Is Cardiomegaly an Indication of “Heart-Sparing Effect” in Small Fetuses?

<b><i>Introduction:</i></b> This study aimed to test the hypothesis that cardiac size is maintained in small fetuses presenting with cardiomegaly. <b><i>Materials and Methods:</i></b> We identified singleton fetuses with estimated fetal weight &#x3c;10th centile and with cardiomegaly without another more likely cardiac or extra-cardiac cause. We used <i>Z</i>-scores for cardiac and thoracic circumferences normalized for gestational age (GA), biparietal diameter (BPD), head circumference (HC), and femur length (FL), obtained from 188 normally grown fetuses. <b><i>Results:</i></b> When comparing chest size, small fetuses had significantly lower thoracic circumferences median <i>Z</i>-scores (IQR) for GA = −4.82 (−6.15 to −3.51), BPD = −2.42 (−4.04 to −1.48), HC = −2.72 (−4.53 to −1.90), and FL = −1.60 (−2.87 to −0.71); <i>p</i> &#x3c; 0.001 for all. When comparing heart size, small fetuses showed lower cardiac circumferences median <i>Z</i>-scores (IQR) for GA = −1.59 (−2.79 to −0.16); <i>p</i> &#x3c; 0.001, similar cardiac circumferences <i>Z</i>-scores for BPD = 0.29 (−0.65 to 1.28); <i>p</i> = 0.284 and HC = 0.11 (−1.13 to 0.96); <i>p</i> = 0.953, and higher cardiac circumferences <i>Z</i>-scores for FL = 0.94 (−0.05 to 2.13); <i>p</i> &#x3c; 0.001. <b><i>Conclusions:</i></b> Our results show that in small fetuses with cardiomegaly, the heart maintains normal dimensions when normalized to cranial diameters and higher dimensions when normalized to long bones. This provides insight into cardiac adaptation to adverse intrauterine environment.

Jobb kamrai adaptáció pulmonalis artériás hypertoniában

Összefoglaló. Pulmonalis artériás hypertoniában (PAH) a tüdőartériák falának átépülése az elsődleges patofiziológiai eltérés, amely a pulmonalis vascularis rezisztencia (PVR) és a pulmonalis nyomás progresszív emelkedéséhez vezet. Ez a nyomásemelkedés a jobb szívfélben az afterload fokozódásához vezet, ami hosszú távon jobbkamra-diszfunkciót és jobbszívfél-elégtelenséget okoz. Az egyre növekvő PVR mellett kialakuló cardialis adaptáció pontos patomechanizmusa nem ismert, de egyes betegek esetén nagyon eltérő lehet az adaptáció mértéke és kialakulásának üteme. A kialakuló myocardium-hypertrophia és -dilatáció mértéke nagyban függ a PAH etiológiájától, de emellett egyéb tényezők – mint az életkor, a neurohumoralis aktiváció mértéke, genetikai és epigenetikai faktorok – is jelentősen befolyásolják. Minél kevésbé képes a jobb kamra megtartani funkcióját az egyre növekvő ellenállással szemben, annál gyorsabban alakul ki a jobbszívfél-elégtelenség, és annál rosszabbak a beteg életkilátásai. Ezen folyamatok jobb megismerése klinikai jelentőséggel bír, mivel a jobb kamrai adaptáció elősegítése javíthatja a betegség kimenetelét. Orv Hetil. 2021; 162(37): 1485–1493. Summary. Remodeling of the pulmonary artery wall is the primary pathophysiological abnormality in pulmonary arterial hypertension leading to a progressive increase in pulmonary vascular resistance (PVR) and pulmonary arterial pressure. The elevation of pressure increases the afterload in the right heart, causing right ventricular dysfunction and right heart failure in the long term. The exact pathomechanism of cardiac adaptation with increasing PVR is unknown, but the degree and rate of adaptation may be very different in patients suffering from pulmonary hypertension. The development of myocardial hypertrophy and dilatation is highly dependent on the etiology of pulmonary hypertension, but is also significantly influenced by other factors such as age, degree of neurohumoral activation, and genetic and epigenetic factors. Right heart failure develops and life expectancy shortens if the right ventricle is unable to maintain its function in the face of increasing resistance. Orv Hetil. 2021; 162(37): 1485–1493.

Abstract 107: Selective Igf-1 Production By Resident Cardiac Macrophages Orchestrates Adaptive Cardiomyocyte Growth During Hypertensive Stress

