Left Ventricular Diastolic Dysfunction Research Articles

Rationale and Design of Prospective, Multicenter, Double-Arm Clinical Trial to Investigate the Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus (TOP-HFPEF Trial).

Recent large clinical trials have revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes not only in patients with heart failure with reduced ejection fraction, but also in patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF). However, the effect of SGLT2 inhibitors on left ventricular (LV) diastolic function is still controversial. The TOP-HFPEF trial (Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus) is a multicenter, double-arm, open-label, confirmatory, investigator-initiated clinical study to investigate the effect of SGLT2 inhibitor on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. The participants are randomly assigned (1:1) to the tofogliflozin group (20mg once daily) or the control group (administration or continuation of antidiabetic drugs other than SGLT2 inhibitors). The estimated number of patients to be enrolled in this trial is 90 in total (45 in each group). The participants are followed up for 52weeks with tofogliflozin or control drugs. The primary endpoint is the change in E/e' assessed by echocardiography from the baseline to the end of this study (52weeks). This trial will also evaluate the effects of tofogliflozin on cardiovascular events, biomarkers, other echocardiographic parameters, the occurrence of atrial fibrillation, and renal function. The TOP-HFPEF trial will clarify the efficacy of an SGLT2 inhibitor, tofogliflozin, on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus.

Relative B-Type Natriuretic Peptide Deficiency May Exist in Diastolic Dysfunction in Subclinical Population.

Background: Heart failure patients are deficient in B-type natriuretic peptide (BNP) but the significance of subclinical BNP deficiency is unclear. Methods and Results: A total of 1,398 subjects without cardiovascular disease, with left ventricular ejection fraction (LVEF) ≥50% and BNP level <100 pg/mL, were selected from a 2005-2008 health checkup in Arita-cho, Japan, and divided into 2 groups: with and without LV diastolic dysfunction (DD+ or DD-). We performed propensity score matching on non-cardiac factors affecting BNP levels and analyzed 470 subjects in each group (372/940 men; median age, 66 years). The DD(+) group showed higher lateral E/e', an index of estimated left ventricular filling pressure, and greater prevalence of concentric hypertrophy (CH) despite similar BNP levels, suggesting a relative deficiency of BNP in DD(+) compared with DD(-). Multivariable logistic regression analysis revealed an increase in BNP correlated with decreased odds of CH (adjusted odds ratio [aOR] 0.663, 95% confidence interval (CI) 0.484-0.909, P=0.011), whereas an increase in lateral E/e' was associated with increased odds of CH (aOR, 2.881; 95% CI, 1.390-5.973; P=0.004). Furthermore, CH in combination with diastolic dysfunction independently predicted major adverse cardiovascular events (hazard ratio 3.272, 95% CI 1.215-8.809; P=0.019). Conclusions: Relative BNP deficiency was associated with CH, which had a poor prognosis in patients with diastolic dysfunction.

Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

N-terminal pro-brain natriuretic peptide is associated with pulmonary hypertension or diastolic dysfunction in patients with systemic sclerosis: An Australian prospective cross-sectional study

