Ventricular End-diastolic Volume Research Articles

Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis.

Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25mg (13.64; 0.26, 27.01) compared to Canagliflozin 100mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10mg (0.45; 0.25, 0.82) and Empagliflozin 10mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10mg (0.81; 0.66, 0.98) compared to Vildagliptin 50mg; the cardiovascular death of Albiglutide 30mg (0.49; 0.28, 0.86) compared to Exenatide 2mg; and the arrhythmic events of Liraglutide 1.8mg (0.49; 0.26, 0.90) compared to Empagliflozin 10mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.

The in-hospital administration of sacubitril/valsartan in acute myocardial infarction: A meta-analysis.

There is a need to address the evidence gap regarding the in-hospital administration of sacubitril/valsartan in acute myocardial infarction patients. After searching MEDLINE, Google Scholars and Scopus, a random-effects meta-analysis of randomized controlled trials comparing the in-hospital administration of the angiotensin receptor-neprilysin inhibitors (ARNis) versus the standard therapy in patients with reduced heart failure due to myocardial infarction was performed. The primary outcome was major adverse cardiovascular events. All-cause mortality, cardiac death, rehospitalization for heart failure, non-fatal myocardial infarction (MI), changes in left ventricular ejection fraction, left ventricular volumes, N terminal pro brain natriuretic peptide and adverse events were the secondary endpoints. Nine studies (eight randomized controlled trials and one echo-substudy) with a total 6597 individuals (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: 3300 patients vs. ARNis: 3297 patients) were included for quantitative analysis. Median follow-up was 6months. Patients receiving an in-hospital coadministration of ARNi had a lower risk of major cardiovascular event [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.32-0.63, P<0.0001] and lower rate of repeat rehospitalization for heart failure (OR 0.40, 95% CI 0.26-0.62, P<0.0001), compared with a standard regimen. Additionally, left ventricle volumes were significantly lower in the ARNi group [left ventricular end-diastolic volume, mean difference (MD) 11.48mL, 95% CI 6.10-16.85, P<0.0001; left ventricular end-systolic volume, MD 7.09mL, 95% CI 2.89-11.29, P=0.0009] with a significant change in left ventricular ejection fraction (MD 3.07, 95% CI 1.61-4.53, P<0.0001), compared with standard therapy. No significant differences were observed in terms of cardiac death, all cause of mortality, non-fatal myocardial infarction and N terminal pro brain natriuretic peptide. Higher rates of iatrogenic hypotensive events were observed in the ARNi group compared with the standard therapy (OR 1.42, 95% CI 1.26-1.60, P value<0.00001). In patients with acute myocardial infarction related heart failure, the in-hospital administration of ARNis was associated with a reduced risk of major cardiovascular events and re-hospitalization for heart failure, as well as cardiac remodelling, but higher rates of hypotensive events compared with standard therapy.

Large sample size MRI measurements to assess the relation between cardiac function and structure and white matter hyperintensity volumes

Abstract Background People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurological diseases such as dementia. CVD and neurological diseases share common risk factors, such as blood pressure, sedentary lifestyle, as well as genomic risk factors such as mutations in APOE4 [1]. It's unclear to what extent the co-occurrence of CVD and neurological diseases is explained by these risk factors, or whether there is a direct association where CVD is a first step towards poorer neurological health. White matter hyperintensities (WMH) of presumed vascular origin are damaged areas in the brain observed through magnetic resonance imaging (MRI). These lesions are associated with progressive neurological disease such as vascular dementia, as well with risk factors for CVD [2]. Purpose We set out to determine to what extent CMR measurements associated with WMH independent of known cerebrovascular risk factors. Methods Cardiac and brain MRI images were analysed for 23,963 UK biobank (UKB) participants. WMH analysis included 5 brain regions (Frontal[F], Parietal[P], Temporal[T], Occipital[O], Basal Ganglia and Thalami [BGT]) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas. Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for: age, difference between age at initial visit and imaging visit, sex, systolic and diastolic blood pressure, Hba1c, household income, educational status, Townsend score and family history of disease (Alzheimer’s, Parkinson's, high blood pressure, stroke, heart disease) . Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain 90% of the cardiac trait variability. Results For 5 cardiac traits (right ventricular stroke volume, left atrial stroke volume, left ventricular stroke volume, left ventricular ejection fraction and right ventricular end diastolic volume) higher values were associated with lower WMH volumes in all brain regions. Additionally, some cardiac traits such as LV cardiac output associated with specific brain regions (T, O, BGT). Additionally, APOE- ε4 stratified analyses indicated, homozygous carriers show a greater association between higher minimum LA and RA volumes and higher WMH volumes in the occipital lobe. Conclusions This study gives an insight into the WMH burden in a large population of adults. It highlights the associations of cardiac traits with white matter hyperintensity volumes in different brain regions independent of known risk factors. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between CVD and cerebrovascular disease.Figure 1Graphical Abstract

Cardiac magnetic resonance characteristics of the athlete's heart: deeper insights into cardiac remodelling

