Cardiogenic shock complicates takotsubo syndrome (TTS) in approximately 10

BACKGROUND:The pathogenesis of Takotsubo syndrome (TTS) is poorly understood, but differences in outcome depending on the triggering factor imply differences in the pathophysiology. Beyond the established trigger-based InterTAK (International Takotsubo Registry) classification, the newly proposed distinction between primary and secondary TTS aims to differentiate emotionally primed heart dysfunction from TTS driven by direct myocardial injury. To explore these potential differences, we utilized cardiovascular magnetic resonance imaging to assess left ventricular function, myocardial edema, and myocardial injury across the InterTAK classification and between primary and secondary TTS. METHODS:For this multicenter cohort study, 110 patients (95% women, age 66±12 years) from the InterTAK registry were included who received cardiovascular magnetic resonance 3 (interquartile range, 2-5) days after symptom onset. Cardiovascular magnetic resonance included assessment of myocardial function, edema (T2-weighted spin-echo and T2-mapping when available), and late gadolinium enhancement. RESULTS:No significant differences were observed in left ventricular volumes, function, or mass across the 3 InterTAK groups or between primary and secondary TTS. Patients with emotional triggers exhibited significantly larger myocardial edema (72% versus 60% for physical triggers; P<0.01), supported by higher T2-mapping values in a subset of 22 patients with T2-mapping. In multivariable regression, only emotional trigger (P<0.01) and the absence of coronary artery disease (P=0.04) were independently associated with the extent of myocardial edema. Secondary TTS showed a higher prevalence of focal or patchy late gadolinium enhancement (primary 19%, secondary 54%; P<0.01). In multivariable logistic regression, secondary TTS (P<0.01) and early cardiovascular magnetic resonance (P=0.02) were associated with the presence of any late gadolinium enhancement. CONCLUSIONS:TTS due to emotional stress is associated with larger myocardial edema, and secondary TTS exhibited late gadolinium enhancement more frequently, indicative of direct myocardial damage. These findings suggest that emotionally primed heart dysfunction and direct myocardial injury contribute to TTS pathophysiology to varying extents, influenced by both the triggering factor and preexisting conditions.

Background: Diabetic heart failure is characterised by predominantly diastolic dysfunction and has been associated with impaired cardiac energetics and inflammation. We recently found evidence of increased endothelial glycocalyx damage in a rat model of diabetic heart failure. This was associated with increased myocardial content of 3-nitrotyrosine (3-NT), a “fingerprint” of peroxynitrite. Increased peroxynitrite results in DNA damage, which then activates poly-ADP-ribose polymerase-1 (PARP-1) to initiate DNA repair. In turn, PARP-1 activation will deplete NAD+ and cause energetic impairment. Hypothesis: We hypothesised that inhibition of PARP-1 would ameliorate cardiac dysfunction observed in diabetic rats, and also the associated impairment of endothelial glycocalyx integrity. Methods: Diabetic heart failure was induced in 8-week-old male Wistar rats with 12 weeks of modified diets and two doses of streptozotocin at 30mg/kg/d. After induction of diabetes, the rats were randomised to receive 3-aminobenzamide (3-AB) at 40mg/kg/d or saline for 6 weeks (n=17/group). At the end of the study, cardiac function was determined via echocardiography. Plasma concentrations of matrix metalloproteinase-9 (MMP-9), as inflammatory stimulus that mediate glycocalyx damage, markers of glycocalyx damage [syndecan-1 [SD-1], heparan sulfate (HS) and hyaluronan (HA)], and angiopoietin-2 (Ang-2) as inducer of increased vascular permeability were measured, as was 3-NT. Results: 3-AB treated rats displayed significantly improved diastolic (E/A and E/E’), but not systolic (EF, global longitudinal strain) function (Fig A-D). While 3-AB did not affect plasma MMP-9, SD-1 or HA, there was significant reduction in Ang-2 and HS (Fig E-I). ANCOVA (Fig J) revealed a direct correlation between Ang-2 and E/E’. Lastly, there was no significant difference in 3-NT between groups. Conclusion: In a rat model of diabetic heart failure, inhibition of PARP-1 with 3-AB for 6 weeks selectively improved diastolic function. There was also reduction in plasma levels of heparan sulfate and angiopoietin-2, suggesting that 3-AB protects the microvascular glycocalyx from damage by PARP-1, presumably by limiting oxidative stress.

