Subclinical leaflet thrombosis after transcatheter aortic valve implantation is associated with silent brain injury on brain magnetic resonance imaging.

AIMS: Whether hypoattenuated leaflet thickening (HALT) following transcatheter aortic valve implantation (TAVI) carries a risk of subclinical brain injury (SBI) is unknown. We investigated whether HALT is associated with SBI detected on magnetic resonance imaging (MRI), and whether post-TAVI SBI impacts the patients' cognition and outcome. METHODS AND RESULTS: We prospectively enrolled 153 patients (age: 78.1 ± 6.3 years; female 44%) who underwent TAVI. Brain MRI was performed shortly post-TAVI and 6 months later to assess the occurrence of acute silent cerebral ischaemic lesions (SCIL) and chronic white matter hyperintensities (WMH). HALT was screened by cardiac computed tomography (CT) angiography (CTA) 6 months post-TAVI. Neurocognitive evaluation was performed before, shortly after and 6 months following TAVI. At 6 months, 115 patients had diagnostic CTA and 10 had HALT. HALT status, baseline, and follow-up MRIs were available in 91 cases. At 6 months, new SCIL was evident in 16%, new WMH in 66%. New WMH was more frequent (100 vs. 62%; P = 0.047) with higher median volume (319 vs. 50 mm3; P = 0.039) among HALT-patients. In uni- and multivariate analysis, HALT was associated with new WMH volume (beta: 0.72; 95%CI: 0.2-1.39; P = 0.009). The patients' cognitive trajectory from pre-TAVI to 6 months showed significant association with the 6-month SCIL volume (beta: -4.69; 95%CI: -9.13 to 0.27; P = 0.038), but was not related to the presence or volume of new WMH. During a 3.1-year follow-up, neither HALT [hazard ratio (HR): 0.86; 95%CI: 0.202-3.687; P = 0.84], nor the related WMH burden (HR: 1.09; 95%CI: 0.701-1.680; P = 0.71) was related with increased mortality. CONCLUSIONS: At 6 months post-TAVI, HALT was linked with greater WMH burden, but did not carry an increased risk of cognitive decline or mortality over a 3.1-year follow-up (NCT02826200).

The Predictive Value of Left Atrial Strain Following Transcatheter Aortic Valve Implantation on Anatomical and Functional Reverse Remodeling in a Multi-Modality Study.

Introduction: Transcatheter aortic valve implantation (TAVI) can improve left ventricular (LV) mechanics and survival. Data on the predictive value of left atrial (LA) strain following TAVI are scarce. We aimed to evaluate the association of LA strain measured shortly post-TAVI with functional and anatomical reverse remodeling of the LA and LV, and its association with mortality. Methods: We prospectively investigated 90 patients who underwent TAVI. Transthoracic echocardiography including strain analysis was performed shortly after TAVI and repeated 6 months later. CT angiography (CTA) was performed for pre-TAVI planning and 6 months post-TAVI. Speckle tracking echocardiography was used to determine LA peak reservoir strain (LASr) and LV global longitudinal strain (LV-GL), LA volume index (LAVi) was measured by TTE. LV mass index (LVMi) was calculated using CTA images. LA reverse remodeling was based on LASr and LAVi changes, whereas LV reverse remodeling was defined as an improvement in LV-GLS or a reduction of LVMi. The association of severely reduced LASr (<20%) at baseline with changes (Δ) in LASr, LAVi, LV-GLS and LVMi were analyzed using linear regression, and Cox proportional hazard model for mortality. Results: Mean LASr and LV-GLS were 17.7 ± 8.4 and -15.3 ± 3.4% at baseline and 20.2 ± 10.2 and -16.6 ± 4.0% at follow-up (p = 0.024 and p < 0.001, respectively). Severely reduced LASr at baseline was associated with more pronounced ΔLASr (ß = 5.24, p = 0.025) and LVMi reduction on follow-up (ß = 5.78, p = 0.036), however, the majority of the patients had <20% LASr on follow-up (44.4%). Also, ΔLASr was associated with ΔLV-GLS (adjusted ß = 2.10, p < 0.001). No significant difference in survival was found between patients with baseline severely reduced LASr (<20%) and higher LASr (≥20%) (p = 0.054). Conclusion: LV reverse remodeling based on LVMi was present even in patients with severely reduced LASr following TAVI, although extensive LA damage based on LA strain was demonstrated by its limited improvement over time. Clinical Trial Registration: (ClinicalTrials.gov number: NCT02826200).

