Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo:Comparison With Myocardial Infarction and General Population

BACKGROUND: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.OBJECTIVES: To investigate cardiovascular mortality and medication use after takotsubo syndrome.METHODS: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010-2017 (n=620) were age, sex and geographically matched to individuals in the general population (1:4, n=2,480) and contemporaneous patients with acute myocardial infarction (1:1, n=620). Electronic health record data linkage of mortality outcomes and drug prescribing were analysed using Cox proportional hazard regression models.RESULTS: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow up. This exceeded mortality rates in the general population [374 (15%)]; hazard ratio [HR] 1.78 [95% confidence interval 1.48-2.15], P<0.0001), especially for cardiovascular (HR 2.47, [1.81-3.39], P<0.001) but also non-cardiovascular (HR 1.48 [1.16-1.87], P=0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR 0.76 [0.62-0.94], P=0.012), which was attributable to lower rates of cardiovascular (HR 0.61 [0.44-0.84], P=0.002) but not non-cardiovascular (HR 0.92 [0.69-1.23], P=0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P=0.01), anti-inflammatory (P=0.002) and psychotropic (P<0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.CONCLUSIONS: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use

Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo:Comparison With Myocardial Infarction and General Population

BACKGROUND: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.OBJECTIVES: To investigate cardiovascular mortality and medication use after takotsubo syndrome.METHODS: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010-2017 (n=620) were age, sex and geographically matched to individuals in the general population (1:4, n=2,480) and contemporaneous patients with acute myocardial infarction (1:1, n=620). Electronic health record data linkage of mortality outcomes and drug prescribing were analysed using Cox proportional hazard regression models.RESULTS: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow up. This exceeded mortality rates in the general population [374 (15%)]; hazard ratio [HR] 1.78 [95% confidence interval 1.48-2.15], P<0.0001), especially for cardiovascular (HR 2.47, [1.81-3.39], P<0.001) but also non-cardiovascular (HR 1.48 [1.16-1.87], P=0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR 0.76 [0.62-0.94], P=0.012), which was attributable to lower rates of cardiovascular (HR 0.61 [0.44-0.84], P=0.002) but not non-cardiovascular (HR 0.92 [0.69-1.23], P=0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P=0.01), anti-inflammatory (P=0.002) and psychotropic (P<0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.CONCLUSIONS: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use

Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy

The HEROIC study was funded by the British Heart Foundation Project Grant no. PG/15/108/31928 (D.K.D.), the Josephine Lansdell British Medical Association 2015 Award (D.K.D.), and the Chief Scientist Office CGA-16-4 Catalytic Grant (D.K.D). D.E.N. is supported by the British Heart Foundation (CH/09/002) and a Wellcome Trust Senior Investigator Award (WT103782AIA).Peer reviewedPublisher PD

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Contributions D.D., A.H., S.G., S.P. and M.D. conceived the study and together with L.v.L., G.L., F.T. obtained the grant funding. AM executed the patient screening, recruitment, intervention planning, carried out all study investigations under respective specialist supervision (A.H./D.C./D.D. for magnetic resonance spectroscopy, F.T./G.L./D.D. for stable isotope investigation, S.G. for exercise intervention, S.P. for clinical supervision/management of diabetes as required, M.D. for all molecular laboratory analyses, A.M. analysed all data and performed statistical analysis under the supervision of G.H. L.v.L. provided expert advice in athletic physiology. Lipidomic analyses were carried out in P.W. laboratory. Blood/skeletal muscle enrichment analyses were carried out in B.F./F.T.-G.L. laboratories respectively, with practical input from R.G. A.R. and L.C. contributed as overall help to deliver study assessments in a technical role. M.K.H. analysed the food diaries. D.E.N. contributed to manuscript writing. D.D. and M.D. were the PhD supervisors for A.M. whose PhD thesis was based on this work. All authors contributed their respective specialist sections in drafting the manuscript.Peer reviewe

Renin-Angiotensin and Endothelin Systems in Patients post Takotsubo Cardiomyopathy

SOURCES OF FUNDING This work was supported by British Heart Foundation PG/15/108/31928, FS/RTF/20/30009, the 2016 Josephine Lansdell BMA Award, Chief Scientist Office Scotland CGA‐16‐4 and NHS Grampian Endowment ES868. ACKNOWLEDGMENTS We thank Ms Lorraine Bruce for help with processing of some of the samples.Peer reviewedPublisher PD

Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy

Background: Acute stress induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable to myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. Methods: In a multi-centre study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age, sex and co-morbidity matched control subjects. During the index event and at 5 months follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched controls underwent investigation at a single time point. Results: Subjects were predominantly middle aged (64±14years) women (90%). When compared to control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 versus 10.5±0.9 ms, p<0.001) and non-ballooning (12.9±0.6 versus 10.5±0.9 ms, p=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 versus 6.5±5.8 pg/mL, p< 0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 versus 1272±177 pg/mL, p=0.01) concentrations, and classical CD14++CD16- monocytes (90±0.5 versus 87±0.9%, p=0.01) were also increased whilst intermediate CD14++CD16+ (5.4±0.3 versus 6.9±0.6%, p=0.01) and non-classical CD14+CD16++ (2.7±0.3% versus 4.2±0.5%, p=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium although there remained persistent elevations in serum interleukin-6 concentrations (p=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4 versus 6.9±0.6%, p=0.01). Conclusions: We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets and an increase in systemic pro-inflammatory cytokines. Many of these changes persisted for at least 5 months suggesting a low-grade chronic inflammatory state

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called “athlete’s paradox”. In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY)

Genomic reconstruction of the SARS-CoV-2 epidemic in England

AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p