EGFR/IGF1R Signaling Modulates Relaxation in Hypertrophic Cardiomyopathy.

BACKGROUND: Diastolic dysfunction is central to diseases such as heart failure with preserved ejection fraction and hypertrophic cardiomyopathy (HCM). However, therapies that improve cardiac relaxation are scarce, partly due to a limited understanding of modulators of cardiomyocyte relaxation. We hypothesized that cardiac relaxation is regulated by multiple unidentified proteins and that dysregulation of kinases contributes to impaired relaxation in patients with HCM. METHODS: We optimized and increased the throughput of unloaded shortening measurements and screened a kinase inhibitor library in isolated adult cardiomyocytes from wild-type mice. One hundred fifty-seven kinase inhibitors were screened. To assess which kinases are dysregulated in patients with HCM and could contribute to impaired relaxation, we performed a tyrosine and global phosphoproteomics screen and integrative inferred kinase activity analysis using HCM patient myocardium. Identified hits from these 2 data sets were validated in cardiomyocytes from a homozygous MYBPC3c.2373insG HCM mouse model. RESULTS: Screening of 157 kinase inhibitors in wild-type (N=33) cardiomyocytes (n=24 563) resulted in the identification of 17 positive inotropes and 21 positive lusitropes, almost all of them novel. The positive lusitropes formed 3 clusters: cell cycle, EGFR (epidermal growth factor receptor)/IGF1R (insulin-like growth factor 1 receptor), and a small Akt (α-serine/threonine protein kinase) signaling cluster. By performing phosphoproteomic profiling of HCM patient myocardium (N=24 HCM and N=8 donors), we demonstrated increased activation of 6 of 8 proteins from the EGFR/IGFR1 cluster in HCM. We validated compounds from this cluster in mouse HCM (N=12) cardiomyocytes (n=2023). Three compounds from this cluster were able to improve relaxation in HCM cardiomyocytes. CONCLUSIONS: We showed the feasibility of screening for functional modulators of cardiomyocyte relaxation and contraction, parameters that we observed to be modulated by kinases involved in EGFR/IGF1R, Akt, cell cycle signaling, and FoxO (forkhead box class O) signaling, respectively. Integrating the screening data with phosphoproteomics analysis in HCM patient tissue indicated that inhibition of EGFR/IGF1R signaling is a promising target for treating impaired relaxation in HCM.

Cardiovascular dysfunction induced by combined exposure to nicotine inhalation and high-fat diet.

Smoking and high-fat diet (HFD) consumption are two modifiable risk factors for cardiovascular (CV) diseases, and individuals who are overweight or obese due to unhealthy diet are more likely to use tobacco products. In this study, we aim to investigate the combined effects of nicotine (the addictive component of all tobacco products) and HFD on CV health, which are poorly understood. C57BL/6N male mice were placed on either HFD (60 kcal% fat) or regular diet (22 kcal% fat) and exposed to air or nicotine vapor for 10-12 wk. CV function was monitored by echocardiography and radiotelemetry, with left ventricular (LV) catheterization and aortic ring vasoreactivity assays performed at end point. Mice on HFD exhibited increased heart rate and impaired parasympathetic tone, whereas nicotine exposure increased sympathetic vascular tone as evidenced by increased blood pressure (BP) response to ganglionic blockade. Although neither nicotine nor HFD alone or in combination significantly altered BP, nicotine exposure disrupted circadian BP regulation with reduced BP dipping. LV catheterization revealed that combined exposure to nicotine and HFD led to LV diastolic dysfunction with increased LV end-diastolic pressure (LVEDP). Moreover, combined exposure resulted in increased inhibitory phosphorylation of endothelial nitric oxide synthase and greater impairment of endothelium-dependent vasodilation. Finally, a small cohort of C57BL/6N females with combined exposure exhibited similar increases in LVEDP, indicating that both sexes are susceptible to the combined effect of nicotine and HFD. In summary, combined exposure to nicotine and HFD leads to greater CV harm, including both additive and new-onset CV dysfunction.NEW & NOTEWORTHY Nicotine product usage and high-fat diet consumption are two modifiable risk factors for cardiovascular diseases. Here, we demonstrate that in mice, combined exposure to inhaled nicotine and high-fat diet results in unique cardiovascular consequences compared with either treatment alone, including left ventricular diastolic dysfunction, dysregulation of blood pressure, autonomic dysfunction, and greater impairment of endothelium-dependent vasorelaxation. These findings indicate that individuals who consume both nicotine products and high-fat diet have distinctive cardiovascular risks.