Abstract Cardiac magnetic resonance (CMR) offers precise quantification for myocardial parameters. Understanding the effects of different training volumes on the athlete’s heart could be the key to distinguishing between cardiac conditions. This study aims to investigate CMR parameters including T1- and T2 mapping in healthy athletes and less active individuals and explore their relationship with training volumes in both sexes. We included healthy athletes (weekly training hours &amp;gt;7) and less active age- and sex-matched control individuals (weekly training hours ≤6), and performed CMR examinations. We assessed ventricular volumes, masses, and function, and conducted T1- and T2-mapping on non-contrast short-axis images. A total of 270 CMR examinations were conducted, comprising 185 athletes (119 males, mean age 22±6 years, weekly training hours: 19±7) and 85 controls (50 males, mean age 26±3 years, weekly training hours: 3±2). In male athletes compared to less active individuals, we observed pronounced signs of sports-related cardiac remodeling, including increased end-diastolic volume and mass index (Left ventricular end-diastolic volume index (LVEDVi): 120±16 vs 97±12 ml/m2, p&amp;lt;0.001; left ventricular mass index (LVMi): 70±14 vs 53±9 g/m2, p&amp;lt;0.001). Similarly, female athletes exhibited significant sports adaptations compared to controls (LVEDVi: 103±12 vs 86±11 ml/m2, p&amp;lt;0.001; LVMi: 54±9 vs 39±5 g/m2, p&amp;lt;0.001). T1-mapping values in athletes were lower than in the control group for both sexes (males: 939±25 vs 961±20 p&amp;lt;0.001, females: 966±21 vs 985±17, p&amp;lt;0.001). T1 values showed negative correlations with training hours (r=-0.362, p&amp;lt;0.001), LVEDVi (r=-0.411, p&amp;lt;0.001), and LVMi (r=-0.546, p&amp;lt;0.001). A significant association between T1 values and training hours persisted across various models. In the raw model, every additional training hour correlated with a T1 reduction of 0.946 ms (p&amp;lt;0.001). Adjusting for age, sex, and heart rate (HR) in model 2, the association remained significant, with each additional training hour corresponding to a T1 reduction of 0.825 ms (p&amp;lt;0.001). Further adjustments for LVMi in model 3 revealed a significant association, with a decrease of 0.565 ms in T1 values for each additional training hour (p=0.002). Among athletes, training years associated with decreased T1 and increased ventricular end-diastolic volumes and myocardial mass indices (LVEDVi: r=0,232, p=0,002; p&amp;lt;0,001; LVMi: r=0,279, p&amp;lt;0,001; T1-mapping: r=-0,169; p=0,026). Examining the differences between sexes we found that female athletes respond slightly less to a unit of exercise compared to males. Our findings underscore that different training hours and invested years have a meaningful impact on physiological adaptation. Female athletes’ heart responds slightly less to these effects. But in both sexes, higher training hours resulted in lower T1 and this relationship persisted independent of the influences of age, HR, and LVMi.

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&amp;lt;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&amp;lt;0.001) and stress MBF (1.38(1.25-1.51) versus 1.55(1.43-1.67) mL/g/min; P&amp;lt;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&amp;lt;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&amp;lt;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.

Genetic and phenotypic architecture of biventricular trabeculation

Abstract Introduction Cardiac trabeculae form a network of muscular strands that line the inner surfaces of the heart, and their development involves molecular pathways that regulate structural complexity. Excessive or hypertrabeculation occurs as part of normal variation in apparently healthy individuals, as an adaptation to altered loading conditions, and is observed in patients with cardiomyopathies (CMs) and heart failure (HF). Purpose In adults, trabeculation is not a prognostic factor independent of the underlying myocardial disease but may play a role in the natural history of ventricular remodelling. We sought to (i) understand the genetic and non-genetic determinants of trabeculation, (ii) understand its role in the causality of disease, and (iii) evaluate trabeculation as a biomarker for diagnosis and stratification. Methods We report genes with a burden of rare variants and novel common variant associations across the allele frequency spectrum for biventricular trabecular morphology in 47,803 participants of the UK Biobank using fractal dimension analysis of cardiac imaging (Figure 1). We assessed environmental modifiers of trabecular morphology, correlation with cardiac traits, phenome-wide association studies, and the relationship with the progression of CMs and HF. Results We identified a burden of trabeculation-associated rare variants in genes that regulate myocardial contractility and cardiac development and GWAS identified novel loci near genes implicated in CMs, conduction traits, and signalling pathways that define the early development of trabeculation. For example, we identified 56 genes with a burden of rare variants and 68 novel loci from GWAS (e.g., CASQ2, CACNA1C, MYBPC3, MYH7, NKX2-5, NOTCH1, TBX20) for the left ventricle. The strongest imaging relationships with trabeculation were with measures of volume and strain. Modifiers of trabeculation included African ancestry, alcohol intake, and physical activity. Carriers of CM-associated pathogenic variants had increased trabeculation. Of participants with CM reported after imaging, 25% had hypertrabeculation on imaging and hypertrabeculation was a risk factor for a subsequent diagnosis of HF (HR=1.3), mitral valve disorders (HR=1.4), bundle branch block (HR=1.2). Comparisons of biventricular trabeculation showed similarities in trabeculation across the ventricles in CM. Reduced right ventricular trabeculation and end-diastolic volume associated with Type-2 diabetes. Conclusions These data provide new insights into the mechanisms that regulate structural complexity in the heart. Changes in trabeculation may occur early in the pathogenesis of heart disease, can be modified by genes regulating pathways outside the sarcomere, and causality depends on the underlying cardiomyopathic substrate. Trabeculation progresses with cardiovascular disease, is a useful marker of remodelling, and identifies novel genetic modifiers of ventricular complexity.Figure 1

Type 2 diabetes individuals have a shorter QRS duration, prolonged QTc interval, flatter T wave, and reduced left ventricular cycle volumes compared to matched controls in the UK Biobank

