Press Release: Hearts Electrical Signals Alters in First Pig-to-Human Cardiac Transplant

Posted on November 03, 2022 by Admin

A recent study at the American Heart Association (AHA) Scientific Sessions 2022* revealed unexpected changes in the electrical conduction system of the first genetically-modified porcine-to-human heart xenotransplant.

Xenotransplantation is the procedure of transplantation/implantation into a human of organs from non-human animal sources. The first pig-to-human heart xenograft was transplanted in January 2022 at the University of Maryland. The recipient survived for 61 days after receiving the xenograft. Research efforts have been underway for this xenotransplantation for over three decades.

Harvesting genetically-modified porcine hearts, the genes of which have been altered for safe transplantation into humans, would become a reality if successful. However, xenotransplantation of organs into a human carries several inherent challenges. With these transplant procedures, there is always the risk of graft rejection, infection, and abnormal heart rhythms.

Study and Results

In the present study, researchers performed a 12-lead electrocardiogram (ECG) during the postoperative period of the patient who underwent the first pig-to-human heart transplantation. The ECG data were obtained every day after the xenotransplantation. The researchers reviewed the following ECG measures: PR interval, QRS complex, and QT interval.

The ECG parameters of the “accepted pig heart transplant in the ‘pig body’” show short PR (50 to 10 milliseconds, ms) and QT (260 to 380 ms) intervals and short QRS (70 to 90 ms). However, the first ECG of the pig-to-human heart xenotransplant showed a relatively longer PR interval of 190 ms, QT interval of 538 ms, and QRS duration of 138 ms.

Prolonged intrinsic PR intervals were stable in the postoperative period with 210 ms. There was evidence of decremental intra-atrial conduction delay on day 12 post-transplantation (PR interval: 380 ms). QRS duration was prolonged but shortened in the postoperative course. High QT intervals (509 ms) persisted with dynamic fluctuations, with the lowest (428 ms) on day 14 post-transplantation.

Conclusion

The ECG of the pig-to-human xenograft revealed prolongation of the typical ECG measures in the donor that included changes in depolarization and repolarization. It was a novel finding that the pig heart in the human showed different ECG parameters compared to the commonly observed findings for native pig hearts.

The protracted ECG parameters persisted and showed dynamic changes in the postoperative period. These are the first insights into the evolving novel field of xenografts suggesting the complex interplay of porcine denervation and inter-species physiology besides the postoperative and medication-associated changes.

Source:

https://www.news-medical.net/news/20221101/First-pig-to-human-cardiac-transplant-alters-hearts-electrical-signals.aspx

Press Release: Between Chronic Diseases and Heart Failure Risk Shared Genetic Etiology

Posted on August 14, 2023 by Admin

Researchers performed a prospective cohort study to investigate the shared genetic etiology between chronic diseases, such as cardiovascular diseases (CVDs), asthma, rheumatoid arthritis (RA), and pathogenesis of heart failure (HF) and whether leukocyte telomere length (LTL), a biomarker of biological aging, modified these relationships.

They performed all study analyses on the clinical and genetic data of a cohort of 404,883 European participants from the United Kingdom (UK) Biobank.

Study

In the present study, researchers used a multi-step approach to explore the associations between genetic susceptibility to chronic diseases, LTL, and HF risk in the UK Biobank data of 404,883 European participants, of which 9,989 were incident HF cases, as observed through the 12.3-year follow-up.

To this end, they first used multivariable Cox regression to prospectively evaluate the associations between 24 previously derived cancer-, inflammation-, and CVD-related polygenic risk scores (PRSs) and future HF risk.

Next, the team used quantitative polymerase chain reaction (qPCR) to investigate how the identified PRSs interacted with measured LTL to modify HF risk. They further analyzed PRSs showing multiplicative interactions with LTL, stratified by LTL quartiles.

Additionally, they evaluated measured associations between LTL and 24 PRSs to determine qualitatively overlapping results with the PRS-HF analyses. Finally, the researchers pursued evidence of the effect of altered LTL (reflecting the aging process) on significant PRSs of HF risk. Mediation analyses helped them estimate the PRSs acting indirectly through LTL.