Age- and sex-dependent cardiovascular impact of maternal perinatal stress and altered dopaminergic metabolism in the medulla oblongata of the offspring.

Maternal major depressive disorder with peripartum onset presents health risks to the mother and the developing fetus. Using a rat model of chronic mild stress, we previously reported on the neurodevelopmental impact of maternal perinatal stress on their offspring. This study examined the cardiovascular impact of maternal perinatal stress on their offspring. The cardiovascular impact was assessed in terms of blood pressure and echocardiographic parameters. The results examined by a three-way ANOVA showed a significant association of cardiovascular parameters with maternal perinatal stress and offspring sex and age. Increased blood pressure was observed in adolescent female and adult male offspring of stress-exposed dams. Echocardiography showed an increase in left atrial dimension and a reduction in left ventricular systolic function in adolescent stress-exposed female offspring. Increased interventricular septum thickness at end-diastole and left ventricular diastolic dysfunction were observed in adult stress-exposed male offspring. The underlying mechanisms of cardiovascular impact were examined in stress-exposed adult offspring by assessing the levels of neurotransmitters and their metabolites in the medulla oblongata using high-performance liquid chromatography. A significant decrease in homovanillic acid, a dopamine metabolite and indicator of dopaminergic activity, was observed in adult stress-exposed female offspring. These results suggest a significant sex- and age-dependent impact of maternal stress during the peripartum period on the cardiovascular system in the offspring that extends to adulthood and suggests a multigenerational effect. The presented data urgently need follow-up to confirm their potential clinical and public health relevance.NEW & NOTEWORTHY We demonstrate that maternal perinatal stress is associated with sex- and age-dependent impact on the cardiovascular system in their offspring. The effect was most significant in adolescent female and adult male offspring. Observed changes in hemodynamic parameters and dopaminergic activity of the medulla oblongata are novel results relevant to understanding the cardiovascular impact of maternal perinatal stress on the offspring. The cardiovascular changes observed in adult offspring suggest a potential long-term, multigenerational impact of maternal perinatal stress.

Anti-bradycardia pacing-impact on patients with HFpEF: a systematic review.

Heart failure with preserved ejection fraction (HFpEF) has become an emerging concern. The protective effect of bradycardia in patients with reduced ejection fraction using beta-blockers or ivabradine does not improve symptoms in HFpEF. This review aims to assess current data regarding the impact of anti-bradycardia pacing in patients with HFpEF. A search was conducted on PubMed, ScienceDirect, Springer, and Wiley Online Library, selecting studies from 2013 to 2023. Relevant and eligible prospective studies and randomized controlled trials were included. Functional status, quality of life, and echocardiographic parameters were assessed. Six studies conformed to the selection criteria. Four were prospective studies with a total of 90 patients analyzed. Two were randomized controlled trials with a total of 129 patients assessed. The 6-min walk test (6MWT) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score improved in all prospective studies. My-PACE trial showed improvements in MLHFQ score (p < 0.001), significant relative lowering in NT-proBNP levels (p = 0.02), and an increased mean daily activity in the personalized accelerated pacing group compared to usual care. RAPID-HF trial proved that pacemaker implantation to enhance exercise heart rate (HR) did not improve exercise capacity and was associated with increased adverse events. HFpEF requires a more individualized approach and quality of life management. This review demonstrates that higher resting HR by atrial pacing may improve symptoms and even outcomes in HFpEF, while a higher adaptive rate during exertion has not been proven beneficial.

Association of cardiometabolic and triglyceride-glucose index with left ventricular diastolic function in asymptomatic individuals.

