Myocardial microstructure assessed by T1 mapping after on-pump and off-pump coronary artery bypass grafting.

Background: The correlation between the release of cardiac biomarkers after revascularization, in the absence of late gadolinium enhancement (LGE) or myocardial edema, and the development of myocardial tissue damage remains unclear. This study sought to identify whether the release of biomarkers is associated with cardiac damage by assessing myocardial microstructure on T1 mapping after on-pump (ONCAB) and off-pump coronary artery bypass grafting (OPCAB). Methods: Seventy-six patients with stable multivessel coronary artery disease (CAD) and preserved systolic ventricular function were included. T1 mapping, high-sensitive cardiac troponin I (cTnI), creatine kinase myocardial band (CK-MB) mass, and ventricular dimensions and function were measured before and after procedures. Results: Of the 76 patients, 44 underwent OPCAB, and 32 ONCAB; 52 were men (68.4%), and the mean age was 63±8.5 years. In both OPCAB and ONCAB the native T1 values were similar before and after surgeries. An increase in extracellular volume (ECV) values after the procedures was observed, due to the decrease in hematocrit levels during the second cardiac resonance. However, the lambda partition coefficient showed no significant difference after the surgeries. The median peak release of cTnI and CK-MB were higher after ONCAB than after OPCAB [3.55 (2.12-4.9) vs. 2.19 (0.69-3.4) ng/mL, P=0.009 and 28.7 (18.2-55.4) vs. 14.3 (9.3-29.2) ng/mL, P=0.009, respectively]. Left ventricular ejection fraction (LVEF) was similar in both groups before and after surgery. Conclusions: In the absence of documented myocardial infarction, T1 mapping did not identify structural tissue damage after surgical revascularization with or without cardiopulmonary bypass (CPB), despite the excessive release of cardiac biomarkers.

Myocardial tissue microstructure with and without stress-induced ischemia assessed by T1 mapping in patients with stable coronary artery disease.

BACKGROUND: Stress-induced myocardial ischemia seems not to be associated with cardiovascular events. However, its effects on myocardial tissue characteristics remain under debate. Thus, we sought to assess whether documented stress-induced ischemia is associated with changes in myocardial microstructure evaluated by magnetic resonance native T1 map and extracellular volume fraction (ECV). METHODS: This is a single-center, analysis of the previously published MASS V Trial. Multivessel patients with a formal indication for myocardial revascularization and with documented stress-induced ischemia were included in this study. Native T1 and ECV values evaluated by cardiac magnetic resonance imaging of ischemic and nonischemic myocardial segments at rest and after stress were compared. Myocardial ischemia was detected by either nuclear scintigraphy or stress magnetic cardiac resonance protocol. RESULTS: Between May 2012 and March 2014, 326 prospective patients were eligible for isolated CABG or PCI and 219 were included in the MASS V trial. All patients underwent resting cardiac magnetic resonance imaging. Of a total of 840 myocardial segments, 654 were nonischemic segments and 186 were ischemic segments. Native T1 and ECV values of ischemic segments were not significantly different from nonischemic segments, both at rest and after stress induction. In addition, native T1 and ECV values of myocardial segments supplied by vessels with obstructive lesions were similar to those supplied by nonobstructive ones. CONCLUSION AND RELEVANCE: In this study, cardiac magnetic resonance identified similar T1 mapping values between ischemic and nonischemic myocardial segments. This finding suggests integrity and stability of myocardial tissue in the presence of stress-induced ischemia.

Chronic troponin elevation assessed by myocardial T1 mapping in patients with stable coronary artery disease.

