The Agreement Between Transthoracic and Transesophageal Echocardiography in the Assessment of Right Ventricular Diastolic Dysfunction Grades in Adult Patients Undergoing Cardiac Surgery: A Prospective Observational Study.

Introduction The importance of right ventricular (RV) diastolic function in cardiac surgery cannot be overstated, as it significantly affects prognosis and long-term outcomes. Conventionally, RV diastolic dysfunction (RVDD) is assessed and graded using criteria from either the American Society of Echocardiography (ASE) or the British Society of Echocardiography (BSE), with measurements done by transthoracic echocardiography (TTE). However, during cardiac surgery, perioperative echocardiographic evaluation is done predominantly by transesophageal echocardiography (TEE). This study aimed to assess the agreement between TTE and TEE in grading RVDD using both ASE and BSE criteria. Methods Key two-dimensional (2D) and Doppler parameters were measured in 81 patients undergoing cardiac surgery by both TTE and TEE after anesthesia induction within 10 minutes of each other, under similar hemodynamic, anesthetic, and ventilatory conditions. RVDD gradings were done separately by TTE and TEE with both ASE and BSE criteria using the measured values of the key parameters by TTE and TEE, respectively. RVDD gradings derived from TTE were compared with those derived from TEE. The tricuspid inflow Doppler and tricuspid annular tissue Doppler parameters were measured in TEE in both mid-esophageal RV inflow-outflow (MERVIO) and deep transgastric RV inflow-outflow (DTGRVIO) views. Gradings were done separately for both views of TEE by using the Doppler values measured in the respective views (TEE-MERVIO and TEE-DTGRVIO). The TTE-derived RVDD grades were compared with those derived by both TEE-MERVIO and TEE-DTGRVIO. Weighted κ values were used to assess observed agreement beyond chance. Inter-rater reliability of the RVDD grades derived by both TTE and TEE (both views) was also checked. Individual 2D and Doppler parameters were compared between TTE and TEE in terms of Bland-Altman limits of agreement. Results As per ASE criteria, disagreement of RVDD by ≥1 grade was seen in 43 (53.1%) patients and by 2 grades in eight (9%) patients when comparing TTE and TEE-MERVIO, yielding a weighted κ of 0.14 (p=0.123). Disagreement by ≥1 grade was observed in 32 (39.5%) patients and by 2 grades in 10 (12.3%) patients when comparing TTE and TEE-DTGRVIO, yielding a weighted κ of 0.3 (p=0.002). Using the BSE Criteria, disagreement of RVDD grades occurred in nine (11.1%) patients when comparing TTE and TEE-MERVIO, yielding an unweighted κ of 0.25 (p=0.295). Disagreement occurred in 12 (14.8%) patients when comparing TTE and TEE-DTGRVIO, yielding an unweighted κ of 0.260 (p=0.187). There was almost perfect agreement between independent raters regarding both TTE- and TEE-derived RVDD grades per the ASE criteria, and substantial to almost perfect agreement per BSE criteria. Bland-Altman analysis of paired data between the TTE- and TEE-measured values of individual 2D and Doppler parameters showed wide limits of agreement. Conclusions This study revealed, at best, only fair agreement between TTE and TEE in grading RVDD. The measured 2D and Doppler echocardiographic parameters showed wide limits of agreement between TTE and TEE. We recommend further research to develop a TEE-based algorithm for grading RVDD, and to evaluate the prognostic effectiveness of perioperative TEE for predicting adverse clinical outcomes associated with RVDD.

Stress Echocardiography for Assessment of Diastolic Function.

PURPOSE OF REVIEW: Diastolic dysfunction is an important, though often underappreciated, cause for exertional dyspnea. Echocardiography enables noninvasive evaluation of diastolic function and filling pressure, but images acquired at rest may be insensitive for detection of exertional abnormalities. This review focuses on stress echocardiography to assess diastolic function, including traditional and novel techniques, with emphasis on specific patient sub-groups in whom this testing may be valuable. RECENT FINDINGS: Emerging data informs patient selection for diastolic stress testing. Further, increasing literature provides considerations for performance and interpretation of diastolic metrics relevant to patients with heart failure with preserved ejection fraction, hypertrophic cardiomyopathy, athletes, and those with microvascular coronary dysfunction. Methods, such as speckle-tracking and multi-modality imaging, provide additional and complementary information for non-invasive diastolic assessment. This review serves as a guide to optimally utilize existing and novel techniques of stress echocardiography for diastolic assessment across a broad range of patients.