BACKGROUND AND AIMS: Obesity and insulin resistance are associated with left ventricular diastolic dysfunction (LVDD) and increased risk of heart failure. Cardiometabolic index (CMI) and triglyceride glucose (TyG) are new indexes to assess visceral obesity and insulin resistance, respectively. The study aimed to investigate the clinical usefulness of these indexes for identifying LVDD individuals. METHODS AND RESULTS: Overall, 1898 asymptomatic individuals were included in this cross-sectional study. Participants underwent anthropometrics, serum biochemical evaluation, and echocardiography. Multiple linear regression analysis revealed that both indexes were independent determinants of diastolic parameters among females; while for males, CMI and TyG were not associated with A velocity. In the multivariate logistic analysis, the proportion of LVDD in the third and fourth quartiles of CMI remained significantly greater than that in the lowest quartile in females (Q3 vs. Q1: odds ratio (OR) = 2.032, 95% confidence interval (CI): 1.181-3.496; Q4 vs. Q1: OR = 2.393, 95% CI: 1.347-4.249); while in males, the incidence of LVDD was significantly greater only in the fourth quartile. For TyG, the presence of LVDD in the fourth quartile was significantly greater in both genders. The discriminant values between the CMI (AUC: 0.704, 95% CI: 0.668-0.739) and TyG (AUC: 0.717, 95% CI: 0.682-0.752) were similar in females. Both indexes performed better in females than in males to identify LVDD. CONCLUSION: The CMI and TyG might both serve as effective tools to identify LVDD in routine health check-ups in primary care, mainly in females. With simpler parameters, the CMI could be utilized in medically resource-limited areas.

HFpEF and sex: understanding the role of sex differences.

Heart failure is a complex clinical syndrome with many etiological factors and complex pathophysiology affecting millions worldwide. Males and females can have distinct clinical presentation and prognosis, and there is an emerging understanding of the factors that highlight the similarities and differences to synthesize and present available data for sex-specific differences in heart failure with preserved ejection fraction (HFpEF). While the majority of data demonstrate more similarities than differences between females and males in terms of heart failure, there are key differences. Data showed that females have a higher risk of developing HFpEF, but a lower risk of mortality and hospitalization. This can be conditioned by different profiles of comorbidities, postmenopausal changes in sex hormone levels, higher levels of inflammation and chronic microvascular dysfunction in females. These factors, combined with different left ventricular dimensions and function, which are more pronounced with age, lead to a higher prevalence of LV diastolic dysfunction at rest and exercise. As a result, females have lower exercise capacity and quality of life when compared to males. Females also have different activities of systems responsible for drug transformation, leading to different efficacy of drugs as well as higher risk of adverse drug reactions. These data prove the necessity for creating sex-specific risk stratification scales and treatment plans.

Remifentanil improves left ventricular diastolic parameters in patients with impaired diastolic function: a prospective clinical study.

BACKGROUND: Left ventricular diastolic dysfunction has a significant impact on perioperative morbidity and mortality, and its incidence is high in elderly individuals. Anesthetic agents may impair diastolic function, which may increase the incidence of perioperative complications. The aim of this prospective, clinical, phase 4 study was to investigate the effects of remifentanil on left ventricle (LV) diastolic function in patients with diastolic dysfunction. The study was performed on 30 spontaneously breathing subjects (aged 60-80 years) with diastolic dysfunction. METHODS: Thirty patients (aged 60-80 years) with diastolic dysfunction scheduled for surgery were recruited between November 2019 and March 2023. Left ventricle function was evaluated once the intravenous remifentanil infusion reached a target-controlled concentration of 2 ng/ml with transthoracic echocardiography. Analysis of systolic function focused on left ventricular ejection fraction and mean mitral annular S velocity (Sm), whereas diastolic function focused on changes in transmitral peak flow (E), E/A, mitral septal and lateral e' waves, E/e' ratios and left atrial volume index following remifentanil infusion. RESULTS: Diastolic function measures of LV (mitral E/e', septal and lateral e' waves) statistically significantly improved (E/e' from 10.6 ± 2.9 cm.sn- 1 to 9.5 ± 2.2 cm.sn- 1; p = 0.006) following remifentanil infusion. Left atrial volume index decreased following remifentanil infusion without statistical significance (from 55 ± 14.4 ml.cm- 2 to 51.6 ± 13.3 ml.cm- 2; p = 0.1). Systolic function (ejection fraction and Sm) did not change following remifentanil infusion. CONCLUSIONS: Remifentanil improves left ventricular diastolic parameters in patients with preexisting diastolic dysfunction. Our study suggests that remifentanil at a plasma concentration of 2 ng.ml- 1 might be used safely in patients with left ventricular diastolic dysfunction.

