The Effect of the Lockdown on Patients With Myocardial Infarction During the COVID-19 Pandemic­A Systematic Review and Meta-Analysis.

BACKGROUND: The phenomenon of declining numbers of patients presenting with myocardial infarction was reported from the beginning of the COVID-19 pandemic onward. It was thought that measures introduced to stem the pandemic, such as the lockdown, contributed to this development. However, the data on hospital admissions, delay times, and mortality are not consistent. METHODS: Our systematic literature review and meta-analysis embraced studies reporting the number of hospital admissions of patients with ST-segment elevation myocardial infarction (STEMI) and/or non-ST-segment elevation myocardial infarction (NSTEMI) during lockdown episodes. We also collected data on patient- and system-related delay times and on mortality. RESULTS: Data from 27 studies on a total of 81 163 patients were included in our meta-analysis. We found that the number of hospital admissions of patients with myocardial infarction was significantly lower during the lockdown than before the pandemic (incidence rate ratio [IRR] = 0.516 [0.403; 0.660], I2 = 98%). This was true both for patients with STEMI (IRR = 0.620 [0.514; 0.746], I2 = 96%) and for patients with NSTEMI (IRR = 0.454 [0.354; 0.584], I2 = 96%). However, we found no significant difference in the time from hospital admission to cardiac catheterization, or in mortality, in relation to the time from symptom onset to first medical contact. CONCLUSION: In this study, we have shown that the lockdown due to COVID-19 was associated with a marked decline in the number of hospital admissions of patients with myocardial infarction. As no significant effect on delay times or mortality was observed, it seems that timely medical care continued to be delivered.

Outcomes of Patients With ST-Segment Elevation Myocardial Infarction Admitted During COVID-19 Pandemic Lockdown in Germany - Results of a Single Center Prospective Cohort Study.

Objective: Since the outbreak of the COVID-19 pandemic, healthcare professionals reported declining numbers of patients admitted with ST-segment myocardial infarction (STEMI) associated with increased in-hospital morbidity and mortality. However, the effect of lockdown on outcomes of STEMI patients admitted during the COVID-19 crisis has not been prospectively evaluated. Methods: A prospective, observational study on STEMI patients admitted to our tertiary care center during the COVID-19 pandemic was conducted. Outcomes of patients admitted during lockdown were compared to those patients admitted before and after pandemic-related lockdown. Results: A total of 147 patients were enrolled in our study, including 57 patients in the pre-lockdown group (November 1, 2019 to March 20, 2020), 16 patients in the lockdown group (March 21 to April 19, 2020), and 74 patients in the post-lockdown group (April 20 to September 30, 2020). Patients admitted during lockdown had significantly longer time to first medical contact, longer door-to-needle-time, higher serum troponin T levels, worse left ventricular end-diastolic pressure, and higher need for circulatory support. After a median follow-up of 142 days, survival was significantly worse in STEMI patients of the lockdown group (log-rank: p = 0.0035). Conclusions: This is the first prospective study on outcomes of STEMI patients admitted during public lockdown amid the COVID-19 pandemic. Our results suggest that lockdown might deteriorate outcomes of STEMI patients. Public health strategies to constrain spread of COVID-19, such as lockdown, have to be accompanied by distinct public instructions to ensure timely medical care in acute diseases such as STEMI.

Effect of the COVID-19 pandemic on mortality of patients with STEMI: a systematic review and meta-analysis.

AIMS: Since the beginning of the SARS-CoV-2 outbreak, hospitals reported declining numbers of patients admitted with ST-segment elevation myocardial infarction (STEMI), indicating that the pandemic might keep patients from seeking urgent medical treatment. However, data on outcomes and mortality rates are inconsistent between studies. METHODS: A literature search and meta-analysis were performed on studies reporting the mortality of patients with STEMI admitted before and during the COVID-19 pandemic using PubMed, Embase and Web of Science. Additionally, prehospital and intrahospital delay times were evaluated. RESULTS: Outcomes of a total of 50 123 patients from 10 studies were assessed. Our study revealed that, despite a significant reduction in overall admission rates of patients with STEMI during the COVID-19 pandemic (incidence rate ratio=0.789, 95% CI 0.730 to 0.852, I2=77%, p<0.01), there was no significant difference in hospital mortality (OR=1.178, 95% CI 0.926 to 1.498, I2=57%, p=0.01) compared with patients with STEMI admitted before the outbreak. Time from the onset of symptoms to first medical contact was similar (mean difference (MD)=33.4 min, 95% CI -10.2 to 77.1, I2=88%, p<0.01) while door-to-balloon time was significantly prolonged in those presenting during the pandemic (MD=7.3 min, 95% CI 3.0 to 11.7, I2=95%, p<0.01). CONCLUSION: The significant reduction in admission of patients with STEMI was not associated with a significant increase of hospital mortality rates. The causes for reduced incidence rates remain speculative. However, the analysed data indicate that acute and timely medical care of these patients has been maintained during the pandemic in most countries. Long-term data on mortality have yet to be determined.

Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency.