Sacubitril/valsartan improves diastolic left ventricular stiffness with increased titin phosphorylation via cGMP-PKG activation in diabetic mice.

Titin, a giant sarcomeric protein, regulates diastolic left ventricular (LV) passive stiffness as a molecular spring and could be a therapeutic target for diastolic dysfunction. Sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor, has been shown to benefit patients with heart failure with preserved ejection fraction. The effect of Sac/Val is thought to be due to the enhancement of the cGMP/PKG pathway via natriuretic peptide. In this study, the effects of Sac/Val on LV diastolic dysfunction are demonstrated in a mouse diabetic cardiomyopathy model focusing on titin phosphorylation. Sac/Val-treated diabetic mice showed a greater increase in myocardial levels of cGMP-PKG than Val-treated and control mice. Conductance catheter analysis showed a significant reduction in LV stiffness in diabetic mice, but not in non-diabetic mice. Notably, diastolic LV stiffness was significantly reduced in Sac/Val-treated diabetic hearts compared with Val-treated or vehicle-treated diabetic mice. The phosphorylation level of titin (N2B), which determines passive stiffness and modulates active contraction, was higher in Sac/Val-treated hearts compared with Val-treated hearts in diabetic mice. Given that alteration of titin phosphorylation through PKG contributes to myocardial stiffness, the beneficial effects of Sac/Val in heart failure might be partly attributed to the induction of titin phosphorylation.

Evaluating the effects of adrenalectomy and mineralocorticoid receptor antagonist on cardiac remodeling and diastolic function in patients with aldosterone-producing adenoma.

Cardiac remodeling and diastolic dysfunction in patients with aldosterone-producing adenomas (APA) can be improved after adrenalectomy. However, the effect of mineralocorticoid receptor antagonist (MRA) treatment remains unclear. The aim of this study is to evaluate the effect of MRA on cardiac remodeling and diastolic dysfunction in patients with PA. We prospectively enrolled patients with APA from 1993 to 2023, who either received medical treatment with MRAs or underwent adrenalectomy. Biochemical characteristics and echocardiographic findings were collected at baseline and one year after treatment. Propensity score matching was conducted based on baseline biochemical characteristics, left ventricular mass index (LVMI), and diastolic function. A total of 467 APA patients were enrolled in the study. After propensity score matching, 159 patients who underwent adrenalectomy were matched with 159 patients who received MRAs. After therapy, patients who received MRAs showed significant improvement in diastolic function after one year of treatment but not LVMI. Compared to the MRA group, the adrenalectomy group had greater improvement in systolic blood pressure, plasma aldosterone concentration, plasma renin activity, aldosterone-to-renin ratio, and LVMI. In multivariable regression analysis, pretreatment echocardiographic values were significantly associated with changes in both LVMI and E/e', while the treatment strategy showed a significant association with changes in LVMI. Thus, one year after therapy, both adrenalectomy and MRA are effective in improving diastolic function in patients with APA. However, adrenalectomy is more effective than MRA treatment in reversing cardiac remodeling in patients with APA.

Prognostic value of exercise tolerance and exercise-induced diastolic dysfunction in elderly patients referred for exercise stress echocardiography.

BACKGROUND: We studied the prognostic value of exercise tolerance and exercise-associated diastolic dysfunction (Ex-DD) in elderly patients referred for exercise stress echocardiography (ExE). METHODS: A total of 674 patients ≥60 years who underwent ExE using the Bruce protocol between January 2017 and December 2020 were included in this study. The prognostic factors examined were exercise tolerance, quantified in metabolic equivalents of tasks (METs), and Ex-DD. Patients were followed for a composite endpoint of all-cause death and cardiovascular hospitalization. RESULTS: 122 (18 %) patients had Ex-DD and had a higher incidence of the combined outcome (23 [19 %] vs. 47 [9 %], p = 0.001) compared to patients without Ex-DD. Patients were classified into the following groups: group A (no Ex-DD and METs≥8.5), group B (either Ex-DD or METs<8.5), and group C (both Ex-DD and METs<8.5). Group B did not show higher mortality (HR: 1.6, p = 0.475) or cardiovascular hospitalization (HR: 1.8, p = 0.08) compared to group A, but showed an increased risk for the combined outcome (HR: 1.9, p = 0.038). Group C was associated with higher mortality (HR: 4.8, p = 0.032), cardiovascular hospitalization (HR: 3.9, p < 0.001), and the combined outcome (HR: 4.0, p < 0.001) compared to group A. CONCLUSIONS: Decreased exercise capacity and Ex-DD were associated with poor outcomes, especially when both findings were present.