Findings

The researchers identified nine PRSs associated with HF risk, including those for various CVDs, RA, and asthma, in a dose-dependent manner. Increased genetic susceptibility to asthma was markedly associated with increased HF risk (P=1.8E-08).

In agreement with previous analyses, they also found evidence that longer phenotypic LTL mediated and strengthened the positive association between asthma genetic susceptibility and HF risk independent of the PRSs. They attributed its role as an effect modifier to the environmentally-determined LTL components (not genetic components). Thus, future studies should incorporate LTL and genetic data into risk stratification analyses.

Intriguingly, the asthma PRS exhibited a super-multiplicative interaction with LTL even though phenotypic LTL was inversely associated with HF. However, LTL mediated 1.13% of the total effect of the asthma PRS on HF risk.

Nonetheless, the study findings reinstate the notion that there is a link between pulmonary diseases, cardiac function, and inflammation. Future studies should elucidate the molecular mechanisms by which LTL exerts its effects and the nature of biological interactions between PRSs and LTL components.

Furthermore, the authors noted a significant overlap between the PRSs for asthma, CVD, CAD, ischemic stroke (ISS) and associations identified in the PRS-HF analyses, indicating potential associations between genetic susceptibility to cardiovascular and pulmonary diseases, phenotypic LTL, and future HF risk.

Conclusion

To summarize, the researchers discovered a high-risk subpopulation for HF comprising people with longer LTL and increased genetic susceptibility to asthma.

The study also highlighted that non-malignant respiratory diseases and LTLs act as effect modifiers in the pathogenesis of HF, a fatal downstream consequence of cardiac dysfunction with a mortality rate as high as some cancers.

Thus, future studies should further investigate the role of LTL and genetics in future HF risk stratification analyses.

Source:

https://www.news-medical.net/news/20230810/Study-examines-shared-genetic-etiology-of-chronic-diseases-and-links-leukocyte-telomere-length-to-heart-failure-risk.aspx

Press Release: In Lowering Heart Disease Risk Mediterranean Diet with a Dairy Twist Shows Promising Results

Posted on September 04, 2023 by Admin

A recent study evaluated how the combination of Mediterranean diet (MedDiet) supplement and dairy foods affected the gut microbiome in Australians at a high risk of cardiovascular disease (CVD).

Study

The current randomized controlled trial (RCT) followed a 2 × 2 cross-over design to compare the benefits of MedDiet supplemented with dairy food (MedDairy) and low-fat (LFD) diet (control) in Australians at high risk of CVD.

This study recruited adults between the ages of 45 and 75 years. All participants had high systolic blood pressure (SBP) but were not under any medication. Individuals who consumed medicinal levels of calcium or omega-3 supplements daily were excluded.

Participants were randomly assigned to any one of the groups, i.e., MedDairy (Group 1) or LFD (Group 2), and dietary interventions continued for 8 weeks, separated by an 8-week washout phase where participants followed their habitual diet. Complete fecal and clinical samples were collected at baseline and at 8 weeks to assess both groups.

Results

At baseline, there were no significant differences between the study groups. Group 1 contained 18 participants, and group 2 contained 16 participants. All participants who were not following MedDiet at baseline exhibited increased MedDiet adherence through the MedDairy intervention. Along with the MedDiet, participants received 3 to 4 servings of any one of the dairy products, such as low-fat Greek yogurt, low-fat milk, cheese (hard, soft, semi-soft), and tzatziki dip.

Fecal microbiota analysis indicated no significant difference in the overall structure and composition of the fecal microbiota between the two study groups. However, a modest decrease in microbial diversity was observed in the LFD group. It must be noted that the MedDairy diet did not result in a significant change in the gut microbiota but considerably altered the abundance of selected bacterial taxa, such as Butyricicoccus, Lachnospiraceae, and Streptococcus, and a reduction in Colinsella and Veillonella.

Conclusion

The findings of the current study highlighted that 8 weeks of a Mediterranean diet supplemented with dairy foods resulted in changes in the relative abundance of certain bacterial taxa. MedDairy diet enhanced Butyricicoccus, which has a positive effect on systolic blood pressure. Therefore, adherence to the MedDairy diet could reduce CVD risks.