Abstract Background Type 2 diabetes is associated with an increased risk of heart failure even in the absence of overt coronary artery disease, though underlying mechanisms are unclear. ECG and cardiac magnetic resonance (CMR) imaging provide windows into subclinical changes in myocardial structure and function and could be exploited to understand this. Purpose We investigate differences in ECG and CMR biomarkers in a large cohort of participants with type 2 diabetes, compared to a matched control cohort. We hypothesise that individuals with diabetes may exhibit concurrent differences in biomarkers, reflecting underlying cardiac remodelling. Methods We carried out a pair-matched cross-sectional study to examine the association between type 2 diabetes and multi-modal cardiac biomarkers. The exposure cohort consists of 1,781 UK Biobank participants with an imaging and ECG visit, prevalent type 2 diabetes and no known cardiovascular events at the time of visit. The control cohort is matched on age, sex and body mass index (BMI), and consists of 1,781 participants without diabetes. ECG and CMR biomarkers derived from UK Biobank data were used as outcome variables. We built four multiple multivariate linear regression models, incrementally adjusted for socio-demographic, lifestyle, and clinical covariates. Results Both cohorts were mostly male (63.6%), had a median age of 67 years [IQR: 72-85] and a median BMI of 27.8 kg/m2 [24.6-31.0]. Individuals with type 2 diabetes were more likely to be non-white (7.9% vs 2.7%, p&amp;lt;0.001), current or previous smokers (43.6% vs 40.6%, p=0.04), have lower diastolic blood pressure (79 [72-85] vs 81 [74-88] mmHg, p&amp;lt;0.001), and take cholesterol medication (72.3% vs 27.2%, p&amp;lt;0.001); anti-hypertensives (56.3% vs 27.3%, p&amp;lt;0.001); insulin (13.7% vs 0.1%, p&amp;lt;0.001); and metformin (53.1% vs 0.1%, p&amp;lt;0.001). They had a higher ventricular rate, shorter QRS duration, longer QTc interval, and flatter T wave amplitude, as well as lower left ventricular end-diastolic and end-systolic volumes, among other differences (Table 1). Covariates including cholesterol medication, metformin, and HbA1c were excluded as they were strongly correlated with diabetes, age and/or sex (Pearson correlation coefficient &amp;gt;0.3 or &amp;lt;-0.3). After full adjustment, we found that the exposure variable, diabetes, had a statistically significant association with ventricular rate, QRS duration, T wave offset, T wave amplitude in lead V3, left ventricular stroke volume and global average thickness (p&amp;lt;0.05) (Table 2). Conclusion Our results reveal that individuals with type 2 diabetes exhibit a shorter QRS, longer QTc, and lower end-diastolic and end-systolic volumes, compared to matched controls. This may be indicative of subclinical cardiac abnormalities, both electrophysiological and mechanical. Our association analysis suggests that other factors correlated with diabetes may be also responsible for certain biomarker differences and their underlying causes.

Understanding the impact of heart failure treatment on cancer growth

Abstract Background Heart failure (HF) is associated with systemic alterations that extend beyond the cardiovascular system. The dysregulation of physiological pathways induced by HF, encompassing inflammatory or neurohormonal pathways, may foster an environment conducive to cancer growth and the spead of metastases. It is unknown whether these alterations are attenuated when HF is treated, and whether certain therapies for HF may yield more significant effects than others. Purpose This study aims to investigate whether myocardial infarction (MI)-induced left ventricular (LV) dysfunction promotes breast cancer growth and triggers the development of lung metastases. Additionally, it compares the potential impact of different therapeutic strategies for LV dysfunction on cancer development. Methods Myocardial infarction (MI) was induced in 11-week-old female BALB/c mice by ligation of the left anterior descending (LAD) coronary artery, leading to LV dysfunction and significant dilation within four weeks. Starting 2 weeks after surgery, mice with ejection fraction (EF) &amp;lt; 40% received daily oral gavage of vehicle or one of three drugs: carvedilol (10 mg/kg), enalapril (20 mg/kg), or empagliflozin (15 mg/kg). Four weeks post-surgery, 2x105 4T1 metastatic breast cancer cells were injected into the 4th mammary fat pad. Tumor volume was measured every two days, starting eight days after injection. Weekly echocardiographic assessments monitored cardiac function until the end of the experiment. Tumors were excised on day 22 after injection. Mice were euthanised on day 28 for post-mortem analysis. MCM2 proliferation staining was performed on lung tissue to quantify metastases. Results Among the HF treatments, only empagliflozin (n=11) induced a significant decrease in both left ventricular end-diastolic and end-systolic volume (Fig. 1.A; p=0.0043; Fig. 1.B; p=0.0186) compared to the vehicle group (n=11). Tumor weight and volume (Fig. 1.C-D) were not different in the HF/vehicle group (n=15) and the sham-operated group (n=13). Carvedilol (n=14) led to a small reduction in tumor weight (Fig. 1.C; p=0.1264), while empagliflozin (n=11) exhibited a significant reduction in both tumor weight (Fig. 1.C; p=0.0306) and volume (Fig. 1.D; p=0.0268). In addition, carvedilol (n=13) significantly reduced lung metastases (Fig. 1.E; p=0.0347) compared to the HF/vehicle group (n=13). Enalapril (n=10) and empagliflozin (n=9) did not significantly impact the development of lung metastases. Conclusion Despite the absence of increased cancer growth post-MI, our findings indicate that specific treatments for HF—namely, carvedilol and empagliflozin—attenuate cancer growth post-MI. Furthermore, carvedilol demonstrated potential in reducing metastatic spread. Additional research is required to uncover the underlying mechanisms both in the presence and absence of HF, and to explore the molecular impact that HF treatments have on various stages of cancer progression.Figure 1

Left atrial remodeling and novel biomarkers in obese patients with heart failure with preserved ejection fraction compared to type-2-diabetics and obese controls: a cardiac magnetic resonance study