Cardiometabolic effects of sacubitril/valsartan in a rat model of heart failure with preserved ejection fraction.

The promising results obtained in the PARADIGM-HF trial prompted the approval of sacubitril/valsartan (SAC/VAL) as a first-in-class treatment for heart failure with reduced ejection fraction (HFrEF) patients. The effect of SAC/VAL treatment was also studied in patients with heart failure with preserved ejection fraction (HFpEF) and, although improvements in New York Heart Association (NYHA) class, HF hospitalizations, and cardiovascular deaths were observed, these results were not so promising. However, the demand for HFpEF therapies led to the approval of SAC/VAL as an alternative treatment, although further studies are needed. We aimed to elucidate the effects of a 9-week SAC/VAL treatment in cardiac function and metabolism using a preclinical model of HFpEF, the Zucker Fatty and Spontaneously Hypertensive (ZSF1) rats. We found that SAC/VAL significantly improved diastolic function parameters and modulated respiratory quotient during exercise. Ex-vivo studies showed that SAC/VAL treatment significantly decreased heart, liver, spleen, and visceral fat weights; cardiac hypertrophy and percentage of fibrosis; lipid infiltration in liver and circulating levels of cholesterol and sodium. Moreover, SAC/VAL reduced glycerophospholipids, cholesterol, and cholesteryl esters while increasing triglyceride levels in cardiac tissue. In conclusion, SAC/VAL treatment improved diastolic and hepatic function, respiratory metabolism, reduced hypercholesterolemia and cardiac fibrosis and hypertrophy, and was able to modulate cardiac metabolic profile. Our findings might provide further insight into the therapeutic benefits of SAC/VAL treatment in obese patients with HFpEF.

Efficacy of Sodium-Glucose 2 Transporter Inhibitors in Heart Failure With Preserved Ejection Fraction: A Narrative Review.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent condition. It occurs more commonly in older patient populations with multiple comorbidities, such as hypertension, diabetes, and obesity. However, managing HFpEF has been challenging due to its complex pathophysiology, and medications effective for heart failure with reduced ejection fraction (HFrEF) have not shown similar efficacy in HFpEF. Sodium-glucose 2 transporter (SGLT2) inhibitors were originally developed for the treatment of type 2 diabetes mellitus, yet several trials and papers have proved their significant role in HFpEF. Through a variety of mechanisms, including natriuresis, diuresis, and anti-inflammatory effects, to name a few, this class of drugs has shown promising results in HFpEF patients. The use of SGLT2 inhibitors in HFpEF has resulted in improvements in several aspects, including biomarkers, imaging, symptomatology, and mortality. Moreover, SGLT2 inhibitors have a favorable safety profile, which is especially significant given the high comorbidity burden in HFpEF patients. This feature is particularly notable given the type of patient being managed. Extensive research is still being undertaken for their use in HFpEF, given the positive results obtained thus far.

Regression of biventricular hypertrophy in acromegalic cardiomyopathy following management of excessive growth hormone secretion.

Acromegalic cardiomyopathy is a significant cardiovascular complication associated with acromegaly, caused by excessive growth hormone production from a pituitary adenoma. Early diagnosis can be challenging due to its insidious nature. This case underscores the critical significance of timely medical intervention, illustrating favorable outcomes resulting from prompt therapeutic measures.

Importance of environmental signals for cardiac morphological development in Atlantic salmon.

The hearts of salmonids display remarkable plasticity, adapting to various environmental factors that influence cardiac function and demand. For instance, in response to cold temperature, the salmonid heart undergoes growth and remodeling to counterbalance the reduced contractile function associated with dropping temperatures. Alongside heart size, the distinct pyramidal shape of the wild salmonid heart is essential for optimal cardiac performance, yet the environmental drivers behind this optimal cardiac morphology remain to be fully understood. Intriguingly, farmed salmonids often have rounded, asymmetrical ventricles and misaligned bulbi from an early age. These deformities are noteworthy given that farmed salmon are often not exposed to natural cues, such as a gradual temperature increase and changing day lengths, during critical developmental stages. In this study, we investigated whether natural environmental conditions during early life stages are pivotal for proper cardiac morphology. Atlantic salmon were raised under simulated natural conditions (low temperature with a natural photoperiod; SimNat) and compared with those reared under simulated farming conditions (SimFarm). Our findings reveal that the ventricle shape and bulbus alignment in SimNat fish closely resemble those of wild salmon, while functional analyses indicate significant differences between SimNat and SimFarm hearts, suggesting diastolic dysfunction and higher cardiac workload in SimFarm hearts. These findings highlight the profound influence of environmental factors such as water temperature and photoperiod on the structural development of the salmonid heart, underscoring the importance of early environmental conditions for cardiac health.

