Follow-up assessment of the microvascular function in patients with long COVID.

Long COVID is a complex pathophysiological condition. However, accumulating data suggests that COVID-19 is a systemic microvascular endothelial dysfunction with different clinical manifestations. In this study, a microvascular function was assessed in long COVID patients (n = 33) and healthy controls (n = 30) using flow-mediated skin fluorescence technique (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Microcirculatory function readings were taken twice, 3 months apart. In addition, we quantified biochemical markers such as the serum L-arginine derivatives and hypoxia-inducible factor 1α (HIF1α) to assess their relation with microvascular parameters evaluated in vivo. In patients with long COVID, serum HIF1α was significantly correlated to IRindex (r = -0.375, p < 0.05). Similarly, there was a significant inverse correlation of serum asymmetric dimethyl-L-arginine levels to both HRmax (r = -0.343, p < 0.05) and HRindex (r = -0.335, p < 0.05). The IR parameters were found lower or negative in long COVID patients and recovered in three-month follow-up. Hypoxia sensitivity value was significantly higher in long COVID patients examined after three months of treatment based on the combination of ACE-inhibitors and beta-adrenolytic compared to baseline condition (85.2 ± 73.8 vs. 39.9 ± 51.7 respectively, p = 0.009). This study provides evidence that FMSF is a sensitive, non-invasive technique to track changes in microvascular function that was impaired in long COVID and recovered after 3 months, especially in patients receiving a cardioprotective therapy.

Left Ventricular Function and Iron Loading Status in a Tertiary Center Hemochromatosis Cohort-A Cardiac Magnetic Resonance Study.

Background: Haemochromatosis (HCH), a common genetic disorder with variable penetrance, results in progressive but understudied iron overload. We prospectively evaluated organ iron loading and cardiac function in a tertiary center HCH cohort. Methods: 42 HCH patients (47 ± 14 years) and 36 controls underwent laboratory workup and cardiac magnetic resonance (CMR), including T1 and T2* mapping. Results: Myocardial T2* (myoT2*), myocardial T1 (myoT1) and liver T2* (livT2*) were lower in patients compared to controls (33 ± 4 ms vs. 36 ± 3 ms [p = 0.004], 964 ± 33 ms vs. 979 ± 25 ms [p = 0.028] and 21 ± 10 ms vs. 30 ± 5 ms [p < 0.001], respectively). MyoT2* did not reach the threshold of clinically significant iron overload (<20 ms), in any of the patients. In 22 (52.4%) patients, at least one of the tissue parameters was reduced. Reduced myocardial T2* and/or T1 were found in 10 (23.8%) patients, including 4 pts with normal livT2*. LivT2* was reduced in 18 (42.9%) patients. MyoT1 and livT2* inversely correlated with ferritin (rs = −0.351 [p = 0.028] and rs = −0.602 [p < 0.001], respectively). LivT2* by a dedicated sequence and livT2* by cardiac T2* mapping showed good agreement (ICC = 0.876 p < 0.001). Conclusions: In contemporary hemochromatosis, significant myocardial iron overload is rare. Low myocardial T2* and/or T1 values may warrant closer follow-up for accelerated myocardial iron overload even in patients without overt liver overload. Cardiac T2* mapping sequence allows for liver screening at the time of CMR.

Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data.

BACKGROUND: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH). METHODS: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab). RESULTS: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia. CONCLUSIONS: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment.

Chronographic Imprint of Age-Induced Alterations in Heart Rate Dynamical Organization.

Beat-to-beat changes in the heart period are transformed into a network of increments between subsequent RR-intervals, which enables graphical descriptions of short-term heart period variability. Three types of such descriptions are considered: (1) network graphs arising from a set of vertices and directed edges, (2) contour plots of adjacency matrices A, representing the networks and transition matrices T, resulting from A, and (3) vector plots of gradients of the matrices A and T. Two indices are considered which summarize properties of A and T: the approximate deceleration capacity and the entropy rate. The method, applied to time series of nocturnal RR-intervals recorded from healthy subjects of different ages, reveals important aspect of changes in the autonomic activity caused by biological aging. Independent of the subject's age, following accelerations, a pendulum-like dynamics appears. With decelerations, this dynamics develops in line with the subject's age. This aging transition can be graphically visualized by vectors connecting the maxima of the transition probabilities of T, which, metaphorically, resemble a chronometer or the hands of a clock.

Aging in autonomic control by multifractal studies of cardiac interbeat intervals in the VLF band.

The heart rate responds dynamically to various intrinsic and environmental stimuli. The autonomic nervous system is said to play a major role in this response. Multifractal analysis offers a novel method to assess the response of cardiac interbeat intervals. Twenty-four hour ECG recordings of RR interbeat intervals (of 48 elderly volunteers (age 65-94), 40 middle-aged persons (age 45-53) and 36 young adults (age 18-26)) were investigated to study the effect of aging on autonomic regulation during normal activity in healthy adults. Heart RR-interval variability in the very low frequency (VLF) band (32-420 RR intervals) was evaluated by multifractal tools. The nocturnal and diurnal signals of 6 h duration were studied separately. For each signal, the analysis was performed twice: for a given signal and for the integrated signal. A multifractal spectrum was quantified by the h(max) value at which a multifractal spectrum attained its maximum, width of a spectrum, Hurst exponent, extreme events h(left) and distance between the maxima of a signal and its integrated counterpart. The following seven characteristics are suggested as quantifying the age-related decrease in the autonomic function ('int' refers to the integrated signal): (a) h(sleep)(max) - h(max)(wake) > 0.05 for a signal; (b) h(int)(max) > 1.15 for wake; (c) h(int)(max) - h(max) > 0.85 for sleep; (d) Hurst(wake) - Hurst(sleep) < 0.01; (e) width(wake) > 0.07; (f) width(int) < 0.30 for sleep; (g) h(int)(left) > 0.75. Eighty-one percent of elderly people had at least four of these properties, and ninety-two percent of young people had three or less. This shows that the multifractal approach offers a concise and reliable index of healthy aging for each individual. Additionally, the applied method yielded insights into dynamical changes in the autonomic regulation due to the circadian cycle and aging. Our observations support the hypothesis that imbalance in the autonomic control due to healthy aging could be related to changes emerging from the vagal function (Struzik et al 2006 IEEE Trans. Biomed. Eng. 53 89-94).