Characteristics of the athlete's heart in aged hypertensive and normotensive subjects.

BACKGROUND: Both hypertension and age-related impairment of the cardiac condition are known to be improved by regular physical training. As relatively few studies have been reported about the older, hypertensive patients, the aim of this study was to establish cardiac benefits of active lifestyle in these subjects. METHODS: Two-dimensionally guided M-mode, Doppler- and tissue Doppler echocardiography was performed in 199 normo- and hypertensive, active and sedentary older (age >60 years) men (N.=111) and women (N.=88). Results were compared either by ANOVA, or by Kruskall-Wallis test. RESULTS: The Left Ventricular Muscle Index (LVMI), which is higher in young active than in sedentary persons, proved to be smaller in the active than sedentary older subjects: men normotensives: actives 83 vs. sedentary ones 98, hypertensives: actives 88 vs. sedentary ones 107, women normotensives: actives 77 vs. sedentary ones 89 g/m3. Diastolic function was better in the active groups demonstrated both by the ratio of the early to atrial peak blood flow velocities (men: normotensives: actives 1.03 vs. sedentary ones 0.76, women normotensives: actives 1.21 vs. sedentary ones 0.9, hypertensives: actives 1.04 vs. sedentary ones 0.88). The tissue Doppler results were also better in the active groups; the difference between the active and sedentary groups was more marked in the normotensive male groups than in the hypertensive ones. CONCLUSIONS: Active lifestyle prevents age-related pathological LV hypertrophy, and attenuates the LV diastolic dysfunction.

Athletic fitness development with electronic monitoring in older adult / Sportolás elektronikus monitorozással idoskorban.

Összefoglaló. Idosebb korban a testgyakorlás különösen fontos az izmok sorvadásának megelozése, valamint a vérnyomás és a testsúly kontrollja céljából. Ma már egyre gyakoribb az idoskorúak részvétele sportversenyeken is. Esettanulmányunk célja a késo felnottkori, illetve idoskori versenyszeru sportolás egészségi alkalmassági feltételeinek, kockázatainak és a teljesítoképesség változásainak bemutatása az elektronikus monitorozás és virtuális versenyzés korában. Esetünkben ez egy idoskorú személy 16 év során (54-70 éves kor) teljesített maratoni futóversenyeinek, valamint virtuális evezoversenyek részvételi és felkészülési adatainak elemzésével valósul meg. Esetünk illusztrálja, hogy az észszeru túlterhelés elve alapján az izmok adaptációja akkor következik be, amikor az edzés terhelése meghaladja az addig már elért terhelési szintet. A sportóra használata az elektronikus pulzusszám és a teljesítmény monitorozásával nemcsak a versenyek és edzések alatt a pulzusszám céltartományban tartására, de hosszabb távú tendenciák felismerésére is hasznosnak bizonyult. Az egészségi állapotnak megfelelo (sportág és intenzitás) idoskori testgyakorlás és sportversenyen való részvétel nemcsak az eronlét megtartását tuzheti ki célul, hanem értékes eronlétfejlesztést is. Orv Hetil. 2021; 162(51): 2061-2066. Summary. With advancing age, exercise becomes particularly important to prevent muscle atrophy and to control blood pressure and weight. Today, participation of aging people in athletic competitions is increasingly common. The aim of our case study is to explore and illustrate the health conditions, development and risk factors of competitive sporting activities of late adult and elderly athletes in the age of electronic monitoring and virtual racing. We processed the preparation and participation data of a total of 16 years of marathon races as well as rowing machine races of an elderly male person (age 54-70). Using a sports watch with electronic heart rate and performance monitoring has proved useful not only for keeping the heart rate in target range, but also for assessing trends in the long run. Our case underscores the value of reasonable overload with advancing age; beneficial muscle adaptation occurs when the workload of an exercise exceeds the previously reached level. Gradual exercise of older adults and participation in athletic competitions can not only maintain fitness but also develop valuable additional strength. Orv Hetil. 2021; 162(51): 2061-2066.