For over 150 years, nitrates have been a cornerstone in the treatment of cardiovascular disease. Nitroglycerin - synthesized by Italian chemist Ascanio Sobrero in 1847 - was initially used in explosives, as the main component of dynamite, by Alfred Nobel. The Scottish physician Lauder Brunton first used amyl nitrite for angina in 1867, and in 1879 the English physician William Murrell described the benefits of nitroglycerin for angina pectoris. Organic nitrates, including nitroglycerin, act as nitric oxide donors, sharing the mechanism of NO release, which induces vasodilation. This paper reviews the fascinating history of nitroglycerin and nitroderivatives, the related discovery of nitric oxide as a cardiovascular signaling molecule, and the 1998 Nobel Prize awarded for this discovery. The paper also succinctly explores current and future roles of nitric oxide donors in cardiovascular treatment.

Patients with chronic kidney disease (CKD) face a high risk of cardiovascular disease. Previous studies reported that endogenous thrombospondin 1 (TSP1) involves right ventricular remodeling and dysfunction. Here we show that a murine model of CKD increased myocardial TSP1 expression and produced left ventricular hypertrophy, fibrosis, and dysfunction. TSP1 knockout mice were protected from these features. In vitro, indoxyl sulfate is driving deleterious changes in cardiomyocyte through the TSP1. In patients with CKD, TSP1 and aryl hydrocarbon receptor were both differentially expressed in the myocardium. Our findings summon large clinical studies to confirm the translational role of TSP1 in patients with CKD.

Journal Article Cardiac biomarkers for diagnosing Takotsubo syndrome Get access Victor Schweiger, Victor Schweiger Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Davide Di Vece, Davide Di Vece First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, ItalyInternal Medicine B, University Medicine Greifswald, Greifswald, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Victoria L Cammann, Victoria L Cammann Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Iva Koleva, Iva Koleva Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Würdinger, Michael Würdinger Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Gilhofer, Thomas Gilhofer Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Katja Rajman, Katja Rajman Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Konrad A Szawan, Konrad A Szawan Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar David Niederseer, David Niederseer Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland https://orcid.org/0000-0003-3089-1222 Search for other works by this author on: Oxford Academic PubMed Google Scholar Rodolfo Citro, Rodolfo Citro Heart Department, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, ItalyDepartment of Vascular Physiopathology, IRCCS Neuromed, Pozzilli, Italy https://orcid.org/0000-0002-7796-6298 Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Carmine Vecchione, Carmine Vecchione Department of Vascular Physiopathology, IRCCS Neuromed, Pozzilli, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Salerno, Italy https://orcid.org/0000-0002-2473-4565 Search for other works by this author on: Oxford Academic PubMed Google Scholar Eduardo Bossone, Eduardo Bossone Division of Cardiology, 'Antonio Cardarelli' Hospital, Naples, Italy https://orcid.org/0000-0003-2769-9950 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sebastiano Gili, Sebastiano Gili Centro Cardiologico Monzino, IRCCS, Milan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Neuhaus, Michael Neuhaus Department of Cardiology, Kantonsspital Frauenfeld, Frauenfeld, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Jennifer Franke, Jennifer Franke Department of Cardiology, Heidelberg University Hospital, Heidelberg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Benjamin Meder, Benjamin Meder Department of Cardiology, Heidelberg University Hospital, Heidelberg, Germany https://orcid.org/0000-0003-0741-2633 Search for other works by this author on: Oxford Academic PubMed Google Scholar Miłosz Jaguszewski, Miłosz Jaguszewski First Department of Cardiology, Medical University of Gdansk, Gdansk, Poland Search for other works by this author on: Oxford Academic PubMed Google Scholar Michel Noutsias, Michel Noutsias Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Maike Knorr, Maike Knorr Center for Cardiology, Cardiology 1, University Medical Center Mainz, Mainz, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Jansen, Thomas Jansen Center for Cardiology, Cardiology 1, University Medical Center Mainz, Mainz, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Fabrizio D'Ascenzo, Fabrizio D'Ascenzo Division of Cardiology, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Francesco Bruno, Francesco Bruno Division of Cardiology, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, Turin, ItalyRoyal Brompton and Harefield Hospitals Trust and Imperial College, London, UK https://orcid.org/0000-0003-0019-0273 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ovidio De Filippo, Ovidio De Filippo Royal Brompton and Harefield Hospitals Trust and Imperial College, London, UK https://orcid.org/0000-0002-4915-9501 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Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank Ruschitzka, Frank Ruschitzka Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Jelena R Ghadri, Jelena R Ghadri Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Christian Templin Christian Templin Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, SwitzerlandSwiss CardioVascularClinic, Private Hospital Bethanien, Zurich, Switzerland Corresponding author. Tel: +044 255 11 11, Email: christian.templin@usz.ch https://orcid.org/0000-0003-0287-4193 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, ehae231, https://doi.org/10.1093/eurheartj/ehae231 Published: 08 May 2024 Article history Received: 22 August 2023 Revision received: 08 March 2024 Accepted: 25 March 2024 Published: 08 May 2024