Abstract Background Elevated filling pressures and subsequent left atrial (LA) dilation are common findings in heart failure with preserved ejection fraction (HFpEF), reflecting a chronic state of the disease and holding prognostic value. HFpEF is thought to develop through a long-term pro-inflammatory state triggered by comorbidities, such as obesity and type 2 diabetes mellitus (T2DM). Emerging biomarkers have shown associations with structural remodeling, but also increased myocardial stiffness. Purpose To elucidate the relationship between LA volume and function, and prognostic biomarkers (NT-proBNP, BNP-32, IL1R1, Galectin-3, and Pentraxin-3) in an obese cohort with T2DM or HFpEF and T2DM, versus healthy obese controls. Methods We conducted a prospective cohort study of 35 obese participants, divided into three groups: T2DM (n=16), HFpEF with T2DM (NYHA II-III, n=13), and healthy obese controls (n=6). Each subject underwent comprehensive CMR at a 3T scanner to assess LA strain and volume. Atrial strain was assessed on 2- and 4-chamber view cine images by experienced CMR investigators using dedicated software. Routine labs and serum levels of biomarkers were measured. If labs or images were repeated, the average was calculated. Statistical significance was determined through ANOVA and student’s t-test for group comparisons and Pearson correlation for associations between LA parameters and biomarker levels. Results Cohorts were evenly matched in terms of demographics, vital signs, and ventricular volumes and functions, as depicted in Table 1. Only one patient in the HFpEF subgroup reported history of atrial fibrillation. Both minimum and maximum LA volumes were significantly elevated in the HFpEF group compared to the T2DM and control groups (p &amp;lt; 0.018). LA strain (conduit, reservoir, and booster) was notably compromised in the HFpEF cohort, contrasting with the obese T2DM group where LA strain values did not differ significantly from those observed in obese controls (Figure 1). Biomarker analysis revealed a marked increase of NT-proBNP, BNP-32, Galectin-3, and Pentraxin-3 in the HFpEF cohort. In the HFpEF cohort, IL1R1 was the only biomarker that was strongly associated with higher left ventricular enddiastolic (r=0.69, p=0.003) and endsystolic volumes (r=0.75, p=0.009). Moreover, IL1R1 was the only biomarker associated with atrial functional changes (booster strain, r=-0.57, p=0.043) in the HFpEF patients. Our findings indicate that ILR1 plays a crucial role in the cardiometabolic (obesity-T2DM) HFpEF phenotype, with its activation leading to advanced cardiac remodeling. Conclusion Obese HFpEF patients with T2DM showed severely altered left atrial morphology and function compared to those that are only obese or obese with T2DM. Moreover, our findings revealed that atrial remodeling in this population is driven by pro-fibrotic inflammatory pathways.Characteristics of the study cohortLeft atrial strain analysis

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.

The impact of multimorbidity on cardiac remodelling in the UK Biobank

Abstract Background/Introduction Previous work has suggested that multimorbidity is associated with higher all-cause mortality and cardiovascular mortality in the UK Biobank (UKB). The impact of multimorbidity on cardiac remodelling as measured by cardiovascular magnetic resonance (CMR) has not been studied in large cohorts. Purpose To determine if CMR biomarkers act as surrogates for adverse cardiovascular outcomes in multimorbidity. Method We analysed 44957 UKB participants who had CMR. Self-reported cancer (UKB field ID 20001) and non-cancer illnesses (UKB field ID 20002) were used to calculate comorbidity count with multi-morbidity defined as 2 or more illnesses. The predictive value of comorbidity count (exposure counts measured in quintiles) on CMR traits (outcomes) was evaluated using a univariable and multivariable generalised linear model. Covariates included sex, age, BMI, smoking status, regular alcohol intake, and the Townsend deprivation index, a measure of socioeconomic deprivation. The first model utilised univariable regression without covariates with subsequent iterations including age and sex and then all covariates. An interaction term was included for age and sex and a quadratic term for age in the models. CMR outcome measures were indexed left ventricular mass (LVM), indexed left ventricular end diastolic volume (LVEDV), indexed left ventricular end systolic volume (LVESV), indexed left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and indexed maximal left atrial volume (LA). The absolute value of GLS was used in the regression models. Variance inflation factor testing was used to check for collinearity. Analyses were completed using R v4.1.1. Results Median comorbidity count was 2. The burden of long-term conditions in this population of European ancestry with largely healthy individuals is lower than in other large population cohorts. Table 1 summarises multivariable analyses for comorbidity count, LVM and GLS. Due to high collinearity relating to age in the model, we centred age around the mean. LVM was higher with multimorbidity (top quintile Beta 0.63 (95% CI 0.23 to 1.04), P = 2.21x10-03). GLS was lower with multimorbidity (top quintile Beta -0.29 (95%CI -0.42 to 0.16), P = 8.10x10-6). LA volume was lower with multimorbidity (top quintile Beta -0.63(95% CI -1.22 to 0.04), P = 3.53 x 10-2). LVEF and other volume measures were not associated with multimorbidity. Conclusion Multimorbidity in this large cohort was associated with adverse cardiac structural and functional remodelling on CMR. These include a lower global longitudinal strain and higher LV mass.