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.

Global longitudinal strain is a surrogate marker for time constant of isovolumic relaxation in post-Fontan operation patients with single right ventricle and preserved ejection fraction.

BACKGROUND: The time constant of isovolumic relaxation is an established index of ventricular relaxation, a major component of diastolic function, even in a single right ventricle. However, the specific echocardiographic parameters for estimating diastolic dysfunction are insufficient for a single right ventricle. This study aimed to investigate the echocardiographic indices associated with time constant of isovolumic relaxation in post-Fontan operation patients with a single right ventricle. METHODS: We included 39 patients with hypoplastic left heart syndrome after Fontan operation with an ejection fraction ≥45% and preserved valve function. First, the correlation between echocardiographic parameters and time constant of isovolumic relaxation was examined, and partial correlation coefficients were calculated using age and heart rate as covariates. Next, univariate regression analysis was performed using time constant of isovolumic relaxation as the objective variable and echocardiographic parameters as independent variables, followed by multivariate regression analysis incorporating parameters with p < 0.10. RESULTS: Among the echocardiographic parameters, global longitudinal strain correlated most strongly with time constant of isovolumic relaxation (r = 0.778, p < 0.001). This was consistent with the partial correlation coefficients (r = 0.707, p < 0.001). Using stepwise multivariate regression analysis, only global longitudinal strain was found to be an independent predictor of time constant of isovolumic relaxation (adjusted R2 = 0.551). CONCLUSIONS: Global longitudinal strain could be used as a surrogate marker of time constant of isovolumic relaxation, an invasive indicator of relaxation impairment, in post-Fontan operation patients with a single right ventricle, preserved ejection fraction, and valve function.

Diagnostic accuracy of artificial intelligence for identifying systolic and diastolic cardiac dysfunction in the emergency department.

INTRODUCTION: Cardiac point-of-care ultrasound (POCUS) can evaluate for systolic and diastolic dysfunction to inform care in the Emergency Department (ED). However, accurate assessment can be limited by user experience. Artificial intelligence (AI) has been proposed as a model to increase the accuracy of cardiac POCUS. However, there is limited evidence of the accuracy of AI in the clinical environment. The objective of this study was to determine the diagnostic accuracy of AI for identifying systolic and diastolic dysfunction compared with expert reviewers. METHODS: This was a prospective, observational study of adult ED patients aged ≥45 years with risk factors for systolic and diastolic dysfunction. Ultrasound fellowship-trained physicians used an ultrasound machine with existing AI software and obtained parasternal long axis, parasternal short axis, and apical 4-chamber views of the heart. Systolic dysfunction was defined as ejection fraction (EF) < 50 % in at least two views using visual assessment or E-point septal separation >10 mm. Diastolic dysfunction was defined as an E:A < 0.8, or ≥ 2 of the following: septal e' < 7 cm/s or lateral e' < 10 cm/s, E:e' > 14, or left atrial volume > 34 mL/m2. AI was subsequently used to measure EF, E, A, septal e', and lateral e' velocities. The gold standard was systolic or diastolic dysfunction as assessed by two independent physicians with discordance resolved via consensus. We performed descriptive statistics (mean ± standard deviation) and calculated the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of the AI in determining systolic and diastolic dysfunction with 95 % confidence interval (CI). Subgroup analyses were performed by body mass index (BMI). RESULTS: We enrolled 220 patients, with 11 being excluded due to inadequate images, resulting in 209 patients being included in the study. Mean age was 60 ± 9 years, 51.7 % were women, and the mean BMI was 31 ± 8.1 mg/kg2. For assessing systolic dysfunction, AI was 85.7 % (95 %CI 57.2 % to 98.2 %) sensitive and 94.8 % (95 %CI 90.6 % to 97.5 %) specific with a LR+ of 16.4 (95 %CI 8.6 to 31.1) and LR- of 0.15 (95 % CI 0.04 to 0.54). For assessing diastolic dysfunction, AI was 91.9 % (95 %CI 85.6 % to 96.0 %) sensitive and 94.2 % (95 %CI 87.0 % to 98.1 %) specific with a LR+ of 15.8 (95 %CI 6.7 to 37.1) and a LR- of 0.09 (0.05 to 0.16). When analyzed by BMI, results were similar except for lower sensitivity in the BMI ≥ 30 vs BMI < 30 (100 % vs 80 %). CONCLUSION: When compared with expert assessment, AI had high sensitivity and specificity for diagnosing both systolic and diastolic dysfunction.

