BACKGROUND: During the COVID-19 pandemic sex-related differences concerning the spectrum of cardiovascular complications have been observed in the acute infection, and during recovery. This study aims to emphasize sex-related disparities regarding left ventricular systolic function (LVSF), right ventricular function (RVF), diastolic dysfunction (DD), and pericardial pathologies during the post-COVID-19 syndrome.
METHODS: 274 patients with post-acute COVID-19 syndrome, 127 men and 147 women, aged under 55, were evaluated within 90 days after the acute illness and followed at 3 and 6 months.
RESULTS: Based on detailed transthoracic echocardiography (TTE), we identified significantly more frequently (p˂0.001) altered LVSF in men, while in women impaired RVF, and DD were significantly more common (p˂0.001). Pericardial impairment did not seem to be influenced by gender. The TTE parameters characterizing these patterns were correlated with the severity of the initial infection and the time elapsed since and alleviated in time. The multivariate regression analysis confirmed these sex-related associations and their impact on patients\' functional status.
CONCLUSIONS: Male patients had a higher tendency to develop altered LVSF, while female subjects had more frequently impaired RVF and DD. These abnormalities alleviated in time and exerted a significant influence on patients\' functional status.

BACKGROUND: The left atrial assist device (LAAD) is a novel continuous-flow pump designed to treat patients with heart failure with preserved ejection fraction, a growing type of heart failure, but with limited device-treatment options. The LAAD is implanted in the mitral plane and pumps blood from the left atrium into the left ventricle. The purpose of this study was to refine the initial design of the LAAD, using results from computational fluid dynamics (CFD) analyses to inform changes that could improve hydraulic performance and flow patterns within the LAAD.
METHODS: The initial design and three variations were simulated, exploring changes to the primary impeller blades, the housing shape, and the number, size, and curvature of the diffuser vanes. Several pump rotational speeds and flow rates spanning the intended range of use were modeled.
RESULTS: Guided by the insight gained from each design iteration, the final design incorporated impeller blades with improved alignment relative to the incoming flow and wider, more curved diffuser vanes that better aligned with the approaching flow from the volute. These design adjustments reduced flow separation within the impeller and diffuser regions. In vitro testing confirmed the CFD predicted improvement in the hydraulic performance of the revised LAAD flow path design.
CONCLUSIONS: The CFD results from this study provided insight into the key pump design-related parameters that can be adjusted to improve the LAAD\'s hydraulic performance and internal flow patterns. This work also provided a foundation for future studies assessing the LAAD\'s biocompatibility under clinical conditions.

OBJECTIVE: Echocardiographic diastolic parameters are used to diagnose and monitor increased left ventricular filling pressure (LVFP) and we hypothesized that increased loading conditions cause increased E/e\'. Our aim was to assess the effect of preload augmentation on diastolic parameters among both healthy subjects and subjects with known cardiac disease.
RESULTS: We included 129 subjects merged from two cohorts; one dialysis cohort (n = 47) and one infusion cohort (n = 82). Echocardiography was performed immediately before and after hemodialysis (HD) or saline infusion, under low and high loading conditions. Elevated LVFP was defined as septal E/e\' ≥ 15 and/or lateral E/e\' ≥ 13 at high-loading conditions. The population was divided according to elevated LVFP (n = 31) and normal LVFP (n = 98). The load difference for the population was 972 ± 460 mL, with no differences in load difference between elevated and normal LVFP (p NS). The subjects with elevated LVFP were older (63 ± 11 vs. 46 ± 16 years, p < .001), and had lower LV ejection fraction (50 ± 14 vs. 59 ± 8.1%, p < .01). After augmented preload, EDV increased in the normal LVFP group (p < .01) but remained unchanged in the elevated LVFP group (p NS). Both E and e\' increased among the subjects with normal LVFP, whereas E/e\' remained unchanged (∆E/e\' +.1 [-.5-1.2]), p NS). Among the subjects with elevated, LVFP we observed increased E but not e\', resulting in significantly increased E/e\' (∆ average E/e\' +2.4 [0-4.0], p < .01).
CONCLUSIONS: Augmented preload does not seem to affect E/e\' among subjects with normal LVFP, whereas E/e\' seems to increase significantly among subjects with elevated LVFP.