Prognostic impact of lean diabetes mellitus on aortic stenosis

Abstract Background Obesity and type 2 diabetes mellitus (DM) has traditionally been thought to coexist. Lean DM is a distinct condition defined by body mass index (BMI) &amp;lt; 25, associated with elevated insulin resistance, rapid beta-cell failure, absence of ketosis and malnutrition. Lean DM has been linked to poor cardiovascular outcomes, but remains an understudied entity in valvular heart disease. Purpose This study aims to demonstrate the prognostic implications of lean DM on aortic stenosis (AS). Methods Between 2011 to 2021, 700 consecutive patients with index echocardiographic diagnoses of aortic stenosis were stratified into 4 groups, namely lean (BMI &amp;lt; 25) DM, lean non-DM, obese (BMI &amp;gt; 25) DM, and obese non-DM. Demographics, co-morbidities, echocardiographic findings and clinical outcomes were collected. Clinical outcomes were compared using Kaplan-Meier curves and a multivariate Cox regression model was constructed. Results 396 (56.6%) patients were female, and 435 (62.1%) patients were of Chinese ethnicity. 279 (39.9%) patients had DM, of whom 155 (55.6%) patients had lean DM. The mean BMI in the lean group was 21.4 ± 2.4 kg/m² compared to 29.5 ± 4.9 kg/m² in the obese group. Irregardless of BMI, higher proportions of DM patients were on baseline antiplatelets and statins compared to non-DM patients. Echocardiographically, obese DM had smaller indexed left ventricular volumes and mass - left ventricular end diastolic volume index (LVEDVi) (65.7 ± 21.7 ml/m² vs. 70.8 ± 23.6 ml/m², p = 0.002) and left ventricular mass index (LVMi) (115.7 ± 31.9 g/m² vs. 116.3 ± 36.5 g/m², p = 0.401) compared to lean DM respectively. Obese DM was associated with more cardiovascular risk factors compared to lean DM in terms of hypertension (91.9%, n = 114 vs. 89.0%, n = 138, p &amp;lt; 0.001), hyperlipidaemia (82.3%, n = 102 vs. 73.5%, n = 114, p &amp;lt; 0.001) and chronic kidney disease (50.8%, n = 62 vs. 45.5%, n = 70, p &amp;lt; 0.001). On the contrary, lean DM was associated with more cardiovascular sequelae of acute myocardial infarction (36.8%, n = 57 vs. 24.2%, n = 30, p &amp;lt; 0.001) compared to obese DM. AS patients with lean DM experienced the highest significant all-cause mortality (71%, n = 110 in lean DM vs. 58.9%, n = 73 in obese DM vs. 49.1%, n = 86 in obese non-DM vs. 65%, n = 160 in lean non-DM, p &amp;lt; 0.001) compared to all other groups. On the contrary, AS patients with lean DM had the lowest heart failure incidence (17.4%, n = 27 in lean DM vs. 23.4%, n = 29 in obese DM vs. 33.1%, n = 58 in obese non-DM vs. 23.2%, n = 57 in lean non-DM, p = 0.009). On multivariate analyses adjusted for age, comorbidities, and echocardiographic parameters, lean DM was an independent predictor of worse all-cause mortality in AS patients (HR 1.60, CI: 1.19 - 2.16, p = 0.010). Conclusion Lean DM in AS patients was associated with worse all-cause mortality. Lean DM was a prognostic marker of all-cause mortality in patients with AS.Figure 1

Mapping renal impairment and cardiac structure and function: observation and genetic insights from 30,000 cardiac magnetic resonance images

Abstract Background The elevated risk of heart failure in kidney dysfunction is well-identified. However, the early alteration of renal impairment on cardiac structure and function, as well as genetic susceptibility associations have not been well reported. We sought to map the early effects of kidney dysfunction on cardiac remodeling with the cardiac magnetic resonance images (MRI) and identify share genetic correlation in community population. Methods Of 29,592 subjects underwent MRI test were recruited from the population-based UK Biobank study from 2006-2010. Renal function was assessed by historical identified chronic kidney disease (CKD), log-transfrom estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRCysC) or serum creatine (eGFRSCr) and urine albumin-to-creatinine ratio (uACR). Multivariable generalized linear regression was used to analyse the association of 4 different kidney function indexes with six cardiac MRI-derived traits: left atria and ventricle, right atria and ventricle, and ascending and descending aortas. Genetic correlation between renal function decline and cardiac traits were evaluated by Mendelian randomization (MR). Results The mean (SD) age of subjects was 54.9 (7.5) years, and 51.1% were women. Observational and MR analysis showed a reliable relationship of lower level of eGFRCysC with reduced biventricular end systolic volume, biventricular ventricular end diastolic volume and left ventricular mass, and lower level of eGFRSCr with reduced left ventricular cardiac output. Conclusions Our study indicates the observational and genetic correlation between kidney function decline and cardiac measurements. These findings provide insights into the potential mechanisms behind their comorbidity and the future development of therapeutics.Renal function decline &amp; Cardiac Imaging

Association of type-D personality and left-ventricular remodelling in patients treated with primary percutaneous intervention after ST-segment elevation myocardial infarction

BackgroundType-D personality is an established predisposing factor for various diseases. Type-D traits have been shown to pose a 26% increased risk of coronary artery disease after controlling for other confounding factors. Significant associations have been reported between type-D personality traits and dyslipidaemia, impaired endothelial function, coronary heart disease (CAD), acute myocardial infarction, and other adverse cardiovascular events.ObjectiveTo assess the association between type-D personality and left-ventricular adverse remodelling in patients treated with percutaneous coronary intervention following index ST-segment elevation myocardial infarction.MethodsAll patients hospitalized and treated with percutaneous coronary intervention (PCI) after their index ST-segment elevation myocardial infarction (STEMI) between 1 January 2022 to 31 December 2023 were prospectively enrolled. Type-D personality traits in the study population were determined at baseline using type-D Scale-14 (DS14) instrument, whereas any positive change in left ventricular end diastolic volume (LVEDV) ≥ 20% at follow up period of 12-months from baseline was defined as left-ventricular adverse remodelling (LVAR). Univariate and multivariate analysis was done to establish the independent predictors of LVAR. The area under receiver-operating characteristic curve (AUROC) was employed to assess the sensitivity and specificity of the identified independent predictors.ResultsA total of 124 patients were enrolled in the study. The mean age of the study population was 67 ± 10 years and the overall incidence of LVAR was found to be 25%. Multivariate regression analysis revealed that type-D personality is a significant independent predictor of LVAR \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:(OR:2.51;95\\%CI:1.16-5.77;p=0.03)$$\\end{document} apart from the already established independent predictors Killip Class\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:(OR:7.30;95\\%CI:3.03-17.55;p<0.0001)$$\\end{document}, baseline Global Longitudinal strain (GLS)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:(OR:2.69;95\\%CI:1.19-6.61;p=0.01)$$\\end{document}, and 3-vessel CAD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:(OR:2.27;95CI:1.10-5.33;p=0.04)$$\\end{document}. In ROC curve analysis type-D personality as an independent predictor of LVAR achieved a sensitivity of 41.4% and a specificity of 87.1%, p < 0.02.ConclusionType-D personality trait is a significant independent predictor of LVAR in patients treated with PCI after their index-STEMI.