The association between cardiovascular disease and carcinogenesis is bidirectional and well-established. Furthermore, cancer treatment improves overall patient survival, potentially at the cost of incremental and fatal cardiovascular disease (CVD). To evaluate (a) In a real-world cohort, the proportion of patients offered cancer chemotherapy who have antecedent CVD (CVDA); (b) The rates of patient admission with subsequent development of CVD (CVDS) requiring hospital admission post assignment to chemotherapy; (c) The impact of CVDA and CVDS on mortality rates relative to those seen in patients without overt CVD (CVD−) and (d) The time course of mortality in CVD− versus CVDS patients. Retrospective analysis was performed in deidentified linked health data sets. Correlates of mortality were evaluated by Cox proportional hazards evaluation. Relative and absolute time-variability of CVD as a primary cause of death were determined. Of the total 17,389 patients, there were 2,159 with CVDA. Over a median follow-up time of 4.6 years, CVDS admissions (n = 8,529) occurred more commonly in the presence of CVDA (70.0

The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

BACKGROUND:The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. OBJECTIVES:This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. METHODS:Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. RESULTS:Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). CONCLUSIONS:This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

BACKGROUND:Heart failure (HF) is predominately a chronic disease. There are overlaps in HF and chronic disease research and care. Chronic disease and HF research are conducted with multiple goals. The overarching goal is "optimized patient outcomes at maximum costeffectiveness". However, observations on patients can come with many variables; thus, we see differences in clinical translation. This document discusses an argument for three important gaps common to HF and chronic disease, i.e., screening, self-management, and patient-reported outcomes (PRO), and provides a glance of how it could fit into the evidence tree. Pertinent arguments for a framework for health services and models of care are provided as a prelude to future consensus.METHODOLOGY:1) A preliminary literature review to identify a taxonomy for cardiovascular research, and 2) a review of the published literature describing the translation of research studies into clinical practice for cardiovascular disorders. A spectrum from observational to large randomized controlled trials to post-marketing studies were identified.DISCUSSION:A brief discussion on traditional research and differences focusing on screening, mixed methods research concepts, and chronic diseases models of care. Six steps to facilitate this: 1) Research design; 2) Research application (translation) i. routine ii. challenges; 3. Transforming research to translational level; 4. Funding and infrastructure; 5. Clinical Centres of Research Excellence (CCRE) and collaboration; 6. Governance and cost-effectiveness.CONCLUSION:Implementation research that aims to link research findings to improved patient outcomes in an efficient and effective way is a neglected area. Skills required to perform implementation research are complex. Ways to maximize translational impacts for chronic disease research to clinical practice are described in a HF context.

Secreted frizzled-related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that may play a role in cardiovascular development and disease. However, there is yet to be a comprehensive investigation into whether circulating SFRP5 can be a biomarker for cardiac function. Plasma SFRP5 levels were measured via ELISA in 262 patients admitted to a cardiology unit. Plasma SFRP5 levels were significantly lower in patients with a history of heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF; p = 0.001). In univariate analyses, SFRP5 levels were also significantly positively correlated with left ventricular ejection fraction (LVEF) (r = 0.52, p < 0.001) and negatively correlated with E/E' (r = -0.30, p < 0.001). Patients with HF, CAD, low LVEF, low triglycerides, high CRP, and high eGFR were associated with lower SFRP5 levels independent of age, BMI, or diabetes after multivariate analysis (overall model r = 0.729, SE = 0.638). Our results show that low plasma SFRP5 levels are independently associated with the presence of HF, CAD, and, importantly, impaired LV function. These results suggest a potential role of SFRP5 as a biomarker, as well as a mediator of cardiac dysfunction independent of obesity and metabolic regulation.