Energy wavelet signal processed ECG and standard 12 lead ECG: Diagnosis of early diastolic dysfunction.

BACKGROUND: Left ventricular (LV) diastolic dysfunction (LVDD) is the result of impaired LV relaxation and identifies those at risk of developing heart failure. Echocardiography has been used as the gold standard to identify early LVDD. The signal processed electrocardiogram (hsECG) has demonstrated effectiveness to detect early LVDD. Whether or not the standard 12­lead electrocardiogram (ECG) can accurately predict early LVDD is not known. METHODS: A standard 12­lead ECG including signal processing (hsECG) was performed in 569 patients. Patients with atrial fibrillation, bundle branch block, pre-excitation, left ventricular hypertrophy or known cardiovascular disease were excluded, leaving 464 examinations for analysis. Early LVDD was diagnosed by established methods using echocardiography. Repolarization abnormalities (T wave discordance) in V1, V6, I and aVL and the hsECG were compared to the echocardiographic findings to establish diagnostic accuracy. RESULTS: A total of 84 (18.1%) patients were diagnosed with early LVDD. A combination of a borderline or abnormal finding on the hsECG produced the best diagnostic model (sensitivity 84.5%, specificity 47.9%). The best performing ECG lead was V1 with a sensitivity of 38.1% and specificity of 92.1%. Regression analysis demonstrated increasing age and V1 to be predictive of LVDD. CONCLUSIONS: The hsECG displayed reasonable ability to detect early LVDD. Other than V1, repolarization abnormalities on the standard 12­lead ECG did not. While lead V1 showed promise in detecting LVDD, whether this or any other simple ECG variable can predict future LVDD would be of further interest.

Factors associated with risk analysis for asymptomatic left ventricular diastolic dysfunction in nondialysis patients with chronic kidney disease.

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108-1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355-48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228-6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051-1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484-5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006-0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

The relationship of systemic and pulmonary arterial parameters with HFpEF scores (H2 FPEF, HFA-PEFF) and diastolic dysfunction parameters in heart failure patients with preserved ejection fraction.

OBJECTIVE: We aimed to show the relationship between pulmonary pulse wave transit time (pPTT), pulmonary artery stiffness (PAS), and aortic stiffness parameters measured by non-invasive methods, HFpEF patients, and HFpEF scores (H2 FPEF, HFA-PEFF). METHOD: A total of 101 patients were included in our study, 52 of whom were HFpEF patients and 49 were control groups without heart failure. Echocardiographic parameters for PAS and pPTT were calculated, along with diastolic parameters that support the diagnosis of HFpEF. Aortic stiffness was assessed using a PWA monitor. Demographic features, laboratory findings, aortic stiffness parameters, and echocardiographic findings including pulmonary artery parameters were compared with the control group. RESULTS: PAS, pPTT, PWV were significantly higher in the HFpEF group than in the control group (p < 0.001). PAS and pPTT correlated positively with HFpEF scores. In linear regression analysis for PAS, a directly positive correlation was found between E/e' and PAS, independent of aortic stiffness. CONCLUSION: These parameters can be used as a predictive value in the diagnosis process of patients with suspected HFpEF. A significant relationship between PAS and ventricular stiffness (E/e') was shown independently of aortic stiffness.

Exploring Sirtuins: New Frontiers in Managing Heart Failure with Preserved Ejection Fraction.

With increasing research, the sirtuin (SIRT) protein family has become increasingly understood. Studies have demonstrated that SIRTs can aid in metabolism and affect various physiological processes, such as atherosclerosis, heart failure (HF), hypertension, type 2 diabetes, and other related disorders. Although the pathogenesis of HF with preserved ejection fraction (HFpEF) has not yet been clarified, SIRTs have a role in its development. Therefore, SIRTs may offer a fresh approach to the diagnosis, treatment, and prevention of HFpEF as a novel therapeutic intervention target.

[The relevance of diastolic reserve of the left ventricle in patients with type 2 diabetes mellitus (literature review).]