A newly developed small-molecule ErbB4 agonist reduces reactive cardiac fibrosis and adverse ventricular remodelling after myocardial infarction in a sex-specific manner

Abstract Background The beneficial effects of the neuregulin/ErbB pathway on the diseased heart have been well-established. The anti-fibrotic and cardioprotective aspects of neuregulin are largely attributable to the activation of the ErbB4 receptor. We recently developed a small-molecule selective ErbB4 agonist, which reduced collagen production in cultured fibroblasts and prevented oxidative-stress induced cardiomyocyte death in vitro. Purpose In order to evaluate the in vivo effects of this small-molecule ErbB4 agonist (referred to as compound, Cpd), we assessed its effect on left ventricular remodelling, cardiac fibrosis and cardiac function in a murine model of myocardial infarction (MI). Since there is a potential interaction between ErbB4 and the oestrogen receptor, we also aimed to evaluate whether these effects were sex-dependent. We hypothesised that Cpd would attenuate left ventricular remodelling, reduce cardiac fibrosis and help retain cardiac function in a sex-specific manner. Methods Mice were divided by sex and then further divided into three experimental groups: a sham group, an MI group receiving Cpd (MI/Cpd), and a control MI group receiving vehicle only (MI/Veh). MI was induced by ligating the left descending coronary artery. Seven days after MI, mice started treatment with either Cpd (2mg/kg/d) or its vehicle through subcutaneous osmotic minipumps. Cardiac ultrasound was performed weekly until mice were sacrificed after four weeks of treatment. Hearts were excised and stained with Masson’s trichrome to assess reactive cardiac fibrosis in the myocardium of the left ventricle, located remote from the infarction scar. A WGA-isolectinB4-DAPI immunofluorescent stain was performed to assess cardiomyocyte cross-sectional area in order to evaluate cardiomyocyte hypertrophy. Results In females (n=25), Cpd significantly decreased left ventricular end-diastolic volume compared to vehicle (LVEDV, Fig.1A, 80±23 µl vs.108±29 µl, p=0.045) and induced a slightly increased left ventricular ejection fraction (LVEF, Fig.1B, 32±12% vs. 22±9%, p=0.086). In addition, Cpd significantly reduced reactive interstitial fibrosis myocardium (Fig.1C, fibrotic area, 1.4±1.0% vs. vehicle: 3.8±3.1%, p=0.0363). In males (n=30), Cpd had no significant effects on either of the parameters mentioned above, (Fig.1E-G). There was no significant treatment effect in either group on cardiomyocyte cross sectional area (Fig.1D, Fig.1H). Conclusion Treatment with the novel small-molecule ErbB4 agonist attenuates left ventricular dilation and reactive interstitial fibrosis after MI in female mice, but not in males. These data support the premise that small molecule-induced ErbB4 activation is a potential new therapy for heart failure, especially in female patients. The mechanisms underlying the sex-dependent effects warrant further exploration.Figure 1

Larger QRS but better hemodynamic function after high output His bundle pacing in patients with heart failure and narrow QRS. A paradox or a new concept?

Abstract Background QRS duration is an important factor in determining Cardiac Resynchronisation Therapy (CRT) response and a useful surrogate for electromechanical dyssynchrony. However, we don’t have studies confirming this concept in conduction system pacing. Purpose We performed His Bundle Pacing (HBP) with high output (3.5V/1msec) in HF patients with dilated or ischemic cardiomyopathy and narrow QRS to evaluate hemodynamic benefit independent of the QRS duration or AV delay shortening. Methods 14 patients with dilated (7 patients) or ischemic (7 patients) cardiomyopathy (EF&amp;lt;35%) and narrow QRS (&amp;lt;120ms) were referred for implantation of a defibrillator. We implanted an ICD- HBP system, and we collected clinical, echocardiographic, and electrocardiographic data. Results We obtained HBP in all 14 patients successfully. PQ after implantation was shorter from 172±48 to 143±16 (P=0.048) so as to pace the ventricle. Baseline QRS duration increased after pacing from 110±15 to 123±16ms (P=0.008) as measured by ECG analyzer. Despite this increase in QRS duration basal mean EF increased from 30±4% to 46±10% (P&amp;lt;0.001) after a median follow-up of 17 months. Left ventricular end-diastolic diameter and left ventricular end-diastolic volume decreased from 62±5 to 57±5mm (P=0.013) and from 195±69 to 126±27ml (P&amp;lt;0.001), respectively. Left ventricular end-systolic volume decreased from 139±58 to 69±27 (P&amp;lt;0.001). TAPSE increased from 19±4 to 27±4. NYHA class decreased by one class in every patient after only one month. HBP threshold was 1.05V±0.7/1msec and raised to 1.33±0.93/1msec (due mainly to 2 patients with very high threshold). The impedance was 588±109 and decreased to 484±69 Ohms. R-wave at implant was 3.2±1.8mV. In 2 out of 14 patients, threshold increased but was still less than 3.5V/1msec. Conclusions HBP in HF patients with dilated or ischemic cardiomyopathy and narrow QRS improves hemodynamic function in right and left ventricle and decreases NYHA class. This benefit appears to be produced by a higher stimulation output despite a larger QRS after pacing. We exclude that a very short AV delay could be favorable, by measuring acute EF changes only after increasing the pacing output without AV delay modifications. To our knowledge these are the first cases of beneficial HBP in HF patients with narrow QRS. Interestingly, larger QRS corresponds to higher EF in patients with high output HIs Bundle Pacing.

