To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.
COVID-19 cases were defined using health record linkage. Each case was ...propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.
Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.
Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.
New Findings
What is the topic of this review?
The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms ...emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic.
What advances does it highlight?
Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies.
Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post‐viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post‐viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID‐related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro‐clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.
Abstract
Aims
Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be ...progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications.
Methods and results
Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g interquartile range (IQR) 0.97–13.48 g to 6.30 g (IQR 1.38–17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85–13.79; P = 0.002).
Conclusion
Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.
Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single ...organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.
There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge ...to global public health and economic activity.
Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness.
205 consecutive patients, age 39 (IQR30.0-46.7) years, 84% male, were assessed 24 (IQR17.1-34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in <50% of patients, with COVID-associated pathology found in 25% of these. In all but three HRCTs, changes were graded 'mild'. There was an extremely low incidence of pulmonary thromboembolic disease or significant cardiac pathology. A specific, focal cognitive deficit was identified in those with ongoing symptoms of fatigue, poor concentration, poor memory, low mood, and anxiety. This was notably more common in patients managed in the community during their acute illness.
Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abnormality in myocardial copper homeostasis is believed to contribute to the development of cardiomyopathy. Trientine, a copper-chelating drug used in the management of patients with Wilson’s ...disease, demonstrates beneficial effects in patients with hypertrophic cardiomyopathy. This review aims to present the updated development of the roles of trientine in hypertrophic cardiomyopathy. The drug has been demonstrated in animal studies to restore myocardial intracellular copper content. However, its mechanisms for improving the medical condition remain unclear. Thus, comprehending its mechanistic aspects in cardiomyopathy is crucial and could help to expedite future research.
Takotsubo cardiomyopathy (TTC) has generally been regarded as a relatively transient disorder, characterized by reversible regional left ventricular systolic dysfunction. However, most patients with ...TTC experience prolonged lassitude or dyspnea after acute attacks. Although this might reflect continued emotional stress, myocardial inflammation and accentuated brain-type natriuretic peptide (BNP) release persist for at least 3 months. We therefore tested the hypotheses that this continued inflammation is associated with (1) persistent contractile dysfunction and (2) consequent impairment of quality of life. Echocardiographic parameters (global longitudinal strain GLS, longitudinal strain rate LSR, and peak apical twist AT) were compared acutely and after 3 months in 36 female patients with TTC and 19 age-matched female controls. Furthermore, correlations were sought between putative functional anomalies, inflammatory markers (T2 score on cardiovascular magnetic resonance, plasma NT-proBNP, and high-sensitivity C-reactive protein levels), and the physical composite component of SF36 score (SF36-PCS). In TTC cases, left ventricular ejection fraction returned to normal within 3 months. GLS, LSR, and AT improved significantly over 3-month recovery, but GLS remained reduced compared to controls even at follow-up (−17.9 ± 3.1% vs −20.0 ± 1.8%, p = 0.003). Impaired GLS at 3 months was associated with both persistent NT-proBNP elevation (p = 0.03) and reduced SF36-PCS at ≥3 months (p = 0.04). In conclusion, despite normalization of left ventricular ejection fraction, GLS remains impaired for at least 3 months, possibly as a result of residual myocardial inflammation. Furthermore, perception of impaired physical exercise capacity ≥3 months after TTC may be explained by persistent myocardial dysfunction.
The NHS Health Check is a preventive programme in the UK designed to screen for cardiovascular risk and to aid in primary disease prevention. Despite its widespread implementation, the effectiveness ...of the NHS Health Check for longer-term disease prevention is unclear. In this study, we measured the rate of new diagnoses in UK Biobank participants who underwent the NHS Health Check compared with those who did not.
Within the UK Biobank prospective study, 48,602 NHS Health Check recipients were identified from linked primary care records. These participants were then covariate-matched on an extensive range of socio-demographic, lifestyle, and medical factors with 48,602 participants without record of the check. Follow-up diagnoses were ascertained from health records over an average of 9 years (SD 2 years) including hypertension, diabetes, hypercholesterolaemia, stroke, dementia, myocardial infarction, atrial fibrillation, heart failure, fatty liver disease, alcoholic liver disease, liver cirrhosis, liver failure, acute kidney injury, chronic kidney disease (stage 3 +), cardiovascular mortality, and all-cause mortality. Time-varying survival modelling was used to compare adjusted outcome rates between the groups.
In the immediate 2 years after the NHS Health Check, higher diagnosis rates were observed for hypertension, high cholesterol, and chronic kidney disease among health check recipients compared to their matched counterparts. However, in the longer term, NHS Health Check recipients had significantly lower risk across all multiorgan disease outcomes and reduced rates of cardiovascular and all-cause mortality.
The NHS Health Check is linked to reduced incidence of disease across multiple organ systems, which may be attributed to risk modification through earlier detection and treatment of key risk factors such as hypertension and high cholesterol. This work adds important evidence to the growing body of research supporting the effectiveness of preventative interventions in reducing longer-term multimorbidity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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