Introduction: Pulmonary arterial hypertension and left ventricular diastolic dysfunction are associated with significant morbidity and mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide has been proposed as part of composite screening algorithms for pulmonary arterial hypertension. Our aim was to assess the prevalence of pulmonary hypertension and diastolic dysfunction, and evaluate their association with serum N-terminal pro-brain natriuretic peptide in systemic sclerosis patients. Methods: Patients with systemic sclerosis were prospectively enrolled to undergo N-terminal pro-brain natriuretic peptide testing and transthoracic echocardiography at a tertiary Australian centre from January to October 2022. We collected demographic and transthoracic echocardiography variables including pulmonary hypertension estimated by tricuspid regurgitant velocity and diastolic dysfunction assessed by the ASE/EACVI 2016 guidelines. Pearson’s correlation coefficient was used to evaluate association between N-terminal pro-brain natriuretic peptide and echocardiographic parameters. Results: Sixty-one patients were enrolled (median age = 62 years (interquartile range = 55–69 years); 84% female). Two-thirds of patients had limited systemic sclerosis (40/61). Five patients (8%) had high likelihood of pulmonary hypertension by transthoracic echocardiography. Seven patients (11%) had diastolic dysfunction; however, seven patients (11%) had indeterminate diastology. Six patients underwent right heart catheterisation, with five patients diagnosed with pulmonary hypertension. N-terminal pro-brain natriuretic peptide in patients with pulmonary hypertension or diastolic dysfunction was significantly higher (median = 207 and 226 pg/mL, respectively) compared to patients without either condition (median = 69 pg/mL, p = 0.01). N-terminal pro-brain natriuretic peptide showed a statistically significant although limited correlation with estimated pulmonary pressures measured by tricuspid regurgitant velocity (r = 0.44, p = 0.002) and left ventricular filling pressures (r = 0.27, p = 0.04). Conclusion: Pulmonary hypertension and diastolic dysfunction are both observed in systemic sclerosis. N-terminal pro-brain natriuretic peptide is associated with both conditions; however, it cannot distinguish between the two disease processes. Right heart catheterisation may be required to make this distinction.

Albuminuria in patients with type 2 diabetes mellitus and newly diagnosed heart failure with preserved ejection fraction

Abstract Funding Acknowledgements None. Aim To evaluate the frequency of albuminuria in patients with type 2 diabetes and newly diagnosed heart failure with preserved ejection fraction Methods 100 patients with T2DM were included (female, 62%; mean age, 64±10 years). Patients were divided into 2 groups with albuminuria (&amp;gt;30 mg albumin/g creatinine) and without albuminuria (&amp;lt;30 mg albumin/g creatinine). HFA-PEFF score was considered as a diagnostic parameter of heart failure with preserved ejection fraction (HFpEF): low probability/excluded HFpEF (&amp;lt;2 points), high probability/confirmed HFpEF (≥5 points), intermediate probability HFpEF (2 -4 points). The detailed echocardiographic criteria for LV diastolic dysfunction (structural parameters), the natriuretic peptide NT-proBNP, urine albumin to creatinine ratio (UACR) were detected in all patients. Results Albuminuria was detected in 55% (n=55) patients with DM, no albuminuria 45% (n=45). Newly diagnosed HFpEF were identified in 46% (n=46) patients, intermediate probability HFpEF in 37% (n=37), low probability/excluded HFpEF in 11% (n=11). Albuminuria was detected in 71% (n=39) of patients with newly diagnosed HFpEF, 22% (n=12) with intermediate probability HF, in 7% (n=4) with excluded HFpEF. In patients with HFpEF albuminuria was associated with the following echo parameters with: E/e’&amp;gt;9(r=0,51; p &amp;lt; 0,001) and Left ventricular mass index (LVMI) ≥115 g/m² (male) or ≥95 g/m² (female) (r=0,68; p &amp;lt; 0,001). Conclusions In patients with type 2 diabetes and newly diagnosed HFpEF the frequency of albuminuria was significantly high and was associated with echo parameters E/e’ ratio and LVMI.

A case report of ATTR-amyloidosis following cardiac transplantation: thick ventricles that look alike

Abstract Background Transthyretin (ATTR-) amyloidosis is more prevalent than initially thought. As much as 13% of patients hospitalized with HFpEF may have ATTR-cardiomyopathy (CM). Conversely, heart transplant patients may manifest left ventricular hypertrophy or diastolic dysfunction, especially late after transplantation. Case Summary We present a case of a 82-year old male heart transplant patient, 31 years following orthotopic heart transplantation. While he was satisfied with his exercise capacity as an octogenarian, several years before he required pacemaker implantation due to 3rd degree AV block, had bilateral carpal tunnel syndrome treated with carpal tunnel release surgery and experienced idiopathic sudden deafness. Based on increasing left ventricular wall thickness during routine follow-up, a diagnosis of ATTR-amyloidosis was suspected. Ultimately, the diagnosis was confirmed non-invasively with a specific scintigraphic exam, while an additional physicochemical stain on an endomyocardial biopsy taken several years before provided pathological proof. We initiated tafamidis, yet stopped this treatment after one month because of gastro-intestinal intolerance. Ultimately, our patient died two years later due to heart failure. Discussion Our case shows the long delay between the onset of transthyretin deposition, the presence of clinical signs and the final diagnosis. Echocardiographic findings suggestive for ATTR-CM include left ventricular hypertrophy and diastolic dysfunction, which are both common in heart transplant patients. Yet, ATTR-CM should be considered in the differential diagnosis, especially late after transplantation, in this closely monitored population.