Editorial FocusCores of Reproducibility in PhysiologyUnderstanding Takotsubo syndrome: first evaluate your mouse modelJohn D. Horowitz and Sven Y. SurikowJohn D. HorowitzCardiovascular Pathophysiology and Therapeutics Group, Basil Hetzel Institute for Translational Research, University of Adelaide, Adelaide, South Australia, Australia and Sven Y. SurikowCardiovascular Pathophysiology and Therapeutics Group, Basil Hetzel Institute for Translational Research, University of Adelaide, Adelaide, South Australia, AustraliaCardiology Unit, Lyell McEwin Hospital, Northern Adelaide Local Health Network, Adelaide, South Australia, AustraliaPublished Online:31 Mar 2023https://doi.org/10.1152/ajpheart.00051.2023This is the final version - click for previous versionMoreSectionsFull TextPDF (309 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations REFERENCES1. Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJet al. International Expert Consensus Document on Takotsubo Syndrome (Part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J 39: 2032–2046, 2018. doi:10.1093/eurheartj/ehy076.Crossref | PubMed | ISI | Google Scholar2. Ong GJ, Girolamo O, Stansborough J, Nguyen TH, Horowitz JD. Incidence and clinical/laboratory correlates of early hypotension in takotsubo syndrome. ESC Heart Fail 8: 2009–2015, 2021. doi:10.1002/ehf2.13277.Crossref | PubMed | Google Scholar3. Neil C, Nguyen TH, Kucia A, Crouch B, Sverdlov A, Chirkov Y, Mahadavan G, Selvanayagam J, Dawson D, Beltrame J, Zeitz C, Unger S, Redpath T, Frenneaux M, Horowitz J. Slowly resolving global myocardial inflammation/oedema in Tako-Tsubo cardiomyopathy: evidence from T2-weighted cardiac MRI. Heart 98: 1278–1284, 2012. doi:10.1136/heartjnl-2011-301481.Crossref | PubMed | Google Scholar4. Scally C, Rudd A, Mezincescu A, Wilson H, Srivanasan J, Horgan G, Broadhurst P, Newby DE, Henning A, Dawson DK. Persistent long-term structural, functional, and metabolic changes after stress-induced (Takotsubo) cardiomyopathy. Circulation 137: 1039–1048, 2018. doi:10.1161/CIRCULATIONAHA.117.031841.Crossref | PubMed | ISI | Google Scholar5. Girolamo OC, Surikow SY, Ong G-J, Nguyen TH, Kucia AM, Chirkov YY, Horowitz JD. TakoTsubo Syndrome: first an acute coronary vasculitis and then prolonged myocarditis? Rev Cardiovasc Med 23: 152, 2022. doi:10.31083/j.rcm2305152.Crossref | Google Scholar6. Paur H, Wright PT, Sikkel MB, Tranter MH, Mansfield C, O'Gara P, Stuckey DJ, Nikolaev VO, Diakonov I, Pannell L, Gong H, Sun H, Peters NS, Petrou M, Zheng Z, Gorelik J, Lyon AR, Harding SE. High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy. Circulation 126: 697–706, 2012. doi:10.1161/CIRCULATIONAHA.112.111591.Crossref | PubMed | ISI | Google Scholar7. Surikow SY, Nguyen TH, Stafford I, Chapman M, Chacko S, Singh K, Licari G, Raman B, Kelly DJ, Zhang Y, Waddingham MT, Ngo DT, Bate AP, Chua SJ, Frenneaux MP, Horowitz JD. Nitrosative stress as a modulator of inflammatory change in a model of Takotsubo syndrome. JACC Basic Transl Sci 3: 213–226, 2018. doi:10.1016/j.jacbts.2017.10.002.Crossref | PubMed | Google Scholar8. Hayashi T, Tiwary SK, Lim KRQ, Rocha-Resende C, Kovacs- A, Weinheimer C, Mann DL. Refining the reproducibility of a murine model of stress-induced cardiomyopathy. Am J Physiol Heart Circ Physiol 324: H229–H240, 2023. doi:10.1152/ajpheart.00684.2022.Link | Google Scholar9. Nguyen TH, Neil CJ, Sverdlov AL, Ngo DT, Chan WP, Heresztyn T, Chirkov YY, Tsikas D, Frenneaux MP, Horowitz JD. Enhanced NO signaling in patients with Takotsubo cardiomyopathy: short-term pain, long-term gain? Cardiovasc Drugs Ther 27: 541–547, 2013. doi:10.1007/s10557-013-6481-x.Crossref | PubMed | Google Scholar10. Nguyen TH, Liu S, Ong GJ, Stafford I, Frenneaux MP, Horowitz JD. Glycocalyx shedding is markedly increased during the acute phase of Takotsubo cardiomyopathy. Int J Cardiol 243: 296–299, 2017. doi:10.1016/j.ijcard.2017.04.085.Crossref | PubMed | Google Scholar Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation CollectionsAJP-Heart CollectionsCores of Reproducibility in PhysiologyThis collection represents best practice in physiology for a particular method or equipment that is in broad, common use. It was developed in response to the challenge to improve transparency and reproducibility in published research results. Related ArticlesRefining the reproducibility of a murine model of stress-induced reversible cardiomyopathy 23 Jan 2023American Journal of Physiology-Heart and Circulatory Physiology More from this issue > Volume 324Issue 5May 2023Pages H630-H632 Crossmark Copyright & PermissionsCopyright © 2023 the American Physiological Society.https://doi.org/10.1152/ajpheart.00051.2023PubMed36897752History Received 26 January 2023 Accepted 2 March 2023 Published online 31 March 2023 Published in print 1 May 2023 KeywordsinflammationisoproterenolmiceTakotsubo syndrome Metrics