Type 2 diabetes mellitus is one of the most common non-infectious diseases in the world. Among people with type 2 diabetes, patients of the older age group. An in understanding of the early cardiovascular manifestations of diabetes occupies an important place in international research and prevention programs, given that cardiac vascular complications are the cause of death in patients with diabetes. Recent studies evaluating left ventricular diastolic dysfunction as a characteristic predictor of diabetic cardiomyopathy by echocardiography. In accordance with the recommendations for diastolic dysfunction, have shown that the algorithm of the informative algorithm is used to determine left ventricular diastolic dysfunction in patients with prognosis in predicting cardiovascular complications.

Prevalence of Diastolic Dysfunction in Critically Ill Patients Admitted to Intensive Care Unit from a Tertiary Care Hospital: A Prospective Observational Study.

Aim: Critically ill individuals may have left ventricular diastolic dysfunction (LVDD) which can prolong their intensive care unit (ICU) stay. The purpose of this study was to determine the prevalence of LVDD in critically ill adult patients requiring mechanical ventilation in ICU, the effect of LVDD on 28-day survival, and weaning from mechanical ventilation. Methodology: A total of 227 adults who had been on mechanical ventilation for more than 48 hours in an ICU were recruited for this study. The study's parameters were recorded on the third day of mechanical ventilation using a low-frequency phased array probe. A simplified definition of LVDD in critically ill adults was utilized to determine the presence or absence of LVDD. Weaning failure and 28-day mortality were noted. Results: The prevalence of LVDD in adults requiring mechanical ventilation in the ICU was found to be 35.4% (n = 79). Patients with LVDD had the odds of having a 28-day mortality increase by 7.48 (95% CI: 3.24-17.26, p < 0.0001). Patients with LVDD had the odds of having weaning failure increase by 5.37 (95% CI: 2.17-13.26, p = 0.0003). Conclusion: Measures should be taken to detect critically ill adults with LVDD with systolic dysfunction or heart failure with preserved ejection fraction early so that their fluid balance, myocardial contractility, and afterload can be optimized to minimize their morbidity and mortality. Highlights: Critically ill adults with LVDD may have adverse outcomes. Hence, protocol should be in place for diagnosing LVDD early in critically ill adults thereby, measures can be taken to minimize morbidity in those patients. How to cite this article: Luitel B, Senthilnathan M, Cherian A, Suganya S, Adole PS. Prevalence of Diastolic Dysfunction in Critically Ill Patients Admitted to Intensive Care Unit from a Tertiary Care Hospital: A Prospective Observational Study. Indian J Crit Care Med 2024;28(9):832-836.

Left Ventricular Diastolic Dysfunction in the Critically Ill: The Rubik's Cube of Echocardiography.

How to cite this article: Kumar V. Left Ventricular Diastolic Dysfunction in the Critically Ill: The Rubik's Cube of Echocardiography. Indian J Crit Care Med 2024;28(9):813-815.

Elevated Blood Pressure and Worsening Cardiac Damage During Adolescence.

OBJECTIVES: To examine the longitudinal course for the development of elevated blood pressure (BP)/hypertension and cardiac damage in adolescents. STUDY DESIGN: From the Avon Longitudinal Study of Parents and Children, UK birth cohort, 1856 (1011 female) 17-year-old adolescents were followed up for 7 years. BP and echocardiography were assessed at ages 17 and 24 years. Elevated/hypertensive BP was defined as ≥130 mm Hg systolic and ≥85 mm Hg diastolic. Left ventricular (LV) mass indexed for height2.7 (LVMI2.7) ≥51 g/m2.7 was defined as LV hypertrophy (LVH) and LV diastolic function (LVDF) E/A <1.5 as LVD dysfunction (LVDD). Data were analyzed with generalized logit mixed-effect models and cross-lagged structural equation temporal path models adjusting for cardiometabolic and lifestyle factors. RESULTS: Over follow-up, the prevalence of elevated systolic BP/hypertension increased from 6.4% to 12.2%, LVH from 3.6% to 7.2%, and LVDD from 11.1% to 16.3%. Cumulative elevated systolic BP/hypertension was associated with worsening LVH in female participants (OR 1.61, CI 1.43-1.80 P < .001) but not in male participants. Elevated systolic BP/hypertension was associated with worsening LVDD in male and female participants. Elevated diastolic BP/hypertension was associated with worsening LVH in male and female participants. In cross-lagged temporal path models, higher baseline systolic BP was associated with LVDF (ß = 0.09, SE = 0.002, P = .029) but not LVMI2.7 at follow-up. Higher baseline cardiac indices were not associated with follow-up systolic BP. Higher baseline diastolic BP was associated with follow-up higher cardiac indices except LVDF. Baseline LVMI2.7 was not associated with follow-up diastolic BP. CONCLUSIONS: Elevated BP/hypertension may temporally precede premature cardiac damage in youth.