Mild renal dysfunction causes aggravated cardiac damage in type 2 diabetic patients: a comprehensive echocardiography study.

We sought to detect left ventricular (LV) adverse alterations in structure and function in type 2 diabetes mellitus (T2DM) patients with or without mild renal dysfunction (MRD) using comprehensive echocardiography techniques and to explore the independent risk factors for LV remodeling (LVR) and dysfunction in these patients. The study included 82 T2DM patients with normal LV ejection fraction (presence (n = 42)/absence (n = 40) of MRD). Age- and gender-matched controls (n = 40) were also recruited. LV structure and function were evaluated using conventional echocardiography and three-dimensional speckle tracking echocardiography (3DSTE). Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were all measured using 3DSTE. Compared with the controls with absolute advantage of LV normal geometry, LVR was more frequently present in the two T2DM groups, with the largest proportion in those with T2DM and MRD (P < 0.001). Fasting plasma glucose (FPG) and MRD were both significant risk factors for LVR in T2DM patients. The detection rates of LV diastolic dysfunction and subclinical systolic dysfunction were significantly higher in the T2DM groups than in the controls (P = 0.000). Moreover, the two case groups also showed significantly lower strain values in multiple directions than the controls (all P < 0.05). FPG was significantly associated with LV diastolic dysfunction, whereas FPG and MRD were both significantly associated with subclinical LV systolic dysfunction in T2DM patients. The combined use of conventional echocardiography and 3DSTE allowed the timely detection of early cardiac damage in T2DM patients with or without MRD.

Conduit Flow Compensates for Impaired Left Atrial Passive and Booster Functions in Advanced Diastolic Dysfunction.

Quantification of left atrial (LA) conduit function and its contribution to left ventricular (LV) filling is challenging because it requires simultaneous measurements of both LA and LV volumes. The functional relationship between LA conduit function and the severity of diastolic dysfunction remains controversial. We studied the role of LA conduit function in maintaining LV filling in advanced diastolic dysfunction. We performed volumetric and flow analyses of LA function across the spectrum of LV diastolic dysfunction, derived from a set of consecutive patients undergoing multiphasic cardiac computed tomography scanning (n=489). From LA and LV time-volume curves, we calculated 3 volumetric components: (1) early passive emptying volume; (2) late active (booster) volume; and (3) conduit volume. Results were prospectively validated on a group of patients with severe aortic stenosis (n=110). The early passive filling progressively decreased with worsening diastolic function (P<0.001). The atrial booster contribution to stroke volume modestly increases with impaired relaxation (P=0.021) and declines with more advanced diastolic function (P<0.001), thus failing to compensate for the reduction in early filling. The conduit volume increased progressively (P<0.001), accounting for 75% of stroke volume (interquartile range, 63-81%) with a restrictive filling pattern, compensating for the reduction in both early and booster functions. Similar results were obtained in patients with severe aortic stenosis. The pulmonary artery systolic pressure increased in a near-linear fashion when the conduit contribution to stroke volume increased above 60%. Maximal conduit flow rate strongly correlated with mitral E-wave velocity (r=0.71; P<0.0001), indicating that the increase in mitral E wave in diastolic dysfunction represents the increased conduit flow. An increase in conduit volume contribution to stroke volume represents a compensatory mechanism to maintain LV filling in advanced diastolic dysfunction. The increase in conduit volume despite increasing LV diastolic pressures is accomplished by an increase in pulmonary venous pressure.