BACKGROUND: Climate change has resulted in an increase in ambient temperatures during the summer months as well as an increase in risk of associated air pollution and of potentially disastrous bushfires throughout much of the world. The increasingly frequent combination of elevated summer temperatures and bushfires may be associated with acute increases in risks of cardiovascular events, but this relationship remains unstudied. We evaluated the individual and cumulative impacts of daily fluctuations in temperature, fine particulate matter of less than 2.5 mm (PM2.5) pollution and presence of bushfires on incidence of acute coronary syndromes and Takotsubo syndrome. METHODS: From November 1, 2019, to February 28, 2020, all admissions with acute coronary syndromes or Takotsubo syndrome to South Australian tertiary public hospitals were evaluated. Univariate and combined associations were sought among each of 1) maximal daily temperature, 2) PM2.5 concentrations, and 3) presence of active bushfires within 200 km of the hospitals concerned. RESULTS: A total of 504 patients with acute coronary syndromes and 35 with Takotsubo syndrome were studied. In isolation, increasing temperature was associated (rs = 0.26, P =.005) with increased incidence of acute coronary syndromes, while there were similar, but nonsignificant correlations for PM2.5 and presence of bushfires. Combinations of all these risk factors were also associated with a doubling of risk of acute coronary syndromes. No significant associations were found for Takotsubo syndrome. CONCLUSION: The combination of high temperatures, presence of bushfires and associated elevation of atmospheric PM2.5 concentrations represents a substantially increased risk for precipitation of acute coronary syndromes; this risk should be factored into health care planning including public education and acute hospital preparedness.

Impairment of the nitric oxide/soluble guanylate cyclase (NO)/sGC) signalling cascade is associated with many forms of cardiovascular disease, resulting not only in compromised vasodilatation but also loss of anti-aggregatory homeostasis. Myocardial ischaemia, heart failure, and atrial fibrillation are associated with moderate impairment of NO/sGC signalling, and we have recently demonstrated that coronary artery spasm (CAS) is engendered by severe impairment of platelet NO/sGC activity resulting in combined platelet and vascular endothelial damage. We therefore sought to determine whether sGC stimulators or activators might normalise NO/sGC homeostasis in platelets. ADP-induced platelet aggregation and its inhibition by the NO donor sodium nitroprusside (SNP), the sGC stimulator riociguat (RIO), and the sCG activator cinaciguat (CINA) alone or in addition to SNP were quantitated. Three groups of individuals were compared: normal subjects (n = 9), patients (Group 1) with myocardial ischaemia, heart failure and/or atrial fibrillation (n = 30), and patients (Group 2) in the chronic stage of CAS (n = 16). As expected, responses to SNP were impaired (p = 0.02) in patients versus normal subjects, with Group 2 patients most severely affected (p = 0.005). RIO alone exerted no anti-aggregatory effects but potentiated responses to SNP to a similar extent irrespective of baseline SNP response. CINA exerted only intrinsic anti-aggregatory effects, but the extent of these varied directly (r = 0.54; p = 0.0009) with individual responses to SNP. Thus, both RIO and CINA tend to normalise anti-aggregatory function in patients in whom NO/sGC signalling is impaired. The anti-aggregatory effects of RIO consist entirely of potentiation of NO, which is not selective of platelet NO resistance. However, the intrinsic anti-aggregatory effects of CINA are most marked in individuals with initially normal NO/sGC signalling, and thus their magnitude is at variance with extent of physiological impairment. These data suggest that RIO and other sGC stimulators should be evaluated for clinical utility in both prophylaxis and treatment of CAS.