The evaluation of the left atrial (LA) size using the LA volume index (LAVI) is clinically relevant due to its prognostic significance in various conditions. Nonetheless, adding a LA function assessment to the LAVI provides further clinical and prognostic information in different cardiovascular (CV) diseases. The assessment of LA function by echocardiography primarily includes volumetric measurements (LA ejection fraction [LAEF]), tissue Doppler imaging (TDI) (mitral annular late diastolic velocity [a\']), and speckle-tracking methods, such as LA longitudinal reservoir strain (LA strain). This review analyzes and discusses the current medical evidence and potential clinical usefulness of these different methods to analyze LA function.

A hypertensive response to exercise is a precursor leading to hypertension, which is a major risk factor for the development of heart failure and diastolic dysfunction. Herein, we aimed to assess blood pressure (BP) in patients with a hypertensive response to exercise and different degrees of diastolic dysfunction. Between January 2009 and December 2014, 373 patients with a hypertensive response to exercise (HRE) and echocardiographic data assessing diastolic function were enrolled at the University Hospital of Zurich. ANCOVA was used to assess the changes in BP response during exercise testing in individuals with different degrees of diastolic dysfunction. Normalization of systolic BP was blunted in patients with grade II and III diastolic dysfunction after 3 min of recovery in univariable [β (95%) - 9.2 (-13.8 to - 4.8) p < .001, -16.0 (-23.0 to 9.0) p < .001, respectively] and adjusted models. In fully adjusted models, when taking maximal effort into account, there were no differences with regard to systolic BP during exercise. Patients without diastolic dysfunction achieved higher heart rates (HRs) [both in absolute terms (p < .001) and as a percentage of the calculated maximum (p = .003)] and greater wattage (p < .001) at maximum exertion. The findings of this cross-sectional study suggest that exercise capacity is compromised in patients with diastolic dysfunction. A hypertensive response to exercise and the finding of a blunted BP recovery may help identify patients at risk of developing heart failure.

Population studies report elevated incidence of cardiovascular events in patients with chronic epilepsy. Multiple pathophysiologic processes have been implicated, including accelerated atherosclerosis, myocardial infarction, altered autonomic tone, heart failure, atrial and ventricular arrhythmias, and hyperlipidemia. These deleterious influences on the cardiovascular system have been attributed to seizure-induced surges in catecholamines and hypoxemic damage to the heart and coronary vasculature. Certain antiseizure medications can accelerate heart disease through enzyme-inducing increases in plasma lipids and/or increasing risk for life-threatening ventricular arrhythmias as a result of sodium channel blockade. In this review, we propose that this suite of pathophysiologic processes constitutes \"The Epileptic Heart Syndrome.\" We further propose that this condition can be diagnosed using standard electrocardiography, echocardiography, and lipid panels. The ultimate goal of this syndromic approach is to evaluate cardiac risk in patients with chronic epilepsy and to promote improved diagnostic strategies to reduce premature cardiac death.

BACKGROUND: Septic cardiomyopathy (SCM) with diastolic dysfunction carries a poor prognosis, and the mechanisms underlying the development of diastolic dysfunction remain unclear. Matrix metalloproteinase-8 (MMP-8) is released from neutrophils and degrades collagen I. MMP-8 levels correlate with SCM severity.
OBJECTIVE: We scrutinized, for the first time, the direct impact of MMP-8 on cardiac systolic and diastolic functions.
METHODS: Isolated rat hearts were perfused with Krebs-Henseleit solution in a Langendorff setup with computer-controlled filling pressures of both ventricles at isovolumetric regime. The end-diastolic pressure (EDP) varied periodically between 3 and 20 mmHg. After baseline recordings, MMP-8 (100 µg/ml) was added to the perfusion. Short-axis views of both ventricles were continuously acquired by echocardiography.
RESULTS: MMP-8 perfusion resulted in progressive decline in peak systolic pressures (Psys) in both ventricles, but without significant changes in their end-systolic pressure-area relationships (ESPARs). Counterintuitively, conspicuous leftward shifts of the end-diastolic pressure-area relationships (EDPARs) were observed in both ventricles. The LV end-diastolic area (EDA) decreased by 32.8±5.7%, (p=0.008), at EDP of 10.5±0.4 mmHg, when LV Psys dropped by 20%. The decline of Psys was primarily due to the decrease in EDA and restoring the baseline EDA by increasing EDP recovered 81.33 ± 5.87% of the pressure drops.
CONCLUSIONS: Collagen I generates tensile (eccentric) stress, and its degradation by MMP-8 causes EDPVR leftward shift, resulting in diastolic and systolic dysfunctions. The diastolic dysfunction explains the clinically observed fluid unresponsiveness, while the decrease in EDV diminishes the systolic functions. MMP-8 can explain the development of SCM with diastolic dysfunction.