Hemodynamic Characterization of Neonates With Congenital Diaphragmatic Hernia-Associated Pulmonary Hypertension by Cardiac Catheterization.

We examined the results of cardiac catheterization in infants with congenital diaphragmatic hernia (CDH) from 2009 to 2020. Catheterization confirmed pulmonary arterial hypertension in all cases (n =  17) and identified left ventricular (LV) diastolic dysfunction (LVDD) in 53%. LVDD was associated with greater respiratory morbidity. Preprocedural noninvasive assessment showed inconsistent agreement with catheterization results.

Association between spirometry pattern, left ventricular diastolic function, and mortality.

BACKGROUND: Spirometric abnormalities have been related to incident heart failure in general population, who generally have preserved left ventricular ejection fraction (LVEF). We aimed to investigate the association between spirometric indices, cardiac functions and clinical outcomes. METHODS: Subjects presenting with exertional dyspnoea and received spirometry and echocardiography were eligible for this study. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)/FVC ratio were measured to define the spirometry patterns: normal (FEV1/FVC ≥ 70%, FVC ≥ 80%), obstructive (FEV1/FVC < 70%, FVC ≥ 80%), restrictive pattern (FEV1/FVC ≥ 70%, FVC < 80%) and mixed (FEV1/FVC < 70%, FVC < 80%). The diastolic dysfunction index (DDi) was the counts of the indicators, including septal e' velocity <7 cm/s, septal E/e' > 15, pulmonary artery systolic pressure > 35 mmHg and left atrial dimension >40 mm. RESULTS: Among a total of 8669 participants (65.8 ± 16.3 years, 56% men), 3739 (43.1%), 829 (9.6%), 3050 (35.2%) and 1051 (12.1%) had normal, obstructive, restrictive and mixed spirometry pattern, respectively. Subjects with restrictive or mixed spirometry pattern had higher DDi and worse long-term survival than those with obstructive or normal ventilation. FVC but not FEV1/FVC was predictive of 5-year mortality, independent of age, sex, renal function, LVEF, DDi, body mass index, and comorbidities (hazard ratio, 95% confidence intervals: .981, .977-.985). Furthermore, there was an inverse nonlinear relationship between FVC and DDi, suggesting the declined FVC may mediate 43% of the prognostic hazard of left ventricular diastolic dysfunction. CONCLUSIONS: The restrictive spirometry pattern or the declined FVC was associated with left ventricular diastolic dysfunction, which aggravated the long-term mortality in the ambulatory dyspnoeic subjects.

Cross-sectional associations between questionnaire-measured physical activity and tissue doppler indices of left ventricular diastolic function.

BACKGROUND: The prevalence of left ventricular (LV) diastolic dysfunction has been increasing over the past decade, and to date, effective pharmacotherapies that enhance LV diastolic function have not yet been identified. Though some data has demonstrated the beneficial effects of exercise training on LV diastolic function, little is known about the adaptations of diastolic function to daily physical activity (PA). Accordingly, our study aimed to investigate the impact of daily PA on tissue Doppler indices of LV diastolic function. METHODS: A total of 432 participants were enrolled for clinically indicated echocardiography from July 2019 to July 2020 at Peking University People's Hospital. Participants aged ≥ 18 years were included if they had stable PA in the past six months and normal LV systolic function. A questionnaire was used to collect demographic characteristics, medical history, and daily PA. According to PA Guidelines for Americans, we identified these participants into low-intensity PA (LPA) group and moderate-high-intensity PA (MHPA) group. Propensity score matching (PSM) was performed to match potential confounding factors between the two groups. The clinical characteristics and echocardiographic parameters between LPA group and MHPA group were compared using student's t-test, Mann-Whitney U test, and chi-square test as appropriate. RESULTS: After matching potential confounding factors using PSM with a 1:3 matching ratio, our final analysis included 86 cases in the MHPA group and 214 cases in the LPA group. All demographic characteristics and comorbidities were statistically similar between the two groups. Compared to the LPA group, the MHPA group showed higher septal e' (7.9 ± 2.9 cm/s versus 7.2 ± 2.6 cm/s, P = 0.047). Other echocardiographic parameters associated with LV diastolic function concerning lateral e' and average E/e', also trended towards improved LV diastolic function in the MHPA group, but failed to reach statistical significance. CONCLUSIONS: Our study demonstrated that moderate-high-intensity daily PA was associated with improved septal e', suggesting that moderate-high-intensity PA could potentially ameliorate LV diastolic dysfunction.