Source:

https://www.news-medical.net/news/20230831/Mediterranean-diet-with-a-dairy-twist-shows-promise-in-lowering-heart-disease-risk.aspx

Press Release: New Danish Study says Wholegrains give Kids a Heart-Healthy Boost

Posted on October 31, 2023 by Admin

Researchers compared the cardiovascular outcomes of refined grains to wholegrains in children. Their randomized cross-over study comprised a cohort of 55 Danish children who were given diets containing either wholegrain or refined oats and rye for eight weeks. Their study findings revealed that wholegrain consumption significantly reduced low-density lipoprotein (LDL) cholesterol, triacylglycerol, and the ratio of total: high-density lipoprotein cholesterol. Wholegrain diets were additionally found to promote the growth of beneficial gut microbiota and reduce fatigue without any negative impacts on child health.

Study

In the present study, researchers employed a randomized cross-over study design to elucidate the outcomes of wholegrain rye and oats (WG) on cardiometabolic risk markers, body composition, and body mass index (BMI) of children aged 8-13. To verify the potential benefits of wholegrains, they compared these outcomes to those from a refined grain (RG) diet.

The study was conducted at the University of Copenhagen and comprised healthy but overweight (BMI +1 standard deviation [SD] above Danish median) Danish children who consumed cereal and bread daily. Children with allergies to whole- or refined grains and those consuming supplements altering their lipid or cardiometabolic profiles were excluded from the study. Recruitment for the study was carried out between August through December 2020.

Wholegrain products consisted of standard breakfast, lunch, and dinner snacks, wherein wholegrains comprised at least 50% of their dry weight. Refined grain products, in contrast, had low quantities of wholegrain and high amounts of refined wheat, corn, and rice. The nutrient and fiber content of WG and RG were separately measured via the Uppsala method at the Swedish University of Agricultural Sciences.

Daily intake of study products (WG or RG) was recorded in grams using kitchen weight balances. Additionally, prior to follow-up examinations, a 4-day dietary record of all food and beverages consumed was reported using the web-based Madlog Classic software. Using the Likert scale, a questionnaire was used to record and assess stool frequency and seven predefined gut symptoms.

Anthropomorphic measurements included weight, height, waist circumference, blood pressure (systolic and diastolic), age, body composition (using dual-energy X-ray absorptiometry [DXA]), and sex-adjusted BMI z-scores. Blood samples were collected for plasma analyses.

Statistical analyses comprised linear mixed models for continuous variables and cumulative link mixed models for ordinal variables.

Results

Weight classification for the 55 included children reported 22% as normal weight, 60% as overweight, and 18% as obese. Of these, 52 completed the study, 26 (50%) of whom were male. Self-reported dietary compliance was high, which was clinically confirmed by plasma alkylresorcinols (AR). Blood analyses revealed that WG diets were associated with lower energy, lower carbohydrates, higher protein, and higher fat than RG diets.

Whole grain diets were observed to reduce plasma LDL cholesterol, triacylglycerol (TG), and total cholesterol while increasing acetate and propionate compared to RG diets. Feces showed an increase in butyrate during the WG diet, but no differences in insulin or glucose could be found between diets. Serum C-reactive protein (CRP) was found to be lower in WG diets, but no changes in BMI or adiposity were found.

Gut microbiota analyses from feces revealed that WG diets resulted in an increase in Faecalibacterium and Dialister populations and a reduction in Collinsella and Ruminococcus.

Conclusion

In the present study, researchers investigated the effects of wholegrains on the cardiovascular health and gut microbiota compositions of Danish children between the ages of 8-13. Their findings reveal that compared to refined grains, WG diets are associated with lower cholesterol and triacylglycerol levels, which previous research has reported are beneficial to long-term cardiovascular health. WG diets also result in improved energy levels and lower fatigue while leaving other body composition metrics unchanged.

Source:

https://www.news-medical.net/news/20231030/Wholegrains-give-kids-a-heart-healthy-boost-says-new-Danish-study.aspx