;0.001), Echo-RegVol (p = 0.003) and CMR-RegVol (p&amp;lt;0.001) were lower in women than in men, while CMR regurgitant fraction(RegFrac) values were similar (p = 0.890). Abnormally increased CMR- (&amp;gt;upper limit bound of UK Biobank reference values) indexed LV end-diastolic(indLVEDV), end-systolic volume(indLVESV) and indLAV were observed in 55%, 29% and 82% of patients, respectively, without sex difference (p = 1, p = 0.9 and p = 0.5). The optimal cut-off values of MR EROA, Echo-RegVol and CMR-RegVol associated with enlarged indLVEDV were lower in women (40mm2, 60ml, 50ml) than in men (45mm2, 77ml, 62ml). The threshold of LVESD ≥40mm showed in women and men high specificity[Sp] (91%, 79%) but poor sensitivity[Se] (40%, 50%) to predict enlarged indLVESV. Accordingly, the best threshold of LVESD to predict enlarged indLVESV was slightly lower in women (35mm, Se=65%, Sp = 71%, AUC=0.72) than in men (37mm, Se=65%, Sp = 68%, AUC=0.72). Replacing absolute by indexed LVESD did not improve the predictive value. In contrast, the best threshold of Echo-indLAV associated with enlarged CMR-indLAV was lower in men (47ml/m2, Se=68%, Sp = 71%, AUC=0.76) than in women (56ml/m2, Se=70%, Sp = 71%, AUC=0.73). Conclusion Despite clear hallmarks of more advanced valve disease, women with primary MR have lower absolute mitral regurgitant volumes and lower ventricular volumes than men. Furthermore, cut-off values of mitral regurgitant volume, effective orifice regurgitant area and LV dimensions for predicting abnormal LV dilatation by CMR are lower in women than in men. Conversely, cut-off values of indexed LA volume by echo for predicting abnormal LA dilatation by CMR are lower in men than in women. Therefore, guideline-based criteria for grading MR and timing of intervention could be sex-specific.

FEATURE-BASED CLUSTERING OF LEFT VENTRICULAR STRAIN CURVE FOR RISK STRATIFICATION IN GENERAL POPULATION

Objective: Global left ventricular (LV) strain has been identified as an important predictor of adverse cardiovascular (CV) events. However, currently only the peak strain is used from the LV deformation curve, neglecting the temporal information hidden in all phases of heart cycle. Therefore, we employed unsupervised machine learning methods on time-series-derived features from LV strain to identify distinct clinical phenogroups associated with the risk of developing adverse events in the general population. Design and method: We prospectively studied 1185 community-dwelling individuals (mean age, 53.2 years; 51.3% women), in whom we acquired clinical and echocardiographic data including LV strain traces at baseline and collected CV events (n = 94) on average 5.2 years later. We utilised Gaussian Mixture Model (GMM) on different features derived from LV strain curve, including slope during systole and diastole, peak strain, slope during late diastole and the duration and height of diastasis (Figure, left panel). We evaluated the clinical significance of the clusters (k) by comparing the clinical characteristics and CV adverse outcome. Results: Based on inertia and BIC scores the optimal number of clusters (k) was 4. The first two clusters had differences in heart rate, but had similar low CV risk profiles. Cluster 4 had the worst CV risk factors combination, and higher prevalence of LV remodelling and diastolic dysfunction (i.e. lowest e ‘velocity and highest E/e’) compared to other clusters. Kaplan–Meier showed an increased cumulative incidence risk for all CV events across clusters (Figure, right panel). After adjustment for traditional risk factors, the risk was significantly higher in clusters 3 (HR: 1.35; 95% CI: 1.01-1.82; P = 0.043) and 4 (HR: 1.32; 95% CI: 1.05-1.67; P = 0.017) than in cluster 1, while the risk of adverse events did not reach the significant level in subjects with an abnormal peak LV strain (&lt;17%) (HR 1.12; P = 0.66). Conclusions: Unsupervised machine learning algorithm employed on features derived from time series LV strain curves identifies clinically meaningful clusters, and provides important prognostic information over the peak LV strain.