Objective: Adaptive cardiomyocyte growth is an essential compensatory response to hypertension. While hypertension activates cardiac immune cells, their role in adaptation is unclear. Here, we define the transcriptional heterogeneity and functional role of cardiac resident macrophages (RMs) in vivo in hypertensive heart disease. Methods: We performed flow cytometry, immunofluorescence, and single-cell transcriptomics on fate-mapped cardiac RMs isolated from mice with angiotensin II infusion in acute (day 4) and chronic hypertensive stress (day 28). Following inducible depletion of RMs or specific genetic deletion of Igf1 in RMs during hypertension in mice, functional outcomes were tested with echocardiography and immunohistochemistry. Lastly, we also performed single-cell RNA sequencing on human cardiac macrophages from healthy and diseased samples. Results: Cardiac RMs possess numerous transcriptionally diverse cell states with a core repertoire of reparative gene programs that includes high expression of Igf1 in normotensive animals. Individual cell states were differentially responsive during hypertension while all maintained their original transcriptional identity. Hypertension drove selective in situ proliferation and numerical expansion of some cardiac RMs, directly correlating with increased cardiomyocyte size. Inducible ablation of RMs, or selective deletion of RM-derived IGF-1 caused complete absence of adaptive cardiomyocyte growth and development of cardiac dysfunction. Single-cell transcriptomics further identified a conserved IGF1 -expressing macrophage subpopulation in human cardiomyopathy. Conclusions: Here, we defined the absolute requirement of cardiac RM-produced IGF-1 in adaptive cardiomyocyte growth during hypertension, identifying a novel and essential pathway of RM-directed cardiac adaptation to disease.

Maternal diabetes and fetal cardiac output

BACKGROUND: The intrauterine environment is a key determinant for long-term health outcomes. Adverse fetal environments, such as maternal diabetes, obesity and placental insufficiency are strongly associated with long-term health risks in children. Little is known about differences in fetal cardiac output hemodynamics of diabetic mothers (DM) vs. non-diabetic mothers (NDM). Our study aims to investigate the left-sided, right-sided, and combined cardiac output (CCO) in fetuses of DM vs. NDM. METHODS: Retrospective data were collected in fetuses of DM (N = 532) and NDM (103) at mean gestational age 24 weeks. Examination included 2D echo and pulse wave Doppler. Wilcoxon rank sum tests and Chi-square tests were used to test for distribution difference of maternal and fetal continuous and categorical measures respectively between DM and NDM. Intraclass correlation coefficients were calculated to assess intra-observer reliability of fetal cardiac measurements. RESULTS: DM mothers had higher mean weight (89.7±22.2 kg) than NDM (76.8±19.8 kg), p < 0.0001 and higher mean BMI (33.4±7.5) than NDM (28.3±5.8), p < 0.0001. C-section delivery occurred in 66% of DM vs. 35% of NDM fetuses. Fetuses of DM mothers had significantly larger semilunar valve diameter, higher left ventricular (LV) output, higher combined cardiac output and lower right ventricle /left ventricle ratio compared to NDM. CONCLUSION: The greater CCO (adjusted for fetal weight), left sided cardiac output in the fetuses of DM, compared to NDM, represent differences in cardiac adaptation to the diabetic environment.

Influencing Factors of Cardiac Adaptation in Adolescent Athletes

Endurance training-induced changes in left ventricular diastolic function and right ventricular parameters have been investigated extensively in adolescent athletes. Our aim was to examine the parameters for adolescent athletes (n=121, 15.1±1.6 years) compared to adult athletes and age-matched non-athletes. We explored the effects of influencing factors on the echocardiographic parameters. Significantly higher E/A (p<0.05) and e’ values (p<0.001) were detected in adolescent athletes compared to age-matched non-athletes’ and also adult athletes’ parameters. Significantly lower structural and functional right ventricular parameters (p<0.05) were detected in adult athletes. In adolescent athletes significantly higher right ventricular diameters, tricuspid S wave, right ventricular end-diastolic and end-systolic area values (p<0.05) were found compared to the matching parameters of non-athletes. We found significantly higher corrected tricuspid annular plane systolic excursion values (p<0.001) in athletes compared to the non-athletes. Based on multivariate analysis lean body mass, body surface area, age and cumulative training time were proved as strong predictive factors of both left ventricular diastolic and right ventricular parameters. Supernormal left ventricular diastolic function and significantly higher right ventricular parameters are indicative of cardiac adaptation. Well-defined cut-off values should be applied to discriminate pathological conditions in the relation of the influencing factors.

Electrocardiographic Changes in Male and Female Amateur Marathon Runners: A Comparison Study

Physical training is gaining popularity among amateurs. Males and females exhibit different cardiac adaptation to exercise. The aim of the study was to compare the incidence of electrocardiographic abnormalities before and after the marathon between sexes. 12-lead electrocardiogram was performed in 40 male (39±8 years) and 27 female (40±7 years) amateur runners: 2–3 weeks before (Stage 1) and immediately after (Stage 2) the marathon. Abnormalities in the resting (Stage 1) and exercise (Stage 2) electrocardiograms were compared between sexes. At rest left atrial enlargement was more frequent in females than males (48 vs. 20%; p<0.05). The incidence of right atrial enlargement was significantly more common at Stage 2 than 1, both in men (43 vs. 0%; p<0.001) and in women (48 vs. 4%; p=0.001). Significant increase of P-wave amplitude was found in male runners after the marathon (0.12±0.05 vs. 0.21±0.09 mV; p<0.001 Stage 1 vs. 2), but was absent in females. QTc prolongation was observed in both sexes, however to a higher degree in males (p<0.05 for the interaction stage and sex). Although both male and female amateur marathon runners exhibit abnormalities in resting and exercise electrocardiograms, men present more exercise-induced electrocardiographic changes, which might indicate a higher propensity for post-marathon arrhythmias. Electrocardiographic screening in amateurs should be considered.