BACKGROUND: Cardiac troponin detected with sensitive assays can be chronically elevated, in the absence of unstable coronary syndromes. In patients with chronic coronary artery disease, clinically silent ischemic episodes may cause chronic troponin release. T1 mapping is a cardiovascular magnetic resonance technique useful in quantitative cardiac tissue characterization. We selected patients with anatomically and functionally normal hearts to investigate associations between chronic troponin release and myocardial tissue characteristics assessed by T1 mapping. METHODS: We investigated the relationship between cardiac troponin I concentrations and cardiovascular magnetic resonance T1 mapping parameters in patients with stable coronary artery disease enrolled in MASS V study before elective revascularization. Participants had no previous myocardial infarction, negative late gadolinium enhancement, normal left ventricular function, chamber dimensions and wall thickness. RESULTS: A total of 56 patients were analyzed in troponin tertiles: nativeT1 and extracellular volume (ECV) values (expressed as means ±â€…standard deviations) increased across tertiles: nativeT1 (1006 ±â€…27 ms vs 1016 ±â€…27 ms vs 1034 ±â€…37 ms, ptrend = 0.006) and ECV (22 ±â€…3% vs 23 ±â€…1.9% vs 25 ±â€…3%, ptrend = 0.007). Cardiac troponin I concentrations correlated with native T1(R = 0.33, P = .012) and ECV (R = 0.3, P = .025), and were independently associated with nativeT1 (P = .049) and ventricular mass index (P = .041) in multivariable analysis. CONCLUSION: In patients with chronic coronary artery disease and structurally normal hearts, troponin I concentrations correlated with T1 mapping parameters, suggesting that diffuse edema or fibrosis scattered in normal myocardium might be associated with chronic troponin release.

Cardiovascular events in patients with coronary artery disease with and without myocardial ischemia: Long-term follow-up.

BACKGROUND: After the results of the ISCHEMIA Trial, the role of myocardial ischemia in the prognosis of coronary artery disease (CAD) was under debate. We sought to comparatively evaluate the long-term prognosis of patients with multivessel CAD with or without documented myocardial ischemia. METHODS: This is a single-center, retrospective, observational cohort study that included patients with CAD obtained from the research protocols database of "The Medicine, Angioplasty or Surgery Study," the MASS Study Group. Patients were stratified according to the presence or absence of myocardial ischemia. Cardiovascular events (overall mortality and myocardial infarction) were tracked from the registry entry up to a median follow-up of 8.7 years. Myocardial ischemia was assessed at baseline by a functional test with or without imaging. RESULTS: From 1995 to 2018, 2015 patients with multivessel CAD were included. Of these, 1001 presented with conclusive tests at registry entry, 790 (79%) presenting with ischemia and 211 (21%) without ischemia. The median follow-up was 8.7 years (IQR 4.04 to 10.07). The primary outcome occurred in 228 (28.9%) patients with ischemia and in 64 (30.3%) patients without ischemia (plog-rank=0.60). No significant interaction was observed with the presence of myocardial ischemia and treatment strategies in the occurrence of the combined primary outcome (pinteration=0.14). CONCLUSIONS: In this sample, myocardial ischemia was not associated with a worse prognosis compared with no ischemia in patients with multivessel CAD. These results refer to debates about the role of myocardial ischemia in the occurrence of cardiovascular events.

Cardiac corpuscles: a “new” morphofunctional entity?

he existence of “transitional muscular structures” between subendocardial branches (Purkinje fibers) and ventricular working muscle fibers (WF) was first described by the German anatomist, Kurt Goerttler, in 1964. He designated them as “subendocardial nucleus organs.” He supposed such fibers functioned as mechanoreceptors, controlling of the intensity of contraction of the ventricular musculature. Brazilian anatomist Ferraz de Carvalho described similar structures in 1993. A thorough literature search failed to identify any other research articles confirming or denying their existence. The objective of this work was to find such structures in subendocardial ventricular walls in human hearts. We collected fifteen formalin-preserved hearts from the Anatomy Department of São Paulo University and sectioned the apical portions on the right and left ventricles according to method used by Goerttler. We utilized conventional histology (light microscopy- LM), scanning electron microscopy (SEM), and a new preservation method called micro- plastination (MP). At the anterior wall of the right ventricle in the subendocardial region between the interventricular septum and moderator band, we found several bundles of fusiform and helicoidal fibers of similar histology to the WF. The bundles measured between 400 and 1150 µm in length and were separated from adjacent muscular fibers by thin collagen fiber, thus acting as a “pseudo capsule.” Some structures seemed to be linked to PF and were appeared to be lymphatic and blood vessels and nerves. We called those structures “cardiac corpuscles” (CC). The observation of the previously “unknown” CC in this initial study confirmed the previous descriptions and its discovery may contribute to new perspectives in the study of cardiac muscle structure and function.