OBJECTIVE: Cardiac diastolic dysfunction (left ventricular diastolic dysfunction [LVDD]) is a well-known predictor of heart failure. We hypothesized that sarcopenia is independently associated with diastolic dysfunction. We aimed to investigate the association of the most recent consensus definition of sarcopenia with LVDD.
METHODS: We included 121 older participants admitted to a cardiology outpatient clinic. We followed the European Working Group on Sarcopenia in Older People 2 definition of confirmed sarcopenia (presence of low muscle mass and low muscle strength). We estimated skeletal muscle mass with bioimpedance analysis and muscle strength by hand grip strength via a Jamar hydraulic hand dynamometer. Skeletal muscle mass was adjusted by body mass index. LVDD was determined by echocardiographic parameters measured per American Society of Echocardiography recommendations. We ran multivariate logistic regression analyses adjusted for well-known risk factors for diastolic dysfunction (i.e., age, sex, obesity, smoking, diabetes mellitus, hypertension, and ischemic heart disease) to detect whether sarcopenia was independently associated with diastolic dysfunction. We gave results in odds ratio (OR) and 95% confidence interval (CI).
RESULTS: Mean age was 69.9 ± 5.8 years, and 38.8% of participants were male. Confirmed sarcopenia was detected in 34.7%, and diastolic dysfunction was detected in 19.8%. In univariate analyses, sarcopenia was associated with diastolic dysfunction (OR, 6.7, 95% CI, 2.4-18.9). Regression analyses showed that two parameters, sarcopenia (OR, 7.4, 95% CI, 2.1-26.6, P = 0.002) and obesity (OR, 5.0, 95% CI, 1.03-24.6, P = 0.046), were associated with diastolic dysfunction.
CONCLUSIONS: This study revealed sarcopenia to be a new risk factor for diastolic dysfunction, adding to its known risk factors. Future longitudinal studies are needed to clarify the factors underlying their copresence.

Growth differentiation factor 15 (GDF15) is a peptide with utility in obesity, as it decreases appetite and promotes weight loss. Because obesity increases the risk for type 2 diabetes (T2D) and cardiovascular disease, it is imperative to understand the cardiovascular actions of GDF15, especially since elevated GDF15 levels are an established biomarker for heart failure. As weight loss should be encouraged in the early stages of obesity-related prediabetes/T2D, where diabetic cardiomyopathy is often present, we assessed whether treatment with GDF15 influences its pathology. We observed that GDF15 treatment alleviates diastolic dysfunction in mice with T2D independent of weight loss. This cardioprotection was associated with a reduction in cardiac inflammation, which was likely mediated via indirect actions, as direct treatment of adult mouse cardiomyocytes and differentiated THP-1 human macrophages with GDF15 failed to alleviate lipopolysaccharide-induced inflammation. Therapeutic manipulation of GDF15 action may thus have utility for both obesity and diabetic cardiomyopathy.

OBJECTIVE: This study investigates the prevalence and prognostic impact of diastolic dysfunction (DD) in patients hospitalized with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) in sinus rhythm.
BACKGROUND: Data regarding the prognostic impact of DD in patients with HFmrEF is limited.
METHODS: From 2016 to 2022, all patients hospitalized with HFmrEF (i.e., left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution. Patients with DD were compared to patients without (i.e., non-DD), further risk stratification was performed according to the severity of DD. The primary endpoint was all-cause mortality at 30 months (interquartile range (IQR) 15-61 months), key secondary endpoint was rehospitalization for worsening HF.
RESULTS: From a total of 1154 patients (median age 68 years, 68% males) hospitalized with HFmrEF, concomitant DD was present in 72% (grade I: 56%, grade II: 14%, grade III: 2%). Patients with DD were older (71 years vs. 65 years; p = 0.001) and presented with higher rates of cardiovascular comorbidities. The presence of DD was not associated with the risk of long-term all-cause mortality (adjusted HR = 0.815; 95% CI 0.612-1.085; p = 0.161) or HF-related rehospitalization (adjusted HR = 0.736; 95% CI 0.442-1.225; p = 0.238). Furthermore, the outcome did not differ in patients with more advanced stages of DD.
CONCLUSIONS: DD is commonly prevalent in patients with HFmrEF, but not associated with long-term prognosis.