The Impact of COVID-19 on the Preparation for the Tokyo Olympics: A Comprehensive Performance Assessment of Top Swimmers.

BACKGROUND: The Olympic preparation of athletes has been highly influenced by COVID and post-COVID syndrome. As the complex screening of athletes is essential for safe and successful sports, we aimed to repeat the 2019-year sports cardiology screening of the Olympic Swim Team before the Olympics and to compare the results of COVID and non-COVID athletes. METHODS: Patient history, electrocardiogram, laboratory tests, body composition analysis, echocardiography, cardiopulmonary exercise test (CPET) were performed. We used time-ranking points to compare swimming performance. RESULTS: From April 2019, we examined 46 elite swimmers (24 ± 4 years). Fourteen swimmers had COVID infection; all cases were mild. During CPET there was no difference in the performance of COVID (male: VO2 max 55 ± 4 vs. 56.5 ± 5 mL/kg/min, p = 0.53; female: VO2 max 54.6 ± 4 vs. 56 ± 5.5 mL/kg/min, p = 0.86) vs. non-COVID athletes (male VO2 max 56.7 ± 5 vs. 55.5 ± 4.5 mL/kg/min, p = 0.50; female 49.6 ± 3 vs. 50.7 ± 2.6 mL/kg/min, p = 0.47) between 2019 and 2021. When comparing the time results of the National Championships, 54.8% of the athletes showed an improvement (p = 0.75). CONCLUSIONS: COVID infection with short-term detraining did not affect the performance of well-trained swimmers. According to our results, the COVID pandemic did not impair the effectiveness of the preparation for the Tokyo Olympics.

The role of hyaluronic acid binding assay in choosing the fertilization method for patients undergoing IVF for unexplained infertility.

PURPOSE: Patients with unexplained infertility may have fertilization problems. Split fertilization (ICSI and conventional IVF on sibling oocytes) is often used to avoid poor fertilization. Our aim was to assess the ability of hyaluronic acid binding (HA-binding) assay to predict spontaneous fertilization during IVF. METHODS: Prospective, blinded, controlled trial. Patients undergoing their first IVF cycle for unexplained infertility were eligible. Split fertilization was used. IVF and ICSI fertilization rates and embryo development based on 3 HA-binding cut-offs (< 60%; 60-80%; >80%) were compared. RESULTS: ICSI fertilization was higher than IVF, but none of the HA-binding cut-off levels predicted those cases where IVF was less effective, therefore ICSI only would have lead to improved outcome. Embryo development and morphology were similar in all cut-off groups. CONCLUSIONS: HA-binding did not predict spontaneous fertilization in patients with unexplained infertility undergoing IVF treatment. When it was used for "screening" it did not help to select the method of fertilization.

Remodeling of integrated contractile tissues and its dependence on strain-rate amplitude.

Here we investigate the origin of relaxation times governing the mechanical response of an integrated contractile tissue to imposed cyclic changes of length. When strain-rate amplitude is held constant as frequency is varied, fast events are accounted for by actomyosin cross-bridge cycling, but slow events reveal relaxation processes associated with ongoing cytoskeletal length adaptation. Although both relaxation regimes are innately nonlinear, these regimes are unified and their positions along the frequency axis are set by the imposed strain-rate amplitude.