Long-term analysis of ventricular function in patients with symptomatic coronary disease who underwent on-pump or off-pump coronary artery bypass grafting.

BACKGROUND: Systemic deleterious effects of cardiopulmonary bypass have been observed in the postprocedural period. Long-term assessment, including ventricular function (VF), is unclear. The objective of this study was to compare the change of left ventricular ejection fractions (LVEFs) during a long-term follow-up of coronary artery disease (CAD) patients who underwent off-pump (OPCAB) or on-pump coronary artery bypass grafting (ONCAB). METHODS: This study is a prespecified analysis of the MASS III trial, which was a single-center and prospective study that enrolled stable CAD patients with preserved VF. The CAD patients in our study were randomized to OPCAB or ONCAB. A transthoracic echocardiogram was performed during follow-up and a LVEF value was obtained. The primary endpoint was the difference between the final LVEF and the baseline LVEF. RESULTS: Of the 308 randomized patients, ventricular function were observed in 225 over a mean of 5.9 years of follow-up: 113 in the ONCAB group and 112 in the OPCAB group. Baseline characteristics were similar between the two groups, but there was a larger proportion of subjects with 3-vessel disease in the ONCAB group. There was no difference in the LVEF at the beginning (P = 0.08), but there was a slight decrease in the LVEF in the ONCAB and OPCAB groups (P < 0.001 in both groups) at 5.9 years. The decline was not significantly different between the two groups (delta of -6% for ONCAB and -5% for OPCAB; P = 0.78). In a multivariate analysis, myocardial infarction in the follow-up was a predictor of an LVEF < 40%. CONCLUSIONS: There was no difference in the long-term development of ventricular function between the surgical techniques, despite a decline in the LVEF in both groups. Trial registration Clinical Trial Registration Information-URL: http://www.controlled-trials.com . REGISTRATION NUMBER: ISRCTN59539154. Date of first registration: 10/03/2008.

Surgical and percutaneous revascularization outcomes based on SYNTAX I, II, and residual scores: a long-term follow-up study.

BACKGROUND: The objective of this study was to evaluate the association of SYNTAX scores I, II, and residual with cardiovascular outcomes of patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and compare both procedures in a long-term follow-up. METHODS: This is a retrospective single-center study from the MASS registry at the Heart Institute of the University of São Paulo, Brazil in which 969 patients with stable coronary artery disease undergoing CABG (559) or PCI (410) were included. We assessed the SYNTAX scores I, II and residual in both interventions. Clinical endpoints were the first occurrence of a composite of overall death, myocardial infarction, stroke, or repeat revascularization (MACCE) and the total occurrence of each component of MACCE. RESULTS: In the CABG sample, SSI had a median of 23 (IQR 17-29.5), median SSII of 25.4 (IQR 19.2-32.8), and median rSS of 2 (IQR 0-6.5); in PCI SSI had a median of 14 (IQR 10-19.1), median SSII of 28.7 (IQR 23-34.2), and median rSS of 4.7 (IQR 0-9). Total of 174 events were documented and CABG patients had a lower rate of MACCE (15.6% vs. 21.2%; adjusted HR 1.98; 95% CI 1.13-3.47; P = 0.016) and repeat revascularization (3.8% vs. 11.5%; adjusted HR 4.35; CI 95% 1.74-10.85; P = 0.002) compared with PCI. No SYNTAX score tertile found a difference in death rate between procedures. In a multivariate analysis, the rSS was an independent predictor for MACCE (HR 1.04; 95% CI 1.01-1.06; P = 0.001). Regarding death, the only independent predictors were ejection fraction and renal function. CONCLUSION: Surgical revascularization resulted in a more complete revascularization and lower rates of major cardiac or cerebrovascular events in a long-term follow-up. Also, grading the incompleteness of revascularization through the residual SYNTAX score identified a higher event rate, suggesting that complete revascularization is associated with a better prognosis.

Effect of diabetic kidney disease on therapeutic strategies for coronary artery disease: ten year follow-up.

