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Atherosclerosis is a widespread disease affecting coronary arteries. Diffuse atherosclerotic disease affects the whole vessel, posing difficulties in determining lesion significance by angiography. Research has confirmed that revascularization guided by invasive coronary physiology indices improves patients' prognosis and quality of life. Serial lesions can be a diagnostic challenge because the measurement of functional stenosis significance using invasive physiology is influenced by a complex interplay of factors. The use of fractional flow reserve (FFR) pullback provides a trans-stenotic pressure gradient (ΔP) for each of the lesions. The strategy of treating the lesion with greater ΔP first and then reevaluating another lesion has been advocated. Similarly, non-hyperemic indices can be used to assess the contribution of each stenosis and predict the effect of lesion treatment on physiology indices. Pullback pressure gradient (PPG) integrates physiological variables of coronary pressure along the epicardial vessel and characteristics of discrete and diffuse coronary stenoses into a quantitative index that can be used to guide revascularization. We proposed an algorithm that integrates FFR pullbacks and calculates PPG to determine individual lesion importance and to guide intervention. Computer modeling of the coronaries and the use of non-invasive FFR measurement together with mathematical algorithms for fluid dynamics can make predictions of lesion significance in serial stenoses easier and provide practical solutions for treatment. All these strategies need to be validated before widespread clinical use.
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Background: Myocardial ischemia is caused by epicardial coronary artery stenosis or atherosclerotic disease affecting microcirculation. Trimetazidine (TMZ), promotes glucose oxidation which optimizes cellular energy processes in ischemic conditions. Small studies demonstrated protective effects of TMZ in terms of reducing myocardial injury after percutaneous coronary intervention (PCI), its effect on microcirculation using contemporary investigative methods has not been studied. The aim of the study was to examine effects of trimetazidine, given before elective PCI, on microcirculation using invasively measured index of microcirculatory resistance (IMR). Methods: This was prospective, single blinded, randomized study performed in a single university hospital. It included consecutive patients with an indication for PCI of a single, de novo, native coronary artery lesion. Patients were randomly assigned to receive either TMZ plus standard therapy (TMZ group) or just standard therapy. Coronary physiology indices fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured before and after PCI using coronary pressure wire. Results: We randomized 71 patients with similar clinical characteristics and risk profile, previous medications and coronary angiograms. Patientshad similar values of Pd/Pa, FFR and CFR prior to PCI procedure. After PCI, FFR values were higher in TMZ group, while IMR values were lower in this group respectively (FFR TMZ + 0.89 ± 0.05 vs. TMZ - 0.85 ± 0.06, p = 0.007; CFR TMZ + 2.1 ± 0.8 vs. TMZ- 2.3 ± 1.3, p = 0.469; IMR TMZ + 18 ± 9 vs. TMZ- 24 ± 12, p = 0.028). In two-way repeated measures ANOVA PCI was associated with change in FFR values (TMZ p = 0.050; PCI p < 0.001; p for interaction 0.577) and TMZ with change in IMR values (TMZ p = 0.034, PCI p = 0.129, p for interaction 0.344). Conclusion: Adding trimetazidine on top of medical treatment prior to elective PCI reduces microvascular dysfunction by lowering postprocedural IMR values when compared to standard therapy alone.
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Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome that is often overlooked, misdiagnosed, and maltreated. Medical treatment poses a significant challenge because of the lack of randomized studies to guide treatment. The initial clinical presentation should guide medical and interventional management. Fibrinolytic agents and anticoagulants should be avoided because they could favor hematoma propagation. In patients with SCAD, antiplatelet therapy should be prescribed especially dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel, whereas potent P2Y12 inhibitors, e.g., ticagrelor and prasugrel, should be avoided. If a stent was used, DAPT should be continued for 12 months. Aspirin only can be an option for patients without "high-risk" angiographic features-thrombus burden, critical stenosis, and decreased coronary flow. Beta-blocking (BB) agents should be used to prevent recurrence of SCAD. There is a general agreement that angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, mineralocorticoid antagonists, and loop diuretics should be used in patients with SCAD experiencing the symptoms of heart failure and a decrease in left ventricular ejection fraction below 50%. Although without firm evidence, statins can be used in SCAD due to their pleiotropic properties. The results of a randomized trial on the use of BB and statins are awaited. Aggregation of data from national registries might point out truly beneficial medications for patients with SCAD.