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

A meta-analysis of left ventricular dysfunction in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine, presenting a considerable morbidity risk. Although evidence consistently indicates an elevated risk of ischemic heart disease among AS patients, debates persist regarding the likelihood of these patients developing left ventricular dysfunction (LVD). Our investigation aimed to determine whether individuals with AS face a greater risk of LVD compared to the general population. To accomplish this, we identified studies exploring LVD in AS patients across five major databases and Google Scholar. Initially, 431 studies were identified, of which 30 met the inclusion criteria, collectively involving 2933 participants. Results show that AS patients had: (1) poorer Ejection Fraction (EF) [mean difference (MD): -0.92% (95% CI: -1.25 to -0.59)], (2) impaired Early (E) and Late (atrial-A) ventricular filling velocity (E/A) ratio [MD: -0.10m/s (95% CI: -0.13 to -0.08)], (3) prolonged deceleration time (DT) [MD: 12.30ms (95% CI: 9.23-15.36)] and, (4) a longer mean isovolumetric relaxation time (IVRT) [MD: 8.14ms (95% CI: 6.58-9.70)] compared to controls. Though AS patients show increased risks of both systolic and diastolic LVD, we found no significant differences were observed in systolic blood pressure [MD: 0.32mmHg (95% Confidence Interval (CI): -2.09 to 2.73)] or diastolic blood pressure [MD: 0.30mmHg (95% CI: -0.40 to 1.01)] compared to the general population. This study reinforces AS patients' susceptibility to LVD without a notable difference in HTN risk.

Transcatheter transfemoral aortic valve replacement in a patient with acromegaly and severe left ventricular myocardial hypertrophy. Case report

Main causes of secondary hypertrophic cardiomyopathy include acromegalic cardiomyopathy. Heart damage in patients with the acromegaly is mediated both by the direct action of growth hormone and insulin-like growth factor-1, and increased deposition of collagen and lymphomononuclear cells in the myocardium, which leads to architectural changes, disturbances in fluid and electrolyte balance, severe left ventricular myocardial hypertrophy, diastolic and systolic left ventricular dysfunction and chronic heart failure. This article presents the world's first described observation demonstrating the possibility of successful transfemoral aortic valve repair to a comorbid patient with severe aortic stenosis according to the potential risks caused by the active form of the acromegaly.

Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data

BackgroundMachine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios.MethodsWe compared the use of six ML classifiers in predicting CVD risk factors using blood-derived metabolomics, epigenetics and transcriptomics data. Upstream omic dimension reduction was performed using either unsupervised or semi-supervised autoencoders, whose downstream ML classifier performance we compared. CVD risk factors included systolic and diastolic blood pressure measurements and ultrasound-based biomarkers of left ventricular diastolic dysfunction (LVDD; E/e' ratio, E/A ratio, LAVI) collected from 1,249 Finnish participants, of which 80% were used for model fitting. We predicted individuals with low, high or average levels of CVD risk factors, the latter class being the most common. We constructed multi-omic predictions using a meta-learner that weighted single-omic predictions. Model performance comparisons were based on the F1 score. Finally, we investigated whether learned omic representations from pre-trained semi-supervised autoencoders could improve outcome prediction in an external cohort using transfer learning.ResultsDepending on the ML classifier or omic used, the quality of single-omic predictions varied. Multi-omics predictions outperformed single-omics predictions in most cases, particularly in the prediction of individuals with high or low CVD risk factor levels. Semi-supervised autoencoders improved downstream predictions compared to the use of unsupervised autoencoders. In addition, median gains in Area Under the Curve by transfer learning compared to modelling from scratch ranged from 0.09 to 0.14 and 0.07 to 0.11 units for transcriptomic and metabolomic data, respectively.ConclusionsBy illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions.