Results with early follicular phase recombinant luteinizing hormone supplementation during stimulation for in vitro fertilization.

OBJECTIVE: To study the effect of early follicular phase recombinant LH supplementation on stimulation outcome among women undergoing IVF using the GnRHa long protocol and recombinant FSH. DESIGN: Randomized, controlled trial. SETTING: Private IVF unit. PATIENT(S): Women under the age of 40 with normal ovarian function undergoing their first or second IVF cycle. INTERVENTION(S): All stimulations followed the standard luteal long GnRHa down-regulation protocol. At suppression, patients in the experimental group received 75 IU of rLH daily for 4 days, and recombinant FSH at a fixed starting dose of 150 IU for the first 5 days was started a day later, on day 2 of rLH. In the control group, patients started rFSH at a fixed dose of 150 IU for the first 5 days at suppression. MAIN OUTCOME MEASURE(S): Baseline, stimulation, embryology parameters, and treatment outcome were compared. Of primary interest, recombinant FSH need during stimulation was assessed. RESULT(S): Stimulation, embryology parameters, and treatment outcome were comparable. The amount of gonadotropins used and medication expense were similar in the two groups. CONCLUSION(S): Early follicular phase recombinant LH supplementation at a daily dose of 75 IU does not improve response to stimulation among normal responder women undergoing IVF.

Bradycardia and B-type natriuretic peptide.

Bradycardia and loss of atrioventricular synchrony can result in increased natriuretic peptide secretion due to increased cardiac wall tension. Antihypertensive beta-blocker therapy has been shown to cause elevated natriuretic peptide levels, as well as to increase the frequency of atrial fibrillation in hypertensive patients. The measurement of natriuretic peptides might help solve the clinical challenge of predicting the patients with high risk for beta-blocker induced atrial fibrillation.

Comparison of serum and follicular fluid hormone levels with recombinant and urinary human chorionic gonadotropin during in vitro fertilization.

OBJECTIVE: To study serum and follicular fluid (FF) hormone levels after the administration of urinary or recombinant hCG to initiate the final stages of oocyte maturation during IVF. DESIGN: Prospective randomized study between 250 microg of recombinant hCG and 7,500 IU of urinary hCG as the final trigger of ovulation during IVF. SETTING: Private IVF center. PATIENT(S): Infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) using the long protocol and recombinant FSH. INTERVENTION(S): IVF treatment. Serum and FF hormone measurements on the day of oocyte collection. MAIN OUTCOME MEASURE(S): Serum and FF E(2), P, hCG, and T levels. RESULT(S): Stimulation parameters, serum and follicular E(2), P, T, and hCG levels were similar in the recombinant and urinary hCG groups. The number of oocytes retrieved from follicles >14 mm, the proportion of mature oocytes, fertilization rate, and pregnancy rate (PR) were also comparable. CONCLUSION(S): Recombinant and urinary hCG provided similar serum and follicular hormonal environments during the final stages of oocyte maturation. The IVF outcome parameters were also comparable. The two medications appear to be equally effective.

Corin is co-expressed with pro-ANP and localized on the cardiomyocyte surface in both zymogen and catalytically active forms.