Left atrial to ventricular volume ratio and relation to fitness, cardiovascular risk factors, and diastolic function in healthy individuals: the HUNT Study.

Aims: Left atrial (LA) and ventricular (LV) remodelling is thought to be balanced in healthy individuals, and the LA end-systolic volume (LAV) to LV end-diastolic volume (LVEDV) ratio (LA:LV) could help discriminate between pathological and physiological LA enlargement. We aimed to assess LA:LV and its associations with age, sex, and cardiovascular risk factors HbA1C, body mass index (BMI), systolic blood pressure, and peak oxygen uptake (VO2peak). The association to measures of LV diastolic function and filling pressures were compared with LAV and LA reservoir strain. Methods and results: Cardiopulmonary exercise testing and measurement of risk factors 10 years apart and echocardiography at follow-up was performed in 1348 healthy adults [52% women, mean (SD) age 59 (12) years] prospectively included in a large population study. All risk factors were significantly associated with LA:LV in univariate analyses, while BMI and VO2peak were significantly associated with LA:LV in adjusted models. A higher LA:LV was associated with increased odds ratio (OR) of diastolic dysfunction [OR (95% CI) 2.6 (2.1, 3.3)]. Measures of LV filling pressures were more closely associated with LA:LV than LAV and LA reservoir strain, but LA reservoir strain was more closely related to some diastolic function measures. In individuals with LAV > 34 mL/m2, the LA:LV explained 29% of variance in VO2peak (P < 0.001). Conclusion: A higher LA:LV was associated with, and may improve, assessment of diastolic dysfunction and filling pressures. The LA:LV differentiates VO2peak in individuals with enlarged LAV and may have a role in evaluating whether LA enlargement reflects pathology.

The size of the left forechamber, also known as the left atrium, is used as a criterion when looking for signs of heart failure. However, an enlarged left atrium is also commonly found in healthy individuals with hearts adapted to exercise training. In the healthy state, both the forechambers and the main chambers (ventricles) are thought to adapt together and enlarge in a balanced way. Therefore, we explored whether an enlarged ratio between the left atrium and the left ventricle was more tightly related to other signs of maladaptation than left atrial size alone. Our results show that the left atrial to ventricular ratio may have a role in distinguishing heart failure from healthy adaptation.

Cardiac MRI in Rheumatic Disease.

Immune-mediated systemic inflammatory disorders present a latent threat for cardiovascular disease. Early involvement may be associated with constitutional symptoms, while clinical evidence of disease may manifest later in an insidious manner. Multimodality imaging is crucial to detect myocardial involvement, with transthoracic echocardiogram as a first-line imaging modality; however, cardiac MRI (CMRI) has the potential to significantly impact our diagnostic and therapeutic approaches through high-fidelity chamber quantification and parametric mapping techniques. Novel imaging techniques are currently under investigation, including stress CMRI, feature tracking CMR, late gadolinium enhancement (LGE) entropy, and 4 dimensional flow CMRI.

Novel Biomarkers of Grade I Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Patients with Metabolic-Dysfunction-Associated Steatotic Liver Disease.

Background/Objectives: Prior research has identified a significant association between heart disease and metabolic-dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms are unclear. This study aimed to identify predictive biomarkers associated with grade I left ventricular diastolic dysfunction (LVDD) in patients with type 2 diabetes mellitus (T2DM). Methods: This single-center, cross-sectional study evaluated 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: This study analyzed 50 patients (mean age 58.0 ± 11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean body mass index (BMI) 34.4 ± 5.9 kg/m2), and a mean HbA1c of 7.9 ± 1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate-to-severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, α2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s', E wave, E/e', E/A, medium E', and septal e' (p < 0.05 for all). α2-macroglobulin > 1.92 g/L (area under the receiver operating characteristic curve (AUROC) = 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score > 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusions: Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as α2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients.

Clinical impact of diastolic dysfunction and atrial fibrillation before and after initiating hemodialysis in patients with end-stage kidney disease.