Effect of Left Ventricular Diastolic Dysfunction on the Cardiopulmonary Exercise Test in Patients with Cardiovascular Disease

Left ventricular diastolic dysfunction exists in patients with heart failure with reduced ejection fraction and causes activity restriction and a poor prognosis, but there have been few reports about exercise tolerance in patients with diastolic dysfunction, regardless of left ventricular ejection fraction (LVEF). In this study, 294 cardiovascular disease patients who performed a cardiopulmonary exercise test (CPX) with an adequate examination by echocardiography at Fukuoka University Hospital from 2011 to 2020 were investigated. Patients were divided into groups with Grade I and Grade II or III diastolic dysfunction according to diagnostic criteria, regardless of LVEF, by echocardiography. After adjusting for age, sex, body mass index, smoking, and LVEF by propensity score matching, we compared the results of CPX between the Grade I and Grade II/III groups. There were no significant differences in hemodynamic parameters, or in the respiratory exchange ratio, oxygen uptake per body weight, oxygen uptake per heart rate, or parameters of ventilatory volume. Ventilatory equivalents per oxygen uptake and per carbon dioxide output were significantly worse in the Grade II/III group from the rest to peak periods during CPX. In conclusion, left ventricular diastolic dysfunction worsens ventilatory efficacy during CPX. This effect potentially contributes to a poor prognosis in left ventricular diastolic dysfunction.

Preoperative echocardiography as a predictor of spinal anesthesia-induced hypotension in older patients with mild left ventricular diastolic dysfunction: a retrospective observational study.

Spinal anesthesia-induced hypotension (SAH) frequently occurs in older patients, many of whom have mild left ventricular (LV) diastolic dysfunction, often asymptomatic at rest. This study investigated the association between preoperative echocardiographic measurements and SAH in older patients with mild LV diastolic dysfunction. We conducted a retrospective observational study using data from electronic medical records. The patients ≥ 65 years old who underwent spinal anesthesia for urologic surgery between January 2016 and December 2017 and whose preoperative echocardiography within 6 months before surgery revealed grade I LV diastolic dysfunction were recruited. SAH was investigated using the anesthesia records. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. A total of 163 patients were analyzed. SAH and significant SAH developed in 55 (33.7%) patients. The mitral inflow E velocity was an independent risk factor for SAH (odds ratio [OR], 0.886; 95% confidence interval [CI], 0.845-0.929; P < 0.001). The area under the ROC curve for mitral inflow E velocity to predict SAH was 0.819 (95% CI, 0.752-0.875; P < 0.001). If mitral inflow E velocity was ≤ 60 cm/s, SAH was predicted with a sensitivity of 83.6% and specificity of 70.4%. The preoperative mitral inflow E velocity demonstrated the greatest predictability of SAH in older patients with mild LV diastolic dysfunction. This may assist in identifying patients at high risk of SAH and guiding preventive strategies in the future.

Electrocardiographic and Echocardiographic changes in Non-Hemodialysis Chronic Kidney Disease Patients: A Cross-Sectional Study

Abstract Chronic Kidney Disease (CKD) patients have a higher risk of cardiovascular manifestations such as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular diseases are the main cause of death in patients with advanced CKD, rather than end-stage kidney disease itself. Essentially, CKD speeds up the ageing process in the cardiovascular system. Objectives: To determine the prevalence of cardiovascular abnormalities in non-hemodialysis CKD patients. Methods: A descriptive cross-sectional study, was conducted in the Department of Medicine, between October 2020 to September 2022. A total of 50 CKD patients were included. The patients were evaluated &amp; enrolled in the study, based on history, general physical examination, systemic examination, Blood Urea, Serum Creatinine, Urine Routine, Electrocardiograph (ECG) and Echocardiography. Results: In the present study Electrocardiograph &amp; echocardiography determined cardiovascular abnormalities in 68% of patients. Among these 50% of patients had Left Ventricular Hypertrophy (LVH) &amp; Left Ventricular Diastolic Dysfunction (LVDD), 8% of patients had Arrhythmias and 6% patients had conduction abnormality, 2% patients had LVH and 2% patients had LVDD. Conclusion: LVH &amp; LVDD are the most common morphological abnormalities observed in our study. We can diagnose Arrhythmias and conduction abnormality by electrocardiogram &amp; echocardiography and refer them for appropriate interventions promptly.