The multi-domain transmembrane serine protease corin cleaves pro-atrial natriuretic peptide (pro-ANP) in vitro to generate an active hormone, ANP. Corin may also contribute to the regulation of the natriuretic peptide system in vivo, and might be an attractive target for treatment of cardiovascular diseases. In order for corin to cleave its substrate pro-ANP, it should be catalytically active and located proximally. However, because knowledge of native corin is limited, we examined the expression, cardiac localization and molecular forms of the native corin protein. Immunofluorescence studies using a series of anti-corin antibodies directed against the stem and protease domains reveal that corin is present on the cell-surface of rat neonatal cardiomyocytes and murine HL-1 cardiomyocyte-like cells. Furthermore, we immunolocalized native corin in pro-ANP expressing cardiomyocytes. Immunoprecipitation of the membrane fraction of mouse heart extract showed that native corin had a relative mass of 205-210 kDa. Under reducing conditions native corin migrates as several different molecular weight forms corresponding to zymogen (uncleaved) and active (cleaved) forms. Studies using a FITC-tagged chloromethyl ketone that mimics the corin cleavage sequence in pro-ANP, suggest that an enzymatically active form of corin is localized to the cell surface of myocardial cells in vivo. Additionally, we showed that the 205-210 kDa form of corin is a glycosylated protein. Treatment of HL-1 cells with tunicamycin reduced the relative mass of expressed corin. We conclude that native corin is a glycosylated protease that is localized on the cell surface of pro-ANP-expressing cardiomyocytes in both zymogen and catalytically active forms.

Bradycardia can induce increased serum natriuretic peptide-level.

Here we report a case of an elderly woman whose antihypertensive beta-blocker therapy induced sinus arrest with a 40 bpm junctional escape rhythm. Although there was no sign of heart failure during bradycardia, a highly elevated amino-terminal pro-brain natriuretic peptide (NT-proBNP) serum level was detected. Cessation of the beta-blocker agent resulted in normal sinus rhythm and a rapid fall in the NT-proBNP serum level. As a rare phenomenon, bradycardia-related cardiomyopathy is discussed.

Endothelin levels in experimental diabetes combined with cardiac hypertrophy.

Diabetes mellitus is associated with endothelial and cardiac dysfunction, and endothelin has been suggested to alter cardiac function by being a positive inotropic agent, modulating the Frank-Starling response, contracting the coronary arteries and inducing tissue proliferation. We investigated endothelin levels in diabetic and in healthy dogs, 1 and 3 days after placing arteriovenous shunts (8 weeks after diabetes induction) in the femoral regions. Right and left ventricular weight/body weight ratios and Nterminal- atrial natriuretic peptide were increased in shunted animals (P < 0.05). Plasma endothelin levels were comparable in healthy and diabetic dogs. Shunted circulation did not change systemic endothelin levels in healthy dogs but reduced endothelin levels in diabetic dogs. The functional significance of altered endothelin responses to acute hemodynamic burden in experimental diabetes needs further investigation.

Effects of experimental diabetes on endothelin-induced ventricular arrhythmias in dogs.

Endothelin-1 (ET-1) is known to have a direct arrhythmogenic effect in the mammalian heart. Diabetes mellitus is accompanied by a series of endothelial and cardiac disfunctions; however, little is known about ET-1-induced direct arrhythmias in diabetes mellitus. Therefore, we infused ET-1 (33 pmol/min) into the left anterior descending coronary artery of 28 mongrel dogs, and measured basic hemodynamic parameters, coronary flow and an electrocardiogram. Diabetes mellitus was induced by alloxan (Group 4) and experiments were carried out 8 weeks later. Metabolically healthy dogs served as controls (Group 2). In a further control group, local hyperglycemia was induced by intracoronary glucose infusion (Group 3). ET-1 infusion induced prolongation of the QT-time and frequency-adjusted QT-time in all groups. Other electrophysiological parameters were comparable between the groups. This was followed by the occurence of ventricular premature beats, coupled extra-beats and later sustained ventricular tachycardia. Most of the experiments were terminated by ventricular fibrillation. The onset of arrhythmias was shorter in diabetic dogs as compared with control and locally hyperglycemic animals (18 +/- 8 minutes versus 24 +/- 8 minutes and 30 +/- 28 minutes, P < 0.05). However, there was no difference in the number of ventricular fibrillations, and the total elapsed time until the termination of the experiments. Therefore, the diabetic heart seems to be more prone to ET-1-induced arrhythmias and this is probably not a result of locally high glucose concentrations.