Microvascular Dysfunction in Patients With Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve.

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups. Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results: The median FFR value was 0.83 [0.79-0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05). Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.

Simplified Assessment of the Index of Microvascular Resistance.

BACKGROUND: To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR). METHODS: This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement. RESULTS: One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, p=0.25; Passing-Bablok coefficient A 0.58, 95% CI -2.42 to 3.53; coefficient B 0.90, 95% CI -0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, p < 0.0001). CONCLUSION: IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory.

Assessment of dapagliflozin effect on diabetic endothelial dysfunction of brachial artery (ADDENDA-BHS2 trial): rationale, design, and baseline characteristics of a randomized controlled trial.

BACKGROUND: Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. METHOD AND RESULTS: ADDENDA-BHS2 is a prospective, single-center, active-controlled, open, randomized trial. Ninety-eight participants (40-70 years old) with HbA1c 7-9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. CONCLUSION: The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations.Trial registration Clinical trial registration: NCT02919345 (September, 2016).

Neoliberalismo e Estado Mínimo: repercussões na atenção à saúde no Distrito Federal / Neoliberalism and the Minimal State: Implications for the health care in the Federal District

Trata-se de um ensaio sobre como a política neoliberal de um governo pode repercutir na promoção e atenção à saúde no Distrito Federal. O presente artigo apresenta as bases do neoliberalismo, estabelece os pressupostos da reorganização em torno de um estado mínimo perante a economia e a sociedade e analisa as possíveis repercussões sobre a promoçãoe atenção à saúde. Para tanto aborda as bases política-administrativas do Programa de Eficiência em Saúde do Governo do Distrito Federal nos últimos dois anos, seus valores de financiamento, comparando-o com outros sistemas nacionais e internacionais que adotaram essa política. Citam ainda experiências que resultaram negativas para a consolidação do SUS um sistema de saúde com características de universalidade e integralidade e chama a atenção para a vulnerabilidade dos sistemas de saúde às políticas governamentais com características neoliberais. Palavras-chave: Neoliberalismo; Estado Mínimo; Atenção à Saúde no Distrito Federal (AU)

This is an essay where the impact of a neoliberal policy on health promotion and medical care in the Federal District is analysed. This article presents the basis of neoliberalism, and it establishes the reorganizational premises of a minimal State related to economics and society, and it analyzes possible implication for health promotion and care. To this end, it addresses the political-administrative basis of the Government of Federal District Health Efficiency Program during the past two years and its financed amounts, and compares it to other domestic and international systems which have adopted this policy. It also quotes experiments resulting negatively to SUS, a health system with universality and integrality features. Also, it calls attention to vulnerability of health systems concerning policies of a government with neoliberal characteristics. Key words: Neoliberalism; Minimal State; Health care in the Federal District (AU)

Neoliberalismo e Estado Mínimo: repercussões na atenção à saúde no Distrito Federal / Neoliberalism and the Minimal State: implications for the health care in the Federal District

Trata-se de um ensaio sobre como a política neoliberal de um governo pode repercutir na promoção e atenção à saúde no Distrito Federal. O presente artigo apresenta as bases do neoliberalismo, estabelece os pressupostos da reorganização em torno de um estado mínimo perante a economia e a sociedade e analisa as possíveis repercussões sobre a promoção e atenção à saúde. Para tanto aborda as bases política-administrativas do Programa de Eficiência em Saúde do Governo do Distrito Federal nos últimos dois anos, seus valores de financiamento, comparando-o com outros sistemas nacionais e internacionais que adotaram essa política. Citam ainda experiências que resultaram negativas para a consolidação do SUS um sistema de saúde com características de universalidade e integralidade e chama a atenção para a vulnerabilidade dos sistemas de saúde às políticas governamentais com características neoliberais.

This is an essay where the impact of a neoliberal policy on health promotion and medical care in the Federal District is analysed. This article presents the basis of neoliberalism, and it establishes the reorganizational premises of a minimal State related to economics and society, and it analyzes possible implication for health promotion and care. To this end, it addresses the political-administrative basis of the Government of Federal District Health Efficiency Program during the past two years and its financed amounts, and compares it to other domestic and international systems which have adopted this policy. It also quotes experiments resulting negatively to SUS, a health system with universality and integrality features. Also, it calls attention to vulnerability of health systems concerning policies of a government with neoliberal characteristics.