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Aim: Coronary bifurcation atherosclerosis depends on its angles, flow, and extensive branching. We investigate the ability of CT coronary angiography (CTCA) to determine atherosclerotic plaque characteristics of "true" bifurcation compared with intravascular ultrasound (IVUS) and the influence on side branch (SB) fate after percutaneous coronary intervention (PCI). Methods and results: The study included 70 patients with 72 "true" bifurcations. Most of the bifurcations were in the left anterior descending-diagonal (Dg) territory [50 out of 72 (69.4%)]. Longitudinal plaque evaluation at the polygon of confluence [carina and 5â mm proximal and distal in the main branch (MB)] showed that carina side MB and SB plaque had occurred with the lowest incidence with fibro-lipid structure (115 ± 63â HU and 89 ± 73â HU, p < 0.001 for all). Bland-Altman analysis showed a discrepancy in measuring mainly the lumen area between CTCA and IVUS in proximal MB [lumen 5.10, 95% CI (95% confidence interval, 4.53-5.68)â mm2, p < 0.001; vessel -1.42, 95% CI (-2.63 to -0.21)â mm2, p = 0.023], carina MB [lumen 3.74, 95% CI (3.37-4.10)â mm2, p < 0.001; vessel -0.48, 95% CI (-1.45 to 0.48)â mm2, p = 0.322], and distal MB [lumen 4.72, 95% CI (4.27-5.18)â mm2, p < 0.001; vessel 0.62, 95% CI (-0.53 to 1.77)â mm2, p = 0.283]. A significant correlation existed between average plaque density on CTCA with a percentage of calcified plaque on IVUS tissue characterization (proximal r = 0.307/p = 0.024, carina 0.469/0.008, distal 0.339/0.024, minimal lumen diameter 0.318/0.020). Circumferential plaque in the proximal MB segment remained an independent predictor of SB compromise [OR 3.962 (95% CI 1.170-13.418)]. Conclusion: Detection and characterization of atherosclerotic plaque by CTCA in non-left main "true" coronary bifurcations can provide useful information about bifurcation anatomy and plaque distribution that can predict outcomes after provisional stenting, thus guiding the interventional strategy to bifurcation PCI.
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BACKGROUND: Ischemia and no obstructive coronary artery disease (INOCA) disproportionately impacts women, yet the underlying pathologies are often not distinguished, contributing to adverse health care experiences and poor quality of life. Coronary function testing at the time of invasive coronary angiography allows for improved diagnostic accuracy. Despite increased recognition of INOCA and expanding access to testing, data lack on first-person perspectives and the impact of receiving a diagnosis in women with INOCA. METHODS: From 2020 to 2021, we conducted structured telephone interviews with 2 groups of women with INOCA who underwent invasive coronary angiography (n=29) at Yale New Haven Hospital, New Haven, CT: 1 group underwent coronary function testing (n=20, of whom 18 received a mechanism-based diagnosis) and the other group who did not undergo coronary function testing (n=9). The interviews were analyzed using the constant comparison method by a multidisciplinary team. RESULTS: The mean age was 59.7 years, and 79% and 3% were non-Hispanic White and non-Hispanic Black, respectively. Through iterative coding, 4 themes emerged and were further separated into subthemes that highlight disease experience aspects to be addressed in patient care: (1) distress from symptoms of uncertain cause: symptom constellation, struggle for sensemaking, emotional toll, threat to personal and professional identity; (2) a long journey to reach a definitive diagnosis: self-advocacy and fortitude, healthcare interactions brought about further uncertainty and trauma, therapeutic alliance, sources of information; (3) establishing a diagnosis enabled a path forward: relief and validation, empowerment; and (4) commitment to promoting awareness and supporting other women: recognition of sex and racial/ethnic disparities, support for other women. CONCLUSIONS: Insights about how women experience the symptoms of INOCA and their interactions with clinicians and the healthcare system hold powerful lessons for more patient-centered care. A coronary function testing-informed diagnosis greatly influences the healthcare experiences, quality of life, and emotional states of women with INOCA.
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Doença da Artéria Coronariana , Isquemia Miocárdica , Humanos , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Qualidade de Vida/psicologia , Isquemia Miocárdica/diagnóstico , Isquemia , PercepçãoRESUMO
Endothelial cell damage related to coronavirus disease 2019 (COVID-19) has been described in multiple vascular beds, and many survivors of COVID-19 report chest pain. This case series describes two previously healthy middle-aged individuals who survived COVID-19 and were subsequently found to have symptomatic coronary endothelial dysfunction months after initial infection.