Temporary atrial septal defect balloon occlusion test as a must in the elderly.

BACKGROUND: Atrial septal defect (ASD) can often remain asymptomatic until adulthood. It still remains unclear whether large ASD closure in senior people should be performed or not. Temporary ASD balloon occlusion test has been suggested as a tool to assess the risk of acute left ventricular heart failure post-ASD closure, and it allows to better distinguish responders from non-responders. CASE PRESENTATION: An 83-year-old man with a long-standing uncorrected secundum ASD was admitted for recently decompensated right-sided heart failure. During hospitalization, this patient was studied with trans-esophageal echocardiography, cardiac magnetic resonance imaging, and right heart catheterization, showing high Qp:Qs ratio and favorable anatomical conditions for percutaneous closure. Because of patient's increasing need for intravenous diuretics and worsening renal function, it was considered that transcatheter ASD closure could improve symptoms, hence it was performed an attempt of percutaneous closure of the ASD with a fenestrated device. Unfortunately, irrespective of ASD being hemodynamically significant, it was found a very significant increase in pulmonary capillary wedge pressure during the temporary balloon occlusion test, supporting the existence of concealed left ventricular diastolic dysfunction. As a result, it was decided to abandon the procedure and not to close the ASD. CONCLUSION: This clinical case illustrates the value of temporary balloon occlusion test before permanent percutaneous closure of ASD in elderly patients, regardless of left ventricular (systolic or diastolic) dysfunction.

Effect of continuous positive pressure ventilation on left ventricular diastolic function E/A ratio in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: Many studies have shown that obstructive sleep apnea (OSA) is related to reduced left ventricular diastolic function. Continuous positive airway pressure (CPAP) is generally recognized as the preferred therapy for OSA. Yet, the effect of CPAP on left ventricular diastolic function in patients with OSA is inconclusive. In order to assess the influence of CPAP on left ventricular diastolic function in patients with OSA, we performed this meta-analysis of clinical experiments. METHODS: PubMed, Web of Science, OVID, Embase, and Cochrane Library from the establishment of the database to July 6, 2022, were searched for clinical trial data. Inclusion criteria for this meta-analysis were: (1) Patients in the experimental group were diagnosed with OSA by polysomnography; (2) CPAP treatment course ≥ 4 weeks; (3) baseline and follow-up data of the diastolic function parameter E/A ratio were reported in the literature. Exclusion criteria were: (1) Central sleep apnea (CSA); (2) comorbid organic heart diseases such as coronary heart disease; (3) age < 18 years old; (4) conference abstracts or duplicate publications. RESULTS: After exclusions, 7 studies (2 RCTs and 5 prospective studies) with 473 subjects (225 in the treatment group and 248 in the matched control group) were included in the meta-analysis. Subgroup analysis indicated that after CPAP therapy, the left ventricular (LV) E/A ratio was significantly increased in patients with OSA (weighted mean difference (WMD) = 0.22, 95% CI = - 0.06-0.38; P = 0.007). Sensitivity analyses showed that the combined results were not influenced by single studies. Publication bias was not significant (Egger's test, P = 0.813). CONCLUSIONS: The results of this meta-analysis suggest that CPAP may improve the E/A ratio in patients with OSA patients. However, the small number of studies (n = 7) decreases confidence in the findings. Thus, carefully designed randomized controlled trials are needed to confirm the findings.