BACKGROUND: Diastolic dysfunction with left ventricular hypertrophy and myocardial fibrosis is an important characteristic of uremic cardiomyopathy in end-stage kidney disease (ESKD). Few studies explored the relationship between changes in diastolic dysfunction and the risk of mortality or cardiovascular outcome in patients with ESKD. We investigated the clinical impact of diastolic dysfunction and atrial fibrillation (AF) on patients starting hemodialysis (HD). METHODS: A total of 718 patients who started HD between 2010 and 2020 were included. We classified patients according to the pre- and post-HD diastolic dysfunction grades (DDG) evaluated by echocardiography. Patients with AF were classified separately. The primary outcome was a composite outcome of all-cause mortality and cardiac complication. RESULTS: The median age was 63 years, and 61.4% were male. Patients were divided into four groups based on pre-HD echocardiography findings. After initiating HD, the patients were classified according to changes in DDG and AF. Composite outcomes were significantly higher in the pre-HD AF groups. However, after adjusting for age and history of ischemic heart disease, pre-HD AF did not affect the composite outcomes. Patients with normal post-HD diastolic function had better outcomes than those with diastolic dysfunction or AF. Furthermore, the deterioration of diastolic dysfunction after HD was associated with an increased risk of composite outcomes. CONCLUSIONS: The deterioration of diastolic dysfunction and newly development of AF after initiating HD were identified as risk factors for mortality and cardiac complications, supporting the clinical importance of the appropriate management of diastolic dysfunction and AF in patients with ESKD.

A Case Series and Review of Literature Describing the Use of Midodrine for Vasopressor Effects in Infants With Congenital Heart Disease.

Midodrine is an oral vasopressor option that allows for discontinuation of intravenous vasopressors for patients with cardiovascular conditions. It does not have a US Food and Drug Administration-labeled indication for use in children, and there is a paucity of literature in patients ≤6 years of age. This case series describes 2 infants with complex congenital heart diseases initiated on midodrine for augmentation of systolic (SBP) or diastolic blood pressure (DBP) to increase coronary perfusion. Case 1 was initiated on midodrine on hospital day 19 at a dose of 0.5 mg (0.17 mg/kg) enterally every 8 hours that was eventually increased to 1 mg (0.33 mg/kg) every 8 hours. Case 2 was initiated on midodrine on hospital day 15 at a dose of 2.5 mg (0.49 mg/kg) enterally every 8 hours, and this was decreased to 1.25 mg (0.25 mg/kg) every 8 hours due to high SBP. Both patients were discharged home on midodrine; other than the initially high SBP for Case 2, no other adverse drug events were noted. While midodrine was effective based on clinical response in these two infants, additional studies are needed due to the lack of safety and efficacy in children <6 years of age.

PDE9A Inhibition Improves Coronary Microvascular Rarefaction and Left Ventricular Diastolic Dysfunction in the ZSF1 Rat Model of HFpEF.

OBJECTIVE: Heart failure with preserved ejection fraction (HFpEF) commonly arises from comorbid diseases, such as hypertension, obesity, and diabetes mellitus. Selective inhibition of phosphodiesterase 9A (PDE9A) has emerged as a potential therapeutic approach for treating cardiometabolic diseases. Coronary microvascular disease (CMD) is one of the key mechanisms contributing to the development of left ventricular (LV) diastolic dysfunction in HFpEF. Our study aimed to investigate the mechanisms by which PDE9A inhibition could ameliorate CMD and improve LV diastolic function in HFpEF. METHODS AND RESULTS: The obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model of HFpEF was employed in which it was found that a progressively developing coronary microvascular rarefaction is associated with LV diastolic dysfunction when compared to lean, nondiabetic hypertensive controls. Obese ZSF1 rats had an increased cardiac expression of PDE9A. Treatment of obese ZSF1 rats with the selective PDE9A inhibitor, PF04447943 (3 mg/kg/day, oral gavage for 2 weeks), improved coronary microvascular rarefaction and LV diastolic dysfunction, which was accompanied by reduced levels of oxidative and nitrosative stress markers, hydrogen peroxide, and 3-nitrotyrosine. Liquid chromatography-mass spectrometry (LC-MS) proteomic analysis identified peroxiredoxins (PRDX) as downregulated antioxidants in the heart of obese ZSF1 rats, whereas Western immunoblots showed that the protein level of PRDX5 was significantly increased by the PF04447943 treatment. CONCLUSIONS: Thus, in the ZSF1 rat model of human HFpEF, PDE9A inhibition improves coronary vascular rarefaction and LV diastolic dysfunction, demonstrating the usefulness of PDE9A inhibitors in ameliorating CMD and LV diastolic dysfunction through augmenting PRDX-dependent antioxidant mechanisms.