Prolonged ventricular activation time as a novel biomarker identifying burn-out phase of hypertrophic cardiomyopathy

Abstract Background Patients with hypertrophic cardiomyopathy (HCM) classically have preserved systolic function and decreased left ventricular end-diastolic volume. However, in a small sub-population, patients paradoxically develop systolic dysfunction, left ventricular dilatation, and ventricular wall thinning, which is known as end-stage hypertrophic cardiomyopathy or "burned-out cardiomyopathy’. Although an electrocardiogram (ECG) is a pivotal tool in HCM, its role in the detection of burned-out HCM has not been investigated. Purpose We assessed the ventricular activation time (VAT), an ECG marker of the duration of ventricular depolarization, as a predictive tool in the detection of the HCM burn-out phase. Methods We prospectively studied consecutive patients diagnosed with HCM via echocardiography at our medical center between 2017 and 2022. The ECG, along with echocardiography, was performed on the same day as the diagnosis. VAT was measured in milliseconds between the onset of the QRS complex to the peak or R wave on the V5 and V6 precordial ECG lead. HCM burn-out phase was supported when the left ventricular ejection fraction (LVEF) was below 50%, measured with echocardiography. Statistical analysis was performed using the SPSS software. Results Forty-five patients with HCM were studied, and their mean age was 51, while 78% (35/45) were male. Echocardiography data upon diagnosis revealed a mean maximum wall thickness of 19 (±3mm) and a mean left ventricular ejection fraction of 65% (±5%). Left ventricular outflow obstruction was present in 31% (14/45). During the study, 24% (11/45) presented atrial fibrillation, 44% (20/45) had an ICD implantation, and 22% (10/45) progressed to the burn-out phase of HCM. HCM patients who presented atrial fibrillation (63±31 vs. 46±14msec, p=0.018) or burn-out phase (65±32 vs. 46±13msec, p=0,009) had a significantly higher VAT than those subsets without. Notably, there was a significant positive relationship between VAT a burn-out phenotype (r=0,385, p=0.009). HCM patients with greater VAT also had a significantly higher risk of presenting a larger left atrial diameter (r=0,295, p=0.048), an increased left ventricular end-diastolic diameter (r=0.306, p=0.041), and a trend of presenting a lower LVEF (r=-0,262, p=0.082). Finally, we revealed a positive relationship between VAT and atrial fibrillation incidence (r=0,352, p=0.018). Conclusion Prolongation of VAT predicts the incidence of burn-out stage in patients with HCM and atrial fibrillation. Therefore, it seems to be a promising, inexpensive ECG marker for HCM progression and severity. Our findings emphasize the pivotal role of the ECG as a useful and inexpensive tool in the diagnostic follow-up of HCM.

Right-sided exercise-induced cardiac remodelling is more pronounced in white than in black elite football players

Abstract Background Most echocardiography studies investigating exercise-induced cardiac remodelling (EICR) in athletes have predominantly focused on left ventricular end-diastolic volume (LVEDV) and wall thickness. Moreover, studies investigating right-sided EICR in individuals with different ethnic backgrounds are scarce, but are needed to assist clinicians in the differentiation between EICR and pathology. Purpose To investigate differences in right-sided EICR between Caucasian (white) and Sub-Saharan (black) male elite football players. Methods We included all male elite football players with echocardiography data from the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise (ELITE) cohort. ELITE collects data from standardised cardiovascular screenings of elite level athletes in the Netherlands, including (but not limited to) standardised resting transthoracic echocardiograms (TTE). Athletes with known cardiovascular disease were excluded. Our primary metrics of interest were right ventricular end-diastolic diameter (RVEDD), maximal dimension of the inferior vena cava (IVC) and right atrial (RA) reservoir, conduit and contractile strain (measured using 2D-Speckle tracking). Secondary metrics of interest included LV ejection fraction (LVEF), LV mass index (LVMi) and left atrial reservoir strain. All metrics of interest were stratified by ethnicity, and indexed for body surface area (BSA) if appropriate. Results A total of 74 elite football players were included (black n = 37; white n = 37), with similar age (18 [2.0] vs 19 [3.0], p = 0.013) and BSA (2 [0.1] vs 2 [0.2] m2, p = 0.268) across ethnicities. There were no differences in indexed LA (35 [10.0] vs 33 [10.0] ml/m2, p = 0.417) and RA volumes (27 [7.4] vs 27 [6.6] ml/m2,p = 0.953). However, black athletes demonstrated smaller max IVC (18 [5.0] vs 25 [5.0] cm, p = &amp;lt;0.001) and RVEDD (40 [2.0] vs 43 [6.0] mm,p = 0.001). Moreover, black athletes demonstrated less RA deformation in the reservoir (31 [8.0] vs 36 [8.0] %, p = 0.003) and contractile phases (9 [4.0] vs 11 [4.0] %, p = 0.017) than white athletes. There were no ethnic-specific differences in RA conduit strain (23 [7.0] vs 25 [6.0] %, p = 0.076). We found no statistically significant differences in LVEF (55 [6.0] vs 55 [6.0] %, p = 0.914), LVMi (92 [15.0] vs 88 [26.8] g/m2, p = 0.236) or LA reservoir strain (32 [7.0] vs 33 [7.0] %, p = 0.157) in black vs white athletes. Conclusion Male elite football players with a Sub-Saharan ethnic background demonstrate less pronounced right-sided EICR than athletes with a Caucasian ethnic background. Our findings emphasize the need for ethnic-specific reference ranges for right-sided EICR to aid in the differentiation between EICR and pathology.