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

Evaluation of left ventricular function in normotensive type-2 dm patients by echocardiography

The prevalence of diabetes mellitus (DM) is increasing globally. Indians are also believed to have a greater degree of insulin resistance and a stronger genetic predisposition to diabetes. Type II DM is a risk factor for cardiovascular disease and cardiovascular complications and these are a major cause of mortality and morbidity in diabetic patients. Left ventricular dysfunction, increased left ventricular wall thickness, increased left ventricular mass, and specific diabetic cardiomyopathy are some of the cardiovascular complications associated with diabetes. So the present study was performed to assess normotensive diabetic patients by echocardiography to evaluate their left ventricular function. A case control cross sectional study was conducted on 40 normotensive type 2 diabetes mellitus patients. 40 patients who were non-diabetic, non-hypertensive were taken as a control. A standard 2D echocardiography with M mode and Doppler was performed on case and control. In our study among 40 cases, 55% were male and 45% were female with mean age of case population being 47.5±7.24 year and among 40 controls, 50% were male and 50% were female with mean age 48.03±7.14 year. Mean BMI in case group was 29.49±2.37 kg/m2 and in control group 29.36±2.46 kg/m2. In our study we found that LVDD was present in 57.5% cases, 47.5% of cases had grade 1 LVDD whereas 10% had grade 2 LVDD. In comparison, only 10% of controls had LVDD with all of them having grade 1 LVDD. Also LV Systolic dysfunction, LVM and LVMI were higher in cases as compared to controls. Thus we concluded that the prevalence of left ventricular diastolic dysfunction in asymptomatic, normotensive patients with type 2 DM without significant coronary artery disease is much higher than previously suspected as evidenced by the results of this study and also of similar other studies and it increases with the duration of Diabetes. Left ventricular systolic dysfunction, LVM and LVMH prevalence were also higher in cases as compared to controls and they also correlate with duration of Diabetes.

Determinants and effects of microvascular obstruction on serial change in left ventricular diastolic function after reperfused acute myocardial infarction

BackgroundAlthough left ventricular (LV) diastolic dysfunction is more related to functional capacity after acute myocardial infarction (AMI), the determinants of LV diastolic functional change after reperfused AMI remain unknown. This study aimed to investigate the effects of microvascular obstruction (MVO) on mid-term changes in LV diastolic function after reperfused AMI.MethodsIn a cohort of 72 AMI patients who underwent successful revascularization, echocardiography and cardiovascular magnetic resonance imaging were repeated at 9-month intervals. The late gadolinium enhancement (LGE) amount, segmental extracellular volume fraction, global LV, and left atrial (LA) phasic functions, along with mitral inflow and tissue Doppler measurements, were repeated.ResultsAmong the included patients, 31 (43%) patients had MVO. During the 9-month interval, LV ejection fraction (EF) and LV global longitudinal strain (GLS) were significantly improved in accordance with a decrease in LGE amount (from 18.2 to 10.3 g, p &amp;lt; 0.001) and LV mass. The deceleration time (DT) of early mitral inflow (188.6 ms–226.3 ms, p &amp;lt; 0.001) and LV elastance index (Ed; 0.133 1/ml–0.127 1/ml, p = 0.049) were significantly improved, but not in conventional diastolic functional indexes. Their improvements occurred in both groups; however, the degree was less prominent in patients with MVO. The degree of decrease in LGE amount and increase in LVEF was significantly correlated with improvement in LV-Ed or LA phasic function, but not with conventional diastolic functional indexes.ConclusionsIn patients with reperfused AMI, DT of early mitral inflow, phasic LA function, and LV-Ed were more sensitive diastolic functional indexes. The degree of their improvement was less prominent in patients with MVO.

Echocardiographic Assessment of Left Ventricular Function in Three Oncologic Therapeutic Modalities in Women with Breast Cancer: The ONCO-ECHO Multicenter Study.