BACKGROUND: The best treatment for coronary artery disease (CAD) in patients with type 2 diabetes (DM2) and chronic kidney disease is unknown. METHODS: This retrospective study included MASS registry patients with DM2 and multivessel CAD, stratified by kidney function. Primary endpoint was combined of mortality, myocardial infarction, or additional revascularization. RESULTS: Median follow-up was 9.5 years. Primary endpoint occurrences among strata 1 and 2 were 53.4% and 40.7%, respectively (P=.020). Mortality rates were 37.4% and 24.6% in strata 1 and 2, respectively (P<.001). We observed a lower rate of major adverse cardiovascular events (MACE) (P=.027 for stratum 1 and P<.001 for stratum 2) and additional revascularization (P=.001 for stratum 1 and P<.001 for stratum 2) for those in the surgical group. In a multivariate analysis, eGFR was an independent predictor of MACE (P=.034) and mortality (P=.020). CONCLUSIONS: Among subjects with DM2 and CAD the presence of lower eGFR rate was associated with higher rates of MACE and mortality, irrespective of treatment choice. CABG was associated with lower rates of MACE in both renal function strata. eGFR was an independent predictor of MACE and mortality in a 10-year follow-up.

Morphomolecular Characterization of Serum Nanovesicles From Microbiomes Differentiates Stable and Infarcted Atherosclerotic Patients.

Microbial communities are considered decisive for maintaining a healthy situation or for determining diseases. Acute myocardial infarction (AMI) is an important complication of atherosclerosis caused by the rupture of atheroma plaques containing proinflammatory cytokines, reactive oxygen species, oxidized low-density lipoproteins (oxLDL), damaged proteins, lipids, and DNA, a microenvironment compatible with a pathogenic microbial community. Previously, we found that archaeal DNA-positive infectious microvesicles (iMVs) were detected in vulnerable plaques and in the sera of Chagas disease patients with heart failure. Now, we characterize and quantify the levels of serum microbiome extracellular vesicles through their size and content using morphomolecular techniques to differentiate clinical outcomes in coronary artery disease (CAD). We detected increased numbers of large iMVs (0.8-1.34 nm) with highly negative surface charge that were positive for archaeal DNA, Mycoplasma pneumoniae antigens and MMP9 in the sera of severe AMI patients, strongly favoring our hypothesis that pathogenic archaea may play a role in the worst outcomes of atherosclerosis. The highest numbers of EVs <100 nm (exosomes) and MVs from 100 to 200 nm in the stable atherosclerotic and control healthy groups compared with the AMI groups were indicative that these EVs are protective, entrapping and degrading infectious antigens and active MMP9 and protect against the development of plaque rupture. Conclusion: A microbiome with pathogenic archaea is associated with high numbers of serum iMVs in AMI with the worst prognosis. This pioneering work demonstrates that the morphomolecular characterization and quantification of iEVs in serum may constitute a promising serum prognostic biomarker in CAD.

Intensive care management of patients with COVID-19: a practical approach.

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic facing humanity since the Spanish flu pandemic in the early twentieth century. Since there is no specific antiviral treatment, optimized support is the most relevant factor in the patient's prognosis. In the hospital setting, the identification of high-risk patients for clinical deterioration is essential to ensure access to intensive treatment of severe conditions in a timely manner. The initial management of hypoxemia includes conventional oxygen therapy, high-flow nasal canula oxygen, and non-invasive ventilation. For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes and plateau pressure is recommended. Cardiovascular complications are frequent and include myocardial injury, thrombotic events, myocarditis, and cardiogenic shock. Acute renal failure is a common complication and is a marker of poor prognosis, with significant impact in costs and resources allocation. Regarding promising therapies for COVID-19, the most promising drugs until now are remdesivir and corticosteroids although further studies may be needed to confirm their effectiveness. Other therapies such as, tocilizumab, anakinra, other anti-cytokine drugs, and heparin are being tested in clinical trials. Thousands of physicians are living a scenario that none of us have ever seen: demand for hospital exceed capacity in most countries. Until now, the certainty we have is that we should try to decrease the number of infected patients and that an optimized critical care support is the best strategy to improve patient's survival.