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Two middle-aged women had evidence suggesting right ventricular hypertrophy on routine electrocardiograms. Their echocardiograms showed right ventricular thickening and cardiac magnetic resonance imaging revealed right ventricular fatty infiltration. Neither patient fulfilled the criteria for arrhythmogenic right ventricular cardiomyopathy, and both had a benign clinical course. (Level of Difficulty: Intermediate.).
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A 62-year-old woman with human T-lymphotropic virus type 1 cell lymphoma developed heart failure after mogamulizumab, an immunotherapy agent. Clinical presentation and cardiac magnetic resonance imaging were consistent with myocarditis, and a recurrence of heart failure occurred after rechallenge with the therapy. (Level of Difficulty: Advanced.).
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AIMS: A diet with modified components, such as a ketogenic low-carbohydrate (LC) diet, potentially extends longevity and healthspan. However, how an LC diet impacts on cardiac pathology during haemodynamic stress remains elusive. This study evaluated the effects of an LC diet high in either fat (Fat-LC) or protein (Pro-LC) in a mouse model of chronic hypertensive cardiac remodelling. METHODS AND RESULTS: Wild-type mice were subjected to transverse aortic constriction, followed by feeding with the Fat-LC, the Pro-LC, or a high-carbohydrate control diet. After 4 weeks, echocardiographic, haemodynamic, histological, and biochemical analyses were performed. LC diet consumption after pressure overload inhibited the development of pathological hypertrophy and systolic dysfunction compared to the control diet. An anti-hypertrophic serine/threonine kinase, GSK-3ß, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotection in GSK-3ß cardiac-specific knockout mice. ß-hydroxybutyrate, a major ketone body in mammals, was increased in the hearts of mice fed the Fat-LC, but not the Pro-LC, diet. In cardiomyocytes, ketone body supplementation inhibited phenylephrine-induced hypertrophy, in part by suppressing mTOR signalling. CONCLUSION: Strict carbohydrate restriction suppresses pathological cardiac growth and heart failure after pressure overload through distinct anti-hypertrophic mechanisms elicited by supplemented macronutrients.
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Dieta Rica em Proteínas e Pobre em Carboidratos , Dieta Cetogênica , Carboidratos da Dieta/metabolismo , Insuficiência Cardíaca/prevenção & controle , Hipertrofia Ventricular Esquerda/prevenção & controle , Miócitos Cardíacos/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Ração Animal , Animais , Células Cultivadas , Carboidratos da Dieta/administração & dosagem , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Valor Nutritivo , Ratos Wistar , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Função Ventricular Esquerda , Remodelação VentricularRESUMO
Study objective: Mentorship is a key component of successful cardiology training. This study sought to understand the alignment of mentorship priorities for fellow-in-training (FIT) mentees and faculty mentors. Design: Cross-sectional survey study. Setting: Online. Participants: Cardiology mentors and FIT mentees in the State of Connecticut. Interventions: None. Main outcome measures: Likert-scale graded valuations on the importance of and satisfaction with various categories of mentorship by both mentors and mentees. Results were analyzed using Mann-Whitney, Kruskal-Wallis and Wilcoxon signed-rank tests, where appropriate. Results: Forty-eight percent of FITs (n = 34) and 16% of faculty mentors (n = 34) responded to the survey. Of those, 74% of FITs identified a mentor within the first year of fellowship either by directly contacting the mentor or meeting them through a clinical rotation. Mentors significantly undervalued the importance to FITs of providing research opportunities (4.5 vs 3.6, p < 0.05), helping them make contacts (4.5 vs 3.7, p < 0.05) and providing job-search support (4.3 vs 3.3, p < 0.05). In contrast, mentors overestimated the value of work-life balance and clinical mentorship to FITs. Conclusions: FITs value support in research, job search support, and networking more than mentors realize, leading to an expectation-satisfaction gap in those areas of mentorship. Further studies to examine how mentors and mentees can best align their expectations may improve the efficacy of the mentorship process.
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Angiografia Coronária , Humanos , Resultado do Tratamento , Valor Preditivo dos Testes , Tomada de Decisão Clínica , Intervenção Coronária Percutânea , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Infarto do Miocárdio/cirurgia , Seleção de Pacientes , Reserva Fracionada de Fluxo MiocárdicoRESUMO
Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.