Background: Oncological treatment of breast cancer may be associated with adverse effects on myocardial function. Objectives: The objective of this study was to compare the influence of three oncological treatment methods of intervention on the echocardiographic (ECHO) parameters of left ventricular function. Materials and Methods: One hundred and fifty-five women with breast cancer were divided into three groups depending on the type of therapy used: group I (AC)-anthracyclines; group II (AC + TZ)-anthracyclines + trastuzumab; and group III (RTls+)-anthracyclines with or without trastuzumab + left-sided radiotherapy. Prospective ECHO examinations were performed at baseline and every 3 months, up to 12 months from the start of the therapy. Patients with a history of chemotherapy or who were diagnosed with heart disease were not included in the study. Results: Out of 155 patients, 3 died due to cancer as the primary cause, and 12 withdrew their consent for further observation. Baseline systolic and diastolic ECHO parameters did not differ between the analyzed groups. Cardiotoxicity, according to the LVEF criteria, occurred during follow-up in 20 patients (14.3%), irrespective of the treatment method used. Diastolic echocardiographic parameters did not change significantly after 12 months in each group, except for the left atrial volume index (LAVi), which was significantly higher in the AC + TZ compared to the values in the RTls+ group. Conclusions: All three oncologic therapeutic modalities in women with breast cancer showed no significant differences in relation to the incidence of echocardiographic cardiotoxicity criterion; however, transient systolic decrease in LVEF was most frequently observed in the AC + TZ therapeutic regimen. Left-sided radiotherapy was not associated with excess left ventricular systolic and diastolic dysfunction during a 12-month follow-up period. The predictors of negative changes in diastolic parameters included age and combined anthracycline and trastuzumab therapy.

Sex-specific cardiovascular remodeling leads to a divergent sex-dependent development of heart failure in aged hypertensive rats.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is continuously rising and predominantly affects older women often hypertensive and/or obese or diabetic. Indeed, there is evidence on sex differences in the development of HF. Hence, we studied cardiovascular performance dependent on sex and age as well as pathomechanisms on a cellular and molecular level. We studied 15-week- and 1-year-old female and male hypertensive transgenic rats carrying the mouse Ren-2 renin gene (TG) and compared them to wild-type (WT) controls at the same age. We tracked blood pressure and cardiac function via echocardiography. After sacrificing the 1-year survivors we studied vascular smooth muscle and endothelial function. Isolated single skinned cardiomyocytes were used to determine passive stiffness and Ca2+-dependent force. In addition, Western blots were applied to analyse the phosphorylation status of sarcomeric regulatory proteins, titin and of protein kinases AMPK, PKG, CaMKII as well as their expression. Protein kinase activity assays were used to measure activities of CaMKII, PKG and angiotensin-converting enzyme (ACE). TG male rats showed significantly higher mortality at 1 year than females or WT male rats. Left ventricular (LV) ejection fraction was specifically reduced in male, but not in female TG rats, while LV diastolic dysfunction was evident in both TG sexes, but LV hypertrophy, increased LV ACE activity, and reduced AMPK activity as evident from AMPK hypophosphorylation were specific to male rats. Sex differences were also observed in vascular and cardiomyocyte function showing different response to acetylcholine and Ca2+-sensitivity of force production, respectively cardiomyocyte functional changes were associated with altered phosphorylation states of cardiac myosin binding protein C and cardiac troponin I phosphorylation in TG males only. Cardiomyocyte passive stiffness was increased in TG animals. On a molecular level titin phosphorylation pattern was altered, though alterations were sex-specific. Thus, also the reduction of PKG expression and activity was more pronounced in TG females. However, cardiomyocyte passive stiffness was restored by PKG and CaMKII treatments in both TG sexes. Here we demonstrated divergent sex-specific cardiovascular adaptation to the over-activation of the renin-angiotensin system in the rat. Higher mortality of male TG rats in contrast to female TG rats was observed as well as reduced LV systolic function, whereas females mainly developed HFpEF. Though both sexes developed increased myocardial stiffness to which an impaired titin function contributes to a sex-specific molecular mechanism. The functional derangements of titin are due to a sex-specific divergent regulation of PKG and CaMKII systems.