Mutations in the molecular co-chaperone Bcl2-associated athanogene 3 (BAG3) are found to cause dilated cardiomyopathy (DCM), resulting in systolic dysfunction and heart failure, as well as myofibrillar myopathy (MFM), which is characterized by protein aggregation and myofibrillar disintegration in skeletal muscle cells. Here, we generated a CRISPR/Cas9-induced Bag3 knockout zebrafish line and found the complete preservation of heart and skeletal muscle structure and function during embryonic development, in contrast to morpholino-mediated knockdown of Bag3. Intriguingly, genetic compensation, a process of transcriptional adaptation which acts independent of protein feedback loops, was found to prevent heart and skeletal muscle damage in our Bag3 knockout model. Proteomic profiling and quantitative real-time PCR analyses identified Bag2, another member of the Bag protein family, significantly upregulated on a transcript and protein level in bag3-/- mutants. This implied that the decay of bag3 mutant mRNA in homozygous bag3-/- embryos caused the transcriptional upregulation of bag2 expression. We further demonstrated that morpholino-mediated knockdown of Bag2 in bag3-/- embryos evoked severe functional and structural heart and skeletal muscle defects, which are similar to Bag3 morphants. However, Bag2 knockdown in bag3+/+ or bag3+/- embryos did not result in (cardio-)myopathy. Finally, we found that inhibition of the nonsense-mediated mRNA decay (NMD) machinery by knockdown of upf1, an essential NMD factor, caused severe heart and skeletal muscle defects in bag3-/- mutants due to the blockade of transcriptional adaptation of bag2 expression. Our findings provide evidence that genetic compensation might vitally influence the penetrance of disease-causing bag3 mutations in vivo.

31 days of COVID-19-cardiac events during restriction of public life-a comparative study.

AIMS: The coronavirus SARS-CoV-2 outbreak led to the most recent pandemic of the twenty-first century. To contain spread of the virus, many nations introduced a public lockdown. How the pandemic itself and measures of social restriction affect hospital admissions due to acute cardiac events has rarely been evaluated yet. METHODS AND RESULTS: German public authorities announced measures of social restriction between March 21st and April 20th, 2020. During this period, all patients suffering from an acute cardiac event admitted to our hospital (N = 94) were assessed and incidence rate ratios (IRR) of admissions for acute cardiac events estimated, and compared with those during the same period in the previous three years (2017-2019, N = 361). Admissions due to cardiac events were reduced by 22% as compared to the previous years (n = 94 vs. an average of n = 120 per year for 2017-2019). Whereas IRR for STEMI 1.20 (95% CI 0.67-2.14) and out-of-hospital cardiac arrest IRR 0.82 (95% CI 0.33-2.02) remained similar, overall admissions with an IRR of 0.78 (95% CI 0.62-0.98) and IRR for NSTEMI with 0.46 (95% CI 0.27-0.78) were significantly lower. In STEMI patients, plasma concentrations of high-sensitivity troponin T at admission were significantly higher (644 ng/l, IQR 372-2388) compared to 2017-2019 (195 ng/l, IQR 84-1134; p = 0.02). CONCLUSION: The SARS-CoV-2 pandemic and concomitant social restrictions are associated with reduced cardiac events admissions to our tertiary care center. From a public health perspective, strategies have to be developed to assure patients are seeking and getting medical care and treatment in time during SARS-CoV-2 pandemic.

Zebrafish otolith biomineralization requires polyketide synthase.

Deflecting biomineralized crystals attached to vestibular hair cells are necessary for maintaining balance. Zebrafish (Danio rerio) are useful organisms to study these biomineralized crystals called otoliths, as many required genes are homologous to human otoconial development. We sought to identify and characterize the causative gene in a trio of homozygous recessive mutants, no content (nco) and corkscrew (csr), and vanished (vns), which fail to develop otoliths during early ear development. We show that nco, csr, and vns have potentially deleterious mutations in polyketide synthase (pks1), a multi-modular protein that has been previously implicated in biomineralization events in chordates and echinoderms. We found that Otoconin-90 (Oc90) expression within the otocyst is diffuse in nco and csr; therefore, it is not sufficient for otolith biomineralization in zebrafish. Similarly, normal localization of Otogelin, a protein required for otolith tethering in the otolithic membrane, is not sufficient for Oc90 attachment. Furthermore, eNOS signaling and Endothelin-1 signaling were the most up- and down-regulated pathways during otolith agenesis in nco, respectively. Our results demonstrate distinct processes for otolith nucleation and biomineralization in vertebrates and will be a starting point for models that are independent of Oc90-mediated seeding. This study will serve as a basis for investigating the role of eNOS signaling and Endothelin-1 signaling during otolith formation.

Mechanisms of otoconia and otolith development.

BACKGROUND: Otoconia are bio-crystals that couple mechanic forces to the sensory hair cells in the utricle and saccule, a process essential for us to sense linear acceleration and gravity for the purpose of maintaining bodily balance. In fish, structurally similar bio-crystals called otoliths mediate both balance and hearing. Otoconia abnormalities are common and can cause vertigo and imbalance in humans. However, the molecular etiology of these illnesses is unknown, as investigators have only begun to identify genes important for otoconia formation in recent years. RESULTS: To date, in-depth studies of selected mouse otoconial proteins have been performed, and about 75 zebrafish genes have been identified to be important for otolith development. CONCLUSIONS: This review will summarize recent findings as well as compare otoconia and otolith development. It will provide an updated brief review of otoconial proteins along with an overview of the cells and cellular processes involved. While continued efforts are needed to thoroughly understand the molecular mechanisms underlying otoconia and otolith development, it is clear that the process involves a series of temporally and spatially specific events that are tightly coordinated by numerous proteins. Such knowledge will serve as the foundation to uncover the molecular causes of human otoconia-related disorders.