AI-based cluster analysis enables outcomes prediction among patients with increased LVM

Abstract Background The traditional classification of left ventricular hypertrophy (LVH) solely based on left ventricular geometry disregards associated comorbidities and clinical characteristics. We aimed to identify unique clinical phenotypes of LVH using unsupervised cluster analysis and explore their association with clinical outcomes. Methods From UK Biobank (UKBB) participants with available left ventricular mass (LVM) estimations, we identified those meeting CMR-based criteria for increased LVM: LVM index ≥ 72 g/m2 for males and LVM index ≥ 55 g/m2 for females. Baseline demographic, clinical, and laboratory data were collected. Using Ward's method, patients were clustered based on 27 variables. The primary outcome was a composite of all-cause mortality with heart failure (HF) admissions, ventricular arrhythmia, and atrial fibrillation (AF). Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results Among CMR-assessed UKBB participants, 4,255 individuals exhibited increased LVM, with an average age of 64 ± 7 years; 2,447 (58%) were females. Cluster analysis identified four distinct subgroups. Over a median 5-year follow-up (IQR: 4-6), 100 patients (2%) died, 118 (2.8%) were hospitalized due to HF, 29 (0.7%) were hospitalized due to VA, and 208 (5%) were hospitalized due to AF. Univariate Cox analysis revealed that compared to the 1st cluster (n=1,578), patients in the 2nd (n=1,296), 3rd (n=824) and 4th (n=557) clusters had 60%, 104%, and 164% increased risk of a major event, respectively (95% CI 1.2-2.16, p&amp;lt;.001 for cluster 2; 95% CI 1.49-2.78, p&amp;lt;.001 for cluster 3; 95% CI 1.92-3.62, p&amp;lt;.001 for cluster 4). Each cluster manifested different phenotypes: cluster 2 comprised mainly overweight females, with the highest prevalence of chronic lung disease; cluster 3, predominantly composed of males, had the highest burden of comorbidities and cardiovascular risk factors; and cluster 4, mostly males, presented with the most abnormal cardiac measures, including left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF). Conclusions Unsupervised cluster analysis identified four subgroups among patients with increased LVM. These subgroups bear notable relevance to overall mortality risk and clinical outcomes. This phenotypic classification holds promise in offering valuable insights regarding clinical course and outcomes in LVH patients.

Exploring the impact of coronary microvascular dysfunction on cardiac remodeling after st-elevation myocardial infarction

Abstract Background The complex interplay between Coronary Microvascular Dysfunction (CMD) and ST-segment Elevation Myocardial Infarction (STEMI) presents significant clinical hurdles. CMD, commonly seen as a complication following STEMI, is associated with adverse cardiovascular outcomes and persistent anginal symptoms. Despite its clinical relevance, the link between CMD post-STEMI and subsequent left ventricular (LV) diastolic dysfunction, along with functional LV remodelling (FLVR), is yet to be fully explored. Purpose Examine the link between CMD 3 months post-STEMI and its impact on FLVR and diastolic dysfunction. Methods This prospective, observational cohort study focused on STEMI patients. At 3-month post-STEMI, a comprehensive coronary physiology assessment of the culprit artery was conducted using the thermodilution method to measure fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR). CMD was identified with an IMR ≥ 25 or a CFR &amp;lt; 2.0, assuming an FFR &amp;gt; 0.80. Diastolic dysfunction was classified according to ASE/EACVI 2016 guidelines. FLVR was categorized as per Surenjav Chimed et al.'s criteria: Group I with no significant changes in LV size or function, Group II with a decrease in LV ejection fraction (LVEF) greater than 5% without LV dilatation, Group III with an increase in left ventricular end-diastolic volume (LVEDV) ≥ 20%, and Group IV showing both an increase in LVEDV ≥ 20% and a decrease in LVEF over 5%. The study aimed to elucidate the relationship between CMD and the progression of FLVR and diastolic dysfunction, tracked over a 12-month period. Results The study involved 210 patients, mostly men (59.5%), with a median age of 65 (IQR: 58–76). At the 3-month follow-up, CMD was observed in 57 (27.1%) patients. CMD patients had a higher female prevalence (63.2% vs. 32.0%; p &amp;lt; 0.001) and more diabetes (42.1% vs. 17.7%; p &amp;lt; 0.001) compared to non-CMD patients. Both groups shared similar body mass indices, medications, and other risk factors. Laboratory results were similar between groups, except brain natriuretic peptide levels were higher in CMD patients (70.0 vs. 37.0 ng/L; p &amp;lt; 0.001). After 12 months, CMD patients demonstrated significantly less recovery in LVEF (-10.00% vs. 8.00%; p &amp;lt; 0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% vs. 1.32%; p &amp;lt; 0.001), and a higher incidence of advanced FLVR (notably in Groups 3 and 4) compared to non-CMD (11.32% vs. 7.28% and 22.64% vs. 1.99%, respectively; p &amp;lt; 0.001). In the adjusted multivariable logistic regression analysis, IMR values independently predicted more severe FLVR and diastolic dysfunction. Conclusions This study highlights that CMD 3 months after STEMI is linked to worse FLVR, diastolic dysfunction, and less recovery in LVEF, emphasizing the need for early CMD detection for better risk assessment. Further research is essential to explore underlying mechanisms and intervention opportunities.LVEF Changes at 12 Months by CMD StatusDiastolic Dysfunction and LV Remodeling