The Heart and COVID-19: What Cardiologists Need to Know. / O Coração e a COVID-19: O que o Cardiologista Precisa Saber.

In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.

Frente à pandemia da doença causada pelo novo coronavírus (COVID-19), o manejo do paciente com fator de risco e/ou doença cardiovascular é desafiador nos dias de hoje. As complicações cardiovasculares evidenciadas nos pacientes com COVID-19 resultam de vários mecanismos, que vão desde lesão direta pelo vírus até complicações secundárias à resposta inflamatória e trombótica desencadeada pela infecção. O cuidado adequado do paciente com COVID-19 exige atenção ao sistema cardiovascular em busca de melhores desfechos.

The Heart and COVID-19: What Cardiologists Need to Know

In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.

O Coração e a COVID-19: O que o Cardiologista Precisa Saber

Frente à pandemia da doença causada pelo novo coronavírus (COVID-19), o manejo do paciente com fator de risco e/ou doença cardiovascular é desafiador nos dias de hoje. As complicações cardiovasculares evidenciadas nos pacientes com COVID-19 resultam de vários mecanismos, que vão desde lesão direta pelo vírus até complicações secundárias à resposta inflamatória e trombótica desencadeada pela infecção. O cuidado adequado do paciente com COVID-19 exige atenção ao sistema cardiovascular em busca de melhores desfechos.

O Coração e a COVID-19: O que o Cardiologista Precisa Saber / The Heart and COVID-19: What Cardiologists Need to Know

Resumo Frente à pandemia da doença causada pelo novo coronavírus (COVID-19), o manejo do paciente com fator de risco e/ou doença cardiovascular é desafiador nos dias de hoje. As complicações cardiovasculares evidenciadas nos pacientes com COVID-19 resultam de vários mecanismos, que vão desde lesão direta pelo vírus até complicações secundárias à resposta inflamatória e trombótica desencadeada pela infecção. O cuidado adequado do paciente com COVID-19 exige atenção ao sistema cardiovascular em busca de melhores desfechos.

Abstract In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.

Hypotheses, rationale, design, and methods for prognostic evaluation of a randomized comparison between patients with coronary artery disease associated with ischemic cardiomyopathy who undergo medical or surgical treatment: MASS-VI (HF).

BACKGROUND: Ischemic cardiomyopathy and severe left ventricular dysfunction are well established to represent the main determinants of poor survival and premature death compared with preserved ventricular function. However, the role of myocardial revascularization as a therapeutic alternative is not known to improve the long-term prognosis in this group of patients. This study will investigate whether myocardial revascularization contributes to a better prognosis for patients compared with those treated with drugs alone and followed over the long term. METHODS: The study will include 600 patients with coronary artery disease associated with ischemic cardiomyopathy. The surgical or drug therapy option will be randomized, and the events considered for analysis will be all-cause mortality, nonfatal infarction, unstable angina requiring additional revascularization, and stroke. The events will be analyzed according to the intent-to-treat principle. Patients with multivessel coronary disease and left ventricular ejection fraction measurements of less than 35% will be included. In addition, myocardial ischemia will be documented by myocardial scintigraphy. Markers of myocardial necrosis will be checked at admission and after the procedure. DISCUSSION: The role of myocardial revascularization (CABG) in the treatment of patients with coronary artery disease and heart failure is not clearly established. The surgical option of revascularizing the myocardium is a procedure designed to reduce the load of myocardial hibernation in patients with heart failure caused by coronary artery disease. On the other hand, the assessment of myocardial viability is frequently used to identify patients with left ventricular ischemic dysfunction in which CABG may add survival benefit. However, the effectiveness of this option is uncertain. The great difficulty in establishing the efficacy of surgical intervention is based on the understanding of viability without ischemia. Thus, this study will include only patients with viable and truly ischemic myocardium to correct this anomaly. TRIAL REGISTRATION: Evaluation of a randomized comparison between patients with coronary artery disease associated with ischemic cardiomyopathy submitted to medical or surgical treatment: MASS-VI (HF), ISRCTN77449548, Oct 10th, 2019 (retrospectively registered).